1
Review J Vestib Res
. 2019;29(2-3):45-56. doi: 10.3233/VES-190655.
Hemodynamic Orthostatic dizziness/vertigo: Diagnostic Criteria
Hyun Ah Kim 1, Alexandre Bisdorff 2, Adolfo M Bronstein 3, Thomas Lempert 4, Marcos Rossi-Izquierdo 5, Jeffrey P Staab 6, Michael Strupp 7, Ji-Soo Kim 8
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PMID: 30883381 DOI: 10.3233/VES-190655
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Abstract
This paper presents the diagnostic criteria for hemodynamic orthostatic dizziness/vertigo to be included in the International Classification of Vestibular Disorders (ICVD). The aim of defining diagnostic criteria of hemodynamic orthostatic dizziness/vertigo is to help clinicians to understand the terminology related to orthostatic dizziness/vertigo and to distinguish orthostatic dizziness/vertigo due to global brain hypoperfusion from that caused by other etiologies. Diagnosis of hemodynamic orthostatic dizziness/vertigo requires: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) orthostatic hypotension, postural tachycardia syndrome or syncope documented on standing or during head-up tilt test; and C) not better accounted for by another disease or disorder. Probable hemodynamic orthostatic dizziness/vertigo is defined as follows: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) at least one of the following accompanying symptoms: generalized weakness/tiredness, difficulty in thinking/concentrating, blurred vision, and tachycardia/palpitations; and C) not better accounted for by another disease or disorder. These diagnostic criteria have been derived by expert consensus from an extensive review of 90 years of research on hemodynamic orthostatic dizziness/vertigo, postural hypotension or tachycardia, and autonomic dizziness. Measurements of orthostatic blood pressure and heart rate are important for the screening and documentation of orthostatic hypotension or postural tachycardia syndrome to establish the diagnosis of hemodynamic orthostatic dizziness/vertigo.

Keywords: Bárány Society; Orthostatic vertigo; autonomic dysfunction; classification; hemodynamic; orthostatic dizziness; orthostatic hypotension; postural tachycardia syndrome.

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2
Review J Vestib Res
. 2019;29(2-3):57-87. doi: 10.3233/VES-190658.
Classification of Vestibular Signs and Examination Techniques: Nystagmus and Nystagmus-Like Movements
Scott D Z Eggers 1, Alexandre Bisdorff 2, Michael von Brevern 3, David S Zee 4, Ji-Soo Kim 5, Nicolas Perez-Fernandez 6, Miriam S Welgampola 7, Charles C Della Santina 8, David E Newman-Toker 4 8
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PMID: 31256095 DOI: 10.3233/VES-190658
Abstract
This paper presents a classification and definitions for types of nystagmus and other oscillatory eye movements relevant to evaluation of patients with vestibular and neurological disorders, formulated by the Classification Committee of the Bárány Society, to facilitate identification and communication for research and clinical care. Terminology surrounding the numerous attributes and influencing factors necessary to characterize nystagmus are outlined and defined. The classification first organizes the complex nomenclature of nystagmus around phenomenology, while also considering knowledge of anatomy, pathophysiology, and etiology. Nystagmus is distinguished from various other nystagmus-like movements including saccadic intrusions and oscillations.View accompanying videos at http://www.jvr-web.org/ICVD.html.

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3
J Allergy Clin Immunol
. 2019 Nov;144(5):1254-1264. doi: 10.1016/j.jaci.2019.06.023. Epub 2019 Jul 2.
Cross-talk Between T H 2 and T H 17 Pathways in Patients With Chronic Rhinosinusitis With Nasal Polyps
Min Wang 1, Nan Zhang 2, Ming Zheng 3, Ying Li 4, Lingling Meng 5, Yu Ruan 4, Jinbo Han 1, Na Zhao 6, Xiangdong Wang 7, Luo Zhang 8, Claus Bachert 9
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PMID: 31271788 DOI: 10.1016/j.jaci.2019.06.023
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Abstract
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. TH2- and TH17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP.

Objective: We sought to investigate the interregulation of TH2 and TH17 pathways in Chinese patients with CRSwNP.

Methods: Levels of key TH2- and TH17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of TH2 and TH17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between TH2- and TH17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored.

Results: Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive TH2- and TH17-related factors. The TH2 cytokines IL-4 and IL-13 inhibited expression of TH17-related factors, whereas the TH17 cytokines IL-17 and TGF-β1 enhanced expression of TH2-related factors. Dexamethasone treatment inhibited both the TH2 and TH17 pathways. A patient's atopic status was related to their TH2 immune response. Edema scores were positively correlated with the TH2 pathway and negatively correlated with the TH17 pathway.

Conclusion: The TH2 and TH17 pathways are mutually exclusive and regulate each other, favoring the development of a TH2 immune response in Chinese patients with CRSwNP.

Keywords: Chronic rhinosinusitis with nasal polyps; T(H)17; T(H)2; endotypes; shift.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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4
Eur J Surg Oncol
. 2019 Jul;45(7):1188-1195. doi: 10.1016/j.ejso.2019.03.032. Epub 2019 Mar 27.
Prospective Validation of an Institutional Treatment Strategy for T1N0M0 Glottic Carcinoma
Simon Beyaert 1, Marc Hamoir 2, Aline Van Maanen 3, Vincent Grégoire 4, Sandra Schmitz 5
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PMID: 30940421 DOI: 10.1016/j.ejso.2019.03.032
Abstract
Introduction: The aim of this study was to assess the validity of a treatment strategy for T1N0 glottic squamous cell carcinoma.

Methods: One hundred and seventeen patients were prospectively treated according to institutional guidelines. using 1) laser microsurgery (L) for exophytic tumor, limited to one vocal cord, without extension to the anterior commissure or the vocal process of the arytenoid cartilage, 2) radiotherapy (RT) for large or infiltrative tumor reaching the anterior commissure or the vocal process of the arytenoid cartilage, poor endoscopic exposure and cT1b or 3) partial laryngectomy (PL) for tumor infiltrating the anterior commissure. Ninety-five patients were treated with RT and 22 with surgery alone (S) [L:19; PL:3].

Results: The 5-year overall survival (OS) and disease-specific survival (DSS) were 81.5% and 97.1% (median follow-up: 73 months), respectively. There was no statistically significant difference in OS or DSS between patients treated with RT or S (logrank test: p = 0.974 and 0.978). The 5-year ultimate local control rate reached 98.3%. The local control rate with larynx preservation was 94.9% with no difference between RT (94.7%) and S (95.5%) (χ2: p = 0.891). Continued smoking after RT was significantly associated with a lower 5-year OS (77.9% versus 87%), [HR 3.458; p = 0.043 (95%CI 1.010-11.837)].

Conclusions: For patients with T1 glottic carcinoma, and based on our previous studies, these data prospectively confirm the oncologic validity of an institutional treatment strategy. Continued smoking after RT correlated with poor OS.

Keywords: Laser microsurgery; Partial laryngectomy; Radiotherapy; Squamous cell carcinoma; T1N0 glottic cancer.

Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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5
J Allergy Clin Immunol
. 2019 Nov;144(5):1228-1241.e9. doi: 10.1016/j.jaci.2019.06.037. Epub 2019 Jul 11.
15-Lipoxygenase 1 in Nasal Polyps Promotes CCL26/eotaxin 3 Expression Through Extracellular Signal-Regulated Kinase Activation
Zhipeng Li 1, Ming Zeng 2, Yanhan Deng 3, Jinming Zhao 4, Xiuxia Zhou 4, John B Trudeau 4, Ezequiel Goldschmidt 5, John A Moore 6, Hongwei Chu 7, Weitian Zhang 8, Shankai Yin 8, Zheng Liu 9, Y Peter Di 4, Stella E Lee 10, Sally E Wenzel 11
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PMID: 31301373 PMCID: PMC6842430 (available on 2020-11-01) DOI: 10.1016/j.jaci.2019.06.037
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Abstract
Background: 15-Lipoxygenase 1 (15LO1) is expressed in airway epithelial cells in patients with type 2-high asthma in association with eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also associated with type 2 inflammation and eosinophilia. CCL26/eotaxin 3 has been reported to be regulated by 15LO1 in lower airway epithelial cells. However, its relation to 15LO1 in patients with CRSwNP or mechanisms for its activation are unclear.

Objective: We sought to evaluate 15LO1 and CCL26 expression in nasal epithelial cells (NECs) from patients with CRSwNP and healthy control subjects (HCs) and determine whether 15LO1 regulates CCL26 in NECs through extracellular signal-regulated kinase (ERK) activation.

Methods: 15LO1, CCL26, and phosphorylated ERK were evaluated in NECs from patients with CRSwNP and HCs. 15LO1/CCL26 and CCL26/cytokeratin 5 were colocalized by means of immunofluorescence. IL-13-stimulated NECs were cultured at an air-liquid interface with or without 15-lipoxygenase 1 gene (ALOX15) Dicer-substrate short interfering RNAs (DsiRNA) transfection, a specific 15LO1 enzymatic inhibitor, and 2 ERK inhibitors. Expression of 15LO1 and CCL26 mRNA and protein was analyzed by using quantitative RT-PCR, Western blotting, and ELISA.

Results: 15LO1 expression was increased in nasal polyp (NP) epithelial cells compared with middle turbinate epithelial cells from patients with CRSwNP and HCs. 15LO1 expression correlated with CCL26 expression and colocalized with CCL26 expression in basal cells of the middle turbinate and NPs from patients with CRSwNP. In primary NECs in vitro, IL-13 induced 15LO1 and CCL26 expression. 15LO1 knockdown and inhibition decreased IL-13-induced ERK phosphorylation and CCL26 expression. ERK inhibition (alone) similarly decreased IL-13-induced CCL26. Phosphorylated ERK expression was increased in NECs from CRSwNP subjects and positively correlated with both 15LO1 and CCL26 expression.

Conclusions: 15LO1 expression is increased in NP epithelial cells and contributes to CCL26 expression through ERK activation. 15LO1 could be considered a novel therapeutic target for CRSwNP.

Keywords: 15-Lipoxygenase 1; CCL26; chronic rhinosinusitis; epithelial cell; extracellular signal-regulated kinase; nasal polyps.

Published by Elsevier Inc.

Cited by 1 article
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6
Review Eur Arch Otorhinolaryngol
. 2020 Jul;277(7):1885-1897. doi: 10.1007/s00405-020-05968-y. Epub 2020 Apr 18.
COVID-19 in Otolaryngologist Practice: A Review of Current Knowledge
Joanna Krajewska 1, Wojciech Krajewski 2, Krzysztof Zub 3, Tomasz Zatoński 3
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PMID: 32306118 PMCID: PMC7166003 DOI: 10.1007/s00405-020-05968-y
Free PMC article
Abstract
Purpose: Otorhinolaryngological manifestations are common symptoms of COVID-19. This study provides a brief and precise review of the current knowledge regarding COVID-19, including disease transmission, clinical characteristics, diagnosis, and potential treatment. The article focused on COVID-19-related information useful in otolaryngologist practice.

Methods: The Medline and Web of Science databases were searched without a time limit using terms "COVID-19", "SARS-CoV-2" in conjunction with "otorhinolaryngological manifestation", "ENT", and "olfaction".

Results: The most common otolaryngological dysfunctions of COVID-19 were cough, sore throat, and dyspnea. Rhinorrhea, nasal congestion and dizziness were also present. COVID-19 could manifest as an isolated sudden hyposmia/anosmia. Upper respiratory tract (URT) symptoms were commonly observed in younger patients and usually appeared initially. They could be present even before the molecular confirmation of SARS-CoV-2. Otolaryngologists are of great risk of becoming infected with SARS-CoV-2 as they cope with URT. ENT surgeons could be easily infected by SARS-CoV-2 during performing surgery in COVID-19 patients.

Conclusion: Ear, nose and throat (ENT) symptoms may precede the development of severe COVID-19. During COVID-19 pandemic, patients with cough, sore throat, dyspnea, hyposmia/anosmia and a history of travel to the region with confirmed COVID-19 patients, should be considered as potential COVID-19 cases. An otolaryngologist should wear FFP3/N95 mask, glasses, disposable and fluid resistant gloves and gown while examining such individuals. Not urgent ENT surgeries should be postponed. Additional studies analyzing why some patients develop ENT symptoms during COVID-19 and others do not are needed. Further research is needed to determine the mechanism leading to anosmia.

Keywords: COVID-19; ENT; Olfaction; Otolaryngological manifestations; SARS-CoV-2.

Conflict of interest statement
The authors declare that they have no conflicts of interests.

Cited by 1 article50 references1 figure
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7
Case Reports Otol Neurotol
. 2019 Oct;40(9):1237-1245. doi: 10.1097/MAO.0000000000002360.
Clinical and Radiological Characteristics of Malignant Tumors Located to the Cerebellopontine Angle and/or Internal Acoustic Meatus
Michael Eliezer 1 2, Hugo Tran 1, Akira Inagaki 3, Benjamin Vérillaud 1, Mariko Takahashi 3, Jean-Paul Marie 4, Charlotte Hautefort 1, Philippe Herman 1, Shingo Murakami 3, Romain Kania 1
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PMID: 31469787 DOI: 10.1097/MAO.0000000000002360
Abstract
Objective: Metastatic lesions to the internal auditory meatus (IAM) and/or the cerebellopontine angle (CPA) are rare and may appear like a vestibular schwannoma (VS). We herein raise the issue of the diagnosis and treatment of nine malignant cases of the CPA and IAM among three referral centers in France and Japan. The aim of this study was 1) to report malignant lesions of the CPA, their diagnosis and treatment, 2) to review the literature, 3) to propose criteria of suspicion for malignant tumors of the CPA.

Methods: Nine patients who had malignant lesions of the CPA and/or IAM for whom the final diagnosis was made by surgery, lumbar puncture, or PET scan were included. The main outcomes measured were: rapid onset of symptoms, association of cochlea-vestibular symptoms with facial palsy, and MRI analysis.

Results: Among the nine patients with malignant tumor of the CPA, 8 of them (89%) had a facial palsy associated with cochlea-vestibular symptoms. Rapid growth of the tumor was observed in 77% (7/9) of the cases in a mean time interval of 4.6 months. The initial diagnosis evoked was VS in 44% of the cases (4/9). Atypical MRI aspect was seen in 67% of the cases (6/9) with bilateral tumors in 55% of cases (5/9).

Conclusion: Although rare, malignant tumors of the CPA and/or IAM should be evoked in case of association of cochleovestibular symptoms and facial palsy, rapid onset and atypical MRI aspect.

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8
J Neurosci
. 2019 Apr 10;39(15):2951-2964. doi: 10.1523/JNEUROSCI.1384-18.2019. Epub 2019 Feb 7.
Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity
Douglas Ruhl 1 2, Ting-Ting Du 1, Elizabeth L Wagner 1, Jeong Hwan Choi 1 3, Sihan Li 1, Robert Reed 1 2, Kitae Kim 1, Michael Freeman 1, George Hashisaki 2, John R Lukens 1, Jung-Bum Shin 4
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PMID: 30733218 PMCID: PMC6462451 DOI: 10.1523/JNEUROSCI.1384-18.2019
Free PMC article
Abstract
Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity.SIGNIFICANCE STATEMENT The clinical application of cisplatin and aminoglycosides is limited due to ototoxic side effects. Here, using pharmaceutical and genetic intervention, we present evidence that two types of programmed cell death, apoptosis and necroptosis, contribute to aminoglycoside and cisplatin ototoxicity. Key molecular factors mediating necroptosis are well characterized and druggable, presenting new avenues for pharmaceutical intervention.

Keywords: aminoglycoside; apoptosis; cisplatin; hair cell; hearing; necroptosis.

Copyright © 2019 the authors.

Cited by 4 articles7 figures
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9
Otol Neurotol
. 2019 Oct;40(9):1134-1138. doi: 10.1097/MAO.0000000000002386.
High Dose of Intratympanic Steroids for Sudden Sensorineural Hearing Loss Salvage
Ahmed Taha 1, Nathan Shlamkovitch, Rani Abu-Eta, Eyal Yeheskeli, Limor Muallem-Kalmovich, Haim Gavriel, Jacob Pitaro
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PMID: 31498293 DOI: 10.1097/MAO.0000000000002386
Abstract
Objective: Intratympanic (IT) steroid administration for sudden sensorineural hearing loss is offered as salvage to patients who failed systemic steroid treatment. Our objective was to study the audiometric and clinical outcomes of patients given salvage therapy with high-dose IT steroids instilled via ventilation tube.

Study design: Retrospective case review.

Setting: Academic secondary medical center.

Patients: One hundred three patients >18 years of age with sudden sensorineural hearing loss who failed systemic steroids and received IT treatment between 2010 and 2018.

Intervention: Following ventilation tube insertion, 1 ml of 10 mg/ml dexamethasone was instilled, twice daily, for 7 days.

Outcome measures: Hearing assessment immediately before and after treatment. Tinnitus and vertigo complaints and risk factors were also retrieved.

Results: Tinnitus had improved in 53 (52%) patients, vertigo in 4 (4%), and aural fullness sensation in 56 (55%) (p < 0.001, p = 0.344, p < 0.001, respectively). The mean pure-tone threshold difference across frequencies following treatment was between 0 and 6 dB. A significant improvement was observed at 250, 500, 1000 Hz (p < 0.001 in all), and at 2000 Hz (p = 0.035). No significant difference was found at 4000 and 8000 Hz (p = 0.055, p = 0.983 respectively). Mean pure-tone average improvement of 4.5 dB was detected in 61 (59%) patients (p = 0.001). The mean speech discrimination score improved by 7% (p = 0.001). Four (22%) diabetic and nine (20%) hypertensive patients had pure-tone average ≥10 dB improvement (p = 0.759, p = 0.852 respectively).

Conclusion: Although more than half of the patients improved clinically, the significance of the slight audiometric improvement should be weighed against the treatment protocol's complications.

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10
J Allergy Clin Immunol
. 2019 Nov;144(5):1242-1253.e7. doi: 10.1016/j.jaci.2019.04.027. Epub 2019 May 11.
Blocking Histone Deacetylase Activity as a Novel Target for Epithelial Barrier Defects in Patients With Allergic Rhinitis
Brecht Steelant 1, Paulina Wawrzyniak 2, Katleen Martens 3, Anne-Charlotte Jonckheere 3, Benoit Pugin 3, Rik Schrijvers 3, Dominique M Bullens 4, Jeroen A Vanoirbeek 5, Krzysztof Krawczyk 6, Anita Dreher 2, Cezmi A Akdis 2, Peter W Hellings 7
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PMID: 31082457 DOI: 10.1016/j.jaci.2019.04.027
Abstract
Background: A defective epithelial barrier is found in patients with allergic rhinitis (AR) and asthma; however, the underlying mechanisms remain poorly understood. Histone deacetylase (HDAC) activity has been identified as a crucial driver of allergic inflammation and tight junction dysfunction.

Objective: We investigated whether HDAC activity has been altered in patients with AR and in a mouse model of house dust mite (HDM)-induced allergic asthma and whether it contributed to epithelial barrier dysfunction.

Methods: Primary nasal epithelial cells of control subjects and patients with AR were cultured at the air-liquid interface to study transepithelial electrical resistance and paracellular flux of fluorescein isothiocyanate-dextran (4 kDa) together with mRNA expression and immunofluorescence staining of tight junctions. Air-liquid interface cultures were stimulated with different concentrations of JNJ-26481585, a broad-spectrum HDAC inhibitor. In vivo the effect of JNJ-26481585 on mucosal permeability and tight junction function was evaluated in a mouse model of HDM-induced allergic airway inflammation.

Results: General HDAC activity was greater in nasal epithelial cells of patients with AR and correlated inversely with epithelial integrity. Treatment of nasal epithelial cells with JNJ-26481585 restored epithelial integrity by promoting tight junction expression and protein reorganization. HDM-sensitized mice were treated with JNJ-26481585 to demonstrate the in vivo role of HDACs. Treated mice did not have allergic airway inflammation and had no bronchial hyperreactivity. Moreover, JNJ-26481585 treatment restored nasal mucosal function by promoting tight junction expression.

Conclusion: Our findings identify increased HDAC activity as a potential tissue-injury mechanism responsible for dysregulated epithelial cell repair, leading to defective epithelial barriers in AR. Blocking HDAC activity is a promising novel target for therapeutic intervention in patients with airway diseases.

Keywords: Allergic rhinitis; epigenetic changes; histone deacetylase; primary nasal epithelial cells; tight junctions.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comment in
Targeting histone deacetylases to restore epithelial barrier integrity: A new option for personalized medicine in patients with allergic airway disorders?
Georas SN.
J Allergy Clin Immunol. 2019 Nov;144(5):1172-1174. doi: 10.1016/j.jaci.2019.09.007. Epub 2019 Sep 23.
PMID: 31557501 No abstract available.
Cited by 4 articles
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11
Clinical Trial J Clin Invest
. 2019 Jul 30;129(10):4523-4538. doi: 10.1172/JCI128865.
Innate and Adaptive Nasal Mucosal Immune Responses Following Experimental Human Pneumococcal Colonization
Simon P Jochems 1 2, Karin de Ruiter 2, Carla Solórzano 1, Astrid Voskamp 2, Elena Mitsi 1, Elissavet Nikolaou 1, Beatriz F Carniel 1, Sherin Pojar 1, Esther L German 1, Jesús Reiné 1, Alessandra Soares-Schanoski 3, Helen Hill 1 4, Rachel Robinson 1 4, Angela D Hyder-Wright 1 4, Caroline M Weight 5, Pascal F Durrenberger 6, Robert S Heyderman 5, Stephen B Gordon 1 7, Hermelijn H Smits 2, Britta C Urban 8, Jamie Rylance 1, Andrea M Collins 1 4 9, Mark D Wilkie 4, Lepa Lazarova 1 4, Samuel C Leong 1 10, Maria Yazdanbakhsh 2, Daniela M Ferreira 1
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PMID: 31361601 PMCID: PMC6763269 DOI: 10.1172/JCI128865
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Abstract
Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Keywords: B cells; Bacterial infections; Immunology; Infectious disease.

Conflict of interest statement
Conflict of interest: The authors have declared that no conflict of interest exists.

Cited by 2 articles78 references7 figures
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12
Observational Study Otol Neurotol
. 2019 Oct;40(9):1139-1147. doi: 10.1097/MAO.0000000000002389.
Early Magnetic Resonance Imaging for Patients With Idiopathic Sudden Sensorineural Hearing Loss in an Emergency Setting
Giorgio Conte 1, Federica Di Berardino 2 3, Diego Zanetti 2 3, Elisabetta Francesca Iofrida 4, Elisa Scola 1, Sara Sbaraini 5, Eliana Filipponi 6, Claudia Cinnante 1, Lorenzo Maria Gaini 4, Umberto Ambrosetti 2 3, Fabio Triulzi 1 7, Lorenzo Pignataro 4 8, Pasquale Capaccio 4 8
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PMID: 31498290 DOI: 10.1097/MAO.0000000000002389
Abstract
Objective: The role of magnetic resonance (MR) imaging in idiopathic sudden sensorineural hearing loss (ISSHL) is controversial due to the inhomogeneity of clinical and MR protocols. The aim of this work is to relate early MR findings obtained immediately after the admission, with the clinical presentation, the audiological findings, and the outcomes of treatment.

Study design: Prospective observational study.

Setting: Tertiary referral university center.

Patients: Forty-seven patients (22 M, 25 F; age: 54.4 ± 17.5 yr) consecutively referred to the Department of Emergency for ISSHL.

Interventions: All patients underwent the diagnostic and therapeutic work-up for ISSHL, and MR imaging within 72 hours from the admission, independently of the symptoms onset. All patients received the same treatment (systemic steroid therapy, intratympanic steroid injection, and hyperbaric oxygen therapy).

Main outcome measure(s): MR patterns, clinical, and laboratory findings.

Results: MR imaging was positive in 25 of 47 cases (53%), with a perfect agreement between clinical and MR examinations (Cohen K = 1) upon the affected ear. Three different radiological patterns were observed: labyrinthine haemorrhage (n = 5), acute inflammatory process (n = 14), isolated blood-labyrinth barrier breakdown (n = 6). By binary logistic regression, only vertigo was associated with a positive MR imaging [B = 2.8; p = 0.011; OR = 9.5 (95% CI: 2.2-40.8)] and the latter was the only variable associated with an unfavorable outcome [(B = 2.8; p = 0.02 OR = 12.8 (95% CI: 2.9-56.7)].

Conclusion: Patients affected by ISSHL with associated vertigo show a higher likelihood of having a positive MR imaging, which, in turn, seems to predict an unfavorable outcome.

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13
J Allergy Clin Immunol
. 2019 Nov;144(5):1377-1390.e4. doi: 10.1016/j.jaci.2019.05.041. Epub 2019 Aug 9.
Dedicator of Cytokinesis Protein 2 Couples With Lymphoid Enhancer-Binding Factor 1 to Regulate Expression of CD21 and B-cell Differentiation
Yukai Jing 1, Danqing Kang 1, Luyao Liu 2, Huang Huang 3, Anwei Chen 4, Lu Yang 1, Panpan Jiang 1, Na Li 5, Heather Miller 6, Zheng Liu 7, Xiaofei Zhu 8, Jun Yang 9, Xiaochuan Wang 2, Jinqiao Sun 10, Zhiping Liu 11, Wanli Liu 12, Xinyuan Zhou 13, Chaohong Liu 14
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PMID: 31405607 DOI: 10.1016/j.jaci.2019.05.041
Abstract
Background: B-cell receptor (BCR) signaling, combined with CD19 and CD21 signals, imparts specific control of B-cell responses. Dedicator of cytokinesis protein 2 (DOCK2) is critical for the migration and motility of lymphocytes. Although absence of DOCK2 leads to lymphopenia, little is known about the signaling mechanisms and physiologic functions of DOCK2 in B cells.

Objective: We sought to determine the underlying molecular mechanism of how DOCK2 regulates BCR signaling and peripheral B-cell differentiation.

Methods: In this study we used genetic models for DOCK2, Wiskott-Aldrich syndrome protein (WASP), and lymphoid enhancer-binding factor 1 deficiency to study their interplay in BCR signaling and B-cell differentiation.

Results: We found that the absence of DOCK2 led to downregulation of proximal and distal BCR signaling molecules, including CD19, but upregulation of SH2-containing inositol 5 phosphatase 1, a negative signaling molecule. Interestingly, DOCK2 deficiency reduced CD19 and CD21 expression at the mRNA and/or protein levels and was associated with reduced numbers of marginal zone B cells. Additionally, loss of DOCK2 reduced activation of WASP and accelerated degradation of WASP, resulting into reduced actin accumulation and early activation of B cells. Mechanistically, the absence of DOCK2 upregulates the expression of lymphoid enhancer-binding factor 1. These differences were associated with altered humoral responses in the absence of DOCK2.

Conclusions: Overall, our study has provided a novel underlying molecular mechanism of how DOCK2 deficiency regulates surface expression of CD21, which leads to downregulation of CD19-mediated BCR signaling and marginal zone B-cell differentiation.

Keywords: B cell; B-cell receptor; CD21; Dedicator of cytokinesis protein 2; lymphoid enhancer–binding factor 1.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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14
Autophagy
. 2019 Jun;15(6):998-1016. doi: 10.1080/15548627.2019.1569926. Epub 2019 Feb 1.
Restoring Autophagic Flux Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Promoting TFEB Nuclear Translocation via Inhibiting MTOR
Bin Ye 1 2 3, Quan Wang 1 2 3, Haixia Hu 1 2 3, Yilin Shen 1 2 3, Cui Fan 1 2 3, Penghui Chen 2 3, Yan Ma 2 3, Hao Wu 2 3, Mingliang Xiang 1 2 3
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PMID: 30706760 PMCID: PMC6526833 DOI: 10.1080/15548627.2019.1569926
Free PMC article
Abstract
Macroautophagy/autophagy dysfunction is associated with many neurodegenerative diseases. TFEB (transcription factor EB), an important molecule that regulates lysosomal and autophagy function, is regarded as a potential target for treating some neurodegenerative diseases. However, the relationship between autophagy dysfunction and spiral ganglion neuron (SGN) degeneration and the role of TFEB in SGN degeneration has not yet been established. Here, we showed that in degenerated SGNs, induced by sensory epithelial cell loss in the cochlea of mice following kanamycin and furosemide administration, the lipofuscin area and oxidative stress level were increased, the nuclear-to-cytoplasmic TFEB ratio was decreased, and the late stage of autophagic flux was impaired. After autophagy dysfunction was partially ameliorated with an MTOR inhibitor, which promoted TFEB translocation into the nucleus from the cytoplasm, we found that the lysosomal deficits were significantly relieved, the oxidative stress level was reduced, and the density of surviving SGNs and auditory nerve fibers was increased. The results in the present study reveal that autophagy dysfunction is an important component of SGN degeneration, and TFEB may be a potential target for attenuating SGN degeneration following sensory epithelial cell loss in the cochlea of mice. Abbreviations: 3-NT: 3-nitrotyrosine; 4-HNE: 4-hydroxynonenal; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ABR: auditory brainstem response; APP: amyloid beta (A4) precursor protein; CLEAR: coordinated lysosomal expression and regulation; CTSB: cathespin B; CTSD: cathespin D; SAMR1: senescence-accelerated mouse/resistance 1; SAMP8: senescence-accelerated mouse/prone 8; MAPK1/ERK2: mitogen-activated protein kinase 1; MTOR: mechanistic target of rapamycin kinase; SGN: spiral ganglion neuron; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscope; TFEB: transcription factor EB.

Keywords: Autophagy dysfunction; MTOR pathway; TFEB; degeneration; oxidative stress; spiral ganglion neuron.

Cited by 4 articles72 references11 figures
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15
Observational Study J Clin Hypertens (Greenwich)
. 2019 Feb;21(2):280-290. doi: 10.1111/jch.13473. Epub 2019 Jan 22.
Relationships Between Cardiometabolic Disorders and Obstructive Sleep Apnea: Implications for Cardiovascular Disease Risk
Xiaolong Zhao 1 2 3, Xinyi Li 1 2 3, Huajun Xu 1 2 3, Yingjun Qian 1 2 3, Fang Fang 1 2 3, Hongliang Yi 1 2 3, Jian Guan 1 2 3, Shan Kai Yin 1 2 3
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PMID: 30667162 DOI: 10.1111/jch.13473
Free article
Abstract
Previous studies have reported the effects of obstructive sleep apnea (OSA) and cardiometabolic disorders on cardiovascular disease (CVD), but associations between cardiometabolic biomarkers and two cardinal features of OSA (chronic intermittent hypoxia and sleep fragmentation) and their interactions on CVD in OSA populations remain unclear. A total of 1727 subjects were included in this observational study. Data on overnight polysomnography parameters, biochemical biomarkers, and anthropometric measurements were collected. Metabolic syndrome (MS), including blood pressure, waist circumference (WC), fasting glucose, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), was diagnosed based on modified criteria of the Adult Treatment Panel III. WC, mean arterial pressure, TG and low-density lipoprotein cholesterol (LDL-C) were independently associated with apnea-hypopnea index (AHI) after adjustment for confounding factors (β = 0.578, P = 0.000; β = 0.157, P = 0.001; β = 1.003, P = 0.019; and β = 4.067, P = 0.0005, respectively). Furthermore, the interaction analysis revealed joint effects between hypertension, obesity, hyperglycemia, and LDL-C dyslipidemia and AHI on CVD. The relative excess risks of CVD due to the interactions with OSA were 2.06, 1.02, 0.48, and 1.42, respectively (all P < 0.05). In contrast, we found no independent effect of the microarousal index (MAI) on CVD. However, LDL-C level and some MS components (WC, TG) were associated with MAI. Our findings indicate that hypoxemia and cardiometabolic disorders in OSA may potentiate their unfavorable effects on CVD. Sleep fragmentation may indirectly predispose patients with OSA to an increased risk of CVD. Thus, cardiometabolic disorders and OSA synergistically influence cardiometabolic risk patterns.

Keywords: cardiovascular disease; dyslipidemia; metabolic syndrome; obstructive sleep apnea; sleep fragmentation.

©2019 Wiley Periodicals, Inc.

Cited by 1 article
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16
J Vestib Res
. 2019;29(5):253-260. doi: 10.3233/VES-190667.
Clinical Characteristics and Associated Factors of Canal Switch in Benign Paroxysmal Positional Vertigo
Geonho Lee 1, Seul-Gi Lee 1, Hee-Sung Park 1, Bong Jik Kim 1, Seong-Jun Choi 2, Jin Woong Choi 1
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PMID: 31256097 DOI: 10.3233/VES-190667
Abstract
Background: Canal switch benign paroxysmal positional vertigo (CS-BPPV) is a transition of BPPV involving one canal to another canal during or after canalith repositioning procedures (CRP).

Objective: To investigate the clinical characteristics of CS-BPPV and its associated factors.

Methods: The data of 2,303 patients with BPPV involving the lateral canal (LC) or posterior canal (PC) were retrospectively analyzed. Demographics, etiologies, and various clinical parameters related to CRP were compared between patients with and without CS-BPPV.

Results: Sixty-eight (2.95%) patients exhibited CS-BPPV. For patients with CS-BPPV from the PC to the LC, as well as those with CS-BPPV from the LC to the PC, the CRP number for the original canal in CS-BPPV was significantly greater than in non-CS-BPPV (P = 0.002). More CRP cycles were required to treat CS-BPPV than non-CS-BPPV involving the same canal. Multivariate analysis showed that CS-BPPV from the LC to the PC was significantly associated with multiple CRP cycles and use of the Gufoni maneuver (P = 0.038 and P < 0.001, respectively).

Conclusions: The use of multiple cycles of CRP and the Gufoni maneuver were significantly associated with the onset of CS-BPPV. Furthermore, more CRP cycles were needed for the treatment of CS-BPPV than for non-CS-BPPV involving the same canal.

Keywords: Benign paroxysmal positional vertigo; Gufoni maneuver; canal conversion; canal switch; canalith repositioning procedures.

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17
J Cell Physiol
. 2019 Dec;234(12):23763-23773. doi: 10.1002/jcp.28944. Epub 2019 Jun 7.
Olfactory Mucosa Stem Cells: An Available Candidate for the Treatment of the Parkinson's Disease
Sara Simorgh 1 2, Rafieh Alizadeh 3, Mina Eftekharzadeh 1, Seyed Mohammad Amin Haramshahi 2, Peiman Brouki Milan 2 4, Maryam Doshmanziari 1, Farnaz Ramezanpour 1, Mazaher Gholipourmalekabadi 4, Morteza Seifi 5, Fatemeh Moradi 1
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PMID: 31173364 DOI: 10.1002/jcp.28944
Abstract
Olfactory ectomesenchymal stem cells (OE-MSCs) possess the immunosuppressive activity and regeneration capacity and hold a lot of promises for neurodegenerative disorders treatment. This study aimed to determine OE-MSCs which are able to augment and differentiate into functional neurons and regenerate the CNS and also examine whether the implantation of OE-MSCs in the pars compacta of the substantia nigra (SNpc) can improve Parkinson's symptoms in a rat model-induced with 6-hydroxydopamine. We isolated OE-MSCs from lamina propria in olfactory mucosa and characterized them using flow cytometry and immunocytochemistry. The therapeutic potential of OE-MSCs was evaluated by the transplantation of isolated cells using a rat model of acute SN injury as a Parkinson's disease. Significant behavioral improvement in Parkinsonian rats was elicited by the OE-MSCs. The results demonstrate that the expression of PAX2, PAX5, PITX3, dopamine transporter, and tyrosine hydroxylase was increased by OE-MSCs compared to the control group which is analyzed with real-time polymerase chain reaction technique and immunohistochemical staining. In the outcome, the transplantation of 1,1'-dioctadecyl-3,3,3'3'-tetramethyl indocarbocyanine perchlorate labeled OE-MSCs that were fully differentiated to dopaminergic neurons contribute to a substantial improvement in patients with Parkinson's. Together, our results provide that using OE-MSCs in neurodegenerative disorders might lead to better neural regeneration.

Keywords: Parkinson's disease; ectomesenchymal stem cells; olfactory mucosa.

© 2019 Wiley Periodicals, Inc.

Cited by 1 article
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18
Meta-Analysis Thyroid
. 2018 Dec;28(12):1662-1673. doi: 10.1089/thy.2018.0244. Epub 2018 Nov 27.
A Systematic Review and Meta-Analysis of Subsequent Malignant Neoplasm Risk After Radioactive Iodine Treatment of Thyroid Cancer
Chi Yun Yu 1, Omar Saeed 2, Alyse S Goldberg 3, Shafaq Farooq 4, Rouhi Fazelzad 5, David P Goldstein 6, Richard W Tsang 7, James D Brierley 7, Shereen Ezzat 8, Lehana Thabane 9, Charlie H Goldsmith 9 10, Anna M Sawka 4
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PMID: 30370820 DOI: 10.1089/thy.2018.0244
Abstract
Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was updated comparing the risk of SMNs in TC patients treated with RAI to TC patients without RAI. Six electronic databases were searched (up to March, 2018), supplemented with a hand search. Two reviewers independently screened citations, reviewed full-text papers, and critically appraised/abstracted data. Random-effects meta-analyses were conducted using crude data and data statistically adjusted for confounders. The outcomes were any SMN and specific SMNs for which sufficient data were available. Results: In total, 3506 unique electronic search citations and 93 full-text papers were examined, including 17 studies (3 systematic reviews and 14 original studies). Published knowledge syntheses were limited by inclusion of small numbers of studies, with two systematic reviews suggesting an increased risk of any SMN and one meta-analysis suggesting a reduced risk of breast SMN after RAI treatment. In a meta-analysis of crude data, the risk ratio of any SMN in RAI-treated TC patients was 0.98 ([confidence interval (CI) 0.76-1.27]; n = 10 studies of 65,539 individuals, heterogeneity Q = 64.26, degrees of freedom [df] = 9, p < 0.001, I2 = 85.99). The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 ([CI 0.97-1.39]; n = 6 studies, data from at least 11,241 TC patients, Q = 10.86, df = 5, p = 0.054, I2 = 53.96). In secondary analyses examining specific SMNs, although relatively rare, the risk of subsequent leukemia was increased, but the risk of multiple myeloma was reduced in RAI-treated TC patients. There was no significant increased relative risk of breast cancer, salivary cancer, or combined hematologic malignancies according to RAI treatment status. Conclusions: The body of evidence on whether 131I treatment of thyroid cancer is associated with the primary outcome of any SMN is highly heterogeneous and complex. More research examining the long-term risk of specific SMNs after 131I treatment is needed.

Keywords: iodine radioisotopes; meta-analysis; radioactive iodine; subsequent malignant neoplasms; systematic review; thyroid cancer.

Cited by 5 articles
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19
Practice Guideline Otolaryngol Head Neck Surg
. 2020 Jan;162(1_suppl):S1-S38. doi: 10.1177/0194599819890327.
Clinical Practice Guideline: Nosebleed (Epistaxis)
David E Tunkel 1, Samantha Anne 2, Spencer C Payne 3, Stacey L Ishman 4, Richard M Rosenfeld 5, Peter J Abramson 6, Jacqueline D Alikhaani 7, Margo McKenna Benoit 8, Rachel S Bercovitz 9, Michael D Brown 10, Boris Chernobilsky 11, David A Feldstein 12, Jesse M Hackell 13, Eric H Holbrook 14, Sarah M Holdsworth 15, Kenneth W Lin 16, Meredith Merz Lind 17, David M Poetker 18, Charles A Riley 19, John S Schneider 20, Michael D Seidman 21 22 23, Venu Vadlamudi 24, Tulio A Valdez 25, Lorraine C Nnacheta 26, Taskin M Monjur 26
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PMID: 31910111 DOI: 10.1177/0194599819890327
Abstract
Objective: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds.

Purpose: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients.

Action statements: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

Keywords: epistaxis; hereditary hemorrhagic telangiectasia (HHT); nasal cautery; nasal packing; nosebleed.

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20
Observational Study Otol Neurotol
. 2019 Oct;40(9):1194-1198. doi: 10.1097/MAO.0000000000002364.
A Prospective Evaluation of Postoperative Opioid Use in Otologic Surgery
Z Jason Qian 1, Jennifer C Alyono 1 2, Ong-Dee Woods 2, Noor Ali 1, Nikolas H Blevins 1 2
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PMID: 31469798 PMCID: PMC7245047 DOI: 10.1097/MAO.0000000000002364
Free PMC article
Abstract
Objective: To prospectively evaluate opioid consumption following adult outpatient otologic surgery.

Study design: Prospective observational.

Setting: Single-tertiary referral center.

Patients: Patients scheduled for otologic surgery who did not have a history of chronic opioid use were recruited between February 2018 and February 2019.

Interventions and main outcome measures: Opioid consumption was queried using telephone or in-person surveys administered between postoperative days 5 and 15. Patient demographics, surgical details, and opioid prescription patterns were abstracted from medical records. Opioid distribution was determined by querying records maintained by the California Department of Justice through a state-wide prescription drug monitoring program mandated since 2016.

Results: Seventy patients were prescribed an average of 68.9 ± 31.8 mg of morphine equivalents (MME) and consumed 47.3 ± 42.9 MME over 2.4 ± 2.3 days postoperatively. Patients who received a postauricular incision were prescribed significantly more than those who underwent transcanal procedures (86.2 vs 55.9 MME; t test, p < 0.001), consumed significantly more (72.2 vs 28.6 MME; t test, p < 0.001), and for a significantly longer duration (3.4 vs 1.6 days; t test, p = 0.001). In the postauricular group, there was no significant difference in consumption between mastoidectomy and nonmastoidectomy subgroups (64.9 vs 89.2 MME; t test, p = 0.151). Eighty percent of transcanal patients consumed 50 MME (10 pills) or less, while 80% of postauricular patients consumed 80 MME (16 pills) or less.

Conclusions: Patients in our cohort consumed approximately 3/4 of the prescribed opioids. Those with postauricular incisions used significantly more than those with transcanal incisions. Postoperative opioid prescription recommendations should be tailored according to the extent of surgery.

Conflict of interest statement
The authors disclose no conflicts of interest.

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21
J Allergy Clin Immunol
. 2019 Oct;144(4):993-1003.e12. doi: 10.1016/j.jaci.2019.06.042. Epub 2019 Jul 19.
Hypomethylation of the IL8 Promoter in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis With Nasal Polyps
Jingyun Li 1, Jian Jiao 1, Ming Wang 1, Yunbo Gao 1, Ying Li 1, Yang Wang 1, Yuan Zhang 2, Xiangdong Wang 3, Luo Zhang 4
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PMID: 31330222 DOI: 10.1016/j.jaci.2019.06.042
Abstract
Background: IL-8 is an important chemokine implicated in the pathogenesis of chronic rhinosinusitis (CRS), but little is known about epigenetic regulation of IL8 in the pathogenesis of CRS.

Objective: We sought to investigate the relationship between the DNA methylation level in the IL8 proximal promoter and CRS in Han Chinese subjects.

Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP; n = 187), patients with chronic rhinosinusitis without nasal polyps (CRSsNP; n = 89), and control subjects (n = 57) were enrolled in 2 independent cohorts. Purified human nasal epithelial cells from each participant were assessed for percentage DNA methylation of CpG sites in the IL8 proximal promoter by using bisulfite pyrosequencing and for functional aspects of methylation status by using in vitro assays.

Results: DNA methylation of CpG sites 1, 2, and 3, respectively, in the IL8 proximal promoter was significantly decreased in human nasal epithelial cells of patients with CRSwNP compared with that in patients with CRSsNP (P < .001) and control subjects (P < .001). Percentage of DNA methylation of the CpG3 site was correlated negatively with both tissue eosinophilic cationic protein (P < .01) and myeloperoxidase (P < .05) levels. IL-1β (P < .001) and TNF-α (P < .01) significantly increased IL8 expression accompanied by a reduction in methylation at the CpG3 site (P < .001). Electrophoretic mobility shift assays demonstrated that methylation status of CpG3 changed the binding of octamer-binding transcription factor 1 and nuclear factor κB.

Conclusion: Decreased DNA methylation of particularly CpG sites in the IL8 proximal promoter might play a role in the pathogenesis of CRSwNP.

Keywords: Chronic rhinosinusitis; DNA methylation; Han Chinese; IL-8 proximal promoter; Octamer-binding transcription factor 1; human nasal epithelial cells; nuclear factor κB.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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22
Epigenetics Chromatin
. 2019 Jun 13;12(1):35. doi: 10.1186/s13072-019-0283-8.
Aberrant Methylation-Mediated Downregulation of lncRNA SSTR5-AS1 Promotes Progression and Metastasis of Laryngeal Squamous Cell Carcinoma
Baoshan Wang 1, Lei Zhao 2, Weiwei Chi 3, Huan Cao 2, Weina Cui 2, Wenxia Meng 2
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PMID: 31196171 PMCID: PMC6563380 DOI: 10.1186/s13072-019-0283-8
Free PMC article
Abstract
Background: Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited.

Results: In the present study, we screen expression profiles of lncRNAs in advanced LSCC patients with paired tumor tissues and corresponding normal tissues by microarrays. We identify numerous differentially expressed transcripts, and after the necessary verification of the transcripts expression in expanded samples, we experimentally validate the expression patterns of the remarkable low expressed gene, SSTR5, and its antisense lncRNA, SSTR5-AS1. Downregulation of SSTR5 is detected in LSCC tissues and laryngeal carcinoma cells. Aberrant DNA hypermethylation of the CpG sites clustered in the exon 1 and accumulation of inactive histone modifications at SSTR5 promoter region may be epigenetic mechanisms for its inactivation in LSCC. SSTR5-AS1 may play antitumor role in LSCC and may be regulated by the hypermethylation of the same CpG sites with SSTR5. SSTR5-AS1 inhibits laryngeal carcinoma cells proliferation, migration, and invasion. SSTR5-AS1 increases the enrichment of MLL3 and H3K4me3 at the promoter region of SSTR5 by interacting with MLL3 and further induces the transcription of SSTR5. Furthermore, SSTR5-AS1 interacts with and recruits TET1 to its target gene E-cadherin to activate its expression.

Conclusion: These findings suggest that the identified lncRNAs and mRNAs may be potential biomarkers in metastatic LSCC, and SSTR5-AS1 may act as a tumor suppressor as well as a potential biomarker for antitumor therapy.

Keywords: Expression; Laryngeal squamous cell carcinoma; Methylation; SSTR5; SSTR5-AS1.

Conflict of interest statement
The authors declare that they have no competing interests.

Cited by 3 articles43 references6 figures
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23
Practice Guideline Otolaryngol Head Neck Surg
. 2020 Apr;162(2_suppl):S1-S55. doi: 10.1177/0194599820909438.
Clinical Practice Guideline: Ménière's Disease
Gregory J Basura 1, Meredith E Adams 2, Ashkan Monfared 3, Seth R Schwartz 4, Patrick J Antonelli 5, Robert Burkard 6, Matthew L Bush 7, Julie Bykowski 8, Maria Colandrea 9, Jennifer Derebery 10, Elizabeth A Kelly 11, Kevin A Kerber 1, Charles F Koopman 12, Amy Angie Kuch 13, Evie Marcolini 14, Brian J McKinnon 15, Michael J Ruckenstein 16, Carla V Valenzuela 17, Alexis Vosooney 18, Sandra A Walsh 19, Lorraine C Nnacheta 20, Nui Dhepyasuwan 20, Erin M Buchanan 20
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PMID: 32267799 DOI: 10.1177/0194599820909438
Abstract
Objective: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies.

Purpose: The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

Keywords: Meniett device; electrocochleography; endolymphatic hydrops; endolymphatic sac decompression; fluctuating aural symptoms; gentamicin; labyrinthectomy; quality of life; sensorineural hearing loss; sodium-restricted diet; vestibular testing.

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24
Comparative Study Otol Neurotol
. 2019 Oct;40(9):1160-1166. doi: 10.1097/MAO.0000000000002366.
Matched Cohort Comparison Indicates Superiority of Precurved Electrode Arrays
Jourdan T Holder 1, Robert J Yawn 2, Ashley M Nassiri 2, Robert T Dwyer 1, Alejandro Rivas 2, Robert F Labadie 2, René H Gifford 1
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PMID: 31469799 PMCID: PMC6999087 (available on 2020-10-01) DOI: 10.1097/MAO.0000000000002366
Free PMC article
Abstract
Objective: Characterize differences in adult cochlear implant outcomes and programming parameters for a straight (CI422/522) and a precurved (CI532) electrode array.

Setting: Cochlear implant (CI) program at a tertiary otologic center.

Patients: Fifty-eight adults were included in the study; 29 were implanted with CI422 or CI522 and 29 were implanted with CI532. Each CI532 recipient was matched to a CI422/522 recipient in terms of age and preoperative hearing thresholds for comparison purposes.

Main outcome measures: Consonant-Nucleus-Consonant (CNC) words, AzBio sentences, residual audiometric thresholds, and Speech Spatial Qualities (SSQ) questionnaire collected 6 months postoperatively were used to characterize outcomes. Pulse duration, maxima, impedances, and overall charge measurements were used to characterize programming parameters.

Results: Postoperative unaided low frequency pure-tone average (LFPTA) was significantly better for the CI532 group. CNC scores were significantly better for the CI532 group. Impedances and pulse duration were significantly lower for the CI532 group, but there was no difference in overall charge between the groups.

Conclusion: The CI532 group showed either similar or statistically superior results on all measures when compared with the CI422/522 suggesting that the CI532 electrode may be an advantageous substitute for the CI522.

Cited by 1 article
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25
Proc Biol Sci
. 2019 Nov 20;286(1915):20192199. doi: 10.1098/rspb.2019.2199. Epub 2019 Nov 13.
Intraspecific Male Combat Behaviour Predicts Morphology of Cervical Vertebrae in Ruminant Mammals
Abby Vander Linden 1, Elizabeth R Dumont 2
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PMID: 31718495 PMCID: PMC6892039 (available on 2020-11-20) DOI: 10.1098/rspb.2019.2199
Free PMC article
Abstract
Cranial weapons of all shapes and sizes are common throughout the animal kingdom and are frequently accompanied by the evolution of additional traits that enhance the use of those weapons. Bovids (cattle, sheep, goats, antelope) and cervids (deer) within the mammal clade Ruminantia are particularly well known for their distinct and varied cranial appendages in the form of horns and antlers, which are used as weapons in intraspecific combat between males for access to mates. Combat in these species takes many forms, including head-on collisions (ramming); stabbing an opponent's head or body with horn tips (stabbing); rearing and clashing downwards with horns (fencing); or interlocking antlers or horns while vigorously pushing and twisting (wrestling). Some aspects of weapon and skull morphology have been linked to combat behaviours in bovid and cervid species, but the contribution of postcranial structures that support these weapons, such as the neck, has not been explored. To investigate the role of the neck in intraspecific combat, we quantified biomechanically relevant linear variables of the cervical vertebrae (C1-C7) from males and females of 55 ruminant species. We then used phylogenetic generalized least-squares regression to assess differences among species that display primarily ramming, stabbing, fencing and wrestling combat styles. In males, we found that wrestlers have longer vertebral centra and longer neural spines than rammers, stabbers or fencers, while rammers have shorter and wider centra and taller neural spine lever arms. These results suggest a supportive role for the cervical vertebrae in resisting forces generated by male-male combat in ruminant mammals and indicate that evolutionary forces influencing cranial weapons also play a role in shaping the supporting anatomical structures.

Keywords: behaviour; cervical vertebrae; evolution; mammals; morphology; sexually selected weapons.

Conflict of interest statement
We declare we have no competing interests.

Cited by 1 article
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26
Cell Rep
. 2019 Apr 16;27(3):860-871.e8. doi: 10.1016/j.celrep.2019.03.072.
Overlapping Activities of Two Neuronal Splicing Factors Switch the GABA Effect From Excitatory to Inhibitory by Regulating REST
Yoko Nakano 1, Susan Wiechert 1, Botond Bánfi 2
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PMID: 30995482 PMCID: PMC6556397 DOI: 10.1016/j.celrep.2019.03.072
Free PMC article
Abstract
A truncating mutation in the mouse Srrm4 gene, which encodes a neuronal splicing factor, causes alternative splicing defects selectively in the ear. The mechanism by which splicing is preserved in the brain of these mice is not known. Here, we show that SRRM3 limits the Srrm4 mutation-associated defects to the ear and that, in cortical neurons, overlapping SRRM3-SRRM4 activity regulates the development of interneuronal inhibition. In vitro, SRRM3 and SRRM4 regulate the same splicing events, but a mutation in mouse Srrm3 causes tremors and mild defects in neuronal alternative splicing, demonstrating unique SRRM3 roles in vivo. Mice harboring mutations in both Srrm3 and Srrm4 die neonatally and exhibit severe splicing defects. In these mice, splicing alterations prevent inactivation of the gene repressor REST, which maintains immature excitatory GABAergic neurotransmission by repressing K-Cl cotransporter 2. Thus, our data reveal that SRRM3 and SRRM4 act redundantly to regulate GABAergic neurotransmission by inactivating REST.

Keywords: GABA-A receptor; GABAergic neurotransmission; KCC2; REST; SRRM3; SRRM4; alternative splicing; calcium imaging; gene expression regulation; neuronal development.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Conflict of interest statement
DECLARATION OF INTERESTS

The authors declare no competing interests.

6 figures
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27
Comment Lancet Oncol
. 2019 Sep;20(9):1195-1196. doi: 10.1016/S1470-2045(19)30484-X. Epub 2019 Jul 24.
Palbociclib: A New Partner for Cetuximab?
Garth W Strohbehn 1, Everett E Vokes 2
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PMID: 31351868 DOI: 10.1016/S1470-2045(19)30484-X
Comment on
Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial.
Adkins D, Ley J, Neupane P, Worden F, Sacco AG, Palka K, Grilley-Olson JE, Maggiore R, Salama NN, Trinkaus K, Van Tine BA, Steuer CE, Saba NF, Oppelt P.
Lancet Oncol. 2019 Sep;20(9):1295-1305. doi: 10.1016/S1470-2045(19)30405-X. Epub 2019 Jul 24.
PMID: 31351869
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28
Plast Reconstr Surg Glob Open
. 2019 Dec 30;7(12):e2573. doi: 10.1097/GOX.0000000000002573. eCollection 2019 Dec.
Physical and Visual Characteristics of the Neck Predicting Gender Perception
Ofer Amir 1 2, Kim Shemer 1 2, Ilan Roziner 1 2, Adi Primov-Fever 2 3
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PMID: 32537312 PMCID: PMC7288875 DOI: 10.1097/GOX.0000000000002573
Free PMC article
Abstract
The association between neck characteristics (physical and visual) and the perception of gender is unclear. This association is critical, especially when the perception of the speakers' gender is of interest, such as in transgender patients. This study was the first to provide basic empirical data on this association among cisgender men and women.

Methods: The necks of 30 adult men and women were measured physically and then photographed and evaluated visually by a group of 10 judges. These judges also evaluated voice recordings of the same speakers. Another group of 124 judges rated the visual and auditory masculinity/femininity of the necks and the voices.

Results: While most physical measures of the neck were larger for men, neck-length did not significantly differ between genders. A stepwise multiple regression model revealed that the single physical measure that consistently differed between genders was neck-girth (P < 0.0001). The single visual-appearance measure that consistently differed between genders was thyroid-protrusion (P = 0.0003). Neck-girth was the only physical characteristic that significantly correlated with gender differences in voice. Furthermore, the size of the thyroid prominence (ie, Adam's apple) was not associated with gender differences in voice.

Conclusions: Neck characteristics (both physical and visual) are significantly associated with the perception of gender. While larger necks are typically perceived as masculine, neck-length is neither associated with gender nor with the speaker's voice characteristics. These findings highlight the importance of examining various physical and visual characteristics of the neck, when considering a feminization confirmation procedure for transgender patients.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.

Conflict of interest statement
Disclosure: The authors have no financial interest to declare in relation to the content of this article.

18 references
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29
Observational Study Respirology
. 2019 Aug;24(8):758-764. doi: 10.1111/resp.13520. Epub 2019 Mar 18.
Multidisciplinary Team Clinic for Vocal Cord Dysfunction Directs Therapy and Significantly Reduces Healthcare Utilization
Malcolm Baxter 1, Laurence Ruane 2 3, Debra Phyland 1, Elizabeth Leahy 2, Emily Heke 2, Kenneth K Lau 4, Kathy Low 2 3, Kais Hamza 5, Martin MacDonald 2 3, Philip G Bardin 2 3
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PMID: 30884033 DOI: 10.1111/resp.13520
Abstract
Background and objective: Multidisciplinary team (MDT) clinics use an integrated approach to individualize care of complex medical conditions. Vocal cord dysfunction (VCD) is a challenging condition that is likely to benefit from MDT clinics but this has not been researched.

Methods: A prospective observational cohort study of a novel VCD MDT clinic was conducted in patients with suspected VCD. Relevant questionnaires, medical history, physical examination, spirometry, dynamic computerized tomography (CT) larynx and laryngoscopy were utilized and patients were allocated to treatment pathways depending on putative diagnosis. Speech pathology intervention with laryngeal retraining (LR) was offered and if LR therapy failed botulinum toxin injection was offered. Primary outcome was reductions in healthcare utilization.

Results: Overall, 80 consecutive patients were included in analyses. A definitive diagnosis of VCD was made in 56 of 80 (70%) patients. After LR (n = 35), emergency department (ED)/hospital admissions declined significantly in the subsequent 12 months (P = 0.001). General practice visits also reduced (P < 0.001). Botulinum toxin injections were administered in 21 patients unresponsive to LR therapy and both general practice and ED/hospital visits declined (P < 0.001 and P = 0.01, respectively) after injection.

Conclusion: A multidisciplinary approach to VCD confers benefit and can be used to allocate appropriate management leading to a reduction in healthcare utilization.

Keywords: asthma; dysfunctional breathing; multidisciplinary team clinic; paradoxical vocal cord movement; vocal cord dysfunction.

© 2019 Asian Pacific Society of Respirology.

Comment in
Multidisciplinary team working for vocal cord dysfunction: Now it's GO time.
Hull JH.
Respirology. 2019 Aug;24(8):714-715. doi: 10.1111/resp.13560. Epub 2019 Apr 11.
PMID: 30977222 No abstract available.
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30
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):797-799. doi: 10.1177/0194599820919741. Epub 2020 Apr 14.
A Commentary on Safety Precautions for Otologic Surgery During the COVID-19 Pandemic
Robert A Saadi 1, Darrin V Bann 1, Vijay A Patel 1, David Goldenberg 1, Jason May 1, Huseyin Isildak 1
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PMID: 32286916 DOI: 10.1177/0194599820919741
Abstract
There are insufficient data regarding the safety of otologic procedures in the setting of the coronavirus disease 2019 (COVID-19) pandemic. Given the proclivity for respiratory pathogens to involve the middle ear and the significant aerosolization associated with many otologic procedures, safety precautions should follow current recommendations for procedures involving the upper airway. Until preoperative diagnostic testing becomes standardized and readily available, elective cases should be deferred and emergent/urgent cases should be treated as high risk for COVID-19 exposure. Necessary otologic procedures on positive, suspected, or unknown COVID-19 status patients should be performed using enhanced personal protective equipment, including an N95 respirator and eye protection or powered air-purifying respirator (PAPR, preferred), disposable cap, disposable gown, and gloves. Powered instrumentation should be avoided unless absolutely necessary, and if performed, PAPR or sealed eye protection is recommended.

Keywords: COVID-19; coronavirus; exposure; otology; safety precautions.

Cited by 2 articles
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31
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):25-30. doi: 10.1097/MOO.0000000000000598.
Latest Developments on Topical Therapies in Chronic Rhinosinusitis
Neil C W Tan 1 2, Alkis J Psaltis 3
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PMID: 31789928 DOI: 10.1097/MOO.0000000000000598
Abstract
Purpose of review: Topical therapies play an important role in the management of chronic rhinosinusitis (CRS). A detailed literature review was undertaken to appraise recent evidence surrounding current topical therapies and novel treatments used in the setting of recalcitrant CRS.

Recent findings: Effective sinus surgery aids in the delivery of topical therapies. Budesonide nasal rinses delivered by saline irrigation offer clinical and symptomatic improvements pre and postoperatively with a well-proven safety profile. Topical steroids may additionally offer direct antibacterial effects as per in-vitro testing. Topical antibiotics are not recommended in routine practice; however, they may be of benefit for short-term eradication therapy. Novel treatments are under keen investigation and include bacteriophage, colloidal silver and manuka honey. The evidence base for these treatments is not robust enough to recommend their routine use at present.

Summary: Topical steroids delivered in conjunction with saline nasal irrigation offer the best combination of treatments in CRS and should be considered a standard of care. Wide surgical access and aggressive surgical debridement of polyposis facilitates the delivery of steroid irrigations to sinonasal mucosa and is associated with improved long-term outcomes following endoscopic sinus surgery. The use of novel treatments remains within the research setting alone.

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32
Eur Arch Otorhinolaryngol
. 2020 Jul;277(7):2133-2135. doi: 10.1007/s00405-020-05982-0. Epub 2020 Apr 22.
Tracheostomy in the COVID-19 Pandemic
Francesco Mattioli 1, Matteo Fermi 2, Michael Ghirelli 2, Gabriele Molteni 3, Nicola Sgarbi 4, Elisabetta Bertellini 4, Massimo Girardis 4, Livio Presutti 2, Andrea Marudi 4
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PMID: 32322959 PMCID: PMC7174541 DOI: 10.1007/s00405-020-05982-0
Free PMC article
Abstract
Purpose: The role of tracheostomy in COVID-19-related ARDS is unknown. Nowadays, there is no clear indication regarding the timing of tracheostomy in these patients.

Methods: We describe our synergic experience between ENT and ICU Departments at University Hospital of Modena underlining some controversial aspects that would be worth discussing tracheostomies in these patients. During the last 2 weeks, we performed 28 tracheostomies on patients with ARDS due to COVID-19 infection who were treated with IMV.

Results: No differences between percutaneous and surgical tracheostomy in terms of timing and no case of team virus infection.

Conclusion: In our experience, tracheostomy should be performed only in selected patients within 7- and 14-day orotracheal intubation.

Keywords: COVID-19; Invasive mechanic ventilation; Tracheostomy.

Conflict of interest statement
The authors declare that they have no conflict of interest.

Cited by 1 article7 references
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33
Aust J Gen Pract
. 2019 May;48(5):289-293. doi: 10.31128/AJGP-09-18-4719.
Paediatric Neck Lumps: An Approach for the Primary Physician
Aaron Smith 1, Matthew Cronin 2
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PMID: 31129940 DOI: 10.31128/AJGP-09-18-4719
Free article
Abstract
Background: Paediatric cervical masses are a common presentation in general practice causing significant parental anxiety and a potential diagnostic dilemma. While these masses are commonly benign, a broad array of diagnostic possibilities exist. Sound knowledge of relevant anatomy and asystematic approach in history, examination and investigations are crucial to ensure appropriate assessment and management.

Objectives: The aims of this article are to review thecommon and red flag causes of paediatric neck masses and to provide apragmatic approach to assessment and management in general practice.

Discussion: While paediatric neck lumps encountered in general practice are most commonly benign, a number of aetiologies require further investigation and aggressive management. A focused history and examination is crucial to ensure red flag conditions are not missed while avoiding unwarranted investigation and parental anxiety.

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34
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):18-24. doi: 10.1097/MOO.0000000000000594.
Updates on Current Evidence for Biologics in Chronic Rhinosinusitis
Melina S Nasta 1, Vasileios A Chatzinakis 1, Christos C Georgalas 2 3
Affiliations expand
PMID: 31789925 DOI: 10.1097/MOO.0000000000000594
Abstract
Purpose of review: The purpose of this review is to present the most important recent developments concerning biologics as a therapeutic option for chronic rhinosinusitis (CRS).

Recent findings: mAb anti-IL-4 receptor α (Dupilumab) was recently approved by Food and Drug Administration (FDA) for patients with CRSwNP and four other biologics are under investigation, with promising preliminary results.

Summary: CRS is a disease associated with a significant symptom burden and high-indirect costs. Despite recent advances in combined approaches, persistent symptoms or recurrences are not uncommon. Monoclonal antibodies, used mainly to treat asthma, have recently been shown to have a positive impact on controlling the symptoms of CRS and reducing the need for endoscopic sinus surgery. Dupilumab, mepolizumab, reslizumab, benralizumab and omalizumab are discussed and their mechanism of action, risk and current evidence on efficacy are presented. Preliminary studies show encouraging results with relatively few side effects. Once the high cost of such therapies is addressed, they could prove an important adjuvant therapy for patients with CRS. Large-scale clinical trials designed to evaluate them are called for.

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35
J Microbiol Methods
. 2019 Aug;163:105653. doi: 10.1016/j.mimet.2019.105653. Epub 2019 Jun 11.
Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Helicobacter Pylori Detection
Saori Horiuchi 1, Ryuichi Nakano 2, Akiyo Nakano 2, Naokuni Hishiya 3, Kenji Uno 4, Yuki Suzuki 2, Ayako Tanouchi 2, Naoki Kakuta 2, Takashi Masui 5, Noriko Jojima 6, Hisakazu Yano 2
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PMID: 31199937 DOI: 10.1016/j.mimet.2019.105653
Abstract
Infection with cagA-positive Helicobacter pylori is associated with gastric cancer. Molecular techniques are vital for accurate H. pylori diagnosis. We developed a loop-mediated isothermal amplification (LAMP) for detecting the H. pylori cagA gene and evaluated its use for clinical diagnosis. A LAMP primer set was designed to recognize the homologous regions of cagA gene sequences of 6 H. pylori strains. LAMP sensitivity was evaluated with serial dilutions of H. pylori ATCC 43504 and fecal specimens; specificity was evaluated with H. pylori ATCC 49396 and CIP 104086. The LAMP sensitivity for H. pylori specimens was 10-1 cfu/tube (reaction time, 37 min), which was 10-fold more sensitive than polymerase chain reaction. LAMP was also highly sensitive and rapid for fecal specimens. It detected cagA gene from ATCC 49396 and CIP 104086. The findings suggest LAMP can be used for diagnosing and screening of H. pylori infections to decrease gastric cancer incidence.

Keywords: Helicobacter pylori; Loop-mediated isothermal amplification; Rapid detection.

Copyright © 2019 Elsevier B.V. All rights reserved.

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36
J Vestib Res
. 2019;29(6):295-307. doi: 10.3233/VES-190688.
Estimating Loss of Canal Function in the Video Head Impulse Test (vHIT)
Kamran Barin 1
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PMID: 31868701 DOI: 10.3233/VES-190688
Abstract
Background: The vestibulo-ocular reflex (VOR) gain is the primary parameter for quantifying and interpreting the video head impulse test (vHIT). Yet, the relationship between the VOR gain and the extent of canal function is not clear.

Objective: The goal of this paper was to determine if the loss of canal function in vHIT can be estimated from the VOR gain.

Methods: A model of the VOR was developed that included linear components for the cupula and the velocity storage mechanism as well as nonlinear components for the vestibular nerve and the vestibular nuclei. Multiple simulations were carried out as the level of function for the right and left VOR pathways was varied systematically over their entire range.

Results: Simulation results were similar to the typical findings in normal individuals as well as in patients with unilateral and bilateral loss of canal function. Based on these simulations, a relationship between the canal function and the VOR gains was established. This relationship was surprisingly independent of most model parameters.

Conclusions: The sum of right and left VOR gains (or 2 times the mean of VOR gains) at a given head velocity is an estimate of the total function of the involved canals. This simple formula can estimate the loss of canal function in purely unilateral lesions. For bilateral lesions, the same formula can estimate the total loss of bilateral function but contributions from individual canals cannot be determined without additional information.

Keywords: Head impulse test; VOR Gain; vestibular loss; vestibulo-ocular reflex (VOR).

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37
Otol Neurotol
. 2019 Oct;40(9):1208-1216. doi: 10.1097/MAO.0000000000002345.
Intraoperative Electrocochleography in Patients With Menière's Disease Undergoing Endolymphatic Sac Decompression and Shunt Surgery
Jameson K Mattingly 1, Kevin Y Zhan 1, Meghan M Hiss 1, Michael S Harris 2, Edward E Dodson 1, Aaron C Moberly 1, Oliver F Adunka 1, William J Riggs 1
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PMID: 31469786 DOI: 10.1097/MAO.0000000000002345
Abstract
Hypothesis: Objective physiologic changes measured using electrocochleography at the round window (ECOG) are observable during endolymphatic sac decompression and shunt surgery (ELS).

Background: Limited effective treatment options are available to patients with Menière's disease (MD) who have failed conservative management, experience persistent vertigo symptoms, and have substantial residual hearing. ELS is a feasible therapeutic option for these patients. However, the efficacy of this procedure has been questioned, and objective measures assessing inner ear physiologic alterations are lacking.

Methods: ECOG was measured in patients with MD undergoing ELS. Stimuli consisted of tone bursts (250, 500, 1000, 2000, 4000 Hz) and 100 μs broadband clicks at various intensities (60-90 dB nHL). Cochlear microphonic (CM), summation potential (SP), compound action potential (AP), SP:AP ratio, and CM harmonic distortions were measured.

Results: ECOG was completed in 18 patients. The mean SP magnitude at 500 Hz changed significantly from -7.1 μV before to -5.1 μV after ELS (p < 0.05). However, the mean SP:AP ratio in those tested (n = 13) did not significantly change after ELS. CM harmonic magnitudes remained unchanged from pre- to post-ELS (n = 12) across all frequencies.

Conclusion: ECOG allows detection of acute electrophysiological changes in the cochlea. However, our results indicate only small objective changes in the low-frequency SP magnitude (500 Hz) immediately after ELS, but not in other frequencies or measures tested (CM, SP:AP, CM harmonic distortions). These results suggest minimal electrophysiological changes occur in the cochlea as a result of ELS.

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38
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):783-794. doi: 10.1177/0194599820921393. Epub 2020 Apr 28.
Best Practice Recommendations for Pediatric Otolaryngology During the COVID-19 Pandemic
Darrin V Bann 1, Vijay A Patel 1, Robert Saadi 1, Neerav Goyal 1, John P Gniady 1, Johnathan D McGinn 1, David Goldenberg 1, Huseyin Isildak 1, Jason May 1, Meghan N Wilson 1
Affiliations expand
PMID: 32340588 DOI: 10.1177/0194599820921393
Abstract
Objective: To review the impact of coronavirus disease 2019 (COVID-19) on pediatric otolaryngology and provide recommendations for the management of children during the COVID-19 pandemic.

Data sources: Clinical data were derived from peer-reviewed primary literature and published guidelines from national or international medical organizations. Preprint manuscripts and popular media articles provided background information and illustrative examples.

Methods: Included manuscripts were identified via searches using PubMed, MEDLINE, and Google Scholar, while organizational guidelines and popular media articles were identified using Google search queries. Practice guidelines were developed via consensus among all authors based on peer-reviewed manuscripts and national or international health care association guidelines. Strict objective criteria for inclusion were not used due to the rapidly changing environment surrounding the COVID-19 pandemic and a paucity of rigorous empirical evidence.

Conclusions: In the face of the COVID-19 pandemic, medical care must be judiciously allocated to treat the most severe conditions while minimizing the risk of long-term sequelae and ensuring patient, physician, and health care worker safety.

Implications for practice: The COVID-19 pandemic will have a profound short- and long-term impact on health care worldwide. Although the full repercussions of this disease have yet to be realized, the outlined recommendations will guide otolaryngologists in the treatment of pediatric patients in the face of an unprecedented global health crisis.

Keywords: COVID-19; SARS-CoV-2; otolaryngology; pediatric otolaryngology.

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39
Observational Study Disaster Med Public Health Prep
. 2019 Dec;13(5-6):849-852. doi: 10.1017/dmp.2018.162.
Riots in Beirut: Description of the Impact of a New Type of Mass Casualty Event on the Emergency System in Lebanon
Mohamad El Warea 1, Roula Sasso 1, Rana Bachir 1, Mazen El Sayed 1 2
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PMID: 31169114 DOI: 10.1017/dmp.2018.162
Abstract
Introduction: In the summer of 2015, Beirut experienced a garbage crisis that led to rioting. Riot control measures resulted in multiple casualties. This study examines injury patterns of riot victims presenting to the emergency department of a tertiary care center in a developing country.

Methods: A retrospective study was conducted in the emergency department of the American University of Beirut Medical Center between August 22 and August 30, 2015. Patients seen in the emergency department with riot injuries were included. Patient characteristics, injuries, and resources utilized in the emergency department were analyzed.

Results: Ninety-five patients were identified. Most patients presented to the emergency department within a short time period. The mean age of the patients was 28.0 ± 8.7 years. Most (90.5%) of the patients were males and 92.6% were protestors. Emergency medical services were utilized by 41.0% of patients. Laceration was the most common presenting complaint (28.5%), and blunt trauma was the most common type of injury (50.5%). The head/face/neck was the most common injured body region (55.8%). Most patients did not require blood tests or procedures (91.6% and 61.0%, respectively), and 91.2% of patients were treated in the emergency department and discharged. One patient required intensive care unit admission and another was dead on arrival.

Conclusions: Most patients had mild injuries on presentation. The emergency department experienced a high influx of patients. Complications and deaths can occur from seemingly nonlethal weapons used during riots and warrant effective prehospital and hospital disaster planning.

Keywords: emergency medicine; mass casualty; prehospital care; riot.

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40
J Biophotonics
. 2019 Apr;12(4):e201800265. doi: 10.1002/jbio.201800265. Epub 2019 Jan 6.
Photoacoustic and Fluorescent Effects in Multilayer Plasmon-Dye Interfaces
Marina V Novoselova 1, Daniil N Bratashov 2, Mustafa Sarimollaoglu 3, Dmitry A Nedosekin 3, Walter Harrington 3, Alex Watts 3, Mikyung Han 3, Boris N Khlebtsov 2 4, Ekaterina I Galanzha 2 3, Dmitry A Gorin 1, Vladimir P Zharov 2 3
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PMID: 30511464 DOI: 10.1002/jbio.201800265
Abstract
Progress in understanding the cell biology and diseases depends on advanced imaging and labeling techniques. Here, we address this demand by exploring novel multilayered nanocomposites (MNCs) with plasmonic nanoparticles and absorbing dyes in thin nonabsorbing shells as supercontrast multimodal photoacoustic (PA) and fluorescent agents in the near-infrared range. The proof of concept was performed with gold nanorods (GNRs) and indocyanine green (ICG) dispersed in a matrix of biodegradable polymers. We demonstrated synergetic PA effects in MNCs with the gold-ICG interface that could not be achieved with ICG and GNRs alone. We also observed ultrasharp PA and emission peaks that could be associated with nonlinear PA and spaser effects, respectively. Low-toxicity multimodal MNCs with unique plasmonic, thermal and acoustic properties have the potential to make a breakthrough in PA flow cytometry and near-infrared spasers in vivo by using the synergetic interaction of plasmonic modes with a nearby absorbing medium.

Keywords: biocompatible polymers; fluorescence; fluorescence quenching; gold nanorods; in vivo flow cytometry; indocyanine green; multilayer composite; photoacoustic effect.

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cited by 3 articles
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41
Otol Neurotol
. 2019 Oct;40(9):1230-1236. doi: 10.1097/MAO.0000000000002346.
Involvement of the Cochlear Aqueduct by Jugular Paraganglioma Is Associated With Sensorineural Hearing Loss
Neil S Patel 1, Michael J Link 1 2, Colin L W Driscoll 1 2, Brian A Neff 1, Jamie J Van Gompel 1 2, John I Lane 3, Matthew L Carlson 1 2
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PMID: 31469795 DOI: 10.1097/MAO.0000000000002346
Abstract
Objective: The etiology of sensorineural hearing loss (SNHL) in patients with jugular paraganglioma (JP) whose tumors lack inner ear fistulae or vestibulocochlear nerve involvement is unknown. Recent literature has proposed that occlusion of the inferior cochlear vein may be causative. Herein, we assess the association between radiologic involvement of the cochlear aqueduct (CA) and the development of SNHL.

Study design: Blinded, retrospective review of imaging and audiometry.

Setting: Tertiary center.

Patients: Adults with JP.

Intervention(s): None.

Main outcome measures: Asymmetric SNHL was assessed continuously as the difference in bone conduction pure-tone average (BCPTA) between ears and as a categorical variable (≥15 dB difference at two consecutive frequencies, or a difference in speech discrimination score of ≥15%). Involvement of the CA was considered present if there was evidence of medial T2 fluid signal loss, contrast enhancement, or bony erosion/expansion.

Results: Of 30 patients meeting inclusion criteria, 15 (50%) had asymmetric SNHL. CA involvement was observed in 87% of patients with asymmetric SNHL compared with 13% in those with symmetric hearing (p = 0.0001). Univariate analysis demonstrated that age, sex, and tumor volume were not associated with asymmetric SNHL. The median difference in BCPTA between ears in patients with CA involvement was 21.3 dB HL compared to 1.2 dB HL in those without CA involvement (p < 0.0001). Regression analysis demonstrates that enhancement within the CA is associated with a BCPTA difference of 19.4 dB HL (p = 0.0006).

Conclusions: Cochlear aqueduct involvement by JP is associated with SNHL in the absence of inner ear fistula, vestibulocochlear nerve involvement, or brainstem compression. Correlation with operative findings or histopathologic evidence of tumor involvement may validate this intriguing imaging finding.

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42
Otol Neurotol
. 2019 Oct;40(9):1148-1152. doi: 10.1097/MAO.0000000000002342.
Factors Influencing Pediatric Cochlear Implant Outcomes: Carolina Sibling Study
Anne Morgan Selleck 1, Lisa R Park, Kevin D Brown
Affiliations expand
PMID: 31436630 DOI: 10.1097/MAO.0000000000002342
Abstract
Objective: To determine the correlation between speech perception performance between pediatric sibling pairs with severe to profound sensory hearing loss receiving cochlear implants, and in cases of discordance in performance, determine which variables negatively impacted performance.

Study design: Retrospective chart review.

Setting: Tertiary academic referral center.

Subjects: Eighty-nine pediatric subjects, 43 sibling groups, under the age of 18 with severe to profound sensory hearing loss who received a cochlear implant with a sibling who also received a cochlear implant.

Intervention: Cochlear implantation.

Main outcome measures: Speech perception scores, consonant-nucleus- consonant score.

Results: A statistically significant correlation was found between speech perception performance of pediatric siblings. Depth of insertion is positively correlated with better speech perception in siblings with discordant results. There was no significant relationship with either electrode type, unilateral/bilateral status, or age of implantation.

Conclusion: Pediatric siblings have a high correlation in speech perception outcomes following cochlear implantation, suggesting family environment plays a strong role. In circumstances in which outcomes between siblings are substantially different, greater depth of implant insertion is correlated with better consonant-nucleus- consonant word scores.

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43
Otol Neurotol
. 2019 Oct;40(9):1253-1259. doi: 10.1097/MAO.0000000000002349.
Transvenous Stent-assisted Coil Embolization for Management of Dehiscent High Jugular Bulb With Tinnitus and Contralateral Hypoplastic Venous Sinuses
Se-Joon Oh 1 2, Deoksoo Kim 1, Jae Il Lee 3, Jun Kyeung Ko 3, Sung-Won Choi 1 2, Soo-Keun Kong 1 2, Eui-Kyung Goh 1 2, Tae Hong Lee 4
Affiliations expand
PMID: 31469796 DOI: 10.1097/MAO.0000000000002349
Abstract
Objectives: This study aimed to evaluate the safety and efficacy of transvenous stent-assisted coil embolization for dehiscent high jugular bulb (HJB) with tinnitus and contralateral hypoplastic venous sinus.

Study design: Case series with chart review.

Setting: Tertiary academic medical center.

Methods: From September 2008 to October 2018, a series of patients with dehiscent HJB presenting with intractable pulsatile tinnitus abated only by ipsilateral jugular vein compression were included. Patients underwent transvenous stent-assisted coil embolization for selective obstruction to the dome of the HJB due to hypoplastic contralateral transverse or sigmoid venous sinus. Technical safety and clinical efficacy were retrospectively analyzed. Clinical outcome measurements included pure-tone audiogram, tinnitus character, and tinnitus handicap inventory and evaluated based on the change during the first 6 months after the procedure.

Results: Subjects included five patients with dehiscent HJB and troublesome pulsatile tinnitus who refused surgery (n = 4), or who experienced recurrence after surgical covering and reinforcement using autologous cartilage (n = 1). The mean age of the five patients (only female) was 45 years. Transvenous stent-assisted coil embolization was technically successful in all patients with symptomatic dehiscent HJB, with no procedure-related complications. Temporary postprocedural headache was observed in two patients, but resolved within 3 days. Symptoms were completely resolved in all cases. There was no recurrence or aggravation of tinnitus during follow-up period.

Conclusions: Transvenous stent-assisted coil embolization for dehiscent HJB with tinnitus and contralateral hypoplastic transverse or sigmoid venous sinus could be a technically safe and clinically effective treatment strategy while preserving cranial venous drainage.

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44
Otol Neurotol
. 2019 Oct;40(9):1224-1229. doi: 10.1097/MAO.0000000000002337.
Delayed Tumor Growth in Vestibular Schwannoma: An Argument for Lifelong Surveillance
Robert J Macielak 1, Neil S Patel 1, Katherine A Lees 1, Christine M Lohse 2, John P Marinelli 3, Michael J Link 1 4, Matthew L Carlson 1 4
Affiliations expand
PMID: 31469794 DOI: 10.1097/MAO.0000000000002337
Abstract
Objective: Previous research has shown that tumor growth during observation of small-to-medium sized sporadic vestibular schwannomas (VSs) occurs almost exclusively within 3 to 5 years following diagnosis. This has led some to consider ending surveillance after this interval. This study seeks to characterize a cohort of patients with tumors that exhibited late growth.

Study design: Retrospective cohort study.

Setting: Tertiary referral center.

Patients: Adults with sporadic VSs who initially elected observation with serial magnetic resonance imaging (MRI) surveillance.

Intervention(s): None.

Main outcome measure(s): Linear tumor growth was measured in accordance with AAO-HNS reporting guidelines. Delayed growth was defined as growth ≥2 mm in linear diameter that was first detected 5 years or more from the initial MRI.

Results: From a total of 361 patients, 172 experienced tumor growth during the interval of observation. Fourteen of these 172 patients (8.1%) experienced late growth occurring at 5 years or beyond. Among patients with delayed growth, the fastest growth rate after extended quiescence was 1.33 mm/yr, and the longest delay before tumor growth detection was 11.1 years. Additional treatment was recommended for six (42.9%) of the patients with delayed growth. Of 68 tumors that remained in the IAC, 11 (16.2%) demonstrated delayed growth. Of 66 tumors that presented in the CPA, 2 (3.0%) demonstrated delayed growth. Initial size was larger for tumors demonstrating early growth compared with those with delayed growth. For tumors within the IAC, those with early growth had a significantly higher median growth rate than those with delayed growth (1.40 vs. 0.45 mm/yr, p < 0.001).

Conclusions: Delayed growth encompassed 8.1% of growing VSs and 3.9% of all observed tumors. Patients with delayed growth exhibited slower growth rates compared with those who were diagnosed with growth early in their observation course. These findings support the need for lifelong surveillance of untreated VSs given the possibility of clinically significant delayed growth. Increasing the time interval between MRI studies after 5 years is a reasonable concession to balance practicalities of cost and convenience with risk of delayed of tumor growth.

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45
J Vestib Res
. 2019;29(6):315-322. doi: 10.3233/VES-190682.
Long-term Outcomes of Triple Semicircular Canal Plugging for the Treatment of Intractable Meniere's Disease: A Single Center Experience of 361 Cases
Daogong Zhang 1, Yafeng Lv 1, Yuechen Han 1, Yawei Li 1, Xiaofei Li 1, Jing Wang 1, Yongdong Song 1, Ligang Kong 1, Huirong Jian 1, Zhaomin Fan 1, Haibo Wang 1
Affiliations expand
PMID: 31640108 DOI: 10.3233/VES-190682
Abstract
Introduction: Meniere's disease is a common chronic inner ear disease. Because the definitive pathogenesis is still unknown, there is currently no cure for this disorder. Semicircular canal plugging (SCP), first used to treat patients with intractable benign paroxysmal positional vertigo, has since been applied to patients with intractable peripheral vertigo. This study was aimed to explore the long-term efficacy of triple semicircular canal plugging (TSCP) in the treatment of intractable Meniere's disease (MD) so as to provide a new method in the framework of treatment with MD.

Methods: Three hundred and sixty-one unilateral MD patients, who were treated with TSCP in our hospital between Dec. 2010 and Sep. 2016, were recruited in this study for retrospective analysis. Vertigo control and auditory function were monitored during a period of two-year follow-up. Seventy three patients who were subjected to intratympanic gentamicin were selected as a control group. Pure tone audiometry, caloric test, vestibular evoked myogenic potential (VEMP) were performed in two-year follow-up.

Results: The total control rate of vertigo in TSCP group was 97.8% (353/361) in the two-year follow-up, with complete control rate of 80.3% (290/361) and substantial control rate of 17.5% (63/361). The rate of hearing loss was 26.3% (95/361). The total control rate of vertigo in intratympanic gentamicin group was 83.6% (61/73), with complete control rate of 63.0% (46/73) and substantial control rate of 20.5% (15/73). The rate of hearing loss was 24.7% (18/73). The vertigo control rate of TSCP was significantly higher than that of chemical labyrinthectomy(χ2 = 24.798, p < 0.05). There was no significant difference of hearing loss rate between two groups. (χ2 = 0.087, p > 0.05).

Conclusion: Triple semicircular canal plugging (TSCP), which can reduce vertiginous symptoms in patients with intractable Meniere's disease (MD), represents an effective therapy for this disorder. It might become a new important method in the framework of treatment with MD.

Keywords: Meniere’s disease; Semicircular canal plugging; Vertigo.

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46
Comment Lancet Oncol
. 2019 Oct;20(10):1328-1329. doi: 10.1016/S1470-2045(19)30495-4. Epub 2019 Aug 12.
Choosing Surgery or Radiotherapy for Oropharyngeal Squamous Cell Carcinoma: Is the Issue Definitely Settled?
Vincent Grégoire 1, Piero Nicolai 2
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PMID: 31416686 DOI: 10.1016/S1470-2045(19)30495-4
Comment on
Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.
Nichols AC, Theurer J, Prisman E, Read N, Berthelet E, Tran E, Fung K, de Almeida JR, Bayley A, Goldstein DP, Hier M, Sultanem K, Richardson K, Mlynarek A, Krishnan S, Le H, Yoo J, MacNeil SD, Winquist E, Hammond JA, Venkatesan V, Kuruvilla S, Warner A, Mitchell S, Chen J, Corsten M, Johnson-Obaseki S, Eapen L, Odell M, Parker C, Wehrli B, Kwan K, Palma DA.
Lancet Oncol. 2019 Oct;20(10):1349-1359. doi: 10.1016/S1470-2045(19)30410-3. Epub 2019 Aug 12.
PMID: 31416685
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47
J Vestib Res
. 2019;29(5):271-279. doi: 10.3233/VES-190676.
Assessing Misperception of Rotation in Benign Paroxysmal Positional Vertigo With Static and Dynamic Visual Images
Jan E Holly 1, Helen S Cohen 2, M Arjumand Masood 1
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PMID: 31450525 DOI: 10.3233/VES-190676
Abstract
Background: Perception of self-motion is difficult for patients to describe. In addition, the relationship between perceived rotation and eye movements is poorly understood, because most studies of patients have investigated only static orientation.

Objective: First, to determine whether patients with benign paroxysmal positional vertigo (BPPV) can use visual images to report perceived rotation elicited by the Dix-Hallpike maneuver. Second, to determine if the direction of patients' perceptions align with data on classical nystagmus direction.

Methods: After the Dix-Hallpike maneuver, BPPV patients viewed images - sketches or video animations - representing possible perceived motions. They selected one or more images representing perception.

Results: All subjects could select images. The directions of the videos were most often backward pitch and/ or ipsilateral roll and yaw relative to body orientation in the supine Dix-Hallpike position, generally consistent with the canal stimulus. Perceived direction of rotation was statistically significantly different from the direction of eye movements as published previously, suggesting a difference in mechanisms for perception and eye movements.

Conclusion: Patients can easily learn to use a video language to describe their experiences. Perception is generally aligned with canal stimulus and nystagmus, but not exactly.

Keywords: Spatial orientation; nystagmus; self-motion perception; vertigo.

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48
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):809-810. doi: 10.1177/0194599820920649. Epub 2020 Apr 14.
Otolaryngology Providers Must Be Alert for Patients With Mild and Asymptomatic COVID-19
Xiaoting Cheng 1, Jialin Liu 2, Ning Li 3, Eric Nisenbaum 4, Qing Sun 5, Bing Chen 1, Roy Casiano 4, Donald Weed 4, Fred Telischi 4, James C Denneny 3rd 6, Xuezhong Liu 4, Yilai Shu 1
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PMID: 32286913 DOI: 10.1177/0194599820920649
Abstract
More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.

Keywords: 2019-nCoV; COVID-19; SARS-CoV-2; coronavirus; health care worker protection.

Cited by 1 article
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49
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):811-812. doi: 10.1177/0194599820920850. Epub 2020 Apr 14.
Navigating the Ethics of COVID-19 in Otolaryngology
Andrew G Shuman 1 2
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PMID: 32284004 DOI: 10.1177/0194599820920850
Abstract
The COVID-19 pandemic has dramatically altered how otolaryngologists contemplate and assume their roles in health care delivery. The ethical implications of this pandemic upon our practice are formidable and distinct from other surgical fields. The salient ethical issues of public health stewardship and safety, distributive justice, and nonabandonment are distilled for the practicing otolaryngologist.

Keywords: COVID19; pandemic response; public health ethics.

Cited by 1 article
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50
Thyroid
. 2018 Dec;28(12):1618-1626. doi: 10.1089/thy.2018.0254. Epub 2018 Nov 22.
Molecular Classification of Thyroid Nodules With Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides
Marcos Tadeu Dos Santos 1 2, Ana Lígia Buzolin 1, Ricardo Ribeiro Gama 2 3, Eduardo Caetano Albino da Silva 4, Rozany Mucha Dufloth 4, David Livingstone Alves Figueiredo 5, André Lopes Carvalho 2 3
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PMID: 30319072 PMCID: PMC6308280 DOI: 10.1089/thy.2018.0254
Free PMC article
Abstract
Background: Thyroid nodules can be identified in up to 68% of the population. Fine-needle aspiration (FNA) cytopathology classifies 20%-30% of nodules as indeterminate, and these are often referred for surgery due to the risk of malignancy. However, histological postsurgical reports indicate that up to 84% of cases are benign, highlighting a high rate of unnecessary surgeries. We sought to develop and validate a microRNA (miRNA)-based thyroid molecular classifier for precision endocrinology (mir-THYpe) with both high sensitivity and high specificity, to be performed on the FNA cytology smear slide with no additional FNA. Methods: The expression of 96 miRNA candidates from 39 benign/39 malignant thyroid samples, (indeterminate on FNA) was analyzed to develop and train the mir-THYpe algorithm. For validation, an independent set of 58 benign/37 malignant FNA smear slides (also classified as indeterminate) was used. Results: In the training set, with a 10-fold cross-validation using only 11 miRNAs, the mir-THYpe test reached 89.7% sensitivity, 92.3% specificity, 90.0% negative predictive value and 92.1% positive predictive value. In the FNA smear slide validation set, the mir-THYpe test reached 94.6% sensitivity, 81.0% specificity, 95.9% negative predictive value, and 76.1% positive predictive value. Bayes' theorem shows that the mir-THYpe test performs satisfactorily in a wide range of cancer prevalences. Conclusions: The presented data and comparison with other commercially available tests suggest that the mir-THYpe test can be considered for use in clinical practice to support a more informed clinical decision for patients with indeterminate thyroid nodules and potentially reduce the rates of unnecessary thyroid surgeries.

Keywords: indeterminate thyroid nodule; miRNA; molecular classifier; molecular diagnostics; precision endocrinology.

Conflict of interest statement
M.T.S. holds equity at ONKOS Molecular Diagnostics. A.L.B. is a formal employee at ONKOS Molecular Diagnostics. R.R.G., E.C.A.S., R.M.D., and A.L.C. are also listed as inventors on the filled patent BR102018003587-8 and are eligible for royalties. The other authors declare no competing financial interests.

Cited by 4 articles29 references1 figure
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51
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):1-5. doi: 10.1097/MOO.0000000000000595.
The Relationship of Chronic Rhinosinusitis and Depression
Kristine A Smith 1 2, Jeremiah A Alt 2
Affiliations expand
PMID: 31789926 DOI: 10.1097/MOO.0000000000000595
Abstract
Purpose of review: The aim of this article is to identify and describe the relationship between chronic rhinosinusitis (CRS) and comorbid depression, including the patient factors that may increase the risk of depression. The impact of comorbid depression on quality of life, response to treatment and healthcare utilization will also be assessed.

Recent findings: CRS is associated with a significantly increased prevalence of depression, where 9-26% of patients with CRS will have physician-diagnosed depression. An additional 40% will have undiagnosed depression that can be identified through screening tools. Patients without polyps are more likely to experience comorbid depression, as are patients with significant sleep dysfunction, olfactory dysfunction, and pain. CRS symptoms do improve with medical and surgical therapy in depressed patients, though baseline and posttreatment scores are worse. A similar degree of benefit from therapy is seen in both depressed and nondepressed patients. CRS treatment does seem to improve depression, whereas the effect of depression specific therapy is unknown. Depressed patients have a significantly larger economic burden because of their increased healthcare utilization and productivity losses.

Summary: Depression is a highly prevalent and impactful comorbidity in patients with CRS. Increased awareness of this relationship may improve patients' overall quality of care.

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52
Exp Biol Med (Maywood)
. 2019 Jul;244(10):824-833. doi: 10.1177/1535370219850084. Epub 2019 May 14.
Liquid-type Non-Thermal Atmospheric Plasma Ameliorates Vocal Fold Scarring by Modulating Vocal Fold Fibroblast
Ho-Ryun Won 1 2, Eun Hye Song 2, Jong Eun Won 3, Hye Young Lee 3, Sung Un Kang 2, Yoo Seob Shin 2 3, Chul-Ho Kim 2 3
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PMID: 31088117 PMCID: PMC6643199 (available on 2020-07-01) DOI: 10.1177/1535370219850084
Free PMC article
Abstract
Injection laryngoplasty is a widely used therapeutic option for drug delivery into vocal folds (VFs). Efficient injectable materials are urgently needed for treating intractable VF disease. Liquid-type non-thermal atmospheric plasma (LTP) has been found to be useful for various biological applications, including in regenerative medicine. We evaluated the effects of LTP on VF regeneration. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by LTP treatment. LTP treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by LPS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit VF scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after LTP injection. Videokymographic analysis showed more improved vibrations in LTP-treated VF mucosa compared to those in non-treated group. In conclusion, LTP treatment enhanced the recruitment and activation of VF-MSCs. Regulated extracellular matrix (ECM) synthesis and eventual functional improvement of scarred VFs were observed upon LTP treatment. The results of this study suggest that LTP injection can enhance wound healing and improve functional remodeling following VF injury.

Impact statement: Voice disorder has a significant impact on life quality, and one of the major causes of this voice disorder is vocal fold scarring. Therefore, various approaches have been tried to treat for voice disorder. However, no method has satisfied all requirements until now. Plasma medicine, which involves the medical application of plasma, is a rapidly developing field. We have confirmed that liquid-type plasma improved vocal fold scarring by mobilizing and activating vocal fold fibroblast. In conclusion, liquid-type plasma is a potential therapeutic agent for promoting vocal fold scarring through simple injection and it may be an alternative therapeutic agent for the current situation to treat voice disorder.

Keywords: Extracellular matrix; lipopolysaccharide; mesenchymal stem cell; vocal fold fibroblast; wound healing.

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53
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):36-45. doi: 10.1097/MOO.0000000000000603.
Multidisciplinary Approaches to Odontogenic Lesions
Rabie M Shanti 1 2, Faizan Alawi 3, Su-Min Lee 4, Aaron J Henderson 1, Neel R Sangal 2, Nithin D Adappa 2
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PMID: 31851019 DOI: 10.1097/MOO.0000000000000603
Abstract
Purpose of review: To give an overview of technical considerations and relevant literature in the management odontogenic pathology with involvement of the maxillary sinus.

Recent findings: Infections, cysts, benign neoplasms (odontogenic and nonodontogenic), and inflammatory conditions impact the maxillary sinus in various ways, could result in significant expansion within the maxillary sinus and significant infections.

Summary: This manuscript provides an overview of common pathologic entities of the oral cavity proper that impacts the maxillary sinus health, with discussion of the role of the otorhinolaryngologist and the dental specialist.

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54
J Aerosol Med Pulm Drug Deliv
. 2019 Jun;32(3):132-148. doi: 10.1089/jamp.2018.1490. Epub 2018 Dec 15.
High-Efficiency Nose-to-Lung Aerosol Delivery in an Infant: Development of a Validated Computational Fluid Dynamics Method
Karl Bass 1, Susan Boc 2, Michael Hindle 2, Kelley Dodson 3, Worth Longest 1 2
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PMID: 30556777 PMCID: PMC6622559 DOI: 10.1089/jamp.2018.1490
Free PMC article
Abstract
Background: Computational fluid dynamics (CFD) provides a powerful tool for developing new high-efficiency aerosol delivery strategies, such as nose-to-lung (N2L) aerosol administration to infants and children using correctly sized aerosols. The objective of this study was to establish numerically efficient CFD solution methods and guidelines for simulating N2L aerosol administration to an infant based on comparisons with concurrent in vitro experiments. Materials and Methods: N2L administration of a micrometer-sized aerosol (mass median aerodynamic diameter [MMAD] = 1.4 μm) was evaluated using concurrent CFD simulations and in vitro experiments. Aerosol transport and deposition was assessed in a new nasal airway geometry of a 6-month-old infant with a streamlined nasal cannula interface, which was constructed as a CFD mesh and three-dimensionally printed to form an identical physical prototype. CFD meshes explored were a conventional tetrahedral approach with near-wall (NW) prism elements and a new polyhedral mesh style with an equally refined NW layer. The presence of turbulence in the model was evaluated using a highly efficient low-Reynolds number (LRN) k-ω turbulence model, with previously established NW corrections that accounted for anisotropic wall-normal turbulence as well as improved NW velocity interpolations and hydrodynamic particle damping. Results: Use of the new polyhedral mesh was found to improve numerical efficiency by providing more rapid convergence and requiring fewer control volumes. Turbulent flow was found in the nasal geometry, generated by the inlet jets from the nasal cannula interface. However, due to the small particle size, turbulent dispersion was shown to have little effect on deposition. Good agreement was established between the CFD predictions using the numerically efficient LRN k-ω model with appropriate NW corrections and in vitro deposition data. Aerosol transmission efficiencies through the delivery tube, nasal cannula, and infant nasal model, based on experimental and CFD predictions, were 93.0% and 91.5%, respectively. Conclusions: A numerically efficient CFD approach was established to develop transnasal aerosol administration to infants and children. Small particle aerosols with aerodynamic diameters of ∼1.5 μm were confirmed to have low inertial depositional loss, and have low deposition from turbulent dispersion, making them ideal for high-efficiency lung delivery through an infant nasal cannula interface.

Keywords: CFD aerosol simulations; CFD validation; excipient-enhanced growth; pharmaceutical aerosol.

Conflict of interest statement
Virginia Commonwealth University is currently pursuing patent protection of excipient-enhanced growth aerosol delivery, aerosol generation devices, and patient interfaces, which if licensed, may provide a future financial interest to the authors.

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55
Meta-Analysis Otol Neurotol
. 2019 Oct;40(9):1126-1133. doi: 10.1097/MAO.0000000000002416.
Non-contrast Magnetic Resonance Imaging for Diagnosis and Monitoring of Vestibular Schwannomas: A Systematic Review and Meta-analysis
Do Hyun Kim 1, Seoungmin Lee 1, Se Hwan Hwang 2
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PMID: 31469788 DOI: 10.1097/MAO.0000000000002416
Abstract
Objective: This study aimed to evaluate the diagnostic accuracy of high-resolution T2-weighted magnetic resonance imaging (T2wi) in terms of detecting vestibular schwannoma compared with gadolinium-enhanced T1-weighted MRI (GdT1wi).

Data sources: Five databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database).

Data selection: Two authors independently searched five databases up to January 2019 on diagnosis of vestibular schwannomas via T2wi.

Data extraction: In the included studies, tumor diameters reported using T2wi were compared with those revealed by GdT1wi and correlation coefficients were calculated. Data on true-positives, true-negatives, false-positives, and false-negatives were extracted from the relevant articles. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Inter-rater agreement among different observers and intra-rater agreement among different measurements made by a single observer was assessed.

Data synthesis: Outcomes subjected to analysis included diagnostic accuracy (the diagnostic odds ratio); summary receiver operating characteristic curve and area under the curve values. The summary intra-class correlation coefficient was used for various random-effects models. The quality of each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Conclusions: T2wi performed without the use of a contrast agent is a highly accurate diagnostic and monitor tool compared with GdT1wi and also demonstrated high reliability. However, further studies are required to confirm the results of this study.

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56
Eur J Surg Oncol
. 2019 Jul;45(7):1171-1174. doi: 10.1016/j.ejso.2019.03.018. Epub 2019 Mar 18.
The Impact of Completion Thyroidectomy
R Sawant 1, K Hulse 2, S Sohrabi 3, J C L Yeo 4, K Pal 5, F W Gibb 6, R Adamson 7, I J Nixon 8
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PMID: 30910458 DOI: 10.1016/j.ejso.2019.03.018
Abstract
Introduction: The oncological benefit of completion thyroidectomy (CT) following thyroid lobectomy (TL) is presumed to be similar to that of upfront total thyroidectomy(TT), from a patient's perspective the risk and inconvenience of further surgery adds significantly to the impact of the overall treatment. The aim of this study is to assess the impact of CT in terms of the duration of admission and associated complications.

Methods: A study of consecutive patients with DTC identified from prospective MDT records of South-East Scotland from 2009 to 2015. Surgical data was extracted from electronic medical record.

Results: Of 361 patients diagnosed with DTC, 161 (45%) had CT. The median postoperative stay was 1 day (range 1-5days). In total 22 patients (14%)suffered complications. Four patients (3%) developed postoperative haematoma. Two (1%) had an identified permanent nerve palsy on the completion side. 13 patients (8%) remained on calcium supplementation for more than 6 months postoperatively and three patients (2%) developed wound complications.

Conclusions: Our study confirms that CT is regularly performed (45%). Recent changes in international guidelines recognize increasing number of patients as eligible for a conservative approach but recommend CT based on whether upfront TT would have been recommended if the TL pathology were known from the outset. Such an approach fails to consider the additional risk and inconvenience of CT on the overall patient experience. Due to a relatively high rate of complications, only those patients who are most likely to benefit from further surgery to facilitate adjuvant radioactive iodine should be offered additional surgery.

Keywords: Completion thyroidectomy; Complications; Hypocalcaemia; Oncological benefits.

Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Comment in
Completion thyroidectomy-indications and complications.
Shaha AR, Michael Tuttle R.
Eur J Surg Oncol. 2019 Jul;45(7):1129-1131. doi: 10.1016/j.ejso.2019.03.028. Epub 2019 Mar 26.
PMID: 30935727 No abstract available.
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57
J Microsc
. 2019 Feb;273(2):127-134. doi: 10.1111/jmi.12768. Epub 2018 Nov 15.
Effects of Object-To-Detector Distance and Beam Energy on Synchrotron Radiation Phase-Contrast Imaging of Implanted Cochleae
S Alireza Rohani 1, John E Iyaniwura 1, Ning Zhu 2, Sumit K Agrawal 1, Hanif M Ladak 1 3 4
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PMID: 30431166 DOI: 10.1111/jmi.12768
Abstract
Objectives: To demonstrate that synchrotron radiation phase-contrast imaging (SR-PCI) can be used to visualize the intrascalar structures in implanted human cochleae and to find the optimal combination of the parameters object-to-detector distance (ODD) and beam energy (E) for visualization.

Materials and methods: Three cadaveric implanted human temporal bones underwent SR-PCI with varying combinations of parameters ODD (3, 2 and 1 m) and E (47, 60 and 72 keV). All images were then reconstructed to a three-dimensional (3D) stack of slices. The acquired 3D images were compared using contrast-to-noise ratios (CNRs) of the basilar membrane (
CNR
BM
 ) and the electrode array (CNRE ) and the standard deviation of the beam streaks (
σ
S
 ). Postprocessing calculations were performed using Matlab (Version 2017b, MathWorks Inc., Natick, MA, U.S.A.) with a standard significance level p < 0.05 to determine the most optimal combination of parameters.

Results: SR-PCI with computed tomography reconstruction provided good visualization of the anatomical features of the implanted cochleae, specifically the exact location of the electrode with respect to the BM. A single-factor ANOVA revealed a significant difference of variance for both CNRE and CNRBM , but failed to show significance for
σ
S
 . A two-sample t-test failed to show any significant difference between CNRE columns of (3 m, 72 keV) and (2 m, 60 keV). The CNRBM was significantly different only at two pairs of columns, when (1 m, 72 keV) was compared against (2 m, 72 keV) and (3 m, 72 keV).

Conclusions: The results of this study show that SR-PCI is a viable method to visualize implanted human cochleae. SR-PCI is less invasive, less labour intensive and is associated with a much lower acquisition time compared to other methods for postimplantation imaging in humans, such as histological sectioning. We found that the optimal combination of E and ODD parameters was 72 keV and 2 m, respectively. These parameters resulted in high-contrast images of the electrode as well as all internal structures of the cochleae.

Lay description: Cochlear implants (CI) are currently the preferred method of treatment for hearing loss. Cochlear implantation surgery involves placement of a metallic, wire-shaped electrode inside the cochlea, the main organ of the human hearing system. Knowledge of the exact location of the electrode after implantation is beneficial in improving the extent of restored hearing. Common clinical imaging modalities such as computed-tomography (CT) are not ideal for providing such information, due to lack of resolution and streaking caused by the metallic electrode. Recent studies have developed algorithms to extract the electrode location from clinical computed-tomography images and have been validated using histology or micro computed-tomography (micro-CT). Synchrotron radiation phase contrast imaging (SR-PCI) is a high-resolution imaging technique used to visualize small structures in three dimensions. Recently, SR-PCI has been shown to be an alternative to histology or micro-CT for imaging the human cochlea. However, it has not been optimized for imaging implanted human cochleae. The main objective of the present work was to find the optimal organization of imaging parameters (i.e., object-to-detector distance and beam energy) for using SR-PCI to image implanted human cochleae. Three cadaveric human cochleae were imaged using five different combinations of imaging parameters at the Canadian Light Source Inc., Saskatoon, SK, Canada. The resulting images were compared both quantitatively and qualitatively. An optimal combination of parameters was found to produce high-contrast images of the both the CI electrode and all internal structures of the cochlea with minimal streaking. SR-PCI is therefore a viable alternative to histological or micro-CT studies for post-surgical imaging of implanted human cochleae.

Keywords: Cochlear implant; image segmentation; phase-contrast imaging; synchrotron radiation.

© 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

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58
Support Care Cancer
. 2020 May;28(5):2407-2413. doi: 10.1007/s00520-019-05035-1. Epub 2019 Sep 6.
Knowledge Matters and Empowers: HPV Vaccine Advocacy Among HPV-related Cancer Survivors
Zeena Shelal 1, Dalnim Cho 2, Diana L Urbauer 3, Qian Lu 2, Bridgette Y Ma 4, Anna M Rohrer 5, Shiney Kurian 1, Erich M Sturgis 6, Lois M Ramondetta 7
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PMID: 31489512 DOI: 10.1007/s00520-019-05035-1
Abstract
Purpose: To describe knowledge about human papillomavirus (HPV), HPV-related care behavior, and advocacy intent (e.g., vaccine recommendation and willingness to become an advocate for vaccination) and to investigate associations between knowledge, HPV-related care behavior, and advocacy intent among HPV-related cancer survivors.

Methods: A cross-sectional online survey was offered through Qualtrics to HPV-related cancer survivors who were either volunteers at a cancer center or patients of survivorship clinics.

Results: A total of 200 survivors responded. Only 33.2% of respondents reported knowing their cancer was HPV-related and 56.8% reported HPV vaccine is safe. Participants who knew that their cancer was caused by HPV were more likely to have vaccinated their children (p < .001). Also, participants who knew that the vaccine is safe were more willing to recommend the vaccine (p < .001), to be a peer mentor for others with HPV-related cancers (43.2% vs. 14.0%, p < .001), and to act as an advocate for increasing vaccination rates (44.1% vs. 24.4%, p = 0.01). Finally, survivors who were aware of the vaccine's effectiveness in decreasing precancerous lesions were more likely to recommend the vaccine (45.7% vs. 12.0%, p = .002).

Conclusions: Raising survivor awareness of the link between HPV and cancer and HPV vaccine safety may increase their willingness to serve as powerful opinion leaders and peer mentors to promote HPV vaccination. Providers may take the simple step of informing patients that their cancer is HPV-related and HPV vaccine is safe to increase the number of informed and empowered survivors.

Keywords: Advocacy; Cervical cancer; Human papillomavirus (HPV); Oropharyngeal cancer; Survivors; Vaccine.

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59
J Neurosci
. 2019 Apr 10;39(15):2860-2876. doi: 10.1523/JNEUROSCI.1811-18.2019. Epub 2019 Jan 29.
Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons
Christopher M Ventura 1, Radha Kalluri 2 3 4
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PMID: 30696730 PMCID: PMC6462445 DOI: 10.1523/JNEUROSCI.1811-18.2019
Free PMC article
Abstract
Vestibular ganglion neurons (VGNs) transmit information along parallel neuronal pathways whose signature distinction is variability in spike-timing; some fire at regular intervals while others fire at irregular intervals. The mechanisms driving timing differences are not fully understood but two opposing (but not mutually exclusive) hypotheses have emerged. In the first, regular-spiking is inversely correlated to the density of low-voltage-gated potassium currents (I KL). In the second, regular spiking is directly correlated to the density of hyperpolarization-activated cyclic nucleotide-sensitive currents (I H). Supporting the idea that variations in ion channel composition shape spike-timing, VGNs from the first postnatal week respond to synaptic-noise-like current injections with irregular-firing patterns if they have I KL and with more regular firing patterns if they do not. However, in vitro firing patterns are not as regular as those in vivo Here we considered whether highly-regular spiking requires I H currents and whether this dependence emerges later in development after channel expression matures. We recorded from rat VGN somata of either sex aged postnatal day (P)9-P21. Counter to expectation, in vitro firing patterns were less diverse, more transient-spiking, and more irregular at older ages than at younger ages. Resting potentials hyperpolarized and resting conductance increased, consistent with developmental upregulation of I KL Activation of I H (by increasing intracellular cAMP) increased spike rates but not spike-timing regularity. In a model, we found that activating I H counter-intuitively suppressed regularity by recruiting I KL Developmental upregulation in I KL appears to overwhelm I H These results counter previous hypotheses about how I H shapes vestibular afferent responses.SIGNIFICANCE STATEMENT Vestibular sensory information is conveyed on parallel neuronal pathways with irregularly-firing neurons encoding information using a temporal code and regularly-firing neurons using a rate code. This is a striking example of spike-timing statistics influencing information coding. Previous studies from immature vestibular ganglion neurons (VGNs) identified hyperpolarization-activated mixed cationic currents (I H) as driving highly-regular spiking and proposed that this influence grows with the current during maturation. We found that I H becomes less influential, likely because maturing VGNs also acquire low-voltage-gated potassium currents (I KL), whose inhibitory influence opposes I H Because efferent activity can partly close I KL, VGN firing patterns may become more receptive to extrinsic control. Spike-timing regularity likely relies on dynamic ion channel properties and complementary specializations in synaptic connectivity.

Keywords: IH; IKL; cAMP; neuronal excitability; spike-timing regularity; vestibular ganglion.

Copyright © 2019 the authors.

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60
J Cancer Res Clin Oncol
. 2020 Jul;146(7):1765-1779. doi: 10.1007/s00432-020-03232-8. Epub 2020 Apr 30.
Risk of Second Primary Cancers in Individuals Diagnosed With Index Smoking- And Non-Smoking- Related Cancers
Eric Adjei Boakye 1 2, Maggie Wang 3, Arun Sharma 4, Wiley D Jenkins 5 6, Nosayaba Osazuwa-Peters 7 8, Betty Chen 4, Minjee Lee 5 6, Mario Schootman 9
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PMID: 32356175 DOI: 10.1007/s00432-020-03232-8
Abstract
Purpose: As the number of cancer survivors in the United States increases, quantifying the risks and burden of second primary cancers (SPCs) among cancer survivors will help develop long-term prevention and surveillance strategies. We describe the risk of developing a SPC among survivors of 10 cancer sites with the highest survival rates in the United States.

Methods: Adult patients diagnosed with an index smoking-related (urinary bladder, kidney and renal pelvis, uterine cervix, oral cavity and pharynx, and colon and rectum) and index non-smoking-related (prostate, thyroid, breast, corpus and uterus, and non-Hodgkin lymphoma) cancers were identified from Surveillance, Epidemiology, and End Results (2000-2015). SPC risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR).

Results: A cohort of 2,903,241 patients was identified and 259,685 (8.9%) developed SPC (7.6% of women and 10.3% of men). All index cancer sites (except prostate) were associated with a significant increase in SPC risk for women and men. Patients diagnosed with smoking-related index cancers (SIR range 1.20-2.16 for women and 1.12-1.91 for men) had a higher increased risk of SPC than patients with non-smoking-related index cancers (SIR range 1.08-1.39 for women and 1.23-1.38 for men) relative to the general population.

Conclusion: We found that 1-in-11 cancer survivors developed a SPC. Given the increasing number of cancer survivors and the importance of SPC as a cause of cancer death, there is a need for increased screening for and prevention of SPC.

Keywords: Cancer survivors; Malignant neoplasm; Second primary cancer; Smoking-associated cancers; Surveillance Epidemiology and End Results (SEER) program.

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61
Eur J Surg Oncol
. 2019 Jul;45(7):1182-1187. doi: 10.1016/j.ejso.2019.03.015. Epub 2019 Mar 15.
Indeterminate Nodules by the Bethesda System for Reporting Thyroid Cytopathology in Israel: Frequency, and Risk of Malignancy After Reclassification of Follicular Thyroid Neoplasm With Papillary-Like Features
Rachel Chava Rosenblum 1, Alexander Shtabsky 2, Silvia Marmor 2, Leonor Trejo 2, Iris Yaish 3, Sophie Barnes 4, Moshe Yehuda 5, Naftali Stern 3, Zmira Silman 6, Karen Michèle Tordjman 3
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PMID: 30928335 DOI: 10.1016/j.ejso.2019.03.015
Abstract
Objective: We aimed to determine the frequency and risk of malignancy (ROM) for indeterminate thyroid nodules, categories III (B3) and IV (B4) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), at a large institution in Israel. Additionally, we investigated the impact of redefining follicular neoplasm with papillary-like nuclear features (NIFTP) as non-malignant on malignancy rates.

Methods: In this retrospective study of all thyroid fine needle aspirations (FNAs) performed at Tel Aviv-Sourasky Medical Center between January 2013 and December 2015, we assessed ROM for B3 and B4 nodules. Potential risk factors thought to affect a-priori ROM were assessed. Suspected NIFTP lesions were re-examined, and if proven, reclassified as benign.

Results: 3701 nodules were sampled in 2919 FNAs performed on 2674 patients. B3 reports comprised 7.7% of all nodules (n = 284); B4 represented 3.6% (n = 132). In multivariate logistic regression, male gender, being of former Soviet Union origin, and smoking increased ROM for B3 nodules by a factor of 7.97 (P = 0.002; CI: 2.2-23.4), 9.15 (P = 0.021; CI:1.4-60.0), and 11.0 (P = 0.001; CI 2.8-44.8), respectively. Reclassifying NIFTP decreased ROM from 14% to 12.5% for B3, and from 26.7% to 25% for B4 nodules. NIFTP comprised 9.5% of previously diagnosed resected malignant tumors.

Conclusions: The relative frequencies of B3 and B4 nodules and their associated malignancy rates were consistent with previous series. Risk factors identified for malignancy may help characterize patients most likely to benefit from surgery. Reclassifying NIFTP had a substantial impact on the ROM in the resected tumors previously diagnosed as malignant.

Keywords: Bethesda system for reporting thyroid cytopathology-BSRTC; Fine needle aspiration-FNA; Follicular neoplasm with papillary like nuclear features-NIFTP; Indeterminate nodules; Risk of malignancy-ROM.

Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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62
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):46-51. doi: 10.1097/MOO.0000000000000596.
Update on Long-Term Outcomes for Chronic Rhinosinusitis in Cystic Fibrosis
Michael T Chang 1, Zara M Patel
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PMID: 31815863 DOI: 10.1097/MOO.0000000000000596
Abstract
Purpose of review: This article reviews the existing body of literature regarding long-term outcomes of various treatments for chronic rhinosinusitis (CRS) in the cystic fibrosis population.

Recent findings: The management of CRS in cystic fibrosis involves a multitude of medical and surgical therapies. Despite their high usage amongst clinicians, corticosteroids and antibiotics currently have little outcome data supporting their use. There is emerging evidence demonstrating beneficial outcomes for DNAse mucolytics and molecular modulators of cystic fibrosis transmembrane conductor regulator (CFTR). Endoscopic sinus surgery (ESS) improves sinonasal outcomes in cystic fibrosis CRS; however, the benefit on pulmonary outcomes remains unclear.

Summary: Successful management of CRS in cystic fibrosis requires multimodal and multidisciplinary care. The long-term outcome data is variable for different treatment modalities. There is recent evidence supporting the role of DNAse mucolytics, CFTR-targeting therapies, and ESS in management of cystic fibrosis CRS.

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63
Radiother Oncol
. 2020 Jun 12;S0167-8140(20)30335-2. doi: 10.1016/j.radonc.2020.06.012. Online ahead of print.
Gross Tumour Volume Delineation in Anal Cancer on T2-weighted and Diffusion-Weighted MRI - Reproducibility Between Radiologists and Radiation Oncologists and Impact of Reader Experience Level and DWI Image Quality
Lisa A Min 1, Younan J L Vacher 2, Luc Dewit 3, Mila Donker 3, Carmelo Sofia 4, Baukelien van Triest 3, Paula Bos 5, Joost J W van Griethuysen 6, Monique Maas 2, Regina G H Beets-Tan 6, Doenja M J Lambregts 2
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PMID: 32540336 DOI: 10.1016/j.radonc.2020.06.012
Abstract
Purpose: To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality.

Methods and materials: We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients. Four readers (senior&junior radiologist; senior&junior radiation oncologist) independently delineated GTVs, first on T2W-MRI only and then on DWI (with reference to T2W-MRI). Maximum Tumour Diameter (MTD) was calculated from each GTV. Mean GTVs/MTDs were compared between readers and between T2W-MRI vs. DWI. Interobserver agreement was calculated as intraclass correlation coefficient (ICC), Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). DWI image quality was assessed using a 5-point artefact scale.

Results: Interobserver agreement between radiologists vs. radiation oncologists and between junior vs. senior readers was good-excellent, with similar agreement for T2W-MRI and DWI (e.g. ICCs 0.72-0.94 for T2W-MRI and 0.68-0.89 for DWI). There was a trend towards smaller GTVs on DWI, but only for the radiologists (P=0.03-0.07). Moderate-severe DWI-artefacts were observed in 11/25 (44%) cases. Agreement tended to be lower in these cases.

Conclusion: Overall interobserver agreement for anal cancer GTV delineation on MRI is good for both radiologists and radiation oncologists, regardless of experience level. Use of DWI did not improve agreement. DWI artefacts affecting GTV delineation occurred in almost half of the patients, which may severely limit the use of DWI for radiotherapy planning if no steps are undertaken to avoid them.

Keywords: Anus Neoplasms; Artifacts; Chemoradiotherapy; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging.

Copyright © 2020. Published by Elsevier B.V.

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64
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):14-17. doi: 10.1097/MOO.0000000000000597.
What Is the Evidence for Fluticasone Exhalation Delivery System in Chronic Rhinosinusitis?
Alexander J Kovacs 1, Khodayar Goshtasbi, Edward C Kuan
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PMID: 31789927 DOI: 10.1097/MOO.0000000000000597
Abstract
Purpose for review: The aim of this article is to review the current literature regarding a novel method of topically delivering nasal steroids, namely exhalation delivery system-fluticasone (EDS-FLU), for the treatment of chronic rhinosinusitis (CRS).

Recent findings: Recent Food and Drug Administration approval of EDS-FLU and increasing evidence surrounding its efficacy and safety has led to an additional tool for the treatment of chronic rhinosinusitis. Compared with placebo, EDS-FLU has demonstrated significant improvements in patients' sinonasal symptoms and overall inflammatory control as well as quality of life measures. Additionally, using EDS-FLU can lead to polyp grade improvement and polyp elimination in patients with chronic rhinosinusitis with polyps. Furthermore, compared with controls, patients who received EDS-FLU were less likely to meet predefined surgical criteria at the conclusion of the study.

Summary: EDS-FLU has demonstrated significant improvement in managing symptoms and polyps in CRS. Receiving EDS-FLU was associated with a significant reduction in the proportion of patients meeting surgical criteria. Further studies are warranted to evaluate the long-term outcomes of EDS-FLU, especially as compared with steroid sprays and topical steroid irrigations, in management of CRS.

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65
Case Reports Med J Malaysia
. 2019 Oct;74(5):450-451.
Dilemma in Management of Cervico-Facial Cystic Hygroma
R Tamilselvi 1, I P Tang 2, S Linger 3, M S Mohd Soffian 4
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PMID: 31649229
Free article
Abstract
Cervico facial cystic hygroma and tongue lymphagioma is rare representative of spectrum of lymphatic malformations. Conservative management with sclerosants alone has proven to be successful. However, sudden enlargement of these cervico facial lymphangiomas leads to catastrophic airway obstruction leading to debility in feeding and speech. Therefore, surgery is indicated in such case to prevent such a catastrophic problem. We report here the case of a 3-yearold boy with cervico facial hygroma involving the tongue. We successfully treated him with a combination of surgery and OK432 injection.

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66
Review Value Health
. 2020 Jun;23(6):791-811. doi: 10.1016/j.jval.2020.02.006. Epub 2020 May 27.
Patient-Reported Morbidity Instruments: A Systematic Review
Arvind Oemrawsingh 1, Nishwant Swami 2, José M Valderas 3, Jan A Hazelzet 4, Andrea L Pusic 5, Richard E Gliklich 6, Regan W Bergmark 7
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PMID: 32540238 DOI: 10.1016/j.jval.2020.02.006
Abstract
Objectives: Although comorbidities play an essential role in risk adjustment and outcomes measurement, there is little consensus regarding the best source of this data. The aim of this study was to identify general patient-reported morbidity instruments and their measurement properties.

Methods: A systematic review was conducted using multiple electronic databases (Embase, Medline, Cochrane Central, and Web of Science) from inception to March 2018. Articles focusing primarily on the development or subsequent validation of a patient-reported morbidity instrument were included. After including relevant articles, the measurement properties of each morbidity instrument were extracted by 2 investigators for narrative synthesis.

Results: A total of 1005 articles were screened, of which 34 eligible articles were ultimately included. The most widely assessed instruments were the Self-Reported Charlson Comorbidity Index (n = 7), the Self-Administered Comorbidity Questionnaire (n = 3), and the Disease Burden Morbidity Assessment (n = 3). The most commonly included conditions were diabetes, hypertension, and myocardial infarction. Studies demonstrated substantial variability in item-level reliability versus the gold standard medical record review (κ range 0.66-0.86), meaning that the accuracy of the self-reported comorbidity data is dependent on the selected morbidity.

Conclusions: The Self-Reported Charlson Comorbidity Index and the Self-Administered Comorbidity Questionnaire were the most frequently cited instruments. Significant variability was observed in reliability per comorbid condition of patient-reported morbidity questionnaires. Further research is needed to determine whether patient-reported morbidity data should be used to bolster medical records data or serve as a stand-alone entity when risk adjusting observational outcomes data.

Keywords: comorbidity; health services; morbidity; patient report; psychometrics; self-report; surveys and questionnaires.

Copyright © 2020. Published by Elsevier Inc.

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67
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):52-60. doi: 10.1097/MOO.0000000000000602.
Frontal Sinus Fractures and Cerebrospinal Fluid Leaks: A Change in Surgical Paradigm
Catherine Banks 1, Jessica Grayson 2, Do Yeon Cho 2, Bradford A Woodworth 2
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PMID: 31834027 DOI: 10.1097/MOO.0000000000000602
Abstract
Purpose of review: Traditionally, frontal sinus trauma has been treated using open incisions to access the anterior and/or posterior table. Mounting evidence indicates frontal sinus trauma can be managed using an endoscopic endonasal approach (EEA) with less morbidity. Such an approach permits preservation of a functional sinus and less reliance on computed tomography for postoperative follow up. The goal of this article is to highlight a shift in paradigm away from open approaches using external incisions towards an EEA to repair cerebrospinal fluid (CSF) leaks and fractures of the frontal sinus.

Recent findings: In a prospective case series of 46 patients undergoing EEA to frontal sinus fractures, 41 patients had active CSF leaks arising from the posterior table of the frontal sinus. A successful endoscopic repair was achieved in 97.6% with only one patient requiring revision Draf IIB surgery. Anterior table fractures were also successfully reduced with excellent cosmesis.

Summary: Endoscopic repair of frontal sinus fractures and CSF leaks is effective and well tolerated. In select patients, it is the preferred treatment as it maintains normal sinus structure and function, minimizing both early and late complications.

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68
Ear Hear
. 2020 Jun 11. doi: 10.1097/AUD.0000000000000894. Online ahead of print.
How Good Are We in Evaluating a Bedside Head Impulse Test?
Athanasia Korda 1, John Patrick Carey 2, Ewa Zamaro 1, Marco Domenico Caversaccio 1, Georgios Mantokoudis 1
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PMID: 32541263 DOI: 10.1097/AUD.0000000000000894
Abstract
Objectives: Clinicians performing a horizontal head impulse test (HIT) are looking for a corrective saccade. The detection of such saccades is a challenge. The aim of this study is to assess an expert's likelihood of detecting corrective saccades in subjects with vestibular hypofunction.

Design: In a prospective cohort observational study at a tertiary referral hospital, we assessed 365 horizontal HITs performed clinically by an expert neurootologist from a convenience sample of seven patients with unilateral or bilateral deficient vestibulo-ocular reflex (VOR). All HITs were recorded simultaneously by video-oculography, as a gold standard. We evaluated saccades latency and amplitude, head velocity, and gain.

Results: Saccade amplitude was statistically the most significant parameter for saccade detection (p < 0.001).The probability of saccade detection was eight times higher for HIT toward the pathological side (p = 0.029). In addition, an increase in saccade amplitude resulted in an increased probability of detection (odds ratio [OR] 1.77 [1.31 to 2.40] per degree, p < 0.001). The sensitivity to detect a saccade amplitude of 1 degree was 92.9% and specificity 79%. Saccade latency and VOR gain did not significantly influence the probability of the physician identifying a saccade (OR 1.02 [0.94 to 1.11] per 10-msec latency and OR 0.84 [0.60 to 1.17] per 0.1 VOR gain increase).

Conclusions: The saccade amplitude is the most important factor for accurate saccade detection in clinically performed head impulse tests. Contrary to current knowledge, saccade latency and VOR gain play a minor role in saccade detection.

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69
Otolaryngol Head Neck Surg
. 2020 Jun 16;194599820934376. doi: 10.1177/0194599820934376. Online ahead of print.
Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study
Chenghao Qiu 1, Chong Cui 2 3, Charlotte Hautefort 4, Antje Haehner 5, Jun Zhao 6, Qi Yao 7, Hui Zeng 8, Eric J Nisenbaum 9, Li Liu 10, Yu Zhao 2 3, Di Zhang 11, Corinna G Levine 9, Ivette Cejas 9, Qi Dai 2 3, Mei Zeng 12, Philippe Herman 4, Clement Jourdaine 4, Katja de With 13, Julia Draf 5, Bing Chen 2 3, Dushyantha T Jayaweera 14, James C Denneny 3rd 15, Roy Casiano 9, Hongmeng Yu 2 3, Adrien A Eshraghi 9, Thomas Hummel 5, Xuezhong Liu 9, Yilai Shu 2 3, Hongzhou Lu 10
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PMID: 32539586 DOI: 10.1177/0194599820934376
Abstract
Objective: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients.

Study design: Multicenter case series.

Setting: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany).

Subjects and methods: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing.

Results: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation.

Conclusions: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Keywords: COVID-19; COVID-19 screening; SARS-CoV-2; anosmia; dysgeusia; gustatory dysfunction; olfactory dysfunction.

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70
Ann Plast Surg
. 2020 Jun 11. doi: 10.1097/SAP.0000000000002462. Online ahead of print.
Benefits of the Multidisciplinary Approach After Curative Surgery for the Treatment of Scalp Angiosarcoma
Kyeong-Tae Lee 1, Jeehyun Moon 1, Han-Sin Jeong 2, Ha Seong Lim 3, So Young Lim 1
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PMID: 32541541 DOI: 10.1097/SAP.0000000000002462
Abstract
Background: Patients with scalp angiosarcoma still present with a dismal prognosis, indicating the need for a multidisciplinary approach. The present study aimed to investigate the treatment outcomes of scalp angiosarcoma with a focus on the effect of radiotherapy and chemotherapy, performed in either an adjuvant or palliative setting, after curative surgical treatment.

Methods: Patients with scalp angiosarcoma without evidence of systemic metastasis who were treated with curative ablative surgery between 2008 and 2018 were assessed. Oncologic outcomes, including recurrence-free survival (RFS) and overall survival (OS), were evaluated.

Results: A total of 23 patients were analyzed. All patients underwent radical resection, most of whom (82.6%) achieved R0 resection. Adjuvant radiotherapy and chemotherapy (all taxane-based) were delivered for 11 and 3 patients, respectively. Recurrence developed in 17 (73.9%) of 23 patients during a mean follow-up period of 18.4 months. The overall 2-year RFS and OS were 15.5% and 44.4%, respectively. Multivariate analysis showed that adjuvant radiotherapy and chemotherapy were associated with a significantly low risk of recurrence. In 17 patients with recurrence, those receiving palliative radiotherapy or chemotherapy had significantly higher OS than those not receiving any treatments. Compared with patients treated during the first half of the study period, those treated during the latter part, who received adjuvant and palliative radiotherapy or chemotherapy more frequently, had significantly favorable OS, with a 2-year OS of 77.8%.

Conclusions: A multidisciplinary approach using radiotherapy and/or chemotherapy combined with curative resection might be associated with better oncologic outcomes in patients with scalp angiosarcoma.

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71
Bioinformatics
. 2019 Aug 1;35(15):2602-2609. doi: 10.1093/bioinformatics/bty1016.
Optimal Gene Filtering for Single-Cell Data (OGFSC)-a Gene Filtering Algorithm for Single-Cell RNA-seq Data
Jie Hao 1, Wei Cao 2 3, Jian Huang 1, Xin Zou 1, Ze-Guang Han 1
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PMID: 30535000 DOI: 10.1093/bioinformatics/bty1016
Abstract
Motivation: Single-cell transcriptomic data are commonly accompanied by extremely high technical noise due to the low RNA concentrations from individual cells. Precise identification of differentially expressed genes and cell populations are heavily dependent on the effective reduction of technical noise, e.g. by gene filtering. However, there is still no well-established standard in the current approaches of gene filtering. Investigators usually filter out genes based on single fixed threshold, which commonly leads to both over- and under-stringent errors.

Results: In this study, we propose a novel algorithm, termed as Optimal Gene Filtering for Single-Cell data, to construct a thresholding curve based on gene expression levels and the corresponding variances. We validated our method on multiple single-cell RNA-seq datasets, including simulated and published experimental datasets. The results show that the known signal and known noise are reliably discriminated in the simulated datasets. In addition, the results of seven experimental datasets demonstrate that these cells of the same annotated types are more sharply clustered using our method. Interestingly, when we re-analyze the dataset from an aging research recently published in Science, we find a list of regulated genes which is different from that reported in the original study, because of using different filtering methods. However, the knowledge based on our findings better matches the progression of immunosenescence. In summary, we here provide an alternative opportunity to probe into the true level of technical noise in single-cell transcriptomic data.

Availability and implementation: https://github.com/XZouProjects/OGFSC.git.

Supplementary information: Supplementary data are available at Bioinformatics online.

© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cited by 1 article
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72
J Vestib Res
. 2019;29(2-3):89-96. doi: 10.3233/VES-190651.
Combined Ionic Direct Current and Pulse Frequency Modulation Improves the Dynamic Range of Vestibular Canal Stimulation
F P Aplin 1, D Singh 1, C C Della Santina 1, G Y Fridman 1
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PMID: 30856136 PMCID: PMC6663569 DOI: 10.3233/VES-190651
Free PMC article
Abstract
Background: Vestibular prostheses emulate normal vestibular function by electrically stimulating the semicircular canals using pulse frequency modulation (PFM). Spontaneous activity at the vestibular nerve may limit the dynamic range elicited by PFM. One proposed solution is the co-application of ionic direct current (iDC) to inhibit this spontaneous activity.

Objective: We aimed to test the hypothesis that a tonic iDC baseline delivered in conjunction with PFM to the vestibular semicircular canals could improve the dynamic range of evoked eye responses.

Methods: Gentamicin-treated chinchillas were implanted with microcatheter electrodes in the vestibular semicircular canals through which pulsatile and iDC current was delivered. PFM was used to modulate vestibulo-ocular reflex (VOR) once it was adapted to a preset iDC and pulse-frequency baseline. Responses to stimulation were assessed by recording the evoked VOR eye direction and velocity.

Results: PFM produced VOR responses aligned to the stimulated canal. Introduction of an iDC baseline lead to a small but statistically significant increase in eye response velocity, without influencing the direction of eye rotation.

Conclusions: Tonic iDC baselines increase the dynamic range of encoding head velocity evoked by pulsatile stimulation, potentially via the inhibition of spontaneous activity in the vestibular nerve.

Keywords: Vestibular system; direct current; electrical stimulation; neural implant; vestibular prosthesis; vestibulo-ocular reflex.

Cited by 1 article5 figures
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73
Clin Biomech (Bristol, Avon)
. 2019 Jun;66:97-106. doi: 10.1016/j.clinbiomech.2017.10.006. Epub 2017 Oct 7.
Geometry and Airflow Dynamics Analysis in the Nasal Cavity During Inhalation
Kiao Inthavong 1, Jiawei Ma 2, Yidan Shang 2, Jingliang Dong 2, Annicka S R Chetty 2, Jiyuan Tu 3, Dennis Frank-Ito 4
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PMID: 29074148 DOI: 10.1016/j.clinbiomech.2017.10.006
Abstract
Background: A major issue among computational respiratory studies is the wide variety of nasal morphologies being studied, caused by both inter-population and inter-subject variations.

Method: Six nasal cavity geometries exhibiting diverse geometry variations were subjected to steady inhalation flow rate of 15L/min. to determine if any consistent flow behaviour could be found.

Findings: Despite vastly different geometries we were able to identify consistent flow patterns including relatively high velocity in the nasal valve region, followed by flow continuing predominantly in the inferior half of the airway. We also found conformity among models where the inhaled air reached a near-conditioned state by the middle of the nasal cavity. Air from the front of the face reached the olfactory regions while air from the lateral sides of the face moved through the inferior half of the nasal cavity.

Interpretation: The ability to predict gross flow features provides a baseline flow field to compare against. This contributes towards establishing well defined flow predictions and be used as a comparison for future larger studies.

Keywords: Air conditioning; CFD; Heat flux; Inhalation; Nasal cavity; wss.

Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Cited by 2 articles
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74
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):6-10. doi: 10.1097/MOO.0000000000000593.
What Is the Evidence for Macrolide Therapy in Chronic Rhinosinusitis?
Marina N Cavada 1 2, Jessica W Grayson 3, Raymond Sacks 1 2 4 5
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PMID: 31834028 DOI: 10.1097/MOO.0000000000000593
Abstract
Purpose of review: To assess the most recent evidence for macrolide therapy in chronic rhinosinusitis (CRS).

Recent findings: Macrolides play a significant role in a select group of patients with CRS. Low-serum and tissue eosinophilia in patients who do not respond to corticosteroid therapy appeared to be an effective predictor of a CRS phenotype suitable for a trial of long-term macrolide therapy. Therapies using half a dose for longer than 12 weeks have noted good outcomes.

Summary: The anti-inflammatory and immunomodulatory effects of macrolides have been demonstrated in several studies. Macrolides have shown an important role in patients who are nonresponsive to corticosteroid therapies, therefore patient selection is key. Previous inconsistencies in results may be due to poor patient selection.

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75
Review Curr Opin Otolaryngol Head Neck Surg
. 2020 Feb;28(1):11-13. doi: 10.1097/MOO.0000000000000600.
Chronic Rhinosinusitis and Sleep Quality
Peter Papagiannopoulos 1, Edward C Kuan 2, Bobby A Tajudeen 1
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PMID: 31789930 DOI: 10.1097/MOO.0000000000000600
Abstract
Purpose of review: To review the recent literature describing the association between chronic rhinosinusitis and its effects on sleep quality.

Recent findings: Chronic rhinosinusitis (CRS) causes significantly worse sleep by both subjective and objective measures. CRS is also strongly associated with obstructive sleep apnea. Treating CRS surgically improves subjective sleep scores.

Summary: CRS worsens sleep quality both subjectively and objectively. Sleep quality is improved after endoscopic sinus surgery.

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76
Otolaryngol Head Neck Surg
. 2020 Jun 16;194599820934380. doi: 10.1177/0194599820934380. Online ahead of print.
Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis
Ameen Biadsee 1 2, Ameer Biadsee 3, Firas Kassem 1 2, Or Dagan 4, Shchada Masarwa 3, Zeev Ormianer 3
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PMID: 32539587 DOI: 10.1177/0194599820934380
Abstract
Objective: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus.

Study design: Case series, study conducted between March 25, 2020, and April 15, 2020.

Setting: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel.

Subjects and methods: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain.

Results: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P < .001 and P = .01, respectively), and 56% of patients reported xerostomia.

Conclusion: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.

Keywords: COVID-19; anosmia; coronavirus; dysgeusia; xerostomia.

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77
PLoS One
. 2020 Jun 16;15(6):e0234731. doi: 10.1371/journal.pone.0234731. eCollection 2020.
Development and Immunopathological Characteristics of an Alternaria-induced Chronic Rhinosinusitis Mouse Model
Seung-Heon Shin 1, Mi-Kyung Ye 1, Dong-Won Lee 1, Mi-Hyun Chae 1, Sung-Yong Choi 1
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PMID: 32544181 DOI: 10.1371/journal.pone.0234731
Free article
Abstract
Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

Conflict of interest statement
The authors have declared that no competing interests exist.

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78
Case Reports J Neuroophthalmol
. 2019 Mar;39(1):129-133. doi: 10.1097/WNO.0000000000000747.
A Tough NUT to Crack: A 47-Year-Old With Diplopia From a Rare Malignancy
Lauren Maloley 1, Jason Helvey, Julia Bridge, Dominick DiMaio, Deepta Ghate, Sachin Kedar
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PMID: 30640313 DOI: 10.1097/WNO.0000000000000747
Cited by 1 article
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79
Otolaryngol Head Neck Surg
. 2020 Jun 16;194599820931084. doi: 10.1177/0194599820931084. Online ahead of print.
Characteristics and Frequency of Children With Severe Obstructive Sleep Apnea Undergoing Elective Polysomnography
Ashank Bains 1, Elizabeth Abraham 1, Adam Hsieh 1, Batsheva R Rubin 1, Jessica R Levi 1 2, Michael B Cohen 1 2
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PMID: 32539583 DOI: 10.1177/0194599820931084
Abstract
Objective: To determine the prevalence and demographics features of pediatric patients with severe obstructive sleep apnea (OSA) who would not undergo preoperative polysomnography (PSG) under current American Academy of Otolaryngology (AAO) guidelines.

Study design: In this retrospective cohort study, we identified patients from the electronic medical record who underwent elective polysomnography for evaluation of sleep-disordered breathing between 2012 and 2018.

Setting: Urban tertiary safety net hospital.

Subjects and methods: A total of 456 patients with a mean (SD) age of 5.7 (3.2) years (263 male, 193 female). Demographic factors (age, sex, race, language, insurance status) and clinical findings (symptom severity, tonsil size) were recorded. The data were analyzed by univariate analysis.

Results: Of 456 patients identified, 66 (14.5%) were found to have severe OSA. African American patients had 3.7 times the odds of severe OSA compared to white patients (95% CI, 1.2-10.8). Patients aged 2 to 3 years had 2.2 times the odds of severe OSA compared to patients aged 4 to 6 years (95% CI, 1.2-4.0). Sex, ethnicity, language, and insurance type were not significantly associated with severity of OSA. The presence of apneic episodes and tonsil size were not found to be statistically significant.

Conclusion: Up to 14.5% of healthy pediatric patients with sleep-disordered breathing may have severe OSA; young age and African American race are statistically significant predictors. Clinical findings, such as tonsil size and symptom severity, were not found to be statistically significant predictors.

Keywords: AAO-HNSF guidelines; diagnostic polysomnography; elective polysomnography; patient safety; severe obstructive sleep apnea; sleep-disordered breathing.

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80
Ann Plast Surg
. 2020 Jun 12. doi: 10.1097/SAP.0000000000002461. Online ahead of print.
Endoscopic "Quick" Septoplasty in Preservation Rhinoplasty
Luca DʼAscanio 1, Michele Ori 2, Valerio Finocchi 3, Nicola Vione 4, Maria Capalbo 5, Giampietro Ricci 2
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PMID: 32541536 DOI: 10.1097/SAP.0000000000002461
Abstract
Background: Preservation rhinoplasty (PR) is revolutionizing rhinoplasty surgery, based on new anatomical studies, advanced tip suture techniques, and refinement of surgical techniques. Septal surgery is a fundamental preparatory stage during PR, especially for the dorsal preservation let/push-down procedure. To increase the predictability of the septoplasty aesthetic effects on the nasal dorsum and further extend the principles of PR to septal surgery, we applied the endoscopic technology to the "quick" septoplasty technique we had already developed in the past decades.

Methods: One hundred sixty-six patients (41 males, 125 females; mean age, 39.7 years; age range, 18-61 years) were submitted to endoscopic "quick" septoplasty for septal deviation during PR procedure. Preoperative evaluation of the nasal dorsum included external examinations of the size, shape, and orientation of the dorsum. Anterior active rhinomanometry was performed in all patients to determine nasal flow resistance preoperatively and 6 months after surgery. Preoperative and postoperative patients' scores on the Nasal Obstruction Septoplasty Effectiveness questionnaire were compared to assess the improvement of nasal symptoms after surgery. The duration of the septoplasty procedure was measured for all the patients. Standard nasal photographic assessment was performed before and 6 months after surgery.

Results: Postoperatively, 98.8% of our patients displayed an improvement of their nasal breathing function. No complication in terms of septal perforation, nasal infection, or bleeding was noticed. No case of turbinoseptal synechiae or cerebrospinal fluid leak was recorded. The dorsum preservation rhinoplasty procedure was successfully completed in all patients. The mean septoplasty operative time, excluding local anesthesia injection and other surgical procedures associated with septal surgery such as turbinoplasty and rhinoplasty, was 11.41 ± 6.23 minutes (range, 9-31 minutes).

Conclusions: Our results show that a short surgical time is needed to perform the proposed endoscopic septoplasty procedure. Such a short operative time allows the physician to both correct septal deviations quickly and correct/reduce the cartilaginous hump, thus representing a fundamental element of PR. In addition, the minimal tissue dissection reduces intraoperative nasal edema, favoring intraoperative aesthetic evaluation.

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81
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):800-803. doi: 10.1177/0194599820919748. Epub 2020 Apr 14.
Pediatric Otolaryngology Divisional and Institutional Preparatory Response at Seattle Children's Hospital After COVID-19 Regional Exposure
Sanjay R Parikh 1 2, Randall A Bly 1 2, Juliana Bonilla-Velez 1 2, John P Dahl 1 2, Sean S Evans 1 2, David L Horn 1 2, Kaalan E Johnson 1 2, Scott C Manning 1 2, Henry C Ou 1 2, Prasanth Pattisapu 1 2, Jonathan A Perkins 1 2, Kathleen C Y Sie 1 2
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PMID: 32286910 DOI: 10.1177/0194599820919748
Abstract
Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions. A significant limitation of this commentary is that it reflects a single institution's joint effort at a moment in time but does not take into consideration future circumstances that could change practice patterns. We still hope dissemination of our overall response at this moment, approximately 8 weeks after our region's first adult case, may benefit other pediatric institutions preparing for COVID-19.

Keywords: COVID-19; endoscopy; pediatric otolaryngology; preparatory response.

Cited by 2 articles
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82
Case Reports J Comp Pathol
. 2019 Nov;173:92-95. doi: 10.1016/j.jcpa.2019.10.007. Epub 2019 Nov 20.
A Branchial Cyst in a Diamond Python (Morelia Spilota)
E Cloup 1, C Thomas 2, J E Cooper 3
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PMID: 31812178 DOI: 10.1016/j.jcpa.2019.10.007
Abstract
A 9-year-old female diamond python (Morelia spilota) was presented with a submandibular swelling. The cytological, macroscopic and histological features of this lesion indicated a diagnosis of branchial (pharyngeal) cyst. Branchial cysts are benign lesions caused by anomalous development of the branchial apparatus and are described rarely in veterinary medicine. We suggest that possible persistence of branchial remnants should be included in the consideration of differential diagnoses for neck masses in adult snakes.

Keywords: branchial cyst; developmental abnormality; diamond python.

Copyright © 2019 Elsevier Ltd. All rights reserved.

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83
OTO Open
. 2020 Jun 2;4(2):2473974X20932497. doi: 10.1177/2473974X20932497. eCollection Apr-Jun 2020.
Examining the Otolaryngology Match and Relationships Between Publications and Institutional Rankings
Evan M Ryan 1, Katie R Geelan-Hansen 1, Kari L Nelson 2, Jayme R Dowdall 1
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PMID: 32537555 PMCID: PMC7268133 DOI: 10.1177/2473974X20932497
Free PMC article
Abstract
This study examines associations among publication number, National Institutes of Health (NIH) funding rank, medical school research rank, and otolaryngology department ranks of otolaryngology applicants during the 2018-2019 match cycle. Information regarding 2018-2019 otolaryngology applicants was collected from Otomatch.com and verified via department websites. Information was also collected regarding 2018 NIH funding rank and 2020 US News & World Report research rank of medical schools and otolaryngology departments. T tests and chi-square analyses were performed. Top 40 NIH funding rank, top 40 medical school research rank, and home institution department rank were separately associated with more publications and higher rates of matching into highly reputed otolaryngology departments (all P < .01). Furthermore, applicants who matched into ranked otolaryngology departments averaged significantly more publications (P < .01). Prospective otolaryngology applicants should take into account NIH funding rank, medical school research rank, and otolaryngology department rank, as they are associated with matching into high-ranking institutions.

Keywords: NIH funding; department rank; otolaryngology match; publication number.

© The Authors 2020.

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84
Oral Surg Oral Med Oral Pathol Oral Radiol
. 2020 Jun 13;S2212-4403(20)30966-4. doi: 10.1016/j.oooo.2020.04.810. Online ahead of print.
Level IV Neck Dissection as an Elective Treatment for Oral Tongue Carcinoma-A Systematic Review and Meta-Analysis
Nativ Weisz Shabtay 1, Ohad Ronen 2
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PMID: 32540318 DOI: 10.1016/j.oooo.2020.04.810
Abstract
Objective: The purpose of our systematic review was to investigate the prevalence of level IV involvement and skip metastases in patients with clinically negative neck (cN0) oral tongue squamous cell carcinoma (OTSCC). The occurrence of occult metastases to lower levels in the neck (levels IV and V) or the development of an erratic distribution of cervical metastases ("skip metastases") that bypass the upper neck levels (levels I to III) and go directly to level IV or V challenges the role of supraomohyoid neck dissection in the treatment of OTSCC; therefore, controversy exists over including level IV cervical nodes during an elective neck dissection of OTSCC.

Study design: Our search included all studies published from 1989 until January 2018 in the Cochrane Library, PubMed, EMBASE, and Web of Science. Abstracts and full-text articles that were deemed potentially relevant were screened. Data from the studies were extracted by using standardized tables, and a meta-analysis was conducted.

Results: In total, 3000 abstracts and 269 full text articles were screened, and 11 studies were included in this analysis. Among the 498 patients included, 16 had level IV involvement, representing involvement of 2.8%. The incidence for skip metastasis to level IV was low as well.

Conclusions: We recommend elective neck dissection that includes levels I to III in selected patients with OTSCC and cN0 neck.

Copyright © 2020 Elsevier Inc. All rights reserved.

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85
Acta Otolaryngol
. 2020 Jun 13;1-8. doi: 10.1080/00016489.2020.1772504. Online ahead of print.
Sleep-related Deglutition and Respiratory Phase Patterns in the Aged With Obstructive Sleep Apnea Under CPAP Therapy
Kiminori Sato 1, Shun-Ichi Chitose 1, Kiminobu Sato 1, Fumihiko Sato 1, Takeharu Ono 1, Hirohito Umeno 1
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PMID: 32536229 DOI: 10.1080/00016489.2020.1772504
Abstract
Background: Respiratory phase patterns associated with deglutition and clearance of pharynx by deglutition are important in protecting airways and lungs against aspiration.Aims/objectives: Sleep-related deglutition and respiratory phase patterns in the aged with obstructive sleep apnea (OSA) before and under CPAP therapy were investigated.Materials and methods: Ten aged adults with severe OSA under CPAP therapy were examined by polysomnography and surface electromyography of the muscles related to swallowing and compared with the same patients before CPAP therapy.Results: Under CPAP therapy, swallowing was also infrequent and absent for long periods. The deeper the sleep stage, the lower the deglutition frequency. The median number of swallows per hour during total sleep time was 1.5 and the median longest deglutition-free period was 74.5 min. Swallows following and/or followed by inspiration, which were observed a great deal before CPAP therapy, were markedly reduced. On the other hand, swallows following and/or followed by expiration markedly increased. Approximately, 73.5% of swallows occurred after expiration and approximately 66.8% were followed by expiration. Respiratory phase patterns associated with sleep-related deglutition improved under CPAP.Conclusions/significance: CPAP therapy improved sleep-related deglutition and respiratory phase patterns in the aged with OSA.

Keywords: CPAP therapy; Sleep-related deglutition; obstructive sleep apnea; respiratory phase pattern; sleep; the aged.

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86
Am J Rhinol Allergy
. 2020 Jun 13;1945892420931713. doi: 10.1177/1945892420931713. Online ahead of print.
House Dust Mite Sublingual Immunotherapy in Children Versus Adults With Allergic Rhinitis
Jin Youp Kim 1, Chae-Seo Rhee 2 3 4 5, Seong H Cho 6, Goun Choe 2, Dong-Young Kim 2, Doo Hee Han 2
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PMID: 32538099 DOI: 10.1177/1945892420931713
Abstract
Background: There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL).

Objective: To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events.

Methods: Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26).

Results: The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups (p < 0.001, both); however, changes in TNSS from baseline did not significantly differ between the two groups (p = 0.365). More patients in adult group were satisfied with SLIT than those in child group (p = 0.050), and changes in RQLQ score from baseline tended to be larger in adult group (p = 0.089). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different.

Conclusion: Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Keywords: adult; allergic; child; clinical efficacy; house dust mite; immunological; nasal; quality of life; rhinitis; sublingual immunotherapy.

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87
Rhinology
. 2020 Jun 15. doi: 10.4193/Rhin19.383. Online ahead of print.
Zinc-depletion Associates With Tissue Eosinophilia and Collagen Depletion in Chronic Rhinosinusitis
M Suzuki 1 2, M Ramezanpour 1, C Cooksley 1, T J Lee 1, B Jeong 1, S Kao 1, T Suzuki 2, A J Psaltis 1, Y Nakamaru 2, A Homma 2, P J Wormald 1, S Vreugde 1
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PMID: 32542237 DOI: 10.4193/Rhin19.383
Abstract
Background: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro.

Methodology: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts.

Results: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion.

Conclusions: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.

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88
Medicine (Baltimore)
. 2020 Jun 12;99(24):e20682. doi: 10.1097/MD.0000000000020682.
DNA Methylation-Based Diagnostic and Prognostic Biomarkers of Nasopharyngeal Carcinoma Patients
Zeng-Hong Wu 1 2, Tao Zhou 1, Hai-Ying Sun 1 3
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PMID: 32541515 DOI: 10.1097/MD.0000000000020682
Free article
Abstract
Nasopharyngeal carcinoma (NPC) is the most common malignant tumor with a remarkable racial and geographical distribution including people in southern China, South East Asia, and the Middle East/North Africa. DNA methylation is an important manifestation of epigenetic modification, has been studied over several decades, and by regulating and controlling the expression of cancer-related genesits, abnormal DNA methylation can influence in a variety of human malignancy tumors.Until now, there is no analysis focus on differentially methylated, differential expressed genes (MDEGs) study, so we make a joint analysis for both gene methylation profiling microarray and gene expression profiling microarray in NPC. Two gene expression datasets (GSE64634 and GSE12452) and gene methylation profiling data set (GSE62336) were downloaded from GEO and analyzed using the online tool GEO2R to identify MDEGs. Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially methylated genes were performed. The STRING database was used to evaluate the interactions of MDEGs and to construct a protein-protein interaction (PPI) network using Cytoscape software. Hub genes were validated with the cBioPortal database.The overlap among the 3 datasets contained 135 hypermethylation genes and 541 hypomethylation genes between NPC and non-NPC samples. A total of 4 genes (TROAP, PCOLCE2, HOXA4, and C1QB) in Hyper-LGs and 14 genes (DYNC1H1, LNX1, RAB37, ALDH3A1, SLC24A4, CP, CEP250, ANK2, DNAI2, MUC13, ACACB, GABRP, STX7, and TTC9) in Hypo-HGs were identified as hub genes.The study of DNA methylation and gene expression provides us a strong support as well as new comprehensive information of MDEGs to the revelation of nasopharyngeal carcinoma's complex pathogenesis. However, further studies are needed to elucidate the biological function of these genes in NPC in the future.

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89
Radiother Oncol
. 2020 Jun 13;S0167-8140(20)30339-X. doi: 10.1016/j.radonc.2020.06.016. Online ahead of print.
Saliva Electrolyte Analysis and Xerostomia-Related Quality of Life in Nasopharyngeal Carcinoma Patients Following Intensity-Modulated Radiation Therapy
Xinmiao Lan 1, Jason Y K Chan 2, Jingya Jane Pu 1, Wei Qiao 3, Siling Pang 1, Wei-Fa Yang 1, Kenneth C W Wong 4, Dora L W Kwong 5, Yu-Xiong Su 6
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PMID: 32544605 DOI: 10.1016/j.radonc.2020.06.016
Abstract
Background and purpose: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and the first-line treatment is radiotherapy. Intensity-modulated radiation therapy (IMRT) can deliver high dose to cancer and low dose to normal tissue, but xerostomia is still one of the complications after IMRT. However, how the concentration of saliva electrolytes be affected by IMRT and the effects on the quality of life are still unknown. In this prospective study, 76 NPC patients were recruited from hospitals in Hong Kong to identify the change of saliva electrolytes and xerostomia-related quality of life before and after IMRT.

Methods and materials: Saliva and questionnaire were collected before IMRT, 1 month, 3 months, 6 months and 12 months after IMRT. The concentration of saliva electrolytes was detected using inductively coupled plasma-optical emission spectroscopy (ICP-OES).

Results: Saliva flow rate significantly decreased after IMRT. Decrease in the mean value of pH was observed but the difference is not statistically significant. The concentrations of potassium, iodine, and calcium decreased and chloride concentration increased after IMRT, while the concentrations of sodium, magnesium, copper or zinc were kept at the same level before and after treatment. Xerostomia-related quality of life was adversely affected by IMRT, but partially recovered after 1 year.

Conclusions: Our study revealed the change of saliva electrolytes and xerostomia-related quality of life in patients undergone IMRT for NPC.

Keywords: Nasopharyngeal carcinoma; Radiotherapy; Saliva electrolytes; Xerostomia.

Copyright © 2020. Published by Elsevier B.V.

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90
Review Trends Cancer
. 2020 Jun 12;S2405-8033(20)30164-3. doi: 10.1016/j.trecan.2020.05.009. Online ahead of print.
Clinical Development of BRAF Plus MEK Inhibitor Combinations
Vivek Subbiah 1, Christina Baik 2, John M Kirkwood 3
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PMID: 32540454 DOI: 10.1016/j.trecan.2020.05.009
Abstract
Genomic profiling shows that many solid tumors are characterized by specific driver aberrations, and this has expanded the therapeutic options for many patients. The mitogen-activated protein kinase (MAPK) pathway is a key cell signaling pathway involved in regulating cellular growth, proliferation, and survival. Driver mutations in the BRAF gene, a key player in the MAPK pathway, are described in multiple tumor types, including subsets of melanoma, non-small cell lung cancer (NSCLC), and anaplastic thyroid cancer (ATC), making BRAF a desirable target for inhibition. BRAF inhibitors have shown efficacy in several cancers; however, most patients eventually develop resistance. To delay or prevent resistance, combination therapy targeting BRAF and MEK, a downstream signaling target of BRAF in the MAPK pathway, was evaluated and demonstrated synergistic benefit. BRAF and MEK inhibitor combinations have been approved for use in various cancers by the US FDA. We review the clinical data for various BRAF plus MEK combination regimens in three cancer types with underlying BRAF driver mutations: melanoma, NSCLC, and ATC. We also discuss practical treatment considerations and management of selected combination therapy toxicities.

Keywords: BRAF V600 mutation; BRAF inhibitor; MEK inhibitor; anaplastic thyroid cancer; melanoma; non-small cell lung cancer.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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91
Comparative Study BMC Surg
. 2020 Jan 29;20(1):18. doi: 10.1186/s12893-020-0685-3.
Comparison of Quality of Life Between Patients Undergoing Trans-Oral Endoscopic Thyroid Surgery and Conventional Open Surgery
Pornthep Kasemsiri 1 2 3, Srongpaun Trakulkajornsak 4, Piyapong Bamroong 5, Kanokkarn Mahawerawat 5, Patorn Piromchai 4, Teeraporn Ratanaanekchai 4 6
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PMID: 31996201 PMCID: PMC6988280 DOI: 10.1186/s12893-020-0685-3
Free PMC article
Abstract
Background: Trans-oral endoscopic thyroidectomy allows obviating scar of the neck that expects to gain quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore, this study compared the QOL outcomes, including cosmetic outcomes, between thyroidectomy by trans-oral endoscopy and conventional open surgery.

Methods: A study was conducted from January 30, 2017 to November 10, 2018. Thirty-two and 38 patients underwent trans-oral endoscopic thyroid surgery and conventional open surgery, respectively. Their quality of life was evaluated at 2, 6, and 12 weeks postoperatively using a thyroid surgery-specific questionnaire and a 36-item short-form questionnaire.

Results: Trans-oral endoscopic group, patients were younger and presented with smaller thyroid nodules (p < 0.05). Regarding surgical outcomes, there were no statistically significant differences between the two groups. Mean operative time was significantly longer in the trans-oral endoscopic group (p < 0.05). The quality of life parameters in the trans-oral endoscopic group was significantly better than in the conventional surgery group (p < 0.05). These parameters included reduction of physical activity, psychosocial impairment, the role of physic, and emotion at 2 weeks after surgery; swallowing impairment, psychosocial impairment, the role of physic, social function and mental health 6 weeks after surgery; tingling and feeling of vitality at 12 weeks after surgery. Cosmetic outcomes and overall satisfaction were significantly better in the trans-oral endoscopic group than in the conventional surgery group at all of our follow up times (p < 0.05).

Conclusions: The trans-oral endoscopic approach allows real scarless on the skin with better cosmetic and QOL outcomes.

Trial registration: This trial was retrospectively registered at the ClinicalTrial.gov (NCT03048539), registered on 4 March 2017.

Keywords: Endoscopy; Quality of life; Scarring; Thyroidectomy.

Conflict of interest statement
The authors declare that they have no competing interests.

23 references
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92
Front Genet
. 2020 May 27;11:495. doi: 10.3389/fgene.2020.00495. eCollection 2020.
Role of Endoplasmic Reticulum Stress in Otitis Media
Hongchun Zhao 1 2, Yanfei Wang 2, Bo Li 3, Tihua Zheng 3, Xiuzhen Liu 4, Bo Hua Hu 5, Juan Che 2, Tong Zhao 3, Jun Chen 2, Maria Hatzoglou 6, Xiaolin Zhang 2, Zhaomin Fan 1, Qingyin Zheng 7
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PMID: 32536938 PMCID: PMC7267009 DOI: 10.3389/fgene.2020.00495
Free PMC article
Abstract
Endoplasmic reticulum (ER) stress occurs in many inflammatory responses. Here, we investigated the role of ER stress and its associated apoptosis in otitis media (OM) to elucidate the mechanisms of OM and the signaling crosstalk between ER stress and other cell damage pathways, including inflammatory cytokines and apoptosis. We examined the expression of inflammatory cytokine- and ER stress-related genes by qRT-PCR, Western blotting, and immunohistochemistry (IHC) in the middle ear of C57BL/6J mice after challenge with peptidoglycan polysaccharide (PGPS), an agent inducing OM. We also evaluated the effect of the suppression of ER stress with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. The study revealed the upregulation of ER stress- and apoptosis-related gene expression after the PGPS treatment, specifically ATF6, CHOP, BIP, caspase-12, and caspase-3. TUDCA treatment of PGPS-treated mice decreased OM; reduced the expression of CHOP, BIP, and caspase 3; and significantly decreased the proinflammatory gene expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These results suggest that PGPS triggers ER stress and downstream proinflammatory gene expression in OM and that inhibition of ER stress alleviates OM. We propose that ER stress plays a critical role in inflammation and cell death, leading to the development of OM and points to ER stress inhibition as a potential therapeutic approach for the prevention of OM.

Keywords: apoptosis; endoplasmic reticulum (ER) stress; otitis media; streptococcal peptidoglycan polysaccharide; tauroursodeoxycholic acid; therapy.

Copyright © 2020 Zhao, Wang, Li, Zheng, Liu, Hu, Che, Zhao, Chen, Hatzoglou, Zhang, Fan and Zheng.

46 references4 figures
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93
Curr Probl Diagn Radiol
. 2020 May 17;S0363-0188(20)30104-3. doi: 10.1067/j.cpradiol.2020.04.009. Online ahead of print.
A Multimodal Diagnostic Approach to Inverted Papilloma: Proposal of a Novel Diagnostic Flow-Chart
Camilla Russo 1, Andrea Elefante 2, Antonio Romano 3, Antonia Cama 3, Maurizio Erra 2, Lorenzo Ugga 2, Lisa Brunetti 4, Gaetano Motta 5, Luigi Califano 3, Maurizio Iengo 6, Elena Cantone 6
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PMID: 32540138 DOI: 10.1067/j.cpradiol.2020.04.009
Abstract
Purpose: Inverted papilloma (IP) is a tumor usually arising from sinonasal cavities, with tendency for recurrence and possible malignant transformation. Along with endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) play a crucial role in defining preoperative staging, tumor origin, and possible differential diagnosis, with significant repercussions on therapeutic planning. However, at present no consensus has been reached concerning IP diagnostic workup. Aim of this study is to assess CT and MRI sensitivity and specificity in identifying IP imaging hallmarks, evaluating their global diagnostic accuracy in order to define a novel diagnostic flowchart.

Methods: We retrospectively analyzed multimodal imaging of patients with histologically confirmed IP and mimics. Two neuroradiologists in consensus retrospectively rated the presence of typical imaging features of IP, both on CT and MRI scans. Sensitivity, specificity and diagnostic accuracy were assessed for both the techniques. Final results were expressed as ROC curves and relative areas under the curve (AUC).

Results: The AUC considering CT parameters were 0.42, whereas the AUC considering MRI parameters were 0.54. Combining the 2 techniques and limiting the evaluation to the most distinctive features such as focal hyperostosis and CCP, the AUC was 0.79.

Conclusion: MRI can provide better tissue characterization and higher diagnostic accuracy in case of suspected IP, whereas CT is more useful in determining bony involvement. Here we propose a possible diagnostic flowchart for IP, based on the assumption that the combination of the imaging techniques allows to optimize the clinical assessment and the subsequent therapeutic planning.

Copyright © 2020 Elsevier Inc. All rights reserved.

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94
Otolaryngol Head Neck Surg
. 2020 Jun 16;194599820931455. doi: 10.1177/0194599820931455. Online ahead of print.
Intranasal Corticosteroid Therapy: Systematic Review and Meta-analysis of Reported Safety and Adverse Effects in Adults
Angela M Donaldson 1, Garret Choby 2, Daniel H Kim 3, Lisa A Marks 4, Devyani Lal 5
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PMID: 32539494 DOI: 10.1177/0194599820931455
Abstract
Objectives: To address concerns related to the safety profile of both Food and Drug Administration (FDA)-approved and non-FDA-approved intranasal corticosteroid (INCS) use in the adult population.

Data source: Systematic review of MEDLINE, PubMed, and EMBASE databases using a comprehensive search strategy including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles.

Review methods: A structured literature search was conducted. Each study was graded for level of evidence using the Oxford Centre for Evidence-Based Medicine. Extracted data included population size, study design, drug (dosage, route, and frequency), presence of hypothalamus pituitary axis suppression, ocular symptoms, and treatment-related adverse events.

Results: A total of 60 studies met inclusion criteria. The studies included use of INCS as metered nasal sprays, drops, injections, aerosols, and irrigations. There were no persistent abnormalities in cortisol level or intraocular pressure change. Meta-analysis of epistaxis showed a significantly increased risk in the FDA-approved treatment group in comparison with control (risk ratio 1.56; 95% confidence interval, 1.13-2.14; P = .007).

Conclusions: Overall, it appears that the use of both FDA and published non-FDA application of INCS are safe in the adult population. Meta-analysis demonstrated an increased risk of epistaxis in patients using INCS compared with placebo. Otherwise, there was no significant difference between in adults in the treatment group and placebo group. As an important caveat, the interpretation of safety of nonstandard INCS is restricted to delivery methods and dosages published in the literature.

Keywords: adverse effect; complication; corticosteroid; intranasal steroid; nasal steroid; side effect; topical steroid; toxicity.

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95
J Oral Maxillofac Surg
. 2020 May 14;S0278-2391(20)30464-X. doi: 10.1016/j.joms.2020.05.011. Online ahead of print.
Nasal Floor Asymmetry Is Associated With Nasal Obstruction
Herbert Riechelmann 1, Mag Gerlig Widmann 2, Barbara Kofler 3, Roman Arminger 4, Christoph Url 3, Aris I Giotakis 5
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PMID: 32544472 DOI: 10.1016/j.joms.2020.05.011
Abstract
Purpose: The role of morphologic characteristics of the nasal cavity in nasal obstruction is not yet sufficiently understood. The aim of this study was to determine which morphometric parameters of the nasal cavity severely impair nasal breathing and when.

Patients and methods: In a hospital-based, computed tomography-morphometric cross-sectional study, we evaluated computed tomography coronal scans of patients with known nasal obstruction scheduled to undergo functional nasal surgical procedures (cases) and trauma patients without facial involvement or known nasal obstruction (controls). The primary predictor variable was case versus control. In both groups, we measured and compared the piriform aperture width; nasal floor canting; piriform aperture vertical height, height-width ratio, and total cross-sectional area; height difference between the right and left nasal floors; and nasal septal thickness; as well as age and gender differences. Metric data means, standard deviations, and 95% confidence intervals were calculated and analyzed.

Results: The sample was composed of 60 patients evenly divided between cases and controls. Of these, 30 were men. The average age of the cases and controls was 27.4 ± 7.8 years and 38.5 ± 18.6 years, respectively (P < .001). The differences in piriform aperture width was not statistically significant between cases and controls (23.3 ± 1.9 mm and 23.8 ± 1.7 mm, respectively; P > .2). In contrast, we found statistically significant differences between cases and controls in nasal floor canting (5.4° ± 4.6° and 1.8° ± 1.5°, respectively; P < .001) and height difference between the right and left nasal floors (1.8 ± 1.2 and 1.0 ± 0.7 mm, respectively; P = .002).

Conclusions: Nasal floor canting of 3° or greater and a height difference between the right and left nasal floors of 1.5 mm or greater may contribute to the etiology of clinically relevant nasal obstruction. A piriform aperture width of 22 mm or less may be considered narrow. Future studies can determine when and how exactly to surgically address a clinically relevant narrow piriform aperture and nasal floor canting.

Copyright © 2020. Published by Elsevier Inc.

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96
Laryngoscope
. 2020 Jun 16. doi: 10.1002/lary.28776. Online ahead of print.
Utility of Transnasal Humidified Rapid Insufflation Ventilatory Exchange for Microlaryngeal Surgery
Michael S Benninger 1, Emily S Zhang 2, Bonnie Chen 3, William S Tierney 1, Basem Abdelmalak 4, Paul C Bryson 1 2 3
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PMID: 32542687 DOI: 10.1002/lary.28776
Abstract
Objective: Microlaryngeal surgery typically requires oxygenation and ventilation via either an endotracheal tube (ETT), jet ventilation (JV), or intermittent apnea with an ETT. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) delivered by high flow nasal cannula has been reported as an alternative technique. This method of apneic oxygenation and ventilation allows for stable, unobstructed visualization of immobile laryngeal structures. We aim to describe the technique and characterize intraoperative parameters related to its safety.

Study design: Case Series.

Methods: The electronic medical record was reviewed for patients who underwent microlaryngoscopy using THRIVE technique. Patient demographics, procedural details, operative parameters, and anesthesia records were reviewed. Descriptive statistics were reported.

Results: A total of 53 patients underwent microlaryngoscopy using THRIVE as the sole method of ventilation, with 62% female. Median age was 51 years, and median BMI was 25 kg/m2 . Most patients were ASA class 2, and most had a Mallampati score of 2. The most common surgical indications were subglottic stenosis, vocal fold lesions, and vocal fold paralysis. Median apnea time was 16 minutes. At the end of case, median end tidal CO2 was 50 mmHg, and median minimum SpO2 was 95. Six cases required supplementation of THRIVE with JV or tracheal intubation for sustained oxygen desaturation. There was an increase in end tidal CO2 of 0.844 mmHg/min of apneic time.

Conclusions: THRIVE is a safe and effective technique for oxygenation and ventilation in microlaryngeal, non-laser surgery in appropriately selected patients. To ensure safety, back-up plans such as jet ventilation and microlaryngeal ETT should be available.

Level of evidence: 4 Laryngoscope, 2020.

Keywords: THRIVE; apneic oxygenation; high-flow nasal oxygen; microlaryngeal surgery; otolaryngology.

© 2020 The American Laryngological, Rhinological and Otological Society, Inc.

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97
Br J Neurosurg
. 2020 Jun 15;1-7. doi: 10.1080/02688697.2020.1779659. Online ahead of print.
Surgical Outcomes in Patients With Endoscopic Versus Transcranial Approach for Skull Base Malignancies: A 10-year Institutional Experience
John W Rutland 1, Corey M Gill 1, Travis Ladner 1, David Goldrich 2, Dillan F Villavisanis 2, Alex Devarajan 1, Akila Pai 1, Amir Banihashemi 3, Brett A Miles 2, Sonam Sharma 4, Priti Balchandani 5, Joshua B Bederson 1, Alfred M Iloreta 2, Raj K Shrivastava 1
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PMID: 32538686 DOI: 10.1080/02688697.2020.1779659
Abstract
Object: The authors performed an extensive comparison between patients treated with open versus an endoscopic approach for skull base malignancy with emphasis on surgical outcomes.Methods: A single-institution retrospective review of 60 patients who underwent surgery for skull base malignancy between 2009 and 2018 was performed. Disease features, surgical resection, post-operative morbidities, adjuvant treatment, recurrence, and survival rates were compared between 30 patients who received purely open surgery and 30 patients who underwent purely endoscopic resection for a skull base malignancy.Results: Of the 60 patients with skull base malignancy, 30 underwent open resection and 30 underwent endoscopic resection. The most common hisotype for endoscopic resection was squamous cell carcinoma (26.7%), olfactory neuroblastoma (16.7%), and sarcoma (10.0%), and 43.3%, 13.3%, and 10.0% for the open resection cohort, respectively. There were no statistical differences in gross total resection, surgical-associated cranial neuropathy, or ability to achieve negative margins between the groups (p > 0.1, all comparisons). Patients who underwent endoscopic resection had shorter surgeries (320.3 ± 158.5 minutes vs. 495.3 ± 187.6 minutes (p = 0.0003), less intraoperative blood loss (282.2 ± 333.6 ml vs. 696.7 ± 500.2 ml (p < 0.0001), and shorter length of stay (3.5 ± 3.7 days vs. 8.8 ± 6.0 days (p < 0.0001). Additionally, patients treated endoscopically initiated adjuvant radiation treatment more quickly (48.0 ± 20.3 days vs. 72.0 ± 20.5 days (p = 0.01).Conclusions: An endoscopic endonasal approach facilitates a clinically meaningful improvement in surgical outcomes for skull base malignancies.

Keywords: Skull base surgery; endoscopic surgery; gross total resection; malignancy; transcranial surgery.

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98
Cureus
. 2020 May 11;12(5):e8060. doi: 10.7759/cureus.8060.
Surgical Management of Choanal Atresia With Intranasal Hegar's Dilator and Transnasal Endoscopic Excision: A 20-year Retrospective Comparative Study
Mohammad A Alshareef 1, Abdullah S Assalem 2, Fatimah Alzubaidi 3, Basem Damanhouri Sr 3, Tariq A Al-Aidarous 4
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PMID: 32537278 PMCID: PMC7286581 DOI: 10.7759/cureus.8060
Free PMC article
Abstract
Background Although choanal atresia (CA) was first described 250 years ago, its description and understanding remain incomplete, as is the distinction between unilateral and bilateral CA. Among the surgical techniques introduced to manage this condition are intranasal Hegar's dilator (IHD) and transnasal endoscopic excision (TNEE). Objectives This study retrospectively evaluated the outcomes and effectiveness of IHD and TNEE in the treatment of patients with CA, including differences in the incidence of re-stenosis with these techniques. Methods Patients diagnosed with CA who underwent surgical interventions in the Otolaryngology Department of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, between 1997 and 2017 were analyzed. Postoperative outcomes including re-stenosis rates were compared in patients who underwent IHD and TNEE. Factors associated with patient outcomes were analyzed, including ages at diagnosis and surgery, nationality, gender, type of atresia (unilateral/bilateral and bony/membranous/mixed), surgical intervention (IHD or TNEE), and re-stenosis and need for revision surgery after IHD and TNEE. Results A total of 30 patients were diagnosed with CA, including 21 (70%) girls and 9 (30%) boys. Of them, 18 (60%) patients were diagnosed at younger than one month of age, 28 (93%) were Saudi nationals, and 20 (67.70%) were aged younger than three months at the time of surgery. Of these 30 patients, 17 (56.70%, all Saudi nationals) underwent IHD, and 13 (43.30%), including 15 Saudi nationals, underwent TNEE. The 17 patients who underwent IHD included 13 (76.50%) girls and 4 (23.50%) boys, whereas the 13 patients who underwent TNEE included 8 (61.50%) girls and 5 (38.50%) boys. Fifteen patients (50%) had mixed-type CA, nine (30%) had bony-type CA, and six (20%) had membranous-type CA. Twenty-six (86.67%) patients underwent primary surgery, whereas four (13.33%) underwent revision surgery; of the latter, three (75%) had undergone primary IHD, and one had undergone primary TNEE. Only one (3.33%) patient experienced re-stenosis after revision surgery, which consisted of IHD. Twelve patients (40%) underwent stenting, with one developing re-stenosis. The relationships between surgical approach and re-stenosis after primary and secondary surgery were not statistically significant. Conclusion The outcomes in patients with CA treated with IHD and TNEE are comparable. Rates of re-stenosis and need for revision surgery do not differ significantly in patients treated with these surgical approaches.

Keywords: choanal atresia; endoscopy; excision; hegar’s dilator; intranasal; surgery; transnasal.

Copyright © 2020, Alshareef et al.

Conflict of interest statement
The authors have declared that no competing interests exist.

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99
Head Neck
. 2020 Jun 16. doi: 10.1002/hed.26325. Online ahead of print.
Added Value of Metastatic Cervical Lymph Node Group V in Nodal Staging of Nasopharyngeal Cancer
Jiraporn Setakornnukul 1, Kullathorn Thephamongkhol 1, Panid Chaysiri 1
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PMID: 32542997 DOI: 10.1002/hed.26325
Abstract
Background: Prognostic significance of posterior cervical lymph node metastasis in nasopharyngeal cancer is largely unknown. This study aims to determine the added prognostic significance of cervical lymph node group V to the standard American Joint Committee on Cancer (AJCC) staging system (eighth edition AJCC) of nasopharyngeal patients with cancer treated with intensity-modulated radiation therapy (IMRT) in terms of overall survival (OS), distant metastatic-free survival (DMFS), and disease-free survival (DFS).

Methods and materials: A retrospective cohort of 199 consecutively diagnosed nasopharyngeal patients with cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in the era of IMRT in a large university hospital in endemic area of Southeast Asia. Pre-treatment imaging studies were thoroughly re-evaluated and re-staged by a board-certified radiologist using radiographic criteria for cervical lymph node metastasis. T and N classifications were reclassified according to the eighth AJCC staging system. Group V (Va and Vb) cervical node was evaluated for its added prognostic significance. Cox's proportional hazard model was used to retrieve hazard ratio (HR), 95% confidence interval and P value for N classification. Harrell's C-statistic (concordance index) was used for test of discrimination and internal validation was calculated by bootstrap method.

Results: This study demonstrated greater separation of OS with HR of 6.75 (95%CI 1.94-23.51, P = .003) by using group Vb only as N3 compared to HR of 4.70 (95%CI 1.37-16.13, P = .014) by using current standard N3 disease (groups IV and Vb). Similarly, N2 with presence of Va shows worsened DFS with HR of 8.70 (95%CI 1.08-69.67, P = .042) compared to N2 without Va with HR of 5.93 (95%CI 0.76-46.00, P = .089). After incorporating cervical group V into nodal staging, the HR and 95%CI among each group was better separated than the eighth AJCC staging system but without significant improvement in C-index.

Conclusion: Cervical lymph node group V is a potentially added prognostic factor to standard TNM staging.

Keywords: Cervical lymph node group V; eight AJCC; nasopharyngeal cancer; prognostic value; radiotherapy.

© 2020 Wiley Periodicals, Inc.

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100
Am J Rhinol Allergy
. 2020 Jun 15;1945892420930953. doi: 10.1177/1945892420930953. Online ahead of print.
The Role of Home Fungal Exposure in Allergic Fungal Rhinosinusitis
Nicholas R Rowan 1 2, Kristina A Storck 1, Rodney J Schlosser 1 3, Zachary M Soler 1
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PMID: 32539434 DOI: 10.1177/1945892420930953
Abstract
Background: Allergic fungal rhinosinusitis (AFRS) is disproportionately identified in patients of low socioeconomic status living in warm, humid climates, and is thought to occur in response to environmental fungal species.

Objective: We hypothesized that micro-geographic differences in fungal exposure contribute to the pathogenesis of AFRS, and compared home fungal exposure of patients with AFRS to normative data and controls.

Methods: Comprehensive prospective enrollment and data capture was completed in 70 patients. Patients with AFRS were compared to a control population with chronic rhinosinusitis with nasal polyposis (CRSwNP) and comorbid atopy. Comprehensive demographics, 22-item sino-nasal outcomes test (SNOT-22) questionnaires, and endoscopy scores were compiled. Using a test strip collection system, a home fungal assessment was completed for each patient, along with detailed questions related to home condition.

Results: Patients with AFRS were more likely to be younger (p<.001), African American (p<.001), from a lower income bracket (p < .012), and less likely to own their home (p < .001). There were no differences in prior surgeries (p=.432), endoscopy scores (p = .409) or SNOT-22 scores (p = .110) between the groups. There were no differences in overall fungal counts between patients with AFRS and controls (p = .981). AFRS patients had a higher prevalence of Basidiospores than controls (p = .034).

Conclusion: This study failed to detect differences in total home fungal exposure levels between those with AFRS and atopic CRSwNP, despite differences in socioeconomic status. This suggests that absolute fungal levels may not be the primary driver in development of AFRS, or that the fungal detection strategies utilized were not representative of patients' overall fungal exposure.

Keywords: allergic fungal rhinoallergic fungal sinusitis; allergy; chronic rhinosinusitis; fungus; nasal polyps; public health; sinusitis; sinusitis sinus surgery.

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