BioMed Research International: Otolaryngology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Association of Polymorphic Variants of miRNA Processing Genes with Larynx Cancer Risk in a Polish Population Wed, 25 Nov 2015 08:54:11 +0000 Laryngeal cancer (LC) is one of the most prevalent types of head and neck cancer. An increasing interest has been focused on the role of microRNA (miRNAs) in LC development. The study group consisted of 135 larynx cancer patients and 170 cancer-free individuals. Nine polymorphisms of pre-miRNA processing genes, DROSHA (rs6877842), DGCR8 (rs3757, rs417309, and rs1640299), RAN (rs14035), XPO5 (rs11077), DICER1 (rs13078 and rs3742330) and TARBP2 (rs784567), were performed by TaqMan SNP Genotyping Assay. It was found that the frequency of the GT and the TT polymorphic variants of XPO5 gene were higher in LC patients than in controls ( and , resp.). In turn, the frequency of the CT genotype of RAN gene was higher in controls than in LC patients (). The TT and the AG of DICER1 gene ( for rs13078 and for rs3742330) as well as the AG and the GG genotypes of TARBP2 gene ( and , resp.) were associated with higher risk of LC occurrence. Our data suggested that polymorphisms of miRNA processing genes might be useful as predictive factors for the LC development. Ewa Osuch-Wojcikiewicz, Antoni Bruzgielewicz, Kazimierz Niemczyk, Olga Sieniawska-Buccella, Alicja Nowak, Anna Walczak, and Ireneusz Majsterek Copyright © 2015 Ewa Osuch-Wojcikiewicz et al. All rights reserved. Pathology of Tinnitus and Hyperacusis-Clinical Implications Mon, 26 Oct 2015 14:10:15 +0000 Aage R. Moller, Richard Salvi, Dirk De Ridder, Tobias Kleinjung, and Sven Vanneste Copyright © 2015 Aage R. Moller et al. All rights reserved. Temporal Bone Pneumatization and Pulsatile Tinnitus Caused by Sigmoid Sinus Diverticulum and/or Dehiscence Sun, 25 Oct 2015 11:36:17 +0000 Background. Although air cells within temporal bone may play an important role in the transmission of pulsatile tinnitus (PT) noise, it has not been studied systematically. Purpose. To evaluate the difference in temporal bone pneumatization between PT patients with sigmoid sinus diverticulum and/or dehiscence (SSDD) and healthy people. Material and Methods. A total of 199 unilateral persistent PT patients with SSDD and 302 control subjects underwent dual-phase contrast-enhanced CT (DP-CECT), to assess the grade of temporal bone pneumatization in each ear. Results. In the bilateral temporal bone of 302 controls, 16 ears were grade I, 53 were grade II, 141 were grade III, and 394 were grade IV. Among the affected ears of 199 PT cases, 1 ear was grade I, 18 were grade II, 53 were grade III, and 127 were grade IV. There was no significant difference in the pneumatization grade between the affected PT ear and either ear in the healthy subjects .  Conclusion. Although air cells within the temporal bone are an important factor in the occurrence of PT, its severity does not differ significantly from the pneumatization of healthy people. Liu Wenjuan, Liu Zhaohui, Zheng Ning, Zhao Pengfei, Dong Cheng, and Wang Zhenchang Copyright © 2015 Liu Wenjuan et al. All rights reserved. The Relevance of Interoception in Chronic Tinnitus: Analyzing Interoceptive Sensibility and Accuracy Sun, 25 Oct 2015 11:10:33 +0000 In order to better understand tinnitus and distress associated with tinnitus, psychological variables such as emotional and cognitive processing are a central element in theoretical models of this debilitating condition. Interoception, that is, the perception of internal processes, may be such a psychological factor relevant to tinnitus. Against this background, 20 participants suffering from chronic tinnitus and 20 matched healthy controls were tested with questionnaires, assessing interoceptive sensibility, and participated in two tasks, assessing interoceptive accuracy: the Schandry task, a heartbeat estimation assignment, and a skin conductance fluctuations perception task assessing the participants’ ability to perceive phasic increases in sympathetic activation were used. To test stress reactivity, a construct tightly connected to tinnitus onset, we also included a stress induction. No differences between the groups were found for interoceptive accuracy and sensibility. However, the tinnitus group tended to overestimate the occurrence of phasic activation. Loudness of the tinnitus was associated with reduced interoceptive performance under stress. Our results indicate that interoceptive sensibility and accuracy do not play a significant role in tinnitus. However, tinnitus might be associated with a tendency to overestimate physical changes. Pia Lau, Miriam Miesen, Robert Wunderlich, Alwina Stein, Alva Engell, Andreas Wollbrink, Alexander L. Gerlach, Markus Junghöfer, Thomas Ehring, and Christo Pantev Copyright © 2015 Pia Lau et al. All rights reserved. Psychophysiological Associations between Chronic Tinnitus and Sleep: A Cross Validation of Tinnitus and Insomnia Questionnaires Sun, 25 Oct 2015 11:09:26 +0000 Background. The aim of the present study was to assess the prevalence of insomnia in chronic tinnitus and the association of tinnitus distress and sleep disturbance. Methods. We retrospectively analysed data of 182 patients with chronic tinnitus who completed the Tinnitus Questionnaire (TQ) and the Regensburg Insomnia Scale (RIS). Descriptive comparisons with the validation sample of the RIS including exclusively patients with primary/psychophysiological insomnia, correlation analyses of the RIS with TQ scales, and principal component analyses (PCA) in the tinnitus sample were performed. TQ total score was corrected for the TQ sleep items. Results. Prevalence of insomnia was high in tinnitus patients (76%) and tinnitus distress correlated with sleep disturbance (). TQ sleep subscore correlated with the RIS sum score (). PCA with all TQ and RIS items showed one sleep factor consisting of all RIS and the TQ sleep items. PCA with only TQ sleep and RIS items showed sleep- and tinnitus-specific factors. The sleep factors (only RIS items) were sleep depth and fearful focusing. The TQ sleep items represented tinnitus-related sleep problems. Discussion. Chronic tinnitus and primary insomnia are highly related and might share similar psychological and neurophysiological mechanisms leading to impaired sleep quality. Martin Schecklmann, Maximilian Pregler, Peter M. Kreuzer, Timm B. Poeppl, Astrid Lehner, Tatjana Crönlein, Thomas C. Wetter, Elmar Frank, Michael Landgrebe, and Berthold Langguth Copyright © 2015 Martin Schecklmann et al. All rights reserved. The Relevance of the High Frequency Audiometry in Tinnitus Patients with Normal Hearing in Conventional Pure-Tone Audiometry Sun, 25 Oct 2015 11:07:07 +0000 Objective. The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz–8 kHz). Here we explored whether the results of the high frequency audiometry (>8 kHz) provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical characteristics. Subjects and Methods. From the database of the Tinnitus Clinic at Regensburg we identified 75 patients with normal hearing thresholds in the conventional pure-tone audiometry. We contrasted these patients with normal and pathological high-frequency audiogram and compared them with respect to gender, age, tinnitus severity, pitch, laterality and duration, comorbid symptoms and triggers for tinnitus onset. Results. Patients with pathological high frequency audiometry were significantly older and had higher scores on the tinnitus questionnaires in comparison to patients with normal high frequency audiometry. Furthermore, there was an association of high frequency audiometry with the laterality of tinnitus. Conclusion. In tinnitus patients with normal pure-tone audiometry the high frequency audiometry provides useful additional information. The association between tinnitus laterality and asymmetry of the high frequency audiometry suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis. Veronika Vielsmeier, Astrid Lehner, Jürgen Strutz, Thomas Steffens, Peter M. Kreuzer, Martin Schecklmann, Michael Landgrebe, Berthold Langguth, and Tobias Kleinjung Copyright © 2015 Veronika Vielsmeier et al. All rights reserved. Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus Sun, 25 Oct 2015 09:04:35 +0000 Background. Repetitive transcranial magnetic stimulation (rTMS) has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. Objective. This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. Methods. 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. Results. Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. Conclusion. Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course. Astrid Lehner, Martin Schecklmann, Timm B. Poeppl, Peter M. Kreuzer, Juliette Peytard, Elmar Frank, and Berthold Langguth Copyright © 2015 Astrid Lehner et al. All rights reserved. Tinnitus and Headache Sun, 25 Oct 2015 07:19:00 +0000 Background. Tinnitus and headache are frequent disorders. Here, we aimed to investigate whether the occurrence of headache among tinnitus patients is purely coincidental or whether tinnitus and headache are pathophysiologically linked. We investigated a large sample of patients with tinnitus and headache to estimate prevalence rates of different headache forms, to determine the relationship between tinnitus laterality and headache laterality, and to explore the relationship between tinnitus and headache over time. Method. Patients who presented at a tertiary referral center because of tinnitus and reported comorbid headache were asked to complete validated questionnaires to determine the prevalence of migraine and tension-type headache and to assess tinnitus severity. In addition, several questions about the relationship between headache and tinnitus were asked. Results. Datasets of 193 patients with tinnitus and headache were analysed. 44.6% suffered from migraine, 13% from tension-type headache, and 5.7% from both. Headache laterality was significantly related to tinnitus laterality and in the majority of patients fluctuations in symptom severity of tinnitus and headache were interrelated. Conclusion. These findings suggest a significant relationship between tinnitus and headache laterality and symptom interaction over time and argue against a purely coincidental cooccurrence of tinnitus and headache. Both disorders may be linked by common pathophysiological mechanisms. Berthold Langguth, Verena Hund, Volker Busch, Tim P. Jürgens, Jose-Miguel Lainez, Michael Landgrebe, and Martin Schecklmann Copyright © 2015 Berthold Langguth et al. All rights reserved. Phoniatrics Tue, 20 Oct 2015 09:11:12 +0000 Haldun Oguz, Markus Hess, and Adam M. Klein Copyright © 2015 Haldun Oguz et al. All rights reserved. Acoustic Coordinated Reset Neuromodulation in a Real Life Patient Population with Chronic Tonal Tinnitus Mon, 19 Oct 2015 10:47:52 +0000 Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus symptoms. To test acoustic coordinated reset neuromodulation as a treatment for chronic, tonal tinnitus under real life conditions, an outpatient study “RESET Real Life” was commissioned by ANM GmbH. Herein we present the results of this study. Methods. In a prospective, open-label, nonrandomized, noncontrolled multicenter clinical study with 200 chronic tinnitus patients, tinnitus questionnaire TBF-12 and Global Clinical Improvement-Impression Scale (CGI-I7) are used to study the safety and efficacy of acoustic coordinated reset neuromodulation. 189 patients completed the last 12-month visit, 11 patients dropped out (8 because of nontreatment related reasons; 2 because tinnitus did not change; and 1 because tinnitus got louder). Results. Acoustic coordinated reset neuromodulation caused a statistically and clinically significant decrease in TBF-12 scores as well as in CGI-I7 after 12 months of therapy under real life conditions. There were no persistent adverse events reported that were related to the therapy. Conclusion. The field study “RESET Real Life” provides evidence for safety and efficacy of acoustic coordinated reset neuromodulation in a prospective, open-label, real life setting. Christian Hauptmann, Armin Ströbel, Mark Williams, Nitesh Patel, Hannes Wurzer, Tatjana von Stackelberg, Uwe Brinkmann, Berthold Langguth, and Peter A. Tass Copyright © 2015 Christian Hauptmann et al. All rights reserved. Automatic Prosodic Analysis to Identify Mild Dementia Mon, 19 Oct 2015 07:37:13 +0000 This paper describes an exploratory technique to identify mild dementia by assessing the degree of speech deficits. A total of twenty participants were used for this experiment, ten patients with a diagnosis of mild dementia and ten participants like healthy control. The audio session for each subject was recorded following a methodology developed for the present study. Prosodic features in patients with mild dementia and healthy elderly controls were measured using automatic prosodic analysis on a reading task. A novel method was carried out to gather twelve prosodic features over speech samples. The best classification rate achieved was of 85% accuracy using four prosodic features. The results attained show that the proposed computational speech analysis offers a viable alternative for automatic identification of dementia features in elderly adults. Eduardo Gonzalez-Moreira, Diana Torres-Boza, Héctor Arturo Kairuz, Carlos Ferrer, Marlene Garcia-Zamora, Fernando Espinoza-Cuadros, and Luis Alfonso Hernandez-Gómez Copyright © 2015 Eduardo Gonzalez-Moreira et al. All rights reserved. Hyperacusis Questionnaire as a Tool for Measuring Hypersensitivity to Sound in a Tinnitus Research Population Sun, 18 Oct 2015 13:34:38 +0000 Hypersensitivity to external sounds is often comorbid with tinnitus and may be significant for adherence to certain types of tinnitus management. Therefore, a clear measure of sensitivity to sound is important. The aim of this study was to evaluate the validity and reliability of the Hyperacusis Questionnaire (HQ) for use as a measurement tool using data from a sample of 264 adults who took part in tinnitus research. We evaluated the HQ factor structure, internal consistency, convergent and discriminant validity, and floor and ceiling effects. Internal consistency was high (Cronbach’s alpha = 0.88) and moderate correlations were observed between the HQ, uncomfortable loudness levels, and other health questionnaires. Confirmatory factor analysis revealed that the original HQ three-factor solution and a one-factor solution were both a poor fit to the data. Four problematic items were removed and exploratory factor analysis identified a two-factor (attentional and social) solution. The original three-factor structure of the HQ was not confirmed. All fourteen items do not accurately assess hypersensitivity to sound in a tinnitus population. We propose a 10-item (2-factor) version of the HQ, which will need to be confirmed using a new tinnitus and perhaps nontinnitus population. Kathryn Fackrell, Constance Fearnley, Derek J. Hoare, and Magdalena Sereda Copyright © 2015 Kathryn Fackrell et al. All rights reserved. Spoken Word Recognition Errors in Speech Audiometry: A Measure of Hearing Performance? Sun, 18 Oct 2015 12:27:58 +0000 This report provides a detailed analysis of incorrect responses from an open-set spoken word-repetition task which is part of a Dutch speech audiometric test battery. Single-consonant confusions were analyzed from 230 normal hearing participants in terms of the probability of choice of a particular response on the basis of acoustic-phonetic, lexical, and frequency variables. The results indicate that consonant confusions are better predicted by lexical knowledge than by acoustic properties of the stimulus word. A detailed analysis of the transmission of phonetic features indicates that “voicing” is best preserved whereas “manner of articulation” yields most perception errors. As consonant confusion matrices are often used to determine the degree and type of a patient’s hearing impairment, to predict a patient’s gain in hearing performance with hearing devices and to optimize the device settings in view of maximum output, the observed findings are highly relevant for the audiological practice. Based on our findings, speech audiometric outcomes provide a combined auditory-linguistic profile of the patient. The use of confusion matrices might therefore not be the method best suited to measure hearing performance. Ideally, they should be complemented by other listening task types that are known to have less linguistic bias, such as phonemic discrimination. Martine Coene, Anneke van der Lee, and Paul J. Govaerts Copyright © 2015 Martine Coene et al. All rights reserved. Stem Cell Therapy in Injured Vocal Folds: A Three-Month Xenograft Analysis of Human Embryonic Stem Cells Sun, 18 Oct 2015 12:15:10 +0000 We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives. Bengt Svensson, Srinivasa R. Nagubothu, Christoffer Nord, Jessica Cedervall, Isabell Hultman, Lars Ährlund-Richter, Anna Tolf, and Stellan Hertegård Copyright © 2015 Bengt Svensson et al. All rights reserved. A Fast Semiautomatic Algorithm for Centerline-Based Vocal Tract Segmentation Sun, 18 Oct 2015 12:13:51 +0000 Vocal tract morphology is an important factor in voice production. Its analysis has potential implications for educational matters as well as medical issues like voice therapy. The knowledge of the complex adjustments in the spatial geometry of the vocal tract during phonation is still limited. For a major part, this is due to difficulties in acquiring geometry data of the vocal tract in the process of voice production. In this study, a centerline-based segmentation method using active contours was introduced to extract the geometry data of the vocal tract obtained with MRI during sustained vowel phonation. The applied semiautomatic algorithm was found to be time- and interaction-efficient and allowed performing various three-dimensional measurements on the resulting model. The method is suitable for an improved detailed analysis of the vocal tract morphology during speech or singing which might give some insights into the underlying mechanical processes. Anton A. Poznyakovskiy, Alexander Mainka, Ivan Platzek, and Dirk Mürbe Copyright © 2015 Anton A. Poznyakovskiy et al. All rights reserved. Validation of Screening Questions for Hyperacusis in Chronic Tinnitus Sun, 18 Oct 2015 11:59:17 +0000 Background. We investigated the validity of the two hyperacusis items of the TSCHQ (Tinnitus Sample Case History Questionnaire) from the TRI (Tinnitus Research Initiative) database by comparing them with the German hyperacusis questionnaire GÜF. Methods. We investigated the association of the GÜF with the TSCHQ screening questions for both the sum score and the single items with correlation, contrast, principal component, and discriminant analysis in a sample of 161 patients with chronic tinnitus. Results. TSCHQ items and the GÜF total score were significantly associated with a special focus on fear and pain related hyperacusis. Factor analysis of the GÜF revealed the three factors “fear and pain related hyperacusis,” “hearing related problems,” and “problems in quality of life.” A discriminant analysis showed a sensitivity of 64% and a specificity of 71% of the TSCHQ items for the establishment of tinnitus patient subgroups with and without hyperacusis. Discussion. Both hyperacusis TSCHQ items can serve as screening questions with respect to self-reported hyperacusis in chronic tinnitus with a specific focus on fear and pain related hyperacusis. However, the multiple dimensions of hyperacusis should be considered for diagnosis and treatment in both scientific and clinical contexts. Martin Schecklmann, Astrid Lehner, Winfried Schlee, Veronika Vielsmeier, Michael Landgrebe, and Berthold Langguth Copyright © 2015 Martin Schecklmann et al. All rights reserved. Acoustic Correlates of Compensatory Adjustments to the Glottic and Supraglottic Structures in Patients with Unilateral Vocal Fold Paralysis Sun, 18 Oct 2015 11:57:05 +0000 The goal of this study was to analyse perceptually and acoustically the voices of patients with Unilateral Vocal Fold Paralysis (UVFP) and compare them to the voices of normal subjects. These voices were analysed perceptually with the GRBAS scale and acoustically using the following parameters: mean fundamental frequency (F0), standard-deviation of F0, jitter (ppq5), shimmer (apq11), mean harmonics-to-noise ratio (HNR), mean first (F1) and second (F2) formants frequency, and standard-deviation of F1 and F2 frequencies. Statistically significant differences were found in all of the perceptual parameters. Also the jitter, shimmer, HNR, standard-deviation of F0, and standard-deviation of the frequency of F2 were statistically different between groups, for both genders. In the male data differences were also found in F1 and F2 frequencies values and in the standard-deviation of the frequency of F1. This study allowed the documentation of the alterations resulting from UVFP and addressed the exploration of parameters with limited information for this pathology. Luis M. T. Jesus, Joana Martinez, Andreia Hall, and Aníbal Ferreira Copyright © 2015 Luis M. T. Jesus et al. All rights reserved. Modulation Spectra Morphological Parameters: A New Method to Assess Voice Pathologies according to the GRBAS Scale Sun, 18 Oct 2015 11:26:52 +0000 Disordered voices are frequently assessed by speech pathologists using perceptual evaluations. This might lead to problems caused by the subjective nature of the process and due to the influence of external factors which compromise the quality of the assessment. In order to increase the reliability of the evaluations, the design of automatic evaluation systems is desirable. With that in mind, this paper presents an automatic system which assesses the Grade and Roughness level of the speech according to the GRBAS perceptual scale. Two parameterization methods are used: one based on the classic Mel-Frequency Cepstral Coefficients, which has already been used successfully in previous works, and other derived from modulation spectra. For the latter, a new group of parameters has been proposed, named Modulation Spectra Morphological Parameters: MSC, DRB, LMR, MSH, MSW, CIL, PALA, and RALA. In methodology, PCA and LDA are employed to reduce the dimensionality of feature space, and GMM classifiers to evaluate the ability of the proposed features on distinguishing the different levels. Efficiencies of 81.6% and 84.7% are obtained for Grade and Roughness, respectively, using modulation spectra parameters, while MFCCs performed 80.5% and 77.7%. The obtained results suggest the usefulness of the proposed Modulation Spectra Morphological Parameters for automatic evaluation of Grade and Roughness in the speech. Laureano Moro-Velázquez, Jorge Andrés Gómez-García, Juan Ignacio Godino-Llorente, and Gustavo Andrade-Miranda Copyright © 2015 Laureano Moro-Velázquez et al. All rights reserved. Over-the-Counter Hearing Aids: A Lost Decade for Change Sun, 18 Oct 2015 09:28:59 +0000 Background. Hearing aids sold directly to consumers in retail stores or through the internet, without individual prescription by audiological professionals, are termed over-the-counter (OTC) devices. This study aimed to determine whether there was any change in the electroacoustic characteristics of OTC devices compared to research carried out a decade earlier. The previous results indicated that most OTC devices were low-frequency-emphasis devices and were unsuitable for elderly people with presbycusis, who were likely to be the major consumers of these products. Methods. Ten OTC devices were selected and their electroacoustic performance was measured. Appropriate clients for the OTC devices were derived, using four linear prescription formulae, and OTC suitability for elderly persons with presbycusis was investigated. Results. OTC electroacoustic characteristics were similar to those in the earlier study. Most OTC devices were not acoustically appropriate for potential consumers with presbycusis. Although several of the devices could match prescriptive targets for individuals with presbycusis, their poor electroacoustic performance—including ineffective volume control function, high equivalent input noise, and irregular frequency response—may override their potential benefit. Conclusion. The low-cost OTC devices were generally not suitable for the main consumers of these products, and there has been little improvement in the appropriateness of these devices over the past decade. Zoe Yee Ting Chan and Bradley McPherson Copyright © 2015 Zoe Yee Ting Chan and Bradley McPherson. All rights reserved. Treatment of Hemorrhagic Vocal Polyps by Pulsed Dye Laser-Assisted Laryngomicrosurgery Sun, 18 Oct 2015 09:26:11 +0000 Objective. Conventional surgical techniques of laryngomicrosurgery (LMS) on hemorrhagic vocal polyps are often difficult due to obscuration of the surgical field by inadvertent bleeding from the lesion, and there are often significant amounts of mucosal epithelium loss. Here, we introduce our surgical technique using pulsed dye laser (PDL), which can effectively resect the polyp with vocal fold mucosa preservation. Methods. Patients who were diagnosed with hemorrhagic vocal polyp and who were surgically managed using PDL from March 2013 to October 2014 were retrospectively reviewed. Preoperative and postoperative clinical outcomes and surgical findings were evaluated. Results. A total of 39 patients were treated with PDL-assisted enucleation LMS. The average age was 43.7 years (range 20–73), and there were 20 males and 19 females (17 professional voice users). In all cases, the hemorrhagic polyp was successfully enucleated after application of PDL, thereby preserving the overlying epithelium. Postoperative voice outcomes were favorable with clear preservation of the vocal fold mucosal wave. Conclusion. PDL-assisted enucleation LMS for the treatment of hemorrhagic vocal polyps can be a safe and effective surgical technique. It can be considered a promising treatment option for hemorrhagic vocal polyps. Hyung Kwon Byeon, Ji Hyuk Han, Byeong Il Choi, Hye Jin Hwang, Ji-Hoon Kim, and Hong-Shik Choi Copyright © 2015 Hyung Kwon Byeon et al. All rights reserved. Nonword Repetition and Speech Motor Control in Children Sun, 18 Oct 2015 09:09:16 +0000 This study examined how familiarity of word structures influenced articulatory control in children and adolescents during repetition of real words (RWs) and nonwords (NWs). A passive reflective marker system was used to track articulator movement. Measures of accuracy were obtained during repetition of RWs and NWs, and kinematic analysis of movement duration and variability was conducted. Participants showed greater consonant and vowel accuracy during RW than NW repetition. Jaw movement duration was longer in NWs compared to RWs across age groups, and younger children produced utterances with longer jaw movement duration compared to older children. Jaw movement variability was consistently greater during repetition of NWs than RWs in both groups of participants. The results indicate that increases in phonological short-term memory demands affect articulator movement. This effect is most pronounced in younger children. A range of skills may develop during childhood, which supports NW repetition skills. Christina Reuterskiöld and Maria I. Grigos Copyright © 2015 Christina Reuterskiöld and Maria I. Grigos. All rights reserved. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children? Sun, 18 Oct 2015 09:06:39 +0000 Objective. To evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. Methods. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Results. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2%) had bilateral responses. Four (9.5%) showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7%) in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. Conclusion. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses. Signe Schuster Grasel, Edigar Rezende de Almeida, Roberto Miquelino de Oliveira Beck, Maria Valéria Schmidt Goffi-Gomez, Henrique Faria Ramos, Amanda Costa Rossi, Robinson Koji Tsuji, Ricardo Ferreira Bento, and Rubens de Brito Copyright © 2015 Signe Schuster Grasel et al. All rights reserved. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing Sun, 11 Oct 2015 12:44:23 +0000 Background. The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. Methods. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Results. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. Conclusions. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine. Derik Lendeckel, Christine Eymann, Philipp Emicke, Georg Daeschlein, Katrin Darm, Serena O’Neil, Achim G. Beule, Thomas von Woedtke, Uwe Völker, Klaus-Dieter Weltmann, Michael Jünger, Werner Hosemann, and Christian Scharf Copyright © 2015 Derik Lendeckel et al. All rights reserved. Diagnostic Accuracy of Obstructive Airway Adult Test for Diagnosis of Obstructive Sleep Apnea Thu, 08 Oct 2015 16:41:59 +0000 Rationale. The gold standard for the diagnosis of Obstructive Sleep Apnea (OSA) is polysomnography, whose access is however reduced by costs and limited availability, so that additional diagnostic tests are needed. Objectives. To analyze the diagnostic accuracy of the Obstructive Airway Adult Test (OAAT) compared to polysomnography for the diagnosis of OSA in adult patients. Methods. Ninety patients affected by OSA verified with polysomnography (AHI ≥ 5) and ten healthy patients, randomly selected, were included and all were interviewed by one blind examiner with OAAT questions. Measurements and Main Results. The Spearman rho, evaluated to measure the correlation between OAAT and polysomnography, was 0.72 (). The area under the ROC curve (95% CI) was the parameter to evaluate the accuracy of the OAAT: it was 0.91 (0.81–1.00) for the diagnosis of OSA (AHI ≥ 5), 0.90 (0.82–0.98) for moderate OSA (AHI ≥ 15), and 0.84 (0.76–0.92) for severe OSA (AHI ≥ 30). Conclusions. The OAAT has shown a high correlation with polysomnography and also a high diagnostic accuracy for the diagnosis of OSA. It has also been shown to be able to discriminate among the different degrees of severity of OSA. Additional large studies aiming to validate this questionnaire as a screening or diagnostic test are needed. Giulio Gasparini, Claudio Vicini, Michele De Benedetto, Fabrizio Salamanca, Giovanni Sorrenti, Mario Romandini, Marcello Bosi, Gianmarco Saponaro, Enrico Foresta, Andreina Laforì, Giuseppe Meccariello, Alessandro Bianchi, Domenico Maurizio Toraldo, Aldo Campanini, Filippo Montevecchi, Grazia Rizzotto, Daniele Cervelli, Alessandro Moro, Michele Arigliani, Riccardo Gobbi, and Sandro Pelo Copyright © 2015 Giulio Gasparini et al. All rights reserved. Influence of Ionizing Radiation on Two Generations of Cochlear Implants Mon, 28 Sep 2015 13:09:14 +0000 The purpose of the present study was to test the behavior of two different generations of cochlear implant systems subjected to a clinical radiotherapy scheme and to determine the maximal acceptable cumulative radiation levels at which the devices show out-of-specification behaviors. Using stereotactic irradiation (Cyberknife, 6 MV photon beam), three Digisonic SP and three Neuro devices were submitted to 5 Gy doses that cumulated to 60 Gy (12 sessions) and 80 Gy (16 sessions), respectively. A follow-up series of irradiation was then applied, in which Digisonic SP devices received two additional fractions of 50 Gy each, cumulating to 160 Gy, and Neuro devices three additional fractions of 20, 40, and 150 Gy, cumulating to 290 Gy. Output current values were monitored during the treatment. At clinical doses, with 60 or 80 Gy cumulative radiation exposure, no single measurement showed more than 10% divergence from the reference measure. The cochlear implants tested in this study showed high resistance to clinically relevant cumulative radiation doses and showed no out-of-bounds behavior up to cumulative doses of 140 or 160 Gy. These observations suggest that cochlear implant users can undergo radiotherapy up to cumulative doses well above those currently used in clinical situations without risk of failure. Nicolas Guevara, Anaïs Gérard, Jeanne Dupré, Delphine Goursonnet, Michel Hoen, Dan Gnansia, Gaëlle Angellier, and Juliette Thariat Copyright © 2015 Nicolas Guevara et al. All rights reserved. Simultaneous Labyrinthectomy and Cochlear Implantation for Patients with Single-Sided Ménière’s Disease and Profound Sensorineural Hearing Loss Mon, 24 Aug 2015 12:33:33 +0000 Objective. To investigate the treatment outcome of a simultaneous labyrinthectomy and cochlear implantation in patients with single-sided Ménière’s disease and profound sensorineural hearing loss. Study Design. Prospective study. Method. Five patients with single-sided Ménière’s disease with active vertigo and functional deafness were included. In all cases, simultaneous cochlear implantation combined with labyrinthectomy surgery was performed. The outcome has been evaluated by the Dizziness Handicap Inventory (DHI) and speech recognition. Results. The combined labyrinthectomy and cochlear implantation led in all patients to a highly significant reduction of dizziness up to a restitutio ad integrum. After activation of the cochlear implant and rehabilitation, a mean monosyllabic speech understanding of 69% at 65 dB was observed. Conclusion. For patients with single-sided Ménière’s disease and profound sensorineural hearing loss the simultaneous labyrinthectomy and cochlear implantation are efficient method for the treatment of vertigo as well as the rehabilitation of the auditory system. G. Doobe, A. Ernst, R. Ramalingam, P. Mittmann, and I. Todt Copyright © 2015 G. Doobe et al. All rights reserved. Hearing Assessment after Treatment of Nasopharyngeal Carcinoma with CRT and IMRT Techniques Sun, 16 Aug 2015 07:43:21 +0000 Objectives. This study analyzed the long-term hearing loss after treatment of primary nasopharyngeal carcinoma to elucidate its causal factors. Methods. Ninety-two nasopharyngeal carcinoma patients were treated with radiotherapy or chemoradiotherapy. Pure tone audiometry was performed before the therapy and annually up to 9 years after completing treatment. The hearing thresholds were corrected for age-related deterioration and compared to the results without adjusting for age. Results. The mean air and bone conduction threshold with and without correction for age-related deterioration differed significantly 2–9 years after completing radiotherapy . The audiometry results with age correction showed a flattened configuration compared to the results without age correction. The total radiation dose and radiation modality showed a causal relationship with a greater incidence of hearing loss after therapy . There was more deterioration in the air and bone hearing thresholds with conformal radiotherapy than intensity-modulated radiotherapy . A radiation dose >72 cGy resulted in more severe hearing loss than <72 cGy . Conclusion. Hearing loss after completing therapy should be corrected for age-related hearing deterioration to reveal the true extent to which the loss is a therapeutic complication. Both the radiation modality used and the dose were significantly associated with hearing loss. Chung-Feng Hwang, Fu-Min Fang, Ming-Ying Zhuo, Chao-Hui Yang, Li-Na Yang, and Hui-Shan Hsieh Copyright © 2015 Chung-Feng Hwang et al. All rights reserved. All Three Rows of Outer Hair Cells Are Required for Cochlear Amplification Thu, 30 Jul 2015 17:29:53 +0000 In the mammalian auditory system, the three rows of outer hair cells (OHCs) located in the cochlea are thought to increase the displacement amplitude of the organ of Corti. This cochlear amplification is thought to contribute to the high sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing system. Recent studies have shown that traumatic stimuli, such as noise exposure and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows. However, the degree of decrease in cochlear amplification caused by such functional losses remains unclear. In the present study, a finite element model of a cross section of the gerbil cochlea was constructed. Then, to determine effects of the functional losses of OHCs on the cochlear amplification, changes in the displacement amplitude of the basilar membrane (BM) due to the functional losses of OHCs were calculated. Results showed that the displacement amplitude of the BM decreases significantly when a single row of OHCs lost its function, suggesting that all three rows of OHCs are required for cochlear amplification. Michio Murakoshi, Sho Suzuki, and Hiroshi Wada Copyright © 2015 Michio Murakoshi et al. All rights reserved. Cleft Palate, Interdisciplinary Diagnosis, and Treatment Tue, 28 Jul 2015 11:48:19 +0000 Pablo Antonio Ysunza, Maria Carmen Pamplona, and Gabriela Repetto Copyright © 2015 Pablo Antonio Ysunza et al. All rights reserved. Clinical Outcomes of Primary Palatal Surgery in Children with Nonsyndromic Cleft Palate with and without Lip Mon, 27 Jul 2015 12:04:44 +0000 This study presents clinical outcomes of primary cleft palate surgery, including rate of oronasal fistula development, rate of velopharyngeal insufficiency (VPI) requiring secondary surgery, and speech outcomes. We examined the effect of cleft type on the clinical outcomes. Retrospective analysis was performed using clinical records of all patients who received a primary palatoplasty at the Cleft Palate Clinic at Seoul Asan Medical Center, South Korea, between 2007 and 2012. The study included 292 patients with nonsyndromic overt cleft palate (±cleft lip). The results revealed that the rate of oronasal fistula was 7.9% and the incidence of VPI based on the rate of secondary palatal surgery was 19.2%. The results showed that 50.3% of all the patients had received speech therapy and 28.8% and 51.4% demonstrated significant hypernasality and articulatory deficits, respectively. The results of the rate of VPI and speech outcomes were significantly different in terms of cleft type. Except for the rate of oronasal fistula, patients with cleft palate generally exhibited better clinical outcomes compared to those with bilateral or unilateral cleft lip and palate. This study suggests that several factors, including cleft type, should be identified and comprehensively considered to establish an optimal treatment regimen for patients with cleft palate. Seunghee Ha, Kyung S. Koh, Heewon Moon, Seungeun Jung, and Tae Suk Oh Copyright © 2015 Seunghee Ha et al. All rights reserved. Flap Necrosis after Palatoplasty in Patients with Cleft Palate Sun, 26 Jul 2015 11:30:19 +0000 Palatal necrosis after palatoplasty in patients with cleft palate is a rare but significant problem encountered by any cleft surgeon. Few studies have addressed this disastrous complication and the prevalence of this problem remains unknown. Failure of a palatal flap may be attributed to different factors like kinking or section of the pedicle, anatomical variations, tension, vascular thrombosis, type of cleft, used surgical technique, surgeon’s experience, infection, and malnutrition. Palatal flap necrosis can be prevented through identification of the risk factors and a careful surgical planning should be done before any palatoplasty. Management of severe fistulas observed as a consequence of palatal flap necrosis is a big challenge for any cleft surgeon. Different techniques as facial artery flaps, tongue flaps, and microvascular flaps have been described with this purpose. This review article discusses the current status of this serious complication in patients with cleft palate. Percy Rossell-Perry Copyright © 2015 Percy Rossell-Perry. All rights reserved. Dimensions of Velopharyngeal Space following Maxillary Advancement with Le Fort I Osteotomy Compared to Zisser Segmental Osteotomy: A Cephalometric Study Sun, 26 Jul 2015 11:15:25 +0000 The objectives of this study are to assess the velopharyngeal dimensions using cephalometric variables of the nasopharynx and oropharynx as well as to compare the Le Fort I osteotomy technique to Zisser’s anterior maxillary osteotomy technique based on patients’ outcomes within early and late postoperative follow-ups. 15 patients with severe maxillary deficiency treated with Le Fort I osteotomy and maxillary segmental osteotomy were assessed. Preoperative, early postoperative, and late postoperative follow-up lateral cephalograms, patient histories, and operative reports are reviewed with a focus on defined cephalometric landmarks for assessing velopharyngeal space dimension and maxillary movement (measured for three different tracing points). A significant change was found between preoperative and postoperative lateral cephalometric measurements regarding the distance between the posterior nasal spine and the posterior pharyngeal wall in Le Fort I osteotomy cases. However, no significant difference was found between preoperative and postoperative measurements in maxillary segmental osteotomy cases regarding the same measurements. The velopharyngeal area calculated for the Le Fort I osteotomy group showed a significant difference between the preoperative and postoperative measurements. Le Fort I osteotomy for advancement of upper jaw increases velopharyngeal space. On the other hand, Zisser’s anterior maxillary segmental osteotomy does not alter the dimension of the velopharyngeal space significantly. Furkan Erol Karabekmez, Johannes Kleinheinz, and Susanne Jung Copyright © 2015 Furkan Erol Karabekmez et al. All rights reserved. In Situ and Home Care Nasopharyngeal Intubation Improves Respiratory Condition and Prevents Surgical Procedures in Early Infancy of Severe Cases of Robin Sequence Sun, 26 Jul 2015 08:52:35 +0000 Aim. To evaluate the clinical outcome of infants with Robin Sequence (RS) and severe respiratory obstruction managed with nasopharyngeal intubation (NPI). Methods. This prospective study was conducted with 107 infants with RS admitted to the Hospital for Craniofacial Anomalies of the University of São Paulo (HRAC-USP), from July 2003 to June 2010, diagnosed with severe RS and treated with NPI. The infants were followed up for the first year of life. Clinical findings, morbidity, and mortality were recorded. Results. Of the 223 infants with RS admitted to the hospital in the period studied, 149 were diagnosed with severe respiratory distress and 107 (71.81%) matched all the inclusion criteria. Of those, 78 (73%) presented Isolated Robin Sequence and 29 (27%) presented other syndromes or anomalies associated with RS. NPI treatment lasted an average of 57 days and the mean hospitalization time was 18 days. Although all infants presented feeding difficulties, 85% were fed orally and only 15% underwent gastrostomy. Morbidity was 14% and no deaths occurred. Conclusions. The children treated with the RS treatment protocol adopted at the HRAC-USP had improved respiratory and feeding difficulties, required a shorter hospitalization time, and presented low morbidity and mortality during the first year of life. The general outcome prevented surgical procedures in early infancy. Isabel Cristina Drago Marquezini Salmen and Ilza Lazarini Marques Copyright © 2015 Isabel Cristina Drago Marquezini Salmen and Ilza Lazarini Marques. All rights reserved. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency Sun, 26 Jul 2015 08:35:51 +0000 Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI). Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management. Pablo Antonio Ysunza, Gabriela M. Repetto, Maria Carmen Pamplona, Juan F. Calderon, Kenneth Shaheen, Konkgrit Chaiyasate, and Matthew Rontal Copyright © 2015 Pablo Antonio Ysunza et al. All rights reserved. Differences in Velopharyngeal Structure during Speech among Asians Revealed by 3-Tesla Magnetic Resonance Imaging Movie Mode Sun, 26 Jul 2015 08:16:42 +0000 Objective. Different bony structures can affect the function of the velopharyngeal muscles. Asian populations differ morphologically, including the morphologies of their bony structures. The purpose of this study was to compare the velopharyngeal structures during speech in two Asian populations: Japanese and Thai. Methods. Ten healthy Japanese and Thai females (five each) were evaluated with a 3-Tesla (3 T) magnetic resonance imaging (MRI) scanner while they produced vowel-consonant-vowel syllable (/asa/). A gradient-echo sequence, fast low-angle shot with segmented cine and parallel imaging technique was used to obtain sagittal images of the velopharyngeal structures. Results. MRI was carried out in real time during speech production, allowing investigations of the time-to-time changes in the velopharyngeal structures. Thai subjects had a significantly longer hard palate and produced shorter consonant than Japanese subjects. The velum of the Thai participants showed significant thickening during consonant production and their retroglossal space was significantly wider at rest, whereas the dimensional change during task performance was similar in the two populations. Conclusions. The 3 T MRI movie method can be used to investigate velopharyngeal function and diagnose velopharyngeal insufficiency. The racial differences may include differences in skeletal patterns and soft-tissue morphology that result in functional differences for the affected structures. Kulthida Nunthayanon, Ei-ichi Honda, Kazuo Shimazaki, Hiroko Ohmori, Maristela Sayuri Inoue-Arai, Tohru Kurabayashi, and Takashi Ono Copyright © 2015 Kulthida Nunthayanon et al. All rights reserved. Laryngeal Neuroendocrine Carcinomas: A Retrospective Study of 14 Cases Wed, 15 Jul 2015 07:57:21 +0000 Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous which present a wide spectrum of pathological and clinical manifestations. Fourteen patients with histologically demonstrated LNEC were collected and analyzed retrospectively. The 14 cases were classified into 3 subtypes: typical carcinoid in 2, atypical carcinoid in 5, and small cell neuroendocrine carcinoma in 7. The mean survival time of the 14 patients in this study was 112.5 months (95% CI, 81.5–143.6). Surgeries were performed for 2 patients of typical carcinoid, and they were alive with no evidence of recurrence after 24 and 47 months of follow-ups. Patients in the atypical carcinoid group were treated with surgeries and postoperative radiotherapy. After 58.4 months of follow-ups (range: 9–144), 2 patients showed no evidence of disease and 1 was lost to follow-up after 72 months. The other 2 patients died of other unrelated diseases. In the small cell neuroendocrine carcinoma group, a combination of chemotherapy and radiotherapy was applied. The mean survival time was 79.7 months (95% CI, 37.9–121.4), and the 5-year survival rate was 53.6%. In conclusion, the clinical behaviors, treatment protocols, and prognosis are different for each subtype of LNECs. Yingying Zhu, Liming Gao, Yunxiao Meng, Wenwen Diao, Xiaoli Zhu, Guojun Li, Zhiqiang Gao, and Xingming Chen Copyright © 2015 Yingying Zhu et al. All rights reserved. Cochlear Implant and Its Related Science Thu, 09 Jul 2015 08:05:20 +0000 Chung-Feng Hwang, Yang Chen, Hung-Ching Lin, Prepageran Narayanan, Seung-Ha Oh, and Eric Truy Copyright © 2015 Chung-Feng Hwang et al. All rights reserved. The Relation between Nonverbal IQ and Postoperative CI Outcomes in Cochlear Implant Users: Preliminary Result Sun, 05 Jul 2015 08:28:19 +0000 Objectives. This study assessed the correlation between performance intelligence and the postoperative cochlear implant (CI) outcome in Korean-speaking children. In addition, the relationship between the performance intelligence subscales and the post-CI speech outcome was evaluated. Materials and Methods. Thirteen pediatric CI users (five males, eight females; median age at implantation 6.2 (range 1.3–14.2) years; median age at intelligence test 9.3 (range 5–16) years) who were tested using the Korean Educational Development Institute-Wechsler Intelligence Scale for children were studied. The correlations between the intelligence scores and 1-2 years postoperative Categories of Auditory Performance (CAP) scores and between subscales of performance and 1-2 years postoperative CAP scores were analyzed. Results. There was no correlation between the categories of verbal intelligence quotient (IQ) and performance IQ for “mentally retarded” and “average,” respectively (Spearman’s rho = 0.42, . There was a strong correlation between performance IQ and the postoperative CAP scale (Spearman’s rho = 0.8977, . “Picture arrangement” and “picture completion,” reflecting social cognition, were strongly correlated with the postoperative CAP scales. Conclusion. Performance intelligence, especially social cognition, was strongly related to the postoperative CI outcome of cochlear implant users. Therefore, auditory rehabilitation, including social rehabilitation, should maximize the postoperative CI outcomes. Mina Park, Jae-Jin Song, Seo Jin Oh, Min-Sup Shin, Jun Ho Lee, and Seung Ha Oh Copyright © 2015 Mina Park et al. All rights reserved. Written Language Ability in Mandarin-Speaking Children with Cochlear Implants Sun, 05 Jul 2015 08:05:46 +0000 Objectives. To examine narrative writing in cochlear implant (CI) children and understand the factors associated with unfavorable outcomes. Materials and Methods. Forty-five CI children in grades 2–6 participated in this study. They received CIs at 4.1 ± 2.1 years of age and had used them for 6.5 ± 2.7 years. A story-writing test was conducted and scored on 4 subscales: Total Number of Words, Words per Sentence, Morphosyntax, and Semantics. Scores more than 1.5 SD lower than the mean of the normal-hearing normative sample were considered problematic. Language and speech skills were examined. Results. Significantly more implanted students were problematic on “Total Number of Words” (), “Words per Sentence” (), and “Semantics” (). Poorer receptive language and auditory performance were independently associated with problematic “Total Number of Words” () and “Semantics” (), respectively. “Semantics” problem was more common in lower graders (grades 2–4) than in higher graders (grades 5-6; ). Conclusion. Implanted children tend to write stories that are shorter, worse-organized, and without a plot, while formulating morphosyntactically correct sentences. Special attention is required on their auditory and language performances, which could lead to written language problems. Che-Ming Wu, Hui-Chen Ko, Yen-An Chen, Yung-Ting Tsou, and Wei-Chieh Chao Copyright © 2015 Che-Ming Wu et al. All rights reserved. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants Sun, 05 Jul 2015 08:04:26 +0000 The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement), electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device). The electrical response, measured using auto-NRT (neural responses telemetry) algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, ), the scalar placement of the electrodes (β = −8.50 ± 1.97, ), and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF). Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas. Frederic Venail, Thibault Mura, Mohamed Akkari, Caroline Mathiolon, Sophie Menjot de Champfleur, Jean Pierre Piron, Marielle Sicard, Françoise Sterkers-Artieres, Michel Mondain, and Alain Uziel Copyright © 2015 Frederic Venail et al. All rights reserved. Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies Sun, 05 Jul 2015 07:58:49 +0000 Background. Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. Methods. The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Results. Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). Conclusions. Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent. Micol Busi, Monica Rosignoli, Alessandro Castiglione, Federica Minazzi, Patrizia Trevisi, Claudia Aimoni, Ferdinando Calzolari, Enrico Granieri, and Alessandro Martini Copyright © 2015 Micol Busi et al. All rights reserved. Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells Sun, 05 Jul 2015 07:45:48 +0000 Previously, we demonstrated that hypoxia (1% O2) enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs). In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR), and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α), proliferating cell nuclear antigen (PCNA), cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation. Hsin-Chien Chen, Jen-Tin Lee, Cheng-Ping Shih, Ting-Ting Chao, Huey-Kang Sytwu, Shiue-Li Li, Mei-Cho Fang, Hang-Kang Chen, Yi-Chun Lin, Chao-Yin Kuo, and Chih-Hung Wang Copyright © 2015 Hsin-Chien Chen et al. All rights reserved. Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation Sun, 05 Jul 2015 06:58:52 +0000 We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average  μm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 μm dia., 250 μm pitch), spanning nearly 28 mm in length and 400 μm in width. We report an average intracochlear stimulating current threshold of  μA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea’s basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 μm resolution), distances ranging from 100 to 565 μm from the cochlea’s central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours. P. Bhatti, J. Van Beek-King, A. Sharpe, J. Crawford, S. Tridandapani, B. McKinnon, and D. Blake Copyright © 2015 P. Bhatti et al. All rights reserved. Evaluation of Intracochlear Trauma Caused by Insertion of Cochlear Implant Electrode Arrays through Different Quadrants of the Round Window Sun, 05 Jul 2015 06:36:19 +0000 Hypothesis. This study aimed to evaluate whether there is a difference in the degree of intracochlear trauma when the cochlear implant electrode arrays is inserted through different quadrants of the round window membrane. Background. The benefits of residual hearing preservation in cochlear implant recipients have promoted the development of atraumatic surgeries. Minimal trauma during electrode insertion is crucial for residual hearing preservation. Methods. In total, 25 fresh human temporal bones were subjected to mastoidectomy and posterior tympanotomy. The cochlear implant electrode array was inserted through the anterosuperior quadrant of the round window membrane in 50% of the bones and through the anteroinferior quadrant in the remaining 50%. The temporal bones were dehydrated, embedded in epoxy, serially polished, stained, viewed through a stereomicroscope, and photographed with the electrode arrays in situ. The resulting images were analyzed for signs of intracochlear trauma. Results. Histological examinations revealed varying degrees of damage to the intracochlear structures, although the incidence and severity of intracochlear trauma were not influenced by the quadrant of insertion. Conclusions. The incidence and severity of intracochlear trauma were similar in all samples, irrespective of electrode array insertion through the anterosuperior or anteroinferior quadrant of the round window membrane. Graziela de Souza Queiroz Martins, Rubens Vuono Brito Neto, Robinson Koji Tsuji, Eloisa Maria Mello Santiago Gebrim, and Ricardo Ferreira Bento Copyright © 2015 Graziela de Souza Queiroz Martins et al. All rights reserved. Stability Testing of a Wide Bone-Anchored Device after Surgery without Skin Thinning Sun, 05 Jul 2015 06:29:27 +0000 Objective. To longitudinally follow the osseointegration using Resonance Frequency Analysis (RFA) for different lengths of abutment on a new wide bone-anchored implant, introduced with the non-skin thinning surgical technique. Study Design. A single-center, prospective 1 year study following adults with bone-anchored hearing implants. Materials and Methods. Implantation was performed and followed for a minimum of 1 year. All patients were operated on according to the tissue preserving technique. A 4.5 mm wide fixture (Oticon Medical) with varying abutments (9 to 12 mm) was used and RFA was tested 1 week, 7 weeks, 6 months, and 12 months later. Implant Stability Quotient (ISQ), was measured from 1 to 100. Stability was compared to a group of patients implanted with another brand (Cochlear BI400) of 4.5 mm fixtures. Results. All 10 adults concluded the study. None of the participants lost their implant during the test period indicating a good anchoring of abutments to the wide fixture tested. Stability testing was shown to vary depending on abutment length and time after surgery and with higher values for shorter abutments and increasing values over the first period of time. One patient changed the abutment from 12 to 9 mm and another from a 9 to a 12 during the year. No severe skin problems, numbness around the implant, or cosmetic problems arose. Conclusion. After 1 year of follow-up, combination of a wide fixture implant and the non-skin thinning surgical technique indicates a safe procedure with good stability and no abutment losses. Malou Hultcrantz Copyright © 2015 Malou Hultcrantz. All rights reserved. Cochlear Dummy Electrodes for Insertion Training and Research Purposes: Fabrication, Mechanical Characterization, and Experimental Validation Sun, 05 Jul 2015 06:27:57 +0000 To develop skills sufficient for hearing preservation cochlear implant surgery, surgeons need to perform several electrode insertion trials in ex vivo temporal bones, thereby consuming relatively expensive electrode carriers. The objectives of this study were to evaluate the insertion characteristics of cochlear electrodes in a plastic scala tympani model and to fabricate radio opaque polymer filament dummy electrodes of equivalent mechanical properties. In addition, this study should aid the design and development of new cochlear electrodes. Automated insertion force measurement is a new technique to reproducibly analyze and evaluate the insertion dynamics and mechanical characteristics of an electrode. Mechanical properties of MED-EL’s FLEX28, FLEX24, and FLEX20 electrodes were assessed with the help of an automated insertion tool. Statistical analysis of the overall mechanical behavior of the electrodes and factors influencing the insertion force are discussed. Radio opaque dummy electrodes of comparable characteristics were fabricated based on insertion force measurements. The platinum-iridium wires were replaced by polymer filament to provide sufficient stiffness to the electrodes and to eradicate the metallic artifacts in X-ray and computed tomography (CT) images. These low-cost dummy electrodes are cheap alternatives for surgical training and for in vitro, ex vivo, and in vivo research purposes. Jan-Philipp Kobler, Anandhan Dhanasingh, Raphael Kiran, Claude Jolly, and Tobias Ortmaier Copyright © 2015 Jan-Philipp Kobler et al. All rights reserved. Comparison of Lyophilized Glutaraldehyde-Preserved Bovine Pericardium with Different Vascular Prostheses for Use as Vocal Cords Implants: Experimental Study Wed, 13 May 2015 14:25:58 +0000 This study compared the use of lyophilized glutaraldehyde-preserved bovine pericardium (LGPBP), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and Teflon felt (TF) as implants for vocal cords (VC) medialization and aimed to assess the endoscopic, macroscopic, and microscopic VC changes after medialization in a canine model. In 18 mongrel dogs, the right VC were medialized with LGPBP and the left were implanted as follows: Group I (): LGPBP and PTFE; Group II (): LGPBP and PET; Group III (): LGPBP and TF. Surgical handling of the implants was compared. Three months after surgery, macroscopic and microscopic changes of VC and implants were evaluated. LGPBP offered the best surgical handling (, Kruskal-Wallis). TF implants showed extrusion (, Kruskal-Wallis) and severe inflammation. All VC formed fibrous capsules around the implants; the ones developed by LGPBP implants were thinner (, ANOVA, Tukey). VC implanted with synthetic materials showed eosinophilic infiltration (, Kruskal-Wallis). We concluded that the LGPBP could be used as an implant for VC medialization because it is biocompatible, easy to handle and remove during surgical procedures, and nonabsorbable or extrudable and produces an inflammatory reaction similar to PTFE and PET. J. Raúl Olmos-Zuñiga, Rogelio Jasso-Victoria, Miguel Gaxiola-Gaxiola, Avelina Sotres-Vega, Claudia Hernández-Jiménez, Matilde Baltazares-Lipp, Fernando Arredondo del Bosque, and Patricio Santillan-Doherty Copyright © 2015 J. Raúl Olmos-Zuñiga et al. All rights reserved. The Correlation of Serum Growth Differentiation Factor-15 Level in Patients with Obstructive Sleep Apnea Tue, 05 May 2015 06:59:58 +0000 Purpose. Growth differentiation factor-(GDF-) is a prognostic biomarker in cardiovascular disorders (CVD). GDF-15 level was not studied in patients with obstructive sleep apnea syndrome (OSAS) before. In this study, we investigated serum GDF-15 levels in OSAS patients and compared them with healthy controls. Material and Methods. Polysomnographically, confirmed forty consecutive OSAS patients (20 men and 20 women) and forty consecutive healthy controls (23 men and 17 women) were enrolled in the study. The samples in each group had similar demographic characteristics and body mass index (BMI) values. Results. In the study, no significant correlation was found about GDF-15 levels of OSAS group and healthy controls. However, there was a significant statistical correlation between age and GDF-15 level. In correlation analysis, there was not any significant correlation between age and BMI. Conclusion. Although various developing biomarkers have been studied in cardiovascular disorders, GDF-15 levels have attracted a widespread interest as predictors of cardiovascular risk. GDF-15 level has not been evaluated previously in patients with OSAS. A significant statistical correlation was found between age and GDF-15 level. To reveal close relation between OSAS and GDF-15, further studies are needed with combination of GDF-15 and other biomarkers in OSAS. Kamran Sari, Huseyin Ede, Zeliha Kapusuz Gencer, Mahmut Ozkiris, Ayse Yesim Gocmen, and Yavuz Selim Intepe Copyright © 2015 Kamran Sari et al. All rights reserved. Relation between Body Structure and Hearing during Soft Tissue Auditory Stimulation Thu, 16 Apr 2015 11:09:25 +0000 Hearing is elicited by applying the clinical bone vibrator to soft tissue sites on the head, neck, and thorax. Two mapping experiments were conducted in normal hearing subjects differing in body build: determination of the lowest soft tissue stimulation site at which a 60 dB SL tone at 2.0 kHz was effective in eliciting auditory sensation and assessment of actual thresholds along the midline of the head, neck, and back. In males, a lower site for hearing on the back was strongly correlated with a leaner body build. A correlation was not found in females. In both groups, thresholds on the head were lower, and they were higher on the back, with a transition along the neck. This relation between the soft tissue stimulation site and hearing sensation is likely due to the different distribution of soft tissues in various parts of the body. Cahtia Adelman, Michal Kaufmann Yehezkely, Shai Chordekar, and Haim Sohmer Copyright © 2015 Cahtia Adelman et al. All rights reserved. Minocycline Protection of Neomycin Induced Hearing Loss in Gerbils Wed, 08 Apr 2015 11:56:00 +0000 This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline. Alan M. Robinson, Irena Vujanovic, and Claus-Peter Richter Copyright © 2015 Alan M. Robinson et al. All rights reserved. NOD-Like Receptor Signaling in Cholesteatoma Thu, 02 Apr 2015 13:51:55 +0000 Background. Cholesteatoma is a destructive process of the middle ear resulting in erosion of the surrounding bony structures with consequent hearing loss, vestibular dysfunction, facial paralysis, or intracranial complications. The etiopathogenesis of cholesteatoma is controversial but is associated with recurrent ear infections. The role of intracellular innate immune receptors, the NOD-like receptors, and their associated signaling networks was investigated in cholesteatoma, since mutations in NOD-like receptor-related genes have been implicated in other chronic inflammatory disorders. Results. The expression of NOD2 mRNA and protein was significantly induced in cholesteatoma compared to the external auditory canal skin, mainly located in the epithelial layer of cholesteatoma. Microarray analysis showed significant upregulation for NOD2, not for NOD1, TLR2, or TLR4 in cholesteatoma. Moreover, regulation of genes in an interaction network of the NOD-adaptor molecule RIPK2 was detected. In addition to NOD2, NLRC4, and PYCARD, the downstream molecules IRAK1 and antiapoptotic regulator CFLAR showed significant upregulation, whereas SMAD3, a proapoptotic inducer, was significantly downregulated. Finally, altered regulation of inflammatory target genes of NOD signaling was detected. Conclusions. These results indicate that the interaction of innate immune signaling mediated by NLRs and their downstream target molecules is involved in the etiopathogenesis and growth of cholesteatoma. Anke Leichtle, Christin Klenke, Joerg Ebmeyer, Markus Daerr, Karl-Ludwig Bruchhage, Anna Sophie Hoffmann, Allen F. Ryan, Barbara Wollenberg, and Holger Sudhoff Copyright © 2015 Anke Leichtle et al. All rights reserved. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro Tue, 31 Mar 2015 13:24:36 +0000 Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation. Katharina Leitmeyer, Andrea Glutz, Vesna Radojevic, Cristian Setz, Nathan Huerzeler, Helen Bumann, Daniel Bodmer, and Yves Brand Copyright © 2015 Katharina Leitmeyer et al. All rights reserved. Preventing Hearing Loss and Restoring Hearing: A New Outlook Wed, 25 Mar 2015 08:06:13 +0000 Srdjan M. Vlajkovic, Peter R. Thorne, Ramesh Rajan, and Jonathan E. Gale Copyright © 2015 Srdjan M. Vlajkovic et al. All rights reserved. Two-Photon Microscopy Allows Imaging and Characterization of Cochlear Microvasculature In Vivo Wed, 25 Mar 2015 06:51:51 +0000 Impairment of cochlear blood flow has been discussed as factor in the pathophysiology of various inner ear disorders. However, the microscopic study of cochlear microcirculation is limited due to small scale and anatomical constraints. Here, two-photon fluorescence microscopy is applied to visualize cochlear microvessels. Guinea pigs were injected with Fluorescein isothiocyanate- or Texas red-dextrane as plasma marker. Intravital microscopy was performed in four animals and explanted cochleae from four animals were studied. The vascular architecture of the cochlea was visualized up to a depth of  μm. Imaging yielded a mean contrast-to-noise ratio (CNR) of . Mean diameter in vivo was  μm for arterioles and  μm for capillaries. In explanted cochleae, the diameter of radiating arterioles and capillaries was measured with  μm and  μm, respectively. The difference between capillaries and arterioles was statistically significant in both experimental setups ( and , two-way ANOVA). Measured vessel diameters in vivo and ex vivo were in agreement with published data. We conclude that two-photon fluorescence microscopy allows the investigation of cochlear microvessels and is potentially a valuable tool for inner ear research. Friedrich Ihler, Mattis Bertlich, Bernhard Weiss, Steffen Dietzel, and Martin Canis Copyright © 2015 Friedrich Ihler et al. All rights reserved. Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss Sun, 22 Mar 2015 08:57:25 +0000 Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required. Teru Kamogashira, Chisato Fujimoto, and Tatsuya Yamasoba Copyright © 2015 Teru Kamogashira et al. All rights reserved. Updates and Knowledge Gaps in Cholesteatoma Research Wed, 18 Mar 2015 12:54:10 +0000 The existence of acquired cholesteatoma has been recognized for more than three centuries; however, the nature of the disorder has yet to be determined. Without timely detection and intervention, cholesteatomas can become dangerously large and invade intratemporal structures, resulting in numerous intra- and extracranial complications. Due to its aggressive growth, invasive nature, and the potentially fatal consequences of intracranial complications, acquired cholesteatoma remains a cause of morbidity and death for those who lack access to advanced medical care. Currently, no viable nonsurgical therapies are available. Developing an effective management strategy for this disorder will require a comprehensive understanding of past progress and recent advances. This paper presents a brief review of background issues related to acquired middle ear cholesteatoma and deals with practical considerations regarding the history and etymology of the disorder. We also consider issues related to the classification, epidemiology, histopathology, clinical presentation, and complications of acquired cholesteatoma and examine current diagnosis and management strategies in detail. Chin-Lung Kuo, An-Suey Shiao, Matthew Yung, Masafumi Sakagami, Holger Sudhoff, Chih-Hung Wang, Chyong-Hsin Hsu, and Chiang-Feng Lien Copyright © 2015 Chin-Lung Kuo et al. All rights reserved. Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-B Pathway Sun, 15 Mar 2015 12:22:11 +0000 Andrographolide (Andro) has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC). However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibited the proliferation and invasion of NPC cells (, resp.). These anticancer activities were associated with cell apoptosis, cell death and induction of cell cycle arrest, and the downregulation of NF-κB target genes. This work provides evidence that NF-κB pathway is a potential therapeutic target and may also be indispensable in the Andro-mediated anticancer activities in nasopharyngeal carcinoma. Tao Peng, Min Hu, Ting-Ting Wu, Cen Zhang, Zhe Chen, Shuo Huang, and Xu-Hong Zhou Copyright © 2015 Tao Peng et al. All rights reserved. Surgical Results of Retrograde Mastoidectomy with Primary Reconstruction of the Ear Canal and Mastoid Cavity Sun, 15 Mar 2015 09:44:41 +0000 The aim of this study was to retrospectively review the long-term hearing results and the impact of mastoid exclusion/obliteration in patients with cholesteatoma (102 ears) who underwent retrograde tympanomastoidectomy and in whom bone chips/paté were applied as the sole materials during the procedure. In 79 ears, this was combined with ossiculoplasty in a single-stage procedure. In >71% of ears, the results of audiometric testing were monitored for more than 2 years. The results suggested there was a significant gain in hearing following surgery, with respect to the postoperative change in both air-conduction thresholds and air-bone gaps (). Linear regression analyses of pure-tone averages at different frequencies, before and after surgery, demonstrated that patients benefitted from a postoperative hearing gain at low and middle frequencies, but their hearing often deteriorated at frequencies of 8000 Hz. As for the impact of the type of tympanoplasty on hearing outcomes, type III-interposition markedly increased hearing gain. The overall rate of postoperative adverse events was 8.8%. We conclude that reconstruction of the ear canal and mastoid via mastoid exclusion/obliteration using bone chips/paté can be considered as an alternative procedure following retrograde mastoidectomy. It gives excellent surgical results and has fewer postoperative adverse events. Chao-Yin Kuo, Bor-Rong Huang, Hsin-Chien Chen, Cheng-Ping Shih, Wei-Kang Chang, Yang-Lien Tsai, Yuan-Yung Lin, Wan-Chun Tsai, and Chih-Hung Wang Copyright © 2015 Chao-Yin Kuo et al. All rights reserved. Oxymatrine Downregulates HPV16E7 Expression and Inhibits Cell Proliferation in Laryngeal Squamous Cell Carcinoma Hep-2 Cells In Vitro Tue, 24 Feb 2015 07:15:35 +0000 Objective. To investigate the possible mechanisms of oxymatrine’s role in anti laryngeal squamous cell carcinoma. Methods. We examined the effects of oxymatrine on the proliferation, cell cycle phase distribution, apoptosis, and the protein and mRNA expression levels of HPV16E7 gene in laryngeal carcinoma Hep-2 cells in vitro. The HPV16E7 siRNA inhibition was also done to confirm the effect of downregulating HPV16E7 on the proliferation in Hep-2 cells. Results. Oxymatrine significantly inhibited the growth and proliferation of Hep-2 cells in a dose-dependence and time-dependence manner. Oxymatrine blocked Hep-2 cells in G0/G1 phase, resulting in an obvious accumulation of G0/G1 phase cells while decreasing S phase cells. Oxymatrine induced apoptosis of Hep-2 cells, whose apoptotic rate amounted to about 42% after treatment with 7 mg/mL oxymatrine for 72 h. Oxymatrine also downregulated the expression of HPV16E7 gene, as determined by the western blotting and reverse transcription-polymerase chain reaction analysis. Knockdown of HPV16E7 effectively inhibited the proliferation of Hep-2 cells. Conclusions. Oxymatrine inhibits the proliferation and induces apoptosis of laryngeal carcinoma Hep-2 cells, which might be mediated by a significant cell cycle arrest in G0/G1 phase and downregulation of HPV16E7 gene. Oxymatrine is considered to be a likely preventive and curative candidate for laryngeal cancer. Xin-Jiang Ying, Bin Jin, Xin-Wei Chen, Jin Xie, Hong-Ming Xu, and Pin Dong Copyright © 2015 Xin-Jiang Ying et al. All rights reserved. Endoscopic/External Approaches in Otorhinolaryngology and Head and Neck Surgery Mon, 23 Feb 2015 07:23:41 +0000 Jan Betka, Karl Hörmann, Manuel Bernal-Sprekelsen, and Jan Plzák Copyright © 2015 Jan Betka et al. All rights reserved. Altered Interhemispheric Functional Coordination in Chronic Tinnitus Patients Thu, 19 Feb 2015 18:58:46 +0000 Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC), to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus. Yu-Chen Chen, Wenqing Xia, Yuan Feng, Xiaowei Li, Jian Zhang, Xu Feng, Cong-Xiao Wang, Yu Cai, Jian Wang, Richard Salvi, and Gao-Jun Teng Copyright © 2015 Yu-Chen Chen et al. All rights reserved. Audiogram Comparison of Workers from Five Professional Categories Tue, 03 Feb 2015 07:39:25 +0000 Introduction. Noise is a major cause of health disorders in workers and has unique importance in the auditory analysis of people exposed to it. The purpose of this study is to evaluate the arithmetic mean of the auditory thresholds at frequencies of 3, 4, and 6 kHz of workers from five professional categories exposed to occupational noise. Methods. We propose a retrospective cross-sectional cohort study to analyze 2.140 audiograms from seven companies having five sectors of activity: one footwear company, one beverage company, two ceramics companies, two metallurgical companies, and two transport companies. Results. When we compared two categories, we noticed a significant difference only for cargo carriers in comparison to the remaining categories. In all activity sectors, the left ear presented the worst values, except for the footwear professionals . We observed an association between the noise exposure time and the reduction of audiometric values for both ears. Significant differences existed for cargo carriers in relation to other groups. This evidence may be attributed to different forms of exposure. A slow and progressive deterioration appeared as the exposure time increased. Alexandre Scalli Mathias Duarte, Alexandre Caixeta Guimarães, Guilherme Machado de Carvalho, Laíza Araújo Mohana Pinheiro, Ronny Tah Yen Ng, Marcelo Hamilton Sampaio, Everardo Andrade da Costa, and Reinaldo Jordão Gusmão Copyright © 2015 Alexandre Scalli Mathias Duarte et al. All rights reserved. Infectious Causes of Cholesteatoma and Treatment of Infected Ossicles prior to Reimplantation by Hydrostatic High-Pressure Inactivation Sun, 01 Feb 2015 12:57:02 +0000 Chronic inflammation, which is caused by recurrent infections, is one of the factors contributing to the pathogenesis of cholesteatoma. If reimplantation of autologous ossicles after a surgical intervention is intended, inactivation of planktonic bacteria and biofilms is desirable. High hydrostatic pressure treatment is a procedure, which has been used to inactivate cholesteatoma cells on ossicles. Here we discuss the potential inactivating effect of high hydrostatic pressure on microbial pathogens including biofilms. Recent experimental data suggest an incomplete inactivation at a pressure level, which is tolerable for the bone substance of ossicles and results at least in a considerable reduction of pathogen load. Further studies are necessary to access how far this quantitative reduction of pathogens is sufficient to prevent ongoing chronic infections, for example, due to forming of biofilms. Wycliffe Omurwa Masanta, Rebecca Hinz, and Andreas Erich Zautner Copyright © 2015 Wycliffe Omurwa Masanta et al. All rights reserved. Frequency of Migraine as a Chief Complaint in Otolaryngology Outpatient Practice Wed, 28 Jan 2015 14:03:49 +0000 Objective. To identify the frequency of typical (headache and dizziness) and common atypical (ear fullness, pressure, pain, tinnitus, facial fullness, and nasal congestion) migraine symptoms as chief complaints among patients presenting to otolaryngology clinic. Methods. This is a descriptive study of prospectively collected data from a general otolaryngology practice. Typical migraine presentations were diagnosed by applying international headache society (IHS) criteria for migraine headache and Neuhauser’s criteria for migrainous vertigo. Atypical otologic and rhinologic migraine symptoms were diagnosed using individualized criteria. Charts were reviewed at 6-month interval from the first presentation. Results. Out of 1002 consecutive patients, 10.8% presented with “migrainous chief complaint.” All migrainous chief complaint patients had a history of headache but not all of them presented with headache. Corrected female to male ratio in the migraine group was 3 to 1; age distributions were significantly different between the migraine and nonmigraine groups by applying -test. Out of the atypical complaints, 86% of the patients had a history of concomitant typical presentation. Conclusion. Actual diagnostic criteria for migraine do not satisfy the diversity of its presentation. Investigating the history of migraine is enough to diagnose most atypical presentations. Sound knowledge about migraine seems essential for any ENT practitioner. Omar Sabra, Maria Muhammad Ali, Maha Al Zayer, and Saleh Altuwaijri Copyright © 2015 Omar Sabra et al. All rights reserved. Does Attempt at Hearing Preservation Microsurgery of Vestibular Schwannoma Affect Postoperative Tinnitus? Mon, 12 Jan 2015 13:57:29 +0000 Background. The aim of this study was to analyze the effect of vestibular schwannoma microsurgery via the retrosigmoid-transmeatal approach with special reference to the postoperative tinnitus outcome. Material and Methods. A prospective study was performed in 89 consecutive patients with unilateral vestibular schwannoma indicated for microsurgery. Patient and tumor related parameters, pre- and postoperative hearing level, intraoperative findings, and hearing and tinnitus handicap inventory scores were analyzed. Results. Cochlear nerve integrity was achieved in 44% corresponding to preservation of preoperatively serviceable hearing in 47% and useful hearing in 21%. Main prognostic factors of hearing preservation were grade/size of tumor, preoperative hearing level, intraoperative neuromonitoring, tumor consistency, and adhesion to neurovascular structures. Microsurgery led to elimination of tinnitus in 66% but also new-onset of the symptom in 14% of cases. Preservation of useful hearing and neurectomy of the eighth cranial nerve were main prognostic factors of tinnitus elimination. Preservation of cochlear nerve but loss of preoperative hearing emerged as the main factor for tinnitus persistence and new onset tinnitus. Decrease of THI scores was observed postoperatively. Conclusions. Our results underscore the importance of proper pre- and intraoperative decision making about attempt at hearing preservation versus potential for tinnitus elimination/risk of new onset of tinnitus. Martin Chovanec, Eduard Zvěřina, Oliver Profant, Zuzana Balogová, Jan Kluh, Josef Syka, Jiří Lisý, Ilja Merunka, Jiří Skřivan, and Jan Betka Copyright © 2015 Martin Chovanec et al. All rights reserved. Quantitative Analysis Linking Inner Hair Cell Voltage Changes and Postsynaptic Conductance Change: A Modelling Study Mon, 05 Jan 2015 14:22:49 +0000 This paper presents a computational model which estimates the postsynaptic conductance change of mammalian Type I afferent peripheral process when airborne acoustic waves impact on the tympanic membrane. A model of the human auditory periphery is used to estimate the inner hair cell potential change in response to airborne sound. A generic and tunable topology of the mammalian synaptic ribbon is generated and the voltage dependence of its substructures is used to calculate discrete and probabilistic neurotransmitter vesicle release. Results suggest an almost linear relationship between increasing sound level (in dB SPL) and the postsynaptic conductance for frequencies considered too high for neurons to phase lock with (i.e., a few kHz). Furthermore coordinated vesicle release is shown for up to 300–400 Hz and a mechanism of phase shifting the subharmonic content of a stimulating signal is suggested. Model outputs suggest that strong onset response and highly synchronised multivesicular release rely on compound fusion of ribbon tethered vesicles. Andreas N. Prokopiou and Emm. M. Drakakis Copyright © 2015 Andreas N. Prokopiou and Emm. M. Drakakis. All rights reserved. Otolaryngology, Head and Neck Surgery Sun, 28 Dec 2014 06:45:05 +0000 Tsung-Lin Yang, Robert L. Ferris, Tetsuya Ogawa, Peter Hwang, Michael Tong, and Mu-Kuan Chen Copyright © 2014 Tsung-Lin Yang et al. All rights reserved. A Clinically Oriented Introduction and Review on Finite Element Models of the Human Cochlea Tue, 04 Nov 2014 06:39:06 +0000 Due to the inaccessibility of the inner ear, direct in vivo information on cochlear mechanics is difficult to obtain. Mathematical modelling is a promising way to provide insight into the physiology and pathology of the cochlea. Finite element method (FEM) is one of the most popular discrete mathematical modelling techniques, mainly used in engineering that has been increasingly used to model the cochlea and its elements. The aim of this overview is to provide a brief introduction to the use of FEM in modelling and predicting the behavior of the cochlea in normal and pathological conditions. It will focus on methodological issues, modelling assumptions, simulation of clinical scenarios, and pathologies. Dimitrios Kikidis and Athanasios Bibas Copyright © 2014 Dimitrios Kikidis and Athanasios Bibas. All rights reserved. Optical Coherence Tomography Guided Laser Cochleostomy: Towards the Accuracy on Tens of Micrometer Scale Thu, 11 Sep 2014 07:29:41 +0000 Lasers have been proven to be precise tools for bone ablation. Applying no mechanical stress to the patient, they are potentially very suitable for microsurgery on fragile structures such as the inner ear. However, it remains challenging to control the laser-bone ablation without injuring embedded soft tissue. In this work, we demonstrate a closed-loop control of a short-pulsed CO2 laser to perform laser cochleostomy under the monitoring of an optical coherence tomography (OCT) system. A foresighted detection of the bone-endosteum-perilymph boundary several hundred micrometers before its exposure has been realized. Position and duration of the laser pulses are planned based on the residual bone thickness distribution. OCT itself is also used as a highly accurate tracking system for motion compensation between the target area and the optics. During ex vivo experimental evaluation on fresh porcine cochleae, the ablation process terminated automatically when the thickness of the residual tissue layer uniformly reached a predefined value. The shape of the resulting channel bottom converged to the natural curvature of the endosteal layer without injuring the critical structure. Preliminary measurements in OCT scans indicated that the mean absolute accuracy of the shape approximation was only around 20 μm. Yaokun Zhang, Tom Pfeiffer, Marcel Weller, Wolfgang Wieser, Robert Huber, Jörg Raczkowsky, Jörg Schipper, Heinz Wörn, and Thomas Klenzner Copyright © 2014 Yaokun Zhang et al. All rights reserved. Electroacoustic Stimulation: Now and into the Future Thu, 04 Sep 2014 00:00:00 +0000 Cochlear implants have provided hearing to hundreds of thousands of profoundly deaf people around the world. Recently, the eligibility criteria for cochlear implantation have been relaxed to include individuals who have some useful residual hearing. These recipients receive inputs from both electric and acoustic stimulation (EAS). Implant recipients who can combine these hearing modalities demonstrate pronounced benefit in speech perception, listening in background noise, and music appreciation over implant recipients that rely on electrical stimulation alone. The mechanisms bestowing this benefit are unknown, but it is likely that interaction of the electric and acoustic signals in the auditory pathway plays a role. Protection of residual hearing both during and following cochlear implantation is critical for EAS. A number of surgical refinements have been implemented to protect residual hearing, and the development of hearing-protective drug and gene therapies is promising for EAS recipients. This review outlines the current field of EAS, with a focus on interactions that are observed between these modalities in animal models. It also outlines current trends in EAS surgery and gives an overview of the drug and gene therapies that are clinically translatable and may one day provide protection of residual hearing for cochlear implant recipients. S. Irving, L. Gillespie, R. Richardson, D. Rowe, J. B. Fallon, and A. K. Wise Copyright © 2014 S. Irving et al. All rights reserved. Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells Sun, 31 Aug 2014 08:06:16 +0000 Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cells in vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced. Ai-Ho Liao, Yi-Lei Hsieh, Hsin-Chiao Ho, Hang-Kang Chen, Yi-Chun Lin, Cheng-Ping Shih, Hsin-Chien Chen, Chao-Yin Kuo, Ying-Jui Lu, and Chih-Hung Wang Copyright © 2014 Ai-Ho Liao et al. All rights reserved. Development of a Test of Suprathreshold Acuity in Noise in Brazilian Portuguese: A New Method for Hearing Screening and Surveillance Thu, 28 Aug 2014 00:00:00 +0000 This paper describes the development of a speech-in-noise test for hearing screening and surveillance in Brazilian Portuguese based on the evaluation of suprathreshold acuity performances. The SUN test (Speech Understanding in Noise) consists of a list of intervocalic consonants in noise presented in a multiple-choice paradigm by means of a touch screen. The test provides one out of three possible results: “a hearing check is recommended” (red light), “a hearing check would be advisable” (yellow light), and “no hearing difficulties” (green light) (Paglialonga et al., Comput. Biol. Med. 2014). This novel test was developed in a population of 30 normal hearing young adults and 101 adults with varying degrees of hearing impairment and handicap, including normal hearing. The test had 84% sensitivity and 76% specificity compared to conventional pure-tone screening and 83% sensitivity and 86% specificity to detect disabling hearing impairment. The test outcomes were in line with the degree of self-perceived hearing handicap. The results found here paralleled those reported in the literature for the SUN test and for conventional speech-in-noise measures. This study showed that the proposed test might be a viable method to identify individuals with hearing problems to be referred to further audiological assessment and intervention. Nara Vaez, Liliane Desgualdo-Pereira, and Alessia Paglialonga Copyright © 2014 Nara Vaez et al. All rights reserved. A Three-Dimensional Finite-Element Model of a Human Dry Skull for Bone-Conduction Hearing Wed, 27 Aug 2014 00:00:00 +0000 A three-dimensional finite-element (FE) model of a human dry skull was devised for simulation of human bone-conduction (BC) hearing. Although a dry skull is a simplification of the real complex human skull, such model is valuable for understanding basic BC hearing processes. For validation of the model, the mechanical point impedance of the skull as well as the acceleration of the ipsilateral and contralateral cochlear bone was computed and compared to experimental results. Simulation results showed reasonable consistency between the mechanical point impedance and the experimental measurements when Young’s modulus for skull and polyurethane was set to be 7.3 GPa and 1 MPa with 0.01 and 0.1 loss factors at 1 kHz, respectively. Moreover, the acceleration in the medial-lateral direction showed the best correspondence with the published experimental data, whereas the acceleration in the inferior-superior direction showed the largest discrepancy. However, the results were reasonable considering that different geometries were used for the 3D FE skull and the skull used in the published experimental study. The dry skull model is a first step for understanding BC hearing mechanism in a human head and simulation results can be used to predict vibration pattern of the bone surrounding the middle and inner ear during BC stimulation. Namkeun Kim, You Chang, and Stefan Stenfelt Copyright © 2014 Namkeun Kim et al. All rights reserved. Adenosine Amine Congener as a Cochlear Rescue Agent Tue, 26 Aug 2014 12:53:06 +0000 We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 g/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses 50 g/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment. Srdjan M. Vlajkovic, Hao Chang, Song Yee Paek, Howard H.-T. Chi, Sreevalsan Sreebhavan, Ravindra S. Telang, Malcolm Tingle, Gary D. Housley, and Peter R. Thorne Copyright © 2014 Srdjan M. Vlajkovic et al. All rights reserved. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage Tue, 26 Aug 2014 09:07:33 +0000 Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN). Yu Jiao, Björn Palmgren, Ekaterina Novozhilova, Ulrica Englund Johansson, Anne L. Spieles-Engemann, Ajay Kale, Samuel I. Stupp, and Petri Olivius Copyright © 2014 Yu Jiao et al. All rights reserved. Kölliker’s Organ and the Development of Spontaneous Activity in the Auditory System: Implications for Hearing Dysfunction Wed, 20 Aug 2014 00:00:00 +0000 Prior to the “onset of hearing,” developing cochlear inner hair cells (IHCs) and primary auditory neurons undergo experience-independent activity, which is thought to be important in retaining and refining neural connections in the absence of sound. One of the major hypotheses regarding the origin of such activity involves a group of columnar epithelial supporting cells forming Kölliker’s organ, which is only present during this critical period of auditory development. There is strong evidence for a purinergic signalling mechanism underlying such activity. ATP released through connexin hemichannels may activate P2 purinergic receptors in both Kölliker’s organ and the adjacent IHCs, leading to generation of electrical activity throughout the auditory system. However, recent work has suggested an alternative origin, by demonstrating the ability of IHCs to generate this spontaneous activity without activation by ATP. Regardless, developmental abnormalities of Kölliker’s organ may lead to congenital hearing loss, considering that mutations in ion channels (hemichannels, gap junctions, and calcium channels) involved in Kölliker’s organ activity share strong links with such types of deafness. M. W. Nishani Dayaratne, Srdjan M. Vlajkovic, Janusz Lipski, and Peter R. Thorne Copyright © 2014 M. W. Nishani Dayaratne et al. All rights reserved. Cortical Electrophysiological Markers of Language Abilities in Children with Hearing Aids: A Pilot Study Tue, 19 Aug 2014 08:11:40 +0000 Objective. To investigate cortical auditory evoked potentials (CAEPs) in pediatric hearing aid (HA) users, with and without language impairment. Design. CAEPs were measured in 11 pediatric HA users (age: 8–12 years) with moderate bilateral sensorineural hearing loss (HL); participants were classified according to language ability. CAEPs were also measured for a control group of 11 age-matched, normal-hearing (NH) children. Results. HL children without language impairment exhibited normal CAEPs. HL children with language impairment exhibited atypical temporal CAEPs, characterized by the absence of N1c; frontocentral responses displayed normal age-related patterns. Conclusion. Results suggest that abnormal temporal brain function may underlie language impairment in pediatric HA users with moderate sensorineural HL. David Bakhos, Hélène Delage, John Galvin, Emmanuel Lescanne, Sylvie Roux, Frédérique Bonnet-Brilhault, and Nicole Bruneau Copyright © 2014 David Bakhos et al. All rights reserved. Shear Wave Elastography: A New Noninvasive Tool to Assess the Intensity of Fibrosis of Irradiated Salivary Glands in Head and Neck Cancer Patients Sun, 17 Aug 2014 08:29:10 +0000 The aim of the study was to assess salivary gland parenchyma by means of sonoelastography in patients irradiated for head and neck squamous cell carcinoma (HNSCC). The studied group consisted of 52 patients after radiotherapy (RT) and 54 healthy volunteers. All of the former were treated for advanced larynx (40), oropharynx (9), or maxilla (3) squamous cancers and suffered from chronic dryness. Ultrasonography (US) and elastography (ES) were performed, as well as an assessment of the amount of saliva and Common Terminology Criteria for Adverse Events (CTCAE) scale. There was a statistical difference between ES values in the RT group and in the controls for parotid glands (41.7 kPa versus 26.03 kPa, ) and for submandibular glands (37.6 kPa versus 22.4 kPa; ). There was a significant correlation between the CTCAE scores and objective saliva amount (), and the median amount of saliva in the examined group was lower than in the reference group (1.86 g versus 2.75 g, ). In conclusion sonoelastography adds a new parameter to ultrasonography in “one touch examination” and may be a useful tool for major salivary gland evaluation during the radiotherapy course and follow-up period. Jarosław Kałużny, Tomasz Kopeć, Ewelina Szczepanek-Parulska, Adam Stangierski, Edyta Gurgul, Marek Ruchała, Piotr Milecki, and Małgorzata Wierzbicka Copyright © 2014 Jarosław Kałużny et al. All rights reserved. The Effects of Acute Stress-Induced Sleep Disturbance on Acoustic Trauma-Induced Tinnitus in Rats Sun, 03 Aug 2014 09:09:21 +0000 Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats. Yiwen Zheng, Lucy Stiles, Yi-Ting Chien, Cynthia L. Darlington, and Paul F. Smith Copyright © 2014 Yiwen Zheng et al. All rights reserved. Reconstruction of Cochlea Based on Micro-CT and Histological Images of the Human Inner Ear Sun, 03 Aug 2014 07:56:34 +0000 The study of the normal function and pathology of the inner ear has unique difficulties as it is inaccessible during life and, so, conventional techniques of pathologic studies such as biopsy and surgical excision are not feasible, without further impairing function. Mathematical modelling is therefore particularly attractive as a tool in researching the cochlea and its pathology. The first step towards efficient mathematical modelling is the reconstruction of an accurate three dimensional (3D) model of the cochlea that will be presented in this paper. The high quality of the histological images is being exploited in order to extract several sections of the cochlea that are not visible on the micro-CT (mCT) images (i.e., scala media, spiral ligament, and organ of Corti) as well as other important sections (i.e., basilar membrane, Reissner membrane, scala vestibule, and scala tympani). The reconstructed model is being projected in the centerline of the coiled cochlea, extracted from mCT images, and represented in the 3D space. The reconstruction activities are part of the SIFEM project, which will result in the delivery of an infrastructure, semantically interlinking various tools and libraries (i.e., segmentation, reconstruction, and visualization tools) with the clinical knowledge, which is represented by existing data, towards the delivery of a robust multiscale model of the inner ear. Christos Bellos, George Rigas, Ioannis F. Spiridon, Athanasios Bibas, Dimitra Iliopoulou, Frank Böhnke, Dimitrios Koutsouris, and Dimitrios I. Fotiadis Copyright © 2014 Christos Bellos et al. All rights reserved. Middle-Ear Microsurgery Simulation to Improve New Robotic Procedures Wed, 23 Jul 2014 11:39:50 +0000 Otological microsurgery is delicate and requires high dexterity in bad ergonomic conditions. To assist surgeons in these indications, a teleoperated system, called RobOtol, is developed. This robot enhances gesture accuracy and handiness and allows exploration of new procedures for middle ear surgery. To plan new procedures that exploit the capacities given by the robot, a surgical simulator is developed. The simulation reproduces with high fidelity the behavior of the anatomical structures and can also be used as a training tool for an easier control of the robot for surgeons. In the paper, we introduce the middle ear surgical simulation and then we perform virtually two challenging procedures with the robot. We show how interactive simulation can assist in analyzing the benefits of robotics in the case of complex manipulations or ergonomics studies and allow the development of innovative surgical procedures. New robot-based microsurgical procedures are investigated. The improvement offered by RobOtol is also evaluated and discussed. Guillaume Kazmitcheff, Yann Nguyen, Mathieu Miroir, Fabien Péan, Evelyne Ferrary, Stéphane Cotin, Olivier Sterkers, and Christian Duriez Copyright © 2014 Guillaume Kazmitcheff et al. All rights reserved. Modelling Cochlear Mechanics Wed, 23 Jul 2014 00:00:00 +0000 The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane (BM). Sounds enter the fluid-filled cochlea and cause deflection of the BM due to pressure differences between the cochlear fluid chambers. These deflections travel along the cochlea, increasing in amplitude, until a frequency-dependent characteristic position and then decay away rapidly. The hair cells can detect these deflections and encode them as neural signals. Modelling the mechanics of the cochlea is of help in interpreting experimental observations and also can provide predictions of the results of experiments that cannot currently be performed due to technical limitations. This paper focuses on reviewing the numerical modelling of the mechanical and electrical processes in the cochlea, which include fluid coupling, micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling. Guangjian Ni, Stephen J. Elliott, Mohammad Ayat, and Paul D. Teal Copyright © 2014 Guangjian Ni et al. All rights reserved. Speech Understanding with a New Implant Technology: A Comparative Study with a New Nonskin Penetrating Baha System Wed, 23 Jul 2014 00:00:00 +0000 Objective. To compare hearing and speech understanding between a new, nonskin penetrating Baha system (Baha Attract) to the current Baha system using a skin-penetrating abutment. Methods. Hearing and speech understanding were measured in 16 experienced Baha users. The transmission path via the abutment was compared to a simulated Baha Attract transmission path by attaching the implantable magnet to the abutment and then by adding a sample of artificial skin and the external parts of the Baha Attract system. Four different measurements were performed: bone conduction thresholds directly through the sound processor (BC Direct), aided sound field thresholds, aided speech understanding in quiet, and aided speech understanding in noise. Results. The simulated Baha Attract transmission path introduced an attenuation starting from approximately 5 dB at 1000 Hz, increasing to 20–25 dB above 6000 Hz. However, aided sound field threshold shows smaller differences and aided speech understanding in quiet and in noise does not differ significantly between the two transmission paths. Conclusion. The Baha Attract system transmission path introduces predominately high frequency attenuation. This attenuation can be partially compensated by adequate fitting of the speech processor. No significant decrease in speech understanding in either quiet or in noise was found. Anja Kurz, Mark Flynn, Marco Caversaccio, and Martin Kompis Copyright © 2014 Anja Kurz et al. All rights reserved. Prevention and Restoration of Hearing Loss Associated with the Use of Cisplatin Tue, 22 Jul 2014 06:29:53 +0000 Background. Cisplatin is a well known platinum-based chemotherapeutic agent used for the treatment of various malignant tumours. A frequent side effect of cisplatin therapy is ototoxicity. Unfortunately, currently there are no available treatments. Material and Methods. Experimental, clinical studies and reviews published between 2004 and 2014 in the English medical literature concerning ototoxicity were selected using Medline, PubMed, and Google Scholar databases. Inclusion criteria were cisplatin-induced ototoxicity and therapy aimed at preventing or curing this disorder. Molecular mechanisms and clinical, audiological, and histological markers of cisplatin-induced ototoxicity are described. Moreover, experimental and clinical strategies for prevention or treatment of hearing loss were also reviewed. Results and Discussion. Experimental studies demonstrate a wide range of otoprotective molecules and strategies efficient against cisplatin-induced hearing loss. However, only dexamethasone proved a slight otoprotective effect in a clinical study. Conclusion. Further research must be completed to bring future therapeutic options into clinical setting. Felician Chirtes and Silviu Albu Copyright © 2014 Felician Chirtes and Silviu Albu. All rights reserved. Screening of Cognitive Function and Hearing Impairment in Older Adults: A Preliminary Study Tue, 22 Jul 2014 06:28:32 +0000 Background. Previous research has found that hearing loss is associated with poorer cognitive function. The question is that when a hearing impairment is being compensated for by appropriately fitted monaural hearing aids, special precautions are still needed when screening cognitive function in older adults. Objective. This research examined cognitive function in elderly hearing aid users who used monaural hearing aids and whether the presence of a hearing impairment should be accounted for when screening cognitive function in these individuals. Methods. Auditory thresholds, sentence reception thresholds, and self-reported outcomes with hearing aids were measured in 34 older hearing aid users to ensure hearing aids were appropriately fitted. Mini-Mental State Examination (MMSE) results obtained in these participants were then compared to normative data obtained in a general older population exhibiting similar demographic characteristics. Stepwise multiple regression analyses were used to examine the effects of demographic and auditory variables on MMSE scores. Conclusions. Results showed that, even with appropriately fitted hearing aids, cognitive decline was significant. Besides the factors commonly measured in the literature, we believed that auditory deprivation was not being fully compensated for by hearing aids. Most importantly, screening of cognitive function should take into account the effects of hearing impairment, even when hearing devices have been appropriately fitted. Lena Lar Nar Wong, Joannie Ka Yin Yu, Shaina Shing Chan, and Michael Chi Fai Tong Copyright © 2014 Lena Lar Nar Wong et al. All rights reserved. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment Tue, 22 Jul 2014 06:24:46 +0000 Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. Yasue Uchida, Saiko Sugiura, Michihiko Sone, Hiromi Ueda, and Tsutomu Nakashima Copyright © 2014 Yasue Uchida et al. All rights reserved. Intracochlear Fluid Pressure Changes Related to the Insertional Speed of a CI Electrode Wed, 16 Jul 2014 12:11:11 +0000 Introduction. To preserve residual hearing the atraumaticity of the cochlea electrode insertion has become a focus of cochlear implant research. In addition to other factors, the speed of insertion is thought to be a contributing factor in the concept of atraumatic implantation. The aim of our study was to observe intracochlear fluid pressure changes due to different insertional speeds of an implant electrode in a cochlear model. Materials and Methods. The experiments were performed using an artificial cochlear model. A linear actuator was mounted on an Advanced Bionics IJ insertional tool. The intracochlear fluid pressure was recorded through a pressure sensor which was placed in the helicotrema area. Defined insertions were randomly performed with speeds of 0.1 mm/sec, 0.25 mm/sec, 0.5 mm/sec, 1 mm/sec, and 2 mm/sec. Results. A direct correlation between speed and pressure was observed. Mean maximum values of intracochlear fluid pressure varied between 0.41 mm Hg and 1.27 mm Hg. Conclusion. We provide the first results of fluid pressure changes due to insertional speeds of CI electrodes in a cochlear model. A relationship between the insertional speed and intracochlear fluid pressure was observed. Further experiments are needed to apply these results to the in vivo situation. I. Todt, P. Mittmann, and A. Ernst Copyright © 2014 I. Todt et al. All rights reserved. Definition of Metrics to Evaluate Cochlear Array Insertion Forces Performed with Forceps, Insertion Tool, or Motorized Tool in Temporal Bone Specimens Tue, 15 Jul 2014 00:00:00 +0000 Introduction. In order to achieve a minimal trauma to the inner ear structures during array insertion, it would be suitable to control insertion forces. The aim of this work was to compare the insertion forces of an array insertion into anatomical specimens with three different insertion techniques: with forceps, with a commercial tool, and with a motorized tool. Materials and Methods. Temporal bones have been mounted on a 6-axis force sensor to record insertion forces. Each temporal bone has been inserted, with a lateral wall electrode array, in random order, with each of the 3 techniques. Results. Forceps manual and commercial tool insertions generated multiple jerks during whole length insertion related to fits and starts. On the contrary, insertion force with the motorized tool only rose at the end of the insertion. Overall force momentum was 1.16 ± 0.505 N (mean ± SD, ), 1.337 ± 0.408 N (), and 1.573 ± 0.764 N () for manual insertion with forceps and commercial and motorized tools, respectively. Conclusion. Considering force momentum, no difference between the three techniques was observed. Nevertheless, a more predictable force profile could be observed with the motorized tool with a smoother rise of insertion forces. Yann Nguyen, Guillaume Kazmitcheff, Daniele De Seta, Mathieu Miroir, Evelyne Ferrary, and Olivier Sterkers Copyright © 2014 Yann Nguyen et al. All rights reserved. The Construct Validity and Reliability of an Assessment Tool for Competency in Cochlear Implant Surgery Thu, 10 Jul 2014 08:31:33 +0000 Introduction. We introduce a rating tool that objectively evaluates the skills of surgical trainees performing cochlear implant surgery. Methods. Seven residents and seven experts performed cochlear implant surgery sessions from mastoidectomy to cochleostomy on a standardized virtual reality temporal bone. A total of twenty-eight assessment videos were recorded and two consultant otolaryngologists evaluated the performance of each participant using these videos. Results. Interrater reliability was calculated using the intraclass correlation coefficient for both the global and checklist components of the assessment instrument. The overall agreement was high. The construct validity of this instrument was strongly supported by the significantly higher scores in the expert group for both components. Conclusion. Our results indicate that the proposed assessment tool for cochlear implant surgery is reliable, accurate, and easy to use. This instrument can thus be used to provide objective feedback on overall and task-specific competency in cochlear implantation. Patorn Piromchai, Pornthep Kasemsiri, Sudanthi Wijewickrema, Ioanna Ioannou, Gregor Kennedy, and Stephen O'Leary Copyright © 2014 Patorn Piromchai et al. All rights reserved. Acute and Long-Term Effects of Noise Exposure on the Neuronal Spontaneous Activity in Cochlear Nucleus and Inferior Colliculus Brain Slices Tue, 08 Jul 2014 05:56:05 +0000 Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss. Moritz Gröschel, Jana Ryll, Romy Götze, Arne Ernst, and Dietmar Basta Copyright © 2014 Moritz Gröschel et al. All rights reserved. Feasibility Study of a Hand Guided Robotic Drill for Cochleostomy Mon, 07 Jul 2014 00:00:00 +0000 The concept of a hand guided robotic drill has been inspired by an automated, arm supported robotic drill recently applied in clinical practice to produce cochleostomies without penetrating the endosteum ready for inserting cochlear electrodes. The smart tactile sensing scheme within the drill enables precise control of the state of interaction between tissues and tools in real-time. This paper reports development studies of the hand guided robotic drill where the same consistent outcomes, augmentation of surgeon control and skill, and similar reduction of induced disturbances on the hearing organ are achieved. The device operates with differing presentation of tissues resulting from variation in anatomy and demonstrates the ability to control or avoid penetration of tissue layers as required and to respond to intended rather than involuntary motion of the surgeon operator. The advantage of hand guided over an arm supported system is that it offers flexibility in adjusting the drilling trajectory. This can be important to initiate cutting on a hard convex tissue surface without slipping and then to proceed on the desired trajectory after cutting has commenced. The results for trials on phantoms show that drill unit compliance is an important factor in the design. Peter Brett, Xinli Du, Masoud Zoka-Assadi, Chris Coulson, Andrew Reid, and David Proops Copyright © 2014 Peter Brett et al. All rights reserved. Mechatronic Feasibility of Minimally Invasive, Atraumatic Cochleostomy Mon, 07 Jul 2014 00:00:00 +0000 Robotic assistance in the context of lateral skull base surgery, particularly during cochlear implantation procedures, has been the subject of considerable research over the last decade. The use of robotics during these procedures has the potential to provide significant benefits to the patient by reducing invasiveness when gaining access to the cochlea, as well as reducing intracochlear trauma when performing a cochleostomy. Presented herein is preliminary work on the combination of two robotic systems for reducing invasiveness and trauma in cochlear implantation procedures. A robotic system for minimally invasive inner ear access was combined with a smart drilling tool for robust and safe cochleostomy; evaluation was completed on a single human cadaver specimen. Access to the middle ear was successfully achieved through the facial recess without damage to surrounding anatomical structures; cochleostomy was completed at the planned position with the endosteum remaining intact after drilling as confirmed by microscope evaluation. Tom Williamson, Xinli Du, Brett Bell, Chris Coulson, Marco Caversaccio, David Proops, Peter Brett, and Stefan Weber Copyright © 2014 Tom Williamson et al. All rights reserved. Quality Assurance of Multiport Image-Guided Minimally Invasive Surgery at the Lateral Skull Base Thu, 03 Jul 2014 09:29:29 +0000 For multiport image-guided minimally invasive surgery at the lateral skull base a quality management is necessary to avoid the damage of closely spaced critical neurovascular structures. So far there is no standardized method applicable independently from the surgery. Therefore, we adapt a quality management method, the quality gates (QG), which is well established in, for example, the automotive industry and apply it to multiport image-guided minimally invasive surgery. QG divide a process into different sections. Passing between sections can only be achieved if previously defined requirements are fulfilled which secures the process chain. An interdisciplinary team of otosurgeons, computer scientists, and engineers has worked together to define the quality gates and the corresponding criteria that need to be fulfilled before passing each quality gate. In order to evaluate the defined QG and their criteria, the new surgery method was applied with a first prototype at a human skull cadaver model. We show that the QG method can ensure a safe multiport minimally invasive surgical process at the lateral skull base. Therewith, we present an approach towards the standardization of quality assurance of surgical processes. Maria Nau-Hermes, Robert Schmitt, Meike Becker, Wissam El-Hakimi, Stefan Hansen, Thomas Klenzner, and Jörg Schipper Copyright © 2014 Maria Nau-Hermes et al. All rights reserved. Semiautomatic Cochleostomy Target and Insertion Trajectory Planning for Minimally Invasive Cochlear Implantation Wed, 02 Jul 2014 11:53:19 +0000 A major component of minimally invasive cochlear implantation is atraumatic scala tympani (ST) placement of the electrode array. This work reports on a semiautomatic planning paradigm that uses anatomical landmarks and cochlear surface models for cochleostomy target and insertion trajectory computation. The method was validated in a human whole head cadaver model ( ears). Cochleostomy targets were generated from an automated script and used for consecutive planning of a direct cochlear access (DCA) drill trajectory from the mastoid surface to the inner ear. An image-guided robotic system was used to perform both, DCA and cochleostomy drilling. Nine of 10 implanted specimens showed complete ST placement. One case of scala vestibuli insertion occurred due to a registration/drilling error of 0.79 mm. The presented approach indicates that a safe cochleostomy target and insertion trajectory can be planned using conventional clinical imaging modalities, which lack sufficient resolution to identify the basilar membrane. Wilhelm Wimmer, Frederic Venail, Tom Williamson, Mohamed Akkari, Nicolas Gerber, Stefan Weber, Marco Caversaccio, Alain Uziel, and Brett Bell Copyright © 2014 Wilhelm Wimmer et al. All rights reserved. Minimally Invasive Multiport Surgery of the Lateral Skull Base Wed, 02 Jul 2014 10:12:04 +0000 Objective. Minimally invasive procedures minimize iatrogenic tissue damage and lead to a lower complication rate and high patient satisfaction. To date only experimental minimally invasive single-port approaches to the lateral skull base have been attempted. The aim of this study was to verify the feasibility of a minimally invasive multiport approach for advanced manipulation capability and visual control and develop a software tool for preoperative planning. Methods. Anatomical 3D models were extracted from twenty regular temporal bone CT scans. Collision-free trajectories, targeting the internal auditory canal, round window, and petrous apex, were simulated with a specially designed planning software tool. A set of three collision-free trajectories was selected by skull base surgeons concerning the maximization of the distance to critical structures and the angles between the trajectories. Results. A set of three collision-free trajectories could be successfully simulated to the three targets in each temporal bone model without violating critical anatomical structures. Conclusion. A minimally invasive multiport approach to the lateral skull base is feasible. The developed software is the first step for preoperative planning. Further studies will focus on cadaveric and clinical translation. Igor Stenin, Stefan Hansen, Meike Becker, Georgios Sakas, Dieter Fellner, Thomas Klenzner, and Jörg Schipper Copyright © 2014 Igor Stenin et al. All rights reserved. A Surgical Navigation System for Guiding Exact Cochleostomy Using Auditory Feedback: A Clinical Feasibility Study Tue, 01 Jul 2014 10:38:53 +0000 In cochlear implantation (CI), the insertion of the electrode array into the appropriate compartment of the cochlea, the scala tympani, is important for an optimal hearing outcome. The current surgical technique for CI depends primarily on the surgeon’s skills and experience level to achieve the correct placement of the electrode array, and the surgeon needs to confirm that the exact placement is achieved prior to completing the procedure. Thus, a surgical navigation system can help the surgeon to access the scala tympani without injuring important organs in the complex structure of the temporal bone. However, the use of a surgical microscope has restricted the effectiveness of the surgical navigation because it has been difficult to deliver the navigational information to the surgeon from outside of the surgeon’s visual attention. We herein present a clinical feasibility study of an auditory feedback function developed as a computer-surgeon interface that can guide the surgeon to the preset cochleostomy location. As a result, the surgeon could confirm that the drilling point was correct, while keeping his or her eyes focused on the microscope. The proposed interface reduced the common frustration that surgeons experience when using surgical navigation during otologic surgeries. Byunghyun Cho, Nozomu Matsumoto, Shizuo Komune, and Makoto Hashizume Copyright © 2014 Byunghyun Cho et al. All rights reserved. Identification of a Novel Methylated Gene in Nasopharyngeal Carcinoma: TTC40 Mon, 30 Jun 2014 11:36:35 +0000 To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC), methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5′-end of the tetratricopeptide repeat domain 40 (TTC40) gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5′-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5′-TTC40 gene hypermethylation. In conclusion, we found that the 5′-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5′-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed. Wajdi Ayadi, Nesrine Allaya, Hanèn Frikha, Emna Trigui, Abdelmajid Khabir, Abdelmonem Ghorbel, Jamel Daoud, Mounir Frikha, Ali Gargouri, and Raja Mokdad-Gargouri Copyright © 2014 Wajdi Ayadi et al. All rights reserved. The Role of Narrow Band Imaging in the Detection of Recurrent Laryngeal and Hypopharyngeal Cancer after Curative Radiotherapy Mon, 30 Jun 2014 07:30:08 +0000 Narrow band imaging is considered a significant improvement in the possibility of detecting early mucosal lesion of the upper aerodigestive tract. Early detection of mucosal neoplastic lesions is of utmost importance for patients survival. There is evidence that, especially in patients previously treated by means of curative radiotherapy or chemoradiotherapy, the early detection rate of recurrent disease is quite low. The aim of this study was to prove whether the videoendoscopy coupled with NBI might help detect recurrent or secondary tumors of the upper aerodigestive tract. 66 patients previously treated by means of RT or CRT with curative intent were enrolled in the study. All patients underwent transnasal flexible videoendoscopy with NBI mode under local anesthesia. When a suspicious lesion was identified in an ambulatory setting, its nature was proved histologically. Many of these changes were not identifiable by means of conventional white light (WL) endoscopy. The accuracy, sensitivity, specificity, and positive and negative predictive value of the method are very high (88%, 92%, 76%, 96%, and 91%, resp.). Results demonstrate that outpatient transnasal endoscopy with NBI is an excellent method for the follow-up of patients with carcinomas of the larynx and the hypopharynx primarily treated with radiotherapy. Michal Zabrodsky, Petr Lukes, Eva Lukesova, Jan Boucek, and Jan Plzak Copyright © 2014 Michal Zabrodsky et al. All rights reserved. The Role of NBI HDTV Magnifying Endoscopy in the Prehistologic Diagnosis of Laryngeal Papillomatosis and Spinocellular Cancer Tue, 17 Jun 2014 08:51:17 +0000 Narrow band imaging (NBI) HDTV (high definition television) magnifying endoscopy is considered to be superior for the accurate display of the microvascular patterns of superficial mucosal lesions. Observation of changes in intraepithelial papillary capillary loops (IPCL) can help distinguish benign from malignant lesions as part of an “optical biopsy.” However, IPCL changes in papillomas may be mistaken for spinocellular cancer (SCC). The aim of the study was to determine whether observing microvascular changes alone is sufficient for discriminating between laryngeal SCC and papillomatosis. An additional aim was to identify associated characteristics that could clarify the diagnosis. The study included 109 patients with a suspected laryngeal tumor or papilloma. HDTV NBI magnifying endoscopy was performed during direct laryngoscopy. It was possible to visualize IPCL changes in 82 out of 109 patients (75.2%). In 71 (86.6%) patients, the diagnosis was correctly determined. In 4 (4.9%) cases, the diagnosis of SCC was expressed on the basis of finding pathologic IPCL, but histology did not demonstrate malignancy. To achieve a correct diagnosis using HDTV NBI magnifying endoscopy, it is important not only to observe changes in the shape of IPCL but also to note possible papillary structures with central-axis capillaries typical of papillomatosis. Petr Lukes, Michal Zabrodsky, Eva Lukesova, Martin Chovanec, Jaromir Astl, Jaroslav A. Betka, and Jan Plzak Copyright © 2014 Petr Lukes et al. All rights reserved. Balloon Dilatation of Pediatric Subglottic Laryngeal Stenosis during the Artificial Apneic Pause: Experience in 5 Children Thu, 12 Jun 2014 08:58:40 +0000 Introduction. Balloon dilatation is a method of choice for treatment of laryngeal stenosis in children. The aim of procedure in apneic pause is to avoid new insertion of tracheostomy cannula. Patients and Methods. The authors performed balloon dilatation of subglottic laryngeal strictures (SGS) in 5 children (3 girls and 2 boys) without tracheotomy. Two of them with traumatic and inflammatory SGS had a tracheal cannula removed in the past. The other 3 children with postintubation SGS had never had a tracheostomy before. The need for tracheostomy due to worsening stridor was imminent for all of them. Results. The total of seven laryngeal dilatations by balloon esophagoplasty catheter in apneic pause was performed in the 5 children. The procedure averted the need for tracheostomy placement in 4 of them (80%). Failure of dilatation in girl with traumatic stenosis and concomitant severe obstructive lung disease led to repeated tracheostomy. Conclusion. Balloon dilatation of laryngeal stricture could be done in the absence of tracheostomy in apneic pause. Dilatation averted threatening tracheostomy in all except one case. Early complication after the procedure seems to be a negative prognostic factor for the outcome of balloon dilatation. J. Lisý, D. Groh, M. Chovanec, M. Marková, V. Suchánek, P. Polášková, and M. Trávníček Copyright © 2014 J. Lisý et al. All rights reserved. Newborn Hearing Screening and Early Diagnostic in the NICU Mon, 09 Jun 2014 00:00:00 +0000 The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%), conductive (1.83%) and auditory neuropathy spectrum (0.19%). Maria Francisca Colella-Santos, Thaís Antonelli Diniz Hein, Gabriele Libano de Souza, Maria Isabel Ramos do Amaral, and Raquel Leme Casali Copyright © 2014 Maria Francisca Colella-Santos et al. All rights reserved. Oncological and Functional Outcome after Surgical Treatment of Early Glottic Carcinoma without Anterior Commissure Involvement Mon, 02 Jun 2014 13:13:13 +0000 Introduction. Glottic carcinoma can be successfully diagnosed in its early stages and treated with high percentage of success. Organ preservation and optimal functional outcomes could be achieved with wide array of surgical techniques for early glottic cancer, including endoscopic approaches or open laryngeal preserving procedures, making surgery the preferred method of treatment of early glottic carcinoma in the last few years. Material and Methods. Prospective study was done on 59 patients treated for Tis and T1a glottic carcinoma over a one-year time period in a tertiary medical center. Patients were treated with endoscopic laser cordectomy (types II–IV cordectomies according to European Laryngological Society classification of endoscopic cordectomies) and open cordectomy through laryngofissure. Follow-up period was 60 months. Clinical and oncological results were followed postoperatively. Voice quality after the treatment was assessed using multidimensional voice analysis 12 months after the treatment. Results. There were no significant differences between oncological and functional results among two groups of patients, though complications were more frequent in patients treated with open cordectomy. Conclusion. Endoscopic laser surgery should be the first treatment of choice in treatment of early glottic carcinomas, though open approach through laryngofissure should be available for selected cases where anatomical factors present limiting adequate tumor removal. Jovica Milovanovic, Ana Jotic, Vojko Djukic, Bojan Pavlovic, Aleksandar Trivic, Sanja Krejovic-Trivic, Andjela Milovanovic, Aleksandar Milovanovic, Vera Artiko, and Bojan Banko Copyright © 2014 Jovica Milovanovic et al. All rights reserved. A Tutorial on Implantable Hearing Amplification Options for Adults with Unilateral Microtia and Atresia Mon, 02 Jun 2014 09:12:42 +0000 Background. Patients with unilateral atresia and microtia encounter problems in sound localization and speech understanding in noise. Although there are four implantable hearing devices available, there is little discussion and evidence on the application of these devices on patients with unilateral atresia and microtia problems. Objective. This paper will review the details of these four implantable hearing devices for the treatment of unilateral atresia. They are percuteaneous osseointegrated bone anchored hearing aid, Vibrant Soundbridge middle ear implant, Bonebridge bone conduction system, and Carina fully implantable hearing device. Methods. Four implantable hearing devices were reviewed and compared. The clinical decision process that led to the recommendation of a device was illustrated by using a case study. Conclusions. The selection of appropriate implantable hearing devices should be based on various factors, including radiological findings and patient preferences, possible surgical complications, whether the device is Food and Drug Administration- (FDA-)/CE-approved, and the finances. To ensure the accurate evaluation of candidacy and outcomes, the evaluation methods should be adapted to suite the type of hearing device. Joannie Ka Yin Yu, Lena Lai Nar Wong, Willis Sung Shan Tsang, and Michael Chi Fai Tong Copyright © 2014 Joannie Ka Yin Yu et al. All rights reserved. Complications of Microsurgery of Vestibular Schwannoma Wed, 28 May 2014 13:00:22 +0000 Background. The aim of this study was to analyze complications of vestibular schwannoma (VS) microsurgery. Material and Methods. A retrospective study was performed in 333 patients with unilateral vestibular schwannoma indicated for surgical treatment between January 1997 and December 2012. Postoperative complications were assessed immediately after VS surgery as well as during outpatient followup. Results. In all 333 patients microsurgical vestibular schwannoma (Koos grade 1: 12, grade 2: 34, grade 3: 62, and grade 4: 225) removal was performed. The main neurological complication was facial nerve dysfunction. The intermediate and poor function (HB III–VI) was observed in 124 cases (45%) immediately after surgery and in 104 cases (33%) on the last followup. We encountered disordered vestibular compensation in 13%, permanent trigeminal nerve dysfunction in 1%, and transient lower cranial nerves (IX–XI) deficit in 6%. Nonneurological complications included CSF leakage in 63% (lateral/medial variant: 99/1%), headache in 9%, and intracerebral hemorrhage in 5%. We did not encounter any case of meningitis. Conclusions. Our study demonstrates that despite the benefits of advanced high-tech equipment, refined microsurgical instruments, and highly developed neuroimaging technologies, there are still various and significant complications associated with vestibular schwannomas microsurgery. Jan Betka, Eduard Zvěřina, Zuzana Balogová, Oliver Profant, Jiří Skřivan, Josef Kraus, Jiří Lisý, Josef Syka, and Martin Chovanec Copyright © 2014 Jan Betka et al. All rights reserved. Cognitive Spare Capacity and Speech Communication: A Narrative Overview Tue, 27 May 2014 11:01:54 +0000 Background noise can make speech communication tiring and cognitively taxing, especially for individuals with hearing impairment. It is now well established that better working memory capacity is associated with better ability to understand speech under adverse conditions as well as better ability to benefit from the advanced signal processing in modern hearing aids. Recent work has shown that although such processing cannot overcome hearing handicap, it can increase cognitive spare capacity, that is, the ability to engage in higher level processing of speech. This paper surveys recent work on cognitive spare capacity and suggests new avenues of investigation. Mary Rudner and Thomas Lunner Copyright © 2014 Mary Rudner and Thomas Lunner. All rights reserved. Primary Surgical Therapy for Locally Limited Oral Tongue Cancer Tue, 20 May 2014 11:05:19 +0000 Objectives. The aim of this study was to assess the efficacy of primary surgical treatment in the management of locally limited oral tongue carcinoma. Methods. A retrospective evaluation was carried out for all patients treated with primary surgery for pT1-pT2 oral tongue carcinomas at a tertiary referral center between 1980 and 2005. All cases were assessed for disease-specific survival and local control rates in relation to T classification, N classification, infiltration depth of the primary tumor, and decision making on neck management and adjuvant therapy. The cases were additionally evaluated for the incidence of major complications and tracheotomies. Results. 263 cases were assessed. The 5-year disease-specific survival rate was 75.2%. Positive neck disease was shown to be a significant negative prognostic factor. The occult metastasis rate was 20.2%. Conclusions. Primary surgical treatment is a very effective modality against T1-T2 oral tongue carcinoma, and a low rate of complications can be anticipated. Konstantinos Mantsopoulos, Georgios Psychogios, Julian Künzel, Frank Waldfahrer, Johannes Zenk, and Heinrich Iro Copyright © 2014 Konstantinos Mantsopoulos et al. All rights reserved. A New Strategy for the Surgical Management of RLN Infiltrated by Well-Differentiated Thyroid Carcinoma Wed, 14 May 2014 00:00:00 +0000 Well-differentiated thyroid carcinoma (WDTC) represents the most common endocrine malignancy. Despite excellent prognoses exceeding 90% in 10-year follow-up, there are clinically controversial issues. One of these is extrathyroidal tumour extension invading recurrent laryngeal nerve (RLN). The spread outside of the thyroid parenchyma and invasion to the surrounding structures, classified as always T4a, are the most important negative prognostic factor for the WDTC. Conversely, resection of the RLN leads to vocal cord paralysis with hoarseness, possible swallowing problems, and finally decreased quality of life. We propose a new algorithm for intraoperative management based on the MACIS classification, which would allow swift status evaluation pre/intraoperatively and consider a possibility to preserve the infiltrated RLN without compromising an oncological radicality. In the case of a preoperative vocal cord paralysis (VCP) and confirmation of the invasive carcinoma, a resection of the RLN and the nerve graft reconstruction are indicated. Preoperatively, unaffected vocal cord movement and intraoperatively detected RLN infiltration by the invasive WDTC require an individual assessment of the oncological risk by the proposed algorithm. Preservation of the infiltrated RLN is oncologically acceptable only in specific groups of patients of a younger age with a minor size of primary tumour. Jan Boucek, Michal Zabrodsky, Martin Kuchar, Ondrej Fanta, Jiri Skrivan, and Jan Betka Copyright © 2014 Jan Boucek et al. All rights reserved. Tanshinone IIA Induces Apoptosis in Human Oral Cancer KB Cells through a Mitochondria-Dependent Pathway Tue, 13 May 2014 00:00:00 +0000 Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer. Pao-Yu Tseng, Wei-Cheng Lu, Ming-Ju Hsieh, Su-Yu Chien, and Mu-Kuan Chen Copyright © 2014 Pao-Yu Tseng et al. All rights reserved. Management of Anterior Skull Base Defect Depending on Its Size and Location Wed, 07 May 2014 07:55:56 +0000 Introduction. We present our experience in the reconstruction of these leaks depending on their size and location. Material and Methods. Fifty-four patients who underwent advanced skull base surgery (large defects, 20 mm) and 62 patients with CSF leaks of different origin (small, 2–10 mm, and midsize, 11–20 mm, defects) were included in the retrospective study. Large defects were reconstructed with a nasoseptal pedicled flap positioned on fat and fascia lata. In small and midsized leaks. Fascia lata in an underlay position was used for its reconstruction covered with mucoperiosteum of either the middle or the inferior turbinate. Results. The most frequent etiology for small and midsized defects was spontaneous (48.4%), followed by trauma (24.2%), iatrogenic (5%). The success rate after the first surgical reconstruction was 91% and 98% in large skull base defects and small/midsized, respectively. Rescue surgery achieved 100%. Conclusions. Endoscopic surgery for any type of skull base defect is the gold standard. The size of the defects does not seem to play a significant role in the success rate. Fascia lata and mucoperiosteum of the turbinate allow a two-layer reconstruction of small and midsized defects. For larger skull base defects, a combination of fat, fascia lata, and nasoseptal pedicled flaps provides a successful reconstruction. Manuel Bernal-Sprekelsen, Elena Rioja, Joaquim Enseñat, Karla Enriquez, Liza Viscovich, Freddy Enrique Agredo-Lemos, and Isam Alobid Copyright © 2014 Manuel Bernal-Sprekelsen et al. All rights reserved. Nasal Region Dimensions in Children: A CT Study and Clinical Implications Mon, 05 May 2014 10:40:39 +0000 Atresias of nasal cavity, especially in young children, pose an essential problem in children’s otolaryngology. Only a few morphometric studies of nasal cavity concerning healthy neonates and young infants without nasal stenosis are available. Multislice computed tomography is a perfect tool enabling a precise evaluation of anatomic structures. The aim of this study was a complex morphometric evaluation of clinically important bone and mucosal structures of nasal cavity and examination of their dependence on age and sex in children up to 3 years of age. 180 children, age range 0–3 years, were divided into 5 age groups, and measurements of 18 distances between skeletal structures and between mucosal structures of nasal cavity were performed on their CT scans. A correlation between the widths of selected bone structures was examined. There were no statistically significant differences in analyzed morphometric parameters between adjacent age groups. The differences were statistically significant only between extreme age groups. There was a correlation between evaluated structures and age. Our results are a valuable supplement of nasal cavity morphometric data of young children. They may be useful in setting reference values of evaluated parameters in children and in diagnosis and planning of surgical treatment in children’s otolaryngology. Wirginia Likus, Grzegorz Bajor, Katarzyna Gruszczyńska, Jan Baron, and Jarosław Markowski Copyright © 2014 Wirginia Likus et al. All rights reserved. Contemporary Hearing Rehabilitation Options in Patients with Aural Atresia Tue, 29 Apr 2014 12:02:21 +0000 Congenital aural atresia is the failure of development of the external auditory canal. It usually occurs in conjunction with microtia, which is the malformation of the auricle due to a failure of development of the external ear. Aural atresia, with or without microtia, may significantly affect the hearing and social life of the patients. It is important for every medical practitioner to be aware of the possible treatment options for hearing rehabilitation in this group of patients. In the era of modern technology, new choices, including Bone-Anchored Hearing Aid (BAHA) (Cochlear Ltd. and Oticon Medical), Vibrant Soundbridge (VSB) (MED-EL, Innsbruck, Austria), and Bonebridge system (BB) (MED-EL, Innsbruck, Austria), provide high-end alternatives to traditional Bone Conduction Hearing Aid and Auditory Canal Reconstruction. All these options have advantages and disadvantages, and they are appropriate for different patients and/or at different ages. This paper aims to provide an overview of the management of hearing rehabilitation in congenital aural atresia patients and a discussion of each treatment option. Jacky F. W. Lo, Willis S. S. Tsang, Joannie Y. K. Yu, Osan Y. M. Ho, Peter K. M. Ku, and Michael C. F. Tong Copyright © 2014 Jacky F. W. Lo et al. All rights reserved. Relationships of Alpha-SMA-Positive Fibroblasts and SDF-1-Positive Tumor Cells with Neoangiogenesis in Nasopharyngeal Carcinoma Sun, 27 Apr 2014 07:47:52 +0000 Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors with poor prognosis in Southern China and Southeast Asia. Angiogenesis-related molecules can be promising therapeutic targets in NPC. To investigate the relationships of cancer-associated fibroblasts (CAFs) and chemokine-related molecules with neoangiogenesis, we compared immunohistochemical analyses of alpha-smooth-muscle actin (α-SMA), stroma-derived factor-1 (SDF-1), and its receptor CXCR4 in primary NPC specimens and chronic nasopharyngitis tissues. In addition, we examined the expression of vascular endothelial growth factor (VEGF-A), and CD133- and VEGF- receptor-2 (VEGFR-2) double positive cells, as endothelial progenitor cells (EPCs). We also assessed CD34-positive microvessels. Significantly higher expression of α-SMA was observed in fibroblasts in NPC stroma. The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells. CXCR4-positive cells and CD133/VEGFR-2- double positive cells were observed in the stroma surrounding cancer nests, and VEGF was detected in both cancer and stromal cells. Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues. Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma. Shumin Wang, Ning Ma, Shosuke Kawanishi, Yusuke Hiraku, Shinji Oikawa, Ying Xie, Zhe Zhang, Guangwu Huang, and Mariko Murata Copyright © 2014 Shumin Wang et al. All rights reserved. Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale Wed, 23 Apr 2014 12:26:03 +0000 With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’s value ) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease. Markéta Čapková, Jana Šáchová, Hynek Strnad, Michal Kolář, Miluše Hroudová, Martin Chovanec, Zdeněk Čada, Martin Šteffl, Jaroslav Valach, Jan Kastner, Čestmír Vlček, Karel Smetana Jr., and Jan Plzák Copyright © 2014 Markéta Čapková et al. All rights reserved. High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas Wed, 23 Apr 2014 07:44:25 +0000 Background. Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and Methods. Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results. Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion. Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence. E. Lukesova, J. Boucek, E. Rotnaglova, M. Salakova, E. Koslabova, M. Grega, T. Eckschlager, B. Rihova, B. Prochazka, J. Klozar, and R. Tachezy Copyright © 2014 E. Lukesova et al. All rights reserved. Bipolar Thermofusion BiClamp 150 in Thyroidectomy: A Review of 1156 Operations Wed, 16 Apr 2014 12:59:34 +0000 Objectives. To compare the bipolar thermofusion BiClamp 150 with conventional ligature techniques for thyroid gland surgery, and report the advantages/disadvantages of both techniques. Methods. In this retrospective comparative study, all thyroid gland operations performed in the ENT Clinic Faculty Hospital Ostrava from 2006 to 2013 were included (1156 operations, 2122 lobes). Patients were categorized into two groups according to the type of vessel sealing method used, group I (BiClamp, operations) and group II (conventional ligature, operations). The number of revision surgeries due to wound hematoma was recorded as a bleeding event. Statistical analysis of the complication rate (bleeding rate, recurrent nerve palsy) and time of duration was performed. Results. The rate of revision surgery performed due to postoperative wound hematoma was significantly lower in group I (15/819, 1.83%) compared with group II (14/337, 4.15%) (). There was no statistically significant difference in the frequency of recurrent laryngeal nerve palsy between groups I and II (). The average surgery time was significantly shorter in group I (). Conclusion. Bipolar thermofusion BiClamp is an effective vessel sealing method that leads to a significant reduction in postoperative wound bleeding rates and reduces surgical time compared with conventional vessel ligature. Tomáš Pniak, Martin Formánek, Petr Matoušek, Karol Zeleník, and Pavel Komínek Copyright © 2014 Tomáš Pniak et al. All rights reserved. Minimally Invasive Video-Assisted versus Minimally Invasive Nonendoscopic Thyroidectomy Tue, 08 Apr 2014 07:23:53 +0000 Minimally invasive video-assisted thyroidectomy (MIVAT) and minimally invasive nonendoscopic thyroidectomy (MINET) represent well accepted and reproducible techniques developed with the main goal to improve cosmetic outcome, accelerate healing, and increase patient’s comfort following thyroid surgery. Between 2007 and 2011, a prospective nonrandomized study of patients undergoing minimally invasive thyroid surgery was performed to compare advantages and disadvantages of the two different techniques. There were no significant differences in the length of incision to perform surgical procedures. Mean duration of hemithyroidectomy was comparable in both groups, but it was more time consuming to perform total thyroidectomy by MIVAT. There were more patients undergoing MIVAT procedures without active drainage in the postoperative course and we also could see a trend for less pain in the same group. This was paralleled by statistically significant decreased administration of both opiates and nonopiate analgesics. We encountered two cases of recurrent laryngeal nerve palsies in the MIVAT group only. MIVAT and MINET represent safe and feasible alternative to conventional thyroid surgery in selected cases and this prospective study has shown minimal differences between these two techniques. Zdeněk Fík, Jaromír Astl, Michal Zábrodský, Petr Lukeš, Ilja Merunka, Jan Betka, and Martin Chovanec Copyright © 2014 Zdeněk Fík et al. All rights reserved. Experimental Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss Mon, 07 Apr 2014 14:00:58 +0000 This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL. Chang-qiang Tan, Xia Gao, Wen-jun Cai, Xiao-yun Qian, Ling Lu, and He Huang Copyright © 2014 Chang-qiang Tan et al. All rights reserved. Biological Basis for Increased Sensitivity to Radiation Therapy in HPV-Positive Head and Neck Cancers Thu, 03 Apr 2014 08:27:35 +0000 Although development of head and neck squamous cell carcinomas (HNSCCs) is commonly linked to the consumption of tobacco and alcohol, a link between human papillomavirus (HPV) infection and a subgroup of head and neck cancers has been established. These HPV-positive tumors represent a distinct biological entity with overexpression of viral oncoproteins E6 and E7. It has been shown in several clinical studies that HPV-positive HNSCCs have a more favorable outcome and greater response to radiotherapy. The reason for improved prognosis of HPV-related HNSCC remains speculative, but it could be owned to multiple factors. One hypothesis is that HPV-positive cells are intrinsically more sensitive to standard therapies and thus respond better to treatment. Another possibility is that HPV-positive tumors uniquely express viral proteins that induce an immune response during therapy that helps clear tumors and prevents recurrence. Here, we will review current evidence for the biological basis of increased radiosensitivity in HPV-positive HNSCC. V. Bol and V. Grégoire Copyright © 2014 V. Bol and V. Grégoire. All rights reserved. Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities Wed, 02 Apr 2014 12:47:37 +0000 The epidemiological researches show that the mutations of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes have played an important role in the hearing loss. This study aims to investigate the mutation spectrum of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes of Han Chinese, Hui people, and Uyghur ethnicities in sensorineural hearing loss (SNHL) patients in northwest of China. Mutational analyses in the three genes were brought by direct sequencing and each fragment was analyzed using an ABI 3730 DNA Sequencer. The mutation frequencies for the three HL causative genes were 34.05% in Han Chinese participants, 27.47% in Hui people, and 14.44% in Uyghur participants, respectively. The prevalence of GJB2 mutations was 13.7%, 11.4%, and 11.4% in Han Chinese, Hui people, and Uyghur participants (, ), respectively. The prevalence of mtDNA 12S rRNA A1555G homozygous mutations was 6.05%, 3.27%, and 1.44% in Han Chinese, Hui people, and Uyghur participants (, ), respectively. The prevalence of SLC26A4 mutations was 14.3%, 12.8%, and 1.6% in Han Chinese, Hui people, and Uyghur participants, respectively. In summary, we find that Uyghur and Hui SNHL individuals vary significantly from Han Chinese patients in three causative HL genes' mutational spectrum, especially for Uyghur. Wan Du, Qiuju Wang, Yiming Zhu, Yanli Wang, and Yufen Guo Copyright © 2014 Wan Du et al. All rights reserved. Clinical Use of Skull Tap Vestibular Evoked Myogenic Potentials for the Diagnoses of the Cerebellopontine Angle Tumor Patients Wed, 02 Apr 2014 09:35:07 +0000 Objective. To document our experiences using a new skull tapping induced Vestibular Evoked Myogenic Potentials (tap VEMPs) technique combined with standard Auditory Vestibular Evoked Myogenic Potentials (AC VEMPs) for advanced clinical assessment of cerebellopontine angle tumor (CPAT) patients. Design and Study Sample. Three patients were selected in order to highlight observations shown in a larger patient population and to show the variability of the findings. Both tap VEMPs and AC VEMPs were acquired from the sternocleidomastoid muscle (SCM) with EMG-based biofeedback and monitoring. Results. The usefulness of VEMPs was demonstrated, indicating the presence of a tumor and contributing additional information as to the involved nerve bundles in two out of the three cases. Conclusion. Due to the sensory organ dependency and related innervations differences, acquiring both AC VEMPs and tap VEMPs is likely to increase the probability of diagnosing CPATs and provide more information on the involved vestibular nerve bundles. This study demonstrates the feasibility of the possible expansion and combination of tap VEMPs and AC VEMPs techniques into a clinical diagnostic battery for advanced assessment of CPAT patients and its contribution as a guideline for the use of tap VEMPs in general. Erdem Yavuz, Magdalena Lachowska, Katarzyna Pierchała, Krzysztof Morawski, Kazimierz Niemczyk, and Rafael E. Delgado Copyright © 2014 Erdem Yavuz et al. All rights reserved. Outcome and Prognostic Factors in T4a Oropharyngeal Carcinoma, Including the Role of HPV Infection Mon, 31 Mar 2014 16:36:37 +0000 Background. The prognosis of patients with advanced oropharyngeal carcinoma (OPSCC) is generally poor. The aim of this study is to investigate the different therapeutic approaches and identify prognostic factors associated with a worse outcome for patients treated for T4a OPSCC, in order to improve treatment selection for the individual. Methods. A retrospective study was conducted on 426 patients with T4a OPC treated between 1980 and 2010. Eleven prognostic factors including treatment modality, lymph node staging, and p16 status as a surrogate marker for human papillomavirus (HPV) infection were analyzed. Results. Univariate analysis showed a significant difference in DSS between N0 and N+ (57.1% versus 26.9%, ), primary surgical and primary nonsurgical treatment (52.7% versus 31.4%, ), and perinodal invasion (51.7% versus 19.9%, ). P16-negative patients tended towards a worse DSS than p16-positive patients (40.2% versus 64.6%, ) but responded better to primary surgery than to nonsurgical treatment (71.4% versus 34.0%, ). Multivariate analysis identified the N category as an independent prognostic factor for survival. Conclusion. The survival of p16-negative patients was worse than p16-positive patients, although they seem to respond better to primary surgery. The strongest independent prognostic factor for T4a carcinomas proved to be the presence of lymph node metastases. Georgios Psychogios, Konstantinos Mantsopoulos, Abbas Agaimy, Kathrin Brunner, Elisabeth Mangold, Johannes Zenk, and Heinrich Iro Copyright © 2014 Georgios Psychogios et al. All rights reserved. Influence of Radiofrequency Surgery on Architecture of the Palatine Tonsils Wed, 26 Mar 2014 00:00:00 +0000 Radiofrequency surgery is a widely used modern technique for submucosal volume reduction of the tonsils. So far there is very limited information on morphologic changes in the human tonsils after radiofrequency surgery. We performed histopathological study of tonsillectomy specimens after previous bipolar radiofrequency induced thermotherapy (RFITT). A total of 83 patients underwent bipolar RFITT for hypertrophy of palatine tonsils. Tonsil volume reduction was measured by 3D ultrasonography. Five patients subsequently underwent tonsillectomy. Profound histopathological examination was performed to determine the effect of RFITT on tonsillar architecture. All tonsillectomy specimens showed the intact epithelium, intact germinal centers, normal vascularization, and no evidence of increased fibrosis. No microscopic morphological changes in tonsillectomy specimens after bipolar RFITT were observed. RFITT is an effective submucosal volume reduction procedure for treatment of hypertrophic palatine tonsils with no destructive effect on microscopic tonsillar architecture and hence most probably no functional adverse effect. Jan Plzak, Pavla Macokova, Michal Zabrodsky, Jan Kastner, Petr Lastuvka, and Jaromir Astl Copyright © 2014 Jan Plzak et al. All rights reserved. Zenker's Diverticulum: Carbon Dioxide Laser Endoscopic Surgery Thu, 06 Mar 2014 13:57:38 +0000 Nowadays endoscopic diverticulotomy is the surgical approach of the first choice in treatment of Zenker's diverticulum. We report our experience with this procedure and try to sum up recent recommendations for management of surgery and postoperative care. Data of 34 patients with Zenker's diverticulum, treated by endoscopic carbon dioxide laser diverticulotomy at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University, University Hospital Motol, Prague, Czech Republic, were prospectively stored and followed in relatively short period from May 2009 to December 2013. The average length of diverticulum was 32 mm. The average duration of surgery was 32 min. The patients were fed via feeding tube for 6.1 days and antibiotics were administered for 7 days. Mean hospitalization time was 7.4 days. We observed one transient recurrent laryngeal nerve paralysis and no other serious complications. Recurrence rate was 3%. We recommend complete transection of the diverticular septum in one procedure, systemic antibiotic treatment and exclusion of transoral intake for minimally 5 days, and contrast oesophagogram before resumption of oral intake to exclude fistula. Open diverticulectomy should be reserved for cases with inadequate endoscopic exposure and for revision surgery for multiple recurrences from endoscopic diverticulotomies. Jan Plzák, Michal Zábrodský, and Petr Lukeš Copyright © 2014 Jan Plzák et al. All rights reserved. Treatment of Laryngoceles: What Is the Progress over the Last Two Decades? Thu, 06 Mar 2014 11:24:21 +0000 Objectives. To review surgical techniques used in the treatment of laryngoceles over the last two decades and point out developments and trends. Materials and Methods. PubMed, the Cochrane Library, and the JBI Library of Systematic Reviews were searched using the term “laryngocele.” Demographic data, type of laryngocele, presence of a laryngopyocele, type of treatment and need for a tracheotomy were assessed. Results. Overall, data on 86 patients were analyzed, culled from 50 articles, of which 41 were case reports and 9 were case series. No single systematic review or meta-analysis or randomized controlled trial has been published on the topic. Altogether, 71 laryngoceles in 63 patients met the criteria for further analysis focusing on surgical treatment. An external approach was selected in 25/29 (86.2%) cases of combined laryngoceles. Microlaryngoscopic resection using a CO2 laser was performed in three cases and endoscopic robotic surgery in one case. The majority of patients with an internal laryngocele, 31/42 (73.8%), were treated using the microlaryngoscopy approach. Conclusions. Microlaryngoscopy involving the use of a CO2 laser has become the main therapeutic procedure for the treatment of internal laryngoceles during the past 20 years. An external approach still remains the main therapeutic approach for the treatment of combined laryngoceles. Karol Zelenik, Lucia Stanikova, Katarina Smatanova, Michal Cerny, and Pavel Kominek Copyright © 2014 Karol Zelenik et al. All rights reserved. Proteomic Study of HPV-Positive Head and Neck Cancers: Preliminary Results Sun, 02 Mar 2014 00:00:00 +0000 Human papillomavirus (HPV) was recently recognized as a new risk factor for head and neck squamous cell carcinoma. For oropharyngeal cancers, an HPV+ status is associated with better prognosis in a subgroup of nonsmokers and nondrinkers. However, HPV infection is also involved in the biology of head and neck carcinoma (HNC) in patients with a history of tobacco use and/or alcohol consumption. Thus, the involvement of HPV infection in HN carcinogenesis remains unclear, and further studies are needed to identify and analyze HPV-specific pathways that are involved in this process. Using a quantitative proteomics-based approach, we compared the protein expression profiles of two HPV+ HNC cell lines and one HPV− HNC cell line. We identified 155 proteins that are differentially expressed () in these three lines. Among the identified proteins, prostate stem cell antigen (PSCA) was upregulated and eukaryotic elongation factor 1 alpha (EEF1α) was downregulated in the HPV+ cell lines. Immunofluorescence and western blotting analyses confirmed these results. Moreover, PSCA and EEF1α were differentially expressed in two clinical series of 50 HPV+ and 50 HPV− oral cavity carcinomas. Thus, our study reveals for the first time that PSCA and EEF1α are associated with the HPV-status, suggesting that these proteins could be involved in HPV-associated carcinogenesis. Géraldine Descamps, Ruddy Wattiez, and Sven Saussez Copyright © 2014 Géraldine Descamps et al. All rights reserved. Early Stage Oropharyngeal Carcinomas: Comparing Quality of Life for Different Treatment Modalities Tue, 25 Feb 2014 14:10:30 +0000 Objective. To compare long-term quality of life outcomes after treating early stage oropharyngeal carcinoma either with surgery, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy. Methods. Questionnaire based method: 111 eligible patients agreed to fill out a quality of life questionnaire. Results. Of the 32 scales contained in the EORTC’s combined QLQ-C30 and HN35, 11 scales show significantly better results for the surgery-only treatment group when compared to either surgery combined with radiotherapy or surgery combined with any type of adjuvant therapy. These eleven scales are role function (), social function (), nausea (), pain (), financial problems (), speech (), social eating (/<0.001), mouth opening (), sticky saliva (/<0.001), swallowing (/<0.001), and dry mouth (). Conclusion. Treatment of early stage oropharyngeal carcinoma with surgery alone has definite advantages over treatments including any form of adjuvant therapy when considering quality of life. Advantages manifest themselves especially in functional aspects of the head and neck realm; however general health aspects as well as psychosocial aspects show improvements as well. This study does not show any indication of QOL-related drawbacks of surgery-only treatment approaches. Don-Felix Ryzek, Konstantinos Mantsopoulos, Julian Künzel, Philipp Grundtner, Johannes Zenk, Heinrich Iro, and Georgios Psychogios Copyright © 2014 Don-Felix Ryzek et al. All rights reserved. The c-MYC Protooncogene Expression in Cholesteatoma Mon, 10 Feb 2014 09:56:38 +0000 Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma. Enikő Palkó, Szilárd Póliska, Zsuzsanna Csákányi, Gábor Katona, Tamás Karosi, Frigyes Helfferich, András Penyige, and István Sziklai Copyright © 2014 Enikő Palkó et al. All rights reserved. Feasibility of Piezoelectric Endoscopic Transsphenoidal Craniotomy: A Cadaveric Study Sun, 09 Feb 2014 12:50:39 +0000 Objective. Endoscopic transsphenoidal approach has become the gold standard for surgical treatment of treating pituitary adenomas or other lesions in that area. Opening of bony skull base has been performed with burrs, chisels, and hammers or standard instruments like punches and circular top knives. The creation of primary bone flaps—as in external craniotomies—is difficult.The piezoelectric osteotomes used in the present study allows creating a bone flap for endoscopic transnasal approaches in certain areas. The aim of this study was to prove the feasibility of piezoelectric endoscopic transnasal craniotomies. Study Design. Cadaveric study. Methods. On cadaveric specimens (), a piezoelectric system with specially designed hardware for endonasal application was applied and endoscopic transsphenoidal craniotomies at the sellar floor, tuberculum sellae, and planum sphenoidale were performed up to a size of 3–5 cm2. Results. Bone flaps could be created without fracturing with the piezoosteotome and could be reimplanted. Endoscopic handling was unproblematic and time required was not exceeding standard procedures. Conclusion. In a cadaveric model, the piezoelectric endoscopic transsphenoidal craniotomy (PETC) is technically feasible. This technique allows the surgeon to create a bone flap in endoscopic transnasal approaches similar to existing standard transcranial craniotomies. Future trials will focus on skull base reconstruction using this bone flap. Peter Valentin Tomazic, Verena Gellner, Wolfgang Koele, Georg Philipp Hammer, Eva Maria Braun, Claus Gerstenberger, Georg Clarici, Etienne Holl, Hannes Braun, Heinz Stammberger, and Michael Mokry Copyright © 2014 Peter Valentin Tomazic et al. All rights reserved. A Novel Homozygous Mutation in the EC1/EC2 Interaction Domain of the Gap Junction Complex Connexon 26 Leads to Profound Hearing Impairment Thu, 16 Jan 2014 12:18:49 +0000 To date, about 165 genetic loci or genes have been identified which are associated with nonsyndromal hearing impairment. In about half the cases, genetic defects in the GJB2 gene (connexin 26) are the most common cause of inner-ear deafness. The genes GJB2 and GJB6 are localized on chromosome 13q11-12 in tandem orientation. Connexins belong to the group of “gap junction” proteins, which form connexons, each consisting of six connexin molecules. These are responsible for the exchange of ions and smaller molecules between neighboring cells. Mutational analysis in genes GJB2 and GJB6 was brought by direct sequencing of the coding exons including the intron transitions. Here we show in the participating extended family a homozygous mutation c.506G>A, (TGC>TAC) p.Cys169Tyr, in the GJB2 gene, which could be proven for the first time and led to nonsyndromal severe hearing impairment in the afflicted patients. The mutation is located in the EC1/EC2 interaction complex of the gap junction connexon 26 complex and interrupts the K+ circulation and therefore the ion homeostasis in the inner ear. The homozygous mutation p.Cys169Tyr identified here provides a novel insight into the structure-function relationship of the gap junction complex connexin/connexon 26. Ralf Birkenhäger, Nicola Prera, Antje Aschendorff, Roland Laszig, and Susan Arndt Copyright © 2014 Ralf Birkenhäger et al. All rights reserved. Oncogenic PIK3CA Mutation and Dysregulation in Human Salivary Duct Carcinoma Wed, 08 Jan 2014 15:10:42 +0000 Salivary duct carcinoma (SDC) is an aggressive malignant tumor with a high mortality, which resembles high-grade breast ductal carcinoma in morphology. The parotid gland is the most common location. Its molecular genetic characteristics remain largely unknown. We have previously reported high incidence of PIK3CA somatic mutations in head and neck squamous cell carcinoma, particularly in pharyngeal cancers. Here we examined the PIK3CA gene expression status and hotspot mutations in six cases of SDC by immunohistochemistry and genomic DNA sequencing. Immunohistochemistry showed that PIK3CA expression was elevated in all six patients with SDC. By DNA sequencing, two hotspot mutations of the PIK3CA gene, E545K (exon 9) and H1047R (exon 20), were identified in two of the six cases. Our results support that oncogenic PIK3CA is upregulated and frequently mutated in human SDC, adding evidence that PIK3CA oncogenic pathway is critical in the tumorigenesis of SDC, and may be a plausible drug target for this rare disease. Wanglong Qiu, Guo-Xia Tong, Andrew T. Turk, Lanny G. Close, Salvatore M. Caruana, and Gloria H. Su Copyright © 2014 Wanglong Qiu et al. All rights reserved. Suppression of Osteopontin Functions by Levocetirizine, a Histamine Receptor Antagonist, In Vitro Mon, 30 Dec 2013 10:19:32 +0000 Objectives. Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro. Methods. Human nasal epithelial cells ( cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively. Key Findings. The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF-κB and AP-1, activation, which were increased by the stimulation of cells with OPN. Conclusions. The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases. Toshimitsu Komatsuzaki, Isao Suzaki, Kojiro Hirano, Ken-Ichi Kanai, Kazuhito Asano, and Harumi Suzaki Copyright © 2013 Toshimitsu Komatsuzaki et al. All rights reserved. Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments Thu, 19 Dec 2013 15:10:46 +0000 Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients. Loredana G. Marcu Copyright © 2013 Loredana G. Marcu. All rights reserved. Medium-Level Laser in Chronic Tinnitus Treatment Tue, 05 Nov 2013 15:57:27 +0000 The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study. K. Dejakum, J. Piegger, C. Plewka, A. Gunkel, W. Thumfart, S. Kudaibergenova, G. Goebel, F. Kral, and W. Freysinger Copyright © 2013 K. Dejakum et al. All rights reserved. An Investigation of Vocal Tract Characteristics for Acoustic Discrimination of Pathological Voices Thu, 31 Oct 2013 18:28:44 +0000 This paper investigates the effectiveness of measures related to vocal tract characteristics in classifying normal and pathological speech. Unlike conventional approaches that mainly focus on features related to the vocal source, vocal tract characteristics are examined to determine if interaction effects between vocal folds and the vocal tract can be used to detect pathological speech. Especially, this paper examines features related to formant frequencies to see if vocal tract characteristics are affected by the nature of the vocal fold-related pathology. To test this hypothesis, stationary fragments of vowel /aa/ produced by 223 normal subjects, 472 vocal fold polyp subjects, and 195 unilateral vocal cord paralysis subjects are analyzed. Based on the acoustic-articulatory relationships, phonation for pathological subjects is found to be associated with measures correlated with a raised tongue body or an advanced tongue root. Vocal tract-related features are also found to be statistically significant from the Kruskal-Wallis test in distinguishing normal and pathological speech. Classification results demonstrate that combining the formant measurements with vocal fold-related features results in improved performance in differentiating vocal pathologies including vocal polyps and unilateral vocal cord paralysis, which suggests that measures related to vocal tract characteristics may provide additional information in diagnosing vocal disorders. Jung-Won Lee, Hong-Goo Kang, Jeung-Yoon Choi, and Young-Ik Son Copyright © 2013 Jung-Won Lee et al. All rights reserved. Effects of Cryotherapy on the Maxillary Antrostomy Patency in a Rabbit Model of Chronic Rhinosinusitis Mon, 28 Oct 2013 14:12:28 +0000 It is acknowledged that many causes of failures in endoscopic sinus surgery are related to scarring and narrowing of the maxillary antrostomy. We assessed the effect of low-pressure spray cryotherapy in preventing the maxillary antrostomy stenosis in a chronic rhinosinusitis (CRS) rabbit model. A controlled, randomized, double-blind study was conducted on 22 New Zealand rabbits. After inducing unilateral rhinogenic CRS, a maxillary antrostomy was performed and spray cryotherapy was employed on randomly selected 12 rabbits, while saline solution was applied to the control group (). The antrostomy dimensions and the histological scores were assessed 4 weeks postoperatively. The diameter of cryotreated antrostomy was significantly larger at 4 weeks than that in the control group. At 4 weeks, the maxillary antrostomy area in the study group was significantly larger than the mean area in the control group (103.92 ± 30.39 mm2 versus 61.62 ± 28.35 mm2, ). Submucosal fibrous tissues and leukocytic infiltration in saline-treated ostia were more prominent than those in cryotreated ostia with no significant differences between the two groups regarding the histological scores. Intraoperative low-pressure spray cryotherapy increases the patency of the maxillary antrostomy at 4 weeks postoperatively with no important local side effects. Anamaria Gocea, Marian Taulescu, Veronica Trombitas, and Silviu Albu Copyright © 2013 Anamaria Gocea et al. All rights reserved. Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion Neurons In Vitro Tue, 22 Oct 2013 16:00:25 +0000 Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochlea in vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabain in vivo varied among mammalian species. Little is known about the ototoxic effects in vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabain in vitro and to provide insights that could explain the comparative ototoxic effects of ouabain in vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damage in vitro was dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways. Yong Fu, Dalian Ding, Lei Wei, Haiyan Jiang, and Richard Salvi Copyright © 2013 Yong Fu et al. All rights reserved. Microbiological Profile of Adenoid Hypertrophy Correlates to Clinical Diagnosis in Children Mon, 23 Sep 2013 08:25:48 +0000 Objective. Adenoid hypertrophy is a common condition in childhood, which may be associated with recurring acute otitis media (RAOM), otitis media with effusion (OME), and obstructive sleep apnea syndrome (OSAS). These different clinical characteristics have some clinical overlap; however, they might be explained by distinct immunologic and infectious profiles and result in various histopathologic findings of adenoid specimens. Methods. A total of 59 children with adenoid hypertrophy undergoing adenoidectomy were studied. Three series of identical adenoid specimens were processed to hematoxylin-eosin (H.E.) and Gram staining and to respiratory virus specific real-time PCR, respectively. Results. According to the clinical characteristics, patients were recruited into three groups: RAOM (). Bacterial biofilms were detected in 21 cases, while at least one of the studied respiratory viruses was detected in 52 specimens. RAOM cases were significantly associated with biofilm existence (). In contrast, OME group was characterized by the absence of bacterial biofilm and by normal mucosa. Showing a statistically significant correlation, all OME cases were positive for human bocavirus (HBoV, ). Conclusions. Bacterial biofilms might contribute to the damage of respiratory epithelium and recurring acute infections resulting in RAOM. In OME cases persisting respiratory viruses, mainly HBoV, can cause subsequent lymphoid hyperplasia leading to ventilation disorders and impaired immunoreactivity of the middle ear cleft. Anita Szalmás, Zoltán Papp, Péter Csomor, József Kónya, István Sziklai, Zoltán Szekanecz, and Tamás Karosi Copyright © 2013 Anita Szalmás et al. All rights reserved. Polymorphisms in the Human Cytochrome P450 and Arylamine N-Acetyltransferase: Susceptibility to Head and Neck Cancers Mon, 16 Sep 2013 14:12:38 +0000 The occurrence of head and neck cancer (HNC) is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s), such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1) oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs), NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1), and two N-acetyltransferase isozymes (NAT1 and NAT2) in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i) the interaction between these genes and the environment, (ii) the impact of genetic defect on protein activity and/or expression, and (iii) the eventual involvement of race in such associations. Rim Khlifi, Olfa Messaoud, Ahmed Rebai, and Amel Hamza-Chaffai Copyright © 2013 Rim Khlifi et al. All rights reserved. A Model for Provision of ENT Health Care Service at Primary and Secondary Hospital Level in a Developing Country Wed, 04 Sep 2013 10:08:37 +0000 ENT problems are the most common reason for a visit to a doctor in both rural and urban communities. In many developing countries, there is a lack of ENT specialists and overburdened hospital facilities. To date, there is no comprehensive study that has evaluated the spectrum of ENT disorders in a rural community. Methods. A prospective study was done for a period of three years to profile the cases presenting to the outpatient clinic in a secondary care hospital and in the camps conducted in tribal areas in Vellore District of Tamil Nadu, India. Trained community volunteers were used to identify ENT conditions and refer patients. Results. A total of 2600 patients were evaluated and treated. Otological symptoms were the most commonly reported with allergic rhinitis being the second most commonly reported. Presbycusis was the most common disability reported in the rural community. The other symptoms presented are largely related to hygiene and nutrition. Conclusion. Using trained community workers to spread the message of safe ENT practices, rehabilitation of hearing loss through provision of hearing aids, and the evaluation and surgical management by ENT specialist helped the rural community to access the service. Lingamdenne Paul Emerson, Anand Job, and Vinod Abraham Copyright © 2013 Lingamdenne Paul Emerson et al. All rights reserved. Auditory Verbal Cues Alter the Perceived Flavor of Beverages and Ease of Swallowing: A Psychometric and Electrophysiological Analysis Tue, 27 Aug 2013 13:24:11 +0000 We investigated the possible effects of auditory verbal cues on flavor perception and swallow physiology for younger and elder participants. Apple juice, aojiru (grass) juice, and water were ingested with or without auditory verbal cues. Flavor perception and ease of swallowing were measured using a visual analog scale and swallow physiology by surface electromyography and cervical auscultation. The auditory verbal cues had significant positive effects on flavor and ease of swallowing as well as on swallow physiology. The taste score and the ease of swallowing score significantly increased when the participant’s anticipation was primed by accurate auditory verbal cues. There was no significant effect of auditory verbal cues on distaste score. Regardless of age, the maximum suprahyoid muscle activity significantly decreased when a beverage was ingested without auditory verbal cues. The interval between the onset of swallowing sounds and the peak timing point of the infrahyoid muscle activity significantly shortened when the anticipation induced by the cue was contradicted in the elderly participant group. These results suggest that auditory verbal cues can improve the perceived flavor of beverages and swallow physiology. Aya Nakamura and Satoshi Imaizumi Copyright © 2013 Aya Nakamura and Satoshi Imaizumi. All rights reserved. Inferior Flap Tympanoplasty: A Novel Technique for Anterior Perforation Closure Tue, 13 Aug 2013 09:23:00 +0000 Objective. To report a novel tympanoplasty modification for anterior tympanic membrane perforation closure. Materials and Methods. A prospective study on 13 patients who underwent inferior tympanoplasty between December 2008 and May 2011 was carried out. In our technique, an inferior rather than a posterior flap is raised and the graft is laid from the inferior direction to obtain better access to the anterior part of the tympanic membrane perforation and provide better support. Results. A total of 13 patients underwent the novel inferior tympanoplasty technique with a mean age of 33 years. Six patients had undergone tympanoplasties and/or mastoidectomies in the past, 3 in the contralateral ear. A marginal perforation was observed in 3 cases, total perforation in 2 and subtotal in 1 case. The mean preoperative pure-tone average was 40.4 dB (10 to 90 dB), compared to 26.5 dB (10 to 55 dB) postoperatively. All perforations were found to be closed but one (92.3% success rate). Conclusions. The inferior tympanoplasty technique provides a favorable outcome in terms of tympanic membrane closure and hearing improvement for anterior perforations, even in difficult and complex cases. It is based on a well-known technique and is easy to implement. Haim Gavriel and Ephraim Eviatar Copyright © 2013 Haim Gavriel and Ephraim Eviatar. All rights reserved. INF-α and Ototoxicity Thu, 25 Jul 2013 14:07:53 +0000 Introduction. INF-α is a common drug for the treatment of hepatitis B and C. Although a variety of related complications are discussed, possible ototoxic effects of this mediation are not well described. Methods and Materials. In a before-after control study, 24 patients who received INF-α for the treatment of hepatitis B and C and 30 normal controls were included. Subjective and objective ototoxicity evaluations via questionnaire, high frequency audiometry, and measuring transiently evoked otoacoustic emissions (TEOAEs) were performed one week before and one month after the prescription of the drug. Results. Subjective hearing complaint, tinnitus, and vertigo were seen in just 3 cases, which was not statistically significant (). In the frequency range of 4000 to 8000 Hz before (9.38 ± 1.0 and 10.7 ± 1.2, resp.) and after (17.9 ± 2.6 and 17.6 ± 2.6, resp.) one month of treatment, a significant difference () was detected. Progressive decreases in amplitude of the OAE during TEOAE measurement in 1, 2, and 4 frequencies among 41.66%, 18.75 %, and 43.75% were observed, respectively. The hearing loss was seen more among older and male cases significantly. Conclusion. The results showed ototoxicity of INF-α that may encourage planning hearing monitoring in patients receiving this drug. Mohammad Reza Sharifian, Shima Kamandi, Hamid Reza Sima, Mohammad Ali Zaringhalam, and Mehdi Bakhshaee Copyright © 2013 Mohammad Reza Sharifian et al. All rights reserved. Button Battery Foreign Bodies in Children: Hazards, Management, and Recommendations Thu, 11 Jul 2013 13:46:01 +0000 Objective. The demand and usage of button batteries have risen. They are frequently inadvertently placed by children in their ears or noses and occasionally are swallowed and lodged along the upper aerodigestive tract. The purpose of this work is to study the different presentations of button battery foreign bodies and present our experience in the diagnosis and management of this hazardous problem in children. Patients and Methods. This study included 13 patients. The diagnostic protocol was comprised of a thorough history, head and neck physical examination, and appropriate radiographic evaluation. The button batteries were emergently extracted under general anesthesia. Results. The average follow-up period was 4.3 months. Five patients had a nasal button battery. Four patients had an esophageal button battery. Three patients had a button battery in the stomach. One patient had a button battery impacted in the left external ear canal. Apart from a nasal septal perforation and a tympanic membrane perforation, no major complications were detected. Conclusion. Early detection is the key in the management of button battery foreign bodies. They have a distinctive appearance on radiography, and its prompt removal is mandatory, especially for batteries lodged in the esophagus. Physicians must recognize the hazardous potential and serious implications of such an accident. There is a need for more public education about this serious problem. Mohammed Hossam Thabet, Waleed Mohamed Basha, and Sherif Askar Copyright © 2013 Mohammed Hossam Thabet et al. All rights reserved. Cytogenetic Abnormality in Exfoliated Cells of Buccal Mucosa in Head and Neck Cancer Patients in the Tunisian Population: Impact of Different Exposure Sources Mon, 24 Jun 2013 15:42:29 +0000 Chromosome/DNA instability could be one of the primary causes of malignant cell transformation. The objective of the present study was to evaluate the spontaneous genetic damages in exfoliated cells of buccal mucosa of head and neck cancer (HNC) by counting micronucleus (MN) and binucleated (BN) cells frequencies. MN and BN frequencies were significantly increased in HNC patients compared with controls (5.53 ± 3.09/1000 cells, 5.63 ± 2.99/1000 cells versus 2.36 ± 2.11/1000 cells, 3.09 ± 1.82/1000 cells, ). Regarding the gender and the age, the frequencies of the MN and BN were significantly higher than those of controls (). The evaluation of the MN and BN frequencies revealed a significant increase () in the cases in relation to the control group after controlling the risk factors (tobacco smoking and chewing and occupational exposure) of HNC. Moreover, MN and BN frequencies were significantly increased in smokers and chewers compared with nonsmokers and nonchewers among patients (). MN frequency was significantly () different between patients occupationally exposed (6.99 ± 3.40/1000 cells) and nonexposed (4.70 ± 2.48/1000 cells) among HNC group. The logistic regression model illustrated that HNC was significantly associated with frequencies of MN (OR = 8.63, ) and BN (OR = 5.62, ). Our results suggest that increased chromosome/DNA instabilities may be associated with HNC. Rim Khlifi, Fatma Trabelsi-Ksibi, Amine Chakroun, Ahmed Rebai, and Amel Hamza-Chaffai Copyright © 2013 Rim Khlifi et al. All rights reserved.