Predicting Matrix test effectiveness for evaluating auditory performance in noise using pure-tone audiometry and speech recognition in quiet in cochlear implant recipients.

INTRODUCTION: Auditory performance in noise of cochlear implant recipients can be assessed with the adaptive Matrix test (MT); however, when the speech-to-noise ratio (SNR) exceeds 15 dB, the background noise has any negative impact on the speech recognition. Here, we aim to evaluate the predictive power of aided pure-tone audiometry and speech recognition in quiet, and establish cut-off values for both tests that indicate whether auditory performance in noise can be assessed using the Matrix sentence test in a diffuse noise environment. METHODS: Here, we assessed the power of pure-tone audiometry and speech recognition in quiet to predict the response to the MT. Ninety-eight cochlear implant recipients were assessed using different sound processors from Advanced Bionics (n=56) and Cochlear (n=42). Auditory tests were performed at least 1-year after cochlear implantation or upgrading the sound processor to ensure the best benefit of the implant. Auditory assessment of the implanted ear in free-field conditions included: pure-tone average (PTA), speech discrimination score (SDS) in quiet at 65 dB, and speech recognition threshold (SRT) in noise that is the SNR at which the patient can correctly recognize 50% of the words using the MT in a diffuse sound field. RESULTS: The SRT in noise was determined in sixty patients (61%) and undetermined in 38 (39%) using the MT. When cut-off values for PTA <36 dB and SDS >41% were used separately, they were able to predict a positive response to the MT in 83% of recipients; using both cut-off values together, the predictive value reached 92%. DISCUSSION/CONCLUSION: As the pure-tone audiometry is standardized universally and the speech recognition in quiet could vary depending on the language used; we propose that the MT should be performed in recipients with PTA <36 dB, and in recipients with PTA >36 dB, a list of Matrix sentences at a fixed SNR should be presented to determine the percentage of words understood. This approach should enable clinicians to obtain information about auditory performance in noise whenever possible.

Auditory outcomes after scala vestibuli array insertion are similar to those after scala tympani insertion 1 year after cochlear implantation.

PURPOSE: In cochlear implantation, a scala vestibuli (SV) insertion of an electrode array is a rare occurrence and is reported to be linked to poor hearing outcomes. Using the same electrode array, the auditory performance of patients with a complete SV location was compared with that of patients having a complete scala tympani (ST) location 1 year after implantation. METHODS: Thirty-three patients were included in this retrospective case-control study (SV, n = 12; ST, n = 21). The matching criteria were electrode array type, age at implantation, and duration of severe or profound deafness. The array location was analyzed using 3D reconstruction of postoperative CT scans. Postoperative audiological evaluation of the implanted ear was performed using pure-tone audiometry, speech recognition of monosyllabic words in quiet, and words and sentences in noise. RESULTS: On the preoperative CT scan, six patients in the SV group presented with both round window (RW) and ST ossification, three with RW ossification alone, and three with no RW ossification. Auditory performance did not differ between SV and ST groups 1 year after cochlear implantation. Speech recognition of words was 49 ± 7.6% and 56 ± 5.0% in quiet and 75 ± 9.5% and 66 ± 6.0% in noise in SV and ST groups, respectively. CONCLUSION: ST insertion is the gold standard that allows the three cochlear scalae to preserve scalar cochlear integrity. However, 1 year after implantation, a planned or unexpected SV insertion is not detrimental to hearing outcomes, providing similar auditory performance in quiet and noise to ST insertion.

Atraumatic Insertion of a Cochlear Implant Pre-Curved Electrode Array by a Robot-Automated Alignment with the Coiling Direction of the Scala Tympani.

INTRODUCTION: Electrode array translocation is an unpredictable event with all types of arrays, even using a teleoperated robot in a clinical scenario. We aimed to compare the intracochlear trauma produced by the HiFocus™ Mid-Scala (MS) electrode array (Advanced Bionics, Valencia, CA, USA) using a teleoperated robot, with an automated robot connected to a navigation system to align the pre-curved tip of the electrode array with the coiling direction of the scala tympani (ST). METHODS: Fifteen freshly frozen temporal bones were implanted with the MS array using the RobOtol® (Collin, Bagneux, France). In the first group (n = 10), the robot was teleoperated to insert the electrode array into the basal turn of the ST under stereomicroscopic vision, and then the array was driven by a slow-speed hydraulic insertion technique with an estimated placement of the pre-curved electrode tip. In the second group (n = 5), 3 points were obtained from the preoperative cone-beam computed tomography: the 2 first defining the ST insertion axis of the basal turn and a third one at the center of the ST at 270°. They provided the information to the automated system (RobOtol® connected with a navigation system) to automatically align the electrode array with the ST insertion axis and to aim the pre-curved tip toward the subsequent coiling of the ST. After this, the electrode array was manually advanced. Finally, the cochleae were obtained and fixed in a crystal resin, and the position of each electrode was determined by a micro-grinding technique. RESULTS: In all cases, the electrode array was fully inserted into the cochlea and the depth of insertion was similar using both techniques. With the teleoperated robotic technique, translocations of the array were observed in 7/10 insertions (70%), but neither trauma nor array translocation occurred with automated robotic insertion. CONCLUSION: We have successfully tested an automated insertion system (robot + navigation) that could accurately align a pre-curved electrode array to the axis of the basal turn of the ST and its subsequent coiling, which reduced intracochlear insertion trauma and translocation.

Cochlear Implant Outcomes in Patients with Neurosarcoidosis.

INTRODUCTION: Audiovestibular symptoms are rare in sarcoidosis, but they may also be the first manifestation of the disease. Sudden or progressive bilateral hearing loss is usually associated with vestibular impairment. The mechanism of hearing loss remains unclear, but clinical presentation and magnetic resonance imaging suggest a retrocochlear site for the lesion in most patients. Several cases of hearing recovery after corticosteroid treatment have been reported. In patients with severe or profound hearing loss, the benefit of cochlear implantation is challenging to predict in the case of auditory neuropathy and is rarely described. We present a case series of cochlear implantation in patients with documented neurosarcoidosis. RESULTS: Seven cases of cochlear implantation in 4 patients with neurosarcoidosis are reported. All of the patients showed a great improvement very quickly in both quiet and noise. Speech performance remained stable over time with a follow-up ranging from 4 to 11 years, even in patients who had disease exacerbation. CONCLUSION: Cochlear implantation is possible in deaf patients with neurosarcoidosis. The excellent benefit obtained in our patients suggests a particular type of neuropathy, but endocochlear involvement cannot be entirely ruled out.

Analysis of forces during robot-assisted and manual manipulations of mobile and fixed footplate in temporal bone specimens.

PURPOSE: To evaluate the forces involved in different manipulations, manual or robot-assisted, applied to the ossicular chain, on normal temporal bones and on an anatomical model of otosclerosis. METHODS: Thirteen cadaveric temporal bones, with mobile footplates or with footplates that were fixed using hydroxyapatite cement, were manipulated, manually or using a robotic arm (RobOtol®). "Short contact" of a mobile footplate was the weakest interaction on the incus. "Long contact" was the same manipulation held for 10 s. "Mobilization" was the smallest visualized movement of the mobile footplate, or the movement necessary to regain mobility of the fixed footplate. A six-axis force sensor (Nano17, ATI) measured the maximal peak of forces, summation of forces applied, and yank. RESULTS: Maximal forces during short (~4 mN) and long contact (~15 mN) were similar for manual and robot-assisted manipulations. For manual manipulation, yank measured during long contact was twice as high compared to robot-assisted manipulation: 6 ± 2.4 (n = 5) and 3 ± 1.3 mN/s (n = 5), respectively (mean ± SD, p < 0.02). For mobilization of the mobile footplate, maximal forces during mobilization were similar during manual and robot-assisted manipulations, respectively: 12 ± 2.5 (n = 6) and 19 ± 7.6 mN (n = 7). Compared with mobilization of a mobile footplate, mobilization of a fixed footplate required ~ 60 and ~ 27 times higher maximal forces for manual and robot-assisted manipulations, respectively: 724 ± 366.4 and 507 ± 283.2 mN. Yank was twice as high during manual manipulation compared to robot-assisted manipulation (p < 0.05). CONCLUSION: Robot-assisted manipulation of the ossicular chain was reliable. Our anatomical model of otosclerosis was successfully developed requiring higher forces for stapes mobilization.

Robot-based assistance in middle ear surgery and cochlear implantation: first clinical report.

PURPOSE: Middle ear surgery may benefit from robot-based assistance to hold micro-instruments or an endoscope. However, the surgical gesture performed by one hand may perturb surgeons accustomed to two-handed surgery. A robot-based holder may combine the benefits from endoscopic exposure and a two-handed technique. Furthermore, tremor suppression and accurate tool control might help the surgeon during critical surgical steps. The goal of this work was to study the safety of an otological robot-based assistant under clinical conditions in a limited series of patients. METHODS: The RobOtol system has been used as an endoscope or a micro instrument holder for this series. Eleven cases were operated on with the robot as an endoscope holder for chronic otitis. Twenty-one cases were operated on with the robot as a micro-instrument holder for otosclerosis (9 cases), transtympanic tube placement (2 cases), or cochlear implantation (10 cases). RESULTS: No complications related to the robot manipulation occurred during surgery nor in postoperative. In the chronic otitis group, all perforations were sealed and 3-month postoperative pure-tone average air-bone gap (PTA ABG) was 15 ± 2.6 dB. In the otosclerosis group, 1-month post-op PTA ABG was 10 ± 1 dB. For cochlear implantation cases, a scala tympani insertion, a vestibular scala translocation occurred and a full scala vestibuli insertion was observed in 7, 2 and 1 case, respectively. CONCLUSION: The RobOtol system has reached the clinical stage. It could be used safely and with accurate control as an endoscope holder or a micro instrument holder in 32 cases.

Long-term residual hearing in cochlear implanted adult patients who were candidates for electro-acoustic stimulation.

PURPOSE: To evaluate the long-term hearing outcomes in cochlear implanted adults with residual hearing at low frequencies, and the proportion of patients using electro-acoustic stimulation (EAS). METHODS: A monocentric retrospective cohort study was performed in a tertiary referral center. Population demographics, surgical approach, pre- and postoperative hearing at low frequencies, in the implanted and contralateral ear, were recorded as well as duration of EAS use. The percentage hearing preservation was calculated according to the formula S (HEARRING group). RESULTS: In total, 63 adults (81 ears) with residual hearing underwent cochlear implantation with intent to use EAS processors. Six different types of electrode array were implanted. The mean pure tone audiometry (PTA) shift after cochlear implantation was 16 ± 15 dB HL (range 0-59 dB HL). Half of the implanted ears had minimal hearing preservation or total hearing loss (HL) at 5.5 years and the cumulative risk of total HL was 50% at 7 years. During the follow-up, total HL occurred in 22 ears. The decrease in hearing levels was similar in both implanted and contralateral ear during follow-up (ns, F = 2.46 ± 3, Linear Mixed Model (LMM)). Only 44 patients found a benefit from EAS at the first fitting. At the last visit, EAS processors were fitted in 30% of the cases. The pre- and postoperative mean PTA thresholds were not predictive of EAS use (Cox's proportional hazards analysis). CONCLUSIONS: Postoperative residual hearing was observed in 93% of implanted ears, but only half of them had an initial benefit from EAS. No predictive factors were found to influence the use of EAS processors.

Benefits of a contralateral routing of signal device for unilateral Naída CI cochlear implant recipients.

PURPOSE: Many bilaterally deaf adults are only able to receive one cochlear implant (CI), resulting in suboptimal listening performance, especially in challenging listening environments. Adding a contralateral routing of signal (CROS) device to a unilateral CI is one possibility to alleviate these challenges. This study examined the benefit of such a CROS device. METHODS: Thirteen adult subjects with at least 6 months of CI use, and no or limited benefit of a hearing instrument in the contralateral ear were included in the study. The perceived benefit of a CROS device in everyday listening environments was evaluated up to 1 year after initial fitting using several questionnaires. Speech intelligibility performance was determined using the French matrix sentence test in quiet and in two speech-in-noise setups and was followed for 3 months after CROS fitting. RESULTS: Subjects indicated high satisfaction with the practical usability of the CROS device and long-term device retention was high. Perceived benefits in everyday listening environments were reported. Formal speech intelligibility tests revealed statistically significant median improvements of 6.93 dB SPL (Wilcoxon Z = 2.380, p = 0.017) in quiet and up to 8.00 dB SNR (Wilcoxon Z = 2.366, p = 0.018) in noise. These benefits were accessible immediately without a need for prolonged acclimatization. CONCLUSIONS: Subjective satisfaction and device retention as well as speech intelligibility benefits in quiet and in noise prove the CROS device to be a valuable addition to a unilateral CI in cases of bilateral deafness where bilateral implantation is not an option.

Improvement of the insertion axis for cochlear implantation with a robot-based system.

It has previously reported that alignment of the insertion axis along the basal turn of the cochlea was depending on surgeon' experience. In this experimental study, we assessed technological assistances, such as navigation or a robot-based system, to improve the insertion axis during cochlear implantation. A preoperative cone beam CT and a mastoidectomy with a posterior tympanotomy were performed on four temporal bones. The optimal insertion axis was defined as the closest axis to the scala tympani centerline avoiding the facial nerve. A neuronavigation system, a robot assistance prototype, and software allowing a semi-automated alignment of the robot were used to align an insertion tool with an optimal insertion axis. Four procedures were performed and repeated three times in each temporal bone: manual, manual navigation-assisted, robot-based navigation-assisted, and robot-based semi-automated. The angle between the optimal and the insertion tool axis was measured in the four procedures. The error was 8.3° ± 2.82° for the manual procedure (n = 24), 8.6° ± 2.83° for the manual navigation-assisted procedure (n = 24), 5.4° ± 3.91° for the robot-based navigation-assisted procedure (n = 24), and 3.4° ± 1.56° for the robot-based semi-automated procedure (n = 12). A higher accuracy was observed with the semi-automated robot-based technique than manual and manual navigation-assisted (p < 0.01). Combination of a navigation system and a manual insertion does not improve the alignment accuracy due to the lack of friendly user interface. On the contrary, a semi-automated robot-based system reduces both the error and the variability of the alignment with a defined optimal axis.

Effect of a liposomal hyaluronic acid gel loaded with dexamethasone in a guinea pig model after manual or motorized cochlear implantation.

Goals of cochlear implantation have shifted from complete insertion of the cochlear electrode array towards low traumatic insertion with minimally invasive techniques. The aim of this study was first to evaluate, in a guinea pig model of cochlear implantation, the effect of a motorized insertion technique on hearing preservation. The second goal was to study a new gel formulation containing dexamethasone phosphate loaded in liposomes (DEX-P). Guinea pigs had a unilateral cochlear implantation with either a manual technique (n = 12), or a motorized technique (n = 15), with a 0.4 mm diameter and 4 mm long array trough a cochleostomy. At the end of the procedure, hyaluronic acid gel containing drug-free liposomes, or liposomes loaded with DEX-P, was injected into the bulla. Auditory brainstem responses thresholds were recorded before surgery and day 2 and 7 after surgery. All the animals had increased auditory brainstem responses thresholds after the cochlear implantation. Implanted animals with the motorized insertion tool experienced a partial hearing recovery at day 7 but not in those implanted with the manual insertion procedure (p < 0.001). In the manually implanted animals, a partial recovery was observed when DEX-P contained in liposomal gel was locally administrated (p < 0.0001). Finally, no additive effect with the motorized insertion was noticed. The deleterious effect of manual insertion, during cochlear implantation, can be prevented with local DEX-P administration in the bulla at day 7. The use of a motorized tool performed more atraumatic electrode array insertion for postoperative hearing.

Five-Year Hearing Outcomes in Bilateral Simultaneously Cochlear-Implanted Adult Patients.

OBJECTIVE: To report the speech performance and sound localization in adult patients 5 years after bilateral simultaneous cochlear implantation and to evaluate the change in speech scores between 1 and 5 years. DESIGN: In this prospective multicenter study, 26 patients were evaluated 5 years after implantation using long straight electrode arrays (MED-EL Combi 40+, standard electrode array, 31 mm). Speech perception was measured using disyllabic words in quiet and noise, with the speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Speech localization measurements were performed in noise under the same test conditions. These results were compared to those obtained at 1 year reported in a previous study. RESULTS: Five years after implantation, an improvement in speech performance scores compared to 1 year after implantation was found for the poorer ear both in quiet and in noise (+12.1 ± 2.6%, p < 0.001). The lower the speech score of the poorer ear at 1 year, the greater the improvement at 5 years, both in quiet (r = -0.62) and at a signal-to-noise ratio of +15 dB (r = -0.58). The sound localization on the horizontal plane in noise provided by bilateral implantation was better than the unilateral one and remained stable after the results observed at 1 year. CONCLUSION: In adult patients simultaneously and bilaterally implanted, the poorest speech scores improved between 1 and 5 years after implantation. These findings are an additional element to recommend bilateral implantation in adult patients. The use of both cochlear implants and speech training sessions for patients with poor performance should continue in the period after 1 year following implantation, since the speech scores will improve over time.

Intratemporal facial nerve schwannoma: clinical presentation and management.

Facial nerve schwannoma is the most common facial nerve tumor, but its therapeutic strategy remains debated. The aim of this study is to analyze the facial nerve function and the hearing outcomes after surgery or wait-and-scan policy in a facial nerve schwannoma series. A monocentric retrospective review of medical charts of patients followed for an intratemporal facial nerve schwannoma between 1988 and 2013 was performed. Twenty-two patients were included. Data were extracted pertaining to the following variables: patient demographics, tumor localization, clinical and imaging features, facial nerve function and hearing levels, and details of surgical intervention. The majority of tumors were located at the geniculate ganglion. Initial symptoms were mainly facial palsy and hearing loss. The average follow-up was 4.8 ± 4.5 years. Nineteen patients underwent surgery, and three patients were observed. After surgery, 11 patients had a stable or improved facial nerve function (57.9 %), and 8 patients had a worsened facial nerve function (42.1 %). Facial nerve function was in the majority of cases a HB grade III, depending on surgical strategy. No patient presented a postoperative HB grade V or VI. Regarding the hearing, it remained stable after surgery in 52.6 % of cases, and improved in 10.5 % of cases. Among monitored patients, facial nerve function and hearing remained stable. Surgery for facial nerve schwannoma is a safe and effective option in the treatment of these tumors.

Variability of the mental representation of the cochlear anatomy during cochlear implantation.

The aim of this study was to assess the mental representation of the insertion axis of surgeons with different degrees of experience, and reproducibility of the insertion axis in repeated measures. A mastoidectomy and a posterior tympanotomy were prepared in five different artificial temporal bones. A cone-beam CT was performed for each temporal bone and the data were registered on a magnetic navigation system. In these five temporal bones, 16 surgeons (3 experts; >50 cochlear implant surgery/year; 7 fellows with few cochlear implant experience, and 6 residents) were asked to determine the optimal insertion axis according to their mental representation. Compared to a planned ideal axis, the insertion axis was better determined by the experts with higher accuracy (axial: 7° ± 1.5°, coronal: 6° ± 1.5°) than fellows (axial: 14° ± 1.7°, coronal: 13° ± 1.7°; p < 0.05), or residents (axial: 15° ± 1.5°; p < 0.001, coronal: 17° ± 1.9°; p < 0.001). This study suggests that mental representation of the cochlea is experience-dependent. A high variation of the insertion axis to the scala tympani can be observed due to the complexity of the temporal bone anatomy and lack of landmarks to determine scala tympani orientation. Navigation systems can be used to evaluate and improve mental representation of the insertion axis to the scala tympani for cochlear implant surgery.

Management of epi- and mesotympanic cholesteatomas by one-stage trans-canal atticotomy in adults.

Surgical management of cholesteatoma limited to the attic and/or mesotympanum remains controversial. The aim of this study is to evaluate the anatomical and the functional results of trans-canal atticotomy in this pathological condition. The records of 27 adult patients treated from 2008 to 2014 who underwent trans-canal atticotomy for primary cholesteatoma surgery were reviewed. Pre-operative physical examination, audiometry, and CT-scan have been analyzed. Intraoperative findings have been described as well as the surgical technique. Anatomical and functional results have been evaluated with a mean follow-up of 24 ± 12.2 months, and the results of a CT-scan performed 1 year after surgery were examined to assess the presence of residual disease. Surgeries were uneventful. During the follow-up, 1 patient (4 %) experienced a retraction of the attical reconstruction; all the other patients had a well-healed tympanic drum with stable attical reconstruction. The mean air-bone gap was 19 ± 12.2 and 10 ± 7.3 dB pre-operatively and post-operatively, respectively (mean ± SD, p = 0.001, paired t test). Twenty-two patients (81 %) had no opacity suggesting residual cholesteatoma in CT-scan. Four patients (15 %) presenting an opacity at CT-scan underwent MRI study that was negative for residual cholesteatoma. One patient (4 %) had displacement of the ossicular prosthesis. In conclusion, cholesteatomas restricted to the attic and/or mesotympanum can be removed in a one-stage technique with no visible residual at 1 year, and with closure of the air-bone gap by 50 %.

Glucocorticoids stimulate endolymphatic water reabsorption in inner ear through aquaporin 3 regulation.

Menière's disease, clinically characterized by fluctuating, recurrent, and invalidating vertigo, hearing loss, and tinnitus, is linked to an increase in endolymph volume, the so-called endolymphatic hydrops. Since dysregulation of water transport could account for the generation of this hydrops, we investigated the role of aquaporin 3 (AQP3) in water transport into endolymph, the K-rich, hyperosmotic fluid that bathes the apical ciliated membrane of sensory cells, and we studied the regulatory effect of dexamethasone upon AQP3 expression and water fluxes. The different AQP subtypes were identified in inner ear by RT-PCR. AQP3 was localized in human utricle and mouse inner ear by immunohistochemistry and confocal microscopy. Unidirectional transepithelial water fluxes were studied by means of (3)H2O transport in murine EC5v vestibular cells cultured on filters, treated or not with dexamethasone (10(-7) M). The stimulatory effect of dexamethasone upon AQP3 expression was assessed in EC5v cells and in vivo in mice. AQP3 was unambiguously detected in human utricle and was highly expressed in both endolymph secretory structures of the mouse inner ear, and EC5v cells. We demonstrated that water reabsorption, from the apical (endolymphatic) to the basolateral (perilymphatic) compartments, was stimulated by dexamethasone in EC5v cells. This was accompanied by a glucocorticoid-dependent increase in AQP3 expression at both messenger RNA (mRNA) and protein level, presumably through glucocorticoid receptor-mediated AQP3 transcriptional activation. We show that glucocorticoids enhance AQP3 expression in human inner ear and stimulate endolymphatic water reabsorption. These findings should encourage further clinical trials evaluating glucocorticoids efficacy in Menière's disease.

Contralateral routing of signal hearing aid versus transcutaneous bone conduction in single-sided deafness.

The aim of this study was to compare a contralateral routing of signal (CROS) hearing aid to a transcutaneous bone-anchored device in the same conditions. This prospective crossover study included 18 adult patients with a single-sided deafness (SSD). After a trial period of 60 days with CROS and 7 days with a transcutaneous bone-anchored device (Alpha 1®, Sophono, Boulder, Colo., USA) on a headband, 13 (72%) patients opted for Alpha 1, 2 patients for CROS, and 3 rejected both rehabilitation methods. Clinical tolerance, satisfaction, hearing performances (pure-tone audiometry, speech test in quiet and in noise, stereo audiometry, sound localization, and Hearing in Noise Test), and quality of life (Glasgow Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit and Glasgow Hearing Aid Benefit questionnaires) were measured at 3 and 12 months after the implantation. Both devices improved equally the hearing in noise and the quality of life. Transcutaneous devices represent an effective option in SSD.

Effect of corticosteroids on facial function after cerebellopontine angle tumor removal: a double-blind study versus placebo.

The aim of this study was to assess the effect of corticosteroids administered intra- and postoperatively on the occurrence of facial palsy after a cerebellopontine angle (CPA) tumor resection, and to investigate pre- and intraoperative prognostic factors. A multicenter, prospective, randomized, double-blind and versus-placebo study was conducted between 2006 and 2010. Three hundred and ten patients operated on for a CPA tumor (96% vestibular schwannomas, 4% miscellaneous) were included by five participating centers. The population was stratified into patients with small (≤15 mm CPA on axial MRI views) and large tumors. In each group, patients were randomized to receive corticosteroid (1 mg/kg/day i.v. methylprednisolone intraoperatively and at postoperative days 1-5) or placebo. Steroids did not affect the facial function at postoperative days 1, 8 and 30 in patients with small or large tumors as evaluated by House and Brackmann grading.

Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway.

Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC) and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity and alveolar Na(+) absorption through a decrease of ENaC subunit expression at the apical membrane of alveolar epithelial cells (AECs). Here, we investigated the mechanism(s) involved in this process in vivo in the ß-Liddle mouse strain mice carrying a truncation of ß-ENaC C-terminus abolishing the interaction between ß-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the channel for endocytosis and degradation and in vitro in rat AECs. Hypoxia (8% O2 for 24 h) reduced amiloride-sensitive alveolar fluid clearance by 69% in wild-type mice but had no effect in homozygous mutated ß-Liddle littermates. In vitro, acute exposure of AECs to hypoxia (0.5-3% O2 for 1-6 h) rapidly decreased transepithelial Na(+) transport as assessed by equivalent short-circuit current Ieq and the amiloride-sensitive component of Na(+) current across the apical membrane, reflecting ENaC activity. Hypoxia induced a decrease of ENaC subunit expression in the apical membrane of AECs with no change in intracellular expression and induced a 2-fold increase in α-ENaC polyubiquitination. Hypoxic inhibition of amiloride-sensitive Ieq was fully prevented by preincubation with the proteasome inhibitors MG132 and lactacystin or with the antioxidant N-acetyl-cysteine. Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport.

Validation method of a middle ear mechanical model to develop a surgical simulator.

Ossicular surgery requires a high dexterity for the manipulation of the fragile and small middle ear components. Currently, the only efficient technique for training residents in otological surgery is through the use of temporal bone specimens, where any existing surgical simulator does not provide useful feedback. The objective of this study was to develop a finite-element model of the human ossicular chain dedicated to surgical simulation and to propose a method to evaluate its behavior. A model was developed based on human middle ear micromagnetic resonance imaging. The mechanical parameters were determined according to published data. To assess its performance, the middle ear transfer function was analyzed. The robustness of our model and the influence of different middle ear components were also evaluated at low frequency by static force pressure simulations. The mechanical behavior of our model in nominal and pathological conditions was in good agreement with published human temporal bone measurements. We showed that the cochlea influences the transfer function only at high frequency and could be omitted from a surgical simulator. In addition, surgeons were able to manipulate the validated middle ear model with a real-time haptic feedback. The computational efficiency of our approach allowed real-time interactions, making it suitable for use in a training simulator.

Use of granules of biphasic ceramic in rehabilitation of canal wall down mastoidectomy.

The objective of this study is to evaluate the anatomical and functional results of rehabilitation of canal wall down (CWD) mastoidectomy using granules of biphasic ceramic. This is a study design retrospective in a tertiary referral centre Fifty-seven patients (59 ears) operated on between 2006 and 2010 of mastoid obliteration with granules of biphasic ceramic (TricOs, Maurepas, France) have been included (55 revisions and 4 first surgeries). Forty-six patients presented already a CWD mastoidectomy. The mean pre-operative bone conduction (BC) was 29 ± 3.4 dB (mean ± SEM) and mean air conduction (AC) was 57 ± 3.2 dB. Cholesteatoma was found in 33 cases. All but seven cases had post-operative otoscopy examination at 1, 3, 6 months, and 1 year postoperative with a CT scan and pure tone audiometry. Mean follow-up was 14 ± 1.8 months (3-35). At one-year follow-up (n = 52), 47 cases (90 %) presented well-healed external auditory canal. Five cases (10 %) of uncovered granules without sign of infection of external auditory canal skin were observed. Mean post-operative threshold was 25 ± 1.8 and 46 ± 1.9 dB for BC and AC , respectively (n = 47). CT scan (n = 42) showed no opacity suggesting residual disease within or behind obliteration. Mastoid obliteration with granules of biphasic ceramic is a safe and effective procedure that allows restoration of a near normal external auditory canal.