Determining the Minimal Clinically Important Difference (MCID) and Responsiveness of the Chinese Version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn): A Prospective Multicenter Study.

OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa (κ) of 0.14 (p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.

Treatment of Acute Otitis Media with Inner Ear Involvement in Adults.

Inner ear involvement (IED) is a rare local complication of the very common acute otitis media (AOM). The most beneficial treatment for IED remains a matter of debate. The aim of this study is to analyze different treatment modalities based on hearing outcomes to contribute to the discussion of therapy for IED in AOM. This retrospective study includes 112 adult patients diagnosed with AOM with IED between 2000 and 2020. Patients either received conservative (systemic antibiotic and systemic steroid therapy), interventional (conservative plus myringotomy and tympanic tube) or operative (interventional plus antrotomy) treatment. Pre- and post-treatment pure tone audiometry was performed. The hearing outcome was compared, and hearing recovery was analyzed based on modified Siegel's criteria. The pre-treatment pure tone average (PTA) was significantly (p < 0.05) higher in the operative group than in the other groups. All treatment modalities led to a significant hearing improvement (p < 0.001). The pre- and post-treatment hearing loss was predominantly observed in high frequencies 2-4 kHz. The operative group showed the highest rate of complete hearing recovery. While all treatment modalities led to a significant improvement in hearing, the operative group showed the most beneficial hearing results in patients with high pre-treatment hearing loss. It remains to be shown if the findings in patients with high pre-treatment hearing loss can be generalized to patients with mild or moderate pre-treatment hearing loss.

Effects of preloads on middle-ear transfer function and acoustic reflex in ossiculoplasty with PORP.

INTRODUCTION: Surgical outcomes in ossiculoplasty with partial ossicular replacement prostheses (PORPs) are greatly influenced by the amount of preload imposed on the PORP. In this study, the attenuation of the middle-ear transfer function (METF) was experimentally investigated for prosthesis-related preloads in different directions, with and without concurrent application of stapedial muscle tension. Different PORP designs were assessed to determine functional benefits of specific design features under preload conditions. METHODS: The experiments were performed on fresh-frozen human cadaveric temporal bones. The effect of preloads along different directions were experimentally assessed by simulating anatomical variance and postoperative position changes in a controlled setup. The assessments were performed for three different PORP designs featuring either a fixed shaft or ball joint and a Bell-type or Clip-interface. Further, the combined effect of the preloads towards the medial direction with tensional forces of the stapedial muscle was assessed. The METF was obtained via laser-Doppler vibrometry for each measurement condition. RESULTS: The preloads as well as the stapedial muscle tension primarily attenuated the METF between 0.5 and 4 kHz. The largest attenuations resulted from the preload towards the medial direction. The attenuation of the METF with stapedial muscle tension was reduced with concurrent PORP preloads. PORPs with a ball joint resulted in reduced attenuation only for preloads along the long axis of the stapes footplate. In contrast to the clip interface, the Bell-type interface was prone to lose coupling with the stapes head for preloads in the medial direction. CONCLUSIONS: The experimental study of the preload effects indicates a direction-dependent attenuation of the METF, with the most pronounced effects resulting from preloads towards the medial direction. Based on the obtained results, the ball joint offers tolerance for angular positioning while the clip interface prevents PORP dislocations for preloads in lateral direction. At high preloads, the attenuation of the METF with stapedial muscle tension is reduced, which should be considered for the interpretation of postoperative acoustic reflex tests.

Three-dimensional quasi-static displacement of human middle-ear ossicles under static pressure loads: Measurement using a stereo camera system.

The time delay and/or malfunctioning of the Eustachian tube may cause pressure differences across the tympanic membrane, resulting in quasi-static movements of the middle-ear ossicles. While quasi-static displacements of the human middle-ear ossicles have been measured one- or two-dimensionally in previous studies, this study presents an approach to trace three-dimensional movements of the human middle-ear ossicles under static pressure loads in the ear canal (EC). The three-dimensional quasi-static movements of the middle-ear ossicles were measured using a custom-made stereo camera system. Two cameras were assembled with a relative angle of 7° and then mounted onto a robot arm. Red fluorescent beads of a 106-125 µm diameter were placed on the middle-ear ossicles, and quasi-static position changes of the fluorescent beads under static pressure loads were traced by the stereo camera system. All the position changes of the ossicles were registered to the anatomical intrinsic frame based on the stapes footplate, which was obtained from µ-CT imaging. Under negative ear-canal pressures, a rotational movement around the anterior-posterior axis was dominant for the malleus-incus complex, with small relative movements between the two ossicles. The stapes showed translation toward the lateral direction and rotation around the long axis of the stapes footplate. Under positive EC pressures, relative motion between the malleus and the incus at the IMJ became larger, reducing movements of the incus and stapes considerably and thus performing a protection function for the inner-ear structures. Three-dimensional tracing of the middle-ear ossicular chain provides a better understanding of the protection function of the human middle ear under static pressured loads as immediate responses without time delay.

Wave propagation across the skull under bone conduction: Dependence on coupling methods.

This study is aimed at the quantitative investigation of wave propagation through the skull bone and its dependence on different coupling methods of the bone conduction hearing aid (BCHA). Experiments were conducted on five Thiel embalmed whole head cadaver specimens. An electromagnetic actuator from a commercial BCHA was mounted on a 5-Newton steel headband, at the mastoid, on a percutaneously implanted screw (Baha® Connect), and transcutaneously with a Baha® Attract (Cochlear Limited, Sydney, Australia), at the clinical bone anchored hearing aid (BAHA) location. Surface motion was quantified by sequentially measuring ∼200 points on the skull surface via a three-dimensional laser Doppler vibrometer (3D LDV) system. The experimental procedure was repeated virtually, using a modified LiUHead finite element model (FEM). Both experiential and FEM methods showed an onset of deformations; first near the stimulation area, at 250-500 Hz, which then extended to the inferior ipsilateral skull surface, at 0.5-2 kHz, and spread across the whole skull above 3-4 kHz. Overall, stiffer coupling (Connect versus Headband), applied at a location with lower mechanical stiffness (the BAHA location versus mastoid), led to a faster transition and lower transition frequency to local deformations and wave motion. This behaviour was more evident at the BAHA location, as the mastoid was more agnostic to coupling condition.

Transcutaneous and percutaneous bone conduction sound propagation in single-sided deaf patients and cadaveric heads.

OBJECTIVE: To investigate transcranial transmission (TT) and the dampening effect of the skin in patients and cadaver heads. DESIGN: In patients a pure tone bone conduction audiogram for ipsilateral and contralateral stimulation was performed. The TT was defined as the difference between ipsilateral and contralateral hearing thresholds. In cadaver heads ipsilateral and contralateral promontory motion was measured using a three-dimensional Laser Doppler Vibrometer system. STUDY SAMPLE: Seven single-sided deaf patients fitted with a Baha® Connect, fifteen single-sided deaf patients without a bone conduction hearing aid and five Thiel-embalmed cadaver heads were included. RESULTS: The TT decreased with increasing frequency in patients and cadaver heads. No significant difference was seen between patients and cadaver heads. Measurements on patients and cadaver heads showed increasing skin attenuation with increasing frequency. However, the dampening effect was 3-12 dB higher in patients than in cadavers at all frequencies. CONCLUSION: The TT was not significantly different for patients compared to cadaver heads. The value of promontory motion to estimate TT in patients need to be further evaluated. The skin attenuates a BC stimulus by 10-20 dB in patients and by a smaller amount in cadaver heads, probably due to changes in the properties of the Thiel-conserved skin.

Multicenter Results With an Active Transcutaneous Bone Conduction Implant in Patients With Single-sided Deafness.

OBJECTIVE: To evaluate the audiological and subjective benefit from hearing rehabilitation with an active bone conduction implant in subjects with single-sided sensorineural deafness (SSD). STUDY DESIGN: Prospective, multicenter, single-subject repeated measures. SETTING: Tertiary referral center, five clinics in Germany and Switzerland. PATIENTS: Seventeen subjects aged 18 years and older with severe to profound unilateral sensorineural hearing loss and contralateral normal hearing were followed up for 24 months. INTERVENTION: Active bone conduction implant. MAIN OUTCOME MEASURES: Speech understanding in noise was assessed in three situations: with signal from front, deaf, or normal hearing side (with noise from front in all set-ups). Subjective benefit was evaluated using the Speech, Spatial, and Qualities of Hearing (SSQ-B) and Bern Benefit in Single-Sided Deafness (BBSS) questionnaire. RESULTS: When the signal was coming from the deaf side the mean improvement of the speech reception threshold in noise ranged from 1.5 up to 2.2 dB with the device and was statistically and clinically significant at all tested timepoints. No significant difference between the aided and unaided situation was found when signal and noise were coming from the front. With the signal from the normal hearing side no clinically significant difference, that is, greater than 1 dB between the aided and unaided situation was found. The SSQ-B and BBSS questionnaire showed an overall improvement with no significant difference between time points. CONCLUSIONS: The study demonstrates long-term efficacy and benefit of the device in adults with SSD. Patients reported substantial and persistent subjective benefit from the active bone conduction implant.

Cost Effectiveness of Cochlear Implantation in Single-Sided Deafness.

OBJECTIVE: To analyze the cost effectiveness of cochlear implantation (CI) for the treatment of single-sided deafness (SSD). STUDY DESIGN: Cost-utility analysis in an adapted Markov model. SETTING: Adults with single-sided deafness in a high-income country. INTERVENTION: Unilateral CI was compared with no intervention. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratios were compared with different cost-effectiveness thresholds ($10,000 to $150,000) for different age, sex, and cost combinations. The calculations were based on the quality-adjusted life year (QALY), national life expectancy tables, and different cost settings. The health utility values for the QALY were either directly collected from published data, or, derived from published data using a regression model of multiple utility indices (regression estimate). RESULTS: The regression estimate showed an increase of the health utility value from 0.62 to 0.74 for SSD patients who underwent CI. CI for SSD was cost effective for women up to 64 years ($50,000 per-QALY threshold), 80 years ($100,000 per-QALY threshold), and 86 years ($150,000 per-QALY threshold). For men, these values were 58, 77, and 84, respectively. Changing the discount rate by up to 5% further increased the cutoff ages up to 5 years. A detailed cost and age sensitivity analysis is presented and allows testing for cost effectiveness in local settings worldwide. CONCLUSIONS: CI is a cost-effective option to treat patients with SSD.

Contribution of the flexible incudo-malleal joint to middle-ear sound transmission under static pressure loads.

The incudo-malleal joint (IMJ) in the human middle ear is a true diarthrodial joint and it has been known that the flexibility of this joint does not contribute to better middle-ear sound transmission. Previous studies have proposed that a gliding motion between the malleus and the incus at this joint prevents the transmission of large displacements of the malleus to the incus and stapes and thus contributes to the protection of the inner ear as an immediate response against large static pressure changes. However, dynamic behavior of this joint under static pressure changes has not been fully revealed. In this study, effects of the flexibility of the IMJ on middle-ear sound transmission under static pressure difference between the middle-ear cavity and the environment were investigated. Experiments were performed in human cadaveric temporal bones with static pressures in the range of +/- 2 kPa being applied to the ear canal (relative to middle-ear cavity). Vibrational motions of the umbo and the stapes footplate center in response to acoustic stimulation (0.2-8 kHz) were measured using a 3D-Laser Doppler vibrometer for (1) the natural IMJ and (2) the IMJ with experimentally-reduced flexibility. With the natural condition of the IMJ, vibrations of the umbo and the stapes footplate center under static pressure loads were attenuated at low frequencies below the middle-ear resonance frequency as observed in previous studies. After the flexibility of the IMJ was reduced, additional attenuations of vibrational motion were observed for the umbo under positive static pressures in the ear canal (EC) and the stapes footplate center under both positive and negative static EC pressures. The additional attenuation of vibration reached 4~7 dB for the umbo under positive static EC pressures and the stapes footplate center under negative EC pressures, and 7~11 dB for the stapes footplate center under positive EC pressures. The results of this study indicate an adaptive mechanism of the flexible IMJ in the human middle ear to changes of static EC pressure by reducing the attenuation of the middle-ear sound transmission. Such results are expected to be used for diagnosis of the IMJ stiffening and to be applied to design of middle-ear prostheses.

Assessment of Surgical Complications With Respect to the Surgical Indication: Proposal for a Novel Index.

Introduction: The Clavien-Dindo classification is a broadly accepted surgical complications classification system, grading complications by the extent of therapy necessary to resolve them. A drawback of the method is that it does not consider why the patient was operated on primarily. Methods: We designed a novel index based on Clavien-Dindo but with respect to the surgical indication. We surveyed an international panel of otolaryngologists who filled out a questionnaire with 32 real case-inspired scenarios. Each case was graded for the surgical complication, surgical indication, and a subjective rating whether the complication was acceptable or not. Results: Seventy-seven otolaryngologists responded to the survey. Mean subjective rating and surgical complication grading for each scenario showed an inverse correlation (r 2 = 0.147, p = 0.044). When grading the surgical complication with respect to the surgical indication, the correlation with the subjective rating increased dramatically (r 2 = 0.307, p = 0.0022). Conclusion: We describe a novel index grading surgical complications with respect to the surgical indication. In our survey, most respondents judged a complication as acceptable or not according to its grade but kept in mind the surgical indication. This subjective judgment could be quantified with our novel index.

Pre-habilitation Before Vestibular Schwannoma Surgery-Impact of Intratympanal Gentamicin Application on the Vestibulo-Ocular Reflex.

Background: Patients with vestibular schwannoma that show residual peripheral-vestibular function before surgery may experience sudden and substantial vestibular loss of function after surgical resection. To alleviate the sudden loss of peripheral-vestibular function after vestibular-schwannoma (VS) resection, pre-surgical intratympanic gentamicin application was proposed. Objective: We hypothesized that this approach allows for a controlled reduction of peripheral-vestibular function before surgery but that resulting peripheral-vestibular deficits may be canal-specific with anterior-canal sparing as observed previously in systemic gentamicin application. Methods: Thirty-four patients (age-range = 27-70 y) with unilateral VS (size = 2-50 mm) were included in this retrospective single-center trial. The angular vestibulo-ocular reflex (aVOR) was quantified before and after (29.7 ± 18.7 d, mean ± 1SD) a single or two sequential intratympanic gentamicin applications by use of video-head-impulse testing. Both aVOR gains, cumulative saccadic amplitudes, and overall aVOR function were retrieved. Statistical analysis was done using a generalized linear model. Results: At baseline, loss of function of the horizontal (20/34) and posterior (21/34) canal was significantly (p < 0.001) more frequent than that of the anterior canal (5/34). After gentamicin application, loss of function of the horizontal (32/34) or posterior (31/34) canal remained significantly (p ≤ 0.003) more frequent than that of the anterior canal (18/34). For all ipsilesional canals, significant aVOR-gain reductions and cumulative-saccadic-amplitude increases were noted after gentamicin. For the horizontal canal, loss of function was significantly larger (increase in cumulative-saccadic-amplitude: 1.6 ± 2.0 vs. 0.8 ± 1.2, p = 0.007) or showed a trend to larger changes (decrease in aVOR-gain: 0.24 ± 0.22 vs. 0.13 ± 0.29, p = 0.069) than for the anterior canal. Conclusions: Intratympanic gentamicin application resulted in a substantial reduction in peripheral-vestibular function in all three ipsilesional canals. Relative sparing of anterior-canal function noted at baseline was preserved after gentamicin treatment. Thus, pre-surgical intratympanic gentamicin is a suitable preparatory procedure for reducing the drop in peripheral-vestibular function after VS-resection. The reasons for relative sparing of the anterior canal remain unclear.

Three-dimensional (3D) Printed Vestibular Schwannoma for Facial Nerve Tractography Validation.

OBJECTIVES: Predicting the course of cranial nerve (CN) VII in the cerebellopontine angle (CPA) on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion MRI based tractography has been used to identify cranial nerve trajectory, but intraoperative validation of this novel approach is challenging. Currently, validation is based on operative report descriptions of the course of cranial nerves, but yields a simplified picture of the three-dimensional (3D) course of CN VII. In this study, we investigate the accuracy of tractography with detailed patient-specific 3D-printed VS tumors. DESIGN: Retrospective case review. SETTING: Tertiary referral center. PARTICIPANTS: Twenty adult VS surgical candidates. MAIN OUTCOME MEASURES: We compared tractography with intraoperative 3D course of CN VII. The surgeons were blinded to tractography and drew the intraoperative course of the CN VII on a patient specific 3D-printed tumor model for detailed comparison with tractography. RESULTS: Of 20 patients, one was excluded due to subtotal removal and inability to assess CN VII course. In the remaining 19 patients, 84% (16/19) tractography was successful. In 94% of tumors with tractography (15/16), the intraoperative description of CN VII course matched the tractography finding. The maximum distance, however, between tractography and intraoperative course of CN VII was 3.7 mm ±â€Š4.2 mm. CONCLUSION: This study presents a novel approach to CN VII tractography validation in VS. Although descriptions of CN VII intraoperatively match tractography, caution is warranted as quantitative measures suggest a clinically significant distance between tractography and CN VII course.

[Experimental Evaluation of the Adhear, a Novel Transcutaneous Bone Conduction Hearing Aid]. / Experimentelle Evaluation des Adhear, eines neuen transkutanen Knochenleitungshörgeräts.

OBJECTIVE: Different bone conduction hearing aids (BCHA) are commercially available. They are attached to the head in different ways. The aim of this work is an experimental evaluation of the performance of a new transcutaneous (surface mounted via adhesive pad) actuator of a BCHA. MATERIAL AND METHODS: Experiments were conducted on a Thiel embalmed whole head cadaver specimen. The electromagnetic actuators from a commercial BCHA (Adhear) was used to provide stepped sine stimulus in the range of 0.1-10 kHz. The BCHA was coupled to a skin surface adhesion that was placed on the mastoid. The response was monitored as motions of the ipsi- and contralateral promontory, and as motions of the ipsi-, top- and contralateral skull surface. Promontory motion was quantified via a three-dimensional laser Doppler vibrometer (3D LDV) system. Analogously, surface motion was registered by sequentially measuring ~200 points on the skull surface (~ 15-20 mm pitch) via 3D LDV. The data were compared to corresponding measurements obtained with a Baha Power that was coupled to skin on the Mastoid via a 5 Newton steelband. RESULTS: Ipsilateral and contralateral promontory vibration for stimulation with the Adhear are comparable to stimulation with the Baha Power on the 5 Newton steelband with regard to frequency dependent amplitude and phase, as well as the contribution of the motion components. The surface motion of the skull experiences a similar complex motion for both stimulation modes. CONCLUSIONS: Although the Adhear is coupled without any pressure to the skin over the mastoid whereas the Baha power is attached with a 5 Newton steelband, the vibration parameters investigated are comparable.

Measuring health-related quality of life in chronic otitis media in a Chinese population: cultural adaption and validation of the Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn).

BACKGROUND: The demand for assessing health-related quality of life (HRQoL) in chronic otitis media (COM) is increasing globally. The currently available Chinese-language patient-reported outcome measurement (PROM) specific for COM includes merely a limited range of related symptoms and dimensions. Hence, in this study, we aim to translate, culturally adapt, and validate the Zurich Chronic Middle Ear Inventory (ZCMEI-21) in Chinese, to enable a comprehensive evaluation of the patients' subjective health outcome in COM. METHODS: We sampled and surveyed 223 COM patients at three tertiary referral centers in China, using the Chinese translation of ZCMEI-21 (ZCMEI-21-Chn) and the EQ-5D questionnaire, a generic measure of HRQoL. Confirmatory factor analysis (CFA) was performed to investigate the structural model fit to the dataset. Cronbach's α and test-retest reliability coefficient were calculated to establish reliability, and correlation was tested between ZCMEI-Chn scores and EQ-5D scores for convergent validity. RESULTS: A total of 208 adult patients with COM were included, with a mean age of 46 years (SD 14 years) and a male proportion of 41% (85/208). A modified bifactor model with ωH of 0.65 and ECV of 0.47 was found to fit the scale scores, indicating fair general factor saturation and multidimensionality of the instrument. ZCMEI-21-Chn demonstrated good reliability (Cronbach's α = 0.88, test-retest reliability = 0.88). The total scores of ZCMEI-21-Chn had a moderate correlation with a question directly addressing HRQoL (r = 0.40, p < 0.001), EQ-5D descriptive system score (r = 0.57, p < 0.001), and EQ-5D visual analogous scale (r = 0.30, p < 0.001). CONCLUSIONS: The ZCMEI-21-Chn is valid, reliable and culturally adapted to Chinese adult patients with COM. This study offers clinicians an efficient and comprehensive instrument to quantify COM patients' self-reported health outcomes, which could facilitate the standardization of HRQoL data aggregation in COM on a global scale.

Dependence of skull surface wave propagation on stimulation sites and direction under bone conduction.

In order to better understand bone conduction sound propagation across the skull, three-dimensional (3D) wave propagation on the skull surface was studied, along with its dependence on stimulation direction and location of a bone conduction hearing aid (BCHA) actuator. Experiments were conducted on five Thiel embalmed whole head cadaver specimens. Stimulation, in the 0.1-10 kHz range, was sequentially applied at the forehead and mastoid via electromagnetic actuators from commercial BCHAs, supported by a 5-N steel band. The head response was quantified by sequentially measuring the 3D motion of ∼200 points (∼15-20 mm pitch) across the ipsilateral, top, and contralateral skull surface via a 3D laser Doppler vibrometer (LDV) system, guided by a robotic positioner. Low-frequency stimulation (<1 kHz) resulted in a spatially complex rigid-body-like motion of the skull that depended on both the stimulation condition and head support. The predominant motion direction was only 5-10 dB higher than other components below 1 kHz, with no predominance at higher frequencies. Sound propagation direction across the parietal plates did not coincide with stimulation location, potentially due to the head base and forehead remaining rigid-like at higher frequencies and acting as a large source for the deformation patterns across the parietal sections.

Human Cochlear Nucleus on 7 Tesla Diffusion Tensor Imaging: Insights Into Micro-anatomy and Function for Auditory Brainstem Implant Surgery.

OBJECTIVE: The cochlear nucleus (CN) is the target of the auditory brainstem implant (ABI). Most ABI candidates have Neurofibromatosis Type 2 (NF2) and distorted brainstem anatomy from bilateral vestibular schwannomas. The CN is difficult to characterize as routine structural MRI does not resolve detailed anatomy. We hypothesize that diffusion tensor imaging (DTI) enables both in vivo localization and quantitative measurements of CN morphology. STUDY DESIGN: We analyzed 7 Tesla (T) DTI images of 100 subjects (200 CN) and relevant anatomic structures using an MRI brainstem atlas with submillimetric (50 µm) resolution. SETTING: Tertiary referral center. PATIENTS: Young healthy normal hearing adults. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Diffusion scalar measures such as fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (Mode), principal eigenvectors of the CN, and the adjacent inferior cerebellar peduncle (ICP). RESULTS: The CN had a lamellar structure and ventral-dorsal fiber orientation and could be localized lateral to the inferior cerebellar peduncle (ICP). This fiber orientation was orthogonal to tracts of the adjacent ICP where the fibers run mainly caudal-rostrally. The CN had lower FA compared to the medial aspect of the ICP (0.44 ±â€Š0.09 vs. 0.64 ±â€Š0.08, p < 0.001). CONCLUSIONS: 7T DTI enables characterization of human CN morphology and neuronal substructure. An ABI array insertion vector directed more caudally would better correspond to the main fiber axis of CN. State-of-the-art DTI has implications for ABI preoperative planning and future image guidance-assisted placement of the electrode array.

Super-resolution Diffusion Tensor Imaging for Delineating the Facial Nerve in Patients with Vestibular Schwannoma.

Objectives Predicting the course of cranial nerves (CNs) VII and VIII in the cerebellopontine angle on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion magnetic resonance imaging dMRI is commonly used for this purpose, but is limited by its resolution. We investigate the use of super-resolution reconstruction (SRR), where several different dMRIs are combined into one dataset. We hypothesize that SRR improves the visualization of the CN VII and VIII. Design Retrospective case review. Setting Tertiary referral center. SRR was performed on the basis of axial and parasagittal single-shot epiplanar diffusion tensor imaging on a 3.0-tesla MRI scanner. Participants Seventeen adult patients with suspected neoplasms of the lateral skull base. Main Outcome Measures We assessed separability of the two distinct nerves on fractional anisotropy (FA) maps, the tractography of the nerves through the cerebrospinal fluid (CSF), and FA in the CSF as a measure of noise. Results SRR increases separability of the CN VII and VIII (16/17 vs. 0/17, p = 0.008). Mean FA of CSF surrounding the nerves is significantly lower in SRRs (0.07 ± 0.02 vs. 0.13 ± 0.03 [axial images]/0.14 ± 0.05 [parasagittal images], p = 0.00003/ p = 0.00005). Combined scanning times (parasagittal and axial) used for SRR were shorter (8 minute 25 seconds) than a comparable high-resolution scan (15 minute 17 seconds). Conclusion SRR improves the resolution of CN VII and VIII. The technique can be readily applied in the clinical setting, improving surgical counseling and planning in patients with VS.

Age Dependent Cost-Effectiveness of Cochlear Implantation in Adults. Is There an Age Related Cut-off?

OBJECTIVE: To analyze the impact of age at implantation on the cost-effectiveness of cochlear implantation (CI). STUDY DESIGN: Cost-utility analysis in an adapted Markov model. SETTING: Adults with profound postlingual hearing loss in a "high income" country. INTERVENTION: Unilateral and sequential CI were compared with hearing aids (HA). MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio (ICER), calculated as costs per quality adjusted life year (QALY) gained (in CHF/QALY), for individual age and sex combinations in relation to two different willingness to pay thresholds. 1 CHF (Swiss franc) is equivalent to 1.01 USD. RESULTS: When a threshold of 50,000 CHF per QALY is applied, unilateral CI in comparison to HA is cost-effective up to an age of 91 for women and 89 for men. Sequential CI in comparison to HA is cost-effective up to an age of 87 for women and 85 for men. If a more contemporary threshold of 100,000 CHF per QALY is applied, sequential CI in comparison to unilateral CI is cost-effective up to an age of 80 for women and 78 for men. CONCLUSIONS: Performing both sequential and unilateral CI is cost-effective up to very advanced ages when compared with hearing aids.

Predictive Value of Pretherapeutic Maximum Standardized Uptake Value (Suvmax) In Laryngeal and Hypopharyngeal Cancer.

The aim of the study was to evaluate whether pretherapeutic metabolic tumor parameters from 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging could predict larynx preservation in laryngeal and hypopharyngeal cancer patients prior to primary chemoradiation. Tumor metabolic parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were retrospectively assessed in a consecutive cohort of laryngeal and hypopharyngeal cancer patients undergoing primary (chemo-)radiation. Main outcome measures were larynx preservation and survival. The study included 97 patients with a median follow-up of 32 months (IQR 20-54.5). For hypopharyngeal cancer, multivariable analysis showed that patients with a primary tumor's SUVmax > 9.5 entailed a higher risk of undergoing salvage pharyngolaryngectomy after chemoradiation (HR = 8.64, 95% CI = 1.1-67.3, P = 0.040). In laryngeal cancer, SUVmax did not predict the need for salvage laryngectomy. The only predictor for larynx preservation in laryngeal cancer patients was T-classification at initial diagnosis (HR = 6.67, 95% CI = 0.82-53.9, P = 0.039). In conclusion, SUVmax of primary tumor could be used as a predictor of larynx preservation prior to primary chemoradiation in hypopharyngeal cancer patients. This information may be important for patient counseling, as high SUVmax was correlated with reduced probability of larynx preservation. However, in laryngeal cancer patients, SUVmax does not seem to be predictive of outcome.

Insufficient evidence for a role of SERPINF1 in otosclerosis.

Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis. To unravel the contribution of genetic variation in this gene to otosclerosis, this gene was re-sequenced in a large population of otosclerosis patients and controls. Resequencing of the 5' and 3' UTRs, coding regions, and exon-intron boundaries of SERPINF1 was performed in 1604 unrelated otosclerosis patients and 1538 unscreened controls, and in 62 large otosclerosis families. Our study showed no enrichment of rare variants, stratified by type, in SERPINF1 in patients versus controls. Furthermore, the c.392C > A (p.Ala131Asp) variant, previously reported as pathogenic, was identified in three patients and four controls, not replicating its pathogenic nature. We could also not find evidence for a pathogenic role in otosclerosis for 5' UTR variants in the SERPINF1-012 transcript (ENST00000573763), described as the major transcript in human stapes. Furthermore, no rare variants were identified in the otosclerosis families. This study does not support a pathogenic role for variants in SERPINF1 as a cause of otosclerosis. Therefore, the etiology of the disease remains largely unknown and will undoubtedly be the focus of future studies.