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PURPOSE: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory. METHODS: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL). RESULTS: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores. CONCLUSIONS: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).

Abstract Microscopic evaluation is one of the most effective methods in materials research. High-quality images are essential to analyze microscopic images using artificial intelligence. To overcome this challenge, we propose the machine learning of “fake micrographs” in this study. To verify the effectiveness of this method, we chose to analyze the optical microscopic images of the crystal growth process of a Ge thin film, which is a material in which it is difficult to obtain a contrast between the crystal and amorphous states. By learning the automatically generated fake micrographs that mimic the crystal growth process, the machine learning model can now identify the low-resolution real micrographs as crystalline or amorphous. Comparing the three types of machine learning models, it was found that ResUNet ++ exhibited high accuracy, exceeding 90%. The technology developed in this study for the automatic and rapid analysis of low-resolution images is widely helpful in material research.

HYPOTHESIS: The objective of this study was to perform detailed height and cross-sectional area measurements of the scala tympani in histologic sections of nondiseased human temporal bones and correlate them with cochlear implant electrode dimensions. BACKGROUND: Previous investigations in scala tympani dimensions have used microcomputed tomography or casting modalities, which cannot be correlated directly with microanatomy visible on histologic specimens. METHODS: Three-dimensional reconstructions of 10 archival human temporal bone specimens with no history of middle or inner ear disease were generated using hematoxylin and eosin histopathologic slides. At 90-degree intervals, the heights of the scala tympani at lateral wall, midscala, and perimodiolar locations were measured, along with cross-sectional area. RESULTS: The vertical height of the scala tympani at its lateral wall significantly decreased from 1.28 to 0.88 mm from 0 to 180 degrees, and the perimodiolar height decreased from 1.20 to 0.85 mm. The cross-sectional area decreased from 2.29 (standard deviation, 0.60) mm 2 to 1.38 (standard deviation, 0.13) mm 2 from 0 to 180 degrees ( p = 0.001). After 360 degrees, the scala tympani shape transitioned from an ovoid to triangular shape, corresponding with a significantly decreased lateral height relative to perimodiolar height. Wide variability was observed among the cochlear implant electrode sizes relative to scala tympani measurements. CONCLUSION: The present study is the first to conduct detailed measurements of heights and cross-sectional area of the scala tympani and the first to statistically characterize the change in its shape after the basal turn. These measurements have important implications in understanding locations of intracochlear trauma during insertion and electrode design.

In the present study we investigated the localization of glucocorticoid receptors (GCR) in the human inner ear using immunohistochemistry. Celloidin-embedded cochlear sections of patients with normal hearing (n = 5), patients diagnosed with MD (n = 5), and noise induced hearing loss (n = 5) were immunostained using GCR rabbit affinity-purified polyclonal antibodies and secondary fluorescent or HRP labeled antibodies. Digital fluorescent images were acquired using a light sheet laser confocal microscope. In celloidin-embedded sections GCR-IF was present in the cell nuclei of hair cells and supporting cells of the organ of Corti. GCR-IF was detected in cell nuclei of the Reisners membrane. GCR-IF was seen in cell nuclei of the stria vascularis and the spiral ligament. GCR-IF was found in the spiral ganglia cell nuclei, however, spiral ganglia neurons showed no GCR-IF. Although GCRs were found in most cell nuclei of the cochlea, the intensity of IF was differential among the different cell types being more intense in supporting cells than in sensory hair cells. The differential expression of GCR receptors found in the human cochlea may help to understand the site of action of glucocorticoids in different ear diseases.

Abstract Objectives Three‐tesla MRI with gadolinium‐based contrast agents is important in diagnosing Ménière's disease. However, contrast agents cannot be used in some patients. By using the compositional difference between the inner ear endolymph and perilymph, we performed basic and clinical research focused on potassium ions and protein to find the optimal parameters for visualizing endolymphatic hydrops on MRI without contrast. We then examined the relationship between severity stage and visualization rate of endolymphatic hydrops. Methods In phantom experiments simulating the endolymph and perilymph, we explored MRI parameters that could be used to separate endolymph from perilymph by gradually changing the inversion time. We then used these parameters to perform both new non‐contrast MRI and contrast MRI on the same day in Ménière's disease patients, and we compared the visualization rates of endolymphatic hydrops under the two modalities. Fifty patients were selected from 478 patients with Ménière's disease of different severity stages; 12 patients had asthma and allergy to contrast agents. Results The higher the disease stage, the higher the endolymphatic hydrops visualization rate. The new non‐contrast MRI gave significantly higher (p

OBJECTIVE: This study aims to identify clinical predictors of treatment response to Eustachian Tube Balloon Dilation (ETBD) as measured by changes in Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores. METHODS: One hundred thirteen patients who underwent ETBD at an institution from 2017 to 2021 completed ETDQ-7 pre- and post-operatively. We conducted multivariable regression analyses with ETDQ-7 normalization (0.5 pre-op - post-op), and quantitative improvement in ETDQ-7 score as outcome variables. Pre-operative ETDQ-7 score, tympanogram type, chronic otitis media, chronic rhinosinusitis (CRS), inferior turbinate hypertrophy, deviated septum, allergic rhinitis, and rhinorrhea were included as covariates. Models controlled for age, sex, ethnicity, prior ear or sinus surgery, and follow-up duration. RESULTS: The mean age was 49 years old. 51% were females, and all patients had pre-operative ETDQ-7 above 2.1. After a mean follow-up period of 13 months, 77% achieved MCID and 37% had normalized. Higher pre-operative ETDQ-7 score was associated with greater ETDQ-7 score improvement (B = 0.60, 95% CI = [0.37, 0.83]) and greater odds of achieving MCID (aOR = 1.65; 95% CI = [1.06, 2.59]). A history of CRS improved chances of achieving MCID (aOR = 4.53; 95% CI = [1.11, 18.55]) and a history of chronic otitis media predicted increased odds of ETDQ-7 normalization (aOR = 2.88; 95% CI = [1.09, 7.58]). CONCLUSIONS: Our findings suggest that ETBD was highly effective among patients with pre-operative ETDQ-7 above 2.1. Furthermore, higher pre-operative ETDQ-7 score, CRS, and chronic otitis media predicted more favorable symptomatic benefit from ETBD. These factors may be important to consider when counseling potential candidates for this procedure.

OBJECTIVE: This study aims to investigate patterns of cochlear ossification (CO) in cadaveric temporal bones of patients who underwent vestibular schwannoma (VS) surgery via the translabyrinthine (TL), middle cranial fossa (MF), or retrosigmoid (RS) approaches. STUDY DESIGN: Histopathologic analysis of cadaveric temporal bones. SETTING: Multi-institutional national temporal bone repository. METHODS: The National Institute of Deafness and Communication Disorders and House Temporal Bone Laboratory at the University of California, Los Angeles and the Massachusetts Eye and Ear Otopathology Laboratory were searched for cadaveric temporal bones with a history of VS for which microsurgery was performed. Exclusion criteria included non-VS and perioperative death within 30 days of surgery. Temporal bones were analyzed histologically for CO of the basal, middle, and apical turns. RESULTS: Of 92 temporal bones with a history of schwannoma from both databases, 12 of these cases met the inclusion criteria. The approaches for tumor excision included 2 MF, 4 RS, and 6 TL approaches. CO was observed in all temporal bones that had undergone TL surgery. Among temporal bones that had undergone MF or RS surgeries, 5/6 had no CO, and 1/6 had partial ossification. This single case was noted to have intraoperative vestibular violation after RS surgery upon histopathologic and chart review. CONCLUSION: In this temporal bone series, all temporal bones that had undergone TL demonstrated varying degrees of CO on histological analysis. MF and RS cases did not exhibit CO except in the case of vestibular violation. When cochlear implantation is planned or possible after VS surgery, surgeons may consider using a surgical approach that does not violate the labyrinth.