Application of artificial intelligence using a convolutional neural network for detecting cholesteatoma in endoscopic enhanced images.

OBJECTIVE: We examined whether artificial intelligence (AI) used with the novel digital image enhancement system modalities (CLARA+CHROMA, SPECTRA A, and SPECTRA B) could distinguish the cholesteatoma matrix, cholesteatoma debris, and normal middle ear mucosa, and observe the middle ear cavity during middle ear cholesteatoma surgery. METHODS: A convolutional neural network (CNN) was trained with a set of images chosen by an otologist. To evaluate the diagnostic accuracy of the constructed CNN, an independent test data set of middle ear images was collected from 14 consecutive patients with 26 cholesteatoma matrix lesions, who underwent transcanal endoscopic ear surgery at a single hospital from August 2018 to September 2019. The final test data set included 58 total images, with 1‒5 images from each modality for each case. RESULTS: The CNN required only 10 s to analyze more than 58 test images. Using SPECTRA A and SPECTRA B, the CNN correctly diagnosed 15 and 15 of 26 cholesteatoma matrix lesions, with a sensitivity of 34.6% and 42.3%, and with a specificity of 81.3% and 87.5%, respectively. CONCLUSION: Our preliminary study revealed that AI and novel imaging modalities are potentially useful tools for identifying and visualizing the cholesteatoma matrix during endoscopic ear surgery. The diagnostic ability of the CNN is not yet appropriate for implementation in daily clinical practice, based on our study findings. However, in the future, these techniques and AI tools could help to reduce the burden on surgeons and will facilitate telemedicine in remote and rural areas, as well as in developing countries where the number of surgeons is limited.

Post-earthquake dizziness syndrome following the 2016 Kumamoto earthquakes, Japan.

This study aimed to examine the types and causes of dizziness experienced by individuals after a major earthquake. This cross-sectional study enrolled healthy participants who experienced the 2016 Kumamoto earthquakes and their aftershocks. Participants completed a questionnaire survey on their symptoms and experiences after the earthquakes. The primary outcome was the occurrence of dizziness and the secondary outcome was the presence of autonomic dysfunction and anxiety. Among 4,231 eligible participants, 1,543 experienced post-earthquake dizziness. Multivariate logistic regression analysis revealed that age (≥21, P < .001), female sex (P < .001), floor on which the individual was at the time (≥3, P = .007), tinnitus/ear fullness (P < .001), anxiety (P < .001), symptoms related to autonomic dysfunction (P = .04), and prior history of motion sickness (P = .002) were significantly associated with the onset of post-earthquake dizziness. Thus suggesting that earthquake-related effects significantly affect inner ear symptoms, autonomic function, and psychological factors. Earthquake-induced disequilibrium may be further influenced by physical stressors, including sensory disruptions induced by earthquake vibrations, changes in living conditions, and autonomic stress. This study increases our understanding of human equilibrium in response to natural disasters.

Cholesteatoma Imaging Using a Digital Image Enhancement System During Endoscopic Ear Surgery.

Supplemental Digital Content,http://links.lww.com/MAO/B68.

Relationship between clinicopathological characteristics and CYLD expression in patients with cholesteatoma.

Middle ear cholesteatoma is a destructive disease in which inflammation plays an important role in development and progression, and there are currently no biomarkers predicting prognosis or recurrence. Cylindromatosis (CYLD), a tumor suppressor deubiquitinase, serves as a negative regulator of inflammation expressed in tissues including the middle ear. To determine the clinical significance of CYLD in acquired cholesteatoma, we evaluated CYLD expression in acquired cholesteatoma tissue by immunostaining and analyzed its correlation with clinicopathological characteristics. Our immunohistochemical analysis revealed that CYLD expression levels were varied in the tissues of acquired cholesteatoma patients. The relative expression levels of CYLD in cholesteatoma exhibited a significant correlation with the grade of otorrhea (R = 0.532, p = 0.039). Moreover, the period of epithelialization was also significantly associated with the relative expression levels of CYLD (R = 0.720, p = 0.002). In addition, CYLD expression tended to be lower in the group with recurrence. These results suggest that low CYLD expression correlates with postoperative recovery of acquired cholesteatoma, while potentially affecting the induction of recurrence. This is the first report showing that low CYLD expression correlates with accelerated disease recovery, and suggests a new aspect of CYLD as a prognostic predictor of acquired cholesteatoma.

Tsukushi is essential for the development of the inner ear.

Tsukushi (TSK)-a small, secreted, leucine-rich-repeat proteoglycan-interacts with and regulates essential cellular signaling cascades. However, its functions in the mouse inner ear are unknown. In this study, measurement of auditory brainstem responses, fluorescence microscopy, and scanning electron microscopy revealed that TSK deficiency in mice resulted in the formation of abnormal stereocilia in the inner hair cells and hearing loss but not in the loss of these cells. TSK accumulated in nonprosensory regions during early embryonic stages and in both nonprosensory and prosensory regions in late embryonic stages. In adult mice, TSK was localized in the organ of Corti, spiral ganglion cells, and the stria vascularis. Moreover, loss of TSK caused dynamic changes in the expression of key genes that drive the differentiation of the inner hair cells in prosensory regions. Finally, our results revealed that TSK interacted with Sox2 and BMP4 to control stereocilia formation in the inner hair cells. Hence, TSK appears to be an essential component of the molecular pathways that regulate inner ear development.

Prenatal electroporation-mediated gene transfer restores Slc26a4 knock-out mouse hearing and vestibular function.

The otocyst, an anlage of the inner ear, presents an attractive target to study treatment strategies for genetic hearing loss and inner ear development. We have previously reported that electroporation-mediated transuterine gene transfer of Connexin30, utilizing a monophasic pulse into Connexin30-/- mouse otocysts at embryonic day 11.5, is able to prevent putative hearing deterioration. However, it is not clear whether supplementary gene transfer can rescue significant morphological changes, caused by genetic deficits. In addition, with the transuterine gene transfer technique utilized in our previous report, the survival rate of embryos and their mothers after treatment was low, which became a serious obstacle for effective in vivo experiments. Here, we set out to elucidate the feasibility of supplementation therapy in Slc26a4 deficient mice, utilizing biphasic pulses, optimized by modifying pulse conditions. Modification of the biphasic pulse conditions during electroporation increased the survival rate. In addition, supplementation of the target gene cDNA into the otocysts of homozygous Slc24a4 knockout mice significantly prevented enlargement of the endolymphatic space in the inner ear areas; moreover, it rescued hearing and vestibular function of mice in vivo.

Role of Dach1 revealed using a novel inner ear-specific Dach1-knockdown mouse model.

The Dach1 gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesised that Dach1 downregulation in the inner ear would lead to SV dysplasia. However, because Dach1 knockout is embryonic lethal in mice, the role of Dach1 in the inner ear is unclear. Here, we established inner ear-specific Dach1-knockdown mice and showed that Dach1 downregulation resulted in hearing loss, reduced endocochlear potential and secondary outer hair cell loss. There were no abnormalities in marginal cells and basal cells in the SV or spiral ligament in inner ear-specific Dach1-knockdown mature mice. However, intermediate cell dysplasia and thinning of the SV were observed. Moreover, dynamic changes in the expression of key genes related to the epithelial-mesenchymal transition were observed in the lateral wall of the cochlear epithelium, which differentiated into the SV in inner ear-specific Dach1-knockdown mice at embryonic stages. In summary, suppression of Dach1 expression in the inner ear caused the epithelial-mesenchymal transition in the lateral wall of cochlear epithelium, resulting in loss of intermediate cells in the SV and SV dysplasia.This article has an associated First Person interview with the first author of the paper.

Non-microscopic Middle Ear Cholesteatoma Surgery: A Case Report of a Novel Head-Up Approach.

OBJECTIVE: To assess the feasibility of a postauricular transcortical mastoidectomy utilizing an exoscope, which offers 3D stereoscopic visualization. STUDY DESIGN: Clinical capsule report. PATIENTS: Two consecutive patients with cholesteatoma involvement in the mastoid cavity were included in the study. INTERVENTION: After transcanal endoscopic surgery, postauricular mastoidectomy utilizing a surgical 3D exoscope was performed. Then, the cholesteatoma in the mastoid cavity was removed through the mastoidectomy opening with endoscopes. RESULTS: The postauricular transcortical mastoidectomy utilizing a 3D exoscope was not only feasible, but importantly, the exoscope took little time to switch to and resulted in a smooth workflow. There was no cholesteatoma recurrence at 9 months. CONCLUSION: During endoscope-based surgery, in patients with cholesteatoma mastoid involvement, we can continue to perform the surgical procedure in a heads-up position utilizing a surgical 3D exoscope. The combination of transcanal endoscopic ear surgery and the postauricular transcortical mastoidectomy utilizing a surgical 3D exoscope is a very novel treatment strategy for cholesteatoma, and it gives us a comfortable and consistent working environment in endoscope-based ear surgery.

Pharyngocutaneous fistula caused by dried 'Kombu' (edible seaweed) after total laryngectomy.

The most common early complication after total laryngectomy is pharyngocutaneous fistula (PCF). However, there are no reports of PCF after total laryngectomy caused by 'Kombu' (edible seaweed) as a foreign body in the digestive tract. A 68-year-old Japanese man had undergone total laryngectomy 5 years previously. He presented with PCF, neck swelling and pain. Video endoscopy showed that a dark green foreign body obstructed the digestive tract. PCF was successfully treated via emergency surgery comprising abscess drainage, foreign body removal and fistula closure. The foreign body was kombu. Clinicians who perform total laryngectomy should know the potential dangers of consuming hygroscopic food items that can cause bolus obstruction of the upper digestive tract and pharyngeal abscess and perforation.

The effect of cochlear implants on vestibular-evoked myogenic potential responses and postural stability.

OBJECTIVE: Current spread by electrical stimulation via inserted cochlear implant (CI) electrodes and the consequential increase in sound input can affect the equilibrium of patients. The aim of the present study was to clarify the effect of CIs on the equilibrium of patients through cervical vestibular-evoked myogenic potential (cVEMP) testing and static stabilometry performed with the CIs turned on (CI-on) and off (CI-off). METHODS: This prospective study included nine adult patients who underwent unilateral cochlear implantation surgery at our institution. cVEMP testing and stabilometry were performed before surgery and repeated after surgery in the CI-on and CI-off modes. RESULTS: Before surgery, cVEMP responses were diminished in five of the nine patients (55.6%), while the results of stabilometry were poor in six patients (66.7%). After surgery, both cVEMP responses and stabilometry findings in the CI-off mode exhibited significant deterioration relative to the preoperative results (cVEMP: 7/9, 77.8%; stabilometry: 7/9, 77.8%). However, in the CI-on mode, there were significant improvements in both test results relative to the findings in the CI-off mode for all patients. CONCLUSION: CIs compensated for the surgical trauma-induced deterioration in static postural stability when turned on, resulting in a considerable improvement. Our findings suggest that postoperative cVEMP testing in the CI-on and CI-off modes will enable more accurate assessment of the saccule-inferior vestibular nerve system function after cochlear implant surgery.

Long-term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer.

BACKGROUND: The purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP). METHODS: A total of 17 patients who underwent SCL-CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index-10 (VHI-10), and voice-related quality of life (V-RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13-36 months (term B), and after 37 months (term C). RESULTS: The mean MPT, MFR, G and B GRBAS subscale, VHI-10, and V-RQOL scores improved significantly over time postoperatively. CONCLUSION: Multiple vocal function parameters improved significantly with time due to self-adaptation to a newly created glottis after surgery.

Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

Five-year postoperative outcomes of modified staged canal wall up tympanoplasty for primary acquired cholesteatoma.

OBJECTIVE: For successful canal wall up tympanoplasty (CWUT) for the treatment of cholesteatoma, the restoration of stable middle ear aeration is also important; however, little is known about the dynamics of such aeration or the optimal surgical procedure. In this study, alternative additional surgical procedure was selected based on the grade of middle ear aeration during the second-stage operation. SUBJECTS AND METHODS: Patients included in this study underwent staged CWUT surgeries with mastoid cortex plasty (MCP) for well-aerated ears (grade 3) and bony mastoid obliteration (BMO) for poorly aerated ears (grade 2-0). Of the 115 ears included in this study, 62 were followed for more than 5 years. Recurrence rates with deep retraction pocket formation were assessed using the Kaplan-Meier survival analysis. The aeration was graded as: 0, no aeration; 1, aeration of only the mesotympanum; 2, aeration of the entire tympanic cavity; and 3, aeration of both the tympanic and mastoid cavities. RESULTS: No recurrence was observed in ears associated with grade 3 aeration that underwent MCP or in ears with grade 2 aeration that underwent BMO during second-stage surgery. For grades 0 and 1 aeration ears, the recurrence rates were 8.1% after 5 years and 12.5% after 10 years (p < 0.05), and the aeration of recurrent ears deteriorated to grade 0. CONCLUSION: Aeration during second-stage surgery predicts the final outcome.

Transplanting mouse induced pluripotent stem cells into mouse otocysts in vivo.

The otocyst is an attractive target for studying treatment strategies for genetic hearing loss and for understanding inner ear development. We have previously reported that trans-uterine supplemental gene therapy in vivo into the otocysts of mice, which had a loss of function mutation in a causative gene of deafness, was able to prevent putative hearing loss. We herein set out to clarify the feasibility of allogenic cell transplantation into the mouse otocysts in vivo. We transplanted naive mouse-derived induced pluripotent stem cells (miPSCs) into the otocysts of wild type mice or connexin (Cx) 30 deficient mice, at embryonic day 11.5 (E11.5). The transplanted m-iPSCs survived in the lumens of the inner ears at E13.5 and E15.5 in wild type mice. In the Cx30 deficient mouse, the transplanted cells survived similarly, with some of the transplanted cells migrating into the lining cells of the lumens of the inner ears at E13.5 and showing tumorigenic cell proliferation at E15.5. In addition, engrafted cells appear to be able to differentiate after the cell transplantation. Our results suggest that otocyst transplanted cells survived and differentiated. A Cx30 deficiency may facilitate cell migration. These findings may offer some hope for cell transplantation therapy for profound genetic hearing loss caused by a Cxs deficiency.

A Case of Periodontal Necrosis following Embolization of Maxillary Artery for Epistaxis.

Embolization of the maxillary artery (MA) is a common treatment modality for refractory epistaxis. Tissue necrosis after embolization of the MA is a rare complication. Here, we reported the first case of the development of necrosis of soft tissue and alveolar bone in the periodontium after embolization. A 48-year-old man with poor oral hygiene and a heavy smoking habit was referred to our clinic due to intractable epistaxis. After treatment with anterior-posterior nasal packing (AP nasal packing), the epistaxis relapsed. Therefore, he underwent embolization of the MA. Although he did not experience epistaxis after embolization, periodontal necrosis developed gradually. The wound healed with necrotomy, administration of antibiotics and prostaglandin, and hyperbaric oxygen therapy. We speculated that the periodontal necrosis was provoked by reduction of blood supply due to embolization and AP nasal packing based on this preexisting morbid state in the periodontium. Poor condition of the oral cavity and smoking may increase the risk of periodontal necrosis after embolization.

Protein transduction therapy into cochleae via the round window niche in guinea pigs.

Cell-penetrating peptides (CPPs) are short sequences of amino acids that facilitate the penetration of conjugated cargoes across mammalian cell membranes, and as such, they may provide a safe and effective method for drug delivery to the inner ear. Simple polyarginine peptides have been shown to induce significantly higher cell penetration rates among CPPs. Herein, we show that a peptide consisting of nine arginines ("9R") effectively delivered enhanced green fluorescent protein (EGFP) into guinea pig cochleae via the round window niche without causing any deterioration in auditory function. A second application, 24 hours after the first, prolonged the presence of EGFP. To assess the feasibility of protein transduction using 9R-CPPs via the round window, we used "X-linked inhibitor of apoptosis protein" (XIAP) bonded to a 9R peptide (XIAP-9R). XIAP-9R treatment prior to acoustic trauma significantly reduced putative hearing loss and the number of apoptotic hair cells loss in the cochleae. Thus, the topical application of molecules fused to 9R-CPPs may be a simple and promising strategy for treating inner ear diseases.

Laryngeal reinnervation featuring refined nerve-muscle pedicle implantation evaluated via electromyography and use of coronal images.

OBJECTIVE: To evaluate the long-term efficacy of laryngeal reinnervation via refined nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction to treat unilateral vocal fold paralysis (UVFP), employing laryngeal electromyography (LEMG), coronal imaging, and phonatory function assessment. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: We retrospectively reviewed 12 UVFP patients who underwent refined NMP implantation with arytenoid adduction. Videostroboscopy, phonatory functional analysis, LEMG, and coronal imaging were performed before and 2 years after surgery. In LEMG analysis, a 4-point scale was employed to grade motor unit (MU) recruitment: 4+ reflected no recruitment, 3+ greatly decreased recruitment, 2+ moderately decreased recruitment, and 1+ mildly decreased activity, associated with less than the full interference pattern. Coronal images were assessed in terms of differences in thickness and the vertical positions of the vocal folds. RESULTS: Phonatory function improved significantly after operation in all patients. In terms of LEMG findings, the preoperative MU recruitment scores were 1+ in no patients, 2+ in 4 patients, 3+ in 1 patient, and 4+ in 7 patients. Postoperative MU recruitment results were 1+ in 6 patients, 2+ in 5 patients, 3+ in 1 patient, and 4+ in no patients. Thinning of the affected fold during phonation was evident preoperatively in 9 of 10 patients. The affected and healthy folds were equal in volume in 4 of 9 patients postoperatively. CONCLUSION: The LEMG findings and coronal imaging suggest that NMP implantation may have enabled successful reinnervation of the laryngeal muscles of UVFP patients.

Neurogenesis of the spiral ganglion cells in the cochlea requires the transcriptional cofactor TIS21.

The molecular mechanisms controlling the proliferation and differentiation of spiral ganglion cells (SGCs) in the inner ear are still largely unknown. TIS21 is a transcriptional cofactor that shows antiproliferative, antiapoptotic, and prodifferentiative effects on neural progenitor cells. To investigate the function of TIS21 during SGC development, we analyzed SGC neurogenesis from embryonic day 13.5 (E13.5) to postnatal day 4 (P4) in Tis21-GFP knock-in mice, in which the protein-encoding exon of the Tis21 gene was replaced by EGFP. Through E13.5 to P4, we found fewer SGCs in homozygous Tis21-GFP knock-in mice than in wild-type mice. Our results suggest that TIS21 is required for development of SGCs. Deleting Tis21 may affect progenitor cells or neuroblasts at the beginning of cochlear-vestibular ganglion formation and would consequently lead to a decrease in the number of SGCs.

Over-adduction of the unaffected vocal fold during phonation in the unilaterally paralyzed larynx.

CONCLUSIONS: Over-adduction of the unaffected vocal fold may not compensate vocal function in unilateral vocal fold paralysis (UVFP). OBJECTIVE: To determine whether over-adduction of the unaffected vocal fold has any impact on vocal function in patients with UVFP. METHODS: A total of 101 patients with UVFP who underwent three-dimensional computed tomographic (CT) examination of the larynx served as subjects. Three-dimensional endoscopic images together with coronal images during phonation were produced to evaluate over-adduction of the unaffected fold, posterior glottal gap, and differences in the vertical position and thickness between the vocal folds. Maximum phonation time (MPT) and mean airflow rate (MFR) were measured. RESULTS: In all, 47 patients showed over-adduction. Their MPT and MFR were 4.9 ± 2.9 s and 653 ± 504 ml/s, respectively. The remaining 54 did not show over-adduction. Their MPT and MFR were 4.7 ± 2.7 s and 574 ± 384 ml/s, respectively. There were no significant differences in MPT or MFR between the two groups. Of the 47 patients with over-adduction, 9 showed no posterior glottal gap. However, their vocal function was not significantly different from that of 38 patients with posterior glottal gap or from that of 43 patients without over-adduction and having a posterior glottal gap.

Laryngeal muscle activity in unilateral vocal fold paralysis patients using electromyography and coronal reconstructed images.

OBJECTIVE: To assess laryngeal muscle activity in unilateral vocal fold paralysis (UVFP) patients using laryngeal electromyography (LEMG) and coronal images. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: Twenty-one patients diagnosed with UVFP of at least 6 months in duration with paralytic dysphonia, underwent LEMG, phonatory function tests, and coronal imaging. A 4-point scale was used to grade motor unit (MU) recruitment: absent = 4+, greatly decreased = 3+, moderately decreased = 2+, and mildly decreased = 1+. Maximum phonation time (MPT) and mean flow rate (MFR) were employed. Coronal images were assessed for differences in thickness and vertical position of the vocal folds during phonation and inhalation. RESULTS: MU recruitment in thyroarytenoid/lateral cricoarytenoid (TA/LCA) muscle complex results were 1+ for 4 patients, 2+ for 5, 3+ for 6, and 4+ for 6. MPT was positively correlated with MU recruitment. Thinning of the affected fold was evident during phonation in 19 of the 21 subjects. The affected fold was at an equal level with the healthy fold in all 9 subjects with MU recruitment of 1+ and 2+. Eleven of 12 subjects with MU recruitments of 3+ and 4+ showed the affected fold at a higher level than the healthy fold. There was a significant difference between MU recruitment and the vertical position of the affected fold. CONCLUSIONS: Synkinetic reinnervation may occur in some cases with UVFP. MU recruitments of TA/LCA muscle complex in UVFP patients may be related to phonatory function and the vertical position of the affected fold.