Pleomorphic Adenoma of the External Auditory Canal From Ceruminous Gland Adenoma: Case Report and Review of the Literature.

We describe a right external auditory canal (EAC) recurrent ceruminous pleomorphic adenoma (CPA) accompanied by itching and review the clinical features and histopathology of this disease. A female in her 70s presented with a right EAC mass accompanied by itching. We initially diagnosed the mass as a ceruminous gland adenoma (CGA) following excisional biopsy. Two years and nine months later, the tumor recurred at the same site. A preoperative computed tomography (CT) scan demonstrated no bone destruction, and magnetic resonance imaging (MRI) showed a 1 × 1 cm mass with a clearly defined margin in the right EAC. We completely excised the recurrent tumor using a transmeatal approach under general anesthesia. Histopathology demonstrated haphazard proliferation of tubule-glandular structures lined by two layers of the epithelium in the hypocellular stroma composed of a mucoid matrix. The recurring tumor was diagnosed as a CPA. Here, an EAC tumor-originally diagnosed as a CGA following excisional biopsy-recurred and was subsequently diagnosed as a CPA. CPA can be considered an unusual variant of CGA.

Case report: Concurrent intravestibular schwannoma mimicking Ménière's disease and cochlear hydrops detected via delayed three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging.

Objective: To present a case of intralabyrinthine schwannoma (ILS) presenting as Ménière's disease diagnosed via 4-h delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) and treated successfully using the translabyrinthine approach. Patient: A patient who was diagnosed with intravestibular ILS. Interventions: The patient underwent comprehensive preoperative neurological examinations and MRI. The tumor was resected using the translabyrinthine approach and was pathologically confirmed as schwannoma based on the surgical specimen. Main outcome measures: Preoperative audiogram and vestibular test findings and MRI images. Results: Preoperatively, pure-tone audiogram showed progressive sensorineural hearing loss only on the affected side. The video head impulse test and vestibular evoked myogenic potential test showed vestibular dysfunction on the affected ear. Immediate gadolinium-enhanced T1-weighted MRI revealed an enhanced region in the vestibule. Meanwhile, magnetic resonance cisternography showed a filling defect. Delayed 3D-FLAIR MRI revealed a signal void in the scala media of the cochlea indicative of cochlear hydrops, and a strong signal in the perilymph at the basal cochlea suggestive of impaired blood-labyrinthine barrier. Conclusion: Delayed 3D-FLAIR MRI is useful in diagnosing concurrent ILSs and endolymphatic hydrops.

Remission of Acute Food Protein-Induced Enterocolitis Syndrome Confirmed by Oral Food Challenges in Japan.

The oral food challenge test (OFC) is the gold standard for evaluating the remission of food protein-induced enterocolitis syndrome (FPIES). Few acute FPIES remissions confirmed by OFC were reported. This study aimed to examine the OFC for Japanese children with acute FPIES to evaluate its remission. A retrospective cohort study was performed on children with acute FPIES with remission evaluation by OFC based on one food challenge dose (1/50, 1/10, 1/2, and full dose per day). Acute FPIES remission was observed in 65.2% of patients (15/23 patients). Vomiting episodes occurred with 1/50 full doses on the first day among 75% of positive patients. The median duration between the onset and OFC was 14 months (IQR, 8-24 months). Soy was the most common causative food, followed by egg yolk, milk, and wheat. All patients could receive OFC safely without intensive care unit care, based on the FPIES OFC protocol. The remission rate of acute FPIES was high. However, vomiting episodes commonly occurred with 1/50 full doses on the first day. This study suggested that our OFC protocol for acute FPIES was safe and feasible, but it might be safer for some patients to start at a minimal loading dose.

Isolated Otolith Dysfunction in Persistent Postural-Perceptual Dizziness.

The aims of this study were to investigate otolith dysfunction, especially isolated otolith dysfunction (with preserved semicircular canal function) in persistent postural-perceptual dizziness (PPPD) patients. Twenty-one patients who had been diagnosed with PPPD were enrolled in this study. The subjects filled out questionnaires [the Dizziness Handicap Inventory (DHI) and the Niigata PPPD Questionnaire (NPQ)] and underwent vestibular evoked myogenic potential (VEMP) tests, video head-impulse tests (vHIT), and stabilometry. Among the 21 subjects with PPPD, 9 showed isolated otolith dysfunction, 4 exhibited both otolith dysfunction and semicircular canal dysfunction, and 2 demonstrated isolated semicircular canal dysfunction. Six subjects exhibited normal VEMP and vHIT results. Concerning the subjects' questionnaire scores and stabilometric parameters, there were no significant differences among subgroups when the subjects were classified according to their VEMP and vHIT results while stabilometric parameters obtained in PPPD subjects were significantly increased than published data of healthy subjects. As precipitating conditions for PPPD, vestibular neuritis was the most frequent and the second most was idiopathic otolithic vertigo. In conclusion, the majority of PPPD patients had otolith dysfunction, and most of them showed isolated otolith dysfunction. Idiopathic otolithic vertigo can be a precipitating factor of PPPD. While otolith dysfunction may be associated with initiation of PPPD symptoms, PPPD symptoms are also considered to be associated with other dysfunctions of the sensory processing system.

Evaluation of risk factors for uric acid elevation in COVID-19 patients treated with favipiravir.

The objective of this retrospective study was to identify the clinical risk factor associated with uric acid elevation in coronavirus disease (COVID-19) patients treated with favipiravir. Uric acid elevation was defined as an unexplained increase of ≥1.5 times in the patient's uric acid level from baseline. Twenty-nine COVID-19 patients were included in the study. Uric acid elevation developed during favipiravir therapy in 12 (41.4%) patients and the median onset time was 4.5 days after starting favipiravir. In multiple logistic regression analysis, the favipiravir dosage (adjusted OR = 1.69 [1.02-2.81], P = 0.044) and younger patient age (adjusted OR = 0.91 [0.83-0.99], P = 0.040) were significant clinical risk factors for uric acid elevation. No significant between-group difference was noted in the uric acid elevation and non-elevation groups in the clinical recovery after favipiravir therapy. The uric acid levels of patients administered with favipiravir should be monitored closely.

An increasing trend of human sapovirus infection in Japan, 2009 to 2019: An emerging public health concern.

BACKGROUND: Human sapovirus (SaV) is an important etiologic agent of childhood diarrhea. This study aims to investigate the burden of SaV infection in childhood diarrhea in Japan from 2009-2019, to understand the changes in SaV infection after the introduction of rotavirus (RV) vaccination in Japan in 2011. METHODS: Stool samples were collected from children aged ≤ 12 years old with acute gastroenteritis (AGE) who visited outpatient clinics of six prefectures in Japan. The viral RNA was detected by RT-PCR and genogroups and genotypes were determined through sequence-based analysis. RESULTS: Among 5697 stool samples, 318 (5.6%) samples remained SaV-positives showing the highest prevalence in June and 12-24 month aged children. The most predominant genotype was GI.1 (56.8%), followed by GI.2 (19.2%), GII.1 (10.8%), GIV.1 (9.4%), GI.3 (1.7%), GII.2 (1.4%), GII.3 and GII.5 (0.3%). Importantly, an increasing trend (P = 0.016) of SaV infection was observed during this period. In particular, SaV-detection rate was increased significantly (P = 0.033) from 4.3% in pre-rotavirus (RV)-vaccination era to 6.1% in post-RV-vaccination era. We provided evidence that this increase in SaV infection was mainly attributed by coinfections. CONCLUSIONS: The upward trend of SaV infection, particularly after the introduction of RV-vaccination, is an emerging concern. Attention should be paid to control this upward trend of SaV infection to ensure maximum benefits of implementation of RV vaccines towards reducing overall childhood diarrhea worldwide.

Characteristics of Kawasaki Disease Patients during the COVID-19 Pandemic in Japan: A Single-Center, Observational Study.

BACKGROUND: Under the Coronavirus disease 2019 (COVID-19) pandemic, manifestations in children with Kawasaki disease (KD) are different between the Western and the Eastern countries. Particularly, there has not been a report comparing a series of KD in Japan, where KD was originally discovered and has a large number of registered cases. METHODS: We compared patients with KD under the period of the COVID-19 pandemic in Japan with the report from Italy during its reported period by a retrospective, cohort, observational study in a Japanese single center. RESULTS: Thirty-two patients with typical KD were treated during the study period, while the Italian study reported 10 patients with the signs of KD. Concerning the proof of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, none (0%) of our KD cases showed a positive result and one and no patients developed the macrophage activation syndrome (MAS) and Kawasaki disease shock syndrome (KDSS), respectively; however, eight (80%) patients in the Italian series were confirmed with SARS-CoV-2 infection. MAS and KDSS developed in six and five patients, respectively. CONCLUSIONS: Cases reported as COVID-19 pandemic-related KD in Italy showed significantly different clinical characteristics from the typical KD symptoms known in Japan. Although they show KD-like manifestations, we cannot conclude that SARS-CoV-2 has the same etiology of our 'classic' KD at the present stage.

Pollen-food allergy syndrome and component sensitization in adolescents: A Japanese population-based study.

Allergic rhino-conjunctivitis with pollen allergy has been prevalent worldwide and Pollen-food allergy syndrome (PFAS) refers to individuals with pollen allergy who develop oral allergy syndrome (OAS) on consuming fruits and vegetables. The prevalence of PFAS varies by region and that in Japanese adolescents remains to be elucidated. In this cross-sectional study, we examined the epidemiological characteristics of PFAS in a general population of Japanese adolescents according to pollen allergy, OAS, and IgE component sensitization. Participants comprised adolescents, at age 13 years, from a prospective birth cohort study in Japan. We administered questionnaires to collect information from parents regarding pollen allergy, PFAS and OAS at each child's age 13 years. ImmunoCAP ISAC was used to assess IgE component sensitization. Among 506 participants with a complete questionnaire and ISAC measurement results, 56.5% had a history of hay fever, 16.0% had a history of OAS, 51.0% had pollen allergy, and 11.7% had a history of PFAS; additionally, 72.7% were sensitized to one or more tree, grass, and/or weed allergens. The most common sensitization (95.7%) among adolescents with pollen allergy was to Japanese cedar (Cry j 1). The most common causal foods were kiwi and pineapple (both 39.0%). Knowledge levels about PFAS were poor among affected adolescents. We found a high prevalence of PFAS among adolescents in Japan. Although it affects approximately 1/10 adolescents in the general population, public awareness regarding PFAS is poor. Interventional strategies are needed to increase knowledge and to prevent PFAS in the general population.

Comparison of Two Hepatitis B Vaccination Strategies Targeting Vertical Transmission: A 10-Year Japanese Multicenter Prospective Cohort Study.

In 1985, a hepatitis B (HB) vaccination strategy against vertical HB virus transmission was introduced in Japan that recommended vaccination of infants at two, three, and five months of age (delayed strategy). This schedule was revised in 2013, recommending to vaccinate at birth and at 1 and 6 months of age (non-delayed strategy). We aimed to compare the vertical HB virus transmission rates and immunogenic responses between these two vaccination strategies. This Japanese multicenter prospective cohort study included 222 infants born between 2008 and 2017 to serum hepatitis B surface (HBs) antigen (HBsAg)-positive mothers. During the study period, 136 and 86 infants received delayed and non-delayed strategies, respectively. A positive vertical HB virus transmission was defined as a positive serum HBsAg status. Seropositive immunogenic response was defined as a serum anti-HBs titer of ≥10 mIU/mL. Post-vaccination serum HBsAg positivity rates did not differ significantly between the delayed (0/136 [0.0%, 95% confidence interval, 0.0-2.7%]) and non-delayed (2/86 [2.3%, 95% confidence interval, 0.3-8.1%]) strategy groups. Seropositive immunogenic response rates were 100.0% (136/136) and 97.7% (84/86), respectively. Although this study was under-powered to detect a statistically significant result, no vertical HB virus transmission was observed in the delayed strategy.

Severe olfactory and gustatory dysfunctions in a Japanese pediatric patient with coronavirus disease (COVID-19).

Coronavirus disease (COVID-19) is often characterized by abnormal olfactory and gustatory symptoms in adults; however, detailed studies on pediatric patients with COVID-19 are extremely limited. A 13-year-old Japanese girl presented with fever and cough, and after 2 days, her olfactory and taste sensations suddenly disappeared. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was performed using a nasopharyngeal swab. Because a positive result was seen, she was admitted on the 7th day of illness. On admission, the visual analogue scale (VAS) score for smell and taste was 0 of 100%. An intravenous olfaction test using prosultiamine (Alinamin test) was performed on the 15th day of illness to evaluate olfaction, and an increase in latency (33 seconds) and a decrease in duration (55 seconds) were observed. In the odor identification test using 12 different odor cards, only 7 odors were correctly identified. On the 18th day of illness, SARS-CoV-2 tested negative in the RT-PCR test; simultaneously, the VAS score for smell and taste fully improved to 100 of 100%. On the 77th day of illness, full recovery was confirmed in the Alinamin test (latency, 7 seconds; duration, 82 seconds). In this present case, an improvement in olfactory and gustatory dysfunctions was observed with negative results in RT-PCR test for SARS-CoV-2.

Impact of swimming school attendance in 3-year-old children with wheeze and rhinitis at age 5 years: A prospective birth cohort study in Tokyo.

BACKGROUND: In Japan, swimming school attendance is promoted as a form of therapy or as a prophylactic measure against asthma in young children. However, the putative beneficial effects have not been sufficiently verified. OBJECTIVE: The aim of the present study was to clarify whether or not swimming school attendance at age 3 years affects the onset and/or improvement of wheeze and rhinitis at age 5 years. METHODS: This study was a single-center, prospective, general, longitudinal cohort study (T-CHILD Study). Between November 2003 and December 2005, 1776 pregnant women were enrolled, and their offspring were followed up until age 5 years. Swimming school attendance at age 3 years and the presence of wheeze and/or rhinitis in the previous one year were examined using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The relationship between swimming school attendance and wheeze and/or rhinitis was analyzed using multivariable logistic regression analysis. RESULTS: Data on the 1097 children were analyzed. At age 3 years, 126 (11.5%) children attended a swimming school, and at age 5 years, the prevalence of wheeze was 180 (16.4%) while that of rhinitis was 387 (35.3%). Swimming school attendance at age 3 showed no significant relationship with the development of either wheeze (aOR 0.83, 95% CI (0.43-1.60) or rhinitis (aOR 0.80, 95% CI (0.43-1.60) at age 5. CONCLUSIONS: Swimming school attendance at age 3 years showed neither a preventive nor therapeutic effect on wheeze or rhinitis at age 5 years. There is thus no scientific evidence yet that swimming school attendance has a positive impact on the development of childhood wheeze or rhinitis.

[A CASE OF EOSINOPHILIC GASTROENTERITIS FOUND BY PICA DURING ORAL IMMUNOTHERAPY].

Eosinophilic esophagitis has been reported as a complication of oral immunotherapy (OIT), but there are only a few reports of eosinophilic gastroenteritis (EGE) occurring after OIT. EGE causes eosinophil infiltration into the gastrointestinal (GI) tract and is characterized by various digestive symptoms. We report the case of a 6-year-old boy with EGE. He was diagnosed as having immediate-type food allergies (egg, milk and wheat) by oral food challenges at 1 year of age. OIT for each food was carried out, and the amounts of the offending foods were able to be gradually increased without causing any immediate-type allergy symptoms. However, the total IgE and specific IgE values were remarkably increased at the age of 4 years and 4 months. He first developed oral mucosa symptoms and vomiting at 4 years and 10 months of age, and they gradually worsened. Stopping eggs and milk alleviated the symptoms. Nevertheless, he still occasionally vomited. He started Pica eating disorder (sand and sponge) due to anemia from 5 years and 10 months of age and developed eosinophilia without diarrhea or bloody stool. Upper and lower GI tract endoscopic examinations found no bleeding. The GI mucosa showed eosinophil infiltration of more than 40/high-power field in the stomach and duodenum, so he was diagnosed with EGE. No eosinophils were found in the esophageal mucosa. His GI symptoms and anemia improved on a multiple-food-elimination diet. Patients undergoing OIT should be closely followed up for a long time, and those with GI symptoms should be evaluated by GI endoscopy.

Avoidance of Hen's Egg Based on IgE Levels Should Be Avoided for Children With Hen's Egg Allergy.

Background: Although hen's egg (HE) allergy was thought to be usually resolved by late childhood, majority of HE allergy patients with a high level of egg white (HEW)-specific IgE could not acquire tolerance for HE by age 8 years. Objective: The aim is to investigate whether the avoidance of HE until 6 years of age increased the risk of heated HE allergy at age 6 years. Methods: This was a retrospective case-control study. The HE tolerance children (n = 17) and children with low-dose HE reactor [a positive reaction to ≤ 4 g of heated HEW in oral food challenges (OFCs)] children (n = 26) were included based on the results of OFC at 6 years old. Multivariate logistic regression analysis was applied to examine the associations between HE avoidance until age 6 years and HE allergy status confirmed by OFC, adjusting the level of ovomucoid-specific IgE (OM-sIgE) during early infancy. Results: A lower proportion of strict avoidance of HE was observed in the HE tolerance group than in the low-dose HE reactor group (6 vs. 46%, p = 0.006). OM-sIgE levels in children younger than 2 years old were significantly higher in the low-dose HE reactor group than those in the HE tolerance group (median [interquartile], 26.7 UA/mL [11.9-53.4] vs. 7.9 UA/mL [0.35-23.4]; p =0.024). The avoidance of HE until 6 years of age increased the risk of heated HE allergy even after adjusting OM-sIgE levels. Conclusions: The long-term avoidance of HE from infancy increased the risk of heated HE allergy confirmed by OFC at age 6 years.

Early Development of Resident Macrophages in the Mouse Cochlea Depends on Yolk Sac Hematopoiesis.

Resident macrophages reside in all tissues throughout the body and play a central role in both tissue homeostasis and inflammation. Although the inner ear was once believed to be "immune-privileged," recent studies have shown that macrophages are distributed in the cochlea and may play important roles in the immune system thereof. Resident macrophages have heterogeneous origins among tissues and throughout developmental stages. However, the origins of embryonic cochlear macrophages remain unknown. Here, we show that the early development of resident macrophages in the mouse cochlea depends on yolk sac hematopoiesis. Accordingly, our results found that macrophages emerging around the developing otocyst at E10.5 exhibited dynamic changes in distribution and in situ proliferative capacity during embryonic and neonatal stages. Cochlear examination in Csf1r-null mice revealed a substantial decrease in the number of Iba1-positive macrophages in the spiral ganglion and spiral ligament, whereas they were still observed in the cochlear mesenchyme or on the intraluminal surface of the perilymphatic space. Our results demonstrated that two subtypes of resident macrophages are present in the embryonic cochlea, one being Csf1r-dependent macrophages that originate from the yolk sac and the other being Csf1r-independent macrophages that appear to be derived from the fetal liver via systemic circulation. We consider the present study to be a starting point for elucidating the roles of embryonic cochlear resident macrophages. Furthermore, resident macrophages in the embryonic cochlea could be a novel target for the treatment of various inner ear disorders.

Prevalence Of Unplanned Readmissions Among Patients Of Military Treatment Facilities.

Understanding readmissions within the Military Health System (MHS) provides important insights to better understand and improve health outcomes for military personnel and their families. We assessed all-cause seven- and thirty-day readmission rates in military treatment facilities by treatment service for patients ages 18-64 for fiscal years 2011-18 using inpatient data from the MHS and the private sector. We compared unplanned readmission rates for the obstetric, medical, and surgical product lines. Readmission rates differed by product line. Seven-day readmission rates ranged from 1.5 percent to 3.3 percent by product line, and thirty-day rates ranged from 3.2 percent to 8.8 percent. The obstetric line had the greatest number of readmissions (391,463) but the lowest seven-day readmission rate (1.5 percent). Readmission rates were lower for the military population than for people in other insurance groups, but military readiness is disrupted by unplanned readmissions. Product-line differences in readmission rates in the MHS suggest opportunities for improvement.

In vitro Methods to Cultivate Spiral Ganglion Cells, and Purification of Cellular Subtypes for Induced Neuronal Reprogramming.

Hearing loss can develop as a consequence of primary auditory neuron degeneration. These neurons are present within the spiral ganglion of the inner ear and co-exist with glial cells that assist in neuronal maintenance and function. There are limited interventions for individuals with hearing impairment, hence novel biological solutions must be explored. Regenerative strategies can benefit from in vitro methods to examine the long-term culture of purified cell populations. The culturing of neuronal, glial, and non-neuronal, non-glial cell types in both neonatal and adult mice is presented along with the whole-organ explant culture of the spiral ganglion. High yields of spiral ganglion glial and non-glial cells were cultured from both neonatal and adult mice. Dissociated spiral ganglion cells from Sox2-EGFP mice were sorted based on EGFP expression using fluorescence activated cell sorting. The EGFP+ fraction included purified glial populations, whereas the EGFP- fraction contained non-glial cells. Purified glial cells could be reprogrammed into induced neurons displaying neuronal markers and morphology at a higher efficiency than non-glial cells. Previous studies have only allowed for the short-term culturing of spiral ganglion cell populations and have placed emphasis on neonatal cells. There has also been a lack of methods able to cultivate pure cell populations. Here, the coupling of transgenic mouse lines, fluorescence activated cell sorting and advanced culture conditions allow cultivation and characterization of neuronal, glial and non-neuronal, non-glial cells from the spiral ganglion. These techniques are used to demonstrate that different spiral ganglion cell subtypes (glial vs. non-glial) display different competencies for direct neuronal reprogramming.

Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation.

The hybrid or electric-acoustic stimulation cochlear implant is indicated in patients with a residual hearing at low frequencies. It provides electric and acoustic stimulation for compensating for high- and low-frequency sounds, respectively. However, the implantation procedure damages the cochlea, resulting in loss of the residual-hearing and diminished effects of the acoustic-hearing in several patients. To prevent hearing loss after implantation, corticosteroids have been used clinically although their effects are limited. As an alternative to corticosteroids, insulin-like growth factor 1 (IGF1) has shown potent effects in various types of cochlear injury. In this study, the effects of IGF1 on hearing preservation were examined after cochlear implantation to a normal-hearing guinea pig model. The electrode was inserted in an atraumatic way through the round window membrane of guinea pigs with the application of a gelatin-sponge soaked with IGF1 or saline. The auditory brainstem response (ABR) was recorded pre-operatively, immediately after cochlear implantation, and 7, 14, 28, and 56 days after electrode insertion. In comparison to the control group, the IGF1-treated group showed better hearing preservation at low frequencies, 7 days after surgery. IGF1 application was effective at low frequencies (2 and 4 kHz) throughout the period of examination. Histological studies revealed that outer hair cell numbers, in the IGF1-treated group, were maintained in the cochlear region responsible for low-frequency hearing (upper midbasal turn) and that there was less fibrous tissue formation around the electrode. Both the outer hair cell counts and the extent of fibrosis significantly correlated with the ABR threshold shifts at low frequencies. These results indicate that IGF1 might attenuate loss of low-frequency hearing after cochlear implantation, suggesting its possible clinical use in soft surgeries involving cochlear implants with electric-acoustic stimulation for hearing preservation.

Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy.

Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.