The error patterns of phonemes in children with prelingual hearing loss: A comparison between hearing aid and cochlear implant users.

OBJECTIVE: To reveal differences in error pattern of phonemes and articulation between children using cochlear implants (CIs) and those using hearing aids (HAs) due to prelingual hearing disorder and help the education of children with prelingual hearing loss. METHOD: Children with prelingual hearing loss who were receiving auditory-verbal preschool education at an auditory center for hearing-impaired children (Fujimidai Auditory Center, Tokyo, Japan) from 2010 to 2020 were analyzed retrospectively. All participants underwent pure tone audiometry and monosyllabic intelligibility tests. The error answers were categorized into five patterns which was characterized by the substitution, addition, omission, failure, and no response according to consonant errors. In addition, the consonant errors classified into the manner of articulation and the differences of error patterns were analyzed between the HA and the CI group descriptively. RESULTS: A total of 43 children with bilateral HAs and 46 children with bimodal CIs or bilateral CIs were enrolled. No significant between-group differences in median phoneme intelligibility were found. The most common error pattern was substitution in both HA and CI groups. The error number of addition pattern in the HA group was smaller than in the CI group. In both groups, the most common errors of articulation were flap errors, and the most common error patterns were flaps to nasals, nasals to nasals, plosives to plosives. In the HA group, plosives and nasals tended not to be recognized and in the CI group plosives were prone to be added to vowels. CONCLUSIONS: There were some different error patterns of articulation and consonant substitution between groups. Clarifying differences of phoneme that are difficult to hear and tend to be misheard would help for creating an effective approach to auditory training for children with hearing loss.

Prediction of Cochlear Implant Effectiveness With Surface-Based Morphometry.

OBJECTIVE: This study aimed to determine whether surface-based morphometry of preoperative whole-brain three-dimensional T1-weighted magnetic resonance imaging (MRI) images can predict the clinical outcomes of cochlear implantation. STUDY DESIGN: This was an observational, multicenter study using preoperative MRI data. SETTING: The study was conducted at tertiary care referral centers. PATIENTS: Sixty-four patients with severe to profound hearing loss (≥70 dB bilaterally), who were scheduled for cochlear implant (CI) surgery, were enrolled. The patients included 19 with congenital hearing loss and 45 with acquired hearing loss. INTERVENTIONS: Participants underwent CI surgery. Before surgery, high-resolution three-dimensional T1-weighted brain MRI was performed, and the images were analyzed using FreeSurfer. MAIN OUTCOME MEASURES: The primary outcome was monosyllable audibility under quiet conditions 6 months after surgery. Cortical thickness residuals within 34 regions of interest (ROIs) as per the Desikan-Killiany cortical atlas were calculated based on age and healthy-hearing control regression lines. RESULTS: Rank logistic regression analysis detected significant associations between CI effectiveness and five right hemisphere ROIs and five left hemisphere ROIs. Predictive modeling using the cortical thickness of the right entorhinal cortex and left medial orbitofrontal cortex revealed a significant correlation with speech discrimination ability. This correlation was higher in patients with acquired hearing loss than in those with congenital hearing loss. CONCLUSIONS: Preoperative surface-based morphometry could potentially predict CI outcomes and assist in patient selection and clinical decision making. However, further research with larger, more diverse samples is necessary to confirm these findings and determine their generalizability.

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial.

PURPOSE: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.

A High Risk of Missing Congenital Cytomegalovirus-Associated Hearing Loss through Newborn Hearing Screening in Japan.

It remains unclear to what extent newborn hearing screening (NHS) detects congenital cytomegalovirus (cCMV)-associated sensorineural hearing loss (SNHL) in Japan. This study aimed to clarify the NHS results and audiological characteristics of patients with cCMV-associated SNHL. A total of 541 individuals with unilateral or bilateral hearing loss of unknown etiology were examined for cCMV infection. cCMV infection was defined by the presence of CMV DNA in the dried umbilical cord detected using real-time quantitative PCR. NHS results and audiological data were retrospectively obtained from medical records. Forty-four cases (8.1%) were positive for cCMV infection. Of them, 33 cases underwent NHS and 13 cases (39.4%) passed NHS bilaterally. The pure-tone audiograms of 21 patients were obtained. There were seven cases of unilateral SNHL, five cases of asymmetric bilateral SNHL, and nine cases of symmetric bilateral SNHL. cCMV-related hearing loss is highly heterogeneous, and there is a high risk of missing this condition through NHS.

The impact of second-hand smoke on ear, nose, and throat diseases and head and neck cancers in Japan: a cross-sectional study using a questionnaire and secondary data from the national health and nutrition survey.

BACKGROUND: The risk of head and neck cancers (HNCs) and ear, nose, and throat (ENT) diseases due to second-hand smoke (SHS) have not been fully assessed. OBJECTIVE: To determine which ENT diseases or HNCs are associated with SHS. MATERIAL AND METHODS: Data from a survey of a cross-sectional sample of ENT patients (n = 1228) on SHS exposure were compared to control-subject data (n = 6598) from a Japan National Health Survey. Multivariate logistic regression and estimated odds ratios (ORs) determined whether SHS-disease associations were related to exposure location and disease occurrence. RESULTS: SHS was significantly associated with acute tonsillitis (OR in workplaces, 2.24 [95% CI, 1.34-3.75]; OR in restaurants, 4.24 [95% CI, 2.50-7.19]; OR in leisure places, 4.72 [95% CI, 2.93-7.62]); recurrent tonsillitis (OR in restaurants, 4.24 [95% CI, 2.52-7.13]; OR in leisure places, 5.29 [95% CI, 3.31-8.46]); facial palsy (OR in home, 2.18 [95% CI, 1.25-3.81]; OR in leisure places, 3.41 [95% CI, 1.97-5.89]); hypopharyngeal cancer (OR in home, 2.51 [95% CI, 1.18-5.36]; OR in workplaces, 2.53 [95% CI, 1.24-5.15]); and laryngeal cancer (OR in home, 2.44 [95% CI, 1.04-5.68]; OR in leisure places, 2.25 [95% CI, 1.00-5.07]). CONCLUSIONS AND SIGNIFICANCE: SHS may contribute to HNCs and ENT diseases, suggesting that merely being in the presence of smokers could increase the risk of head and neck morbidities.

Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0-1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24-68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options.This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

Assessment of speech perception in deaf or hard of hearing children who received auditory-verbal therapy with hearing aids or cochlear implants.

OBJECTIVES: To reframe the criteria for pediatric cochlear implants (CIs) in Japan, we investigated monosyllabic and word speech perception at the time of school entry in deaf or hard of hearing (D/HH) children who underwent auditory-verbal therapy (AVT) with hearing aids (HAs) or CIs in early childhood. METHODS: D/HH children who started AVT at Fujimidai Auditory Center for Hearing-Impaired Children before the age of 1 year and who underwent auditory assessment in the previous year of schooling (at the age of 5 or 6) from 2010 to 2020 were enrolled in this study. The results of hearing level tests with or without amplification and monosyllabic and word speech discrimination were assessed. RESULTS: The children with profound hearing impairment (>90 dB HL) had worse speech perception than children with CIs. The children with severe hearing impairment (>70-90 dB HL) did not show any significant differences in speech perception compared with the children with CIs. The children with HAs with a wearing threshold <40 dB HL did not show any significant differences in speech perception from the children with CIs. CONCLUSION: D/HH children with audiologic thresholds greater than 90 dB HL or aided thresholds greater than 40 dB HL should be considered for CIs to ensure development of appropriate listening and spoken language.

Effective sound therapy using a hearing aid and educational counseling in patients with chronic tinnitus.

OBJECTIVE: This study aimed to assess the effectiveness of our sound therapy with appropriate hearing aid fitting and periodic hearing aid adjustment in patients with chronic tinnitus. METHODS: We conducted a retrospective study. The study included 490 individuals who received treatment with hearing aids for chronic tinnitus at least for 3 months. To determine the effects of tinnitus on patients' quality of life, the participants completed a series of questionnaires, including the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS) for loudness and annoyance, and questionnaires of subjective symptom improvement. Data were collected at entry and 3 months and 1 year after treatment initiation. RESULTS: All 490 participants completed the questionnaires at 3 months; however, only 312 completed them at 1 year. The mean ± standard deviation THI score before treatment decreased significantly at 3 months (490 participants: 53 ± 25 to 11 ± 16 and 312 participants: 55 ± 24 to 12 ± 16) and 1 year (55 ± 24 to 9 ± 14) (P < 0.01). The mean VAS score for tinnitus loudness before treatment decreased significantly at 3 months (490 participants: 70 ± 22 to 25 ± 27 and 312 participants: 71 ± 22 to 27 ± 26) and 1 year (71 ± 22 to 21 ± 28) (P < 0.01). In addition, the mean VAS score for tinnitus annoyance before treatment decreased significantly at 3 months (490 participants: 75 ± 26 to 20 ± 26 and 312 participants: 75 ± 25 to 23 ± 27) and 1 year (75 ± 25 to 17 ± 26) (P < 0.01). Approximately 80% of patients noticed improvements in their tinnitus annoyance and loudness, as determined by their responses to the questionnaires of subjective symptom improvement. CONCLUSION: The results of this study suggest that treatment with sound therapy may ameliorate the symptoms of chronic tinnitus associated with hearing loss.

Cochlear Implantation in Cases of Inner Ear Malformation: A Novel and Simple Grading, Intracochlear EABR, and Outcomes of Hearing.

OBJECTIVE: To propose a simple grading of inner ear malformation (IEM) and investigate intracochlear electrical auditory brainstem response (EABR) and outcomes for hearing in terms of the novel grading system. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Sixty patients with IEMs who received cochlear implants. INTERVENTION: Grading according to observation of modiolus deficiency and/or internal auditory canal (IAC) cochlear nerve deficiency (CND). MAIN OUTCOME MEASURE: Intracochlear EABR and categories of auditory performance (CAP) scores were assessed; children in school were categorized according to the type of school attended. RESULTS: Among 60 patients, 38% were classified as Grade I (modiolus present + normal cochlear nerve), 22% as grade II (modiolus deficiency + normal cochlear nerve), 33% as grade III (modiolus present + IAC CND), and 7% as grade IV (modiolus deficiency + IAC CND). During the operation, 93% of Grade I, 36% of Grade II, 23% of Grade III, and 50% of Grade IV patients showed typical EABR waves. CAP scores of 4 or more were obtained from 91% of Grade I, 62% of Grade II, 35% of Grade III, and 25% of Grade IV. Whereas none of children in Grades III and IV entered main stream school, 55% of Grade I and 25% of Grade II entered mainstream schools. CONCLUSIONS: Outcomes of hearing with cochlear implantations in IEM children depend on the severity of IEM and IAC CND. Our novel grading of IEM is simple and can be useful for understanding the severity of IEM.

EABR measurements during cochlear implantation in one-year-old, infant, child, adult, and elderly patients.

BACKGROUND: Clinical application of electrically-evoked intracochlear auditory brainstem responses (eABRs) for evaluation of brainstem maturity or aging changes has not been well investigated. AIM/OBJECTIVE: We compare the eV latencies of intraoperative eABR measurements in one-year-olds, infants, children, adults, and the elderly, with the goal of investigating the changes in the brainstem auditory pathway due to development and aging. MATERIALS AND METHODS: We studied 58 ears of 51 patients who underwent cochlear implantation between 2013 and 2019 using MED-EL's Concerto or Synchrony implants with Flex28 or Flex soft electrodes. EABRs were recorded during cochlear implantation. The stimuli were delivered by the MED-EL Maestro to the apical, middle, and basal turn electrodes at stimulus levels 1000, 800, and 600 cu, with a pulse width of 30 µs. RESULTS: In eABRs recorded from electrodes installed at both the mastoid and nape, there was no difference in latency between age groups within each stimulus level. CONCLUSION AND SIGNIFICANCE: ABR latency was not affected by development after age one and aging of the brainstem auditory pathway. Our study will be useful as a control in identifying abnormal eABR wave configurations in patients with cochlear malformations, cochlear nerve deficiencies, or auditory neuropathy, regardless of age.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Age-related change of auditory functional connectivity in Human Connectome Project data and tinnitus patients.

BACKGROUND: We reported that tinnitus patients showed reduced levels of auditory functional connectivity (FC) in comparison with normal hearing control subjects, and that we succeeded in objective diagnosis of tinnitus with 86% sensitivity and 74% specificity by focusing only on auditory-related FC. However, the age-related change of auditory FC is not clarified. In this study, we examine age-related change of the auditory FC using the database of Human Connectome Project (HCP) and compared with our database of tinnitus patients. METHOD: From the HCP database HCP Lifespan Pilot project, we studied five age groups, 8 to 9 years old, 14 to 15, 25 to 35, 45 to 55, and 65 to 75. We also applied our tinnitus patients' resting-state functional magnetic resonance imaging (fMRI) database, which is divided into three generations; 20 to 40 years old, 40 to 60, and 60 to 80 to compare with the HCP database. The resting state fMRI analyses were performed using the CONN toolbox version 18. As auditory-related regions, Heschl's gyrus, planum temporale, planum polare, operculum, insular cortex, and superior temporal gyrus were set as the regions of interest from our previous reports. RESULT: Auditory FC is strongest among adolescents and reduces with age. But the auditory FC of tinnitus patients were significantly less than those of HCP data in each generation. CONCLUSION: Although auditory FC decreases with age, tinnitus patients have less auditory FC compared with age-matched controls. The age-matched cutoff values are necessary for an objective diagnosis of tinnitus with resting state fMRI.

A multicenter phase II trial of paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA-SCCHN. METHODS: Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration-time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2 , 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. RESULTS: Thirty-five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment-related death was seen. CONCLUSIONS: PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA-SCCHN.

Electrically evoked ABR during cochlear implantation and postoperative development of speech and hearing abilities in infants with common cavity deformity as a type of inner ear malformation.

Background: The electrically evoked auditory brainstem response (eABR) during cochlear implantation in common cavity (CC) deformity has not been clinically well studied.Aim/Objective: To investigate the eABR wave configuration during cochlear implantation, the postoperative development of hearing, and educational settings in infants with CC deformity.Materials and Methods: Nine infants who were congenitally deaf and found to have CC deformity and suspected cochlear nerve deficiency by temporal bone CT and MRI were studied. All of them underwent sequential and unilateral cochlear implantation and their eABRs were recorded during the surgery. The postoperative development was followed up.Results: eABRs of all the nine infants with CC deformity showed that the mean peak of the evoked wave V (eV) was the same as that in controls at latencies but was twofold higher than that in controls at thresholds and their postoperative hearing thresholds improved markedly.Conclusion and Significance: The brainstem auditory pathways of the infants were considered intact on the basis of the eV peak latencies in the eABRs. The postoperative development of their speech and hearing abilities and their educational settings varied, probably because of the twofold higher thresholds of their eABRs and limited number of auditory neural units.

A clinical and genetic study of 16 Japanese families with Waardenburg syndrome.

The purpose of this study is to profile the clinical and genetic features of Japanese Waardenburg syndrome (WS) patients and validate the W index. Sixteen Japanese WS families with congenital sensorineural hearing loss were included in the study. The inner canthal, interpupillary, and outer canthal distances (ICD, IPD, and OCD) were measured for all patients, and patients were screened for presence of PAX3, MITF, SOX10, and EDNRB mutations. The WS patients were clinically classified under the current W index as follows: 13 families with WS1, 2 families with WS2, and 1 family with WS4. In the 13 WS1 families, genetic tests found PAX3 mutations in 5 families, MITF mutations in 4 families, SOX10 mutations in 3 families, and EDNRB mutations in 1 family. 61% of clinically classified WS1 patients under the current W index conflicted with the genetic classification, which implies W index is not appropriate for Japanese population. Resetting the threshold of W index or novel index formulated with ethnicity matched samples is necessary for clinical classification which is consistent with genetic classification for WS patients with distinct ethnicity.

Development of vestibular ocular reflex and gross motor function in infants with common cavity deformity as a type of inner ear malformation.

Background： The function of common cavity deformity demonstrated by temporal bone CT and MRI has been unknown. AIM/OBJECTIVE: To investigate the developmental changes of vestibular ocular reflex and acquisition of postural control in infants with common cavity deformity. MATERIAL AND METHODS: Eight infants who were congenitally deaf complicated by common cavity deformity were studied. The damped rotational chair test was carried out to evaluate vestibular ocular reflex. Acquisition of head control and independent walking in these infants was compared with that in normal infant's milestones of gross motor development. RESULTS: All of the eight infants with common cavity deformity did not show per-rotatory nystagmus in the damped rotational chair test around the first year of life. However, a normal number of beats and a longer duration of per-rotatory nystagmus for their age were recorded at around three or four years of age. CONCLUSIONS AND SIGNIFICANCE: In the eight infants with common cavity deformity, vestibular ocular reflex was not present around the first year of life, but appeared after three or four years probably because of some vestibular sensory cells. Head control and independent walking were delayed but eventually acquired by the central vestibular compensation.

Elongated EABR wave latencies observed in patients with auditory neuropathy caused by OTOF mutation.

OBJECTIVES: We sought to determine how the pathology altered electrically evoked auditory brainstem responses (EABRs) in patients with hearing loss by evaluating EABRs in auditory neuropathy patients with OTOF mutations comparing with various types of congenital deafness. METHODS: We included 15 patients with congenital hearing loss, grouped according to pathology: OTOF mutations (n = 4), GJB2 mutations (n = 4), SLC26A4 mutations (n = 4), or cytomegalovirus infections (n = 3). EABRs were recorded when patients underwent cochlear implantation surgery. We evaluated the latencies and amplitudes of the recorded EABRs and compared them statistically between four groups. RESULTS: The EABR latencies of Wave III and Wave V, and of the interval between them, were significantly longer in the OTOF mutation group than in the GJB2 and SLC26A4 mutation groups (Wave III) and in all three other groups (Wave V and Wave III-V latency); amplitudes were not significantly different between groups. CONCLUSIONS: Our results suggest OTOF mutations cause delayed (or slowed) postsynaptic neurotransmission, although the presumed mechanism involved reduced presynaptic transmission between hair cells and spiral ganglion neurons. LEVEL OF EVIDENCE: Mainly a case report.

Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial.

OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.

Auditory Related Resting State fMRI Functional Connectivity in Tinnitus Patients: Tinnitus Diagnosis Performance.

OBJECTIVE: The purpose of the present study was to investigate functional connectivity in tinnitus patients with and without hearing loss, and design the tinnitus diagnosis performance by resting state functional magnetic resonance imaging (rs-fMRI). SUBJECTS AND METHODS: Nineteen volunteers with normal hearing without tinnitus, 18 tinnitus patients with hearing loss, and 11 tinnitus patients without hearing loss were enrolled in this study. The subjects were evaluated with rs-fMRI, and region of interests (ROIs) based correlation analyses were performed using the CONN toolbox version 16 and SPM version 8. The correlation coefficients from individual level results were converted into beta values. RESULTS: With a beta threshold of more than 0.2, 91% of all possible connections between auditory-related ROIs (Heschl's gyrus, planum temporale, planum polare, operculum, insular cortex, superior temporal gyrus) in the control group remained intact, whereas 83 and 66% of such connections were present in the hearing loss and the normal-hearing tinnitus group. However, between non-auditory-related ROIs, the rates of intact connections at a beta threshold of more than 0.2 were 17% in the control group, and 16 and 15% in the tinnitus groups. When resting state fMRI positive is defined as less than 9% of all possible connections between auditory-related ROIs with a beta threshold of more than 0.7, the sensitivity and specificity of tinnitus diagnosis is 86 and 74%, respectively. CONCLUSIONS: The associations between auditory-related networks are weakened in tinnitus patients, even if they have normal hearing. It is possible that rs-fMRI can be a tool for objective examination of tinnitus, by focusing the auditory-related areas.

A rare case of bilateral vagus nerve schwanomatosis.

Schwanomatosis is the third most common form of neurofibromatosis. Schwanomatosis affecting the vagus nerve is particularly rare. In this report, we describe an extremely rare case bilateral vagus nerve schwanomatosis in a 45-year-old male patient. The patient initially presented with bilateral neck tumors and hoarseness arising after thoracic surgery. We performed left neck surgery in order to diagnose and resect the remaining tumors followed by laryngeal framework surgery to improve vocal cord closure and symptoms of hoarseness. Voice recovery was successfully achieved after surgery. An appropriate diagnosis and surgical tumor resection followed by phonosurgery improved patient quality of life in this rare case.