Epidemiology, aetiology and diagnosis of congenital hearing loss via hearing screening of 153 913 newborns.

BACKGROUND: Congenital hearing loss (HL), one of the most common paediatric chronic conditions, significantly affects speech and language development. Its early diagnosis and medical intervention can be achieved via newborn hearing screening. However, data on the prevalence and aetiology of congenital HL in infants who fail newborn hearing screening are limited. METHODS: The sample population included 153 913 infants who underwent newborn hearing screening, and the prevalence of congenital HL, defined as moderate to profound bilateral HL (BHL) or unilateral HL (UHL) (≥40 dB HL), in one prefecture of Japan was measured to minimize the loss-to-follow-up rate, a common factor affecting the screening procedure. Comprehensive aetiological investigation, including physiology, imaging, genetic tests, and congenital cytomegalovirus screening, was performed on children diagnosed with congenital HL. RESULTS: The calculated prevalence of congenital HL was 1.62 per 1000 newborns (bilateral, 0.84; unilateral, 0.77). More than half of the cases with congenital bilateral or severe to profound UHL showed genetic aetiology or cochlear nerve deficiency (CND), respectively. Approximately 4% and 6% of the cases of congenital BHL and UHL were associated with congenital cytomegalovirus infection and auditory neuropathy spectrum disorder, respectively. CONCLUSIONS: This is an epidemiological and comprehensive aetiological study of congenital HL, as determined via newborn hearing screening according to its severity and laterality, in a large-scale general population of a developed country. Our findings can serve as a reference for optimizing care and intervention options for children with HL and their families.

Auditory Neuropathy Spectrum Disorder Progressing with Motor and Sensory Neuropathy Caused by an ATP1A1 Variant.

We encountered a 27-year-old Japanese woman with sensorineural deafness progressing to motor and sensory neuropathy. At 16 years old, she had developed weakness in her lower extremities and hearing impairment, which gradually deteriorated. At 22 years old, combined audiological, electrophysiological, and radiological examination results were consistent with auditory neuropathy spectrum disorder (ANSD). Genetic analyses identified a previously reported missense variant in the ATP1A1 gene (NM_000701.8:c.1799C>G, p.Pro600Arg). Although sensorineural deafness has been reported as a clinical manifestation of ATP1A1-related disorders, our case suggested that ANSD may underlie the pathogenesis of deafness in ATP1A1-related disorders. This case report broadens the genotype-phenotype spectrum of ATP1A1-related disorders.

The relationship between preoperative factors and the pattern of longitudinal improvement in speech perception following cochlear implantation.

BACKGROUND: Many studies have discussed the factors influencing hearing outcomes after cochlear implantation, but few have addressed improvements in speech perception for these patients over time. OBJECTIVE: To investigate the relationship between preoperative factors and the pattern of longitudinal improvement in speech perception following cochlear implantation (CI). MATERIALS AND METHODS: This study enrolled 83 patients (96 ears) who underwent CI at Shinshu University Hospital. The patients were assessed up to 12 months after CI by a monosyllable test, and showed either delayed improvement (DI), early improvement (EI), or stable improvement (SI) when compared with their preoperative score. Eight preoperative variables were also examined for their effects on speech perception over time. RESULTS: The DI, EI, SI groups comprised 35.4%, 43.8%, and 20.8% of all patients, respectively. Patients in the DI group were older at surgery than those in the EI and SI groups, and their onset age were also older than that in the SI group. No other preoperative variables showed significant differences across the three groups. CONCLUSIONS AND SIGNIFICANCE: Our findings revealed that age at implantation and age at onset of hearing loss significantly affected the improvement pattern of speech perception. Age may be useful in predicting recovery of speech perception after CI.

Impact of Low Skeletal Muscle Mass on the Prognosis of Patients with Head and Neck Cancer Treated Nonsurgically.

INTRODUCTION: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. METHODS: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. RESULTS: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. CONCLUSION: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

Audiological Features in 63 Patients With Cochlear Nerve Deficiency.

OBJECTIVE: We aimed to investigate the clinical features of cochlear nerve deficiency (CND), and in particular, the long-term course of hearing disability and audiogram shapes. STUDY DESIGN: Retrospective observational nonrandomized group study. SETTING: Academic medical center. PATIENTS/INTERVENTIONS: The subjects were 63 children with congenital hearing loss who visited our hospital between 2009 and 2019 and underwent MRI, based on which they were diagnosed with CND. There were 61 cases of unilateral CND and two cases of bilateral CND. MAIN OUTCOME MEASURES: Imaging tests by MRI and CT and audiometric assessments by pure-tone audiometry and distortion product otoacoustic emission were performed. RESULTS: Among the cases of CND diagnosed by assessing the cochlear nerve on MRI, approximately 20% of the bony cochlear nerve canals that could be assessed on CT were normal. Of the 61 cases diagnosed with unilateral CND, 55 cases had cochlear nerve aplasia (90.2%), and six had cochlear nerve hypoplasia (9.8%), with a mean hearing ability of 92.2 and 94.6 dB HL, respectively. Thus, the majority of cases had severe-to-profound hearing loss. The overall audiometric patterns were 78.7% flat, 9.8% cookie-bite, and 9.8% high-frequency. Six of 61 cases (9.8%) had a distortion product otoacoustic emission (DPOAE) response based on the affected side, and none of the cases lost the response during follow-up. CONCLUSIONS: Herein, we report the largest study on CND and performed CND image and audiometric assessments. Accurately in diagnosing CND requires not only CT but also MRI assessment. Hearing loss is often severe to profound; however, various audiometric patterns have been observed. CND includes a small number of cases that respond to DPOAE, indicating that some CND cases are clinically diagnosed with auditory neuropathy spectrum disorder (ANSD). A sustained DPOAE response might help in differentiating CND from other ANSDs. Children with congenital deafness who have passed the newborn hearing screening by DPOAE should be examined by MRI to rule out CND.

Frequency and natural course of congenital cytomegalovirus-associated hearing loss in children.

BACKGROUND: Congenital cytomegalovirus-associated hearing loss (cCMV-associated HL) is a common cause of congenital or early-onset deafness. Although cCMV infection has been reported to lead to various types of HL, the natural course of cCMV-associated HL over a long period is not yet known. OBJECTIVES: To investigate the clinical phenotype of cCMV-associated HL in the largest study to date. METHODS: Thirty-one CMV-positive children, diagnosed by examining CMV DNA extracted from their dried umbilical cords retrospectively, were divided into unilateral and bilateral HL groups, and their hearing ability was evaluated using pure-tone audiometry and auditory steady-state response over time. RESULTS: Thirteen patients (41.9%) had unilateral HL and 18 (58.1%) had bilateral HL. In most cases of unilateral cCMV-associated HL, the ear with better hearing maintained a normal hearing threshold. Notably, in most cases of both unilateral and bilateral HL, the ear with worse hearing ultimately showed severe to profound HL. CONCLUSION: Our findings revealed that the natural course of cCMV-associated HL was different between the cases of unilateral and bilateral HL, as well as between the ears with better or worse hearing in all cases. These findings indicate that accurate diagnosis could enable proper follow-up and management of cCMV-associated HL in children.

Vibrant soundbridge implantation prior to auricular reconstruction with unilateral microtia-atresia.

We presented the first successful application of VSB implantation prior to auriculoplasty, which can provide hearing improvement in safe conditions and open new strategies for earlier hearing rehabilitation in unilateral microtia-atresia children.

Preoperative Arterial Embolization to Avoid Intraoperative Bleeding during Endoscopic Sinus Surgery for Organized Hematoma of the Maxillary Sinus: A Case Series and Literature Review.

Purpose: This study aimed to evaluate the safety and efficacy of preoperative arterial embolization of organized hematoma of the maxillary sinus. Material and Methods: Seven patients who were pathologically diagnosed with an organized hematoma of the maxillary sinus and who underwent endoscopic sinus surgery following preoperative arterial embolization for the same from July 2013 to April 2020 at our hospital were included. A literature review of the PubMed database was performed to identify 13 cases on organized hematomas of the maxillary sinuses. The embolization and nonembolization groups comprised patients who underwent preoperative embolization (n = 10, seven from this study and three from literature) and those who did not undergo preoperative embolization (n = 10, from literature), respectively. Outcomes of embolization including embolization-related complications and postoperative bleeding were assessed, and volumes of intraoperative blood loss and duration of surgery were compared between the groups. Results: No preoperative embolization-related complications were observed in our cases. The volume of surgical blood loss in the seven cases varied from 0 to 100 mL with a median of 30 mL, and the duration of surgery ranged from 45 to 166 minutes with a median of 112 minutes. The volume of blood loss was significantly lower for the embolization group than that for the nonembolization group (p = 0.0031). There was no statistically significant difference regarding duration of surgery between the groups (p > 0.10). Conclusions: Preoperative embolization of an organized hematoma of the maxillary sinus is a safe and effective method that helps prevent serious intraoperative hemorrhage.

Haplotype Analysis of GJB2 Mutations: Founder Effect or Mutational Hot Spot?

The GJB2 gene is the most frequent cause of congenital or early onset hearing loss worldwide. In this study, we investigated the haplotypes of six GJB2 mutations frequently observed in Japanese hearing loss patients (i.e., c.235delC, p.V37I, p.[G45E; Y136X], p.R143W, c.176_191del, and c.299_300delAT) and analyzed whether the recurring mechanisms for each mutation are due to founder effects or mutational hot spots. Furthermore, regarding the mutations considered to be caused by founder effects, we also calculated the age at which each mutation occurred using the principle of genetic clock analysis. As a result, all six mutations were observed in a specific haplotype and were estimated to derive from founder effects. Our haplotype data together with their distribution patterns indicated that p.R143W and p.V37I may have occurred as multiple events, and suggested that both a founder effect and hot spot may be involved in some mutations. With regard to the founders' age of frequent GJB2 mutations, each mutation may have occurred at a different time, with the oldest, p.V37I, considered to have occurred around 14,500 years ago, and the most recent, c.176_191del, considered to have occurred around 4000 years ago.

Prevalence and clinical features of hearing loss caused by EYA4 variants.

Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports.

A case of cervical subcutaneous abscess due to Bordetella hinzii.

We present a case of subcutaneous infection caused by Bordetella hinzii in a healthy male. The isolate was successfully identified by gyrB gene sequencing. B. hinzii cannot be distinctively identified using 16S rRNA gene sequencing or by biochemical methods. The number of cases infected with B. hinzii might be underestimated owing to the difficulty in accurate identification, which can be achieved by gyrB gene sequencing to gain knowledge about the species.

Etiology of single-sided deafness and asymmetrical hearing loss.

CONCLUSIONS: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention. OBJECTIVES: The study aimed to clarify the etiology of SSD and AHL patients. METHODS: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing. RESULTS: In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.