Intraoperative EABR Testing Predicts Strength of Cochlear Implant Stimulation Optimized After Long-Term Use in Pediatric Malformation Ears.

OBJECTIVE: This study focused on the intensities of cochlear implant (CI) stimulation in pediatric CI users with inner ear malformation or cochlear nerve deficiency (CND). In this population, CI programming is difficult because a large intensity of CI stimulation is required to achieve sufficient hearing, but the excess CI stimuli often induce facial nerve stimulation. We aimed to assess whether the results of intraoperative electrically evoked auditory brainstem responses (EABRs) testing predict maximum current levels of CI stimuli (cC levels) optimized by a behavioral-based method after long-term CI use. STUDY DESIGN: A retrospective case review. SETTING: A tertiary referral CI center. PATIENTS: A total of 116 ears with malformations (malformation group) and 63 control ears (control group) from patients younger than 18 years who received CI. The malformation group comprised 23 ears with a common cavity (CC), 26 with incomplete partition type 1 (IP-1), 26 with incomplete partition type 2 (IP-2), and 41 with CND. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Correlation between intraoperative EABR results and cC levels determined by the behavioral-based CI programming after long-term CI use. RESULTS: The CC, IP-1, and CND ears required significantly larger cC levels than the IP-2 ears and control groups. However, the cC levels increased to reach the plateau 1 year after surgery in all groups. Among the malformation group, 79 ears underwent intraoperative EABR testing. Greater than 80% of the CC, IP-1, and IP-2 ears and 54.8% of the CND ears exhibited evoked wave V (eV) and were included in the eV-positive category. Myogenic responses but no eV were observed in 18.2, 15.0, and 35.5% of the CC, IP-1, and CND ears, defined as the myogenic category. No eV or myogenic response was elicited in 9.7% of the CND ears. We focused on minimum current levels that elicited eV (eV levels) in the eV-positive category and maximum current levels that did not elicit any myogenic responses (myogenic levels) in the myogenic category. A significant relationship was detected between the eV levels and the cC levels. When analyzed in each malformation type, the eV levels significantly correlate with the cC levels in the CC and CND ears but not in the IP-1 and IP-2 ears, probably because of slight variation within the IP-1 group and the small number of the IP-2 group. The myogenic category did not show a significant relationship between the myogenic levels and cC levels, but the cC levels were similar to or smaller than the myogenic levels in most ears. CONCLUSIONS: This study confirmed that intraoperative EABR testing helps predict the optimal cC levels in malformation ears. EABR-based CI programming immediately after cochlear implantation, followed by behavioral-based CI programming, may allow us to achieve early postoperative optimization of CI maps even in young children with severe malformations.

Management of Already Inserted Ventilation Tubes During Pediatric Cochlear Implantation: To Remove or Leave the Tube?

OBJECTIVE: Ventilation tube (VT) insertion is usually recommended before cochlear implantation (CI) in pediatric cochlear implant candidates with recurrent acute otitis media (AOM) or chronic otitis media with effusion (OME). However, there is no consensus on whether the VT is beneficial even after CI, that is, whether the tube should be removed or left in place during CI. This study aimed to assess the effect of tube placement after CI, especially on the incidence of post-CI AOM, in pediatric cochlear implant recipients who had undergone VT insertion before CI because of recurrent AOM or chronic OME. STUDY DESIGN: A retrospective medical record review. SETTING: A tertiary referral cochlear implant center. PATIENTS: This study recruited 58 consecutive ears of children who underwent VT insertion followed by CI at age 7 years or younger between 2004 and 2021. Before October 2018, we removed the VT simultaneously with CI (removed group, 39 ears), while since then, the tube has remained in place during CI (retained group, 19 ears). INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: The primary outcome was the proportion of ears that developed AOM at post-CI 6 months in the removed and retained groups. RESULTS: The age at CI was significantly higher in the removed group than in the retained group (mean [standard deviation]: the removed group, 2.9 [1.2] yr; the retained group: 1.5 [0.8] yr; p < 0.001). The removed group showed a significantly higher proportion of ears with post-CI AOM (8 of 39 ears; 20.5%) than the retained group (none of 19 ears; 0%) 6 months after CI ( p = 0.044). The AOM-free proportion at post-CI 12 months was 76.9% in the removed group and 83.3% in the retained group, demonstrating no significant difference ( p = 0.49), probably because the VT was spontaneously extruded in the retained group at a median of 6.5 months after CI. Throughout the study period, 17 ears (13 from the removed group) were affected by post-CI AOM. Of these, three ears in the removed group and two in the retained group after spontaneous extrusion of the VT were hospitalized and treated with intravenous antibiotics for AOM that had failed to respond to oral antibiotic therapy. Only one ear in the removed group required an explanation of the infected implant. None suffered from chronic perforation of the tympanic membrane or secondary cholesteatoma after VT insertion or meningitis associated with post-CI AOM. CONCLUSION: Our results suggest that in CI for children who already have a VT because of a recurrent AOM or chronic OME, retaining the tube in position, rather than removing the tube, may decrease the incidence of AOM at least within 6 months after CI, during which most cochlear implant device infection was reported in the pediatric population.

A multicenter study to investigate the positive rate of SARS-CoV-2 in middle ear and mastoid specimens from otologic surgery patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19). Otologic surgeries with drilling by powered instruments induce significant aerosols, which may induce SARS-CoV-2 transmission to medical staff if SARS-CoV-2 exists in the middle ear and mastoid cavity. During a COVID-19 pandemic, therefore, confirming a negative COVID-19 test prior to otologic surgery is recommended. However, previous coronavirus studies demonstrated that coronavirus was detected in the middle ear in some patients even though the polymerase chain reaction (PCR) test using their nasopharyngeal swab was negative. This study aimed to elucidate the probability of a positive SARS-CoV-2 PCR test in the middle ear or mastoid specimens from otologic surgery patients in whom SARS-CoV-2 was not detected by preoperative PCR test using a nasopharyngeal swab. METHODS: We conducted a prospective, multicenter clinical study. Between April 2020 and December 2021, during the COVID-19 pandemic, 251 ears of the 228 participants who underwent otologic surgery were included in this study. All participants had no symptoms suggesting COVID-19 or close contact with a confirmed COVID-19 patient two weeks prior to the surgery. They were also negative in the SARS-CoV-2 PCR tests using a nasopharyngeal swab before surgery. We collected mucosa, granulation, bone dust with mucosa or fluid from the middle ear or mastoid for the SARS-CoV-2 PCR tests during each otologic surgery. RESULTS: The median age of the participants at surgery was 31.5 years old. Mastoidectomy using a powered instrument was conducted in 180 of 251 otologic surgeries (71.8%). According to intraoperative findings, active inflammation in the middle ear or mastoid cavities was evident in 20 otologic surgeries (8.0%), while minor inflammation was observed in 77 (30.7%). All SARS-CoV-2 PCR tests of otologic specimens showed a negative result. No patient suffered from COVID-19 within two months after otologic surgery. Furthermore, no hospital-acquired infections associated with otologic surgery occurred in our institutions CONCLUSIONS: Our results showed that PCR testing did not detect SARS-CoV-2 in middle ear and mastoid specimens, suggesting that the risk of transmission of SARS-CoV-2 is not high in otologic surgeries even using powered instruments when both clinical and laboratory tests are confirmed to be negative for COVID-19.

Etiology of hearing loss affects auditory skill development and vocabulary development in pediatric cochlear implantation cases.

BACKGROUND: Cochlear implantation (CI) is an effective treatment for severe-to-profound hearing loss patients and is currently used as the standard therapeutic option worldwide. However, the outcomes of CI vary among patients. AIMS/OBJECTIVES: This study aimed to clarify the clinical features for each etiological group as well as the effects of etiology on CI outcomes. MATERIALS AND METHODS: We collected clinical information for 308 pediatric cochlear implant cases, including the etiology, hearing thresholds, age at CI, early auditory skill development, total development, monosyllable perception, speech intelligibility and vocabulary development in school age, and compared them for each etiology group. RESULTS: Among the 308 CI children registered for this survey, the most common etiology of hearing loss was genetic causes. The genetic etiology group showed the most favorable development after CI followed by the unknown etiology group, syndromic hearing loss group, congenital CMV infection group, inner ear malformation group, and cochlear nerve deficiency group. CONCLUSIONS AND SIGNIFICANCE: Our results clearly indicated that the etiology of HL affects not only early auditory skill development, but also vocabulary development in school age. The results of the present study will aid in more appropriate CI outcome assessment and in more appropriate intervention or habilitation programs.

High Riding Jugular Bulb Protruding Into Tympanic Cavity: Longitudinal Radiologic Study in a Deaf Child.

BACKGROUND: High riding jugular bulb (HRJB) develops after 2 years and is rare at younger ages. High riding jugular bulb sometimes protrudes into the tympanic cavity, which can cause hemorrhagic complications during otologic surgery. CASE PRESENTATION: We describe a congenitally deaf child with bilateral inner ear malformations and a right-sided HRJB on CT at 9 months. This child had undergone left cochlear implantation (CI) at 19 months, and right CI was planned at 6 years. However, we decided not to perform the right CI because preoperative CT images revealed that the right jugular bulb (JB) was enlarged and protruded into the tympanic cavity, completely covering the round window (RW). CONCLUSION: This is the first pediatric case in which a longitudinal CT scan proves that HRJB develops and protrudes over time. These findings suggest that the earlier the HRJB forms, the larger it may grow. We must keep in mind the possibility of the enlargement and protrusion of HRJB.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Which is better? Anterior or posterior referencing for femoral component position in total knee arthroplasty.

When sizing the femoral component or determining its placement in total knee arthroplasty (TKA), if the anterior-posterior diameter of the femoral condyle is between component sizes, the selected size will differ depending on whether anterior referencing (AR) or posterior referencing (PR) is used. As a result, the amount of resected bone will also vary. In the present prospective study, we compared the two referencing methods to determine which is more suitable for individual patients. We recruited 58 patients (92 joints) who received TKA using the standard technique with intermediate-size components. AR was used in 26 joints, and PR in 23 joints. Seventeen of the patients underwent same-day bilateral TKA in which components of different sizes were used for the left and right joints. AR resulted in significantly smaller anterior and posterior offsets than PR. Preoperative clinical evaluation revealed no significant differences among cases in which intermediate-size components were indicated, or those in which components of different sizes were indicated. When an intermediate-sized component was indicated using the AR method, moving the sizer forward resulted in a larger posterior gap, but this technique was nevertheless considered acceptable. AR is likely to be more suitable than PR as it achieves more physiological anterior clearance.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss.

Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin.

Clinical practice guidelines for diagnosis and treatment of chronic tinnitus in Japan.

Clinical practice guidelines in Japan for tinnitus were published in May 2019. Effective treatment of tinnitus contributes to quality of life and may improve depression, anxiety, and cognitive function. The highest priority of treatment recommended by this guideline involves educational counseling, including an explanation of the mechanisms of tinnitus. Understanding tinnitus pathology has also been reported to be a therapeutically effective educational counseling strategy. Further, explaining how sound therapy such as tinnitus retraining therapy (TRT) works is effective. Psychological and cognitive behavioral therapies may be an option. Here, the hearing aid is coupled with a sound generator in order to administer sound therapy for patients with more-severe symptoms. In Japan, it can be difficult to perform psychotherapy alongside otorhinolaryngology, and exemplary sound therapy is more likely to be carried out. In any case, the purpose of treatment is not to eliminate tinnitus, but rather reduce distress that manifests in response to tinnitus by promoting sensory adaptation. Clinically, the most important subject is not the loudness of tinnitus, but the severity of tinnitus distress. TRT consists of educational counseling and sound therapy. The tinnitus handicap inventory (THI) is used to measure the distress level for tinnitus and to determine treatment priorities. Rehabilitation of tinnitus is important because anxiety and depression are often observed in patients with severe tinnitus. Additionally, drug administration should be avoided. As a surgical treatment, a cochlear implant can affect tinnitus symptoms. It is essential to establish a treatment policy according to the disease condition and degree of distress.

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients.

The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD.

First Implant-Induced Changes in Rostral Brainstem Impair Second Implant Outcomes in Sequential Bilateral Cochlear Implant Children With Long Inter-Implant Delay.

HYPOTHESIS: Long-term unilateral use of a cochlear implant (CI) induces abnormal maturation of the rostral brainstem innervating the contralateral ear. BACKGROUND: In sequential bilateral CI children with long inter-implant delay, both sides of auditory cortices were dominantly activated by the first CI, but mechanisms of this abnormal development of the auditory system remain unclear. METHODS: Fifteen sequential bilateral CI children with long delay (mean ±â€ŠSD, 28.7 ±â€Š12.1 mo) underwent electrically evoked auditory brainstem response (EABR) testing using each of the first and second CI (CI1 and CI2, respectively), immediately after the second implantation. CI1 and CI2 were implanted at age of 23.7 ±â€Š9.6 and 53.1 ±â€Š12.1 months (mean ±â€ŠSD), respectively. Apical-to-basal difference in electrically evoked interwave III-V latencies (eIII-eV slope) which decreases with implant use was compared between the CI1 and CI2 sides. Their speech perception scores were evaluated 3 years after the second implantation. RESULTS: eIII-eV slopes evoked by the CI2 showed less mature pattern than those by the CI1. This CI2 versus CI1 difference in eIII-eV slopes, however, reduced as the inter-implant delay was prolonged, suggesting CI1-induced maturation of the rostral brainstem innervating the second ear before the second implantation. The smaller CI2 versus CI1 difference in eIII-eV slopes at the second implantation was correlated to poorer outcomes using the CI2 than the CI1. CONCLUSIONS: In this population, long-term unilateral CI use induced re-organization of the rostral brainstem innervating the second ear, which affected hearing outcomes using the CI2. Evaluation of eIII-eV slopes at the second implantation may be useful to predict hearing outcomes with CI2.

Prognostic impact of incisional or excisional biopsy of cervical lymph node metastases of solid tumors.

OBJECTIVES: In performing an open biopsy of a neck mass, an incisional biopsy may increase the risk of cancer cell seeding and dissemination that, ultimately, worsens a patient's survival. The aim of this study was to compare the impact of incisional and excisional biopsies of cervical lymph node metastases of solid tumors on patients' survival. METHODS: A retrospective review was made of patients with cervical metastases of solid tumors who underwent an open biopsy for a diagnosis between 2005 and 2015. Sixty-four patients met the criteria out of 524 open biopsy cases undertaken during the period. Survival analyses were estimated from 33 cases whose initial symptoms were the presence of a neck mass, using two modes of biopsy: excisional and incisional. RESULTS: The 2-year overall survival rates in incisional and excisional biopsy groups were 65% and 43%, respectively, and 2-year disease-specific survival rates were 74% and 43%, respectively. The differences were not significant. For lung cancer or head and neck cancer subgroups, survival differences between incisional and excisional biopsy groups were also not significant. CONCLUSIONS: A carefully targeted physical examination and performing a fine needle aspiration are essential to establish a diagnosis for the etiology of an unknown neck mass. In performing an open biopsy, the effect of an incisional biopsy on patients' survival was no worse than that of an excisional biopsy, despite the latter being theoretically preferable.

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.

A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 µg of HGF per vocal fold; Step II received 3 µg of HGF; and Step III received 10 µg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus.

Facial flushing after alcohol intake as a predictor for a high risk of synchronous or metachronous cancer of the upper gastrointestinal tract.

BACKGROUND: In Japan, there has been a lot of reports showing an association between facial flushing after light alcohol consumption and heterozygosity for inactive aldehyde dehydrogenase-2 (ALDH2). Persons with inactive ALDH2 may have a higher risk of alcohol-related oral, pharyngeal and esophageal cancers, compared with those with wild-type ALDH2. The purpose of this study was to examine whether flushers with oral or pharyngeal squamous cell carcinoma have an increased risk of synchronous or metachronous cancer of the upper gastrointestinal (UGI) tract. METHODS: A retrospective study was performed by medical chart review and through a questionnaire sent to 285 patients treated for oral and pharyngeal cancer. Responses were obtained from 150 patients (52.6%), who were classified as flushers or non-flushers, smokers (≥20 pack-year; 1 pack-years = number of cigarettes/20 per day) or non-smokers, and drinkers (≥14 units of alcohol consumption per week; 1 unit = 22 g) or non-drinkers. Relationships of these factors with occurrence of second primary cancers (SPCs) in the UGI tract were investigated. RESULTS: In Kaplan-Meier analysis, there was a significantly higher rate of SPC at 5 years in flushers and drinkers, but no relationship with smoking. In multivariate analyses, a history of flushing was significantly associated with SPC in the UGI tract (HR 2.64, 95% CI 1.25-5.52, P = 0.0109), but not with smoking or alcohol consumption. CONCLUSIONS: A simple interview on history of facial flushing after alcohol intake can be useful for identifying patients at high risk for synchronous or metachronous cancers of the UGI tract.

Audio-visual speech perception in prelingually deafened Japanese children following sequential bilateral cochlear implantation.

OBJECTIVES: An effect of audio-visual (AV) integration is observed when the auditory and visual stimuli are incongruent (the McGurk effect). In general, AV integration is helpful especially in subjects wearing hearing aids or cochlear implants (CIs). However, the influence of AV integration on spoken word recognition in individuals with bilateral CIs (Bi-CIs) has not been fully investigated so far. In this study, we investigated AV integration in children with Bi-CIs. METHODS: The study sample included thirty one prelingually deafened children who underwent sequential bilateral cochlear implantation. We assessed their responses to congruent and incongruent AV stimuli with three CI-listening modes: only the 1st CI, only the 2nd CI, and Bi-CIs. The responses were assessed in the whole group as well as in two sub-groups: a proficient group (syllable intelligibility ≥80% with the 1st CI) and a non-proficient group (syllable intelligibility < 80% with the 1st CI). RESULTS: We found evidence of the McGurk effect in each of the three CI-listening modes. AV integration responses were observed in a subset of incongruent AV stimuli, and the patterns observed with the 1st CI and with Bi-CIs were similar. In the proficient group, the responses with the 2nd CI were not significantly different from those with the 1st CI whereas in the non-proficient group the responses with the 2nd CI were driven by visual stimuli more than those with the 1st CI. CONCLUSION: Our results suggested that prelingually deafened Japanese children who underwent sequential bilateral cochlear implantation exhibit AV integration abilities, both in monaural listening as well as in binaural listening. We also observed a higher influence of visual stimuli on speech perception with the 2nd CI in the non-proficient group, suggesting that Bi-CIs listeners with poorer speech recognition rely on visual information more compared to the proficient subjects to compensate for poorer auditory input. Nevertheless, poorer quality auditory input with the 2nd CI did not interfere with AV integration with binaural listening (with Bi-CIs). Overall, the findings of this study might be used to inform future research to identify the best strategies for speech training using AV integration effectively in prelingually deafened children.

Round Window Application of an Active Middle Ear Implant: A Comparison With Hearing Aid Usage in Japan.

OBJECTIVE: To report on the safety and efficacy of an investigational active middle ear implant (AMEI) in Japan, and to compare results to preoperative results with a hearing aid. DESIGN: Prospective study conducted in Japan in which 23 Japanese-speaking adults suffering from conductive or mixed hearing loss received a VIBRANT SOUNDBRIDGE with implantation at the round window. Postoperative thresholds, speech perception results (word recognition scores, speech reception thresholds, signal-to-noise ratio [SNR]), and quality of life questionnaires at 20 weeks were compared with preoperative results with all patients receiving the same, best available hearing aid (HA). RESULTS: Statistically significant improvements in postoperative AMEI-aided thresholds (1, 2, 4, and 8 kHz) and on the speech reception thresholds and word recognition scores tests, compared with preoperative HA-aided results, were observed. On the SNR, the subjects' mean values showed statistically significant improvement, with -5.7 dB SNR for the AMEI-aided mean and -2.1 dB SNR for the preoperative HA-assisted mean. The APHAB quality of life questionnaire also showed statistically significant improvement with the AMEI. CONCLUSION: Results with the AMEI applied to the round window exceeded those of the best available hearing aid in speech perception as well as quality of life questionnaires. There were minimal adverse events or changes to patients' residual hearing.