Speech recognition scores in bilateral and unilateral atretic ears.

OBJECTIVE: Congenital aural atresia causes severe conductive hearing loss disturbing auditory development. The differences in speech recognition were investigated between bilateral and unilateral aural atresia. DESIGN: The maximum speech recognition scores (SRSs) were compared between patients with bilateral and unilateral aural atresia. In patients with unilateral aural atresia, the maximum SRSs were compared between the atretic and unaffected ears. Furthermore, the correct response rates for test material monosyllables were compared with those of patients with sensorineural hearing loss (SNHL), which had been previously obtained. STUDY SAMPLE: Twenty-four patients with aural atresia (8 bilateral, and 16 unilateral) participated. RESULTS: The maximum SRS in unilateral atretic ears (median: 72%) was significantly lower than that in unaffected ears (median: 89%) (p < 0.05) and in bilateral atretic ears (median: 91%) (p < 0.05). Patients with aural atresia had relatively high correct response rates for monosyllables with low correct response rates by patients with SNHL. Conversely, incorrect responses were obtained for several words for which high correct-response rates were attained by patients with SNHL. CONCLUSIONS: Poor unilateral atretic-ear development may induce low speech recognition, and the mechanisms underlying speech-recognition reduction differ from those in SNHL.

Long-term (16-26 years) follow-up outcome of steroid therapy in refractory autoimmune sensorineural hearing loss.

Autoimmune sensorineural hearing loss (ASHL) is a rare disease of uncertain etiology, with no established treatment strategy. The duration of morbidity is increased in refractory cases; and therefore, the preservation of hearing and the prevention of adverse effects with steroid therapy are serious long term issues to consider. Long-term follow up of patients treated for ASHL was performed retrospectively in order to elucidate the pathogenesis of ASHL, evaluate the consequences of steroid therapy, and determine a promising treatment course. The cohort in this study consists of four female patients with refractory ASHL that were followed for 16-26 years. Three patients already had profound deafness on one side, probably due to ASHL, before the initiation of steroid treatment. ASHL was managed with steroid administration and the hearing was evaluated through regular audiometric tests (173-212 times). The relationship between pure tone threshold average and steroid dose was reviewed over a long-term follow-up period for each patient. During follow-up, hearing deficit progressed rapidly several times in all patients, as did responsiveness to steroid therapy. Long-term high-dose steroid therapy was not required for hearing maintenance. Hearing thresholds were nearly maintained in three patients during the 16- to 21- year follow-up, and gradually declined over a 26-year follow-up period in one patient. Considering the progress due to presbycusis, the maintenance of hearing was considered sufficient in all patients. No serious adverse effects were observed in any of the patients. Management of patients affected by ASHL with regular audiometry allowed for hearing maintenance without the morbidity of prolonged steroid therapy. The current observations give insight into the pathogenesis of ASHL pathogenesis and establish an efficient course of treatment.

Effect of fixation place on airborne sound in cartilage conduction.

When a transducer is placed on aural cartilage, relatively loud sound becomes audible in a conduction form termed cartilage conduction (CC). Previous studies have revealed the acoustical differences between CC and conventional air or bone conduction. This study elucidates the working principle of CC through measurements of threshold shifts by water injection into the ear canal under various fixation place conditions. Seven volunteers with normal hearing participated. A lightweight transducer was fixed for three CC conductions (on the tragus, antitragus, and intertragal incisure), and two non-CC conditions (on the pre-tragus and mastoid). Thresholds were measured at 500, 1000, and 2000 Hz in the 0%-, 40%-, and 80%-water injection conditions. Results for the three CC conditions revealed unique features different from those for the non-CC conditions. For the CC conditions, the thresholds increased by the 40%-water injection at all frequencies. However, with additional water injection (80%-water injection), the thresholds decreased at 500 and 1000 Hz; in particular, dramatically at 500 Hz. The results suggest that a direct vibration of the aural cartilage is important to obtaining the significant contribution of airborne sound to hearing above 1000 Hz. Fixation place results in no significant difference in acoustic features among CC conditions.

Sound localisation ability using cartilage conduction hearing aids in bilateral aural atresia.

OBJECTIVE: Patients with bilateral aural atresia often exhibit poor sound localisation due to bone conduction (BC) features. However, most patients using cartilage conduction (CC) hearing aids reported improvement of sound localisation. DESIGN: CC hearing aids were fitted binaurally. Subsequently, sound localisation was evaluated in three conditions: unaided, aided with previously used hearing aids (air conduction or BC hearing aids), and aided with CC hearing aids. Ears were evaluated with eight loudspeakers positioned in a full-circle at 45-degree interval. Loudspeakers were classified into left and right by midline and front and back by horizontal line. The abilities to distinguish left from right and front from back were compared among three conditions. STUDY SAMPLE: Thirteen patients with bilateral aural atresia participated. RESULTS: The ability to distinguish sounds originating from left or right for participants aided with CC hearing aids was significantly better than that for other conditions (p < 0.05). For distinguishing sounds originating from front or back, unaided ears were significantly better than ears aided with CC hearing aids (p < 0.05). CONCLUSIONS: CC hearing aids provide the ability to distinguish left from right in patients with bilateral aural atresia.

Effects of noise exposure on neonatal auditory brainstem response thresholds in pregnant guinea pigs at different gestational periods.

AIM: Noise exposure during pregnancy has been reported to cause fetal hearing impairment. However, little is known about the effects of noise exposure during various gestational stages on postnatal hearing. In the present study, we investigated the effects of noise exposure on auditory brainstem response (ABR) at the early, mid-, and late gestational periods in newborn guinea pigs. METHODS: Pregnant guinea pigs were exposed to 4-kHz pure tone at a 120-dB sound pressure level for 4 h. We divided the animals into four groups as follows: the control, early gestational exposure, mid-gestational exposure, and late gestational exposure groups. ABR thresholds and latencies in newborns were recorded using 1-, 2-, and 4-kHz tone burst on postnatal days 1, 7, 14, and 28. Changes in ABR thresholds and latencies were measured between the 4 × 4 and 4 × 3 factorial groups mentioned above (gestational periods × postnatal days, gestational periods × frequencies). RESULTS: The thresholds were low in the order of control group < early gestational exposure group < mid-gestational exposure group and late gestational exposure group. Noise exposure during pregnancy influenced ABR thresholds in neonatal guinea pigs. CONCLUSION: This is the first study to show that noise exposure during the early, mid-, and late gestational periods significantly elevated ABR thresholds in neonatal guinea pigs.

Autocorrelation factors and intelligibility of Japanese monosyllables in individuals with sensorineural hearing loss.

Some Japanese monosyllables contain consonants that are not easily discernible for individuals with sensorineural hearing loss. However, the acoustic features that make these monosyllables difficult to discern have not been clearly identified. Here, this study used the autocorrelation function (ACF), which can capture temporal features of signals, to clarify the factors influencing speech intelligibility. For each monosyllable, five factors extracted from the ACF [Φ(0): total energy; τ1 and ϕ1: delay time and amplitude of the maximum peak; τe: effective duration; Wϕ(0): spectral centroid], voice onset time, speech intelligibility index, and loudness level were compared with the percentage of correctly perceived articulations (144 ears) obtained by 50 Japanese vowel and consonant-vowel monosyllables produced by one female speaker. Results showed that median effective duration [(τe)med] was strongly correlated with the percentage of correctly perceived articulations of the consonants (r = 0.87, p < 0.01). (τe)med values were computed by running ACFs with the time lag at which the magnitude of the logarithmic-ACF envelope had decayed to -10 dB. Effective duration is a measure of temporal pattern persistence, i.e., the duration over which the waveform maintains a stable pattern. The authors postulate that low recognition ability is related to degraded perception of temporal fluctuation patterns.

Cartilage conduction hearing.

Sound information is known to travel to the cochlea via either air or bone conduction. However, a vibration signal, delivered to the aural cartilage via a transducer, can also produce a clearly audible sound. This type of conduction has been termed "cartilage conduction." The aural cartilage forms the outer ear and is distributed around the exterior half of the external auditory canal. In cartilage conduction, the cartilage and transducer play the roles of a diaphragm and voice coil of a loudspeaker, respectively. There is a large gap between the impedances of cartilage and skull bone, such that cartilage vibrations are not easily transmitted through bone. Thus, these methods of conduction are distinct. In this study, force was used to apply a transducer to aural cartilage, and it was found that the sound in the auditory canal was amplified, especially for frequencies below 2 kHz. This effect was most pronounced at an application force of 1 N, which is low enough to ensure comfort in the design of hearing aids. The possibility of using force adjustments to vary amplification may also have applications for cell phone design.

Impact of immune-related adverse events on survival outcomes in extensive-stage small cell lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors have recently become the standard of care in the first-line treatment of extensive-stage small cell lung cancer. Although immune-related adverse events have been reported to influence prognosis in non-small cell lung cancer patients, few studies have investigated the prognostic value of immune-related adverse events in small cell lung cancer patients. In this study, we evaluated the prognosis of patients who developed immune-related adverse events after first-line treatment with immune checkpoint inhibitor-based chemotherapy for extensive-stage small cell lung cancer. METHODS: We enrolled 90 patients with extensive-stage small cell lung cancer who received immune checkpoint inhibitor-based chemotherapy as first-line treatment from September 2019 to December 2022 in six hospitals in Japan. The patients were categorized into groups with and without immune-related adverse events. RESULTS: There were 23 patients with and 67 without immune-related adverse events. Seventeen patients had grade 1-2 immune-related adverse events, and nine (including overlapping cases) had grade ≥3. The most frequent immune-related adverse event was a skin rash. The median survival time was 22 months in patients with immune-related adverse events and 9.3 months in patients without immune-related adverse events. The hazard ratio was 0.40 (95% confidence interval: 0.19-0.83, p = 0.013). CONCLUSIONS: The results of this study show that immune-related adverse events are associated with improved survival outcomes in patients with extensive-stage small cell lung cancer.

Cartilage Conduction Sounds in Cases of Wearing Different Transducers on a Head and Torso Simulator with a Manipulated Ear Pinna Simulator.

Cartilage conduction is known widely as a third hearing transmission mechanism after the air and bone conduction methods, and transducers dedicated to the production of cartilage conduction sounds have been developed by several Japanese companies. To estimate the acoustic performance of the five cartilage conduction transducers selected for this study, both airborne sounds and cartilage conduction sounds were measured. Airborne sounds can be measured using a commercial condenser microphone; however, cartilage conduction sounds are impossible to measure using a conventional head and torso simulator (HATS), because the standard-issue ear pinna simulator cannot reproduce cartilage conduction sounds with the same spectral characteristics as the corresponding sounds measured in humans. Therefore, this study replaced the standard-issue simulator with a developed pinna simulator that can produce similar spectral characteristics to those of humans. The HATS manipulated in this manner realized results demonstrating that transducers that fitted the entrance to the external auditory canal more densely could produce greater cartilage conduction sounds. Among the five transducers under test, the ring-shaped device, which was not much larger than the entrance to the canal, satisfied the spectral requirements.

Cartilage Conduction Hearing Aids in Clinical Practice.

A relatively loud sound is audible when a vibrator is attached to the aural cartilage. This form of conduction is referred to as cartilage conduction (CC). In Japan, a new type of hearing aid has been developed using CC and has been available in clinical practice since 2017. A clinical study conducted prior to its launch demonstrated its benefits, particularly in patients with aural atresia who were unable to use air conduction hearing aids. Several studies have been published on the benefits of CC hearing aids since their introduction into clinical practice. Most of the patients included in these studies had canal stenosis or aural atresia, and the purchase rates of CC hearing aids in these patients were relatively high. However, the number of patients with canal-open ears was small, with overall poor results in the trials, with the exception of patients with continuous otorrhea. CC hearing aids are considered a good option for compensating for hearing loss in ears with canal stenosis or atresia in both bilateral and unilateral cases. However, CC hearing aids are not currently considered the first choice for patients with a canal-open ear.

Hearing Outcomes of a New Cartilage Conduction Device vs Bone Conduction Devices.

OBJECTIVE: To compare audiometric outcomes of a new cartilage conduction hearing device (CCD) with traditional bone conduction hearing devices (BCDs). STUDY DESIGN: Clinical trial and crossover study design. SETTING: Tertiary academic center. METHODS: Sixteen adults (19 ears) with congenital aural atresia or overclosed ear canals who previously underwent BCD implantation were fitted with a CCD. Audiometric data were collected with use of the BCD and the CCD. RESULTS: The mean pretreatment 4-frequency pure tone average was 81 dB. The mean aided pure tone averages with the BCD and CCD were 27 and 32 dB (P = .002), and the mean functional gains were 54 and 49 dB (P = .002), respectively. The mean consonant-nucleus-consonant scores with the BCD were 90% (best aided) and 80% (aided ear isolated), and those with the CCD were 86% and 76%. Mean AzBio scores were 90% (quiet), 77% (+10 dB SNR [signal to noise ratio]), and 52% (+5 dB SNR) when isolating the BCD ear and 90%, 73%, and 41% when isolating the CCD ear. No difference in speech scores achieved statistical significance except the AzBio isolated to the aided ear in the +5-dB SNR condition, which favored the BCD (P = .01). CONCLUSION: Pure tone audiometric outcomes with the BCD show a small advantage over the CCD, with the difference driven mainly by high-frequency responses. Speech outcomes were equivalent apart from the +5-db SNR condition, which favored the BCD.

Late-onset and congenital hearing loss detected using AABR due to congenital cytomegalovirus infection that improved with valganciclovir.

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities. Auto auditory brainstem response (AABR) is a simple hearing test and used for the purpose of neonatal hearing screening, but can use it for early detection hard of hearing within the study age of the model. We experienced two case of asymptomatic CMV infection in which congenital and late-onset hearing loss were diagnosed early with AABR, and hearing loss improved with valganciclovir.

Next-generation sequencing clarified why first-line treatment with osimertinib was ineffective in an autopsied case of EGFR-mutated lung squamous cell carcinoma.

Epidermal growth factor receptor (EGFR)-mutated squamous cell carcinoma (SCC) is less common than adenocarcinoma. The third-generation EGFR-tyrosine kinase inhibitor, osimertinib, is effective in EGFR-mutated lung adenocarcinoma, but its efficacy in EGFR-mutated lung SCC is unclear. The patient was an 83-year-old male. He was diagnosed with SCC of the lung, and molecular analysis revealed that the tumor was positive for EGFR exon19 deletion. He was treated with osimertinib 80 mg/day. No adverse events were observed, but after 18 days of therapy, he complained of dyspnea, and a computed tomography scan showed enlarged lung cancer. The case was categorized as a progressive disease. The patient died 3 weeks later. The autopsy findings confirmed the diagnosis of lung SCC, with morphology and immunohistochemical staining identical to the tumor obtained by bronchoscopy. Next-generation sequencing showed the presence of TP53 R158L, CDK6, and KRAS amplifications. The current case report shows that next-generation sequencing can explain why osimertinib is ineffective in EGFR-mutated SCC.

Prognostic Value of CXCL12 in Non-Small Cell Lung Cancer Patients Undergoing Tumor Resection.

Adjuvant chemotherapy is commonly indicated in lung cancer patients undergoing surgical therapy because tumor recurrence is frequent. A biomarker that can predict tumor recurrence in the postoperative period is currently unavailable. CXCR4 receptor and its ligand CXCL12 play important roles in metastasis. This study investigated the value of tumor CXCL12 expression to predict prognosis and indicate adjuvant chemotherapy in non-small cell lung cancer patients. This study enrolled 82 non-small cell lung cancer patients. The expression of CXCL12 was evaluated by immunohistochemistry. The degree of CXCL12 expression was assessed using the Allred score system. Among all subjects, the progression-free survival and overall survival were significantly prolonged in cancer patients with low tumor expression of CXCL12 compared to patients with high tumor expression. Multivariate analysis showed that the increased level of CXCL12 is a significant predictor of progression-free survival and overall survival in NSCLC patients. Among subjects with high tumor CXCL12 expression, progression-free survival and overall survival were significantly improved in patients treated with adjuvant chemotherapy compared to untreated patients. These results suggest the potential value of tumor CXCL12 expression as a marker to predict prognosis and to indicate adjuvant chemotherapy after surgical tumor resection in non-small cell lung cancer patients.

Bone and Cartilage Conduction.

Auditory sensation is an important sensation for human beings [...].

Evaluation of the Recovery of Idiopathic Sudden Sensorineural Hearing Loss Based on Estimated Hearing Disorders.

Various prognostic factors for idiopathic sudden sensorineural hearing loss (SSNHL) have been reported. Hearing loss directly derived from idiopathic SSNHL is important for understanding underlying pathogenesis and outcomes. We assessed the usefulness of evaluating hearing loss and recovery of idiopathic SSNHL on the basis of estimated hearing loss. The study included 115 patients whose characteristics and outcomes of hearing loss were investigated. The effects of vertigo/dizziness and age on hearing thresholds before/after treatment, nonaffected ear threshold, estimated hearing loss, improvement of hearing loss, and estimated remaining hearing loss were investigated. Vertigo/dizziness was a significant prognostic factor for hearing. In vertigo/dizziness patients, significantly more severe hearing loss and poorer improvement of hearing loss were observed above 500 Hz and below 1000 Hz, respectively. Severe hearing disorder remained at all frequencies. Conversely, post-treatment thresholds were significantly higher in the older population (≥65 years), although no differences in pretreatment thresholds were observed between the younger (≤64 years) and older populations. However, on the basis of nonaffected ear thresholds, previously existing hearing loss could have influenced the outcome. Thus, comparison of hearing outcomes between affected and nonaffected ears is essential for understanding hearing loss and outcomes in idiopathic SSNHL cases with existing hearing disorder.

Factors Influencing the Purchase Rate of Cartilage Conduction Hearing Aids.

BACKGROUND: Innovated hearing aids (HAs), termed cartilage conduction hearing aids (CC-HAs), show good performance in patients with closed ears and continuous otorrhea. However, factors other than the ear condition that influence the purchase rate of CC-HAs remain unclear. PURPOSE: To identify the factors that influence the purchase rate of CC-HAs. RESEARCH DESIGN: A correlational study. STUDY SAMPLE: A total of 249 patients were enrolled. DATA COLLECTION AND ANALYSIS: The patients' demographics, clinical characteristics, outcomes, and CC-HA transducer types were compared. The data were analyzed for six groups classified based on the ear condition. RESULTS: In the unilateral closed-ear group, the purchase cases were significantly younger than the nonpurchase cases (p < 0.05). Regarding the outcomes in the bilateral closed-ear group, the purchase cases showed significantly better-aided thresholds at 0.25 and 0.5 kHz than the nonpurchase cases. No significant differences in the functional gains and speech recognition scores were found between purchase and nonpurchase cases in all six groups. Regarding the transducer type, the continued-use rate of the simple transducer type was significantly lower in the bilateral chronic continuous otorrhea, bilateral open, and unilateral open groups. CONCLUSION: In the closed ears, no remarkable negative factors were found. Transducer type had a significant influence on the continued-use rate in the nonclosed ears including the ears with chronic continuous otorrhea, although the purchase rate of CC-HAs in the bilateral chronic continuous otorrhea group was comparable to the closed ears.

Is the Efficacy of Adding Ramucirumab to Docetaxel Related to a History of Immune Checkpoint Inhibitors in the Real-World Clinical Practice?

Reports on the efficacy of second-line treatment with cytotoxic agents after treatment with immune checkpoint inhibitors are limited. Here, we retrospectively evaluated patients in the real-world clinical practice treated with docetaxel or docetaxel plus ramucirumab. Ninety-three patients treated with docetaxel or docetaxel plus ramucirumab as a second- or later-line therapy were included. The patients were categorized into the following four treatment groups: docetaxel group (n = 50), docetaxel/ramucirumab group (n = 43) and pretreated (n = 45) and untreated (n = 48) with immune checkpoint inhibitor groups. The docetaxel/ramucirumab group showed an overall response rate of 57.1% in patients pretreated with immune checkpoint inhibitors and 20% in untreated patients. The docetaxel group showed an overall response rate of 15.4% in patients pretreated with immune checkpoint inhibitors and 5.0% in untreated patients. The median time-to-treatment failure and the median survival time were longer in the docetaxel/ramucirumab group than in the docetaxel group in both immune checkpoint inhibitor-pretreated and -untreated groups. There was no difference in time-to-treatment failure and overall survival between immune checkpoint inhibitor-pretreated and -untreated groups in each docetaxel and docetaxel/ramucirumab treatment group. In conclusion, our real-world data show that the addition of ramucirumab to docetaxel was superior to docetaxel monotherapy for improving time-to-treatment failure and overall survival, irrespective of previous treatment with immune checkpoint inhibitors.

Efficacy and Safety of Amrubicin in Small Cell Carcinoma Previously Treated with Immune Checkpoint Inhibitors and Chemotherapy.

Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed the efficacy and safety of amrubicin as a second-line treatment for extensive-stage small cell lung cancer after chemotherapy and immune checkpoint inhibitor combination therapy. The study enrolled 150 patients with extensive-stage small cell lung cancer. The efficacy and the incidence of adverse events were compared between patients previously treated with immune checkpoint inhibitors and patients without previous immune checkpoint inhibitor treatment. One hundred and twenty-three patients were eligible. There was no difference in objective response rate, time-to-treatment failure, progression-free survival, and overall survival between both groups. The incidence of adverse events was similar in both treatment groups. Pretreatment with immune checkpoint inhibitors was not associated with an increase in amrubicin-related adverse events. This study shows that the efficacy of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with immune checkpoint inhibitors. Amrubicin-related adverse events did not increase in patients previously treated with immune checkpoint inhibitors.