Genome-wide association study indicates novel associations of annexin A13 to secretory and GAS2L2 with mucous otitis media.

To evaluate the genetics of chronic nonsuppurative otitis media (OM). We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: combined chronic nonsuppurative OM (7034 cases) (included serous and mucous chronic OM), mucous chronic OM (5953 cases), and secretory chronic OM (1689 cases). Individuals without otitis media were used as controls (417,745 controls). We used immunohistochemistry (IHC) of the murine middle ear to evaluate the expression of annexin A13. Four loci were significantly associated (p < 1.7 × 10-8) with nonsuppurative OM. Three out of the four association signals included missense variants in genes that may play a role in otitis media pathobiology. According to our subtype-specific analyses, one novel locus, located near ANXA13, was associated with secretory OM. Three loci (near TNFRSF13B, GAS2L2, and TBX1) were associated with mucous OM. Immunohistochemistry of murine middle ear samples revealed annexin A13 expression at the apical pole of the Eustachian tube epithelium as well as variable intensity of the secretory cells of the glandular structure in proximity to the Eustachian tube. We demonstrated that secretory and mucous OM have distinct and shared genetic associations. The association of GAS2L2 with ciliary epithelium function and the pathogenesis of dysfunctional mucosa in mucous OM is suggested. The abundant expression of annexin A13 in the Eustachian tube epithelium, along with its role in apical transport for the binding and transfer of phospholipids, indicates the role of annexin A13 and phospholipids in Eustachian tube dysfunction.

The Effectiveness of Unilateral Cochlear Implantation on Performance-Based and Patient-Reported Outcome Measures in Finnish Recipients.

Understanding speech is essential for adequate social interaction, and its functioning affects health, wellbeing, and quality of life (QoL). Untreated hearing loss (HL) is associated with reduced social activity, depression and cognitive decline. Severe and profound HL is routinely rehabilitated with cochlear implantation. The success of treatment is mostly assessed by performance-based outcome measures such as speech perception. The ultimate goal of cochlear implantation, however, is to improve the patient's QoL. Therefore, patient-reported outcomes measures (PROMs) would be clinically valuable as they assess subjective benefits and overall effectiveness of treatment. The aim of this study was to assess the patient-reported benefits of unilateral cochlear implantation in an unselected Finnish patient cohort of patients with bilateral HL. The study design was a prospective evaluation of 118 patients. The patient cohort was longitudinally followed up with repeated within-subject measurements preoperatively and at 6 and 12 months postoperatively. The main outcome measures were one performance-based speech-in-noise (SiN) test (Finnish Matrix Sentence Test), and two PROMs [Finnish versions of the Speech, Spatial, Qualities of Hearing questionnaire (SSQ) and the Nijmegen Cochlear Implant Questionnaire (NCIQ)]. The results showed significant average improvements in SiN scores, from +0.8 dB signal-to-noise ratio (SNR) preoperatively to -3.7 and -3.8 dB SNR at 6 and12 month follow-up, respectively. Significant improvements were also found for SSQ and NCIQ scores in all subdomains from the preoperative state to 6 and 12 months after first fitting. No clinically significant improvements were observed in any of the outcome measures between 6 and 12 months. Preoperatively, poor SiN scores were associated with low scoring in several subdomains of the SSQ and NCIQ. Poor preoperative SiN scores and low PROMs scoring were significantly associated with larger postoperative improvements. No significant association was found between SiN scores and PROMs postoperatively. This study demonstrates significant benefits of cochlear implantation in the performance-based and patient-reported outcomes in an unselected patient sample. The lack of association between performance and PROMs scores postoperatively suggests that both capture unique aspects of benefit, highlighting the need to clinically implement PROMs in addition to performance-based measures for a more holistic assessment of treatment benefit.

Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic TMC1 Variants.

Sensorineural hearing loss (SNHL) is one of the most common sensory deficits worldwide, and genetic factors contribute to at least 50−60% of the congenital hearing loss cases. The transmembrane channel-like protein 1 (TMC1) gene has been linked to autosomal recessive (DFNB7/11) and autosomal dominant (DFNA36) non-syndromic hearing loss, and it is a relatively common genetic cause of SNHL. Here, we report eight Finnish families with 11 affected family members with either recessively inherited homozygous or compound heterozygous TMC1 variants associated with congenital moderate-to-profound hearing loss, or a dominantly inherited heterozygous TMC1 variant associated with postlingual progressive hearing loss. We show that the TMC1 c.1534C>T, p.(Arg512*) variant is likely a founder variant that is enriched in the Finnish population. We describe a novel recessive disease-causing TMC1 c.968A>G, p.(Tyr323Cys) variant. We also show that individuals in this cohort who were diagnosed early and received timely hearing rehabilitation with hearing aids and cochlear implants (CI) have reached good speech perception in noise. Comparison of the genetic data with the outcome of CI rehabilitation increases our understanding of the extent to which underlying pathogenic gene variants explain the differences in CI rehabilitation outcomes.

Comparing the Speech Perception of Cochlear Implant Users with Three Different Finnish Speech Intelligibility Tests in Noise.

BACKGROUND: A large number of different speech-in-noise (SIN) tests are available for testing cochlear implant (CI) recipients, but few studies have compared the different tests in the same patient population to assess how well their results correlate. METHODS: A clinically representative group of 80 CI users conducted the Finnish versions of the matrix sentence test, the simplified matrix sentence test, and the digit triplet test. The results were analyzed for correlations between the different tests and for differences among the participants, including age and device modality. RESULTS: Strong and statistically significant correlations were observed between all of the tests. No floor or ceiling effects were observed with any of the tests when using the adaptive test procedure. Age or the length of device use showed no correlation to SIN perception, but bilateral CI users showed slightly better results in comparison to unilateral or bimodal users. CONCLUSIONS: Three SIN tests that differ in length and complexity of the test material provided comparable results in a diverse CI user group.

Improvements in Hearing and in Quality of Life after Sequential Bilateral Cochlear Implantation in a Consecutive Sample of Adult Patients with Severe-to-Profound Hearing Loss.

Bilateral cochlear implantation is increasing worldwide. In adults, bilateral cochlear implants (BICI) are often performed sequentially with a time delay between the first (CI1) and the second (CI2) implant. The benefits of BICI have been reported for well over a decade. This study aimed at investigating these benefits for a consecutive sample of adult patients. Improvements in speech-in-noise recognition after CI2 were followed up longitudinally for 12 months with the internationally comparable Finnish matrix sentence test. The test scores were statistically significantly better for BICI than for either CI alone in all assessments during the 12-month period. At the end of the follow-up period, the bilateral benefit for co-located speech and noise was 1.4 dB over CI1 and 1.7 dB over CI2, and when the noise was moved from the front to 90 degrees on the side, spatial release from masking amounted to an improvement of 2.5 dB in signal-to-noise ratio. To assess subjective improvements in hearing and in quality of life, two questionnaires were used. Both questionnaires revealed statistically significant improvements due to CI2 and BICI. The association between speech recognition in noise and background factors (duration of hearing loss/deafness, time between implants) or subjective improvements was markedly smaller than what has been previously reported on sequential BICI in adults. Despite the relatively heterogeneous sample, BICI improved hearing and quality of life.

The long-term learning effect related to the repeated use of the Finnish matrix sentence test and the Finnish digit triplet test.

Objectives: To assess are there learning-related improvements in the speech reception thresholds (SRTs) for the Finnish matrix sentence test (FMST) and the Finnish digit triplet test (FDTT) in repeated use over 12 months.Design: Test sessions were scheduled at 0, 1, 3, 6 and 12 months, and each session included five FMST measurements and four FDTT measurements. The within-session and inter-session improvements in SRTs were analysed with a linear mixed model.Study sample: Fifteen young normal-hearing participants.Results: Statistically significant mean improvements of 2.0 dB SNR and 1.2 dB SNR were detected for the FMST and the FDTT, respectively, over the 12-month follow-up period. For the FMST, majority of the improvement occurred during the first two test sessions. For the FDTT, statistically significant differences were detected only in comparison to the first test session and to the first test measurement of every session over the 12-month follow-up.Conclusions: Repeated use of the FMST led to significant learning-related improvements, but the improvements appeared to plateau by the third test session. For the FDTT, the overall improvements were smaller, but a significant within-session difference between the first and consecutive FDTT measurements persisted throughout the test sessions.

The Finnish simplified matrix sentence test for the assessment of speech intelligibility in the elderly.

Objective: A simplified version of the Finnish matrix sentence test (FMST) was developed to improve the reliability of hearing diagnostic for children and for patients with limited working memory capacity and/or vocabulary.Design: Study 1 evaluated the word matrix of the Finnish simplified matrix sentence test (FINSIMAT) to rule out systematic differences between the new FINSIMAT test lists, and to provide reference values for normal-hearing (NH) young adults (YA). In Study 2, the FINSIMAT and the FMST were evaluated in elderly listeners with mild-to-moderate hearing impairment (HI).Study sample: Twenty NH YAs participated in Study 1, and 16 elderly HI adults participated in Study 2.Results: For NH YAs, the reference speech reception threshold (SRT50) estimate and the slope for the FINSIMAT were -11.2 ± 1.0 dB signal-to-noise ratio (SNR) and 19.4 ± 1.9%/dB SNR. For the elderly HI listeners, the mean SRT50 estimates for the FINSIMAT and FMST were -4.1 and -3.6 dB SNR, respectively. The correlation between the FMST and FINSIMAT results was strong (r2 = 0.78, p < 0.001).Conclusion: The FINSIMAT showed comparable characteristics to the FMST and proved feasible for measurements in elderly HI listeners.

The efficacy of microphone directionality in improving speech recognition in noise for three commercial cochlear-implant systems.

Objectives: To investigate the effect of fixed and adaptive microphone directionality on speech reception threshold (SRT) in noise when compared to omnidirectional mode in unilateral cochlear-implant (CI) use for three different CI systems.Methods: Twenty-four CI recipients with bilateral severe-to-profound hearing loss participated in the study. Eight recipients of each CI system were enrolled, and their SRT in noise was measured when the speech and noise signals were co-located in the front to serve as a baseline. The acute effect of different microphone directionalities on SRT in noise was measured with the noise emanating at 90° in the horizontal plane from the side of the CI sound processor (S0NCI).Results: When compared to the baseline condition, the individual data revealed fairly similar patterns within each CI system. In the S0NCI condition, the average improvement in SRT in noise for fixed and adaptive directionalities over the omnidirectional mode was statistically significant and ranged from 1.2 to 6.0 dB SNR and from 3.7 to 12.7 dB SNR depending on the CI system, respectively.Discussion: Directional microphones significantly improve SRT in noise for all three CI systems. However, relatively large differences were observed in the directional microphone efficacy between CI systems.

A New Slim Modiolar Electrode Array for Cochlear Implantation: A Radiological and Histological Study.

HYPOTHESIS: To explore the results of a new slim modiolar electrode array (SMA) with respect to intracochlear placement and trauma evaluated by detailed radiologic imaging and histology. BACKGROUND: Hearing and structure preservation is the goal of cochlear implantation for advanced hearing outcomes. Currently, this is most consistently achieved with thin lateral wall electrodes. Modiolar electrodes are located nearer the modiolus and may provide some electrophysiological advantages, but have a greater tendency for causing insertion trauma. METHODS: The SMA was implanted in 20 fresh-frozen human temporal bones (TB). All TBs were scanned pre- and postoperatively with cone beam computed tomography. For atraumatic insertion, the round window approach was preferred. Scalar localization and trauma were analyzed by three-dimensional image fusion reconstructions of the pre- and postimplant scans. The TBs underwent histologic examination to validate the radiologic findings. RESULTS: Insertion through the round window was performed in 19 TBs and through a cochleostomy in one TB. In one TB trauma in the form of scala translocation was identified radiologically and histologically. In the remaining TBs there was no insertion trauma. Adequate modiolar localization of the SMA was found in 19 of 20 TBs. The mean angular insertion depth was 400 degrees without correlation to cochlea size. There was no significant statistical difference between the radiological and histological measurements of electrode localization. CONCLUSION: The SMA showed consistent and atraumatic insertion results in TBs. Pre- and postimplant cone beam computed tomography with image fusion was shown to be very accurate for the assessment of electrode position and insertion trauma.

The development and evaluation of the Finnish digit triplet test.

OBJECTIVES: The aim of the study was to develop a reliable and easily accessible screening test for primary detection of hearing impairment. METHODS: Digits 0-9 were used to form quasirandom digit triplets. First, digit specific intelligibility functions and speech recognition thresholds (SRTs) were determined. To homogenize the test material digits with steep intelligibility function slopes were chosen and level correction up to ±2 dB were applied to the digits as needed. Evaluation measurements were performed to check for systematic differences in intelligibility between the test lists and to obtain normative reference function for normal-hearing listeners. RESULTS: The mean SRT and the final slope of the test lists were -10.8 ± 0.1 dB signal-to-noise ratio (SNR) and 21.7 ± 1.8%/dB, respectively (measurements at constant level; inter-list variability). The mean SRT and slope of the test subjects were -10.8 ± 0.5 dB SNR and 23.4 ± 5.2%/dB (measurements at constant level; inter-subject variability). The mean SRT for normal-hearing young adults for a single adaptive measurement is -9.8 ± 0.9 dB SNR. CONCLUSION: The Finnish digit triplet test is the first self-screening hearing test in the Finnish language. It was developed according to current standards, and it provides reliable and internationally comparable speech intelligibility measurements.

Characteristics and international comparability of the Finnish matrix sentence test in cochlear implant recipients.

OBJECTIVES: The first Finnish sentence-based speech test in noise--the Finnish matrix sentence test--was recently developed. The aim of this study was to determine the characteristics of the new test with respect to test-retest reliability, speech recognition curve, and international comparability in Finnish cochlear implant (CI) recipients. DESIGN: The speech reception thresholds (SRT) were measured by means of an adaptive test procedure and compared with the results of the traditional Finnish word test. Additional measurements for concurrent slope and SRT estimation were conducted to determine the speech recognition curve and to check the test-retest reliability. STUDY SAMPLE: The measurements were performed on 78 Finnish CI recipients. In a subset of 25 patients, additional measurements for test-retest reliability and slope determination were performed. RESULTS: The mean SRT was -3.5 ± 1.7 dB SNR, with only a weak correlation with the Finnish word test. Test-retest reliability was within ± 1 dB and the mean slope of the speech recognition curve was 14.6 ± 3.6 %/dB. The rehabilitation results were similar to the results published for the German matrix test. CONCLUSIONS: The Finnish matrix test was found to be suitable and efficient in CI recipients with similar characteristics as the German matrix test.