IMPORTANCE: Surgery remains the gold standard in cholesteatoma treatment. However, the rate of recurrence is significant and the development of new nonsurgical treatment alternatives is warranted. One of the possible molecular pathways to target is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.

OBJECTIVE: To investigate the JAK/STAT pathway in the middle ear mucosa in patients with acquired cholesteatoma compared with middle ear mucosa from healthy controls.

DESIGN: Case-control study.

SETTING: Linköping University Hospital, Sweden, and Karolinska Institutet, Stockholm, Sweden. Sampling period: February 2011 to December 2016.

PARTICIPANTS: Middle ear mucosa from 26 patients with acquired cholesteatoma undergoing tympanoplasty and mastoidectomy, and 27 healthy controls undergoing translabyrinthine surgery for vestibular schwannoma or cochlear implantation was investigated.

MAIN OUTCOMES/MEASURES: The expression of Interleukin-7 receptor alpha, JAK1, JAK2, JAK3, STAT5A, STAT5B, and suppressor of cytokine signaling-1 (SOCS1) were quantified using quantitative polymerase chain reaction. In addition, expression level of cyclin D2, transforming growth factor beta 1, thymic stromal lymphopoietin, CD3, and CD19 was evaluated.

RESULTS: In cholesteatoma-adjacent mucosa, SOCS1 was significantly upregulated (p= 0.0003) compared with healthy controls, whereas STAT5B was significantly downregulated (p = 0.0006). The expression of JAK1, JAK2, JAK3, and STAT5A did not differ significantly between groups.

CONCLUSIONS AND RELEVANCE: To the best of our knowledge, this is the first article reporting dysregulation of the JAK/STAT pathway in cholesteatoma-adjacent mucosa. The main finding is that important players of the aforementioned pathway are significantly altered, namely SOCS1 is upregulated and STAT5B is downregulated compared with healthy controls.

The middle ear is a small and hard to reach compartment, limiting the amount of tissue that can be extracted and the possibilities for studying the molecular mechanisms behind diseases like cholesteatoma. In this paper 14 reference gene candidates were evaluated in the middle ear mucosa of cholesteatoma patients and two different control tissues. ACTB and GAPDH were shown to be the optimal genes for the normalisation of target gene expression when investigating middle ear mucosa in multiplex qPCR analysis. Validation of reference genes using c-MYC expression confirmed the suitability of ACTB and GAPDH as reference genes and showed an upregulation of c-MYC in middle ear mucosa during cholesteatoma. The occurrence of participants of the innate immunity, TLR2 and TLR4, were analysed in order to compare healthy middle ear mucosa to cholesteatoma. Analysis of TLR2 and TLR4 showed variable results depending on control tissue used, highlighting the importance of selecting relevant control tissue when investigating causes for disease. It is our belief that a consensus regarding reference genes and control tissue will contribute to the comparability and reproducibility of studies within the field.

Purpose The aim of the study was to investigate the change in health-related quality of life ( HRQoL) after canal wall up cholesteatoma surgery, using the Glasgow Benefit Inventory (GBI). Methods Data from a consecutive group of 47 adults scheduled for primary cholesteatoma surgery using canal wall up (CWU) with obliteration, from January 2005 to December 2009, were analysed. Information was extracted from a medical database, and complementary data from patient files and audiograms were collected and recorded retrospectively. The GBI questionnaire was used for the assessment of HRQoL after surgery. Results There was no finding of residual or recurrent cholesteatomas in the study group. Hearing was improved at 1 and 3 years postoperatively. No patient suffered a total hearing loss. The overall GBI scores showed an improved HRQoL after surgery. Twenty-nine (85%) patients benefitted from surgery, 1 (3%) had no change, and 4 (12%) expressed deterioration. Conclusions Cholesteatoma surgery using CWU with obliteration gives an improved HRQoL for the majority of patients. The GBI questionnaire provides complementary information to hearing and healing results after cholesteatoma surgery.

Objective: To study the development of the bilateral benefit in children using bilateral cochlear implants by measurements of speech recognition and sound localization. Design: Bilateral and unilateral speech recognition in quiet, in multi-source noise, and horizontal sound localization was measured at three occasions during a two-year period, without controlling for age or implant experience. Longitudinal and cross-sectional analyses were performed. Results were compared to cross-sectional data from children with normal hearing. Study sample: Seventy-eight children aged 5.1-11.9 years, with a mean bilateral cochlear implant experience of 3.3 years and a mean age of 7.8 years, at inclusion in the study. Thirty children with normal hearing aged 4.8-9.0 years provided normative data. Results: For children with cochlear implants, bilateral and unilateral speech recognition in quiet was comparable whereas a bilateral benefit for speech recognition in noise and sound localization was found at all three test occasions. Absolute performance was lower than in children with normal hearing. Early bilateral implantation facilitated sound localization. Conclusions: A bilateral benefit for speech recognition in noise and sound localization continues to exist over time for children with bilateral cochlear implants, but no relative improvement is found after three years of bilateral cochlear implant experience.

Purpose: The aim of the study was to examine pre-operative expectations and the postoperative experiences related to cochlear implants (CI) in CI-users and their significant others. Methods: A questionnaire was used and the responses were analysed by means of The Qualitative Content Analysis. All adults implanted between 1992 and 2010, who had had their implants for a minimum of 12 months (n = 120) were contacted. Response rate was high (90.8%), and all-inclusive answers were received from 101 CI-users (84.2%). Results: The overall sense of increased well-being and life satisfaction was described as having lived in two different worlds, one with the auditory stimulation and one without. In the overall sense of increased well-being and satisfaction three interwoven subcategories, alienation - normality, fear - autonomy, and living a social life emerged. When CI-users and their significant others recalled the time prior to receiving the CI, a sense of fear was present with origins in the concern for the respondents (CI-users) ability to cope and care independently in society. Conversely, after the implantation both parties emphasized the notion of a distinct transformation within the CI-user towards autonomy. Communication was highlighted as a large part of living social life. Conclusion: The CI increases well-being and satisfaction for both CI-users and their significant others, which is especially evident regarding enhanced autonomy, normality and living social life.

Objective: To investigate the influence of cardiovascular diseases on hearing impairment (HI) among adults. Furthermore, to seek other potential risk factors for HI, such as smoking, obesity, and socioeconomic class. Design: A cross-sectional, unscreened, population-based, epidemiological study among adults. Study sample: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Results: Cardiovascular diseases did not increase the risk for HI in a propensity-score adjusted logistic regression model: OR 1.24, 95% CI 0.79 to 1.96 for HI defined by better ear hearing level (BEHL), and OR 1.48, 95% CI 0.96 to 2.28 for HI defined by worse ear hearing level (WEHL), in the 0.5-4 kHz frequency range. Heavy smoking is a risk factor for HI among men (BEHL: OR 1.96, WEHL: OR 1.88) and women (WEHL: OR 2.4). Among men, obesity (BEHL, OR 1.85) and lower socioeconomic class (BEHL: OR 2.79, WEHL: OR 2.28) are also risk factors for HI. Conclusion: No significant association between cardiovascular disease and HI was found.

Objective: This study includes a battery of psychoacoustical and electrophysiological tests to quantitatively investigate the changes in the frequency and the temporal features of the human auditory periphery caused by aging (presbyacusis) and noise-induced lesions, two common types of sensorineural hearing impairments. The scores are comparatively analyzed.

Design: These clinical experiments have been implemented in MATLAB software.

Study sample: 20 normal hearing adults (aged 30-54), 20 older hearing-impaired subjects (aged 65-70) with no history of Ototoxic medication or noise exposure and 7 adult men with a traceable noise-induced hearing impairment.

Results: The observed temporal and spectral declines are generally consistent with the high-frequency audiometric loss depicted by the audiogram, for each group. Moreover, the test battery provides valuable information on the frequency sensitivity, temporal resolution, loudness growth, compression and otoacoustic emissions.

Conclusion: These scores are compared with the predictions of a physiologicallybased cochlear model to provide evidence about specific inner-ear pathologies, beyond what the audiogram can indicate. Among these 7 clinical experiments, the results from the forward temporal masking test, the categorical loudness discrimination test and the distortion product otoacoustic emission test provide the most differential information about the underlying cellular lesions. The results indicate that the reduction in the temporal resolution is substantially age-relate since the presbyacusis listeners, unlike the other groups, obtained almost no benefit from the temporal cues provided by the gap duration at any of the experiments. Moreover, the results suggest that the DPOAEs reflect the cellular lesions associated with the acoustic overstimulation rather than the age-related strial degenerations.

The purpose of the study was to examine neurophysiological, cognitive and linguistic development in deaf and hearing-impaired children (5–7 years of age) with CI and/or hearingaids and how a phonological intervention programme may influence this development. The deaf and hearing-impaired children were compared with age-matched hearing children. The results reveal that deaf and hearing-impaired children had equivalent or close to equivalent performance levels compared to hearing children for cognitive and linguistic tasks with relatively low demands on phonological processing, whereas there was a substantial and significant difference between the groups for cognitive tasks involving explicit phonological processing. The results indicate that there is a relationship between age at implant and neurophysiological, cognitive and linguistic development, where early implantation promotes faster development. The childrens´ cognitive performance increased as a function of phonological intervention.

OBJECTIVE:

To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated.

STUDY DESIGN:

Multicenter survey in 8 European centers.

SUBJECTS:

One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study.

RESULTS:

We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies.

DISCUSSION:

Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.