Early Results With the New Active Bone-Conduction Hearing Implant: A Systematic Review and Meta-Analysis.

OBJECTIVE: The bone conduction implant (BCI) 602 is a new transcutaneous BCI with smaller dimensions. However, limited patient numbers restrict the statistical power and generalizability of the current studies. The present systematic review and meta-analysis summarize early audiological and medical outcomes of adult and pediatric patients implanted with the BCI 602 due to mixed or conductive hearing loss. DATA SOURCE: Following the Preferred Reporting items for Systematic Reviews and Meta-analyses guidelines, 108 studies were reviewed, and 6 (5.6%) were included in the meta-analysis. REVIEW METHOD: The data on study and patient characteristics, surgical outcomes, and audiological test results were extracted from each article. Meta-analysis employed the fixed-effect and random-effects models to analyze the mean differences (MDs) between pre- and postoperative performances. RESULTS: In total, 116 patients were evaluated, including 64 (55%) adult and 52 (45%) pediatric patients. No intraoperative adverse events were reported, while postoperative complications were reported in 2 (3.1%) adult and 2 (3.8%) pediatric patients. Studies consistently showed significant improvements in audiological outcomes, quality of life, and sound localization in the aided condition. In the meta-analysis, we observed a significant difference in the unaided compared to the aided condition in sound field thresholds (n = 112; MD, -27.05 dB; P < 0.01), signal-to-noise ratio (n = 96; MD, -6.35 dB; P < 0.01), and word recognition scores (n = 96; MD, 68.89%; P < 0.01). CONCLUSION: The implantation of the BCI 602 was associated with minimal surgical complications and excellent audiological outcomes for both the pediatric and the adult cohort. Therefore, our analysis indicates a high level of safety and reliability. Further research should focus on direct comparisons with other BCIs and long-term functional outcomes.

Experience With the New Active Transcutaneous Bone-Conduction Implant With Smaller Dimensions.

OBJECTIVE: Recently, the Bonebridge 602 implant was introduced. Its smaller dimensions facilitate implantation even in surgically demanding cases. However, in extreme anatomical conditions, implant lifts are still required. We intended to report on the medical and audiological outcomes of all patients implanted with the implant with a secondary focus on the safety, efficacy, and feasibility of the use of 1-mm lifts. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: We retrospectively analyzed all patients implanted with the Bonebridge 602. Patient demographics and surgically-specific data were collected from the medical charts. Furthermore, audiological results were assessed. Outcomes were compared between implantations with versus without lifts. RESULTS: Twenty-one devices were implanted during the study period. Satisfactory audiological results were observed, while no intra- or postoperative adverse events occurred. The majority of patients were daily users at the end of the observation period (n = 20/21, 95.2%), and one patient (n = 1/21, 4.8%) was a nonuser after 6 months of use because of subjective dissatisfaction. Due to anatomical considerations, 1-mm lifts were used in 4 implantations (19.0%). The application of lifts did not result in prolonged surgical times, complications, or shorter time of use, nor did it negatively affect audiometric results. CONCLUSION: Implantations with the new and smaller Bonebridge were associated with gratifying medical and audiological outcomes. Still, in extreme anatomical conditions, 1-mm lifts are necessary. Nonetheless, surgical placement with the help of lifts seems safe, effective, and feasible, and is a viable option in cases with challenging anatomies due to previous surgeries or anomalies.

Progressive Sensorineural Hearing Loss in Vibrant Soundbridge Users Requiring Cochlear Implantation.

Less than 20% of patients with sensorineural hearing loss (HL) provided with the Vibrant Soundbridge (VSB) experience a progressive HL and warrant cochlear implantation (CI). The aim of this study was to identify possible predictors of progressive HL prior to VSB implantation. This retrospective study included all consecutive ears with sensorineural HL provided with the VSB between 1998 and 2016. The patient cohort was divided in a study group comprising patients who underwent CI (CI group) after years of VSB usage and those who did not require VSB replacement during the observational time (control group). Pre- and postoperative pure-tone audiometry thresholds were compared among the two groups. Fifteen out of 81 VSB devices (18.5%) required a CI. The CI group had higher preoperative air-conduction (AC) thresholds than the control group (64.3 ± 8.9 dB vs. 56.3 ± 12.9 dB; p = 0.007) at the time of the VSB implantation. On average, the CI group was significantly younger (39.1 ± 12.3 years vs. 52.6 ± 16.2 years; p = 0.003). In conclusion, VSB users with higher preoperative AC thresholds and younger age at the time of VSB implantation might be at risk for progressive HL within the upcoming eight years and need a further CI surgery. Preoperative counseling is particularly advisable in this patient group.

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.

Safety and Efficacy of Implantation of the Bonebridge Active Transcutaneous Bone-Conduction Device Using Implant Lifts.

BACKGROUND: Implant lifts were recently introduced to facilitate implantation of the Bonebridge and to reduce the risk of uncovering the sigmoid sinus and/or dura. PURPOSE: The current study analyzed medical, technical, and audiological outcomes of implantation with the Bonebridge implant using lifts. RESEARCH DESIGN: This was a retrospective study on all consecutive patients implanted with a bone-conduction hearing implant at a tertiary medical referral center between March 2012 and October 2018. Outcome measures were complications, explantations, and revisions and the mean time of implant use. Audiological results were assessed as well. Outcomes were evaluated for devices implanted with BCI Lifts and compared with those implanted without lifts. RESULTS: In the study period, 13 out of a total of 54 implantations were conducted using one or two 1- to 4-mm BCI Lifts. During the follow-up period, two complications occurred and both in patients implanted without lifts (2/41; 4.9%). All patients in the lifts group were using the implant at the end of observation period. No statistically significant difference was observed in functional hearing gain or word-recognition improvement at 65 dB between two groups. CONCLUSIONS: The use of BCI Lifts in Bonebridge implantations was not associated with adverse events during the observation period. The clinical follow-up revealed no complications in implantations requiring lifts. Furthermore, the functional hearing gain and the word-recognition improvement did not differ from those of devices implanted without lifts. Data indicate safety and efficacy for Bonebridge implantations using lifts.

Impact of air pollution on symptom severity during the birch, grass and ragweed pollen period in Vienna, Austria: Importance of O3 in 2010-2018.

Air pollution is a threat to the general population, especially to pollen allergy sufferers in urban environments. Different air quality parameters have hitherto been examined which add to the burden of pollen allergy sufferers. Parameters such as NO2, SO2, PM10, PM2.5, and O3 are supposed to have additional impact, not only on health in general (increase in asthma, allergy sensitization frequency), but also on pollen grains (increase of allergenicity). However, it remains unknown if those air quality parameters increase symptom severity during the pollen season. We selected the birch, grass, and ragweed pollen seasons as different time periods throughout the year and analyzed the relationship of symptom data to pollen, air quality, and meteorological data (temperature, relative humidity) for the metropolis of Vienna (Austria). A linear regression model was computed based on different symptom data, and both pollen and air quality data were tested simultaneously. Ozone was positively and significantly associated with symptom scores in all three seasons, whereas this was only rarely the case with other pollutants. Therefore, only ozone was selected for further analysis in a model including meteorological parameters. In this model, effect estimates of ozone were attenuated but remained significant for the grass pollen season. The lack of significance in the other seasons may be attributed to the less numerous symptom data entries and the shorter duration of the pollen seasons for birch and ragweed. All other air quality parameters usually showed lower concentrations during the pollen seasons and displayed little variation. This might explain the lack of a clear signal. Our results suggest that today's allergic population is already affected by air quality (rising O3 levels). Air quality should be considered as well in pollen information and pollen allergy studies in general because of its increasing importance in the light of global warming.

The reliability of hearing implants: report on the type and incidence of cochlear implant failures.

Objectives: This study presents the data collected through a database on the type and incidence of cochlear implant device failures and major complications and quantifies the risk of failures across time based on the Association for the Advancement of Medical Instrumentation (AAMI) CI86:2017 standard. Methods: Information on reliability of MED-EL cochlear implants was collected from the MED-EL complaint database between 2003 and2013. Explants were categorized and device reliability was calculated according to the AAMI CI86:2017 standard principles. Results: Data were collected for 11662 devices (5462 children, 6200 adults). The mean duration of follow up was 46.16 months. The total failure rate for all devices and all subjects was 2.41%. Medical related explants (MRE) were significantly worse for children than for adults with the ceramic implants, C40+ (p = 0.008) and PULSAR (p = 0.020). Device failure explants (DFE) were significantly worse for children than for adults with all four devices in the study, the C40+ (p < 0.001), PULSAR (p < 0.001), SONATA (p < 0.001), and CONCERTO (p = 0.023). The mean annual failure rate for all subjects and devices was 0.63% (1.03% for children, 0.28% for adults). The mean annual failure rate was 0.90% for the C40+; 0.57% for the PULSAR; 0.46% for the SONATA; and 0.39% for the CONCERTO. Conclusions: Compared to adults, children had significantly worse MRE and DFE due to a higher risk of head trauma and more vulnerable skull anatomy. Further, the authors conclude that the AAMI standard will ensure a more comprehensive and transparent evaluation of cochlear implant reliability in the future.

Cross-sectional study on the occurrence of Frey's syndrome following superficial parotidectomy or extracapsular dissection.

BACKGROUND: Most studies that examine postoperative outcomes after parotidectomy in patients with benign parotid gland tumors are based on retrospective chart reviews. Data about long-term results in patients with parotid gland surgery with patient contact are still sparsely published. METHODS: During the period of 1960-2005, a total of 127 patients underwent either extracapsular dissection (ECD) or superficial parotidectomy (SP) and were available for interview. Patients were questioned about their postoperative outcome after parotid gland surgery. RESULTS: The mean follow-up was 21.5 years. A total of 42 and 85 patients underwent ECD and SP, respectively. No significant differences were observed in the rates of permanent facial paralysis (SP 1.2% vs. ECD 7.1%; p = 0.1053) or recurrence (SP 4.7% vs. ECD 11.9%; p = 0.1557), and Frey's syndrome was diagnosed only after SP (10.6% vs. 0% after ECD, p = 0.0293). Frey's syndrome was detected more often compared to retrospective chart analysis. CONCLUSION: We conclude that Frey's syndrome is underdiagnosed after SP without standardized follow-up examinations. Long-term follow-up should be applied to detect and treat gustatory sweating.

Medical, Technical and Audiological Outcomes of Hearing Rehabilitation with the Bonebridge Transcutaneous Bone-Conduction Implant: A Single-Center Experience.

Bone-conduction implants are a standard therapeutic option for patients with conductive, unilateral, or mixed hearing loss who either do not tolerate conventional hearing aids or can benefit from surgery. The aim of this study was to evaluate long-term medical and technical outcomes, and audiological results with the Bonebridge transcutaneous bone-conduction implant. This retrospective study included all patients implanted with a bone-conduction hearing implant at a tertiary medical referral center between March 2012 and October 2018. Medical and technical outcomes included the mean length of implant usage, medical and technical complications (skin and wound infection, lack of benefit, technical failure), explantations and revisions, coupling approaches, implant failure rate, implant survival and the implant loss for added follow-up years. Auditory results were measured by functional hearing gain and the Freiburger monosyllabic test at 65 dB sound pressure level. Sixty-four patients were included in the study; five of these were implanted bilaterally (69 devices). Five unilaterally implanted patients were lost to follow-up. The mean follow-up was 27.1 months (range: 0.2 months-6.3 years). The mean implant usage was 25.9 months (range: 0.2 months-6.3 years). Fifty-seven implants (89.1%) were in use at the end of the follow-up period. Complications occurred in six ears (9.4%). Five implants (7.8%) were explanted without reimplantation. Device failure occurred in one implant (1.6%), which was possibly caused by recurrent head trauma. The rate of implant loss due to technical device failure (damage to device) was 1 per 72 follow-up years. The mean improvement on the Freiburger monosyllabic test (52.1%, p = 0.0001), and in functional hearing gain across frequencies (26.5 dB, p = 0.0001) was significant. This single-center follow-up reveals the medical and technical reliability of a transcutaneous bone-conduction implant for hearing rehabilitation because complication and revision rates were low. The majority of patients still used the device at the end of the observation period. Implantation resulted in favorable hearing outcomes in comparison to that of unaided conditions. Cautious patient selection mainly regarding co-morbidities, the history of chronic otologic diseases and proper surgical technique seems to be crucial in reducing complications.

Single Sided Deaf Cochlear Implant Users in the Difficult Listening Situation: Speech Perception and Subjective Benefit.

OBJECTIVES: Patients with single-sided deafness (SSD) have great difficulties in listening situations which rely on binaural auditory processing. The purpose of this study was to examine to which extent a cochlear implant (CI) can improve speech perception outcomes in various noisy listening environments. Additionally, the ability to use interaural level differences for sound localization and subjective benefit with the CI were assessed. METHODS: Ten single-sided deaf patients with CI were tested in different loudspeaker configurations with and without the CI. A multi-source noise field (MSNF) with uncorrelated noise from four different directions was used in addition to a setup with the signal from the CI side and noise from the normal-hearing side (SCINNH, azimuth of ±45 degrees). Ten normal-hearing subjects were used as a control for the setup. Speech understanding was measured by an adaptive sentence test (Oldenburg Sentence Test, OLSA) in stationary speech shaped noise and temporally modulated noise to assess the benefit in each listening situation. Sensitivity to interaural level differences was measured in a lateralization experiment. Furthermore, patients completed the Bern Benefit in Single-Sided Deafness (BBSS) questionnaire to assess subjective benefit with the CI. RESULTS: An overall average benefit in speech reception threshold (SRT) of 1.6 dB (±0.6 dB standard error of the mean [SEM]) was observed in the binaural listening condition (with CI) in all conditions. In the MSNF setup thresholds improved by 0.4 dB (±0.5 dB SEM) and in the SCINNH configuration by 2.7 dB (±0.7 dB SEM). The choice of masking noise effect also had a significant effect on the SRT outcome. The lateralization performance of the SSD users was on a par with the normal hearing group. BBSS scores reflect the overall benefit with the CI apparent in the speech test results. CONCLUSION: Patients with single-sided deafness do benefit from a CI in difficult listening environments and are able to localize sound based on interaural level differences. Considering these outcomes, cochlear implantation represents a promising treatment option for patients with single-sided deafness.

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEXSOFT electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties.

AdOnco database - six years' experience with the documentation of clinical and scientific data on patients with head and neck cancer.

PURPOSE: To report the experience with AdOnco, a computerized database for head and neck cancer patients. PATIENTS AND METHODS: AdOnco is a Filemaker Pro 6.0 based database integrated into the local network of the host ENT department. It is used by the physicians as a clinical and scientific documentation system to store and retrieve information about all patients with head and neck cancer referred to the host oncology center. This study reviews the achievements to date of AdOnco and, as an example of its enormous data evaluation potential, presents survival curves of patients with laryngeal cancer undergoing laser resection. RESULTS: Over a period of six years, the data of 881 patients with head and neck cancer were entered into the AdOnco database. CONCLUSION: AdOnco has proven to be a useful patient database and documentation system which has become an integral and essential part of daily clinical routine and also a valuable research tool.

Does dexamethasone inhibit the antineoplastic effect of cisplatin and docetaxel in head and neck cancer cells?

BACKGROUND/AIM: Comedication with glucocorticoids such as dexamethasone is frequently given to head and neck cancer patients treated with chemotherapy. However, an increasing body of evidence suggests that dexamethasone may induce resistance to antineoplastic agents. The present study was the first to investigate the effect of dexamethasone on the antiproliferative activity of cisplatin and docetaxel in vitro in squamous cell carcinoma of the head and neck (SCCHN) cell lines. MATERIALS AND METHODS: The cytotoxic effect of cisplatin and docetaxel on eight SCCHN cell lines was determined for each drug alone or with increasing concentrations of dexamethasone. Cell growth inhibition and viability were measured quantitatively after 24, 48, 72 hours of treatment using water-soluble-tetrazolium-test and lactate dehydrogenase assays. Absolute tumor cell numbers were determined by cell counting in a Rosenthal chamber. RESULTS: Cisplatin and docetaxel alone inhibited the growth of all eight SCCHN cell lines significantly (p=0.012). The antiproliferative activity of both agents was not decreased by the addition of dexamethasone in any of the cell lines (p>0.05). CONCLUSION: Dexamethasone does not interfere with the cytotoxic action of cisplatin or docetaxel in the investigated SCCHN cell lines.

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Glucocorticoids such as dexamethasone are widely used as comedication in the treatment of head and neck cancer, e.g., to improve appetite and decrease weight loss and fatigue in patients with advanced disease or as antiallergic and antiemetic prophylaxis during anti-EGFR therapy. However, the literature suggests that dexamethasone induces resistance to antineoplastic agents in many solid tumor models in vitro and in vivo. Since this phenomenon has never been investigated in head and neck cancer, the present study was conducted to investigate the effect of dexamethasone on the antiproliferative activity of cetuximab in vitro in squamous cell carcinoma of the head and neck (SCCHN) cell lines. The antiproliferative effect of the anti-EGFR agent cetuximab alone and in combination with increasing concentrations of dexamethasone was examined in eight SCCHN cell lines at three different time-points (24, 48 and 72 h). Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Absolute tumor cell numbers were determined by cell counting in a Rosenthal chamber. Cetuximab alone inhibited the growth of all eight SCCHN cell lines significantly (p=0.008). In some cases the addition of dexamethasone reduced the antiproliferative activity of cetuximab (p

Cetuximab enhances the efficacy of bortezomib in squamous cell carcinoma cell lines.

PURPOSE: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade) in combination with cetuximab in squamous cell carcinoma cell lines (SCC). METHODS: Dose-escalation studies were performed in five squamous cell carcinoma cell lines using bortezomib or cetuximab alone or in combination. Cell survival and growth inhibition were measured quantitatively using an MTT and LDH assay. RESULTS: Bortezomib alone showed a significant antiproliferative activity in all SCC cell lines (P < 0.042), and the activity was further significantly enhanced by the addition of cetuximab (P < 0.043). CONCLUSIONS: Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in SCC cell lines. Combination therapy of SCC with bortezomib and cetuximab might be less toxic than conventional drug regimens used in the treatment of these tumors.

Effects of combination treatment of bortezomib and dexamethasone in SCCHN cell lines depend on tumor cell specificity.

Bortezomib has recently become the new treatment standard for relapsed or refractory multiple myeloma. We previously demonstrated that bortezomib also had a significant growth-inhibiting and apoptotic effect on squamous cell carcinoma of the head and neck (SCCHN) cells in vitro. Preclinical evidence has provided a rationale for combining bortezomib with dexamethasone in multiple myeloma, suggesting that the therapeutic effects of the two agents might be additive. These findings are in contrast with the results achieved in solid tumor models where the addition of dexamethasone reduced the efficacy of other antineoplastic drugs. In the present study, we investigated the effect of dexamethasone in combination with bortezomib in SCCHN cell lines for the first time. The antiproliferative effect of bortezomib alone or in combination with increasing concentrations of dexamethasone was investigated in four SCCHN cell lines. Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Bortezomib alone inhibited the growth of all four SCCHN cell lines significantly (p<0.047). The addition of dexamethasone leads to a clear tumor cell decline and showed a trend in enhancing the growth-inhibitory effect of bortezomib although the difference failed to reach statistical significance (p>0.05). Our first results show that dexamethasone increased the cytotoxic activity of bortezomib in most SCCHN cell lines investigated. These findings might be dependent on molecular factors such as the degree of tumor cell differentiation and proliferation rate. Therefore, further studies will be required to elucidate these molecular factors to substantiate our findings from a cancer biological point of view.

Effect of bortezomib and cetuximab in EGF-stimulated HNSCC.

BACKGROUND: Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, the antitumor effect of bortezomib (Velcade) in combination with cetuximab was investigated in epidermal growth factor (EGF)-stimulated head and neck squamous cell carcinoma cell lines (HNSCC). MATERIALS AND METHODS: Dose escalation studies were performed with five EGF-stimulated squamous cell carcinoma cell lines using bortezomib alone or in combination with cetuximab. Growth inhibitory and cell decline effects were measured quantitatively using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assay. RESULTS: Bortezomib alone showed no significant antiproliferative activity in any EGF-stimulated HNSCC cell line (p > 0.05), whereas the combination of bortezomib and cetuximab had highly significant antitumoral activity (p < 0.043). CONCLUSION: Our results indicate that cetuximab increases the cytotoxic activity of bortezomib in EGF-stimulated HNSCC cell lines. A combination treatment of HNSCC with bortezomib and cetuximab may allow a therapeutical regimen to be developed that is less toxic than the conventional drugs used for these tumors.