Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A.

BACKGROUND: Selective glucocorticoid receptor modulators (SEGRMs) comprise a novel class of drugs promising both reduced side effects and similar pharmacological potency relative to glucocorticoids, which presently serve as the only clinical treatment for many otologic disorders. In the first otologic SEGRM experiment in an animal model of noise trauma, we compare the effects of Compound A (a SEGRM) and dexamethasone (potent glucocorticoid). METHODS: Forty adult guinea pigs received experimental treatment once daily for ten days. The animals were divided into four cohorts based on the treatment received: Compound A (1 mg/kg or 3 mg/kg), dexamethasone (1 mg/kg) as gold standard, or water as negative control. After five applications, animals were exposed to broadband noise (8-16 kHz) at 115 dB for three hours. Hearing thresholds were determined by recording auditory brainstem responses to clicks and noise bursts (1-32 kHz) and were assessed a week prior to and immediately after exposure, as well as on days 1, 3, 7, 14, 21, and 28. Cochleae were prepared as whole-mounts or embedded and sectioned for histological analysis. RESULTS: Relative to the control treatments, Compound A failed to preserve auditory thresholds post-noise exposure with statistical significance. Histological analyses confirm the physiological result. CONCLUSION: The present findings suggest that Compound A does not have substantial otoprotective capacities in a noise trauma model.

Sustained release of triamcinolone acetonide from an intratympanically applied hydrogel designed for the delivery of high glucocorticoid doses.

The pharmacokinetic properties and tolerability of a triamcinolone acetonide poloxamer 407 hydrogel for intratympanic application were investigated in a guinea pig model. Evaluation of in vivo release kinetics showed very high initial perilymph drug levels, with clinically relevant levels present for a minimum of 10 days. Assessment of auditory brainstem response thresholds showed a minimal, delayed and transient threshold shift, which was apparent on day 3 and resolved by day 10. No relevant histological changes of the middle and inner ear structures were noted, and hair cell counts showed no significant differences between treated and untreated ears. Thus, the triamcinolone-acetonide-loaded poloxamer 407 hydrogel is an effective vehicle for sustained high-dose inner ear glucocorticoid delivery.

FS4, FS4-p, and FSP: a 4-month crossover study of 3 fine structure sound-coding strategies.

OBJECTIVES: The aim of the present study was to compare two novel fine structure strategies "FS4" and "FS4-p" with the established fine structure processing (FSP) strategy. FS4 provides fine structure information on the apical four-electrode channels. With FS4-p, these electrodes may be stimulated in a parallel manner. The authors evaluated speech perception, sound quality, and subjective preference. DESIGN: A longitudinal crossover study was done on postlingually deafened adults (N = 33) who were using FSP as their default strategy. Each participant was fitted with FS4, FS4-p, and FSP, for 4 months in a randomized and blinded order. After each run, an Adaptive Sentence test in noise (Oldenburger Sentence Test [OLSA]) and a Monosyllable test in quiet (Freiburger Monosyllables) were performed, and subjective sound quality was determined with a Visual Analogue Scale. At the end of the study the preferred strategy was noted. RESULTS: Scores of the OLSA did not reveal any significant differences among the three strategies, but the Freiburger test showed a statistically significant effect (p = 0.03) with slightly worse scores for FS4 (49.7%) compared with FSP (54.3%). Performance of FS4-p (51.8%) was comparable with the other strategies. Both audiometric tests depicted a high variability among subjects. The number of best-performing strategies for each participant individually was as follows: (a) for the OLSA: FSP, N = 10.5; FS4, N = 10.5; and FS4-p, N = 12; and (b) for the Freiburger test: FSP, N = 14; FS4, N = 9; and FS4-p, N = 10. A moderate agreement was found in the best-performing strategies of the Speech tests within the participants. For sound quality, speech in quiet, classical, and pop music were assessed. No significant effects of strategy were found for speech in quiet and classical music, but auditory impression of pop music was rated as more natural in FSP compared with FS4 (p = 0.04). It is interesting that at the end of the study, a majority of the participants favored the new coding strategies over their previous default FSP (FSP, N = 13; FS4, N = 13; FS4-p, N = 7). CONCLUSIONS: In summary, FS4 and FS4-p offer new and further options in audio processor fitting, with similar levels of speech understanding in noise as FSP. This is an interesting result, given that the strategies' presentation of temporal fine structure differs from FSP. At the end of the study, 20 of 33 subjects chose either FS4 or FS4-p over their previous default strategy FSP.

Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events.

Background and Objective: The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process. Methods: A systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types. Results: A total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4-6.6%) of ETFO, 28.6% (26.6-30.6%) of ESD, and 0.53% (0.2-1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1-1.3%), 11% (9.2-13.0%), and 3.2% (2.5-3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed. Conclusion: Considering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications.

Protection of inner ear function after cochlear implantation: compound action potential measurements after local application of glucocorticoids in the guinea pig cochlea.

BACKGROUND: Cochlear implant users with residual hearing often benefit greatly from simultaneous electric and acoustic stimulation. However, implantation can cause trauma to the inner ear, resulting in poorer hearing postoperatively. We investigated whether a single local injection of glucocorticoids can reduce hearing loss in long-term implanted guinea pigs. METHODS: Three groups of animals underwent bilateral surgery. One ear was implanted with an electrode, and the contralateral ear received a cochleostomy only. A single dose of the glucocorticoids triamcinolone or dexamethasone, or of artificial perilymph was infused into cochleae via cochleostomy. Compound action potentials were measured before and after application and for 3 months postoperatively. Tissue growth was measured as the percentage of the total area of the scala tympani that was obliterated. RESULTS: Ears subjected to cochleostomy only and treated with glucocorticoids demonstrated a mild hearing loss. In the implanted ears, both glucocorticoids preserved hearing at least temporarily. The volume of tissue growth within the scala tympani was not reduced, and there was no relation between the amount of tissue and hearing loss. CONCLUSIONS: Both glucocorticoids show a potential benefit for hearing preservation in implanted ears. Glucocorticoid therapy may be useful to protect residual hearing during cochlear implantation.

Assessment of the subjective benefit of electric acoustic stimulation with the abbreviated profile of hearing aid benefit.

CONCLUSION: This study demonstrates that electric-acoustic stimulation (EAS) significantly decreases the subjective impairment in speech perception. OBJECTIVES: To assess the subjective benefit of EAS over the first 12 months after EAS fitting using the Abbreviated Profile of Hearing Aid Benefit (APHAB). METHOD: Twenty-three EAS users, implanted with either the PULSAR(CI)(100) FLEX(EAS) provided with the DUET EAS processor or the COMBI40+ Medium provided with the TEMPO+ speech processor, were included. Electric stimulation was activated about 1 month postoperatively; ipsilateral acoustic stimulation was added 2 months thereafter. EAS benefit was measured preoperatively with only a hearing aid and postoperatively at EAS fitting and then 3, 6 and 12 months after EAS fitting using the APHAB. RESULTS: Subjects reported significant improvements in the global score with a mean decrease in impairment from 74% preoperatively to 45% after 3 months of EAS use. Furthermore, clinical relevance was demonstrated in multiple subscales between preoperative and first fitting reflecting a true benefit of EAS with a probability of 95%.

Long-Term Outcome and Comparison of Treatment Modalities of Temporal Bone Paragangliomas.

INTRODUCTION: Temporal bone paragangliomas are rare tumors with high vascularization and usually benign entity. A variety of modalities, including gross total resection, subtotal resection, conventional or stereotactic radiotherapy including gamma-knife, embolization, and wait-and-scan strategy can be considered. The aim of this study was to compare long-term outcomes of different primary treatment modalities in temporal bone paragangliomas. MATERIALS AND METHODS: Patients with temporal bone paragangliomas treated between 1976 and 2018 at a tertiary referral center were retrospectively analyzed in this study. Collected patient data of 42 years were analyzed and long-term results including interdisciplinary management were assessed. Patient outcomes were compared within the different therapy modalities according to tumor control rate and complications. Clinical characteristics, radiological imaging, tumor extent and location (according to Fisch classification), symptoms, and follow-up were evaluated and a descriptive analysis for each treatment modality was performed. Tumor recurrence or growth progression and respective cranial nerve function before and after therapy were described. RESULTS: A total of 59 patients were treated with a single or combined treatment modality and clinical follow-up was 7 (13) years (median, interquartile range). Of the included patients 45 (76%) were female and 14 (24%) male (ratio 3:1) with a patient age range from 18 to 83 years. Total resection was performed on 31 patients, while 14 patients underwent subtotal resection. Eleven patients were treated with conventional primary radiotherapy or gamma-knife radiosurgery. Pulsatile tinnitus (n = 17, 29%) and hearing impairment (n = 16, 27%) were the most common symptoms in our patient group. Permanent lower cranial nerve deficits were observed only in patients with large tumors (Fisch C and D, n = 14, 24%). Among the 45 patients who were treated surgically, 88% of patients with Fisch A and B paragangliomas had no recurrent disease, while no tumor growth was perceived in 83% of patients with Fisch C and D paragangliomas. CONCLUSION: In conclusion, we propose surgery as a treatment option for patients with small tumors, due to a high control rate and less cranial nerve deficits compared to larger tumors. Although patients with Fisch C and D temporal bone paraganglioma can be treated surgically, only subtotal resections are possible in many cases. Additionally, frequent occurrence of cranial nerve deficits in those patients and tumor growth progression in long-term follow-up examinations make a combination of the therapy modalities or a primary radiotherapy more suitable in larger tumors.

High Prevalence of MYO6 Variants in an Austrian Patient Cohort With Autosomal Dominant Hereditary Hearing Loss.

INTRODUCTION: Genetic hearing loss (HL) is often monogenic. Whereas more than half of autosomal recessive (AR) cases in Austria are caused by mutations in a single gene, no disproportionately frequent contributing genetic factor has been identified in cases of autosomal dominant (AD) HL. The genetic characterization of HL continues to improve diagnosis, genetic counseling, and lays a foundation for the development of personalized medicine approaches. METHODS: Diagnostic HL panel screening was performed in an Austrian multiplex family with AD HL, and segregation was tested with polymerase chain reaction and Sanger sequencing. In an independent approach, 18 unrelated patients with AD HL were screened for causative variants in all known HL genes to date and segregation was tested if additional family members were available. The pathogenicity of novel variants was assessed based on previous literature and bioinformatic tools such as prediction software and protein modeling. RESULTS: In six of the 19 families under study, candidate pathogenic variants were identified in MYO6, including three novel variants (p.Gln441Pro, p.Ser612Tyr, and p.Gln650ValfsTer7). Some patients carried more than one likely pathogenic variant in known deafness genes. CONCLUSION: These results suggest a potential high prevalence of MYO6 variants in Austrian cases of AD HL. The presence of multiple rare HL variants in some patients highlights the relevance of considering multiple-hit diagnoses for genetic counseling and targeted therapy design.

Long-Term Outcome of Hearing Rehabilitation With An Active Middle Ear Implant.

OBJECTIVE: To assess the audiological and long-term medical and technical follow-up outcomes of an active middle ear implant. METHODS: This was a retrospective medical chart analysis of all patients provided with an active middle ear implant in a tertiary academic medical referral center between September 1, 1998, and July 31, 2015. Main outcome measures were medical and technical complications, revisions, reimplantations, explantations, coupling approaches, mean time of use, pre- and postoperative hearing thresholds, functional hearing gain across frequencies (250-4,000 Hz), and Freiburg monosyllablic word test at 65 dB. RESULTS: One hundred and three patients were identified. Fifteen were implanted bilaterally (n = 118 Vibrant Soundbridge devices [MED-EL, Innsbruck, Austria]). Seventy-seven devices were implanted for sensorineural and 41 for mixed and conductive hearing loss. Patients used the implant for 6.7 years (range 0.7 months-17.9 years) on average. Ninety-one patients (77.12%) were using the device at the end of the observation period. An overall complication rate of 16.1% was observed. The revision and explantation rates were higher for devices implanted between 2004 and 2006. The device failure rate was 3.4%. Audiological evaluation showed significant hearing gains for both hearing loss patient groups. CONCLUSION: This long-term follow-up reveals the reliability of the active middle ear implant in a single center. Overall complication rate and device failure rate are acceptable. The complication rate was higher during implementation of alternative coupling approaches. The audiological benefit was satisfactory in patients with all hearing loss types. The majority of implanted patients used the implant at the end of the observation period. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:477-481, 2019.

Variance of angular insertion depths in free-fitting and perimodiolar cochlear implant electrodes.

OBJECTIVE: To assess the variance in cochlear implant electrode insertion depth in degrees around the modiolus (angular insertion depth) in free-fitting and perimodiolar electrode arrays. MATERIALS AND METHODS: Twenty-eight fresh human temporal bones were implanted with free-fitting cochlear implant electrodes, and 18 bones were implanted using perimodiolar electrode arrays. Specimens were embedded, and 2-dimensional radiographs were obtained to assess angular insertion depths. Histologic serial sections of undecalcified bones were then evaluated to analyze intracochlear electrode positions. Finally, linear surgical insertion depths (in millimeters) were correlated with angular insertion depth (degrees around the modiolus). RESULTS: A moderate variance of angular insertion depth was documented for both free-fitting and perimodiolar electrode arrays. Full insertions into the scala tympani ranged from 540 to 630 degrees with free-fitting arrays and from 270 to 375 degrees with perimodiolar electrodes. In free-fitting devices, a linear relationship between linear (in millimeters) and angular (degrees) insertion depths was observed. Insertions into scala vestibuli were observed in 9 of 28 and 5 of 18 of the specimens for free-fitting and perimodiolar electrodes, respectively. Additionally, scala vestibuli insertions showed greater angular insertion depths when compared with scala tympani implantations. CONCLUSION: Variances in angular insertion depths seem to be moderate and similar in free-fitting and perimodiolar electrode arrays. Scala vestibuli insertions showed greater angular insertion depths than comparable insertions into the scala tympani. In perimodiolar electrodes, angular insertion depths equal or greater than 390 degrees suggested scala vestibuli placement.

Electric acoustic stimulation of the auditory system: results of a multi-centre investigation.

CONCLUSION: A high rate of hearing preservation during cochlear implantation for electric acoustic stimulation (EAS) is possible, even when surgery is conducted by a number of different surgeons. OBJECTIVES: This study aimed to determine the degree of hearing preservation using surgery for EAS in a European multi-centre clinical investigation. It also aimed to demonstrate the effect of EAS in individuals with residual low frequency hearing, both on speech perception and on subjective quality of life measures. PATIENTS AND METHODS: Eighteen patients with profound high frequency hearing loss were recruited in five participating European centres. Subjects were assessed based on an audiologic test battery, as well as on a subjective hearing aid benefit questionnaire. Each subject underwent attempted hearing preservation cochlear implantation using the MED-EL C40 + device with a Medium electrode. Residual ipsilateral hearing and speech discrimination abilities were assessed at defined intervals up to 12 months after the combined electric-acoustic mode was introduced. RESULTS: Results showed that some degree of hearing preservation was possible in 15718 patients. All subjects showed statistically significant benefit on all three speech perception tests over time. These significant benefits were also reflected in the subjective benefit outcomes.

A new combined speech processor for electric and acoustic stimulation--eight months experience.

PURPOSE: Electric acoustic stimulation (EAS) relies on the preservation of low-frequency hearing and adequate amplification of these frequencies. EAS has been achieved by fitting the cochlear implant (CI) speech processor together with an ipsilateral in-the-ear hearing aid. This study will evaluate the outcomes when CI/EAS users upgrade to a new combination of hearing aid and speech processor in 1 device (DUET). METHOD: Nine EAS patients participated in this study. Before switchover and after 2 and 8 months of DUET device use, they were assessed using monosyllables and sentences in quiet and in noise. Additionally, a questionnaire, the Abbreviated Profile for Hearing Aid Benefit (APHAB), was used to evaluate subjective impressions. RESULTS: All subjects performed equally well, or even better, after switchover. This was also demonstrated over time. The participants with EAS before switchover performed equally afterwards, while those who used CI only did markedly better with the new device, especially in noisy conditions. Slight preference for the new system was also demonstrated with the APHAB. CONCLUSION: All subjects showed benefit in noise; CI-only users before switchover particularly benefited from the new hearing system. Those who applied EAS before switchover performed equally well. The DUET allows individuals better access to EAS.

Identification of a rare COCH mutation by whole-exome sequencing : Implications for personalized therapeutic rehabilitation in an Austrian family with non-syndromic autosomal dominant late-onset hearing loss.

BACKGROUND: Non-syndromic autosomal dominant hearing impairment is characteristically postlingual in onset. Genetic diagnostics are essential for genetic counselling, disease prognosis and understanding of the molecular mechanisms of disease. To date, 36 causative genes have been identified, many in only individual families. Gene selection for genetic screening by traditional methods and genetic diagnosis in autosomal dominant patients has therefore been fraught with difficulty. Whole-exome sequencing provides a powerful tool to analyze all protein-coding genomic regions in parallel, thus allowing the comprehensive screening of all known genes and associated alterations. METHODS: In this study, a previously undiagnosed late-onset progressive autosomal dominant hearing loss in an Austrian family was investigated by means of whole-exome sequencing. Results were confirmed by Sanger sequencing. RESULTS: A previously described c.151C>T missense (p.Pro51Ser) mutation in the LCCL (limulus factor C, cochlin, late gestation lung protein Lgl1) domain of the cochlin gene (COCH) was identified as causative and segregated with disease in five members of the family. Molecular diagnostics led to the decision to perform cochlear implantation in an index patient who subsequently showed excellent postoperative auditory performance. The c.151C>T mutation was not found in 18 screened Austrian families with autosomal dominant hearing loss but was represented alongside other known pathogenic mutant COCH alleles in the Genome Aggregation Database (gnomAD) in European populations. A combined allele frequency of 0.000128 implies an orphan disease frequency for COCH-induced hearing loss of 1:3900 in Europe. CONCLUSIONS: Exome sequencing successfully resolved the genetic diagnosis in a family suffering from autosomal dominant hearing impairment and allowed prediction of purported auditory outcome after cochlear implantation in an index patient. Personalized treatment approaches based on the molecular mechanisms of disease may become increasingly important in the future.

Iron oxide particle-enhanced magnetic resonance imaging for detection of benign lymph nodes in the head and neck: how reliable are the results?

AIM: To evaluate the accuracy of ultrasmall paramagnetic iron oxide (USPIO: Sinerem)-enhanced MRI in patients with head and neck cancer and enlarged lymph nodes compared with current staging examinations using histology as a gold standard. PATIENTS AND METHODS: Seventeen patients with a histologically proven squamous cell cancer of the head and neck (SCCHN) and different N-stages underwent a non-enhanced and a USPIO-enhanced MRI examination. Signal intensity (SI) was measured in a region of interest evaluation. Pathohistological examination was used as a reference. RESULTS: On a patient basis, USPIO-enhanced MRI showed a higher specificity and diagnostic accuracy (94%) compared with non-enhanced MRI (53%). One patient showed a lymph node of 6 mm in the short axial diameter which was suggested as being metastatic in Sinerem-enhanced MRI according to the enhancement pattern of Sinerem. This patient was staged as N1 with Sinerem-enhanced MRI. The histopathological examination did not confirm the Sinerem-enhanced MRI result. CONCLUSION: The high values for the specifity and diagnostic accuracy of Sinerem- enhanced MRI justifies further investigations with this contrast agent. USPIO-enhanced MRI could be advantageous in avoiding surgical overtreatment.

Scala tympani cochleostomy II: topography and histology.

OBJECTIVE: To assess intracochlear trauma using two different round window-related cochleostomy techniques in human temporal bones. METHODS: Twenty-eight human temporal bones were included in this study. In 21 specimens, cochleostomies were initiated inferior to the round window (RW) annulus. In seven bones, cochleostomies were drilled anterior-inferior to the RW annulus. Limited cochlear implant electrode insertions were performed in 19 bones. In each specimen, promontory anatomy and cochleostomy drilling were photographically documented. Basal cochlear damage was assessed histologically and electrode insertion properties were documented in implanted bones. RESULTS: All implanted specimens showed clear scala tympani electrode placements regardless of cochleostomy technique. All 21 inferior cochleostomies were atraumatic. Anterior-inferior cochleostomies resulted in various degrees of intracochlear trauma in all seven bones. CONCLUSION: For atraumatic opening of the scala tympani using a cochleostomy approach, initiation of drilling should proceed from inferior to the round window annulus, with gradual progression toward the undersurface of the lumen. While cochleostomies initiated anterior-inferior to the round window annulus resulted in scala tympani opening, many of these bones displayed varying degrees of intracochlear trauma that may result in hearing loss. When intracochlear drilling is avoided, the anterior bony margin of the cochleostomy remains a significant intracochlear impediment to in-line electrode insertion.

Demands on caring relatives of head and neck cancer patients.

BACKGROUND: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups. MATERIAL AND METHODS: Patients' relatives were assessed using an anonymous self-report questionnaire that was established in our department by expanding on a questionnaire for cancer patients' relatives from the psycho-oncologic society in Switzerland. The evaluation was multidimensional, cancer specific, and relative based. RESULTS: Relatives feel confronted themselves with cancer, although indirectly. The majority of the respondents were of the opinion that simultaneous psychological care of the patients and for the caring relatives would be helpful to cope with the situation. CONCLUSION: This study shows the significant impact of cancer on caring relatives of head and neck cancer patients. In our opinion, health services should become more aware of this potential to ensure that the needs of the involved patient relatives are met as well as those of the patients.

Masking release with changing fundamental frequency: Electric acoustic stimulation resembles normal hearing subjects.

It has been shown that patients with electric acoustic stimulation (EAS) perform better in noisy environments than patients with a cochlear implant (CI). One reason for this could be the preserved access to acoustic low-frequency cues including the fundamental frequency (F0). Therefore, our primary aim was to investigate whether users of EAS experience a release from masking with increasing F0 difference between target talker and masking talker. The study comprised 29 patients and consisted of three groups of subjects: EAS users, CI users and normal-hearing listeners (NH). All CI and EAS users were implanted with a MED-EL cochlear implant and had at least 12 months of experience with the implant. Speech perception was assessed with the Oldenburg sentence test (OlSa) using one sentence from the test corpus as speech masker. The F0 in this masking sentence was shifted upwards by 4, 8, or 12 semitones. For each of these masker conditions the speech reception threshold (SRT) was assessed by adaptively varying the masker level while presenting the target sentences at a fixed level. A statistically significant improvement in speech perception was found for increasing difference in F0 between target sentence and masker sentence in EAS users (p = 0.038) and in NH listeners (p = 0.003). In CI users (classic CI or EAS users with electrical stimulation only) speech perception was independent from differences in F0 between target and masker. A release from masking with increasing difference in F0 between target and masking speech was only observed in listeners and configurations in which the low-frequency region was presented acoustically. Thus, the speech information contained in the low frequencies seems to be crucial for allowing listeners to separate multiple sources. By combining acoustic and electric information, EAS users even manage tasks as complicated as segregating the audio streams from multiple talkers. Preserving the natural code, like fine-structure cues in the low-frequency region, seems to be crucial to provide CI users with the best benefit.

The role of alternative GJB2 transcription in screening for neonatal sensorineural deafness in Austria.

CONCLUSION: Alterations within a novel putative Exon 1a within the gap junction beta 2 (GJB2) gene may play a role in the development of genetic hearing impairment in Austria. OBJECTIVES: Mutations in the GJB2 gene are the most common cause of hereditary sensorineural deafness. Genome-wide screening for alternative transcriptional start sites in the human genome has revealed the presence of an additional GJB2 exon (E1a). This study tested the hypothesis of whether alternative GJB2 transcription involving E1a may play a role in the development of congenital sensorineural deafness in Austria. METHODS: GJB2 E1a and flanking regions were sequenced in randomized normal hearing control subjects and three different patient groups with non-syndromic hearing impairment (NSHI), and bioinformatic analysis was performed. Statistical analysis of disease association was carried out using the Cochran-Armitage test for trend. RESULTS: A single change 2410 bp proximal to the translational start site (c.-2410T > C, rs7994748, NM_004004.5:c.-23 + 792T > C) was found to be significantly associated with the common c.35delG GJB2 mutation (p = .009). c.35delG in combination with c.-2410CC occurred at a 6.9-fold increased frequency compared to the control group. Additionally, one patient with idiopathic congenital hearing loss was found to be homozygous c.-2410CC.

Adjuvant docetaxel, cisplatin and 5-fluorouracil (TPF) in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: In this phase II study, the efficacy and toxicity of a triple chemotherapy with docetaxel, cisplatin and 5- Fluorouracil (TPF) was evaluated in the adjuvant therapy of locoregionally advanced cancer of the head and neck. This represented the first use of polychemotherapy as single adjuvant therapy after surgery. PATIENTS AND METHODS: Twenty patients with stage II-IV (UICC) squamous cell carcinoma of the head and neck (SCCHN) were treated by surgery of the primary and the regional lymph nodes. Four weeks after surgery, all patients received polychemotherapy consisting of docetaxel 75 mg/m2 day 1, cisplatin 100 mg/m2 day 1 and 5- Fluorouracil (5- FU) 1000 mg/m2 days 1 through 4 (total dose 4000 mg/m2), on days 1, 22 and 43 for a maximum of 3 cycles. The performance status of all patients at the beginning of the chemotherapy was 0-1 according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: Fifty-eight cycles were administered to the 20 patients. The major acute toxicities were mucositis (2 patients) and febrile neutropenia (4 patients). One patient dropped out after the first cycle because of severe mucositis. After a median follow-up of 16.5 months (range, 1-41 months), the median time to progression was 20 months (range, 16-22 months). The estimated overall survival according to Kaplan-Meier at the median time of follow-up was 90%. No distant metastases were detectable after the adjuvant chemotherapy with TPF in locally advanced SCCHN, neither were late effects observed. CONCLUSION: TPF was tolerated, with an acceptable toxicity profile, in patients with a good performance status. The preliminary results appear to justify further investigations to evaluate the efficacy of this modality in the adjuvant setting.

A phase II trial of docetaxel, cisplatin and 5-fluorouracil in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).

BACKGROUND: In this phase II study, for the first time the efficacy and toxicity of triple chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with recurrent head and neck cancer was evaluated. PATIENTS AND METHODS: Twenty-four patients with stage IV (UICC) recurrent squamous cell carcinoma of the head and neck (SCCHN), with different tumor sites, were treated with a polychemotherapy consisting of docetaxel 75 mg/m2 day 1, cisplatin 100 mg/m2 day 1 and 5-fluorouracil (5-FU) 1000 mg/m2 days 1 through 4 (total dose 4000 mg/m2) on days 1, 22 and 43, for a maximum of 3 cycles. The performance status of all patients at the start of the chemotherapy was 0-2, according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: Sixty-eight cycles were administered to 24 patients. The reversible major acute toxicities were afebrile neutropenia in 6 patients and emesis in 4 patients. One patient died, probably because of myocardial infarction related to treatment. A remission was observed in 10 patients. Six patients showed a complete remission and 4 patients a partial remission. The median time to progression was 10 months (range, 4-42 months), the median overall survival after treatment was 13 months (range, 6-48 months) and the median recurrence-free survival was 12 months (range, 10-18 months). CONCLUSION: In terms of toxicity, TPF seems to be a feasible option for the treatment of recurrent SCCHN in patients with a compromised performance status. These results justify further investigations to evaluate the efficacy of this treatment.