The vibrating ossicular prosthesis in children and adolescents: a retrospective study.

PURPOSE: The primary objective of the retrospective study was to collect speech intelligibility data on children and adolescents implanted with the vibrating ossicular prosthesis (VORP) 503. METHODS: This was a retrospective, multicentre study on 55 children and adolescents from 6 German clinics aged between 5 and 17 years suffering from mixed or conductive hearing loss implanted with a VORP 503. Pre- and postoperative bone-conduction pure tone thresholds were measured at 0.5, 1, 2 and 4 kHz, and word recognition scores in the unaided and VORP 503-aided conditions using monosyllabic speech intelligibility tests measured at 65-dB sound pressure level (SPL) were determined. RESULTS: Mean pre- and postoperative bone-conduction thresholds remained unchanged, showing the preservation of inner ear hearing. Speech intelligibility assessed in quiet at 65-dB SPL improved on average from 24.5% (SD ± 25.4) unaided to 86.4% (SD ± 13.4) aided. The average improvement of 61.9% (SD ± 25.3) was clinically and statistically significant. A total of three complications were found in the medical records of 55 subjects. The responsible investigators judged these events as procedure related. CONCLUSION: The treatment of children suffering from conductive or mixed hearing loss with the VORP 503 implant demonstrates excellent aided benefit in terms of speech understanding and only minor complications.

Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns-Results of a non-interventional study of the DeCOG.

BACKGROUND: Advanced cutaneous squamous cell carcinoma (aSCC) is an area of unmet medical need and no treatment standards are established. Recently, an anti-PD-1 inhibitor received FDA breakthrough therapy designation. The aim of the study was to describe the clinical course, therapeutic management and prognosis of aSCC under real-life conditions. PATIENTS AND METHODS: In a retrospective study performed in 24 German and Austrian hospitals and doctor's offices, patient and tumour characteristics of patients diagnosed with aSCC between January 1, 2010 and December 31, 2011 and their disease course was documented. Advanced SCC comprised either locally advanced SCCs (laSCC) or metastatic SCCs (mSCC) with any kind of metastatic spread. RESULTS: Data of 190 patients with aSCC were analysed. Median age at time of diagnosis of aSCC was 78 years. LaSCC was diagnosed in 76 patients (40%), 114 patients (60%) had mSCC. Once diagnosed with laSCC, most patients (59%) did not receive any therapy, whereas in 92% of mSCC patients at least one type of therapy was performed. Only 32 patients (29 mSCC, 3 laSCC) received systemic antitumour therapies, mostly EGFR inhibitor-based regimens. Mean duration of response was short (17-months laSCC patients, 3-months mSCC patients). Only 2 patients achieved a complete response, 27% had a partial response, 43% disease stabilisation. At diagnosis of aSCC, ECOG status was 0-1 in most patients. Non-malignant comorbidities influenced the decision on SCC-specific therapy in 39 patients (21%). CONCLUSIONS: Our data show the high medical need for efficient and tolerable antitumour therapies and demonstrate that despite older age and comorbidities, most patients can be expected to be fit for treatment. This study provides a historical context for emerging aSCC treatments.

Electrogustometry and contact endoscopy findings in patients with head and neck malignancies treated with chemotherapy, radiotherapy, or radiochemotherapy.

This study aimed to investigate in parallel changes in gustatory function, changes in morphology of the fungiform papillae, as well as changes in the shape and density of the vessels of the tip of the tongue in patients treated with chemotherapy, radiotherapy, or radiochemotherapy. Twenty patients (7 females and 13 males; age range: 42-78 years) with head and neck malignancies (hypopharynx, larynx, oropharynx, and parotid) treated with radiochemotherapy (n = 8), chemotherapy (n = 8), or radiotherapy (n = 4) were prospectively studied. In all patients, electrogustometry and contact endoscopy were performed. Radiotherapy-treated patients exhibited higher electrogustometry thresholds and greater alterations in the morphology and vascularization of the fungiform papillae than the other two groups. Radiochemotherapy patients had less pronounced changes of the electrogustometry threshold and fungiform papillae structure compared with radiotherapy patients. Chemotherapy alone caused less severe change in both electrogustometry threshold and fungiform papillae structure than radiotherapy or radiochemotherapy. Radiotherapy alone caused greater disorders of taste-related anatomic parameters and electrogustometry thresholds compared with chemotherapy and combined radiochemotherapy.

Changes in electrogustometry thresholds, tongue tip vascularization, density and form of the fungiform papillae in smokers.

The objective of this study was to evaluate differences in gustatory function in smokers of both sexes and identify any differences in the shape, density and vascularisation of the fungiform papillae (fPap) of smokers' tongue. Additional aim was to investigate any relation between the age, pack years and differences in shape, density, vascularization of fPap and sex. In 166 smokers (81 males, 85 females, age range 20-80 years), divided in age groups, electrogustometry (EGM) thresholds at the chorda tympani area, at the soft palate area and at the area of the vallate papillae were recorded bilaterally. Morphology and density of the fPap and blood vessels' density and morphology at the tip of the tongue were examined using contact endoscopy (CE). EGM thresholds of all smoking subjects tended to increase compared to the non-smoking participants. Morphology, vascularization and density of fPap were found to be worse in smokers than in non-smokers. Interestingly, some participants, despite having increased number of pack years, tended to have almost similar EGM thresholds with non-smoking subjects of the same age group. Smoking tends to affect density, morphology and vascularization of the fPap. There is a correlation between the duration of smoking (pack years) and the afore-mentioned parameters. The use of τ-Kendall criterion provided useful information about the different correlation between the EGM thresholds and vascularization, the EGM thresholds and morphology of fPap and EGM thresholds and density of fPap. The majority of smokers had elevated EGM thresholds compared to non-smokers. Smoking is an important factor which can lead to decreased taste acuity. The combination of methods, such as EGM and CE, can provide useful information about the morphology and function of taste buds. Of interest, women are less affected than men, irrespective of the age group.

Memantine's action against aminoglycoside-induced ototoxicity.

The objectives of this study were (1) to assess the protective role of NMDA antagonists against the ototoxic effects of aminoglycosides, (2) to provide any possible evidence between ototoxicity due to aminoglycosides and excitotoxicity. An animal experiment was conducted. Twenty-eight, 3-month-old female New Zealand rabbits, weighing 1,000-1,500 g, were studied prospectively for 28 days after intramuscular administration of amikacin (15 mg/kg/day divided into two equal doses) for 14 days. Twenty-one rabbits were categorized into three equal treatment groups and seven animals received no medication and served as the control group. The animals of A, B and C groups were injected, intramuscularly, with amikacin 15 mg/kg/day, divided into two equal doses every day for 14 days. Animals of group A received in parallel memantine (per os) and those of group B received p.o. the same volume of placebo solution. The rabbits of the third group (group C) received on the 15th day and every 2 days for the next 2 weeks, until the day 28, memantine of the same quantity as the members of group A. Differences in DPOAE amplitudes, and therefore in cochlear activity, between group A and group B were revealed. DPOAE amplitudes of group B were further reduced compared to the respective amplitudes in rabbits of group A. No improvement was observed in DPOAE measurements performed after the discontinuation of injections. The findings in group C should be examined separately. The measurements showed apparent reversal ototoxic effects in four of the animals. The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. The administration of NMDA antagonists has been shown to prevent, at least to some extent, toxic damage to hair cells in guinea pigs, treated with aminoglycoside antibiotics.

Clinical trial results with the MED-EL fine structure processing coding strategy in experienced cochlear implant users.

OBJECTIVES: To assess the subjective and objective performance of the new fine structure processing strategy (FSP) compared to the previous generation coding strategies CIS+ and HDCIS. METHODS: Forty-six adults with a minimum of 6 months of cochlear implant experience were included. CIS+, HDCIS and FSP were compared in speech perception tests in noise, pitch scaling and questionnaires. The randomized tests were performed acutely (interval 1) and again after 3 months of FSP experience (interval 3). The subjective evaluation included questionnaire 1 at intervals 1 and 3, and questionnaire 2 at interval 2, 1 month after interval 1. RESULTS: Comparison between FSP and CIS+ showed that FSP performed at least as well as CIS+ in all speech perception tests, and outperformed CIS+ in vowel and monosyllabic word discrimination. Comparison between FSP and HDCIS showed that both performed equally well in all speech perception tests. Pitch scaling showed that FSP performed at least as well as HDCIS. With FSP, sound quality was at least as good and often better than with HDCIS. CONCLUSIONS: Results indicate that FSP performs better than CIS+ in vowel and monosyllabic word understanding. Subjective evaluation demonstrates strong user preferences for FSP when listening to speech and music.

Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array.

BACKGROUND: The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720 degrees . When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea. METHODS: Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. RESULTS: Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. CONCLUSIONS: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. TRIAL REGISTRATION: The Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.

Reliability of cochlear implants.

BACKGROUND: The long-term reliability of cochlear implants over time is an important issue for patients and cochlear implant teams. The calculation of cumulative survival rates including all hard failures of cochlear implants is suitable to report objectively about cochlear implant reliability. METHODS: This is a report of 192 cochlear implants from different manufacturers in adults (n = 58) and children (n = 134). RESULTS: The overall cumulative implant survival rate was 91.7% for a period of 11 years. The main reasons for hard failures were design errors of the products and direct or indirect trauma to the cochlea implant site (especially in children) with consecutive breaks of the implant body or electrodes. CONCLUSIONS: To improve our knowledge about reliability of cochlear implants more studies on cumulative long time survival of cochlear implants are needed, where functional failures and complications for whatever reason (design, mechanical, electronic, medical) are included. Cochlear implant reliability data should be considered during the choice of an implant for each individual patient.

Vascular endothelial growth factor expression, vascularization and proliferation in paragangliomas.

OBJECTIVE/HYPOTHESIS: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth. STUDY DESIGN: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases. METHODS: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells. RESULTS: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group. CONCLUSIONS: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies.

DPOAE-grams in patients with acute tonal tinnitus.

OBJECTIVE: To investigate cochlear outer hair cell function in patients with acute tonal tinnitus and normal or near-normal hearing threshold. STUDY DESIGN AND SETTING: Prospective controlled study in an academic tertiary health center. Distortion products of otoacoustic emissions (DPOAE)-grams of 32 ears with acute tonal tinnitus and normal hearing or minimal hearing loss were compared with those of 17 healthy nontinnitus ears. RESULTS: Tinnitus ears exhibited relatively increased amplitudes of DPOAE at high frequencies (4-6.3 kHz) when compared with the group of healthy ears and relatively decreased DPOAE amplitudes at middle frequencies (1650-2400 Hz). Statistically significant ( P < 0.01) increased mean values of DPOAE amplitudes were observed only at a frequency of f2 equal to 4.9 kHz. CONCLUSIONS AND SIGNIFICANCE: These findings suggest an altered functional state of the outer hair cells at a selected high-frequency region of the cochlea in ears with acute tonal tinnitus and normal or near-normal hearing threshold.

Epidural hematoma after cochlear implantation in a 2.5-year-old boy.

OBJECTIVE: Report a case of an epidural hematoma after cochlear implantation in a 2.5-year-old boy, the diagnostic and therapeutical emergency management, as well as the postinterventional course and rehabilitation of the child. STUDY DESIGN: Retrospective case review. PATIENT: Two and a half-year-old boy, suffering from early onset, profound sensorineural hearing loss had been diagnosed at an age of 1.5 years, which had been more severe on the right side initially, but had progressed to bilateral deafness. INTERVENTION AND COMPLICATION: Cochlear implantation on the left side, followed up by an extensive epidural hematoma, causing intracranial compression with a midline shift of 15 mm to the right side. This initial complication was followed up by arterial infarction not only of the middle but also the posterior as well as the anterior cerebral artery, most likely caused by incarceration through the tentorium. RESULTS: After immediate neurosurgical intervention and intensive care treatment including low-dose anticoagulation and high doses of corticosteroids, the child recuperated completely within 3 weeks without any remaining neurologic deficits. CONCLUSION: In cochlear implantation, especially if placement of the implant housing is associated with considerable bone work, epidural hematoma has to be considered as an extremely rare, but life-threatening, complication.

Steroid and vasoactive treatment for acute deafness after attempted hearing preservation acoustic neuroma surgery.

OBJECTIVE: To investigate whether intravenous steroid and vasoactive therapy in the acute postoperative period improves hearing outcome in patients who develop acute deafness after attempted hearing preservation surgery for acoustic neuroma (AN) through a retrosigmoid or a middle cranial fossa approach. STUDY DESIGN AND SETTING: Retrospective controlled study in a tertiary care center. Thirty-six patients who had developed acute deafness after hearing preservation surgery for treatment of an AN were reviewed. Preoperative AAOHNS hearing class was A in 2, B in 2 and D in 32 patients. Twenty-seven patients were treated with prednisolone, hydroxyethyl starch 3% and pentoxifylline intravenously for a period of at least 5 days. Nine patients (controls) did not receive any specific steroid or vasoactive therapy. RESULTS: All patients in both groups remained deaf. CONCLUSIONS: Intravenous therapy with prednisolone, hydroxyethyl starch 3% and pentoxifylline in the acute postoperative period does not improve hearing in patients who develop acute deafness after attempted hearing preservation surgery for AN.

Evidence for a possible NOS back-up system in the organ of Corti of the guinea pig.

Recently, the two Ca(2+)/calmodulin-regulated nitric oxide synthase isoforms, nNOS and eNOS, and NO itself have been identified in the cochlea of vertebrates using specific antibodies and a new fluorescence indicator. In order to acquire more information about the quantitative and spatial distribution of these two constitutively expressed NOS isoforms (cNOS) in the organ of Corti at the cellular and subcelluar levels, ultrathin sections of London resin (LR) White-embedded cochleae of the guinea pig were incubated with various concentrations of commercially available antibodies to nNOS and eNOS. The immunoreactivity was visualized by a gold-labeled secondary antibody and the amount of the immunoreactions/microm(2) was quantified for different cell types and subcellular regions. Both NOS isoforms were identified to varying degrees in the same cell types and subcellular regions. A prominent eNOS immunoreactivity was identified in nearly every cell type. In all analyzed animals the highest number of gold-coupled anti-eNOS antibodies was always seen in the cells of the reticular lamina, especially in the cuticular structures of outer and inner hair cells, pillar cells and apical Deiters' cells. Also the microtubuli-containing cytoplasmic regions of Deiters' cells were scattered with gold-coupled anti-eNOS antibodies. A clear eNOS immunoreaction was also found in the remaining cytoplasm of inner and outer hair cells and in the apical Deiters' cells. Numerous anti-nNOS antibodies were located in the outer hair cells and in the cuticular structures of the apical Deiters' cells. The amount of the gold-labeled anti-nNOS antibodies in the cuticular plates of the pillar cells and outer hair cells and in the cytoplasm of inner hair cells and apical Deiters' cells were clearly less but still above unspecific background labeling. The spatial co-localization of the two NOS isotypes in the same cell regions was proven in double-labeling experiments. The spatial distribution of the two cNOS isoforms confirmed recent findings of other authors who localized NO distribution and production sites. The cNOS co-expression with similar function in the same cell type and subcellular regions may represent a functional "back-up system" in which one NOS isoform can replace the other in case of pathophysiological malfunction.

Long-term results after interval therapy with intratympanic gentamicin for Menière's disease.

OBJECTIVES: The new single-shot and interval treatment for Menière's disease with gentamicin was designed to avoid cochlear damage during treatment with gentamicin. METHODS: To date, 90 patients were treated with the single-shot or interval gentamicin therapy. Fifty-seven cases of Menière's disease were followed up prospectively between 2 and 4 years. During one treatment series, a maximum of three intratympanic gentamicin injections within 15 days were applied, each consisting of 0.3 mL (12 mg) of gentamicin (days 1, 8, and 15). Thirty of these 57 patients (53%) needed only one injection to be controlled (single-shot treatment). RESULTS: Vertigo attacks were completely controlled in 95% and partially controlled in 5%, whereas hearing remained unchanged or even improved. Tinnitus as well as aural fullness were controlled in approximately 50% of the cases. CONCLUSION: Our results with this group of patients after interval-treatment or single-shot application of intratympanic gentamicin demonstrate the effectiveness of this treatment modality with very low side effects, and, although our experience is still limited, it allows for expanding the indication on early cases of Menière's disease before permanent hearing loss occurs. Even cases of bilateral Menière's disease can be treated successfully using this method. Cochleotoxic side effects can be prevented by treatment intervals of 7 days.

Localization of the two constitutively expressed nitric oxide synthase isoforms (nNOS and eNOS) in the same cell types in the saccule maculae of the frog Rana pipiens by immunoelectron microscopy: evidence for a back-up system?

There is growing evidence for a nitric oxide/cyclic GMP pathway of signal transduction in the vestibular system. Recently, two isoforms of nitric oxide (NO) synthase (nNOS and eNOS) and NO itself have been identified at the light microscopic level in the vestibulocochlear system of mice using specific antibodies and a new fluorescence indicator. In order to acquire more information about signal transduction and tissue modulation in this neuroepithelium at the cellular and subcellular levels, ultrathin sections of London Resin White-embedded saccule maculae of the frog Rana pipiens were incubated with various concentrations of commercially available antibodies to nNOS and eNOS. The immunoreactivity was visualized by a gold-labelled secondary antibody and the amount of the immunoreactions per microm2 was quantified for the different cell types and subcellular regions. Significant eNOS immunoreactivity was identified in the hair bundles, cuticular plates and the rest of the cytoplasm of the hair cells as well as in different subcellular regions of the supporting cells. Gold-labelled anti-nNOS antibodies stained mainly stereovilli and cuticular structures of hair cells and supporting cells, whereas the number of the immunoreactions in the remaining cytoplasm of both cell types was near the background level. The spatial co-localization of the two NOS isotypes in the same cell regions of hair cells and supporting cells was confirmed in double-labelling experiments. The immunocytochemical findings are suggestive of a redundant system in which one NOS isoform can (partially) replace the other. The different subcellular localization of the NOS isoforms may allow for isoform specific regulation of NOS activity by different Ca2+ currents at the subcellular level, underlining the importance of NO-regulated processes in neuroepithelia of the inner ear.

Association of proliferative activity and size in acoustic neuroma: implications for timing of surgery.

OBJECT: Acoustic neuroma is the most frequent benign tumor of the cerebellopontine angle, and surgery is still the most common form of treatment. To gain better insight into the dysregulated mechanisms causing growth of acoustic neuroma, the authors studied the proliferative activity of 34 consecutive samples by analyzing immunohistochemical staining with Ki-67 and proliferating cell nuclear antigen (PCNA), and apoptosis based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Data from these analyses were correlated with clinical parameters (that is, tumor size, duration of symptoms, and patient age). METHODS: Apoptotic cells were found in none of the tumors. Proliferation measured on staining with Ki-67 and PCNA correlated with tumor size, but not with patient age or duration of symptoms. The authors demonstrated that tumors 18 mm or smaller in diameter have lower proliferation indices and growth rates, compared with tumors larger than 18 mm with high proliferative indices and growth rates. Additionally, they observed that these more aggressive, larger tumors occur mostly in patients younger than 50 years of age. CONCLUSIONS: Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.