Dependence of Cochlear Duct Length Measurement on the Resolution of the Imaging Dataset.

HYPOTHESIS: Measurements of the cochlear duct length (CDL) are dependent on the resolution of the imaging dataset. BACKGROUND: Previous research has shown highly precise cochlear measurements using 3D-curved multiplanar reconstruction (MPR) and flat-panel volume computed tomography (fpVCT). Thus far, however, there has been no systematic evaluation of the imaging dataset resolution required for optimal CDL measurement. Therefore, the aim of this study was to evaluate the dependence of CDL measurement on the resolution of the imaging dataset to establish a benchmark for future CDL measurements. METHODS: fpVCT scans of 10 human petrous bone specimens were performed. CDL was measured using 3D-curved MPR with secondary reconstruction of the fpVCT scans (fpVCT SECO ) and increasing resolution from 466 to 99 µm. In addition, intraobserver variability was evaluated. A best-fit function for calculation of the CDL was developed to provide a valid tool when there are no measurements done with high-resolution imaging datasets. RESULTS: Comparison of different imaging resolution settings showed significant differences for CDL measurement in most of the tested groups ( p < 0.05), except for the two groups with the highest resolution. Imaging datasets with a resolution lower than 200 µm showed lower intraobserver variability than the other resolution settings, although there were no clinically unacceptable errors with respect to the Bland-Altman plots. The developed best-fit function showed high accuracy for CDL calculation using resolution imaging datasets of 300 µm or lower. CONCLUSION: 3D-curved MPR in fpVCT with a resolution of the imaging dataset of 200 µm or higher revealed the most precise CDL measurement. There was no benefit of using a resolution higher than 200 µm with regard to the accuracy of the CDL measurement.

Precise evaluation of the postoperative cochlear duct length by flat-panel volume computed tomography - Application of secondary reconstructions.

OBJECTIVE: There is still a lack in precise postoperative evaluation of the cochlea because of strong artifacts. This study aimed to improve accuracy of postoperative two-turn (2TL) and cochlear duct length (CDL) measurements by applying flat-panel volume computed tomography (fpVCT), secondary reconstruction (fpVCTSECO) and three-dimensional curved multiplanar reconstruction. METHODS: First, 10 temporal bone specimens with or without electrode were measured in multi-slice computed tomography (MSCT), fpVCT and fpVCTSECO and compared to high-resolution micro-CT scans. Later, pre- and postoperative scans of 10 patients were analyzed in a clinical setting. RESULTS: Concerning 2TL, no statistically significant difference was observed between implanted fpVCTSECO and nonimplanted micro-CT in 10 temporal bone specimens. In contrast, there was a significant discrepancy for CDL (difference: -0.7 mm, P = 0.004). Nevertheless, there were no clinically unacceptable errors (±1.5 mm). These results could be confirmed in a clinical setting. Using fpVCTSECO, CDL was slightly underestimated postoperatively (difference: -0.5 mm, P = 0.002) but without any clinically unacceptable errors. CONCLUSION: fpVCTSECO can be successfully applied for a precise measurement of the cochlear lengths pre- and postoperatively. However, users must be aware of a slight systematic underestimation of CDL postoperatively. These results may help to refine electrode selection and frequency mapping.

Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation.

PURPOSE: For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCTSECO) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. METHODS: Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCTSECO) of patients with and without implanted electrodes. RESULTS: Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCTSECO with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCTSECO compared to MSCT. CONCLUSION: The combination of fpVCTSECO and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.

Highly precise navigation at the lateral skull base by the combination of flat-panel volume CT and electromagnetic navigation.

This study aimed to evaluate the feasibility and accuracy of electromagnetic navigation at the lateral skull base in combination with flat panel volume computed tomography (fpVCT) datasets. A mastoidectomy and a posterior tympanotomy were performed on 10 samples of fresh frozen temporal bones. For registration, four self-drilling titanium screws were applied as fiducial markers. Multi-slice computed tomography (MSCT; 600 µm), conventional flat panel volume computed tomography (fpVCT; 466 µm), micro-fpVCT (197 µm) and secondary reconstructed fpVCT (100 µM) scans were performed and data were loaded into the navigation system. The resulting fiducial registration error (FRE) was analysed, and control of the navigation accuracy was performed. The registration process was very quick and reliable with the screws as fiducials. Compared to using the MSCT data, the micro-fpVCT data led to significantly lower FRE values, whereas conventional fpVCT and secondary reconstructed fpVCT data had no advantage in terms of accuracy. For all imaging modalities, there was no relevant visual deviation when targeting defined anatomical points with a navigation probe. fpVCT data are very well suited for electromagnetic navigation at the lateral skull base. The use of titanium screws as fiducial markers turned out to be ideal for comparing different imaging methods. A further evaluation of this approach by a clinical trial is required.

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation.

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects.

Different Neurogenic Potential in the Subnuclei of the Postnatal Rat Cochlear Nucleus.

In patients suffering from hearing loss, the reduced or absent neural input induces morphological changes in the cochlear nucleus (CN). Neural stem cells have recently been identified in this first auditory relay. Afferent nerve signals and their impact on the immanent neural stem and progenitor cells already impinge upon the survival of early postnatal cells within the CN. This auditory brainstem nucleus consists of three different subnuclei: the anteroventral cochlear nucleus (AVCN), the posteroventral cochlear nucleus (PVCN), and the dorsal cochlear nucleus (DCN). Since these subdivisions differ ontogenetically and physiologically, the question arose whether regional differences exist in the neurogenic niche. CN from postnatal day nine Sprague-Dawley rats were microscopically dissected into their subnuclei and cultivated in vitro as free-floating cell cultures and as whole-mount organ cultures. In addition to cell quantifications, immunocytological and immunohistological studies of the propagated cells and organ preparations were performed. The PVCN part showed the highest mitotic potential, while the AVCN and DCN had comparable activity. Specific stem cell markers and the ability to differentiate into cells of the neural lineage were detected in all three compartments. The present study shows that in all subnuclei of rat CN, there is a postnatal neural stem cell niche, which, however, differs significantly in its potential. The results can be explained by the origin from different regions in the rhombic lip, the species, and the various analysis techniques applied. In conclusion, the presented results provide further insight into the neurogenic potential of the CN, which may prove beneficial for the development of new regenerative strategies for hearing loss.

Precise Evaluation of the Cochlear Duct Length by Flat-panel Volume Computed Tomography (fpVCT)-Implication of Secondary Reconstructions.

HYPOTHESIS: Flat-panel volume computed tomography (fpVCT) and secondary reconstruction allow for more accurate measurements of two-turn length (2TL), cochlear duct length (CDL), and angular length (AL). BACKGROUND: Cochlear geometry is a controversially debated topic. In the meantime, there are many different studies partly reporting highly divergent values. Our aim is to discuss the differences and to propose a radiological possibility to improve cochlear measurements using 3D-curved multiplanar reconstruction and fpVCT. METHODS: Performing different image modalities and settings, we tried to find a clinically usable option that allows for a high degree of accuracy. Therefore, we tested them against reference values of high-definition micro-computed tomography. RESULTS: Comparison of 99 µm slice thickness secondary reconstruction of fpVCT and reference showed no significant differences for 2TL and CDL (p ≥ 0.05). Accordingly, ICC (intraclass correlation) values were excellent (ICC ≥ 0.75; lower limit of confidence interval [CI] ≥ 0.75; Cronbach's alpha [α] ≥ 0.9). Evaluating AL, there was a significant difference (difference: -17.27°; p = 0.002). The lower limit of the CI of the ICC was unacceptable (ICC = 0.944; lower limit of CI = 0.248; α = 0.990). Regarding the Bland-Altman plots, there were no clinically unacceptable errors, but a systematic underestimation of AL. CONCLUSION: Secondary reconstruction is a suitable tool for producing reliable data that allow the accurate measurement of 2TL and CDL. The option of generating these reconstructions from raw data limits the need for higher radiation doses. Nevertheless, there is an underestimation of AL using secondary reconstructions.

Severe tracheobronchial harm due to lithium button battery aspiration: An in vitro study of the pathomechanism and injury pattern.

BACKGROUND: Button battery incidents have become a rising medical issue in recent years, especially for infants. The increasing number of these cases can be explained by the expanding use of objects of everyday life and toys. As a result, button batteries in many households are ubiquitous in different states of charge. The extremely long shelf-life and the increasing energy densities of lithium button batteries boost the potential medical complications of accidental swallowing. OBJECTIVE: The study aimed to analyze the pathophysiology of damage to tracheobronchial structures by button batteries aspiration over time. METHODS: CR2032 and CR927 lithium button batteries (3.2/3.0 V) were exposed to porcine trachea preparations intraluminal at 37 °C in intervals up to 36 h. Measurements were made of the voltage curve, the discharge current, and the resulting pH values around the electrodes. The effects on tissue were examined using macroscopic time-lapse images and microscopic pictures of sections of the fixed specimens over time. FINDINGS: The examinations showed a tissue electrolysis reaction directly after the beginning of battery exposure, which led to an immediate coagulation impairment of the respiratory epithelium. Over time, a strongly alkaline environment was established around the batteries. The resulting tissue colliquation caused profound tissue damage beyond the basal membrane of the mucosa, affecting the tracheobronchial cartilage after only 4 h of exposure time. After 12 h, there was significant necrosis of the annular ligaments of the trachea and the peribronchial pulmonary tissue. After completion of the experimental exposure time of 36 h, there was still a sufficient residual voltage on all button batteries of the experiments. CONCLUSIONS: Besides accidental ingestion, the aspiration of button batteries is a life-threatening situation. The partial or complete acute airway obstruction in the trachea or the bronchi initially is the leading symptom, as with any foreign body aspiration. However, the results of the investigations show that even after a short exposure time, relevant tissue damage can be caused by the electrolysis reaction of the battery. After 12 h, a profound destruction of cartilage, connective tissue, and smooth muscles was observed in vitro, which may cause significant consequential damage in vivo. These findings reveal the need for rapid diagnosis and immediate foreign body removal after any battery ingestion. Moreover, the results show how relevant prevention of these accidents is, and that future safety modifications of these types of battery by the manufacturers would be appropriate.

Isolation and Characterization of Neural Stem Cells from the Rat Inferior Colliculus.

The inferior colliculus (IC) is a nucleus of the auditory pathway and its fourth relay station. It integrates afferent information from the superior olivary complex and the cochlear nucleus. To date, no causal therapeutic options are known for damaged neuronal structures in this area. Regenerative medicine offers a potential approach to causally treating hearing impairment. After neural stem cells had been identified in certain areas of the auditory pathway, the question arouses, whether the IC also has a neurogenic potential. Cells from the IC of postnatal day 6 rats were extracted and cultured as neurospheres. Cells in the neurospheres showed mitotic activity and positive stain of neural stem cell markers (Nestin, DCX, Atoh1, and Sox-2). In addition, single cells were differentiated into neuronal and glial cells shown by the markers ß-III-tubulin, GFAP, and MBP. In summary, basic stem cell criteria could be detected and characterized in cells isolated from the IC of the rat. These findings will lead to a better understanding of the development of the auditory pathway and may also be relevant for identifying causal therapeutic approaches in the future.

Bilateral cochlear implantation is regarded as very beneficial: results from a worldwide survey by online questionnaire.

PURPOSE: Bilateral cochlear implant (CI) provision is now widely regarded as the most beneficial hearing intervention for acceptable candidates. This study sought to determine if a number of well-regarded hearing professionals at highly reputable clinics shared similar practices and beliefs regarding bilateral CI provision, use, and rehabilitation in children and adults. METHODS: An 11-question online questionnaire was created and distributed to all 27 clinics in the HEARRING group. Questions 1-5 asked for facts; questions 6-11 asked for opinions. RESULTS: 20 completed questionnaires were returned. All 20 respondents reported that their clinics perform bilateral cochlear implantation in children; 18 do so in adults. Regarding the fact-based questions, bilateral CI provision is more commonly performed and more likely to be reimbursed in children than in adults. Children are also much more likely to be implanted simultaneously than are adults. Regarding the opinion-based questions, respondents gave broadly similar answers. Communication between the CIs and speech coding strategies specifically developed for bilateral CI users were regarded as the two future technologies that would most enhance the benefit of bilateral CI use. CONCLUSIONS: Most clinics in the HEARRING group are very familiar with bilateral CI provision and hold similar opinions on its results and benefits. Hopefully the results described herein will lead to a greater acceptance and regular reimbursement of bilateral CI provision, especially in adults.

Cochlear Implantation in Chronic Otitis Media: Investigation of Long-term Speech Comprehension and Rate of Complications.

OBJECTIVE: To analyze the long-term speech comprehension and rate of complications of cochlear implantation in chronic otitis media. STUDY DESIGN: Retrospective data analysis. SETTING: Tertiary referral center with a large cochlear implant program. MAIN OUTCOME MEASURE: Speech perception scores in quiet and background noise and rate of complications. PATIENTS: Forty ears from a total of 38 patients with a mean age of 63.28 ±â€Š2.16 years at the time of implantation were included. RESULTS: Patients with a history of multiple ear surgeries, with no alternative option for hearing restoration than a cochlear implant, were implanted with satisfactory results in regard to speech comprehension. Preoperative bone conduction PTA4 correlated to postoperative speech comprehension scores in background noise. The rate of complications was low, but higher than in cases of cochlear implantation in normal middle ears. CONCLUSION: Cochlear implantation in chronic otitis media can be a satisfactory and safe procedure, if the surgery technique and aftercare is appropriate to the altered anatomy.

Patterned semiconductor structures modulate neuronal outgrowth: Implication for the development of a neurobionic interface.

Auditory implants stimulate the neurons by broad electrical fields, which leads to a low number of spectral channels. A reduction in the distance between the electrode and the neuronal structures might lead to better electrical transduction. The use of microstructured semiconductors offers a large number of contacts, which could attract neurons and stimulate them individually. To investigate the interaction between neurons and semiconductors, differentiated neuronal precursor cells were cultured on silicon wafers. Different structures were added on the wafers by electron beam lithography, and deep reactive ion etching in different depths (2 and 7 µm). Grooved surfaces guided the neurons and resulted in straight oriented axons, but neuronal outgrowth was impaired by the 7 µm grooves. Within the 7 µm structures, the neuronal cell body was totally encased and the nuclei were deformed from a round to an elliptical shape. On both square and cylindrical structures neuronal bridging could be detected in different forms, either between the tops of the structures or between the bottom and the top. Furthermore, neuronal bridges were established on the lateral part of the structures, and change in direction of neuronal growth was induced by the structure. Finally, it could be shown that neuronal growth cones were particularly attracted by the top of the cylinders, which might allow for the stimulation of neurons via this structure. In conclusion, study results indicate that structured semiconductors can modulate neuronal growth and its direction, offering a novel method for the development of new implants with improved neuronal stimulation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 65-72, 2018.

A polydopamine peptide coating enables adipose-derived stem cell growth on the silicone surface of cochlear implant electrode arrays.

The simultaneous application of neurotrophic factors with cochlear implantation is proposed to enhance the bioelectrical interface between electrodes and auditory neurons, and thus improve speech intelligibility in patients with cochlear implants (CIs). In cell-based approaches, the goal is to colonize CIs with cells producing neurotrophic factors. This study aims to evaluate whether a polydopamine (PD) functionalization of the hydrophobic silicone surface of the electrode carrier enables colonization of adipose-derived stem cells known to deliver neurotrophic factors. Surface characteristics of PD-coated silicone samples and electrode carriers were determined, and the proliferation and viability of adipose-derived stem cells (ASCs) on these surfaces were subsequently analyzed. A homogenous PD coating and cell growth with regular morphology was observed on coated silicone samples and electrode arrays. Hydrophilicity and cell viability was significantly enhanced by PD surface modification. Insertion forces of coated electrode arrays did not increase compared with untreated CIs. Hence, PD coating of the silicone surface of CIs might allow for sufficient colonization with ASCs as a continuous source of neurotrophic factors. © 2017 Wiley Periodicals, Inc. J Biomater Res Part A: 106B: 1431-1438, 2018.

Long-term changes in the properties of skin-derived fibroblasts following irradiation of the head and neck.

The tumor stroma performs an important role in carcinogenesis. It predominantly consists of fibroblasts and the connective tissue produced by them, and undergoes a multitude of interactions with the surrounding cancer cells. Since irradiation is part of the majority of therapeutic strategies for head and neck squamous cell carcinoma, more information regarding the effects of a previous irradiation on the tumor stroma is desirable. In the present study, fibroblasts were cultivated from human non-irradiated and pre-irradiated skin of the neck for 48 h. Subsequently, analyses of cell viability, apoptosis, necrosis and motility were conducted via MTT assay, Annexin V/propidium iodide staining, electronic cell counting for 4 consecutive days, and scratch assay. Pre-irradiated fibroblasts exhibited a significantly slower growth rate as well as increased rates of apoptosis and necrosis. They also exhibited significantly decreased motility compared with non-irradiated fibroblasts. These results indicated the long-term effects of irradiation on fibroblasts, which may affect cancer recurrence in the irradiated region via the tumor stroma. More information, such as that regarding the secretory capacities of pre-irradiated fibroblasts, is required to evaluate the possible therapeutic implications of these findings.

Pathophysiology of esophageal impairment due to button battery ingestion.

BACKGROUND: The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi. METHODS: The lithium button battery type CR2032, used most frequently in daily life, was exposed in preparations of porcine esophagi and incubated under the addition of artificial saliva at 37 °C. A total of eight esophagi were analysed by different methods. Measurements of the pH value around the battery electrodes and histological studies of the tissue damage were carried out after 0.5-24 h exposure time. In addition, macroscopic time-lapse images were recorded. Measurements of the battery voltage and the course of the electric current supplemented the experiments. FINDINGS: The investigations showed that the batteries caused an electrolysis reaction in the moist environment. The positive electrode formed an acidic and the negative electrode a basic medium. Consequently, a coagulation necrosis at the positive pole, and a deep colliquation necrosis at the minus pole occurred. After an exposure time of 12 h, tissue damage caused by the lye corrosion was observed on the side of the negative electrode up to the lamina muscularis. The corrosion progressed up to the final exposure time of 24 h, but the batteries still had sufficient residual voltage, such that further advancing damage would be expected. CONCLUSIONS: Button battery ingestion in humans poses an acute life-threatening danger and immediate endoscopic removal of the foreign body is essential. After only 2 h exposure time, significant damage to the tissue could be detected, which progressed continuously to complete esophageal perforation. The primary prevention of battery ingestion is therefore of particular importance.

Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

BACKGROUND: A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. METHODS: We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. RESULTS: In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. DISCUSSION/CONCLUSION: ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival.

Additive antitumor effects of celecoxib and simvastatin on head and neck squamous cell carcinoma in vitro.

Lipid-lowering statins as well as non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to possess cancer-protective effects in many epidemiologic cohort studies. However, the underlying mechanisms of these findings are mostly unknown. To evaluate possible additive antitumor effects of statins and NSAIDs in vitro, PJ-41 and HLaC78 head and neck squamous cell carcinoma cells (HNSCC) were treated with 40 µM celecoxib, 50 µM simvastatin or a combination of both. Analysis of tumor viability, proliferation, apoptosis, cell cycle changes and secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) was conducted via MTT assay, Annexin V-propidium iodide test, cell cycle analysis, colony assay and enzyme-linked immunosorbent assay (ELISA). Celecoxib and simvastatin alone as well as a combined treatment showed a significant reduction in tumor cell viability, proliferation and secretion of IL-6 and IL-8 compared to the control group. The combined treatment even proved to have significantly greater effects. We postulate that simvastatin and celecoxib have additive antitumor effects on HNSCC in vitro, which warrants further investigation.

Stable Longitudinal Performance of Adult Cochlear Implant Users for More Than 10 Years.

OBJECTIVE: To analyze the long-term performance of cochlear implant patients. STUDY DESIGN: Retrospective longitudinal study. SETTING: Tertiary referral center with a large cochlear implant program. MAIN OUTCOME MEASURE: Speech perception scores in quiet and in background noise in the short-term (1.12 ±â€Š0.15 yr) and long-term (12.61 ±â€Š2.34 yr) after implantation. PATIENTS: Fifty-eight implanted ears from 55 patients with a mean age of 51.80 ±â€Š1.757 years at the time of implantation were included. RESULTS: Speech perception scores were stable in the long-term for up to 20 years postimplantation. When alteration of speech perception over time was investigated in relation to the age at implantation, there was a deterioration of the scores in quiet in older patients (>60 years old at the time of surgery). In addition the speech comprehension in noise was negatively correlated with the age at the time of the test. CONCLUSION: The speech perception abilities of cochlear implant users are stable in the long-term and at the most may be affected by the age of the patients, as it is known from acoustic hearing.

Zinc oxide nanoparticles antagonize the effect of Cetuximab on head and neck squamous cell carcinoma in vitro.

Zinc oxide nanoparticles (ZnO-NPs) are being used in many cosmetic products and have been shown to induce tumor-selective cell death in human head and neck squamous cell carcinoma (HNSCC) in vitro. Cetuximab is a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), whose effectiveness for HNSCC, alone or in combination with cytostatic drugs, has been demonstrated intensively in the last decades. Nanoparticles are known to interact with protein structures and thus may influence their functionality. The aim of the current study was to evaluate the effect of ZnO-NPs on the antitumor properties of Cetuximab in HNSCC in vitro. Two HNSCC cell lines (FaDu and HLaC-78) were treated with 0.1, 1 or 10 µM Cetuximab as well as 0, 0.1 or 1 µg/ml ZnO-NP. Qualitative assessment of ZnO-NP was conducted via transmission electron microscopy (TEM) and immunofluorescence staining. Evaluation was done via the MTT-assay after 24, 48 and 72 hours of incubation with Cetuximab and ZnO-NPs. ZnO-NPs were shown to antagonize the anti-tumor effects of Cetuximab in a time-dependent as well as dose-dependent way. These findings suggest an inhibitory interaction of ZnO-NPs with Cetuximab, which warrants further investigation.