Monitoring Cochlear Health With Intracochlear Electrocochleography During Cochlear Implantation: Findings From an International Clinical Investigation.

OBJECTIVES: Electrocochleography (ECochG) is emerging as a tool for monitoring cochlear function during cochlear implant (CI) surgery. ECochG may be recorded directly from electrodes on the implant array intraoperatively. For low-frequency stimulation, its amplitude tends to rise or may plateau as the electrode is inserted. The aim of this study was to explore whether compromise of the ECochG signal, defined as a fall in its amplitude of 30% or more during insertion, whether transient or permanent, is associated with poorer postoperative acoustic hearing, and to examine how preoperative hearing levels may influence the ability to record ECochG. The specific hypotheses tested were threefold: (a) deterioration in the pure-tone average of low-frequency hearing at the first postoperative follow-up interval (follow-up visit 1 [FUV1], 4 to 6 weeks) will be associated with compromise of the cochlear microphonic (CM) amplitude during electrode insertion (primary hypothesis); (b) an association is observed at the second postoperative follow-up interval (FUV2, 3 months) (secondary hypothesis 1); and (c) the CM response will be recorded earlier during electrode array insertion when the preoperative high-frequency hearing is better (secondary hypothesis 2). DESIGN: International, multi-site prospective, observational, between groups design, targeting 41 adult participants in each of two groups, (compromised CM versus preserved CM). Adult CI candidates who were scheduled to receive a Cochlear Nucleus CI with a Slim Straight or a Slim Modiolar electrode array and had a preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted, were recruited from eight international implant sites. Pure tone audiometry was measured preoperatively and at postoperative visits (FUV1 and follow-up visit 2 [FUV2]). ECochG was measured during and immediately after the implantation of the array. RESULTS: From a total of 78 enrolled individuals (80 ears), 77 participants (79 ears) underwent surgery. Due to protocol deviations, 18 ears (23%) were excluded. Of the 61 ears with ECochG responses, amplitudes were < 1 µV throughout implantation for 18 ears (23%) and deemed "unclear" for classification. EcochG responses >1 µV in 43 ears (55%) were stable throughout implantation for 8 ears and compromised in 35 ears. For the primary endpoint at FUV1, 7/41 ears (17%) with preserved CM had a median hearing loss of 12.6 dB versus 34/41 ears (83%) with compromised CM and a median hearing loss of 26.9 dB ( p < 0.014). In assessing the practicalities of measuring intraoperative ECochG, the presence of a measurable CM (>1 µV) during implantation was dependent on preoperative, low-frequency thresholds, particularly at the stimulus frequency (0.5 kHz). High-frequency, preoperative thresholds were also associated with a measurable CM > 1 µV during surgery. CONCLUSIONS: Our data shows that CM drops occurring during electrode insertion were correlated with significantly poorer hearing preservation postoperatively compared to CMs that remained stable throughout the electrode insertion. The practicality of measuring ECochG in a large cohort is discussed, regarding the suggested optimal preoperative low-frequency hearing levels ( < 80 dB HL) considered necessary to obtain a CM signal >1 µV.

Audiological profile of adult Long COVID patients.

INTRODUCTION: Hearing loss is one of the self-reported symptoms of Long COVID patients, however data from objective and subjective audiological tests demonstrating diminished hearing in Long COVID patients has not been published. MATERIALS AND METHODS: Respondents of a large Long COVID online survey were invited to the ENT-department for an otologic exam. The participants were split into three groups based on their history of SARS-CoV-2 infection and persistence of symptoms. Respondents with a history of a SARS-CoV-2 infection were allocated to the Long COVID group, if they reported persistent symptoms and to the Ex COVID group, if they had regained their previous level of health. Participants without a history of SARS-CoV-2 infection made up the No COVID control group. In total, 295 ears were examined with otoscopy, tympanograms, pure tone audiometry and otoacoustic emissions. Ears with known preexisting hearing loss or status post ear surgery, as well as those with abnormal otoscopic findings, non-type A tympanograms or negative Rinne test were excluded. RESULTS: Compared to the No COVID and Ex COVID groups, we did not find a clinically significant difference in either hearing thresholds or frequency specific TEOAEs. However, at 500 Hz the data from the left ear, but not the right ear showed a significantly better threshold in the Ex COVID group, compared to Long COVID and No COVID groups. Any of the other tested frequencies between 500 Hz and 8 kHz were not significantly different between the different groups. There was a significantly lower frequency-specific signal-to-noise-ratio of the TEOAEs in the Long COVID compared to the No COVID group at 2.8 kHz. At all other frequencies, there were no significant differences between the three groups in the TEOAE signal-to-noise-ratio. CONCLUSION: This study detected no evidence of persistent cochlear damage months after SARS-CoV-2 infection in a large cohort of Long COVID patients, as well as those fully recovered.

Cochlear Implantation: Concept, Results Outcomes and Quality of Life. / Cochlea-Implantation: Konzept, Therapieergebnisse und Lebensqualität.

Cochlear implant today are an essential method of auditory rehabilitation in patients with severe to profound hearing loss. Due to the rapid development of implant technology the results have been markedly improved. Today about 80 % of patients can use the telephone and children achieve near to normal hearing and speech development. In consequence, more patients are candidates for a cochlear implant today including those with high frequency deafness and single sided deafness. However, today only 60,000 out of 1 Million CI-candidates in Germany have been implanted so far. In future multi modal universal auditory implants will provide combined electric-mechanical stimulation to make best use of the residual auditory hearing and the electrical stimulation of the auditory nerve. They allow a continuous adaptation of the stimulation strategy onto the given functional status of haircells and auditory nerve fibers especially in cases of progressive hearing loss. Brain computer interfaces will allow the automated fitting and adaptation to the acoustic scene by optimizing the signal processing for best possible auditory performance. Binaural hearing systems will improve directional hearing and speech perception in noise. Advanced implants are composed of individualized electrodes by additive manufacturing which can be inserted atraumaticly by a computer and robot assisted surgery. After insertion they automatically adept to the anatomy of the individual cochlear. These advanced implants are composed with additional integrated biological components for the preservation of residual hearing and regeneration of neural elements to improve the electrode nerve interface. This will allow to increase the number of electrical contacts as a major step towards the bionic ear. This will allow overcoming the principal limits of today's cochlear implant technology. Advanced care models will allow an easy way for the patient towards hearing preservation cochlear implantation under local anesthesia using minimal invasive high precision cochlear implant surgery. These implant systems will become a personal communicator with improved connectivity. Remote care and self-fitting will empower the patient to optimize his own hearing.

Towards single-trial classification of invasively recorded auditory evoked potentials in cochlear implant users.

Objective.One promising approach towards further improving cochlear implants (CI) is to use brain signals controlling the device in order to close the auditory loop. Initial electroencephalography (EEG) studies have already shown promising results. However, they are based on noninvasive measurements, whereas implanted electrodes are expected to be more convenient in terms of everyday-life usability. If additional measurement electrodes were implanted during CI surgery, then invasive recordings should be possible. Furthermore, implantation will provide better signal quality, higher robustness to artefacts, and thus enhanced classification accuracy.Approach.In an initial project, three additional epidural electrodes were temporarily implanted during the surgical procedure. After surgery, different auditory evoked potentials (AEPs) were recorded both invasively (epidural) and using surface electrodes, with invasively recorded signals demonstrated as being markedly superior. In this present analysis, cortical evoked response audiometry (CERA) signals recorded in seven patients were used for single-trial classification of sounds with different intensities. For classification purposes, we used shrinkage-regularized linear discriminant analysis (sLDA). Clinical speech perception scores were also investigated.Main results.Analysis of CERA data from different subjects showed single-trial classification accuracies of up to 99.2% for perceived vs. non-perceived sounds. Accuracies of up to 89.1% were achieved in classification of sounds perceived at different intensities. Highest classification accuracies were achieved by means of epidural recordings. Required loudness differences seemed to correspond to speech perception in noise.Significance.The proposed epidural recording approach showed good classification accuracy into sound perceived and not perceived when the best-performing electrodes were selected. Classifying different levels of sound stimulation accurately proved more challenging. At present, the methods explored in this study would not be sufficiently reliable to allow automated closed-loop control of CI parameters. However, our findings are an important initial contribution towards improving applicability of closed auditory loops and for next-generation automatic fitting approaches.

Superior semicircular canal dehiscence: a narrative review.

BACKGROUND: Described just over 20 years ago, superior semicircular canal dehiscence remains a relatively unknown and easily missed cause of dizziness and auditory symptoms. OBJECTIVE: This review focused on the origin, presenting symptoms and underlying pathophysiology of superior semicircular canal dehiscence, and the available treatment options. MAIN FINDINGS AND CONCLUSION: The bony dehiscence acts as a 'third window', affecting inner-ear homeostasis, and resulting in hypersensitivity and a vestibular response to lower sound level stimuli. The third window effect explains the pressure- and sound-induced vertigo, oscillopsia, and nystagmus, as well as autophony, conductive hyperacusis and tinnitus. The origin of superior semicircular canal dehiscence is linked to the combination of a congenital or developmental factor, and a 'second event' like head trauma, rapid pressure changes or age-related factors. Computed tomography of the temporal bone and reduced vestibular-evoked myogenic potential thresholds can confirm the diagnosis. Despite only retrospective cohorts, surgery is considered a safe treatment option, targeting mainly vestibular but also auditory symptoms, with transmastoid approaches gaining popularity.

Cochlea implantation in patients with superficial hemosiderosis.

INTRODUCTION: Superficial hemosiderosis is a sub-form of hemosiderosis in which the deposits of hemosiderin in the central nervous system damage the nerve cells. This form of siderosis is caused by chronic cerebral hemorrhages, especially subarachnoid hemorrhages. The diversity of symptoms depends on the respective damage to the brain, but in most of the cases it shows up as incipient unilateral or bilateral hearing loss, ataxia and signs of pyramidal tracts. We are investigating the question of whether cochlear implantation is a treatment option for patients with superficial hemosiderosis and which strategy of diagnostic procedure has to be ruled out preoperatively. MATERIALS AND METHODS: In a tertiary hospital between 2009 and 2018, we examined (N = 5) patients with radiologically confirmed central hemosiderosis who suffered from profound hearing loss to deafness were treated with a cochlear implant (CI). We compared pre- and postoperative speech comprehension (Freiburg speech intelligibility test for monosyllables and HSM sentence test). RESULTS: Speech understanding improved on average by 20% (monosyllabic test in the Freiburg speech intelligibility test) and by 40% in noise (HSM sentence test) compared to preoperative speech understanding with optimized hearing aids. DISCUSSION: The results show that patients with superficial siderosis benefit from CI with better speech understanding. The results are below the average for all postlingual deaf CI patients. Superficial siderosis causes neural damages, which explains the reduced speech understanding based on central hearing loss. It is important to correctly weigh the patient's expectations preoperatively and to include neurologists within the therapy procedure.

Melkersson-Rosenthal syndrome in the context of sarcoidosis: a case report.

BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

Monitoring of the auditory pathway maturation after early intervention during the first year of life in infants with sensorineural hearing loss.

PURPOSE: The objective of this study was to investigate the auditory pathway maturation monitored by auditory brainstem responses (ABR) in infants with hearing loss during the first year of life. ABR were used to estimate hearing thresholds and the effect of early intervention strategies using hearing aids (HA). METHODS: Click-evoked ABRs were measured in 102 infants aged from 0 to 12 months to determine their individual auditory threshold. Early therapy intervention was recommended before 12 months of age and analyzed. To evaluate the effect of hearing amplification on auditory maturation, different subgroups of infants with moderate hearing loss were analyzed and the auditory pathway maturation was determined based on IPL I-V shortening. RESULTS: Overall, 110 ears (54.0% of 204 ears) with mild to profound HL showed threshold changes of 10 dB up to 60 dB in the follow-up ABR testing. HA were prescribed at the age of 3.8 ± 3.9 months. Cochlear implantation (CI) was performed in cases of repeated profound HL at the age of 9.9 months ± 4.5 months. A significant shortening of IPL I-V in all subgroups of infants (with and without risk factors) who received HA was shown and assumed auditory pathway maturation. CONCLUSION: An early intervention using optimally fitted HA influenced auditory pathway maturation and may lead to improvements of hearing thresholds during the first year of life in infants. This study underscores the importance of not only providing HAs to infants, but also controlling for hearing threshold changes ensuring that HAs provide the optimal level of intervention or CI is indicated.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

Exploratory tympanotomy in sudden sensorineural hearing loss for the identification of a perilymphatic fistula - retrospective analysis and review of the literature.

OBJECTIVE: The diagnostic value of exploratory tympanotomy in sudden sensorineural hearing loss remains controversial. This study and review were performed to identify the incidence of perilymphatic fistula in patients with sudden sensorineural hearing loss. The effectiveness of tympanotomy for sealing of the cochlear windows in cases with perilymphatic fistula was evaluated. METHODS: A search in common databases was performed. Overall, 5034 studies were retrieved. Further, a retrospective analysis on 90 patients was performed. RESULTS: Eight publications dealing with tympanotomy in patients with sudden sensorineural hearing loss were identified. In 90 patients diagnosed with sudden sensorineural hearing loss and undergoing exploratory tympanotomy, 10 patients (11 per cent) were identified with a perilymphatic fistula, and this corresponds to the results obtained from our review (13.6 per cent). CONCLUSION: There was no significant improvement after exploratory tympanotomy and sealing of the membranes for patients with a definite perilymphatic fistula.

Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes.

BACKGROUND: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting. The Cav1.3-/- mice have already been extensively characterized and show structural changes in the inner ear. Therefore, they were used in this study as a model to investigate whether SLOT can detect structural differences in the murine cochlea. MATERIALS AND METHODS: Whole undissected cochleae from Cav1.3-/- and wild-type mice of various postnatal stages were immunostained and analyzed by SLOT. The results were compared to cochlea preparations that were immunostained and analyzed by fluorescence microscopy. In addition, cochlea preparations were stained with osmium tetraoxide. RESULTS: Visualization by SLOT showed that the staining of nerve fibers at P27 in Cav1.3-/- mice was almost absent compared to wild-type mice and earlier timepoints (P9). The analysis of cochlea preparations confirmed a reduction of the radial nerve fibers. In addition, a significantly reduced number of ribbon synapses per inner hair cell (IHC) at P20 and P27 in the apical part of the cochlea of Cav1.3-/- mice was detected. CONCLUSION: The visualization of whole non-dissected cochleae by SLOT is a suitable tool for the analysis of gross phenotypic changes, as demonstrated by means of the Cav1.3-/- mouse model. For the analysis of finer structures of the cochlea, however, further methods must be used.

Epidural recordings in cochlear implant users.

OBJECTIVE: In the long term it is desirable for CI users to control their device via brain signals. A possible strategy is the use of auditory evoked potentials (AEPs). Several studies have shown the suitability of auditory paradigms for such an approach. However, these investigations are based on non-invasive recordings. When thinking about everyday life applications, it would be more convenient to use implanted electrodes for signal acquisition. Ideally, the electrodes would be directly integrated into the CI. Further it is to be expected that invasively recorded signals have higher signal quality and are less affected by artifacts. APPROACH: In this project we investigated the feasibility of implanting epidural electrodes temporarily during CI surgery and the possibility to record AEPs in the course of several days after implantation. Intraoperatively, auditory brainstem responses were recorded, whereas various kinds of AEPs were recorded postoperatively. After a few days the epidural electrodes were removed. MAIN RESULTS: Data sets of ten subjects were obtained. Invasively recorded potentials were compared subjectively and objectively to clinical standard recordings using surface electrodes. Especially the cortical evoked response audiometry depicted clearer N1 waves for the epidural electrodes which were also visible at lower stimulation intensities compared to scalp electrodes. Furthermore the signal was less disturbed by artifacts. The objective quality measure (based on data sets of six patients) showed a significant better signal quality for the epidural compared to the scalp recordings. SIGNIFICANCE: Altogether the approach revealed to be feasible and well tolerated by the patients. The epidural recordings showed a clearly better signal quality than the scalp recordings with AEPs being clearer recognizable. The results of the present study suggest that including epidural recording electrodes in future CI systems will improve the everyday life applicability of auditory closed loop systems for CI subjects.

[Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes. German version]. / Scannende laseroptische Tomographie in einem neuropathischen Mausmodell : Visualisierung von strukturellen Veränderungen.

BACKGROUND: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting. The Cav1.3-/- mice have already been extensively characterized and show structural changes in the inner ear. Therefore, they were used in this study as a model to investigate whether SLOT can detect structural differences in the murine cochlea. MATERIALS AND METHODS: Whole undissected cochleae from Cav1.3-/- and wildtype mice of various postnatal stages were immunostained and analyzed by SLOT. The results were compared to cochlea preparations that were immunostained and analyzed by fluorescence microscopy. In addition, cochlea preparations were stained with osmium tetraoxide. RESULTS: Visualization by SLOT showed that the staining of nerve fibers at P27 in Cav1.3-/- mice was almost absent compared to wildtype mice and earlier timepoints (P9). The analysis of cochlea preparations confirmed a reduction of the radial nerve fibers. In addition, a significantly reduced number of ribbon synapses per inner hair cell (IHC) at P20 and P27 in the apical part of the cochlea of Cav1.3-/- mice was detected. CONCLUSION: The visualization of whole non-dissected cochleae by SLOT is a suitable tool for the analysis of gross phenotypic changes, as demonstrated by means of the Cav1.3-/- mouse model. For the analysis of finer structures of the cochlea, however, further methods must be used.

[Implementation of a SharePoint-based quality-assured document control system to achieve optimized patient safety]. / Implementierung eines SharePoint-basierten qualitätsgesicherten Dokumentenlenkungssystems zur Erreichung einer optimierten Patientensicherheit.

BACKGROUND: Where the facts relating to a patient's case are not unambiguously laid out, this constitutes a risk for the patient. A requirement, therefore, in the many documents necessitated by a given therapy is to achieve unambiguity, thus avoiding risks and enhancing the safety of treatment. The aim of this study was to arrive at this unambiguity using a systematic approach. MATERIALS AND METHODS: During the course of a project, all clinically relevant documents generated by the department were converted from an uncontrolled form stored within the department's IT system to a SharePoint-based, controlled form. To this end, a means of systematization was developed that reflects the organizational realities of the department. RESULTS: The relevant documents are now available only in a controlled form using a SharePoint system. Access to these documents was successfully achieved for all employees. Any change to the documents is now logged. CONCLUSION: The project can be viewed as exemplary in nature, since its outcome represents a multidimensional contribution to patient safety that can be regarded as an important milestone in a given department's clinical culture. It may also be beneficial as a model for other equally motivated departments as well as being useful from an interdisciplinary perspective.

[Reactions in the organ of Corti to electrical stimulation : StED technology for detecting changes]. / Reaktionen im Corti-Organ auf elektrische Stimulation : StED-Technologie zum Nachweis von Veränderungen.

Increasing numbers of cochlear implant patients have residual hearing. Despite surgical and pharmacological efforts to preserve residual hearing, a significant number of these patients suffer a late, unexplained loss of residual hearing. Surgical trauma can be excluded as the cause. To investigate this phenomenon and because cells in their native environment react differently to stimuli (such as electrical current) than isolated cells, whole-organ explants from cochleae may be a better model. For early detection of synaptic changes in the organ of Corti, a high-resolution microscopic technique such as stimulated emission depletion (StED) can be used. The aim of this study was establishment of a qualitative and quantitative technique to determinate changes in the organ of Corti and its synapses after electrical stimulation. Explanted organs of Corti from postnatal rats (P2-4) were cultured on a coverslip for 24 h and subsequently exposed to biphasic pulsed electrical stimulation (amplitude 0.44-2.0 mA, pulse width 400 µs, interpulse delay 120 µs, repetition 1 kHz) for another 24 h. For visualization, the cytoskeleton and the ribbon synapses were stained immunocytochemically. For an early detectable response to electrical stimulation, the number of synapses was quantified. Organs of Corti without electrical stimulation served as a reference. Initial research has shown that electrical stimulation can cause changes in ribbon synapses and that StED can detect these alterations. The herein established model could be of great importance for identification of molecular changes in the organ of Corti in response to electrical or other stimuli.

Intraluminal three-dimensional optical coherence tomography - a tool for imaging of the Eustachian tube?

OBJECTIVES: The cause of Eustachian tube dysfunction often remains unclear. Therefore, this study aimed to examine the feasibility and possible diagnostic use of optical coherence tomography in the Eustachian tube ex vivo. METHODS: Two female blackface sheep cadaver heads were examined bilaterally. Three conditions of the Eustachian tube were investigated: closed (resting position), actively opened and stented. The findings were compared (and correlated) with segmented histological cross-sections. RESULTS: Intraluminal placement of the Eustachian tube with the optical coherence tomography catheter was performed without difficulty. Regarding the limited infiltration depth of optical coherence tomography, tissues can be differentiated. The localisation of the stent was accurate as was the lumen. CONCLUSION: The application of optical coherence tomography in the Eustachian tube under these experimental conditions is considered to be a feasible, rapid and non-invasive diagnostic method, with possible diagnostic value for determining the luminal shape and superficial lining tissue of the Eustachian tube.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Publisher Correction: Spiral Form of the Human Cochlea Results from Spatial Constraints.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

[Cochlear implantation in a girl with 7q-microdeletion syndrome]. / Cochleaimplantatversorgung eines Mädchens mit 7q-Mikrodeletionssyndrom.

One of the rare genetic diseases with sensory hearing loss is the microdeletion 7q syndrome. First described in the 1990s, only 7 cases of patients with this disease are described in the literature. Although this mutation is not well known, otological treatment is necessary if the DFNA5 gene is affected. A mutation in this gene leads to progressive hearing loss. Affected children therefore need regular evaluation of their hearing to ensure adequate treatment with hearing aids at early stages. We now present a case of an affected child with sensory hearing loss, mental retardation and anogenital malformations. In the following we describe the course of disease and possible treatment options. We especially describe the possibility of cochlear implantation. We can show with this case report that, even though massive mental retardation is shown, cochlear implantation is useful in this patient. Associated disabilities as cardiac and pulmonary problems may occur and should be treated before cochlear implantation. This is the first report of cochlear implantation in a child affected with microdeletion 7q syndrome.