[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.

[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.

[20 Years of Bilateral Cochlear Implantation - an Analysis of the Implanted Patients]. / 20 Jahre bilaterale Cochleaimplantation ­ eine Analyse seither implantierter erwachsener Patienten.

Binaural hearing is essential for localization abilities and improves the speech perception in noise. Since 20 years, bilateral cochlear implantation is routinely performed to restore binaural hearing. In this cross-sectional study, we evaluated speech perception in quiet (Freiburger monosyllables, Hochmair-Schulz-Moser (HSM) sentence test, each at 70 dB) and in noise (HSM test, signal-to-noise ratio 10 dB) in 103 out of 165 adult patients who were bilaterally implanted in Würzburg between 1995 and June 2014. In almost half the patients, the second implanted side showed the better speech perception. Compared to the first implanted side, the average monosyllable scores with bilateral implants were improved from 54 to 63% and the HSM scores from 86 to 96%. In noise the speech perception improved from 47 to 65%. The speech perception of the second implanted side was independent of the time interval between the implantation of both sides in this cohort of postlingually deafened patients. This cross-sectional data underline the importance of bilateral cochlear implantation for speech understanding in quiet and even more in noise and thus, for the everyday life. For this, bilateral cochlear implantation should be the generally accepted standard in the treatment of deaf patients.

Labeling Adipose-Derived Stem Cells with Hoechst 33342: Usability and Effects on Differentiation Potential and DNA Damage.

Adipose-derived stem cells (ASCs) have been extensively studied in the field of stem cell research and possess numerous clinical applications. Cell labeling is an essential component of various experimental protocols and Hoechst 33342 (H33342) represents a cost-effective and easy methodology for live staining. The purpose of this study was to evaluate the labeling of rat ASCs with two different concentrations of H33342 (0.5 µg/mL and 5 µg/mL), with particular regard to usability, interference with cell properties, and potential DNA damage. Hoechst 33342 used at a low concentration of 0.5 µg/mL did not significantly affect cell proliferation, viability, or differentiation potential of the ASCs, nor did it cause any significant DNA damage as measured by the olive tail moment. High concentrations of 5 µg/mL H33342, however, impaired the proliferation and viability of the ASCs, and considerable DNA damage was observed. Undesirable colabeling of unlabeled cocultivated cells was seen in particular with higher concentrations of H33342, independent of varying washing procedures. Hence, H33342 labeling with lower concentrations represents a usable method, which does not affect the tested cell properties. However, the colabeling of adjacent cells is a drawback of the technique.

[Direct Drive Simulation - Sound-Simulation of the Vibrant Soundbridge®]. / Direct Drive Simulation - Klangsimulation des Vibrant Soundbridge®-Hörens.

BACKGROUND: The Direct-Drive-Simulation (DDS) tends to simulate the sound quality of hearing with the active middle ear implant Vibrant Soundbridge(®) (VSB). Up to now a scientific evaluation of the validity is missing. Furthermore, the test procedure has not been described yet. Aim of this study was to evaluate the test validity and to describe the test realization in detail. MATERIAL AND METHODS: 10 patients evaluated their sound impression on scales from 1 to 10 concerning sound quality during DDS, postoperative free field testing at least 3 month after the first fitting of the VSB and in the everyday life situation. 3 patients were implanted bilaterally. Together, 36 data sets could be analyzed. RESULTS: Coupling of the Floating Mass Transducer (FMT), which was placed inside of a silicone probe during DDS was successful in all cases. In 11 out of 13 cases the coupling quality was judged as "good" an only in 2 cases as "medium". None of the patients needed local anesthesia. Comparing the evaluation of the sound impression during DDS preoperatively, and with the implanted VSB in free field testing and in everyday life no significant differences were found. CONCLUSION: The DDS offers the possibility of a realistic preoperative sound simulation of the "VSB-hearing" in case of sensorineural hearing loss. Thus, the test is supposed to facilitate the patient's decision towards possible treatment options. The specialist gets additional information regarding the indication especially when audiologic indication criteria are critical. The DDS should be a basic part of the preoperative diagnostic prior to VSB-implantation.

[Auditory evoked potentials: basics and clinical applications]. / Akustisch evozierte Potenziale: Grundlagen und klinische Anwendung.

Auditory evoked potentials (AEPs) are elicited at various levels of the auditory system following acoustic stimulation. Electrocochleography is a technique for recording AEPs of the inner ear. The recording is performed by means of a needle electrode placed on the promontory or non-invasive with tympanic membrane or ear canal electrodes. Clinically, electrocochleography is used for the diagnosis of auditory neuropathy spectrum disorder (ANSD) and endolymphatic hydrops. According to their latencies, AEPs of the central auditory pathway are subdivided into early, middle and late (cortical) AEPs. These AEPs are recorded via surface scalp electrodes. Normally, the larger EEG masks AEPs. For unmasking the AEP, several techniques are applied. Early AEPs or auditory brainstem responses (ABR) are the most widely used AEPs for functional evaluation of the auditory pathway. In contrast to otoacoustic emissions, early AEPs can detect ANSD. Thus, they are more suitable for hearing screening in newborns. For this purpose automated procedures are implemented.

Human mesenchymal stem cells promote cancer motility and cytokine secretion in vitro.

Interactions of human mesenchymal stem cells (hMSC) with tumors are controversially discussed since there is evidence for both tumor progression as well as tumor inhibition by hMSC. The objective of the present study is to investigate whether hMSC support cell motility and cytokine secretion in a head and neck squamous cell carcinoma cell line (HLaC 78). A spheroid model was generated in which the ultrastructure of spheroids was analyzed using scanning electron microscopy (SEM). The migration capability was monitored in a monolayer as well as in a spheroid model. The variation in migration and secretion of interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF), as well as the expression of the multidrug resistance gene (MDR-1) was investigated. Finally, the alteration in the cell cycle was analyzed by flow cytometry. SEM showed a tight cell-cell contact with extensive secretion of extracellular matrix. The migration and invasion capability of HLaC 78 was enhanced by hMSC. Cancer cell motility was also increased by hMSC as well as secretion of the cytokines IL-6, IL-8 and VEGF. hMSC did not induce the expression of MDR-1 in HLaC 78, and there was no alteration in the cell cycle of HLaC 78 after cocultivation with hMSC. Our results confirm the important role of hMSC in cancer biology since both an enhancement of cell motility as well as cytokine secretion could be shown. However, based on these findings and those in the current literature, caution must be applied when using hMSC as a carrier for tumor therapy in cancer treatment.

DiI labeling of human adipose-derived stem cells: evaluation of DNA damage, toxicity and functional impairment.

INTRODUCTION: Adipose tissue-derived stem cells (ASCs) have become the primary focus of tissue engineering research. To understand their functions and behavior in in vitro and in vivo models, it is mandatory to track the implanted cells and distinguish them from the resident or host cells. A common labeling method is the use of fluorescent dyes, e.g. the lipophilic carbocyanine dye, DiI. This study aimed to analyze potential DNA damage, toxicity and impairment of the functional properties of human ASCs after labeling with DiI. METHODS: Cytotoxicity was measured using the MTT assay and DNA damage was determined by means of the comet assay. Potential apoptotic effects were determined using the annexin V-propidium iodide test. Differentiation potential was evaluated by trilineage differentiation procedures in labeled and unlabeled ASCs. Proliferation as well as migration capability was analyzed, and the duration and stability of DiI labeling in ASCs during in vitro expansion was observed over a period of 35 days. RESULTS: DiI labeling did not cause genotoxic effects 15, or 30 min or 24 h after the labeling procedure, and there were no cytotoxic effects until 72 h afterwards. No impairment of proliferation or migration capability or differentiation potential could be determined. However, after 35 days, only 37% of labeled cells could be detected using the fluorescence microscope, which indicates a decrease in staining stability during in vitro expansion. CONCLUSION: DiI is a convenient method for ASCs labeling which causes no toxic effects and does not impair the proliferation, migration or differentiation potential of ASCs after the labeling procedure.

Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro.

Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 µM and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells.

Bisphosphonate-induced osteonecrosis of the external ear canal: a retrospective study.

In 2003, osteonecrosis of the jaw was described as an intraoral complication of bisphosphonate therapy. More recently, cases of avascular necrosis of the hip were reported in patients with long-lasting bisphosphonate therapy. Thus, it was the aim of the present study to analyze cases of benign osteonecrosis of the external ear canal and to retrospectively identify a possible relationship to long-lasting bisphosphonate therapy. 13 patients with osteonecrosis of the external ear canal operated on between 2005 and 2009 were included. Patient histories were reviewed for possible previous or current bisphosphonate therapy. Three patients with osteonecrosis of the external ear canal and long-term bisphosphonate therapy could be identified. They had been treated either for breast cancer or multiple myeloma. Certainly, the jaw is an area of increased risk for developing osteonecrosis with its high mechanical stress and intraoral bacterial flora. However, osteonecrosis of the hips and the external ear canal in patients receiving long-term bisphosphonate therapy necessitate further investigation of a possible systemic, bisphosphonate-related phenomenon.

[Short and long term results of endolymphatic sac surgery: a patient-questionnaire based study]. / Die Saccotomie in der Behandlung des M. Ménière: Beurteilung der kurz-, mittel- und langfristigen Ergebnisse anhand eines Patientenfragebogens.

INTRODUCTION: The endolymphatic sac surgery for the treatment of Meniere's disease has been described since the 1920s. The success rate of this technique in terms of vertigo control has been reported to be 50-80%. However, the value of this treatment method remained controversial. Furthermore, the reliable identification of the endolymphatic sac intraoperatively can be challenging in some cases. This study examines the short-, middle- and long-term results in a larger cohort of patients. MATERIALS AND METHODS: In 74 patients, vertigo control, tinnitus and degree of satisfaction was evaluated by means of a questionnaire retrospectively. Additionally, the diagnostic value of the electrocochleography (EcochG) was determined. RESULTS: The overall vertigo control rate was more than 70% in patients followed up for two years and has reached 81% in patients followed up for more than two years. Hearing preservation rate was 61%. Tinnitus has disappeared in 11% and improved in 23% of the patients. In 47% of the patients it was unchanged and in 19% worsened. The difference in EcochG results pre- versus postoperative was highly significant. CONCLUSIONS: ELSS is a useful tool in the management of Ménière's disease, in particular in patients that do not benefit sufficiently from conservative therapy.

[Megadolichobasilar anomaly causing acute deafness with vertigo]. / Megadolichobasilaris als Ursache einer akuten Taubheit mit Schwindel.

Megadolichobasilar anomaly, a dilatant arteriopathy of the basilar artery attributable to chronic arterial hypertension, can cause cranial nerve compression syndromes of the cerebellopontine angle or infarcts of the vertebrobasilar circulation. In this paper, we report on a patient with known megadolichobasilar anomaly and a partially thrombosed fusiform aneurysm of the basilar artery, who presented with acute-onset vertigo and subsequent deafness due to thromboembolic occlusion of the labyrinthine artery. Because of the vascular origin of the patient's symptoms, his vertigo disappeared over time while the deafness persisted.

[Exostoses of the external auditory canal. Is the cold water hypothesis valid for patients in continental areas?]. / Exostosen des äusseren Gehörgangs. Gilt die Kaltwassertheorie auch für Patienten aus Binnengebieten?

INTRODUCTION: Exostoses of the external auditory meatus are benign masses of tympanal bone that can lead to infections of the external auditory meatus in advanced cases and then need surgical treatment. Regular irritation of the auditory meatus by exposure to cold water was implicated in the causation of exostoses long ago. The present study investigates the cold water hypothesis in a patient group of continental origin. The surgical procedures and results are discussed. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: We present the epidemiological and aetiological data and postoperative findings recorded for 144 patients (167 procedures) who underwent surgical removal of exostoses from the external auditory meatus in the hospital in Würzburg within 11 years. In attempt to glean further information about the aetiology, patients were also asked to complete a questionnaire on participation in water sports and their symptoms before and since the operation. RESULTS: Most of the patients (94%) had taken part in water sports for some years, more than 80% of them several times weekly. The most common indication for surgical removal was recurrent infection of the external ear. Although 50% of the patients reported improved hearing, no higher sound threshold was observed. Reversible complications (ear drum performation, tinnitus, opening of mastoid cells) were observed in 18% of the patients. One patient had a stenosis of the auditory canal caused by scar tissue. CONCLUSIONS: Surgical removal of exostoses in the external auditory canal is frequently fraught with controllable complications. The indications for their surgical removal should be strictly applied; the presence of exostoses in isolation is not an acceptable indication for surgery. Removal of exostoses is an adequate way of avoiding recurrent external ear infections. Improved hearing can be expected only if the self-cleaning function of the external auditory meatus is improved.

Brain-derived neurotrophic factor treatment does not improve functional recovery after hair cell regeneration in the pigeon.

CONCLUSIONS: Brain-derived neurotrophic factor (BDNF) supply to the inner ear does not improve the time course or the extent of functional recovery after hair cell regeneration. Specifically it does not improve the residual threshold elevation observed after the completion of spontaneous recovery. OBJECTIVE: The avian inner ear is capable of hair cell regeneration and substantial functional recovery, but residual hearing deficits remain. We investigated whether functional recovery can be improved by intracochlear application of BDNF, which plays an important role in auditory ontogenesis and maintenance during adult life. METHODS: Hair cells in adult pigeons were destroyed by local application of gentamicin. After 3 days either BDNF or control solution was administered to the scala tympani by implanted osmotic minipumps for 8 weeks. Auditory brain stem responses (ABR) to tone pips were used to assess recovery of hearing thresholds in both groups. RESULTS: The application of gentamicin caused a frequency-dependent hearing loss that ranged from 24.8 dB SPL at low frequencies to 66.2 dB SPL at high frequencies. After day 10 substantial recovery was observed, but a significant threshold shift remained. The time course of recovery in the control and BDNF-treated groups was similar, without significant residual threshold differences in any frequency range.

Evaluating cochlear implant trauma to the scala vestibuli.

OBJECTIVES: Placement of cochlear implant electrodes into the scala vestibuli may be intentional, e.g. in case of blocked scala tympani or unintentional as a result of trauma to the basilar membrane or erroneous location of the cochieostomy. The aim of this study was to evaluate the morphological consequences and cochlear trauma after implantation of different cochlear implant electrode arrays in the scala vestibuli. DESIGN: Human temporal bone study with histological and radiological evaluation. SETTING: Twelve human cadaver temporal bones were implanted with different cochlear implant electrodes. Implanted bones were processed using a special method to section undecalcified bone. MAIN OUTCOME MEASURES: Cochlear trauma and intracochlear positions. RESULTS: All implanted electrodes were implanted into the scala vestibuli using a special approach that allows direct scala vestibuli insertions. Fractures of the osseous spiral lamina were evaluated in some bones in the basal cochlear regions. In most electrodes, delicate structures of the organ of Corti were left intact, however, Reissner's membrane was destroyed in all specimens and the electrode lay upon the tectorial membrane. In some bones the organ of Corti was destroyed. CONCLUSIONS: Scala vestibuli insertions did not cause severe trauma to osseous or neural structures, thus preserving the basis for electrostimulation of the cochlea. However, destruction of Reissner's membrane and impact on the Organ of Corti can be assumed to destroy residual hearing.

[Evaluation of an electrode design for the combined electric-acoustic stimulation]. / Evaluation eines Elektrodendesigns für die kombinierte elektrisch-akustische Stimulation.

BACKGROUND: The objective of this study was to assess the intracochlear position and the extent of trauma to cochlear structures using the C40(+) M electrode (MED-EL, Innsbruck, Austria), which was especially designed for the combined electric acoustic stimulation. METHODS: Five human temporal bones were implanted using a standard cochlear implant procedure featuring mastoidectomy, posterior tympanotomy, and promontory cochleostomy. For the cochleostomy, an inferior approach with preservation of the endosteum of the cochlea was used to contribute to hearing preservation in the in vivo condition. RESULTS: All insertions of the new electrode array were performed into the scala tympani of the cochlea. The average insertion depth was 288 degrees. Apically, 4 of the 5 implantations were completely atraumatic. One bone showed a rupture of the basilar membrane only at the tip of the electrode. However, 4 of the 5 arrays produced severe trauma to basal cochlear structures. Two pathomechanisms, the direct traumatization through drilling of the cochleostomy or the indirect traumatization via buckling of the array could be distinguished. CONCLUSIONS: Due to the reduced contact spacing and its flexible body, the C40(+) M electrode is suitable for cochlear implantations with hearing preservation and combined electric and acoustic stimulation of the auditory system. Modifications of the surgical pathway to the cochlea should help to minimize the risk of basal cochlear trauma.