[Development of the publication activity at the German university hospitals for Otorhinolaryngology, Head and Neck Surgery during the SARS-CoV-2-pandemic in 2020]. / Entwicklung der Publikationsleistung der Universitätskliniken für Hals-Nasen-Ohrenheilkunde, Kopf- und Hals-Chirurgie während der SARS-CoV-2-Pandemie im Jahr 2020 in Deutschland.

INTRODUCTION: The SARS-CoV-2 pandemic has led to profound limitations in patient care and student teaching at the University Hospitals of Otorhinolaryngology (ORL). In contrast, the impact on research has been variable. To classify the pandemic-related effect on research, the development of the number of scientific publications of the German ORL university hospitals before and during the pandemic was analyzed. MATERIAL AND METHODS: The publication performance between 2015 and 2020 of the 39 current chairmen was surveyed using a literature search (Pubmed). All entries relating to the chairmen of the university hospital as first, last or co-author were included. The absolute and relative development of each author's publication performance was determined and evaluated using nonparametric statistical methods. RESULTS: A total of 2420 publications could be documented. From 2015 to 2019, an average of 368 publications were published per year. In 2020, this number increased by 57.9 % to 581 publications. While the number of monthly publications remained constant between 2015 and 2019, a significant increase was seen from May 2020 up to a maximum of 74 publications in September 2020. In 2020, 34 articles (5.9 %) had a thematic relation to the SARS-CoV-2 pandemic, with 7 of these papers (20.6 %) resulting from cross-site publications. CONCLUSION: In 2020, the number of scientific publications was raised to more than 1.5 times the usual annual publications. This increase was clearly related in time to the reduction of elective patient care during the SARS-CoV-2 pandemic starting in mid-March 2020. Probably, free time capacities enabled this increased publication output. Our results confirm the great scientific potential of the ORL university hospitals, which has been successfully implemented despite the pandemic.

["Online from tomorrow on please": comparison of digital framework conditions of curricular teaching at national university ENT clinics in times of COVID-19 : Digital teaching at national university ENT clinics]. / "Ab morgen bitte online": Vergleich digitaler Rahmenbedingungen der curricularen Lehre an nationalen Universitäts-HNO-Kliniken in Zeiten von COVID-19 : Digitale Lehre an nationalen Universitäts-HNO-Kliniken.

BACKGROUND: The corona crisis not only affects professional activities but also teaching and learning at universities. Buzzwords, such as e­learning and digitalization suggest the possibility of innovative teaching approaches that are readily available to solve the problems of teaching in the current COVID-19 pandemic. The current conversion to digital teaching is not primarily driven by didactic rationale or institutional strategy but by external circumstances. OBJECTIVE: The aim of the study was to determine the teaching situation at national university ENT clinics and academic teaching hospitals at the start of the virtual corona summer semester in 2020. MATERIAL AND METHODS: A specifically self-designed questionnaire regarding the local situation and conditions as well as nationwide scenarios was sent to all 39 national university ENT clinics and 20 ENT departments at academic teaching hospitals. RESULTS: A total of 31 university hospitals and 10 academic teaching hospitals took part in the survey. There were obvious discrepancies between available resources and effectively available digital teaching and learning contents. Further criticism was expressed regarding the communication with the medical faculty, the digital infrastructure and particularly the frequent lack of collaboration with central support facilities, such as media, didactics and datacenters. CONCLUSION: There are positive examples of successful transformation of classroom teaching to an exclusively virtual summer semester 2020 within the university ENT clinics; however, critical ratings of assistant professors and medical directors regarding the current teaching situation predominated. A time-critical strategic advancement is urgently needed.

[Regional distribution of the cochlear implant (CI) centers in Germany]. / Regionale Verteilung der Cochlea-Implantat (CI)-versorgenden Einrichtungen in Deutschland.

The treatment of patients with severe hearing loss or deafness with a cochlear implant (CI) represents a standard in Germany today. However, there is hardly any data on the current number of clinical CI centers (CI clinics) and their geographical distribution. The patient self-help organization, German Cochlear Implant Society (DCIG), and the German Society for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) have therefore initiated a survey to determine the regional distribution, the range of services, the consideration of existing quality standards and cooperation with patient self-help organizations of the individual clinical CI centers.For this purpose, a total number of 170 ENT departments or their directors (37 professors and 133 chief physicians), respectively, were contacted by e-mail and provided with a questionnaire. The survey took place from October 2019 to February 2020.Of the 170 departments contacted, 71 (41.8 %) took part in the survey. Of these, 70 departments (98.6 %) confirmed to perform CI surgeries. Thus, 41.8 % of all clinics contacted reported to perform CI surgeries (70 of 170 clinics), while this information was not available from 99 clinics. All 70 clinical CI centers (100 %) reported to conduct CI surgeries on adults, 60 centers (85.7 %) also on children (< 18 years). 36 departments (51.4 %) reported that the total number of CI surgeries at their facility in 2018 was more than 50. In 64 departments (91.4 %), the recommendations of the DGHNO-KHC on CI care (according to the White Paper CI care 2018) were followed. A collaboration between the department and patient self-help organization was confirmed by 67 institutions (95.7 %). The geographical distribution of the clinical CI centers showed a heterogeneous distribution pattern between the individual federal states and also within the respective federal state.The work presented here is a first assessment of the situation with regard to the regional distribution of clinical CI centers in Germany. A clustering of CI centers was noticeable in metropolitan areas, sometimes with several facilities in one city. The predominant attention to quality-related aspects, such as the consideration of the DGHNO-KHC white paper and the cooperation with patient self-help, is gratifying. The limitations of the study result from limited participation in the survey (41.8 % of the contacted clinics).

[Strategies for a regenerative therapy of hearing loss. German version]. / Strategien für eine regenerative Therapie der Schwerhörigkeit.

Despite impressive technical progress in the field of conventional hearing aids and implantable hearing systems, the hopes for the treatment of inner ear diseases such as hearing loss and tinnitus have become increasingly directed toward regenerative therapeutic approaches. This review discusses the currently most promising strategies for hair cell regeneration in the inner ear to treat hearing loss, including stem cell-based, gene transfer-based, and pharmacological interventions. Furthermore, previous milestones and ground-breaking work in this scientific field are identified. After many years of basic research, the first clinical trials with a regenerative therapeutic approach for hearing-impaired patients were recently initiated. Although there is still a long and bumpy road ahead until a true breakthrough is achieved, it seems more realistic than ever that regenerative therapies for the inner ear will find their way into clinical practice.

Strategies for a regenerative therapy of hearing loss.

Despite impressive technical progress in the field of conventional hearing aids and implantable hearing systems, the hopes for the treatment of inner ear diseases such as hearing loss and tinnitus have become increasingly directed toward regenerative therapeutic approaches. This review discusses the currently most promising strategies for hair cell regeneration in the inner ear to treat hearing loss, including stem cell-based, gene transfer-based, and pharmacological interventions. Furthermore, previous milestones and ground-breaking work in this scientific field are identified. After many years of basic research, the first clinical trials with a regenerative therapeutic approach for hearing-impaired patients were recently initiated. Although there is still a long and bumpy road ahead until a true breakthrough is achieved, it seems more realistic than ever that regenerative therapies for the inner ear will find their way into clinical practice.

[Molecular biology of hearing]. / Molekularbiologie des Gehörs.

The inner ear is our most sensitive sensory organ and can be subdivided into 3 functional units: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear habors the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In the past years there was significant progress in research on the molecular basis of hearing. More and more genes and proteins which are related to hearing can be identified and characterized. The increasing knowledge on these genes contributes not only to a better understanding of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss.

[Characterization of stem cells derived from the neonatal auditory sensory epithelium]. / Charakterisierung von Stammzellen des neonatalen auditorischen Sinnesepithels.

BACKGROUND: In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. MATERIAL AND METHODS: We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. RESULTS: Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. CONCLUSION: Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

[In vitro neurite outgrowth induced by BDNF and GDNF in combination with dexamethasone on cultured spiral ganglion cells]. / Neuritenwachstum in vitro durch BDNF und GDNF in Kombination mit Dexamethason auf kultivierte Spiralganglienzellen.

BACKGROUND: The efficacy of cochlear implant performance depends, among many other factors, on the number of excitable spiral ganglion cells (SGCs) and the nerve-electrode interface. In earlier animal studies it has been demonstrated that neurotrophic factors are effective to improve SGC survival after experimentally induced deafness. With regard to their anti-inflammatoric and anti-proliferative effects, glucocorticoids (e. g. dexamethasone) are potentially interesting therapeutic agents to reduce connective tissue formation around the inserted electrode. The biological effects of a combined intervention of neurotrophic factors with steroids on SGCs are unknown. Therefore the objective of the study was to investigate possible trophic or even toxic effects of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and dexamethasone on neurite outgrowth of cultivated SGCs. METHODS: By using dissociated postnatal spiral ganglion cells (p3-5) for cultivation in the present study, the influence of the mentioned factors in various concentrations and combinations on neurite outgrowth of SGCs was analysed. RESULTS: Our results indicate significant trophic effects for BDNF (50 ng/ml) and a combination of BDNF with dexamethasone (100 ng/ml) on SGC neurite outgrowth. In contrast, single application of GDNF or dexamethasone in different concentrations caused no significant changes on neurite outgrowth when compared to the control condition. CONCLUSIONS: Neurite outgrowth induced by neurotrophic factors could not be observed to be reduced when dexamethasone is given at the same time. Therefore the demonstrated results provide a basis for further animal studies in this field of research.

[Neurotrophic factor expression in vestibular schwannoma. An overview]. / Expression neurotropher Faktoren im Vestibularisschwannom--eine Ubersicht.

The vestibular schwannoma is a benign, slow-growing neoplasm that originates from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This tumor entity accounts for 6 % of all intracranial tumors and the annual incidence of newly diagnosed vestibular schwannoma is reported as 13 per million. The molecular pathogenesis of both sporadic vestibular schwannoma and those occurring in neurofibromatosis type II appears to be associated with an aberration of a tumor suppressor gene on chromosome 22q12. The biological background for the various growth patterns of vestibular schwannoma is, however, largely unknown. This differing clinical and biological behaviour of vestibular schwannoma may be explained by the presence of neurotrophic factors. The results of recent immunohistochemical studies demonstrate the co-expression of transforming growth factor (TGF)-beta 1 and glial cell line-derived neurotrophic factor (GDNF) in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor. Moreover, expression of numerous different neurotrophic factors has been shown in studies of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a biological role in development, maintainance or growth of vestibular schwannoma. In this article, we summarize the findings on neurotrophic factor expression and discuss their characteristics and biological role in vestibular schwannoma.

Co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor in vestibular schwannoma.

HYPOTHESIS: Transforming growth factor-beta1, glial cell line-derived neurotrophic factor, and their receptors are expressed in vestibular schwannoma, and the expression data correlate with the proliferation activity (Ki-67 labeling index) and the clinical growth rate of vestibular schwannoma tissue. BACKGROUND: Glial cell line-derived neurotrophic factor is a potent growth factor for the central and peripheral nervous system. Recent results demonstrate that glial cell line-derived neurotrophic factor requires transforming growth factor-beta to exert its trophic effect on neural tissue. A functional role, including that in Schwann cell proliferation, is discussed for both transforming growth factor-beta1 and glial cell line-derived neurotrophic factor. METHODS: Immunohistochemical analysis for transforming growth factor-beta1 and glial cell line-derived neurotrophic factor and their receptors TbetaR II, GFRalpha-1, and Ret was performed on formalin-fixed, paraffin-embedded archival surgical specimens. The Ki-67 labeling index (mean Ki-67 labeling index and highest Ki-67 labeling index for Antoni Type A and Type B regions) and the clinical growth rate of vestibular schwannoma were determined and correlated with the expression patterns of the examined neurotrophic factors and their receptors. RESULTS: Results demonstrate co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor with higher levels in Antoni Type A than in Antoni Type B regions. Ninety-five percent of vestibular schwannomas exhibited transforming growth factor-beta1 immunoreactivity, and glial cell line-derived neurotrophic factor expression was found in 100% of vestibular schwannoma specimens. Fifty percent of vestibular schwannoma displayed TbetaR II immunostaining, 100% showed positive reactions for GFRalpha-1, and 86% showed positive reactions for Ret. Statistical analysis revealed no significant correlation in neurotrophin expression related to sex, age, tumor size, clinical growth rate, or Ki-67-labeling indices. CONCLUSIONS: Expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor may suggest a biological role for both growth factors in vestibular schwannomas. Trophic transforming growth factor-beta/glial cell line-derived neurotrophic factor synergism seems possible and is underscored by co-expression of both neurotrophic factors and their receptors.