[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.

[Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts]. / Das Tumormikromilieu bei Speicheldrüsenkarzinomen ­ mögliche Konsequenzen für neue Therapiekonzepte.

INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA­4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.

[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.

Patient's perspective on long-term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2-year follow-up.

OBJECTIVE: Evaluation of patients' perspective on long-term complications after superficial parotidectomy for benign lesions. DESIGN: A prospective nonrandomized controlled multicenter study. SETTING: Three university-based tertiary referral centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in Germany). PARTICIPANTS: 130 adult patients, who underwent a primary superficial parotidectomy for benign tumors of the parotid gland, were consecutively included from 09/2010 to 05/2012. 61 patients completed every follow-up examination. MAIN OUTCOME MEASURES: Complications were evaluated using the validated German-language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at each follow-up visit. RESULTS: At 6 months after surgery, 90% characterized hypoesthesia as the most disturbing problem, followed by fear of revision surgery (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia improved significantly during the follow-up period (all P < .05), but still posed a problem for 78% of the patients after 2 years. Pain, which initially bothered 53% of the patients, significantly decreased, whereas impairment due to Frey's syndrome significantly increased during the follow-up (6 vs 24 months; P = .002 and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and anxiety affected patients with unvarying severity during the 2 years (all P > .05). CONCLUSIONS: From patients' perspective, sensation loss posed the major subjective problem after superficial parotidectomy. Appearance of the scar, and fear of revision surgery impaired more than 50% of the patients in their daily life without significant improvement during the 2 years postoperatively. Although superficial parotidectomy is a highly standardized and safe procedure, limited parotidectomy for proven benign parotid salivary gland neoplasms is more likely to result in patients with minimal or no displeasing complications.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Influence of backside loading on the floating mass transducer: An in vitro experimental study.

HYPOTHESIS: The vibration of the floating mass transducer (FMT) of a single active middle-ear implant (AMEI) is distinctly influenced by the properties of the material coupled to its back side. BACKGROUND: In round window vibroplasty, the FMT needs to be padded against the surrounding bone opposite from the round window membrane. This represents one factor influencing its performance as a round window driver. Therefore, we examined the effects of different materials linked to the back side of an FMT on its vibration range. METHODS: The back side of an FMT was glued to a silicone cylinder 1.0 mm in diameter and 1.0 mm - 1.5 mm in length and of 40A, 50A or 70A Shore hardness; to cartilage of equivalent size; or to a round window soft coupler (RWSC), all firmly fixed on a steel plate. The vibrations were determined by a laser Doppler vibrometer (LDV) measuring the velocity of the centre point on the front side of the FMT. RESULTS: The materials on the back side of the FMT significantly influenced the vibration range of the FMT. The RWSC and silicone of 40A Shore hardness allowed for the highest detected velocities, while cartilage led to a distinct reduction similarly to 70A silicone. CONCLUSION: The coupling on the back side of an FMT distinctly affects its vibration range. In this regard, the RWSC and silicone of 40A Shore hardness yield the least impairment of vibration. Thus, the RWSC may be a feasible option in round window vibroplasty when additionally connected to the FMT opposite from the round window membrane.

Surgical anatomy of the round window-Implications for cochlear implantation.

BACKGROUND: The round window is an important portal for the application of active hearing aids and cochlear implants. The anatomical and topographical knowledge about the round window region is a prerequisite for successful insertion for a cochlear implant electrode. OBJECTIVE OF REVIEW: To sum up current knowledge about the round window anatomy and to give advice to the cochlear implant surgeon for optimal placement of an electrode. TYPE OF REVIEW: Systematic Medline search. SEARCH STRATEGY: Search term "round window[Title]" with no date restriction. Only publications in the English Language were included. All abstracts were screened for relevance, that is a focus on surgical anatomy of the round window. The search results were supplemented with hand searching of selected reviews and reference lists from included studies. EVALUATION METHOD: Subjective assessment. RESULTS: There is substantial variability in size and shape of the round window. The round window is regarded as the most reliable surgical landmark to safely locate the scala tympani. Factors affecting the optimal trajectory line for atraumatic electrode insertion are anatomy of the round window, the anatomy of the intracochlear hook region and the variable orientation and size of the cochlea's basal turn. CONCLUSIONS: The very close relation to the sensitive inner ear structures necessitates a thorough anatomic knowledge and careful insertion technique, especially when implanting patients with residual hearing. In order to avoid electrode migration between the scalae and to achieve protect the modiolus and the basilar membrane, it is recommended to aim for an electrode insertion vector from postero-superior to antero-inferior.

Reliability of Eustachian tube function measurements in a hypobaric and hyperbaric pressure chamber.

OBJECTIVES: Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases-especially because more and more operative therapies are being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear. METHODS: Twenty-five participants (50 ears) were exposed to phases of compression and decompression in a hypo- and hyperbaric pressure chamber. The ET function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF)-were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test-retest reliability. RESULTS: ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altman graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases. CONCLUSIONS: We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.

Prediction of outcome by lymph node ratio in patients with parotid gland cancer.

OBJECTIVE: Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma. METHODS: In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five-year overall survival rates were determined by subgroups based on LNR value. RESULTS: Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour-node-metastasis (TNM)-stage, UICC-stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043). CONCLUSIONS: After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate.

[The pressure-equalizing function of the Eustachian tube : Evaluation in a hypo-/hyperbaric pressure chamber]. / Druckausgleichende Funktion der Eustachischen Röhre : Evaluation in einer hypo-/hyperbaren Druckkammer.

BACKGROUND: The Eustachian tube connects the tympanic cavity (cavum tympani) and the nasopharynx, and enables pressure equalization between the middle ear and ambient pressure. Functional pressure compensation is very important for flying and diving in particular, due to non-physiologically large pressure differences. OBJECTIVE: Evaluation of the pressure-equalizing function of the Eustachian tube is still a clinical challenge. This review article evaluates the existing data. METHODS: Based on a selective literature search, different methods for evaluation of tube function are presented and evaluated, with special reference to evaluation of the pressure-equalizing function in a hypo-/hyperbaric pressure chamber. RESULTS: The pressure chamber enables the dynamics of active and passive pressure compensation to be provoked and also permits accurate measurement of pressures in the millibar range. CONCLUSION: A pressure chamber seems to be suitable to evaluate Eustachian tube function and therapeutic approaches to tube dysfunction. Further studies are needed to assess the value of the pressure chamber in combination with other functional tests.

Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

OBJECTIVE: Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. STUDY DESIGN/METHODS: The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. RESULTS: In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). CONCLUSION: Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A.

The incidence of Warthin tumours and pleomorphic adenomas in the parotid gland over a 25-year period.

OBJECTIVES: Pleomorphic adenoma (PA) is reported to be the most common benign parotid tumour followed by Warthin tumour (WT), but the proportion of these two entities might have changed. DESIGN: Retrospective file analysis. SETTING: Tertiary referral head and neck centre. PARTICIPANTS: Patients who underwent a parotidectomy within a period of 25 years (1990-2014). MAIN OUTCOME MEASURES: Rate of occurrence of PA and WT as well as the development of the PA/WT ratio over the years. RESULTS: Overall, 1818 patients with WT (707, 38.9%) and PA (1111, 61.1%) were identified. There was a dominance of PA over WT in all years. An increase in percentage of WT, from 24% in 1990 to 48% in 2014, in comparison with PA was evident. CONCLUSIONS: In our single-institution hospital-based material of parotidectomies, the percentage of WT in comparison with PA has significantly increased over the last 25 years.

The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL.

Dysregulated T-cell leukemia/lymphoma-1A (TCL1A), a modulator in B-cell receptor (BCR) signaling, is causally implicated in chronic lymphocytic leukemia (CLL). However, the mechanisms of the perturbed TCL1A regulation are largely unknown. To characterize TCL1A-upstream networks, we functionally screened for TCL1A-repressive micro-RNAs (miRs) and their transcriptional regulators. We identified the novel miR-484 to target TCL1A's 3'-UTR and to be downregulated in CLL. In chromatin immunoprecipitations and reporter assays, the oncogenic transcription factor of myeloid cells, EVI1, bound and activated the miR-484 promoter. Most common in CLL was a pan-EVI1 transcript variant. EVI1 protein expression revealed distinct normal-tissue and leukemia-associated patterns of EVI1/TCL1A co-regulation. EVI1 levels were particularly low in TCL1A-high CLL or such cellular subsets. Global gene expression profiles from a 337-patient set linked EVI1 networks to BCR signaling and cell survival via TCL1A, BTK and other molecules of relevance in CLL. Enforced EVI1, as did miR-484, repressed TCL1A. Furthermore, it reduced phospho-kinase levels, impaired cell survival, mitigated BCR-induced Ca-flux and diminished the in vitro ibrutinib response. Moreover, TCL1A and EVI1 showed a strongly interactive hazard prediction in prospectively treated patients. Overall, we present regressive EVI1 as a novel regulatory signature in CLL. Through enhanced TCL1A and other EVI1-targeted hallmarks of CLL, this contributes to an aggressive cellular and clinical phenotype.

Acoustic effects of a superior semicircular canal dehiscence: a temporal bone study.

A dehiscence of the superior semicircular canal is said to be responsible for a number of specific and unspecific ear symptoms and possible a conductive hearing loss of up to 40 dB. As in vivo a dehiscence would not be opened against air, but is naturally patched with dura and the brain, it was our aim to investigate the effects of an superior semicircular canal dehiscence on the air conduction hearing in fresh human temporal bones with different boundary conditions. At ten fresh human temporal bones, we investigated the transmission of sound energy through the middle and inner ear using a round window microphone and laser Doppler vibrometer for perilymph motions inside the dehiscence. After baseline measurements, the superior semicircular canal was opened. We investigated the change of the transfer function when the canal is opened against air (pressure equivalent water column), against a water column and when it is patched with a layer of dura. Opening the superior semicircular canal resulted in a loss of sound transmission of maximal 10-15 dB only in frequencies below 1 kHz. When covering the dehiscence with a water column, the conductive hearing component was reduced to 6-8 dB. Placing a dura patch on top of the dehiscence resulted in a normalization of the transfer function. If our experiments are consistent with the conditions in vivo, then superior semicircular canal dehiscence does not lead to an extensive and clinically considerable conductive air conduction component.