Publications by authors named "Karl Hörmann"

186 Publications

Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

Neurol Res Pract 2021 May 4;3(1):23. Epub 2021 May 4.

Klinik und Poliklinik für Hör-, Stimm- und Sprachheilkunde, Universitäres Dysphagiezentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Introduction: Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies.

Recommendations: This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with.

Conclusions: The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf ).
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http://dx.doi.org/10.1186/s42466-021-00122-3DOI Listing
May 2021

A new form of irritant rhinitis to filtering facepiece particle (FFP) masks (FFP2/N95/KN95 respirators) during COVID-19 pandemic.

World Allergy Organ J 2020 Oct 6;13(10):100474. Epub 2020 Oct 6.

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center, Mainz, Germany.

Filtering facepiece particle (FFP) masks are important items of personal protective equipment in fighting COVID-19 pandemic. They shall protect the wearer of the mask from particles, droplets, and aerosols, but they also can prevent the spread of aerosol-transmitted viruses if the wearer becomes infected. Most often, FFP respirators consist of multiple layers of non-woven fabric made from polypropylene. Worldwide, FFP respirators are subject to various regulatory standards that specify physical properties and performance characteristics. During the SARS-CoV-2 pandemic, health authorities have temporarily repealed standards for respirators. We report on 46 patients that presented with rhinitis-like symptoms strongly associated to the use of FFP masks. Some of them were obliged to use FFP masks in their work environment. Nasal endoscopy showed edemata of the nasal mucosa that significantly decreased after a period of non-use of FFP masks. Subjectively reported symptom levels decreased after cessation of FFP use for 3 or more days. The presence of polypropylene fibres isolated from nasal rinsing solution was significantly associated with the use of FFP masks in our patients. Material safety and performance deregulation of FFP masks can pose a health risk. Thus, especially health care professionals and other individuals with occupational need for FFP masks should be aware of possible hazards that come with COVID-19 pandemic protection measures.
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http://dx.doi.org/10.1016/j.waojou.2020.100474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538121PMC
October 2020

Changes in Vestibular Function in Patients With Head-and-Neck Cancer Undergoing Chemoradiation.

Ear Nose Throat J 2020 Sep 14:145561320949482. Epub 2020 Sep 14.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany.

Introduction: While the cochleotoxicity of cisplatin has been well investigated, less is known about the effects of platinum-based chemotherapy on the vestibular system. In particular, there is a lack of prospective studies using modern laboratory vestibular testing that examine the effects of cisplatin on the semicircular canals and on the otolith organs. The aim of the present study was, therefore, to investigate the vestibulotoxic effect of cisplatin in patients with head and neck tumors who are undergoing chemoradiation.

Methods: Forty-five patients undergoing cisplatin-based chemoradiation for head and neck cancer received a vestibular assessment consisting of anamnesis, a horizontal video head impulse test (vHIT), ocular and cervical vestibular evoked myogenic potential testing, as well as pure tone audiometry. This assessment was performed before therapy, 6 weeks after therapy, and 3 months after therapy.

Results: Video head impulse test showed a significantly reduced median gain 6 weeks after chemoradiation. In addition, significantly more refixational saccades could be detected after therapy. Vestibular evoked myogenic potential testing results also revealed significant changes, whereas pure tone audiometry did not. None of the patients mentioned "dizziness" during the follow-up examinations.

Conclusion: We demonstrated a vestibulotoxic effect of cisplatin-based chemoradiation in patients with head and neck cancer. Future studies are needed to better understand cisplatin-induced vestibulotoxicity and to identify possible vestibuloprotective substances. Still, before and after chemoradiation, patients should undergo not only auditory testing but also vestibular testing in order to detect potential vestibular loss as soon as possible and to quickly initiate vestibular physiotherapy.
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http://dx.doi.org/10.1177/0145561320949482DOI Listing
September 2020

Telemedicine allows quantitative measuring of olfactory dysfunction in COVID-19.

Allergy 2021 03 20;76(3):868-870. Epub 2020 Jul 20.

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center, Mainz, Germany.

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http://dx.doi.org/10.1111/all.14467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361410PMC
March 2021

Nightly Hypoxia Does Not Seem to Lead to Otolith Dysfunction in Patients With Obstructive Sleep Apnea.

Ear Nose Throat J 2020 Apr 27:145561320922126. Epub 2020 Apr 27.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Germany.

Objectives: Obstructive sleep apnea (OSA) is a common sleep disorder, which is associated with recurrent oxygen desaturation during sleep. It has already been shown that nocturnal hypoxia may lead to cochlear dysfunction in patients with OSA. Less is known whether hypoxia during sleep also impacts vestibular function in those patients. Thus, the aim of the presented study was to assess a potential vestibulotoxic effect of nightly desaturations with hypoxia in patients with OSA by investigating a possible correlation between respiratory parameters and vestibular function tests.

Methods: A total of 56 patients were included in the study and underwent a fully attended cardiorespiratory polysomnography (PSG). Vestibular function was assessed using video head impulse test to evaluate horizontal semicircular canal function and cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) to measure otolith function. Descriptive data analysis was conducted and correlation analysis between selected PSG parameters and the results of vestibular testing was performed using Kendall τ coefficient.

Results: A significant correlation between vestibular function and respiratory polysomnographic parameters could not be demonstrated in the study ( > .05) but cVEMP and oVEMP results showed a trend toward a correlation with oxygen desaturation indices and apnea-hypopnea index. Additionally, otolith hypofunction was more prevalent in patients with hypertension as well as OSA.

Conclusion: The results of our study show that there is no significant correlation between vestibular function and sleep apnea parameters, although otolith dysfunction might be more prevalent in patients with OSA and hypertension.
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http://dx.doi.org/10.1177/0145561320922126DOI Listing
April 2020

ARIA guideline 2019: treatment of allergic rhinitis in the German health system.

Allergol Select 2019 30;3(1):22-50. Epub 2019 Dec 30.

Department of Dermatology, University Medical Center Mainz,Mainz, Germany.

Background: The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases.

Methods: ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system.

Results: The present ICP (integrated care pathway) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers.

Discussion: A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.
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http://dx.doi.org/10.5414/ALX02120EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066682PMC
December 2019

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer.

Clin Epigenetics 2019 05 3;11(1):67. Epub 2019 May 3.

Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA).

Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression.

Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies.
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http://dx.doi.org/10.1186/s13148-019-0666-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499986PMC
May 2019

Peripheral Vestibular Disorders: An Epidemiologic Survey in 70 Million Individuals.

Otol Neurotol 2019 01;40(1):88-95

Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Heidelberg.

Background: Dizziness is a common complaint in medicine. Nevertheless, there is a lack of valid data concerning the age and gender distribution of dizziness disorders within a larger population. Therefore, the aim of the present study is to undertake a representative epidemiological survey that examines all age groups of an entire population and describes the age and gender distribution of the most common peripheral vestibular disorders.

Methods: A population-based epidemiological survey based on confirmed ICD-10 codes, of an entire national population was performed. The population-based data of 70,315,919 patients were leveraged, as provided by 123 statutory health insurance companies in Germany. Patients of all age groups were analyzed. Outcome measures were age and gender distribution and the prevalence of unspecific vertigo, Meniere's disease, benign paroxysmal positional vertigo, vestibular neuritis, and other peripheral vestibular disorders.

Results: The prevalence among the recorded diagnoses was 6.5% (6,461/100,000 individuals), with women (N = 2,973,323; 65.4%) being significantly more frequently affected by vertigo than men (N = 1,570,240; 34.6%; p < 0.001). Vertigo is rare in childhood (i.e., up to 10-14 yr of age). Subsequently, the prevalence of the analyzed diseases increases with age, up to a peak between 74 and 94 years.

Conclusions: The results demonstrate that peripheral vestibular disorders are common in a developed country, across all age groups and a specific distribution of these disorders can be identified for every age group and gender. The impact of these disorders on the German healthcare system is currently underestimated.
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http://dx.doi.org/10.1097/MAO.0000000000002013DOI Listing
January 2019

Influence of static magnetic fields on human myoblast/mesenchymal stem cell co‑cultures.

Mol Med Rep 2018 Mar 20;17(3):3813-3820. Epub 2017 Dec 20.

Department of Anesthesiology and Intensive Care Medicine, St. Josefs‑Hospital, D‑49661 Cloppenburg, Germany.

The results of surgical repair of extensive muscle tissue defects are still of primary concern, leaving patients with residual cosmetic and functional impairments. Therefore, skeletal muscle tissue engineering attempts to grow functional neo‑tissue from human stem cells to promote tissue regeneration and support defect closure. Despite intensive research efforts, the goal of stable induction of myogenic differentiation in expanded human stem cells by using clinically feasible stimuli, has not yet been reached to a sufficient extent. Therefore, the present study investigated the differentiation potential of static magnetic fields (SMFs), using co‑cultures of human satellite cells and human mesenchymal stem cells (MSCs). It has previously been demonstrated that SMFs may act as a promising myogenic stimulus. Tests were performed on co‑cultures with and without SMF exposure, using growth medium [high growth factor concentrations (GM)] and differentiation medium [low growth factors concentrations (DM)]. AlamarBlue® assay‑based cell proliferation analysis revealed no significant difference between co‑cultures with, vs. without SMF stimulation, regardless of growth factor concentrations in the cell culture medium. To determine the degree of differentiation in co‑cultures under stimulation with SMFs, semi‑quantitative gene expression measurements of the following marker genes were performed: Desmin, myogenic factor 5, myogenic differentiation antigen 1, myogenin, adult myosin heavy chain 1 and skeletal muscle α1 actin. In neither GM nor DM was a steady, significant increase in marker gene expression detected. Verifying the gene expression findings, immunohistochemical antibody staining against differentiation markers revealed that SMF exposure did not enhance myogenic maturation. Therefore, SMF treatment of human satellite cell/MSC co‑cultures did not result in the desired increase in myogenic differentiation. Further studies are required to identify a suitable stimulus for skeletal muscle tissue engineering.
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http://dx.doi.org/10.3892/mmr.2017.8334DOI Listing
March 2018

Transition from Acute to Chronic Tinnitus: Predictors for the Development of Chronic Distressing Tinnitus.

Front Neurol 2017 20;8:605. Epub 2017 Nov 20.

Otorhinolaryngology, University Medical Centre Mannheim, Mannheim, Germany.

Background: Acute tinnitus and its transition to chronic tinnitus are poorly investigated, and factors associated with amelioration exacerbation are largely unknown. Aims of this study were to identify early predictors for the future development of tinnitus severity.

Method: Patients with tinnitus of no longer than 4 weeks presenting at an otolaryngologist filled out questionnaires at inclusion (T1), as well as 3 (T3), and 6 months (T4) after tinnitus onset. 6 weeks after onset, an interview was conducted over the phone (T2). An audiogram was taken at T1, perceived tinnitus loudness, and tinnitus-related distress were assessed separately and repeatedly together with oversensitivity to external sounds and the levels of depression and anxiety. Furthermore, coping strategies with illness were recorded.

Results: Complete remission until T4 was observed in 11% of the 47 participants, while voiced complaints at onset were stable in the majority. In the subgroup with a relevant level of depression at T1, tinnitus-related distress worsened in 30% until T4. For unilateral tinnitus, perceived loudness in the chronic condition correlated strongly with hearing loss at 2 kHz on the tinnitus ear, while a similar correlation was not found for tinnitus located to both ears or within the head.

Conclusion: Results suggest early manifestation of tinnitus complaints, and stress the importance of screening all patients presenting with acute tinnitus for levels of depression and tinnitus-related distress. Furthermore, hearing levels should be monitored, and use of hearing aids should be considered to reduce tinnitus loudness after having ascertained that sound sensitivity is within normal range.
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http://dx.doi.org/10.3389/fneur.2017.00605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701924PMC
November 2017

Development of a new software and test setup for analyzing hVOR in very young children by vHIT.

J Vestib Res 2017 ;27(2-3):155-162

Section of Phoniatrics, Pedaudiology and Neurootology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Introduction: Earlier work revealed that vHIT examination is often difficult to perform on very young children. In particular, the calibration of the system can be difficult, as active cooperation of the patient is required. Additionally, the patient must be able to follow the examiner's instructions, which is challenging for very young children. Therefore, the aim of the present study was to develop and validate a new, software-based approach enabling vHIT testing of young children and infants.

Methods And Materials: Six patients (3 boys and 3 girls) aged 5-36 months were included in a prospective, monocentric study between January 2015 and August 2015.The newly developed intuitive software enabled calibration of the eye position signal with the subjects fixating on animated animal graphics which were projected on a screen. Testing ten healthy adults validated this new calibration and measurement method. After calibration, a vHIT goggle (EyeSeeCam ©) was used to perform head impulses in the horizontal plane while the patient was watching a movie sitting on their parent's lap or in a baby chair. At least 15 impulses to each side were obtained and the occurrence of refixation saccades was analyzed. All tests were performed by one of two experienced examiners.

Results: The new calibration method and modified test setup provided reproducible results for all patients tested. An increased incidence of artifacts was not observed. In 2 patients, more than one test was needed. None of the included children showed catch-up overt or catch-up covert saccades. There was no gain reduction of more than two standard deviations as compared to the normative results published in the literature on vHIT examinations of children.

Conclusion: The proposed protocol allows vHIT testing in very young children and infants (aged 5 months to 3 years). The study emphasizes that vHIT is an easy and sensitive screening tool to evaluate vestibular function in children and should be used as the gold standard in pediatric vestibular assessment.
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http://dx.doi.org/10.3233/VES-170611DOI Listing
June 2018

Heated air humidification versus cold air nebulization in newly tracheostomized patients.

Head Neck 2017 12 9;39(12):2481-2487. Epub 2017 Oct 9.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Ruprecht-Karls Universität Heidelberg, Germany.

Background: After tracheostomy, the airway lacks an essential mechanism for warming and humidifying the inspired air with the consequent functional impairment and discomfort. The purpose of this study was to compare airway hydration with cold-air nebulization versus heated high-flow humidification on medical interventions and tracheal ciliary beat frequency (CBF).

Methods: Newly tracheostomized patients (n = 20) were treated either with cold-air nebulization or heated humidification. The number of required tracheal suctioning procedures to clean the trachea and tracheal CBF were assessed.

Results: The number of required suctions per day was significantly lower in the heated humidification group with medians 3 versus 5 times per day. Mean CBF was significantly higher in the heated humidification group (6.36 ± 1.49 Hz) compared to the cold-air nebulization group (3.99 ± 1.39 Hz).

Conclusion: The data suggest that heated humidification enhanced mucociliary transport leading to a reduced number of required suctioning procedures in the trachea, which may improve postoperative patient care.
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http://dx.doi.org/10.1002/hed.24917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698730PMC
December 2017

Innovative Surgery for Obstructive Sleep Apnea: Nerve Stimulator.

Adv Otorhinolaryngol 2017 17;80:116-124. Epub 2017 Jul 17.

Obstructive sleep apnea (OSA) as a multifactorial disease is treated with continuous positive airway pressure (CPAP) as the gold standard. Yet, if patients suffer from CPAP incompliance, traditional OSA surgery only targets morphological changes of the upper airway while neglecting functional issues. With the advent of upper airway stimulation, and in particular hypoglossal nerve stimulation as a treatment option, a highly effective, clinically proven and functional therapy with good evidence is available. This article gives a comprehensive overview of current and upcoming hypoglossal nerve stimulation systems (Inspire, ImThera, and Nyxoah), the specific advantages of this approach, the selection criteria and screening process, relevant clinical data, and a description of the different implantation procedures. Upper airway stimulation and hypoglossal nerve stimulation appears to be a long-term, low-morbidity treatment for moderate-to-severe OSA patients suffering from CPAP incompliance.
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http://dx.doi.org/10.1159/000470880DOI Listing
October 2017

[Handling and reprocessing of semicritical medical devices in the ENT - a prospective study].

Laryngorhinootologie 2017 Aug 12;96(8):536-543. Epub 2017 Jun 12.

Numerous laws, guidelines and recommendations govern the handling and reprocessing of semi-critical medical devices in the field of ENT. Although mechanically reprocessing is characterized as a preferential, manual reprocessing is still conducted in most ENT clinics and medical practices for reasons of cost and practicability. In the presented study, we developed an optimized hygienic concept for reprocessing of medical products in the field of ENT.A demand analysis of rigid endoscopes and of ENT equipment was carried out based on hypothesis that only mechanical reprocessing was performed for the entire instrumentation. Additionally, patient-free activities like preparing instrumentation for examination were investigated. As a result, we could demonstrate that such patient-free activities represent a considerable time factor and as a consequence a cost factor in daily patient care. Necessary investments for only mechanical reprocessing of instrumentation including rigid endoscopes are considerably high, since number of endoscopes have to be kept very high.
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http://dx.doi.org/10.1055/s-0043-110858DOI Listing
August 2017

Impact of Small Molecules on β-Catenin and E-Cadherin Expression in HPV16-positive and -negative Squamous Cell Carcinomas.

Anticancer Res 2017 06;37(6):2845-2852

Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.

Background: The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial-mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status.

Materials And Methods: Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay.

Results: All agents reduced β-catenin and E-cadherin expression of HPV16-negative cells. Increased E-cadherin expression was observed after treatment with gefitinib and dasatinib in HPV16-positive cells.

Conclusion: All substances, nilotinib, dasatinib, erlotinib and gefitinib have a significant impact on β-catenin and E-cadherin expression in both HPV16-positive and HPV16-negative cells in vitro. Alterations of β-catenin and E-cadherin could provide novel insights for future targeted therapies of head and neck SCC.
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http://dx.doi.org/10.21873/anticanres.11636DOI Listing
June 2017

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma.

Oncol Lett 2017 May 13;13(5):3269-3276. Epub 2017 Mar 13.

Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells. MMP-9 and VEGFR-1 expression was evaluated using an ELISA in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cell lines, following treatment with nilotinib, dasatinib, erlotinib and gefitinib. A statistically significant reduction in MMP-9 and VEGFR-1 expression was observed in the p16-negative HNSCC 11A cells following treatment with all inhibitors (P<0.05). VEGFR-1 expression was significantly increased in p16-positive SCC cells following treatment with nilotinib, dasatinib, erlotinib and gefitinib (P<0.05). The expression of MMP-9 and VEGFR-1 was significantly altered by treatment with nilotinib, dasatinib, erlotinib and gefitinib . The results of the present study are attributed to the efficacy of the tested drugs and present potential compensatory strategies of cancer cells to avoid the antiangiogenic properties of the tested tyrosine kinase inhibitors .
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http://dx.doi.org/10.3892/ol.2017.5844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431333PMC
May 2017

[Isolated High Frequency hVOR Lesion in Patients with Chronic Dizziness].

Laryngorhinootologie 2017 Jul 9;96(7):461-466. Epub 2017 May 9.

Universitäts-HNO-Klinik, Universitätsmedizin Mannheim, Mannheim.

In the presented study video-head impulse test (vHIT) was performed in 72 patients with complaints of dizziness for more than 3 months who did not show any pathology in rotatory chair testing or caloric test, in order to analyzed high frequency vestibular-ocular-reflex (VOR). Retrospective data analyzed of rotatory chair testing, caloric tests and vHIT results were accomplished in 72 patients. Gain, gain variance and the occurrence of catch-up saccades were measured. 10 patients (n=10; 13.8%) showed pathologic vHOR results with reduced gain. In the remaining 62 patients, a median gain of 0.85 when tested to the right respectively 0.87 when tested to the left side was assed. Especially in patients with normal results in rotatory chair testing and caloric testing, who complain of persistent dizziness and imbalance, high frequency hVOR should also be evaluated using vHIT in order to objectify and document an isolated high frequency hVOR lesion.
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http://dx.doi.org/10.1055/s-0042-124507DOI Listing
July 2017

Unilateral Cochlear Implantation Reduces Tinnitus Loudness in Bimodal Hearing: A Prospective Study.

Front Neurol 2017 7;8:60. Epub 2017 Mar 7.

Audiology, Medical Faculty Mannheim, Department of Otorhinolaryngology, Heidelberg University , Mannheim , Germany.

Perceptive and receptive aspects of subjective tinnitus like loudness and tinnitus-related distress are partly independent. The high percentage of hearing loss in individuals with tinnitus suggests causality of hearing impairment particularly for the tinnitus percept, leading to the hypothesis that restoration of auditory input has a larger effect on tinnitus loudness than on tinnitus-related distress. Furthermore, it is assumed that high levels of depression or anxiety prevent reductions of tinnitus loudness and distress following restoration of activity in the cochlea. This prospective study investigated the influence of unilateral cochlear implant (CI) on tinnitus in 19 postlingually deafened adults during 6 months following implantation. All had bimodal provision with the other ear being continuously supported by a hearing aid. On the day before CI implantation (T1, T2), and at about 3 and 6 months postsurgery (T3, T4), participants were questioned about their current tinnitus. Loudness was rated on a Numeric Rating Scale, distress was assessed by the TQ12 Tinnitus Questionnaire, and depression and anxiety were recorded with the Hospital Anxiety and Depression Scale. At T2, 79% experienced tinnitus, one participant developed tinnitus after implantation. Following implantation, tinnitus loudness was reduced significantly by 42%, while reductions in tinnitus-related distress (-24%), depression (-20%), and anxiety (-20%) did not attain statistical significance. Significant correlations existed between tinnitus measures, and between postimplantation tinnitus-related distress and anxiety and depression scores. Moreover, improvement of hearing in the CI ear was significantly correlated with reduction in tinnitus loudness. A new aspect of this study is the particular influence of CI provision on perceptive aspects of preexisting tinnitus (hypothesis 1), with the effect size regarding postimplant reduction of perceived tinnitus loudness (1.40) being much larger than effect sizes on the reduction of tinnitus-related distress (0.38), depression (0.53), and anxiety (0.53). Contrary to expectation both tinnitus measures reduce even in the majority of CI recipients with increased levels of anxiety or depression. This suggests that reduction of the tinnitus signal by restoring activity in the cochlea cannot be entirely compensated for by central tinnitus mechanisms and results in a reduction of perceptive and less so of reactive aspects of subjective tinnitus.
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http://dx.doi.org/10.3389/fneur.2017.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339283PMC
March 2017

Olfaction in patients with allergic rhinitis: an indicator of successful MP-AzeFlu therapy.

Int Forum Allergy Rhinol 2017 03 26;7(3):287-292. Epub 2016 Nov 26.

Interdisciplinary Centre "Smell & Taste," Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany.

Background: The purpose of this study was to investigate the effect of MP-AzeFlu on olfaction and the interaction between severity of allergic rhinitis and olfactory improvement after therapy.

Methods: A prospective, multicenter, observational study was performed on 47 patients with persistent allergic rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and the proof of allergen sensitization from positive skin-prick tests, specific immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory function was assessed at baseline and at 1 and 3 months of therapy using the "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a visual analog scale (VAS) at each given time-point.

Results: MP-AzeFlu was found to be associated with a significant improvement in TDI score, from 23.7 at baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of treatment. Furthermore, a highly significant improvement of symptoms over time (p < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be demonstrated. Most importantly, there was a highly significant interaction between the severity of allergic rhinitis and olfactory function (p < 0.001) and VAS (p < 0.001).

Conclusion: MP-AzeFlu is associated with olfactory improvement in persistent allergic rhinitis patients. Further, the modified ARIA severity classification is an indicator of patients' olfactory function. Moreover, assessment of olfaction seems to be a reliable indicator of the clinical success of antiallergic/antiinflammatory therapy.
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http://dx.doi.org/10.1002/alr.21877DOI Listing
March 2017

[Using a Standardized Questionnaire for Coagulation Assessment in Children Undergoing Tonsillectomy].

Laryngorhinootologie 2017 May 10;96(5):299-305. Epub 2016 Nov 10.

Klinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum Essen.

A 2006 position paper suggests assessing coagulation status via a standardized questionnaire instead of performing routine coagulation testing for children undergoing tonsillectomy/adenotomy. The aim of the presented study was to evaluate whether this paradigm change led to a change in the incidence of secondary bleeding. Descriptive statistical analysis of existing clinical data was performed to evaluate the incidence and characteristics of secondary bleeding in children after tonsillectomy/adenotomy in 2003 vs. 2009. In 2003, 352 children underwent surgery. Secondary bleeding occurred in 25 cases (7.1%), 18, (6.1%) of which required surgical treatment. In 2009, 20 out of 293 children who had undergone tonsillectomy/adenotomy suffered from secondary bleeding, 14 required (4.7%) surgical treatment. There was no significant difference in the incidence of bleeding between those years. In 5 children who suffered from secondary bleeding in 2003, preoperative diagnostic blood coagulation testing was performed, none of them showed abnormal results. Furthermore, none of the diagnostic blood coagulation tests performed after secondary bleeding in both groups showed any abnormalities. Using a standardized questionnaire instead of a diagnostic blood coagulation testing for preoperative coagulation assessment does not have an influence on the incidence of secondary bleeding after tonsillectomy/adenotomy. The results of this study suggest that secondary bleeding is not is not caused by abnormal hemostasis.
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http://dx.doi.org/10.1055/s-0042-117643DOI Listing
May 2017

Targeted Therapies in HPV-positive and -negative HNSCC - Alteration of EGFR and VEGFR-2 Expression In Vitro.

Anticancer Res 2016 Jun;36(6):2799-807

Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.

Background: Angiogenesis plays a crucial role in the formation and progression of tumor growth in head and neck squamous cell carcinoma (HNSCC). The tyrosine kinase receptors epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are essential for mediation of pro-angiogenic signals. Nilotinib, dasatinib, erlotinib and gefitinib are tyrosine kinase inhibitors and approved as targeted therapies for several tumor entities other than HNSCC. In this study, we sought to evaluate the alteration of EGFR and VEGFR-2 expression by these tyrosine kinase inhibitors with respect to the human papillomavirus (HPV)-status in squamous cell carcinoma (SCC) tumor cells.

Materials And Methods: Expression patterns of EGFR and VEGFR-2 were determined by enzyme linked immunosorbent assay (ELISA) in HNSCC 11A, HNSCC 14C and p-16-positive CERV196 tumor cell lines. These cells were incubated with nilotinib, dasatinib, erlotinib and gefitinib (5-20μmol/l) and compared to a chemonaive control. The incubation time was 24, 48, 72 and 96 h.

Results: All tested substances led to a statistically significant reduction (p<0.05) of EGFR protein expression levels in HPV-negative cells compared to the negative control. Surprisingly, a statistically significant increase in VEGFR-2 expression was observed after exposure to all tested substances especially after exposure to erlotinib treatment.

Conclusion: Nilotinib, dasatinib, erlotinib and gefitinib cause significant changes in protein expression of EGFR and VEGFR-2 in vitro. Besides the anti-angiogenic impact of the substances, as shown for the decrease of EGFR expression, we also observed an increase of VEGFR-2 expression. These contradictive effects could be interpreted as a compensatory up-regulation by the tumor cell.
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June 2016

Tonsillectomy with Uvulopalatopharyngoplasty in Obstructive Sleep Apnea.

Dtsch Arztebl Int 2016 Jan;113(1-02):1-8

Department of Otorhinolaryngology, Head and Neck Surgery, Sleep Disorders Center, University Hospital Mannheim, Department of Otorhinolaryngology, University Hospital Klinikum rechts der Isar, Technische Universität München, Mannheim Institute of Public Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Essen University Hospital-Department of Otorhinolaryngology, Head and Neck Surgery.

Background: Obstructive sleep apnea (OSA) is a very common disorder (prevalence 2-7% in women, 7-14% in men). It impairs the quality of life and increases mortality. Conservative treatment with continuous positive airway pressure is highly effective, but patient compliance is variable. Surgical treatments are controversial, as only a few are supported by evidence from controlled clinical trials.

Methods: Adult patients with OSA, CPAP intolerance, and oropharyngeal obstruction were included in the trial. All underwent polysomnography (PSG) and were randomly allotted to one of two groups. Patients in the treatment group underwent tonsillectomy with uvulopalatopharyngoplasty (TE-UPPP) within one month. All patients had a follow-up PSG at three months, and all PSGs were evaluated in blinded fashion. The primary outcome variable was the apneahypopnea index (AHI) as determined by PSG. Other outcome variables were subjective symptoms (daytime sleepiness, quality of life), complications, and patient satisfaction.

Results: 42 patents were included in the trial (23 in the treatment group, 19 in the control group). The baseline AHI was 35.7 ± 19.4/hr in the control group and 33.7 ± 14.6/hr in the treatment group. The corresponding figures at 3 months were 28.6 ± 19.4/hr in the control group and 15.4 ± 14.1/hr in the treatment group (p = 0.036). The intervention also led to significant improvement in daytime sleepiness and in snoring, according to the patients' and their bed partners' assessment. 97% of the patients who underwent surgery were satisfied with the outcome. 65% of them needed no further treatment for OSA.

Conclusion: TE-UPPP significantly improved apnea/hypopnea, daytime sleepiness, and snoring compared to control (i.e., no) treatment. It is a safe and effective treatment for OSA..
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http://dx.doi.org/10.3238/arztebl.2016.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746403PMC
January 2016

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia.

Pediatr Res 2016 05 13;79(5):731-5. Epub 2016 Jan 13.

Department of General Paediatrics, University Children´s Hospital Muenster, Muenster, Germany.

Background: In asthmatic airways secondary ciliary dyskinesia contributes to impaired mucociliary clearance. To investigate underlying mechanisms, we studied the effects of cytokines associated with asthma phenotype on the ciliary beat frequency (CBF) in a cell culture model of ciliated human respiratory epithelial cells.

Methods: Nasal respiratory epithelial cells of 21 patients were used to prepare multicellular cells (spheroids) in the presence of the T helper (TH) 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13, and the TH1 cytokine interferon gamma (IFN-γ). CBF was determined by high-speed video microscopy.

Results: Addition of IL-4 and IL-13 and IL-4 + IL-13 decreased the mean CBF by 17, 21, and 22%, respectively, compared with untreated controls. Addition of IL-5 and IL-9 lead to an increase in mean CBF (20 and 10%, respectively). Lower concentrations of IFN-γ (0.1 and 1 ng/ml) decreased mean CBF and higher concentrations (10 ng/ml) increased CBF by 6%. Addition of IFN-γ to IL-13 reversed the effect of IL-13 on the CBF of spheroids.

Conclusion: Cytokines directly influence the ciliary function of respiratory epithelium and contribute to the impaired mucociliary clearance in asthmatic disease. Our study encourages further research to investigate IFN-γ as a treatment option in diseases with impaired mucociliary clearance like asthma.
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http://dx.doi.org/10.1038/pr.2016.8DOI Listing
May 2016

CpG-Oligodeoxynucleotides in Chronic Rhinosinusitis Cell Culture.

In Vivo 2016 Jan-Feb;30(1):47-52

Department of Otorhinolaryngology Head and Neck Surgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Unlabelled: In chronic rhinosinusitis (CRS) an important feature is the infiltration of eosinophils, triggered by T-helper type 2 cells (TH2). Binding of the CpG oligodeoxynucleotide (CpG-ODN) ligand to toll-like receptor 9 (TLR9) induces a shift from a TH2- to a TH1-type response. We evaluated the hypothesis that CpG-ODN could reduce the predominantly TH2-driven response in our cultures.

Materials And Methods: Twenty samples from CRS patients with (CRSwNP) and without nasal polyposis (CRSsNP) were cultivated. The expression of interleukin 5 (IL-5), eotaxin 3 and matrix metalloprotease 9 (MMP-9) were evaluated with and without CpG-ODN.

Results: Addition of CpG did not influence the expression of IL-5 and eotaxin-3 DNA. Elevated MMP-9 expression in cultures from CRSwNP and CRSsNP patients could be established.

Conclusion: CpG does not reduce the attraction of eosinophils since no reduced IL-5 expression was measured in our cultures. Yet, MMP-9 - an important factor in tissue remodelling - was elevated in cultures from CRS patients.
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September 2016

Drug delivery and drug targeting with parenteral lipid nanoemulsions - A review.

J Control Release 2016 Feb 14;223:85-98. Epub 2015 Dec 14.

Karl-Franzens-University of Graz, Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Member of BioTechMed Graz, Universitätsplatz 1, A-8010 Graz, Austria. Electronic address:

Lipid nanosized emulsions or nanoemulsions (NE) are oil in water dispersions with an oil droplet size of about 200nm. This size of oil droplets dispersed in a continuous water phase is a prerequisite for the parenteral, namely intravenous administration. Many parenteral nutrition and drug emulsions on the market confirm the safe use of NE over years. Parenteral emulsions loaded with APIs (active pharmaceutical ingredients) are considered as drug delivery systems (DDS). DDS focuses on the regulation of the in vivo dynamics, such as absorption, distribution, metabolism, and extended bioavailability, thereby improving the effectiveness and the safety of the drugs. Using an emulsion as a DDS, or through the use of surface diversification of the dispersed oil droplets of emulsions, a targeted increase of the API concentration in some parts of the human body can be achieved. This review focuses on NE similar to the marketed once with no or only low amount of additional surfactants beside the emulsifier from a manufacturing point of view (technique, used raw materials).
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http://dx.doi.org/10.1016/j.jconrel.2015.12.016DOI Listing
February 2016

Clinical Outcome and Quality of Life After a Multimodal Therapy Approach to Ear Keloids.

JAMA Facial Plast Surg 2015 Sep-Oct;17(5):333-9

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Mannheim, University of Heidelberg, Mannheim, Germany.

Importance: Keloids are fibroproliferative scars that can cause a huge psychological burden and severe problems for patients, such as depression. Many treatment options exist; however, recurrence rates, especially with monotherapy, remain high.

Objective: To investigate the recurrence rate and changes in quality of life after multimodal therapy.

Design, Setting, And Participants: A total of 33 patients with 42 auricle keloids (24 female and 9 male patients; mean [SD] age, 27 [17] years) were enrolled in a prospective cohort study and underwent intramarginal keloid excision and multimodal therapy. Patients were observed postoperatively in the outpatient Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Mannheim, from August 1, 2007, through September 30, 2014, with a mean (SD) follow-up of 30 (19) months (through August 31, 2014). A retrospective analysis of clinical outcomes was performed from September 1 through November 15, 2014.

Interventions: Excision followed by 6 intralesional corticosteroid injections at 4- to 6-week intervals and individually customized pressure splints applied at least 5 nights a week for 6 months.

Main Outcomes And Measures: Keloid recurrence rate and subjective handling of the pressure splint were evaluated during clinical visits. Quality of life was measured after the end of therapy with a 3-part questionnaire, including the Glasgow Benefit Inventory (GBI).

Results: After excluding 4 patients (with 5 keloids) for nonadherence to treatment, 3 of 37 keloids recurred, for a recurrence rate of 8% among 29 patients. Insecure handling of the pressure splint significantly correlated with a higher relapse rate (mean subjective handling score in patients with a relapse, 3.60; P = .02). Four of 8 patients with recurrent keloids had poor adherence to adjuvant pressure therapy, which suggests an association between keloid recurrence and adherence to adjuvant pressure therapy. Patients received the 3-part questionnaire by mail to collect data on quality of life. Of 43 patients approached, 33 treated with multimodal therapy completed the questionnaire for a return rate of 77%. Improvement in quality of life after keloid treatment was significant in recurrence-free patients, with a mean GBI score of 22.53 (P < .001).

Conclusions And Relevance: The present study showed an improvement in quality-of-life scores after multimodal therapy for keloids. Because poor adherence to the use of ear splints correlated with a higher recurrence rate of keloids, efforts are needed to improve adherence and minimize recurrence.

Level Of Evidence: 3.
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http://dx.doi.org/10.1001/jamafacial.2015.0881DOI Listing
March 2016

Superior canal dehiscence syndrome in children--a case report.

Int J Pediatr Otorhinolaryngol 2015 Sep 6;79(9):1573-8. Epub 2015 Jul 6.

, Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Germany.

Initially described in 1998, superior semicircular canal dehiscence syndrome (SCDS) has become a well-studied neurootologic entity in adults by now. Unfortunately, experience with children is limited and a diagnostic and therapeutic algorithm is lacking. The article therefore wants to provide an overview of the existing literature on superior semicircular canal dehiscence syndrome in children. Furthermore a diagnostic algorithm for daily clinical life based on a case report from an eleven-year-old girl is presented.
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http://dx.doi.org/10.1016/j.ijporl.2015.05.022DOI Listing
September 2015

Clinical experience with video Head Impulse Test in children.

Int J Pediatr Otorhinolaryngol 2015 Aug 9;79(8):1288-93. Epub 2015 Jun 9.

University Hospital Mannheim, Department of Otorhinolaryngology Head and Neck Surgery, Mannheim , Germany.

Background: A standardized diagnostic protocol for children's vestibular assessment is still missing in daily clinical life. As rotatory chair testing and caloric test are usually not tolerated well by children, the aim of our study was not only to evaluate the importance and practicability of the video head impulse test performed in children with and without balance problems, but also to outline a diagnostic algorithm for children with balance problems.

Methods: Fifty-five children aged 3-16 years have been included in this prospective monocentric study. Balance was assessed using results from health screening examinations of the participants and results from a specific dizziness questionnaire for children. The children were then divided in two groups: group I without any sign of vestibular development disorder and group II with possible signs for a pathological equilibrium development. Horizontal vestibulo-ocular reflex (HVOR) was assessed using a video-oculography system device (EyeSeeCam(©)). Gain at 40, 60, and 80ms and gain variance has been measured. Furthermore, it was evaluated how calibration of the system was tolerated by the participants, how the test itself was accomplishable in children, and which difficulties arose during testing.

Results: Reproducible test results were accomplished in 42 children (75%). Children with no balance problems in history showed a median gain of 1.02 (±0.28). A significant gain reduction between 40 and 80ms was found (P<0.05). Catch-up saccades were found in none of the children. Children with balance problems had a significantly reduced gain. (0.47±0.3; P<0.05) In this group, catch-up saccades could be detected in 4 out of 6 patients. For both groups, performing the test approximately took 20min, which is significantly longer than in adults (P<0.05). Calibration of the system with laser dots was easily doable in children aged 6 and older, whereas children between 3 and 5 years had better calibration results using colorful little icons.

Conclusions: Video head impulse test is a sensitive and efficient vestibular test in children, which is tolerated well by children aged 3-16 years. Therefore, video head impulse test can be easily used as a screening tool to detect vestibular dysfunction in the pediatric population.
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http://dx.doi.org/10.1016/j.ijporl.2015.05.034DOI Listing
August 2015

Targeting mTOR and AREG with everolimus, sunitinib and sorafenib in HPV-positive and -negative SCC.

Anticancer Res 2015 Apr;35(4):1951-9

Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany.

Background/aim: Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm appearing in the upper aerodigestive tract and the sixth most common cancer worldwide. The five-year survival rate remains poor despite advances in surgery, radiation and chemotherapy. Furthermore, the incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is rising. Thus, innovative therapy approaches are imperative in order to improve the situation. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) and sorafenib and sunitinib, multityrosine kinase inhibitors, have been notably effective in the therapy of different tumor entities. The modest side-effects and oral application of the drugs might improve patient compliance. Expression levels of mTOR and Amphiregulin (AREG) in p16-positive and -negative SCC (squamous cell carcinoma) and the effect of everolimus, sorafenib or sunitinib on the expression levels of these target proteins were assessed. As far as we are aware of, this is one of the first in vitro studies to evaluate the effect of these small-molecule drugs with regard to the p16 status of SCC cells.

Materials And Methods: p16-negative HNSCC 11A and 14C cells and p16-positive CERV196 cells were exposed to different concentrations of everolimus, sorafenib and sunitinib for 2-8 days. Expression levels of mTOR and AREG were determined by enzyme-linked immunosorbent assay (ELISA) and compared against a chemonaïve control.

Results: AREG and mTOR were expressed in all tested cell lines. CERV196 displayed a remarkable increase of mTOR expression compared to p16-negative HNSCC. On the contrary, AREG levels were reduced by 50% in CERV196. Everolimus, sorafenib and sunitinib significantly reduced mTOR expression. Everolimus significantly decreased AREG expression independently of the HPV status. Sunitinib and sorafenib increased AREG expression in HNSCC 11A and 14C but not in CERV196.

Conclusion: The applied drugs showed remarkable suppression of mTOR expression, which might delay tumor progression. Interestingly, sorafenib and sunitinib increased AREG in HNSCC 11A and 14C, which could be a possible evasive mechanism following incubation with these drugs. On the contrary, p16-positive CERV196 showed increased susceptibility to sorafenib and sunitinib concerning suppression of AREG expression. Further studies are required to evaluate the HPV-dependent differences of therapy response and the possible consequences for treatment options.
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April 2015

Endoscopic/external approaches in otorhinolaryngology and head and neck surgery.

Biomed Res Int 2015 23;2015:958453. Epub 2015 Feb 23.

Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, University Hospital Motol, V Uvalu 84, 150 06 Prague 5, Czech Republic.

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http://dx.doi.org/10.1155/2015/958453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352752PMC
May 2016