Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[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.

Omalizumab in patients with NSAIDs-exacerbated respiratory disease.

BACKGROUND: The association of acetylsalicylic acid (ASA) intolerance, chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, or chronic urticaria is known as NSAID-exacerbated respiratory disease (N-ERD). N-ERD patients often suffer from recurrent nasal polyps, severe asthma or also from urticaria. The aim of the present study was to retrospectively analyze the clinical efficacy of anti-IgE antibody treatment with omalizumab in patients with confirmed N-ERD. METHODS: In the open trial with patients receiving verum patients with CRSwNP, confirmed N-ERD by oral or nasal ASA challenges, asthma or chronic urticaria were included in the study. Rhinological and pulmonary parameters were evaluated before and after 3, 6 and 9 months of therapy by rhinological questionnaires (CRS VAS-scores and RSOM-31), nasal polyp (NP)-, ACT-scores and FEV1 values. Urticaria activity was monitored clinically. N-ERD patients with aspirin desensitization were included as control group (follow-up 9 months). RESULTS: In the omalizumab group 16 patients were included (10 female, 6 male, mean age 51 yrs). CRS symptoms, RSOM-31- and NP-score decreased significantly following omalizumab therapy compared to baseline. The ACT-score (MV 16.5 to 20.6) and FEV1values (MV 80 % to 89 %) improved significantly. No urticaria symptoms were reported after 3 months. Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP. In the control group (8 female, 8 male, mean age 45 yrs) the NP-score was unchanged. CONCLUSIONS: Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period.

[IgG4-Related Orbitopathy as an Important Differential Diagnosis of Advanced Silent Sinus Syndrome. German version]. / IgG4-assoziierte Orbitopathie als wichtige Differenzialdiagnose eines fortgeschrittenen Silent-Sinus-Syndroms.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

IgG4-related orbitopathy as an important differential diagnosis of advanced silent sinus syndrome.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

Improvement in tinnitus distress, health-related quality of life and psychological comorbidities by cochlear implantation in single-sided deaf patients.

BACKGROUND: Patients with single-sided deafness (SSD) lack the ability localize sound sources and have difficulty with speech-in-noise hearing. In addition, there is a high prevalence of tinnitus distress. These problems may result in reduced health-related quality of life (HRQoL) and psychological comorbidities. This study aimed to investigate the influence of treatment with a cochlear implant (CI) on HRQoL, tinnitus distress, psychological comorbidities, and audiological parameters in SSD patients. METHODS: This retrospective study included 20 patients with postlingually acquired SSD (13 women, 7 men, mean age 57.0 years). Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire (NCIQ) and the Medical Outcome Study Short Form 36 Survey (SF-36). Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ), psychological comorbidities were evaluated with validated questionnaires, and speech perception and hearing ability were measured with validated speech tests. RESULTS: Postoperatively, the mean total NCIQ score (p < 0.0001) and four subscores improved significantly, as did tinnitus distress (p < 0.05). Anxiety symptoms (Generalized Anxiety Disorder questionnaire, GAD-7) decreased significantly after CI. Speech perception improved significantly, particularly "hearing with background noise" (p < 0.05, Oldenburg Inventory, OI) and "localization" (p < 0.001, OI), as well as the Oldenburg Sentence Test (OlSa) scores for with vs. without CI when speech was presented from the SSD side and noise was presented from the normal hearing side (SSSDNNH; p < 0.005). CONCLUSION: CI in SSD patients is a powerful procedure to improve HRQoL, reduce tinnitus distress, and improve psychological comorbidities. Additionally, it is beneficial for hearing improvement, particularly in noise and for directional hearing.

[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.

The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common yet under-recognised chronic inflammatory disease of the nose and paranasal sinuses that is classified according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. METHODS: This paper reports the methodology and descriptive results of the Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort. We established a large CRS cohort within the GALEN consortium (European FP6 research initiative) to identify inflammatory endotypes, the natural disease course, and its impact on health-related quality of life (HRQoL). Detailed information on the impact of CRS on HRQoL, comorbidity incidence, objective disease measures, and medical and surgical treatments were collected. RESULTS: This multicentre cross-sectional case-control study recruited 935 adults (869 eligible for analysis: 237 CRSsNP; 445 CRSwNP; 187 controls [reference group]). Comorbidities such as asthma, allergy, eczema, food allergy, urticaria, and chronic obstructive pulmonary disease were significantly more frequent in CRS patients. Nasal corticosteroids, antibiotics, and oral corticosteroids were the most common treatments. Significantly more CRSwNP patients reported previous sinonasal surgery. CONCLUSIONS: This study provides detailed information that facilitates studying CRS and its main phenotypes. However, patient distribution of this study does not necessarily reflect disease distribution in the general population.

The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life.

BACKGROUND: Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database. METHODOLOGY: Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery). RESULTS: Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery. CONCLUSIONS: CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.

[The subjective perception of the vertical-a valuable parameter for determination of peripheral vestibular disorder in Menière's disease in the chronic phase?] / Die subjektive Vertikalenwahrnehmung ­ ein wertvoller Parameter für die Bestimmung der peripher vestibulären Störung bei M. Menière in der chronischen Phase?

The perception of verticality is mainly based on utricular afferent signals and central processing of the transmitted signals. However, there are also extracranial receptors that make a considerable contribution to the perception of verticality. With the subjective visual vertical (SVV) for the utricle and the subjective trunk vertical (STV), two different parameters are available that are not fully understood in terms of their response to physiologic and pathologic changes. The aim of this work was to determine SVV and STV under certain positions of the head and trunk as well as under the influence of Menière's disease (MD) as a chronic vestibular disease. In a prospective clinical study, 26 patients with MD and 39 healthy volunteers were recruited. Subjects were examined with C­SVV glasses and with the three-dimensional trunk excursion chair, while head and torso positions were varied. In both groups, SVV determination is clearly more accurate with an earth-vertical head alignment than with a lateral head tilt (right: MM and control group: p = 0.001; left: MM p = 0.001, control group p = 0.000). If the torso is deflected laterally and the head is held straight, the SVV is significantly more accurate (left p = 0.003, right p = 0.015). The SRV was not affected by the presence of unilateral MD, while pathologic SVV values, if present, indicated the affected side. The results of our study support the assumption that in addition to SVV, SRV is an independent parameter for verticality perception and differs from the SVV in terms of lateralizing a peripheral vestibular deficit. These results suggest that the STV may depend not only on utricular function but also on extracranial afferent signals, and not be significantly altered by the presence of a hydropic peripheral vestibular lesion.

[Nasal provocation with increased ASA dose: improved "non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated disease" (N­ERD) detection rate in chronic rhinosinusitis patients]. / Nasale ASS-Provokationen mit erhöhter Dosierung: verbesserte Detektionsrate der ASS-Intoleranz bei chronischer Rhinosinusitis.

BACKGROUND: Analgesic intolerance (AI) is an important diagnostic feature of disease progression in patients with chronic rhinosinusitis (CRS) accompanied by nasal polyps (CRSwNP) and asthma. OBJECTIVE: The aim of the present study was to determine whether increasing the concentration of acetylsalicylic acid (ASA) used in the diagnostic nasal challenge would improve detection of ASA intolerance (NSAIDs-exacerbated respiratory disease, N­ERD). METHODS: Patients with CRSwNP, asthma, and with (CRSwNP-AAI, n = 20) or without (CRSwNP-A, n = 15) anamnestically reported AI, as well as control subjects with CRS but no nasal polyps, asthma, or AI (n = 15), were challenged nasally with 16 mg ASA and, in case of a negative result, with 25 mg of ASA. RESULTS: In CRSwNP-AAI subjects, the challenge with 16 mg ASA resulted in detection of AI in 80% of cases; increasing the challenge of ASA to 25 mg improved the AI detection to 95%. In CRSwNP-A subjects, the detection of AI increased from 40% (16 mg ASA) to 53% (25 mg ASA). In the control group, no reaction to nasal ASA challenge was detected. No difference in the diagnosis of positive reactions after provocation was found when using the German vs. the European recommended evaluation criteria. Mild pulmonary symptoms occurred in 2 (10%) CRSwNP-AAI patients following the 16 mg ASA challenge. CONCLUSION: In patients with CRSwNP, asthma, and anamnestic AI, nasal provocation can effectively confirm the diagnosis of N­ERD and can also be recommended for patients with recurrent CRSwNP and asthma but without reported AI. Increasing the ASA challenge to 25 mg increases the overall detection rate.

[Improvement in tinnitus distress, health-related quality of life and psychological comorbidities by cochlear implantation in single-sided deaf patients. German version]. / Verbesserung von Tinnitusdistress, Lebensqualität und psychologischen Komorbiditäten durch Cochleaimplantation einseitig ertaubter Patienten.

BACKGROUND: Patients with single-sided deafness (SSD) lack the ability localize sound sources and have difficulty with speech-in-noise hearing. In addition, there is a high prevalence of tinnitus distress. These problems may result in reduced health-related quality of life (HRQoL) and psychological comorbidities. This study aimed to investigate the influence of treatment with a cochlear implant (CI) on HRQoL, tinnitus distress, psychological comorbidities, and audiological parameters in SSD patients. METHODS: This retrospective study included 20 patients with postlingually acquired SSD (13 women, 7 men, mean age 57.0 years). Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire (NCIQ) and the Medical Outcome Study Short Form 36 Survey (SF-36). Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ), psychological comorbidities were evaluated with validated questionnaires, and speech perception and hearing ability were measured with validated speech tests. RESULTS: Postoperatively, the mean total NCIQ score (p < 0.0001) and four subscores improved significantly, as did tinnitus distress (p < 0.05). Anxiety symptoms (Generalized Anxiety Disorder questionnaire, GAD-7) decreased significantly after CI. Speech perception improved significantly, particularly "hearing with background noise" (p < 0.05, Oldenburg Inventory, OI) and "localization" (p < 0.001, OI), as well as the Oldenburg Sentence Test (OlSa) scores for with vs. without CI when speech was presented from the SSD side and noise was presented from the normal hearing side (SSSDNNH; p < 0.005). CONCLUSION: CI in SSD patients is a powerful procedure to improve HRQoL, reduce tinnitus distress, and improve psychological comorbidities. Additionally, it is beneficial for hearing improvement, particularly in noise and for directional hearing.

[Ear aid in Myanmar]. / Ohrenhilfe in Myanmar.

As the example of a small team working in Myanmar since 2010 has demonstrated, it is possible to achieve sustainable success in medical education and training in foreign countries with relatively little effort, in this case in middle ear surgery. The main requirements are outstanding communication within the team as well as with the authorities, organizations, and colleagues on site. Equally important is mindful and respectful work in the hosting country and the consideration of cultural particularities. Essential contributing factors for long-term success are intercultural exchange, interpersonal relationships, and especially the motivation of colleagues on site, which together create a foundation of trust. This trust combined with regular exchange visits enables constant professional development according to the current needs.

Age-corrected hearing loss after chemoradiation in cervical cancer patients.

OBJECTIVE: This study aimed to evaluate subjective and objective hearing loss in cervical cancer patients after chemoradiation with cisplatin (mono). PATIENTS AND METHODS: A total of 51 cervical cancer patients with indication for chemoradiation were included. Pure tone and impedance audiometry were performed before and after chemoradiation. Hearing loss was scaled according to ASHA criteria. Subjective hearing was assessed with the Oldenburger Sentence Test. To consider age-dependent changes, hearing loss was corrected for age and the time interval between measurements. RESULTS: Median age at diagnosis was 46 years, 46% were active/former smokers (n = 24), 28 (54%) patients were never-smokers. Median total weekly cisplatin dose was 70 ± 14.2 mg. Cumulative doses of cisplatin during chemoradiation ranged between 115.2 and 400 mg cisplatin (mean 336.1 mg, median 342 ± 52.7 mg). The median interval between last chemotherapy and second audiometry was 320 ± 538 days (35-2262 days). Changes in hearing threshold ≥20 dB were experienced by 32/52 patients (62%) following chemoradiation, 55% of them for frequencies ≥6000 Hz. No statistically significant hearing loss remained after chemoradiation upon correction for age and time interval. Patients >40 years had a higher risk of hearing loss than younger patients. Objective data on hearing function did not correlate with subjective hearing loss and did not impair daily activity in any patient. CONCLUSION: Chemoradiation with cumulative cisplatin doses up to 400 mg did not lead to significant impairment of objective or subjective hearing. For cervical cancer patients undergoing chemoradiation, standard audiometry is not indicated.

[Hearing rehabilitation with cochlear implants and cognitive abilities]. / Hörrehabilitation mithilfe von Cochleaimplantaten und kognitive Fähigkeiten.

The relevance of assessing cognitive functioning is increasing against the background of the continuing demographic changes. Up to a few years ago the focus was on the effects of cochlear implantation in children born deaf in comparison to healthy individuals. Currently, the question arises whether hearing rehabilitation in the elderly, e.g. by postlingual cochlear implantation, has a protective effect on cognitive functioning and therefore on the risk of onset of dementia. This review describes the association of cognitive functioning with hearing disorders and cochlear implantation. Historical aspects of intelligence testing are illustrated. Knowledge on cognitive aspects in elderly persons with hearing disorders and cochlear implants is rare in the currently available literature. Initial findings indicate a positive correlation between hearing improvement and cognitive functioning. Further studies are urgently required in order to elucidate appropriate guidelines for the treatment of patients with cognitive deficits and hearing impairment.

[Molecular networks of hypoxia and neuronal apoptosis in the cochlea]. / Molekulare Netzwerke von Hypoxie und neuronaler Apoptose in der Cochlea.

BACKGROUND: In organotypic cultures, the modiolus (MOD) region of newborn rats shows a fourfold higher rate of cell death than the organ of Corti (OC). The differing vulnerability of OC and MOD cells is related to differential expression of numerous genes (DEG). MATERIALS AND METHODS: Organotypic cultures of OC and MOD of 3-5-day-old rats were exposed to a normoxic or a hypoxic (pO2 10-20 mmHg; 5 h) atmosphere. Cell death rate and gene expression as detected by c­DNA microarray analysis were determined 24 h after the culture was created. Genes with modified expression (n = 60) were analyzed for biological processes according to the DAVID Gene Ontology Database (GO). Molecular networks were created using the STRING and ConsensusPathDB databases. RESULTS: The network of the GO annotations "hypoxia", "inflammation", and "mechanical stimulus" indicates the existence of two gene clusters: a cluster with pro-inflammatory genes (Ccl3, Cxcl2, Cxcr4, Ccl20) and a cluster with hypoxia-associated genes (e.g., c-Jun, Hif1a, and Vegfa). The network of the GO annotations "positive and negative regulation of neuron apoptotic process" suggests that the differential expression of c-Jun, Ngfr, and Casp3 is important for regulation of programmed cell death in neuronal cells of the OC and MOD. CONCLUSION: While c­JUN acts as an important modulator of the balance between cell death and survival, the associations of NGFR and CASP3 seem to be significant for the initiation of cell death. The evaluation and application of findings from biostatistical databases is important for understanding the function of individual genes and gene clusters in medically relevant biological processes.

Tufted angiomas of the head and neck.

BACKGROUND: Tufted angiomas (TAs) are uncommon benign vascular tumors mostly located cutaneously or subcutaneously in the skin of the neck and upper trunk, which appear during childhood and grow slowly. TAs are a variant of lobular capillary hemangiomas. This is the first study to provide an overview of the current literature in combination with the authors' own clinical experience on this rare entity in the head and neck area with non-dermatological localization. METHODS: A selective Medline and Google Scholar database search was performed. Additionally, we conducted an ICD-10-based database search on hemangiomas (D18.0) in the Charité SAP patient records. RESULTS: We identified 13 reports in the literature consisting of 16 cases of TA of the head and neck. Males were predominantly affected by TAs (70.6%). The mean age of the patients at the time of surgery was 31.5 years; the mean maximum diameter of the tumors was 16.3 mm. Additionally, we report on one case of TA in our Department of Head and Neck Surgery. A male patient presented with swelling and redness of the left upper eyelid. Radiological examination with computed tomography showed a suprabulbar tumor with a diameter of 13 mm. The tumor was surgically removed via a transcutaneous blepharoplasty approach with the patient under general anesthesia. DISCUSSION: There is only one other case report on the surgical excision of an intra-orbital TA described to date. Here, we present an epidemiological overview, therapeutic considerations, and differential diagnoses.