[Antiseptics in otorhinolaryngology-a substance overview]. / Antiseptika in der HNO-Heilkunde ­ eine Substanzübersicht.

For preoperative skin antisepsis, alcohol-containing iodine solutions and octenidine are suitable. For wound antisepsis, polyhexanide and hypochlorous acid (HOCL) are also available, but only PVP-iodine and HOCL can be applied to cartilage. Chlorhexidine should only be used as mouth- and bodywash for Staphylococcus aureus (MRSA) decolonization. For the many other throat antiseptics, evidence of clinical efficacy is lacking. For decolonization of the nares, polyhexanide and octenidine are available as nasal gels, but these are inferior to mupirocin for MRSA decolonization. PVP-iodine and HOCL are safe to use for nasal irrigation, but only HOCL has proven effective to improve symptoms of chronic rhinosinusitis. All antiseptics exhibit a certain ototoxicity. With an intact eardrum, acetic acid-containing eardrops can be used to prevent and treat external otitis and myringitis. When the eardrum is perforated, only alcohol-free PVP-iodine and HOCL may be used.

Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned.

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL. METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8. RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred. CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

Calculated parenteral initial treatment of bacterial infections: Infections in the ear, nose, throat and mouth and jaw area.

This is the sixth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the antibacterial treatment of more severe infections of the ear, the nose, the throat and the maxillofacial region, including odontogenic and salivary gland infections.

Microbiome and Culture Based Analysis of Chronic Rhinosinusitis Compared to Healthy Sinus Mucosa.

The role of bacteria in chronic rhinosinusitis (CRS) is still not well understood. Whole microbiome analysis adds new aspects to our current understanding that is mainly based on isolated bacteria. It is still unclear how the results of microbiome analysis and the classical culture based approaches interrelate. To address this, middle meatus swabs and tissue samples were obtained during sinus surgery in 5 patients with CRS with nasal polyps (CRSwNP), 5 patients with diffuse CRS without nasal polyps (CRSsNP), 5 patients with unilateral purulent maxillary CRS (upm CRS) and 3 patients with healthy sinus mucosa. Swabs were cultured, and associated bacteria were identified. Additionally, parts of each tissue sample also underwent culture approaches, and in parallel DNA was extracted for 16S rRNA gene amplicon-based microbiome analysis. From tissue samples 4.2 ± 1.2 distinct species per patient were cultured, from swabs 5.4 ± 1.6. The most frequently cultured species from the swabs were Propionibacterium acnes, Staphylococcus epidermidis, Corynebacterium spp. and Staphylococcus aureus. The 16S-RNA gene analysis revealed no clear differentiation of the bacterial community of healthy compared to CRS samples of unilateral purulent maxillary CRS and CRSwNP. However, the bacterial community of CRSsNP differed significantly from the healthy controls. In the CRSsNP samples Flavobacterium, Pseudomonas, Pedobacter, Porphyromonas, Stenotrophomonas, and Brevundimonas were significantly enriched compared to the healthy controls. Species isolated from culture did not generally correspond with the most abundant genera in microbiome analysis. Only Fusobacteria, Parvimonas, and Prevotella found in 2 unilateral purulent maxillary CRS samples by the cultivation dependent approach were also found in the cultivation independent approach in high abundance, suggesting a classic infectious pathogenesis of odontogenic origin in these two specific cases. Alterations of the bacterial community might be a more crucial factor for the development of CRSsNP compared to CRSwNP. Further studies are needed to investigate the relation between bacterial community characteristics and the development of CRSsNP.

Reduction of olfactory sensitivity during normobaric hypoxia.

OBJECTIVE: Acute mountain sickness (AMS) is caused by a low partial pressure of oxygen and may occur above 2500m. The aim of this research was to evaluate olfactory and gustatory abilities of healthy subjects during baseline conditions and after seven hours of normobaric hypoxia. METHODS: Sixteen healthy subjects were assessed using the Sniffin' Sticks, as well as intensity and pleasantness ratings. Gustatory function was evaluated utilizing the Taste Strips. Experiments were carried out under baseline conditions (518m altitude) followed by a second testing session after seven hours of normobaric hypoxia exposure (comparable to 4000m altitude). RESULTS: During normobaric hypoxia olfactory sensitivity and intensity estimates were significantly reduced. CONCLUSIONS: We conclude that normobaric hypoxia leads to a significant decrease of olfactory sensitivity and intensity ratings.

Frequency of bilateral cervical metastases in hypopharyngeal squamous cell carcinoma: a retrospective analysis of 203 cases after bilateral neck dissection.

The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. A retrospective chart review was performed of 203 patients with hypopharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. A high frequency of contralateral metastases above 20% was detected for all carcinomas affecting the midline and those involving the medial wall of the pyriform sinus except of T1-stages (13%) and a low frequency for laterally located primaries (3%). Ipsilateral nodal status predicted contralateral neck metastases. Bilateral neck dissection should be recommended for primaries affecting the midline and T2-4 tumors involving the medial wall of the pyriform sinus.

Labial Salivary Glands in Infants: Histochemical Analysis of Cytoskeletal and Antimicrobial Proteins.

Human labial glands secrete mucous and serous substances for maintaining oral health. The normal microbial flora of the oral cavity is regulated by the acquired and innate immune systems. The localization and distribution of proteins of the innate immune system were investigated in serous acinar cells and the ductal system by the method of immunohistochemistry. Numerous antimicrobial proteins could be detected in the labial glands: ß-defensin-1, -2, -3; lysozyme; lactoferrin; and cathelicidin. Cytoskeletal components such as actin, myosin II, cytokeratins 7 and 19, α- and ß-tubulin were predominantly observed in apical cell regions and may be involved in secretory activities.

Atmospheric Pressure and Onset of Episodes of Menière's Disease - A Repeated Measures Study.

BACKGROUND: External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière's disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. METHODS: Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004-2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. RESULTS: A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. CONCLUSIONS: Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future.

Susceptibility-weighted angiography visualizes hypoxia in cerebral veins.

OBJECTIVES: The objective of this study was to evaluate the influence of short- and long-term hypoxia on the depiction of cerebral veins in the susceptibility-weighted angiography (SWAN) sequence. MATERIALS AND METHODS: In the context of a study on brain adaptation mechanisms to hypoxia, 16 healthy men (aged 20-28 years) were studied through magnetic resonance imaging (MRI) under room air conditions, short-term-hypoxia (7 minutes before and during the MRI scan), and long-term hypoxia (8.5 hours before and during the MRI scan). Oxygen saturation was continuously measured using a finger-mounted pulse oximeter. Two independent blinded readers compared the 3 scans of each participant and graded the SWAN source images and minimum intensity projections according to the size, number, and signal intensity of the cerebral veins. Signal intensities of deep cerebral veins were measured, and signal intensity proportions of deep cerebral veins to different parenchymal brain regions were calculated. RESULTS: Nine subjects could be included in the study. In all of them, both readers correctly distinguished the 2 hypoxia scans from the baseline scan, grading the SWAN images acquired under hypoxic conditions as visualizing cerebral veins more prominently. Signal intensities of the deep cerebral veins and signal intensity proportions were significantly lower in the hypoxia scans. No significant differences between short-term and long-term hypoxia were found on visual inspections and signal intensity measurements. This correlated with the results of the pulse oximetry: mean O2 saturation values were 97.9% ± 1.2% (baseline), 84.1% ± 3.8% (short-term hypoxia), and 82.8% ± 4.4% (long-term hypoxia), respectively. CONCLUSIONS: Hypoxia leads to visible and measurable changes in cerebral veins as depicted through SWAN. Possible clinical implications of this finding include stroke and tumor imaging and need further investigation.

No evidence of intracranial hypertension in trekkers with acute mountain sickness when assessed noninvasively with distortion product otoacoustic emissions.

AIMS: The role of intracranial hypertension in acute mountain sickness (AMS) is a matter of debate. Distortion product otoacoustic emissions (DPOAEs) can be used to monitor the intracranial pressure (ICP) noninvasively with a level decrease at the frequencies f2=1 and 1.5 kHz indicating elevated ICP. METHODS: DPOAEs (f2=1, 1.5, 2, 3, and 4 kHz), oxygen saturation (Sao2) and the Lake Louise score (LLS) to assess AMS were measured in trekking tourists on the Mount Everest trek in Nepal at 2610 m and 5170 m. RESULTS: Paired data of both altitudes could be obtained of 187 subjects. All results are given in mean±SD. Sao2 was 94.8±2.7% at 2610 m and 79.0±6.9% at 5170 m. While at 2610 m, none of the study subjects had AMS (LLS 0.04±0.02), at 5170 m 82 (43.9%) had AMS when defined as LLS>2, and 31 (16.6%) when defined as LLS>4 (LLS 2.8±2.2). DPOAE levels decreased at altitude in all frequencies without a difference between trekkers with AMS and without AMS. Low Sao2 correlated with high LLS. Low Sao2 correlated with larger DPOAE level decrease only at f2=1 kHz, while the other frequencies showed no correlation. DPOAE level decrease and LLS showed no correlation. CONCLUSIONS: Our data suggest that subjects with AMS symptoms did not have higher ICP compared to healthy subjects. Consequently, it seems unlikely that intracranial hypertension accounts for the symptoms of AMS.

Immunolocalization of antimicrobial and cytoskeletal components in the serous glands of human sinonasal mucosa.

Secretory cells in the seromucous glands of paranasal sinuses secrete antibacterial proteins for innate immune mucosal integrity. We studied the localization of antimicrobial and cytoskeletal components of the human seromucous glands and respiratory epithelium of the maxillary sinus and the ethmoidal cells by immunohistochemical methods. The presence of a variety of defense proteins such as lysozyme, lactoferrin, cathelicidin, and defensin-1, -2, -3 point to a crucial role in the immune defense for the respiratory tract. Cytoskeletal proteins such as actin, myosin 2, cytokeratin 7 and 19, α- and ß-tubulin, investigated for the first time in glands of paranasal sinuses, showed a stronger expression at the apical and lateral cell membrane. The localization of the cytoskeletal proteins might point to their participation in exocrine secretory processes and stabilizing effects.

Complex level alterations of the 2f(1)-f(2) distortion product due to hypoxia.

OBJECTIVE: For diagnostic purposes and a better understanding of the pathophysiology of inner ear hearing disorders it would be of great interest to have parameters available that indicate inner ear hypoxia. In animal studies typical hypoxia-related alterations of the 2f1-f2 distortion product otoacoustic emissions (DPOAE) such as a reversible level decrease and destabilization could be demonstrated. The goal of this study was to investigate whether these hypoxia-associated alterations can also be observed in humans because this might help develop a new diagnostic tool for patients with inner ear disorders. METHODS: In 16 volunteers DPOAE levels were continuously measured at first under normal room air conditions, during and after 8.5h of oxygen deprivation (13% O2) and during re-oxygenation. Saturation of oxygen of arterial blood (SaO2) was monitored. RESULTS: The mean SaO2 during the hypoxic interval was 78%. A significant decrease in DPOAE level under hypoxia occurred in five different test persons at one or more frequencies (f2=1, 1.5, 2, 3, and 4kHz). A destabilization of the DPOAE level with considerable fluctuations during hypoxia was observed in nine subjects at one or more frequencies. Furthermore, the so called 'post hypoxia effect' could be observed in five participants. CONCLUSION: The observations made here have been described similarly in animal studies and seem to be characteristic of metabolic disorders of the cochlea caused by hypoxia. To our knowledge, this is the first study to examine DPOAE level alterations over time in humans under conditions of normobaric hypoxia. If DPOAE destabilization is observed in a clinical setting in patients with certain inner ear hearing disorders hypoxia can be suspected as one underlying pathophysiological cause which might influence treatment decisions.

Comparative Study between the Surgeon's Intraoperative Evaluation and Histopathology for Diagnosis of Laryngeal Lesions.

Objective. To compare the surgeon's evaluation and histopathology for diagnosis of laryngeal lesions. Material. A clinical survey was distributed to laryngeal surgeons, ENT clinicians, and students in 2013 at the Department of Otorhinolaryngology in Rostock. Participants were asked to anonymously identify laryngeal pathologies and to assess the severity of the lesion starting from hyperplasia and inflammation over moderate dysplasia to early laryngeal cancer. Images of similar clinical laryngeal lesions were demonstrated in a multiple-choice modus to assess the surgeon's intraoperative evaluation. The questionnaires were digitally processed and evaluated. The results were correlated with histopathology and compared between experienced laryngeal surgeons, clinicians inexperienced in laryngeal surgery, and medical students from the Medical Faculty of the University of Rostock. Results. Sensitivity and specificity varied among the various groups, being highest in experienced laryngeal surgeons. In this group, sensitivity, specificity, positive and negative predictive value, and accuracy were 85%, 56%, 44%, 90%, and 65%, respectively. In 4% and 31%, laryngeal disease was underdiagnosed and overdiagnosed, respectively. In this group, Kappa statistics resulted in Kappa 0.32 (P < 0.001). Conclusion. This clinical survey clearly demonstrates that conformity between histopathology and evaluation of the laryngeal lesion depends on the surgeon's experience.

Effects of acoustic stimuli used for vestibular evoked myogenic potential studies on the cochlear function.

OBJECTIVE: To study if acoustic stimuli used for vestibular evoked myogenic potential (VEMP) studies can damage the cochlea. STUDY DESIGN: Prospective diagnostic study. SETTING: Academic tertiary referral center. METHODS: In 30 young healthy adults aged between 20 and 35 years without any audiovestibular disorders, cVEMP studies were performed in a standard setting (tone burst, 500 Hz, 133 dB SPL, stimuli rate 200). Before and after acoustic stimulation for the cVEMP examination, the cochlear function was measured using pure tone audiometry and distortion product otoacoustic emissions (DPOAE). Additionally, the subjects were asked about ear symptoms. RESULTS: In all subjects, cVEMP could be recorded. Eight (27%) of them reported subjective hearing symptoms direct after the VEMP examination. All were again free of complaints on the next day. Hearing thresholds did not deteriorate in pure tone audiometry. DPOAE levels decreased on the exposed side in the high-frequency range (4,000-6,000 Hz). The subjects with subjective ear symptoms had a stronger level decrease. In a follow-up measurement 24 hours later, the DPOAE levels showed recovery. CONCLUSION: Acoustic stimuli used to elicit VEMP were found to have an adverse effect on the cochlear function. A clinically relevant hearing loss was not found in our study in healthy adults. Subjective auditory symptoms were reversible within 24 hours. Nevertheless, the stimulus levels and the number of repetitions should be kept as low as possible.

Influence of the individual DPOAE growth behavior on DPOAE level variations caused by conductive hearing loss and elevated intracranial pressure.

OBJECTIVES: Minor conductive hearing loss (CHL) can compromise the evaluation of the inner ear function with distortion product otoacoustic emissions (DPOAE). Elevation of the intracranial pressure (ICP) is also expected to alter the middle ear (ME) sound transmission. An impaired ME sound transmission leads to an attenuation of the DPOAE primary tone levels (L1 and L2) during forward transmission and of DPOAE levels (LDP) during backward transmission. The effect of the attenuation of L1 and L2 is complex and might have unexpected effects on DPOAE levels. In this work, CHL- and ICP-induced alterations of LDP versus L1 growth functions (constant L2 and increasing L1) are investigated. The first aim of this study is to explain how alterations of ME sound transmission can affect DPOAEs and to characterize the dependency of DPOAE level alterations on L2,L1 combinations and on the individual shape of LDP versus L1 growth functions. The second aim is to identify analogies between CHL- and ICP-induced alterations of DPOAEs and to discuss implications for a potential noninvasive ICP monitoring. DESIGN: This study focuses on general theoretical considerations, supported by selected experimental observations in different species and simulations. DPOAEs were measured in guinea pigs before and after induction of a CHL (1 ear) and during increased ICP (1 ear), and in humans during changes of the postural position to alter the ICP (4 ears). RESULTS: In both CHL and elevated ICP, DPOAE levels are not only reduced, but LDP versus L1 growth functions exhibit a shift to higher L1. The absolute DPOAE level alterations strongly depend on the L2,L1 combinations and the individual shape of the LDP versus L1 growth functions. In steeper LDP versus L1 growth functions, the DPOAE level alterations exhibit a larger variation. DPOAE levels can even increase. The largest variation can be found in ears with a nonmonotonic DPOAE growth behavior. An example of a guinea pig ear is presented with a nonmonotonic DPOAE growth behavior and a CHL of 4 dB, where the DPOAE level alterations varied between -32 and +9 dB depending on L1. CONCLUSIONS: The data enable a more comprehensive view of DPOAE level alterations during CHL and elevated ICP. The observations also explain the problem that DPOAE and ICP alterations do not correlate linearly. An evaluation of the shift of the LDP versus L1 growth function along the L1 axis provides a potential tool to improve both the assessment of the inner ear function in the presence of a CHL and noninvasive ICP monitoring with DPOAEs.

Modeling the measurements of cochlear microcirculation and hearing function after loud noise.

OBJECTIVE: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. STUDY DESIGN: Randomized controlled trial. Setting. Animal study. Subjects and Methods. After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. RESULTS: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2 dB SPL (60 minutes) only in animals exposed to loud noise. CONCLUSION: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo.

Does laryngopharyngeal reflux cause intraoral burning sensations? A preliminary study.

Intraoral burning sensations are a common problem in the otolaryngological practice. The aim of this study was to evaluate if laryngopharyngeal reflux can cause intraoral burning sensations by measuring oropharyngeal acid reflux. Patients with recurring intraoral burning sensations underwent oropharyngeal pH monitoring in our outpatient clinic. The pH catheter was placed at the level of the uvula. The catheter contained an externally worn transmitter, which wirelessly sent the data to a monitor. In addition, patients were instructed to indicate meals or the occurrence of burning sensations by pressing provided buttons on the monitor. Corresponding events of burning sensations and a significant decrease in oropharyngeal pH values should be visualized. Twenty two patients suffering from recurring intraoral burning sensations underwent oropharyngeal pH measurement for 21-25 h. We could find oropharyngeal reflux episodes in 11 patients. However, we could not detect any episodes of burning sensations in the mouth corresponding with a decrease in oropharyngeal pH values. Our results suggest that there is no causal connection between LPR episodes and the occurrence of intraoral burning sensations in the examined patients. Although further studies with more patients are necessary in the future, we conclude from our findings that recurring intraoral burning sensations are not an indication for proton pump inhibitor therapy.

Frequency of bilateral cervical metastases in oropharyngeal squamous cell carcinoma: a retrospective analysis of 352 cases after bilateral neck dissection.

BACKGROUND: The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma (HNSCC) and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. To date there is limited information about contralateral and bilateral cervical lymph node metastases of oropharyngeal carcinoma. METHODS: A retrospective chart review was performed of 352 patients with oropharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. RESULTS: Carcinomas of the tonsillar fossa starting with a T2 classification and carcinomas of the soft palate, base of tongue, and pharyngeal wall at any stage showed a high frequency of bilateral metastases. CONCLUSIONS: Bilateral neck dissection should be recommended for all but T1 and selected cases of T2 carcinomas of the tonsillar fossa.