Round-Window Vibroplasty: Systematic Review and Meta-Analysis of Audiological Effectiveness With Different Round-Window Coupling Techniques.

OBJECTIVE: Active middle ear implants can be directly coupled to the round-window (RW) membrane via RW Vibroplasty. The objectives of this systematic review were to summarize data on different RW coupling techniques and to investigate their effect on audiological and safety outcomes using meta-analyses. DATABASES REVIEWED: PubMed (MEDLINE), Cochrane Library, and Embase (DIMDI). METHODS: All publications reporting on audiological outcomes in human patients after RW Vibroplasty were included. Two independent reviewers carried out screening and data extraction. Meta-analyses and meta-regression were used to evaluate the potential effects of surgical and demographic parameters on primary audiological outcomes. Adverse events were extracted and tabulated for qualitative analysis. RESULTS: Fourteen different combinations of surgical coupling parameters were identified in 61 included publications. Overall, data from 23 publications could be used for meta-analyses. Significantly better aided sound-field thresholds were reported for RW Vibroplasty performed without a dedicated coupler and using fascia as interponate, compared with RW Vibroplasty with an RW coupler or without an interponate. These effects were not found in other outcomes (i.e., functional gain, word recognition score). Reporting of adverse events was relatively heterogeneous, with 32 explicit mentions of revision surgery after the loss of coupling efficacy. CONCLUSION: There are numerous publications investigating the effectiveness of coupling active middle ear implants to the RW membrane. However, studies are typically undersampled and of low evidence level. Using meta-analyses, weighted means, and qualitative analyses enabled a summary of the existing literature on audiological and safety outcomes after RW Vibroplasty. Individual selection of the most appropriate coupling modality with standardized intraoperative measurement and careful patient follow-up may be considered key factors for achieving effective RW coupling.

Functional Outcomes and Quality of Life after Cochlear Implantation in Patients with Long-Term Deafness.

Background: Hearing-related quality of life (QoL) after cochlear implantation (CI) is as important as audiological performance. We evaluated the functional results and QoL after CI in a heterogeneous patient cohort with emphasis on patients with long-term deafness (>10 years). Methods: Twenty-eight patients (n = 32 implanted ears, within n = 12 long-term deaf ears) implanted with a mid-scala electrode array were included in this retrospective mono-centric cohort study. Speech intelligibility for monosyllables (SIM), speech reception thresholds (SRT50) and QoL with Nijmegen Cochlear Implant Questionnaire (NCIQ) were registered. Correlation of SIM and QoL was analyzed. Results: SIM and SRT50 improved significantly 12 months postoperatively up to 54.8 ± 29.1% and 49.3 ± 9.6 dB SPL, respectively. SIM progressively improved up to 1 year, but some early-deafened, late implanted patients developed speech understanding several years after implantation. The global and all subdomain QoL scores increased significantly up to 12 months postoperatively and we found a correlation of SIM and global QoL score at 12 months postoperatively. Several patients of the "poor performer" (SIM < 40%) group reported high improvement of hearing-related QoL. Conclusions: Cochlear implantation provides a benefit in hearing-related QoL, even in some patients with low postoperative speech intelligibility results. Consequently, hearing-related QoL scores should be routinely used as outcome measure beside standard speech understanding tests, as well. Further studies with a prospective multi-centric design are needed to identify factors influencing post-implantation functional results and QoL in the patient group of long-term deafness.

Long-term audiological benefit with an active transcutaneous bone-conduction device: a retrospective cohort analysis.

PURPOSE: To evaluate long-term audiological, surgical and safety outcomes of a complex patient cohort treated with an active transcutaneous bone-conduction device (tBCD). METHODS: This retrospective, monocentric cohort analysis involves 31 adults with conductive (CHL) and mixed hearing loss (MHL). For outcome analysis, study results were divided into short-term follow-up data (< 12 months) and long-term follow-up data (> 12 months). RESULTS: 31 patients with a total person-time of 90.4 years and an average number of 3.2 ± 1.5 preoperatively performed surgeries on the implanted side were investigated. Mean BCD-aided PTA4 thresholds were significantly lower than unaided PTA4AC before surgery (64.7 ± 16.1 dB HL; CHL 50.6 ± 10.6 dB HL; MHL 72.8 ± 12.8 dB HL) and did not change between short-term (42.3 ± 13.1 dB HL; CHL 35.8 ± 6.8 dB HL; MHL 45.2 ± 14.3 dB HL) and long-term (43.4 ± 10.0 dB HL; CHL 35.8 ± 4.3 dB HL; MHL 48.1 ± 9.6 dB HL) follow-up periods. Speech intelligibility in the Freiburg monosyllables test at 65 dB improved significantly, from 16.3 ± 21.5% (CHL 26.8 ± 19.0%; MHL 8.7 ± 20.5%) in the unaided condition to 82.7 ± 15.5% (CHL 90.0 ± 12.2%; MHL 79.4 ± 16.3%) in the short-term and 85.5 ± 13.2% (CHL 93.8 ± 7.9%; MHL 79.5 ± 13.3%) BCD-aided in the long-term follow-up periods. Ten minor procedure-related and 6 implant-related (5 minor, 1 major) AEs occurred over the total follow-up period. CONCLUSION: The device provides satisfactory audiological and speech benefit over long-term follow-up periods, up to 7 years. Explant rates were very low, while the overall rate of manageable AEs was high in this complex patient cohort. The device is considered a safe and effective option in the long-term hearing rehabilitation of patients with CHL and MHL.

Automated detection of electrically evoked stapedius reflexes (eSR) during cochlear implantation.

INTRODUCTION: In cochlear implantation, objective fitting methods are needed to optimize audiological results in small children or patients with poor compliance. Intraoperatively measured electrically evoked stapedius reflexes (eSR) can be used as a marker for the patient's discomfort level. The aim of this study was to develop and evaluate an automated detection method for eSR and to compare it to the detection rate of the surgeon and independent observers. METHODS: Cochlear implantation using a fully digital surgical microscope was performed. Movements of the stapedius tendon were recorded and analyzed by means of computer vision technique. Differences in eSR elicited by stimulating electrodes at different cochlear locations (basal, middle and apical) were analyzed. The eSR detection rate of the image processing algorithm was compared to the surgeon's detection rate and to those of two less experienced observers. RESULTS: A total of 387 electrically impulses were applied. The stimulation of middle turn electrodes showed significantly higher detection rates (50.4%) compared to the basal (40.0%; p = 0.001) and apical (43.6%; p = 0.03) turn. The software identified significantly more of the applied stimuli (58.4%) compared to the surgeon (46.3%; p = 0.0007), the intermediate observer (37.7%; p < 0.0001) and the unexperienced observer (41.3%; p < 0.0001). CONCLUSION: The feasibility of an automated intraoperative software-based detection of eSR is demonstrated. By improving the eSR detection methods and their clinical applicability, their utility in objective cochlear implant fitting may be substantially increased.

Patient-reported long-term benefit with an active transcutaneous bone-conduction device.

PURPOSE: To evaluate the long-term benefits in hearing-related quality of life, patient satisfaction and wearing time of patients rehabilitated with an active transcutaneous bone-conduction device. Adverse events and audiological outcomes are reported as secondary outcomes. METHODS: This retrospective, mono-centric cohort analysis involves 16 adults with conductive or mixed hearing loss with a mean device experience of 51.25 months. Patient-reported outcome measures were assessed using the short version of the Speech, Spatial and Qualities of Hearing Scale (SSQ12-B) and the German version of the Audio Processor Satisfaction Questionnaire (APSQ). Audiological outcomes as well as incidence of adverse events were obtained from patients´ charts. RESULTS: The hearing-related quality of life improved significantly within all subscales of the SSQ12-B scoring a mean overall of 2.95 points. Patient satisfaction measured with the APSQ scored 8.8 points on average. Wearing times differed considerably and patients with lower levels of education seemed to use their device longer compared to patients with academic education. Eight minor adverse events were documented, all of which resolved during follow-up. The mean gain in word recognition score at the last follow-up measured at 65 dB was 75.9%, while speech reception threshold was lowered by 35.1 dB. CONCLUSION: Even after several years, patients report significant benefits in hearing-related quality of life and device satisfaction. In combination with a low rate of minor adverse events and significantly improved audiological outcomes, the device is considered as a comfortable and effective option in hearing rehabilitation.

Three-dimensional force analysis of surgical manipulations at the long process of the incus.

PURPOSE: Surgical manipulation with application of inappropriate force may damage middle ear structures leading to hearing loss. This work analyzes the forces applied in simulated otosurgical exercises in a laboratory set-up by measuring the spatial components of applied forces with objective assessment criteria. With these criteria, the individual force characteristics applied by the surgeon can be quantified and an objective feedback can be given about their surgical maneuvers. METHODS: A natural size model of the human incus was mounted on a load cell to measure the spatial forces in all three directions during different manipulation tasks performed under the microscope by ten surgeons from our department having different levels of experience in otosurgery. The motions of the incus model and the instrument tip were recorded simultaneously with a video camera. RESULTS: Independent of surgical experience, a three-dimensional force pattern could be detected with components transverse to the desired force directions. The measured forces applied by trainees showed larger variations in magnitude, in spatial distribution and in temporal course than those applied by experienced surgeons. A better repeatability of identical tasks, constancy of force patterns and low peak force values could be seen in the group of experienced surgeons. CONCLUSIONS: The laboratory system presented in this study using simultaneous video and 3-D force registration allows the objective assessment of surgical manipulations, e.g., at the long process of the incus. Training with video and force feedback provides information about surgical techniques and skill development of surgeons and has the potential to shorten the learning curve and to diminish intra-operative risks to patients.

Diagnostic Value of the Magnetic Resonance Imaging With Intratympanic Gadolinium Administration (IT-Gd MRI) Versus Audio-Vestibular Tests in Menière's Disease: IT-Gd MRI Makes the Difference.

OBJECTIVE: Our aim was to evaluate the validity and reliability of clinically relevant tests in the diagnosis of Menière's disease (MD) according to the criteria formulated during 2015 as well as their efficacy in detecting endolymphatic hydrops (EH). The focus was on: three-dimensional fluid-attenuated inversion recovery-SPectral Attenuated Inversion Recovery (3D-FLAIR-SPAIR) sequences using 3 Tesla magnetic resonance imaging (3T MRI) performed 24 hours after intratympanic Gadolinium injection (IT-Gd) in comparison with the functional tests pure tone audiometry (PTA), caloric test, video head impulse test (vHIT), and cervical-vestibular-evoked-myogenic-potentials (cVEMP). STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Primary eligibility criteria were given clinical suspicion of MD and the performance of an IT-Gd MRI leading to a group of 31 patients and 52 ears to be analyzed separately. MAIN OUTCOME MEASURE (S): Reanalysis of the raw diagnostic data leading to comparability of IT-Gd MRI, PTA, caloric test, vHIT, and cVEMP concerning their valency for clinically diagnosed MD and quantifiability of EH. RESULTS: Considering sensitivity, specificity, and the likelihood-ratio only the IT-Gd MRI displayed results qualifying it as a viable device for MD-diagnostics in regards to the criteria of 2015 (p = 0.01), it even provides direct imaging evidence for the underlying pathology of the disease. Furthermore, the comparison between MRI images and test results of caloric test, vHIT and cVEMP revealed that neither of these diagnostic functional tests serves as a reliable indicator for EH. CONCLUSIONS: It appears that the diagnosing process of MD would benefit from turning IT-Gd MRI into a standard diagnostic procedure in cases of suspected MD, displaying better results than caloric test, vHIT, and cVEMP.

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.

Optical coherence tomography and confocal laser scanning microscopy as non-invasive tools in the diagnosis of sinonasal inverted papilloma: a pilot study.

Optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) are light-based imaging techniques that allow for a visualization of microscopic tissue properties in vivo. Our study was to examine whether they allow for differentiation of inverted papilloma (IP) from nasal polyps (NP). Five cases of IP and NP, respectively, were investigated intraoperatively with OCT and CLSM. Biopsies were taken of the investigated area and were analyzed ex vivo with OCT and CLSM and then underwent HE-staining for standard light microscopy. On OCT images, IP showed the characteristic inverted character of the epithelium, that was thicker with a high degree of variability of thickness compared to the thin and homogenous epithelium of NP. In addition, the characteristic stromal edema of NP could be visualized. On CLSM images, the typical epithelial invaginations of IP appeared as crypts, while in NP the highly organized cylindric epithelium could be visualized. In vivo, OCT acquired images of sufficient quality to visualize these characteristics, while CLSM did not. Our study demonstrates that OCT and CLSM can distinguish IP from NP. Further technical development is required to apply the techniques clinically to guide intranasal biopsies or even to make them dispensable.

Sevoflurane at 1.0 MAC together with remifentanil and propofol produces clinically acceptable intubation conditions at the vocal cords: A prospective randomized study.

Objective The overall intubation conditions after tracheal intubation with remifentanil, propofol, and sevoflurane at 1.0 minimum alveolar concentration (MAC) are worse than with rocuronium at 0.45 mg/kg. Therefore, we compared the intubation conditions and laryngeal morbidity (vocal cord injuries, hoarseness, and sore throat) with sevoflurane at 1.2 and 1.4 MAC versus 1.0 MAC. Methods In this prospective clinical trial, 90 patients were randomized to 3 groups: the sevoflurane 1.0, 1.2, and 1.4 MAC groups. At 3 min, tracheal intubation was performed and the patients' intubation conditions were assessed. The vocal cords were examined for injury by videolaryngoscopy. Additionally, the incidence and severity of laryngeal morbidity were compared between women and men. Results Acceptable intubation conditions were seen in 72% of the patients without significant differences between the groups. Overall, vocal cord injuries (oedema) occurred in three (4%) patients. Women reported sore throat more often than men (51% vs. 21%, respectively). Conclusions Intubation conditions were not improved with higher sevoflurane concentrations. The incidence and severity of sore throat were greater in women than men. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT 01896245.

Hearing Impairment Affects Dementia Incidence. An Analysis Based on Longitudinal Health Claims Data in Germany.

Recent research has revealed an association between hearing impairment and dementia. The objective of this study is to determine the effect of hearing impairment on dementia incidence in a longitudinal study, and whether ear, nose, and throat (ENT) specialist care, care level, institutionalization, or depression mediates or moderates this pathway. The present study used a longitudinal sample of 154,783 persons aged 65 and older from claims data of the largest German health insurer; containing 14,602 incident dementia diagnoses between 2006 and 2010. Dementia and hearing impairment diagnoses were defined according to International Classification of Diseases, Tenth Revision, codes. We used a Kaplan Meier estimator and performed Cox proportional hazard models to explore the effect of hearing impairment on dementia incidence, controlling for ENT specialist care, care level, institutionalization, and depression. Gender, age, and comorbidities were controlled for as potential confounders. Patients with bilateral (HR = 1.43, p<0.001) and side-unspecified (HR = 1.20, p<0.001) hearing impairment had higher risks of dementia incidence than patients without hearing impairment. We found no significant effect for unilateral hearing impairment and other diseases of the ear. The effect of hearing impairment was only partly mediated through ENT specialist utilization. Significant interaction between hearing impairment and specialist care, care level, and institutionalization, respectively, indicated moderating effects. We discuss possible explanations for these effects. This study underlines the importance of the association between hearing impairment and dementia. Preserving hearing ability may maintain social participation and may reduce the burden associated with dementia. The particular impact of hearing aid use should be the subject of further investigations, as it offers potential intervention on the pathway to dementia.

On the origin of ear clicks during deglutition or pressure equalization.

To explore the origin of clicking sounds in the ear during deglutition or other pharyngeal movements, which are interpreted differently in the literature. Experimental study at a tertiary referral centre. Acoustic phenomena during a forced opening test of the Eustachian tube (ET) were studied in a temporal bone model. Additionally, in vivo experiments were carried out in healthy volunteers for ruling out movements of the ossicular chain or the drumhead as potential causes of clicks. Thus, acoustic recordings were performed parallel to stapedius or tensor reflex measurements or pneumatic video endoscopies of the tympanic membrane. Obviously the acoustic signals (clicks) appear when the tube opens, which could be visualized and acoustically recorded during forced opening tests in temporal bone experiments. Middle ear muscle contractions with movements of the tympanic membrane did not cause any click events. Together with the results of a previous paper (9) we interpret the clicks as disruptions of fluid or mucus films covering the mucosa during the ET opening. The final goal of our studies is to use such clicks as indicators of ET openings in a new tube function test, which has to be elaborated.

Positioning Accuracy in Otosurgery Measured with Optical Tracking.

OBJECTIVES: To assess positioning accuracy in otosurgery and to test the impact of the two-handed instrument holding technique and the instrument support technique on surgical precision. To test an otologic training model with optical tracking. STUDY DESIGN: In total, 14 ENT surgeons in the same department with different levels of surgical experience performed static and dynamic tasks with otologic microinstruments under simulated otosurgical conditions. METHODS: Tip motion of the microinstrument was registered in three dimensions by optical tracking during 10 different tasks simulating surgical steps such as prosthesis crimping and dissection of the middle ear using formalin-fixed temporal bone. Instrument marker trajectories were compared within groups of experienced and less experienced surgeons performing uncompensated or compensated exercises. RESULTS: Experienced surgeons have significantly better positioning accuracy than novice ear surgeons in terms of mean displacement values of marker trajectories. The instrument support and the two-handed instrument holding techniques significantly reduce surgeons' tremor. The laboratory set-up presented in this study provides precise feedback for otosurgeons about their surgical skills and proved to be a useful device for otosurgical training. CONCLUSIONS: Simple tremor compensation techniques may offer trainees the potential to improve their positioning accuracy to the level of more experienced surgeons. Training in an experimental otologic environment with optical tracking may aid acquisition of technical skills in middle ear surgery and potentially shorten the learning curve. Thus, simulated exercises of surgical steps should be integrated into the training of otosurgeons.

"Physiological" Ear Clicking: Its Origin and Potential Usability as a Test Tool for the Eustachian Tube Function.

OBJECTIVE: To explore the origin of "physiological" ear clicks during deglutition or other pharyngeal movements, which, in contrast to disturbing frequent clicks under pathologic conditions, mostly remain unnoticed by the patient. STUDY DESIGN: Clinical experimental study at a tertiary referral center. METHODS: Ear clicks were recorded by a microphone sealing the external ear canal parallel to endoscopic or manometric evaluations of the Eustachian tube function. RESULTS: Obviously, the acoustic signals (clicks) appear when the tube opens. The clicks might be explained by a disruption of fluid or mucus films covering the mucosa. As in our tests clicks could be recorded regularly, they might potentially be used as indicators in a new tube function test, which has to be elaborated.

Regional Pattern of Dementia and Prevalence of Hearing Impairment in Germany.

OBJECTIVES: To determine the association between hearing impairment and dementia. DESIGN: Cross-sectional study. SETTING: Claims data of the Allgemeine Ortskrankenkasse, the largest public health insurance company in Germany. PARTICIPANTS: Age-stratified sample of all insured persons aged 65 and above in the first quarter of 2007 (N = 1,338,462). MEASUREMENTS: Metaregression analysis on the association between regional prevalence of dementia and hearing impairment controlled for major vascular risk factors, including hypertension, hypercholesterolemia, diabetes mellitus, and cerebrovascular disease. Dementia and hearing impairment diagnoses were defined according to International Classification of Diseases, Tenth Revision, codes. Ninety-five regions were distinguished according to the two-digit postal code of the place of residence. RESULTS: A significant association was found between regional prevalences of dementia and hearing impairment that was preserved when controlling for major vascular risk factors (P = .003). Regional dementia prevalence increased by approximately 0.23% when the prevalence of hearing impairment increased by 1 standard deviation. CONCLUSION: The relationship between hearing impairment and dementia has been repeatedly demonstrated on the individual level. The results of the current study confirm that this relationship also exists on a regional level. These findings underscore the potential role of hearing impairment as a risk factor for dementia that will be relevant for the management of elderly patients in general practice.

Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany.

The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.

Can nasal decongestants improve eustachian tube function?

OBJECTIVE: To evaluate the effect of nasal decongestants on eustachian tube (ET) opening. STUDY DESIGN: A prospective nonrandomized study. SETTING: A tertiary referral center. PATIENTS: Twenty-four patients (44 ears) with intact eardrums, 39 patients (43 ears) having a noninfected eardrum defect, and six patients with an upper airway infection. INTERVENTIONS: Nasal or intratympanal (in perforated ears) application of a nasal decongestant (xylometazoline 0.1%). MAIN OUTCOME MEASURES: Change of tube opening quality (yes or no; better or worse) measuring tube opening parameters (pressure, latency) using the Estève method and pressure equalization tests (swallowing at negative and positive external ear canal pressures). RESULTS: In most cases, nasal decongestion or intratympanal use of decongestants have no effect on ET opening. Improvement in tube opening is rather an exception and, in a minority of patients, a reduced ET function was evident. CONCLUSION: Our acute studies revealed no improvement in eustachian ventilatory tube function with the administration of nasal decongestants.

The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma.

Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.

Conservative management of post-intubation tracheal tears-report of three cases.

Iatrogenic tracheal rupture is a rare complication after intubation. We present three patients with tracheal tears. In all of these patients, a common finding was a lesion of the posterior tracheal wall with postoperative subcutaneous and emphysema as the first clinical sign of the rupture. Diagnosis and follow-up were based on clinical and endoscopic findings and chest computed tomography (CT) scans. In our cases with progressive subcutaneous and mediastinal emphysema or dyspnea, we performed a tracheotomy and bypassed the lesion with a tracheostomy tube to avoid an increase in air leakage into the mediastinum. Under broad-spectrum antibiotic therapy, no mediastinitis occurred and all patients survived without sequelae. Closure of tracheostomy was scheduled for 1-2 months after tracheal injury. Analysis of surgical and anesthesiological procedures revealed no abnormalities and the accumulation of tracheal injuries was considered as accidental. We found that in clinically stable patients with spontaneous breathing and with no mediastinitis, a conservative management of tracheal tears is a safe procedure.