Occlusion of the Lateral Semicircular Canal, Endolymphatic Sac Surgery, and Cochlear Implantation: A Low Destructive Treatment for Unilateral Ménière's Disease and Deafness.

INTRODUCTION: Surgical treatment of Ménière's disease (MD) and deafness aims to treat vertigo and hearing disabilities. Current treatment options like labyrinthectomy and cochlear implantation (CI) have shown acceptable results but are destructive. Less destructive procedures, like the occlusion of the lateral semicircular canal and endolymphatic sac surgery, have been shown to be successful in vertigo control. The combination of both procedures with CI has not been investigated; therefore the objective of this study was to investigate the outcome of this combination in patients with single-sided MD and moderately severe to complete sensorineural hearing loss. METHODS: In this retrospective study, 10 patients with single-sided MD and moderately severe to complete sensorineural hearing loss were included. In all of them, a single-staged surgery, which consisted of CI, endolymphatic sac surgery, and occlusion of the lateral semicircular canal, was performed. The surgery was performed after a failed conservative therapy trial. The clinical outcome was evaluated by the Dizziness Handicap Inventory (DHI) and audiological tests. These were assessed preoperatively, 3 and 6 months after surgery. An MRI with a hydrops sequence was performed to support the clinical diagnosis. RESULTS: After the combined surgery, the mean DHI testing improved significantly from 71 to 30. Mean audiological monosyllabic speech testing outcome with the cochlea implant was 65% at 65 dB. The residual hearing of 2 patients could be preserved after the surgical procedure. CONCLUSION: The combination of occlusion of the lateral semicircular canal, endolymphatic sac surgery, and CI is an efficient low traumatic treatment for patients with a single-sided MD and moderately severe to complete sensorineural hearing loss.

Upregulation of key factors of viral entry of corona- and influenza viruses upon TLR3-signaling in cells from the respiratory tract and clinical treatment options by 1,8-Cineol.

At the end of the 2019 coronavirus pandemic (COVID-19), highly contagious variants of coronaviruses had emerged. Together with influenza viruses, different variants of the coronavirus currently cause most colds and require appropriate drug treatment. We have investigated the expression of important factors for the replication of these viruses, namely transmembrane protease serine subtype 2 (TMPRSS2), neuropilin1 (NRP1), and angiotensin converting enzyme 2 (ACE2) or tumor necrosis factor-α (TNF-α) after toll like receptor-3 (TLR-3) stimulation using RT-qPCR and flow cytometry (FC) analysis. As model served primary fibroblasts derived from the lung and nasal cavity, as well as epidermal stem cells and fully matured respiratory epithelium. The stimulated cell cultures were treated with pharmaceuticals (Dexamethasone and Enzalutamide) and the outcome was compared with the phytomedicine 1,8-Cineol. The stimulation of TLR3 is sufficient to induce the expression of exactly those targets that were highly expressed in the corresponding culture type, specifically ACE2 and TMPRSS2 in respiratory epithelial stem cells and NRP1 in fibroblast cells. It seems this self-perpetuating cycle of infection-driven upregulation of key viral replication factors by the innate immune system represents an evolutionary advantage for viruses using these transcripts as viral replication factors. Likewise, to the standard pharmaceuticals with proven clinical efficiency, 1,8-Cineol was able to disrupt this self-perpetuating cycle. Considering the minor side effects and negligible pharmacological interactions with other drugs, it is conceivable that an adjuvant or combinatorial therapy with 1,8-Cineol for respiratory diseases caused by corona- or influenza viruses would be beneficial.

Permanent occlusion of the Eustachian tube: a retrospective study on reopening procedures.

PURPOSE: This study retrospectively evaluated the efficacy and versatility of reopening procedures for the permanent occlusion of the cartilaginous Eustachian tube (POET) by analyzing four consecutive cases. METHODS: The study included all patients diagnosed with POET who suffered from Eustachian tube occlusion and glue ear. A combined approach of endoscopic transnasal/transoral laser surgery was utilized to reopen the POET. This was subsequently followed by balloon dilation (BET) and stenting for a duration of six weeks. In one distinct case, the Eustachian tube orifice was approached via a transtympanic method, where a balloon catheter was placed. The primary outcome measures targeted the success rate of reopening, which was quantified using audiological outcomes and Eustachian tube patency verified by a positive Valsalva maneuver. RESULTS: Four patients, with an age range of 14-62 years (mean age of 29.3 years), were subject to Eustachian tube reopening. The duration of follow-up varied between 10 and 24 months, averaging at 16.2 months. Notably, 75% of the surgically treated ears displayed no evidence of glue ear upon their last follow-up and showed restoration of Eustachian tube patency. The procedures were executed without any surgical complications. The causes for POET in these patients were heterogeneous: two were attributed to scarring post adenoidectomy, one to occlusion following orthognathic surgery and the remaining one due to prior radiotherapy treatment for squamous cell carcinoma located at the soft palate. DISCUSSION: Total occlusion of the cartilaginous Eustachian tube may be linked to persistent middle ear diseases. It is imperative to conduct nasopharyngeal endoscopy in these cases. The findings from this study suggest that the Eustachian tube reopening procedure is predominantly effective and safe for patients with POET stemming from a variety of pathologies. Future research should focus on exploring advanced stenting devices and necessitate longer follow-up periods for comprehensive understanding.

[Increase in the natural hearing threshold after treatment with cochlear implants]. / Anstieg der natürlichen Hörschwelle nach Cochleaimplantatversorgung.

More than 5% of the world's population suffers from disabling hearing loss. If the cause of hearing loss is unclear, it is referred to as idiopathic sudden sensorineural hearing loss (ISSNHL). After failure of standard treatment, the use of hearing aids or a cochlear implant is generally recommended. In this case, a 55-year-old patient was treated with cochlear implantation (CI) after ISSNHL and unsuccessful conservative therapy. Approximately 1 year after implantation and 7 years after the sudden hearing loss, subjective measurements revealed restoration of the hearing threshold.

Hit and run oncogeneses in head and neck cancers requires greater investigation.

Head and neck cancers are unique in so far that two major oncogenic viruses, Epstein Barr virus (EBV) and Human papillomavirus (HPV) infect adjacent anatomy and cause nasopharyngeal and oropharyngeal cancers, respectively. Dominant recognized carcinogens are alcohol and tobacco but some head and neck cancers have been found to have mixed carcinogens (including betel leaf, areca nuts, slaked lime, viruses, etc.) involved in their oncogenesis and conversely, groups of patients with unknown or less dominant carcinogens involved in their development. These cancers may have had viral involvement in the past but then lost most of their viral nucleic acids (be they DNA and/or RNA) below a detection threshold, thus rendering them virus-negative. Some of these virus-negative tumors appear to have mutagenic signatures associated with virus-positive cancers,  for example, from the APOBEC defense mechanism which is known to mutate viral nucleic acids as well as cause collateral damage to host DNA, with subsequent development of strongly viral prejudiced mutational signatures. These mechanisms are likely to be less efficient at oncogenesis than traditional EBV and HPV oncogenes directly driving mutagenesis, thus accounting for the smaller frequencies of these cancers found. More profound investigations of these unusual tumors are warranted to dissect out these mechanistic pathways.

Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes.

BACKGROUND: New concepts for a more effective anti-cancer therapy are urgently needed. Experimental flaws represent a major counter player of this development and lead to inaccurate and unreproducible data as well as unsuccessful translation of research approaches into clinics. In a previous study we have created epithelial cell cultures from head and neck squamous cell carcinoma (HNSCC) tissue. METHODS: We characterize primary cell populations isolated from human papillomavirus positive HNSCC tissue for their marker expression by RT-qPCR, flow cytometry, and immunofluorescence staining. Their sensitivity to MDM2-inhibition was measured using cell viability assays. RESULTS: Primary HNSCC cell cultures showed the delayed formation of spheroids at higher passages. These spheroids mimicked the morphology and growth characteristics of other established HNSCC spheroid models. However, expression of epithelial and mesenchymal markers could not be detected in these cells despite the presence of the HNSCC stem cell marker aldehyde dehydrogenase 1 family member A1. Instead, strong expression of B- and T-lymphocytes markers was observed. Flow cytometry analysis revealed a heterogeneous mixture of CD3 + /CD25 + T-lymphocytes and CD19 + B-lymphocytes at a ratio of 4:1 at passage 5 and transformed lymphocytes at late passages (≥ passage 12) with CD45 + CD19 + CD20 + , of which around 10 to 20% were CD3 + CD25 + CD56 + . Interestingly, the whole population was FOXP3-positive indicative of regulatory B-cells (Bregs). Expression of transcripts specific for the Epstein-Barr-virus (EBV) was detected to increase in these spheroid cells along late passages, and this population was vulnerable to MDM2 inhibition. HPV + HNSCC cells but not EBV + lymphocytes were detected to engraft into immunodeficient mice. CONCLUSIONS: In this study we present a primary cell culture of EBV-infected tumor-infiltrating B-lymphocytes, which could be used to study the role of these cells in tumor biology in future research projects. Moreover, by describing the detailed characteristics of these cells, we aim to caution other researchers in the HNSCC field to test for EBV-infected lymphocyte contaminations in primary cell cultures ahead of further experiments. Especially researchers who are interested in TIL-based adopted immunotherapy should exclude these cells in their primary tumor models, e.g. by MDM2-inhibitor treatment. BI-12-derived xenograft tumors represent a suitable model for in vivo targeting studies.

Review of potential medical treatments for middle ear cholesteatoma.

Middle ear cholesteatoma (MEC), is a destructive, and locally invasive lesion in the middle ear driven by inflammation with an annual incidence of 10 per 100,000. Surgical extraction/excision remains the only treatment strategy available and recurrence is high (up to 40%), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review was targeted at connecting the dysregulated inflammatory network of MEC to pathogenesis and identification of pharmaceutical targets. We summarized the numerous basic research endeavors undertaken over the last 30+ years to identify the key targets in the dysregulated inflammatory pathways and judged the level of evidence for a given target if it was generated by in vitro, in vivo or clinical experiments. MEC pathogenesis was found to be connected to cytokines characteristic for Th1, Th17 and M1 cells. In addition, we found that the inflammation created damage associated molecular patterns (DAMPs), which further promoted inflammation. Similar positive feedback loops have already been described for other Th1/Th17 driven inflammatory diseases (arthritis, Crohn's disease or multiple sclerosis). A wide-ranging search for molecular targeted therapies (MTT) led to the discovery of over a hundred clinically approved drugs already applied in precision medicine. Based on exclusion criteria designed to enable fast translation as well as efficacy, we condensed the numerous MTTs down to 13 top drugs. The review should serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history. Video Abstract.

Middle ear cholesteatoma (MEC) is a destructive and locally invasive ulcerated lesion in the middle ear driven by inflammation which occurs in 10 out of 100,000 people annually. Surgical extraction/excision is the only treatment strategy available and recurrence is high (up to 40% after ten years), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review is focused on the connections between inflammation and MEC pathogenesis. These connections can be used as attack points for pharmaceuticals. For this we summarized the results of research undertaken over the last 30 + years. MEC pathogenesis can be described by specific inflammatory dysregulation already known from arthritis, Crohn's disease or multiple sclerosis. A hallmark of this dysregulation are positive feedback loops of the inflammation further amplifying itself in a vicious circle-like manner. We have identified over one hundred drugs which are already used in clinic to treat other inflammatory diseases, and could potentially be repurposed to treat MEC. To improve and expedite clinical success rates, we applied certain criteria based on our literature searches and condensed these drugs down to the 13 top drugs. We hope the review will serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history.

Viral and Clinical Oncology of Head and Neck Cancers.

PURPOSE OF REVIEW: This study assesses the current state of knowledge of head and neck squamous cell carcinomas (HNSCC), which are malignancies arising from the orifices and adjacent mucosae of the aerodigestive tracts. These contiguous anatomical areas are unique in that 2 important human oncoviruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are causally associated with nasopharyngeal and oropharyngeal cancers, respectively. Mortality rates have remained high over the last 4 decades, and insufficient attention paid to the unique viral and clinical oncology of the different subgroups of HNSCC. RECENT FINDINGS: We have compared and contrasted the 2 double-stranded DNA viruses and the relevant molecular oncogenesis of their respective cancers against other head and neck cancers. Tobacco and alcohol ingestion are also reviewed, as regard the genetic progression/mutation accumulation model of carcinogenesis. The importance of stringent stratification when searching for cancer mutations and biomarkers is discussed. Evidence is presented for a dysplastic/pre-invasive cancerous phase for HPV+ oropharyngeal cancers, and analogous with other HPV+ cancers. This raises the possibility of strategies for cancer screening as early diagnosis will undoubtedly save lives. Staging and prognostication have changed to take into account the distinct biological and prognostic pathways for viral+ and viral- cancers. Diagnosis of pre-cancers and early stage cancers will reduce mortality rates. Multi-modal treatment options for HNSCC are reviewed, especially recent developments with immunotherapies and precision medicine strategies. Knowledge integration of the viral and molecular oncogenic pathways with sound planning, hypothesis generation, and clinical trials will continue to provide therapeutic options in the future.

Influence of Intracochlear Air on Experimental Pressure Measurements.

INTRODUCTION: Intracochlear pressure changes have been assumed to play a central role in hearing preservation during cochlear implantation. The pressure in different settings has been evaluated (temporal bones vs. cochlea models) and was found to have advantages and disadvantages. Experimentally, problems have been discussed to influence the results substantially. OBJECTIVE: The aim of the present study was to evaluate the effect of intracochlear air on the measurements in a cochlea model by using a fiber optic pressure sensor. MATERIALS AND METHODS: The experiments were performed in an uncurled 3D printed full cochlea model. A microfiber-optic pressure sensor was inserted, and intracochlear pressures were evaluated under 3 conditions: (1) cochlea model filled to 100% with fluid, (2) cochlea model filled with air, and (3) cochlea model filled to approximately 50% with fluid. Since the cochlea model is transparent, a direct visualization of air under the microscope was possible when performing the insertions. RESULTS: In the first condition, the mean intracochlear pressure at the end of the insertion was 0.044 psi (SD 0.012, 95% CI). In the second setting, the results were similar. In the last scenario, with 50% filling, the mean intracochlear pressure was statistically significantly different with a mean value of 0.074 psi (SD 0.013, 95% CI) (p < 0.0044, ANOVA). Besides this, in the last condition with 50% fluid, a plateau was formed when the fiber optic reached the air portion. CONCLUSION: The results obtained in a 3D printed full cochlea model show the importance of a direct evaluation of air inside the experimental setting. The exclusion of intracochlear air should be an important factor for the choice of the model for intracochlear pressure measurement (temporal bone vs. cochlea model).

Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.

BACKGROUND: Cholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies. METHODS: We isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry. RESULTS: Under standard culture conditions, we detected a tissue-independent higher expression of IL-1ß and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1ß, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation. CONCLUSION: We propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence. Video Abstract.

Mouthrinses against SARS-CoV-2: anti-inflammatory effectivity and a clinical pilot study.

PURPOSE: The scope of this research endeavor was the determination of the applicability of over the counter mouthwash solutions in reducing the viral load in the saliva of COVID-19 patients and hence decreasing their infectivity. Beyond that, new experimental mouthwashes were investigated in terms of a possible positive immune modulation, which might offer an additional opportunity for a positive pharmaceutical effect. METHODS: The effectivity of the mouth washing solution was determined on 34 hospitalized COVID-19 patients by measuring the viral load by RT-qPCR in pharyngeal swabs, which were taken before and after rinsing. The inflammatory modulation thru the experimental solutions was assayed in an in vitro model of virus infected nasopharyngeal epithelium cells. RESULTS: The clinical pilot study demonstrated that the mouth rinsing solution was able to reduce the viral load by about 90% in the saliva of most patients. This reduction was determined to persist for about 6 h. In the experimental solutions, the ingredients dexpanthenol and zinc were able to reduce the expression of proinflammatory cytokines in the cell culture model, while the antiviral response was not altered significantly. CONCLUSION: We recommend the application of mouth wash solutions to COVID-19 patients, since our results indicate a reduction in infectivity and might govern the protection of health care professionals. Further improvement to the over the counter formulation can be made by utilizing zinc and dexpanthenol, as they which might be beneficial for the patients' health.

A novel technique for patulous Eustachian tube augmentation.

OBJECTIVE: To determine the effectiveness of a soft-tissue bulking agent comparing novel approaches of Eustachian tube (ET) augmentation procedures: transpalatinatal Eustachian tube augmentation in local and general anesthesia versus an augmentation with velotraction under general anesthesia. The clinical endpoint was the resolution of symptoms related to unilateral patulous Eustachian tube dysfunction (PETD) requiring no additional revision augmentations. STUDY DESIGN: Combined retrospective clinical chart review. SETTING: Tertiary referral center. METHODS: Patients suffering from PETD underwent one of the following procedures: Group (A) transpalatinatal soft-tissue bulking agent with infiltration/augmentation under local anesthesia in a sitting position, group (B) transpalatinatal soft-tissue bulking agent infiltration/augmentation under general anesthesia in the flat position or group (C) infiltration/transoral augmentation of the ET with velotraction under general anesthesia in a flat position. The requirement to repeat the procedure due to recurrence of any PETD-related symptoms was recorded and retrospectively analyzed. RESULTS: A total of 50 procedures were executed in 50 patients with unilateral PETD. The necessity to perform a second procedure has analyzed a mean of 6 months postoperatively (range: 6-17 months). Compared to the transpalatinatal augmentation in local anesthesia (group A) (100% success rate), the 6-month failure rate was significantly higher for transpalatinatal augmentation under general anesthesia (group B) (80% success rate) and velotraction augmentation under general anesthesia (group C) (67% success rate). Patient cohort with transpalatinatal augmentation under general anesthesia required 20% and augmentation with velotraction under general anesthesia in 33% revision augmentation procedures reviewed at 6 months follow-up (mean follow-up 11.2 months). CONCLUSIONS: Although all different approaches resulted in a reduction of PETD related symptoms, the transpalatinatal ET augmentation in local anesthesia achieved a statistically significant superior clinical improvement. A complete resolution of PETD related symptoms was obtained and required additional procedures. This improvement may be related to the intraoperative "feedback" by the patients in local anesthesia in the sitting position eliminating the necessity for repeated procedures.

Reactive oxygen species in cancer stem cells of head and neck squamous cancer.

One of the greatest challenges in systemic treatment of head and neck squamous cell carcinoma (HNSCC) is a small tumor cell population, namely, cancer stem-like cells (CSC). CSC can regenerate and maintain a heterogenic tumor by their self-renewal capacity. Their potential ability to be more resistant to and survival after chemo- and radiation therapy was also identified. Further studies have shown that reactive oxygen species (ROS) contribute to this CSC-associated resistance. In this review, we focus on the current knowledge of HNSCC-CSC, with regard to ROS as a possible and novel therapeutic approach in targeting CSC.

Stapes Prosthesis Length: One Size Fits All?

BACKGROUND: The insertion of the stapes piston into the vestibule provides the physical basis for a successful stapedotomy. In routine clinical practice, two different ways to handle prosthesis length are performed: (1) an individualized measurement of the stapes prosthesis length or (2) a standard prosthesis length for all cases. OBJECTIVE: The objective of this study was to compare both ways of handling prosthesis length and the effect of these methods on insertional prosthesis depth. MATERIAL AND METHOD: We retrospectively evaluated 39 patients after performing a stapedotomy for radiologically estimated vestibular stapes prosthesis insertion depth. The individual measured length data were hypothetically changed to a standard length of 4.75, 5, 5.25, and 5.5 mm, and the insertion depths were compared. RESULTS: The individually measured prosthesis lengths led to an insertion depth between 0.2 and 1.6 mm (mean 0.74 mm). The ratio of insertion depth/vestibular depth was between 8 and 59.1% (mean 26.6%). The different assumed standard lengths led to different rates of the vestibulum positions and possible bony contacts at the vestibulum floor. CONCLUSION: The individual measurement led to a zero rate of the vestibulum positions of stapes prosthesis pistons with a low insertion depth/vestibular depth ratio.

Comparative Analyses of Tumour Volume Doubling Times for Periocular and Non-periocular Head and Neck Basal Cell Carcinomas.

Basal cell carcinomas are the commonest solid malignancy in humans and thought to grow faster in the periocular region. We measured growth rates between periocular and non-periocular nodular basal cell carcinomas in the head and neck region from high-resolution digital photos and operative notes. The non-periocular basal cell carcinomas (head and neck) showed a mean tumour volume doubling time of 129.8 ± 21.74 (n = 79) days, and the periocular basal cell carcinoma a mean of 177.5 ± 37.21 (n = 47) days. The unpaired t-test with Welch correction showed that this difference was not significant (p = 0.2719). The mean tumour volume doubling time was 147.59 ± 37.75 days for head and neck basal cell carcinomas overall. For the first time, tumour volume doubling times for nodular basal cell carcinomas in the periocular versus non-periocular regions for the head and neck area were analysed, with no significant differences demonstrated. Further, comparison of basal cell carcinoma growth rates with other common solid tumours confirmed that basal cell carcinomas are slow growing malignancies.

Heterogeneity of Head and Neck Squamous Cell Carcinoma Stem Cells.

Current systemic cancer treatment in head and neck squamous cell carcinoma (HNSCC) is moving toward more personalized approaches such as de-escalation protocols human-papilloma-virus dependent HNSCC or application of checkpoint inhibitors. However, these treatments have been challenged by cancer stem cells (CSC), a small population within the bulk tumor, which are leading to treatment failure, tumor recurrence, or metastases. This review will give an overview of the characteristics of HNSCC-CSC. Specifically, the mechanisms by which HNSCC-CSC induce tumor initiation, progression, recurrence, or metastasis will be discussed. Although evidence-based treatment options targeting HNSCC-CSC specifically are still being sought for, they warrant a promise for additional and sustainable treatment options where for HNSCC patients where others have failed.

Cervicofacial and mediastinal emphysema after balloon eustachian tuboplasty (BET): a retrospective multicenter analysis.

PURPOSE: Balloon Eustachian tuboplasty (BET) is a new treatment modality addressing chronic obstructive dysfunction of the Eustachian tube (ET). So far, BET has been deemed a safe procedure under general anesthesia with only minor adverse effects. However, individual cases of postoperative emphysema have been reported. In the present retrospective multicenter analysis we determined the incidence rate of this potentially life threatening complication after BET. METHODS: In total we collected data from 3,670 BET procedures performed on 2,272 patients in four tertiary care ENT departments. RESULTS: Ten cases of postoperative cervicofacial emphysema were documented, whereas only in 3 of them a pneumomediastinum was developed. None of the affected patients developed at any time serious clinical signs or symptoms besides cutaneous crepitations. A complete resolution and recovery of the emphysema occurred in all patients under antibiotic prophylaxis and abstinence from Valsalva maneuver within the first 2-6 postoperative days. CONCLUSIONS: Possible causes for the development of these postinterventional emphysemas are considered to be mucosal injuries of the ET during manipulations for the correct position of the insertion instrument, through a "kinking" of the balloon catheter or even due to the relative rigid catheter itself, although its form is regarded to be atraumatic. The complication rate of postoperative emphysema was 0.27% (95% CI 0.13-0.50%). The above facts in addition to only minor and transient overall complications after BET reported in literature, can label this procedure as a safe treatment with a low risk profile.

Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.

BACKGROUND: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. METHODS: HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival. RESULTS: HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04). CONCLUSIONS: Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.

1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis.

The common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial superinfections, resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential for 1,8-cineole to treat primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates poly(I:C)-induced activity of the antiviral transcription factor interferon regulatory factor 3 (IRF3), while simultaneously reducing proinflammatory nuclear factor (NF)-κB activity in human cell lines, inferior turbinate stem cells (ITSCs) and in ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared with poly(I:C) alone, whereas NF-κB activity was reduced. Accordingly, 1,8-cineole- and poly(I:C) treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared with the poly(I:C) treatment approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with lipopolysaccharide (LPS) and 1,8-cineole compared with the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on proinflammatory NF-κB signalling, and may thus broaden its field of application.