Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients. Tissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median </≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate. A high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004). Only in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC.

Granulocyte-colony stimulating factor (G-CSF)/nicotinamide phosphoribosyltransferase (NAMPT) signaling has been shown to be crucial for the modulation of neutrophil development and functionality. As this signaling pathway is significantly suppressed by type I interferons (IFNs), we aimed to study how the regulation of neutrophil differentiation and phenotype is altered in IFN-deficient mice during granulopoiesis. The composition of bone marrow granulocyte progenitors and their Nampt expression were assessed in bone marrow of type I IFN receptor knockout (Ifnar1^-/-) mice and compared to wild-type animals. The impact of NAMPT inhibition on the proliferation, survival, and differentiation of murine bone marrow progenitors, as well as of murine 32D and human HL-60 neutrophil-like cell lines, was estimated. The progressive increase of Nampt expression during neutrophil progenitor maturation could be observed, and it was more prominent in IFN-deficient animals. Altered composition of bone marrow progenitors in these mice correlated with the dysregulation of apoptosis and altered differentiation of these cells. We observed that NAMPT is vitally important for survival of early progenitors, while at later stages it delays the differentiation of neutrophils, with moderate effect on their survival. This study shows that IFN-deficiency leads to the elevated NAMPT expression in the bone marrow, which in turn modulates neutrophil development and differentiation, even in the absence of tumor-derived stimuli.

The capability of Pseudomonas aeruginosa and Staphylococcus aureus to form biofilm on varying CI component materials differs in the presence and absence of bioactive glass (BAG). The application of BAG induces significant changes in biofilm morphology which can be visualized via scanning electron microscopy (SEM). Bacterial biofilm formation on medical devices, such as cochlear implants (CI), can lead to chronic infections. Interestingly, BAG of type S53P4 seems to be a promising tool for use in the reduction of biofilm development. Primarily, four bacterial species known to cause implant-related infections, P.aeruginosa (ATCC9027), S. aureus (ATCC6538), Staphylococcus epidermidis (ATCC12228) and Streptococcus pyogenes (ATCC19615) were analyzed regarding their capacity to form biofilm on CI components manufactured from three kinds of material: silicone, platinum and titanium. Subsequently, P. aeruginosa and S. aureus biofilms were visualized using scanning electron microscopy, comparing BAG-treated biofilm with non-treated biofilm. The four bacterial species presented biofilm-forming capabilities in a species and surface dependent manner. Metal CI components allowed for the greatest proliferation of biofilm. S. aureus and P. aeruginosa showed the highest rate of biofilm formation on polystyrene surfaces. For both species, SEM revealed altered biofilm morphology after treatment of S53P4 BAG. This study indicates that bacterial biofilm formation and structure on CI components is dependent on the surface composition, altering between metal and silicone surfaces. After application of BAG, changes in biofilm morphology on CI components were observed. These data highlight the impact of BAG on bacterial biofilm morphology.

Hypothesis: Biofilm formation on cochlear implant (CI) surfaces differs between bacterial species and can be reduced by the application of S53P4 bioactive glass. Background: The formation of bacterial biofilms on medical devices, such as cochlear implants, can lead to chronic infections resulting in the need for implant removal. In this study, various surfaces of three CI implant kits from different manufacturers were examined for bacterial biofilm formation and reduction of a pre-existing biofilm by the application of bioactive glass. Methods: Biofilm formations of 4 bacterial species causing implant-related infections were tested on 17 different surfaces: Pseudomonas aeruginosa (ATCC9027), Staphylococcus aureus (ATCC6538), Staphylococcus epidermidis (ATCC12228), and Streptococcus pyogenes (ATCC19615). For P. aeruginosa and S. aureus biofilm reduction after application of S53P4 bioactive glass was evaluated. Results: All tested microbial species formed biofilms on the examined CI surfaces in a strain-dependent manner. For S. aureus, a significantly higher biofilm formation on metal components compared with silicone was found whereas the other strains did not show a material specific biofilm formation. Application of S53P4 bioactive glass resulted in a significant reduction of P. aeruginosa and S. aureus mature biofilm. Conclusion: The four bacteria species displayed biofilm formation on the CI surfaces in a species- and material-specific manner. The results show that bioactive glass can reduce biofilm formation on CI materials in vitro. Future studies are necessary to confirm the results in vivo.

Introduction: Real-time visualization of intraoperative electrocochleography (ECochG) potentials via a digital microscope during cochlear implantation can provide direct feedback during electrode insertion. The aim of this prospective, randomized study of 50 patients was to obtain long-term data with a focus on residual hearing preservation and speech understanding. Material and methods: Cochlear implantations were performed in 50 patients (26 female, 24 male) with residual hearing using a digital microscope. Patients were randomized into two groups. Intraoperative ECochG potentials were either displayed directly in the surgeon’s field of view (picture-in-picture display, PiP) or not directly in the field of view (without picture-in-picture display, without PiP). Residual hearing preservation and speech comprehension were recorded within a 1-year follow-up period, compared between groups (PiP versus without PiP) and to a control group of 26 patients implanted without ECochG. Results: Mean insertion time was significantly longer in the picture-in-picture group (p = 0.025). Residual hearing preservation after 6 weeks at 250 Hz was significantly better in the picture-in-picture group (p = 0.017). After one year, 76% of patients showed residual hearing in the picture-in-picture group (62% without picture-in-picture technique, p = n.s.). Use of the picture-in-picture technique resulted in better long-term pure tone residual hearing preservation at 250, 500, and 1000 Hz. Speech intelligibility improved by 46% in the picture-in-picture group (38% without picture-in-picture). Discussion: This study is the first to describe long-term results in a large cohort of cochlear implant patients in whom digital visualization of intraoperative ECochG was used. Our results show that visualization of intraoperative ECochG has a positive effect on residual hearing preservation.