Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation.

PURPOSE: For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCTSECO) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. METHODS: Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCTSECO) of patients with and without implanted electrodes. RESULTS: Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCTSECO with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCTSECO compared to MSCT. CONCLUSION: The combination of fpVCTSECO and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.

[Application areas of medical apps in otolaryngology]. / Anwendungsgebiete medizinischer Apps in der HNO­Heilkunde.

The use of medical apps is becoming increasingly important as it offers new solutions in healthcare. Steadily growing computing and storage capacities in combination with high-precision sensors make smartphones effective tools for medical diagnostics and treatment. The use of this technology offers immense advantages, such as direct availability or independence from opening times. However, it also harbors risks such as unfiltered data storage and transmission. The consulting physician should exercise great care when selecting and recommending apps, particularly since only a few have been certified as medical devices to date. There is a steadily growing range of products on the market for otorhinolaryngology. The scientific evidence and quality of the apps vary widely, but tools exist for their validation by physicians and patients. The present training course is intended to help increase knowledge in this new, rapidly developing area.

Investigation of Cellular Function and DNA Integrity during 2D in vitro Culture of Human Salivary Gland Epithelial Cells.

In vitro culture of human salivary gland epithelial cells (SGEC) is still a challenge. A high quantity and quality of cells are needed for the cultivation of 3D matrices. Furthermore, it is known that DNA damage is supposed to be an important factor involved in carcinogenesis. This study investigates cellular function and DNA integrity of human SGEC during 3 passage steps in 2 groups (group 1: n = 10; group 2: n = 9). Cellular function was analyzed by immunofluorescence, transmission electron microscopy (TEM), and quantitative real-time polymerase chain reaction (qPCR). DNA integrity was tested via the comet assay. Immunohistochemistry and qPCR results showed stable α-amylase and pan-cytokeratin levels; TEM revealed functional cells; and no significant DNA damage could be detected in the comet assay during 3 culture steps. The study shows that not only at cellular but also at DNA level human SGEC can be safely quantified over 3 passages for preclinical tissue engineering without loss of differentiation and function.

Medical Apps in Oto-Rhino-Laryngology. / Medizinische Apps in der HNO-Heilkunde.

The implementation of mobile information and communication technology in the field of health services, e. g. in the form of apps, is becoming increasingly important. Unfortunately, the necessary quality criteria are often mising. Thus, it seems important, that in addition to an app controlling authority highly qualified health care professionals participate in the development of these applications. For reasons of liability, however, the physician must exercise great caution in the selection and recommendation of medical apps, especially considering, that only a few apps are certified as medical devices. There are a large number of medical apps on the market, with only a small proportion being assigned to the field of otorhinolaryngology. The areas of audiology, sleep medicine and allergology are most frequently represented. Althouhgh there is increasing scientific work on this topic in the field of otorhinolaryngology, there is a lack of scientific evidence of contents and results, as is generally the case of medical apps. However, there are other possibilities for users to rate medical apps regarding defined qualitiy criteria such as functionality, scientific integrity, but also data privacy. None of the apps assessed by such a evaluation tool met all the required quality criteria, but the applied instrument helped to better assess the application. However, it was possible to consider the quality criteria in the developmental process of an medical app for the field of otorhinolaryngoglogy. In summary, the present work provide a comprehensive insight into the topic "Apps in Otorhinolaryngology" with the aim to use these modern aids in a beneficial way.

[Mesenchymal stem cells: Cancer promoting effects or tumor suppression - A current overview]. / Mesenchymale Stammzellen: Tumorfördernde oder -hemmende Eigenschaften ­ Ein aktueller Überblick.

The multimodal treatment of cancer deals with cancer cells as well as with the cancer surrounding stroma. This stroma contains non-malignant cells like fibroblasts, immune cells as well as mesenchymal stem cells (MSC). MSC have the ability to migrate towards cancer tissue. In the current literature the impact of MSC on cancer cells is discussed divergently. The majority of the current publications reveal an induction of cancer progression by MSC. Four main processes namely the secretion of soluble factors and cell-cell contact, the transdifferentiation of MSC into carcinoma associated fibroblasts, the improvement of neoangiogenesis and the induction of immune suppression are responsible for cancer progression. This publication gives an overview on the current literature.

Smartphone video nystagmography using convolutional neural networks: ConVNG.

BACKGROUND: Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances. METHODS: A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the "two one-sample t-test" (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation. RESULTS: ConVNG tracking accuracy reached 9-15% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms' precision was inferior to VOG. CONCLUSIONS: ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.

Concept and first Implementation of an intracochlearly navigated Electrode Array for Cochlear Implantation.

Cochlear implants (CI) are an established treatment for people with deafness or severe hearing loss. To restore patients' hearing an electrode array (EA) of the CI is inserted into the cochlea to stimulate the auditory nerve. Thereby, the exact positioning and gentle insertion of the EA is crucial for optimal hearing perception outcome. Currently, only microscopic vision is available for entering the cochlea, but the critical intracochlear process during EA insertion is like a "black box" and the surgeon has to rely on haptic feedback. Methods for visualizing the insertion process during surgery are inaccurate or not suitable for routine use due to radiation exposure. To address this problem, we developed a computer-assisted and image-guided cochlear implantation system with an exact real-time visualization of the EA position during the insertion process. The system is based on an electromagnetic tracking system that measures the position and orientation of a sensor integrated into the tip of a EA prototype and visualizes it in presurgical image data. A first experiment with our system showed that a EA prototype could be inserted into a cochlea of a human temporal bone and placed with an accuracy of [Formula: see text]. A maximum insertion angle of 120° was achieved.

Vestibular Aqueduct Morphology and Meniere's Disease-Development of the "Vestibular Aqueduct Score" by 3D Analysis.

Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.

Precise evaluation of the postoperative cochlear duct length by flat-panel volume computed tomography - Application of secondary reconstructions.

OBJECTIVE: There is still a lack in precise postoperative evaluation of the cochlea because of strong artifacts. This study aimed to improve accuracy of postoperative two-turn (2TL) and cochlear duct length (CDL) measurements by applying flat-panel volume computed tomography (fpVCT), secondary reconstruction (fpVCTSECO) and three-dimensional curved multiplanar reconstruction. METHODS: First, 10 temporal bone specimens with or without electrode were measured in multi-slice computed tomography (MSCT), fpVCT and fpVCTSECO and compared to high-resolution micro-CT scans. Later, pre- and postoperative scans of 10 patients were analyzed in a clinical setting. RESULTS: Concerning 2TL, no statistically significant difference was observed between implanted fpVCTSECO and nonimplanted micro-CT in 10 temporal bone specimens. In contrast, there was a significant discrepancy for CDL (difference: -0.7 mm, P = 0.004). Nevertheless, there were no clinically unacceptable errors (±1.5 mm). These results could be confirmed in a clinical setting. Using fpVCTSECO, CDL was slightly underestimated postoperatively (difference: -0.5 mm, P = 0.002) but without any clinically unacceptable errors. CONCLUSION: fpVCTSECO can be successfully applied for a precise measurement of the cochlear lengths pre- and postoperatively. However, users must be aware of a slight systematic underestimation of CDL postoperatively. These results may help to refine electrode selection and frequency mapping.

Utilization of Smartphone Depth Mapping Cameras for App-Based Grading of Facial Movement Disorders: Development and Feasibility Study.

BACKGROUND: For the classification of facial paresis, various systems of description and evaluation in the form of clinician-graded or software-based scoring systems are available. They serve the purpose of scientific and clinical assessment of the spontaneous course of the disease or monitoring therapeutic interventions. Nevertheless, none have been able to achieve universal acceptance in everyday clinical practice. Hence, a quick and precise tool for assessing the functional status of the facial nerve would be desirable. In this context, the possibilities that the TrueDepth camera of recent iPhone models offer have sparked our interest. OBJECTIVE: This paper describes the utilization of the iPhone's TrueDepth camera via a specially developed app prototype for quick, objective, and reproducible quantification of facial asymmetries. METHODS: After conceptual and user interface design, a native app prototype for iOS was programmed that accesses and processes the data of the TrueDepth camera. Using a special algorithm, a new index for the grading of unilateral facial paresis ranging from 0% to 100% was developed. The algorithm was adapted to the well-established Stennert index by weighting the individual facial regions based on functional and cosmetic aspects. Test measurements with healthy subjects using the app were performed in order to prove the reliability of the system. RESULTS: After the development process, the app prototype had no runtime or buildtime errors and also worked under suboptimal conditions such as different measurement angles, so it met our criteria for a safe and reliable app. The newly defined index expresses the result of the measurements as a generally understandable percentage value for each half of the face. The measurements that correctly rated the facial expressions of healthy individuals as symmetrical in all cases were reproducible and showed no statistically significant intertest variability. CONCLUSIONS: Based on the experience with the app prototype assessing healthy subjects, the use of the TrueDepth camera should have considerable potential for app-based grading of facial movement disorders. The app and its algorithm, which is based on theoretical considerations, should be evaluated in a prospective clinical study and correlated with common facial scores.

Highly precise navigation at the lateral skull base by the combination of flat-panel volume CT and electromagnetic navigation.

This study aimed to evaluate the feasibility and accuracy of electromagnetic navigation at the lateral skull base in combination with flat panel volume computed tomography (fpVCT) datasets. A mastoidectomy and a posterior tympanotomy were performed on 10 samples of fresh frozen temporal bones. For registration, four self-drilling titanium screws were applied as fiducial markers. Multi-slice computed tomography (MSCT; 600 µm), conventional flat panel volume computed tomography (fpVCT; 466 µm), micro-fpVCT (197 µm) and secondary reconstructed fpVCT (100 µM) scans were performed and data were loaded into the navigation system. The resulting fiducial registration error (FRE) was analysed, and control of the navigation accuracy was performed. The registration process was very quick and reliable with the screws as fiducials. Compared to using the MSCT data, the micro-fpVCT data led to significantly lower FRE values, whereas conventional fpVCT and secondary reconstructed fpVCT data had no advantage in terms of accuracy. For all imaging modalities, there was no relevant visual deviation when targeting defined anatomical points with a navigation probe. fpVCT data are very well suited for electromagnetic navigation at the lateral skull base. The use of titanium screws as fiducial markers turned out to be ideal for comparing different imaging methods. A further evaluation of this approach by a clinical trial is required.

Cochlear Duct Length Measurements in Computed Tomography and Magnetic Resonance Imaging Using Newly Developed Techniques.

OBJECTIVE: Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT). STUDY DESIGN: Retrospective data analyses of 42 cochleae. SETTING: Tertiary care medical center. METHODS: Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method. RESULTS: CDL values were significantly shorter in MRI by MPR (d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR (d = 1.67 mm) and ECA (d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI (d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL). CONCLUSION: In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.

Precise Evaluation of the Cochlear Duct Length by Flat-panel Volume Computed Tomography (fpVCT)-Implication of Secondary Reconstructions.

HYPOTHESIS: Flat-panel volume computed tomography (fpVCT) and secondary reconstruction allow for more accurate measurements of two-turn length (2TL), cochlear duct length (CDL), and angular length (AL). BACKGROUND: Cochlear geometry is a controversially debated topic. In the meantime, there are many different studies partly reporting highly divergent values. Our aim is to discuss the differences and to propose a radiological possibility to improve cochlear measurements using 3D-curved multiplanar reconstruction and fpVCT. METHODS: Performing different image modalities and settings, we tried to find a clinically usable option that allows for a high degree of accuracy. Therefore, we tested them against reference values of high-definition micro-computed tomography. RESULTS: Comparison of 99 µm slice thickness secondary reconstruction of fpVCT and reference showed no significant differences for 2TL and CDL (p ≥ 0.05). Accordingly, ICC (intraclass correlation) values were excellent (ICC ≥ 0.75; lower limit of confidence interval [CI] ≥ 0.75; Cronbach's alpha [α] ≥ 0.9). Evaluating AL, there was a significant difference (difference: -17.27°; p = 0.002). The lower limit of the CI of the ICC was unacceptable (ICC = 0.944; lower limit of CI = 0.248; α = 0.990). Regarding the Bland-Altman plots, there were no clinically unacceptable errors, but a systematic underestimation of AL. CONCLUSION: Secondary reconstruction is a suitable tool for producing reliable data that allow the accurate measurement of 2TL and CDL. The option of generating these reconstructions from raw data limits the need for higher radiation doses. Nevertheless, there is an underestimation of AL using secondary reconstructions.

Systematic analysis of button batteries', euro coins', and disk magnets' radiographic characteristics and the implications for the differential diagnosis of round radiopaque foreign bodies in the esophagus.

OBJECTIVES: Button battery (BB) ingestion can cause life-threatening complications such as esophageal perforation, and mediastinitis. Chest radiography is the method of choice to diagnose BB ingestion. Therefore, an adequate interpretation of X-ray imaging by physicians is mandatory. The study aimed to analyze relevant diagnostic aspects of BB X-ray imaging, and retrospective analysis of the imaging of radiopaque foreign bodies. METHODS: All commercially available BBs and different foreign bodies such as euro coins (EC) and disk magnets (DM) were listed according to their sizes and compositions. Furthermore, an X-ray analysis of a test set of BBs, ECs and DMs was performed at angles of 0°, 45°, and 90°. Retrospective assessment of radiological characteristics was performed for patients with a round and radiopaque foreign body in the esophagus RESULTS: Only BBs with a diameter of at least 20 mm had a reliable positive double rim sign at scan angles of 90°, and 45°. The step-off effect was visible in all BBs regardless of the diameter. DMs and ECs presented a homogeneous X-ray weakening at all investigated scan angles. In the retrospective analysis all five cases of BB ingestion showed a double rim sign, all fifteen cases of coin ingestion a homogeneous X-ray weakening. A corrugated margin was detected for 10 cent, 20 cent and 50 cent coins. CONCLUSIONS: BBs with a diameter of at least 20 mm showed, depending on the battery model, a more or less pronounced double rim sign and step-off effect in conventional X-ray imaging. However the double rim sign can be simulated by for example a pot magnet.

Effects of the novel polyphenol conjugate DPP-23 on head and neck squamous cell carcinoma cells in vitro.

Despite partial advances in therapy for patients suffering from head and neck squamous cell carcinomas (HNSCC), prognosis still remains poor with minimal improvement in survival for over the last several decades. Some agents found are known to cause cancer cell death in vitro by promoting cellular reactive oxygen species (ROS) accumulation. This is particularly of interest as some cancer cells are more sensitive to ROS than normal cells. It could be shown that the novel polyphenol conjugate (E)-3-(3',5'-Dimethoxyphenyl)-1-(2'-methoxyphenyl)prop-2-en-1-one (DPP-23) offers antitumor effects by the selective generation of ROS without an indication of toxicity in normal tissues in vitro and in vivo. In order to further evaluate the role of DPP-23 as a potential agent in head and neck oncology, the present study investigated its cytotoxic effects on well-established HNSCC cell lines such as HLaC 78 and FaDu, as well as primary human bone marrow stem cells (hBMSCs) and human peripheral blood lymphocytes in vitro. As DPP-23 is not commercially available, it was synthesized via a 'cold' procedure of the Claisen-Schmidt condensation. Following cell treatment with DPP-23 for 24 h, viability and apoptosis were measured via a MTT assay and the Annexin V-propidium iodide test. The results suggest a dose-dependent cytotoxicity in the tested HNSCC tumor cell lines, as well as in hBMSC and lymphocytes. In contrast to previous findings, these preliminary results indicate that the cytotoxic effects of DPP-23 in benign cells may be notably greater than previously suspected. This may indicate a limitation for in the feasibility, or at least of the systemic application, of DPP-23 for patients with HNSCC.

Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro.

Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems.

Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer.

Activation of receptor tyrosine kinases, such as fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and VEGF receptor (VEGFR), has been implicated in tumor progression and metastasis in human pancreatic cancer. In this study, we investigated the effects of TKI258, a tyrosine kinase inhibitor to FGFR, PDGFR, and VEGFR on pancreatic cancer cell lines (HPAF-II, BxPC-3, MiaPaCa2, and L3.6pl), endothelial cells, and vascular smooth muscle cells (VSMC). Results showed that treatment with TKI258 impaired activation of signaling intermediates in pancreatic cancer cells, endothelial cells, and VSMCs, even upon stimulation with FGF-1, FGF-2, VEGF-A, and PDGF-B. Furthermore, blockade of FGFR/PDGFR/VEGFR reduced survivin expression and improved activity of gemcitabine in MiaPaCa2 pancreatic cancer cells. In addition, motility of cancer cells, endothelial cells, and VSMCs was reduced upon treatment with TKI258. In vivo, therapy with TKI258 led to dose-dependent inhibition of subcutaneous (HPAF-II) and orthotopic (L3.6pl) tumor growth. Immunohistochemical analysis revealed effects on tumor cell proliferation [bromodeoxyuridine (BrdUrd)] and tumor vascularization (CD31). Moreover, lymph node metastases were significantly reduced in the orthotopic tumor model when treatment was initiated early with TKI258 (30 mg/kg/d). In established tumors, TKI258 (30 mg/kg/d) led to significant growth delay and improved survival in subcutaneous and orthotopic models, respectively. These data provide evidence that targeting FGFR/PDFGR/VEGFR with TKI258 may be effective in human pancreatic cancer and warrants further clinical evaluation.