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Institute
- Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen (28) (remove)
Sonstige beteiligte Institutionen
The benefits of cochlear implantation in children with severe hearing impairments are widely known; however, there is no consensus regarding which minimal outcome measurements (MOMs) should be used to determine outcomes in this population with pediatric cochlear implant (CI). Therefore, the authors aim to propose a MOM test battery for pediatric CI recipients that can facilitate international multi-center research and collaboration. A pediatric MOM test battery was developed and agreed-upon by members of the HEARRING group across 30 expert clinics in the field of hearing implantation. The MOM test battery was chosen based on a literature search that focused on outcome measurements applied in clinical trials involving children with a hearing implant. Members of the HEARRING group were then asked to evaluate each of the pediatric MOM tests used. The final pediatric MOM test battery was defined for different chronological age categories (six weeks–18 years) at different suggested test intervals. The test battery includes objective hearing measurements, aided and unaided audiometry, speech perception tests in quiet and in noise, subjective hearing assessments, assessment of language development, and mental and motor development. This study presents a consensus on a MOM test battery for pediatric CI recipients that was agreed upon by members of the HEARRING group. This test battery should allow for international multi-center research to be able to extend and share evidence that will guide future clinical practice and research efforts in pediatric populations with CI.
Purpose
While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.
Methods
Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference.
Results
[18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples.
Conclusion
FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.
Purpose
While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.
Methods
Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference.
Results
[\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples.
Conclusion
FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.
Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.
Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes
(2021)
Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.
Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.
Hintergrund
Die E‑Zigarette erfreut sich in den letzten Jahren zunehmender Beliebtheit. Die Frage nach der Toxizität ist jedoch noch nicht eindeutig geklärt, und es herrscht global Unsicherheit im Umgang mit der E‑Zigarette.
Ziel
Ziel der vorliegenden Arbeit war es, Propylenglykol, ein Hauptbestandteil der Liquide, in Bezug auf mögliche akute Entzündungsreaktionen, zyto- und genotoxische Auswirkungen auf humane Nasenschleimhautzellen zu untersuchen.
Material und Methoden
Die Nasenschleimhautzellen wurden von zehn Probanden im Air-Liquid-Interface kultiviert und anschließend mit unterschiedlichen Konzentrationen des Propylenglykols bedampft. Die Analyse erfolgte mittels Trypanblau-Test, Comet-Assay, Mikrokerntest und IL-6- und IL-8-Sandwich-ELISA.
Ergebnis
Der Trypanblau-Test zeigte keine Reduktion der Vitalität. Im Sandwich-ELISA konnte kein Anstieg der IL-6- und IL-8-Konzentrationen nachgewiesen werden. Im Comet-Assay zeigte das Olive Tail Moment eine Schädigung im Vergleich zur Negativkontrolle in allen untersuchten Konzentrationen. Zudem zeigte sich eine dosisabhängige Schädigung. Im Mikrokerntest konnte ein Unterschied zwischen dem Reinstoff und der Negativkontrolle gefunden werden.
Schlussfolgerung
Es zeigten sich möglicherweise reparable DNS-Schädigungen im Comet-Assay. Im Mikrokerntest konnten diese nur in der Reinstoffkonzentration bestätigt werden. Es sollte ein restriktiver Umgang mit der E‑Zigarette erfolgen, bis insbesondere Langzeitstudien vorliegen. Zudem ist eine eindeutige Deklaration der Inhaltsstoffe der Liquide durch die Hersteller zu fordern, um weitergehende Schädigungspotenziale untersuchen zu können.
Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors
(2021)
Background
The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT.
Methods
Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software.
Results
The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly.
Conclusion
In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.
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.
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.