Purpose: In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [¹⁸F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [¹⁸F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer’s tonsillar ring, the novel PET tracer [⁶⁸Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. Methods: Eight patients with suspicion of a malignant tumor in Waldeyer’s tonsillar ring or a CUP syndrome were examined. PET/CT scans with [¹⁸F]-FDG and [⁶⁸Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. Results: Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [¹⁸F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [⁶⁸Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUV_max for the primary tumors was 21.29 ± 7.97 for ¹⁸F-FDG and 16.06 ± 6.29 for ⁶⁸Ga-FAPI, respectively (p = 0.2). The mean SUV_max for the healthy contralateral tonsils was 8.38 ± 2.45 for [¹⁸F]FDG and 3.55 ± 0.47 for [⁶⁸Ga]FAPI (p < 0.001). The SUV_max ratio of [⁶⁸Ga]FAPI was significantly different from [¹⁸F] FDG (p = 0.03). Mean TBR_max for the [⁶⁸Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [¹⁸F]FDG (10.90 vs. 4.11). Conclusion: Non-invasive imaging of FAP expression by [⁶⁸Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [¹⁸F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [⁶⁸Ga]FAPI PET/CT imaging.

Background: The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea. Methods: Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Results: Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusions: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Trial registration: The Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.

Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.

Objective: To examine the long-term results of an active middle-ear implant (AMEI) with floating-mass transducer (FMT) technology. Study Design: Prospective cohort study of German-speaking patients implanted with an AMEI between 2006 and 2013. Setting: Single-center study. Patients: Eighty-three patients. Intervention: AMEI with FMT technology implantation. Main Outcome Measures: Long-term outcome (27 mo; range, 12–84 mo) for FMT position in correlation with pure-tone audiometry, auditory thresholds for frequency-modulated (warble) tones, vibroplasty thresholds for pure tones, and speech audiometry in quiet and noise. Results: In 15.6% of patients, a revision surgery was necessary to improve functional performance of the AMEI, and the highest revision rate was found with FMT coupling to the round window not using couplers. A peak number of revision surgeries were observed 3 years after the initial surgery. Stable audiological results (pure-tone audiometry and speech audiometry in quiet and noise) were observed up to 84-month post-surgery. Incus vibroplasty (classic indication) showed a significantly lower functional gain compared with oval and round window vibroplasty. Vibroplasty in combined or conductive hearing loss showed no functional difference between forward and reverse stimulation of the cochlea; however, significantly lower vibroplasty thresholds were detected when using a coupler. Conclusions: The AMEI with FMT technology can be safely used in treatment of patients with mild-to-severe sensorineural, conductive, or mixed hearing loss. Optimized coupling, especially in incus vibroplasty, has to be developed to achieve enhanced audiological results.

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, which were determined via post-operative high-resolution flat panel volume computer tomography and clinical fitting software. The outcome measures were speech understanding in quiet and noise and self-perceived sound quality with the CBF map and with the ABF map. Participants were 10 experienced bilateral CI users. The ABF map provided better speech understanding in quiet and noisy environments compared to the CBF map. Additionally, two approaches of reducing the frequency-to-place mismatch revealed that participants are more likely to accept the ABF map if their electrode array is inserted deep enough to stimulate the apical region of their cochlea. This suggests an Angular Insertion Depth of the most apical contact of around 720°–620°. Participants had better speech understanding in quiet and noise with the ABF map. The maps’ self-perceived sound quality was similar. ABF mapping may be an effective tool for compensating the frequency-to-place mismatch in experienced bilateral CI users.