Abstract Aim The main goal of this prospective clinical study was to evaluate the outcome of inlay-retained fixed dental prostheses (FDPs) made from heat-pressed lithium-disilicate glass-ceramic. ...Methods Forty-five FDPs were placed in 42 patients (21 women, mean age 36.1 years and 21 men, mean age 42.0 years). The FDPs replaced 4 premolars and 19 molars in the maxilla and 4 premolars and 18 molars in the mandible. Preparations were performed in accordance with general principles for ceramic inlay restorations. Five of the 45 FDPs were hybrid-retained restorations, i.e. one abutment tooth with an inlay retainer and one with a full crown retainer. All FDPs were pressed in one piece using lithium-disilicate ceramic (IPS e.max Press, Ivoclar Vivadent). The minimum dimensions for the proximal connector were 4 mm in height and 4 mm in width (16 mm2 ) with a minimum occlusal ceramic thickness of 1.5 mm. The surfaces of the inlay retainer were conditioned by etching with hydrofluoric acid 5% and silane application. Standard adhesive luting techniques were performed using a dentin adhesive (Syntac Classic, Ivoclar Vivadent) and a resin composite (Variolink II, Ivoclar Vivadent). Clinical follow-up examinations were performed annually. Results The mean observation periods were 70 months (minimum 4, maximum 123 months). Twenty-seven FDPs (60%) failed during the observation period and had to be replaced. The Kaplan–Meier survival rate for inlay-retained FDPs was 57% after 5 years and 38% after 8 years, while for hybrid-retained FDPs it was 100% after 5 and 60% after 8 years. Conclusions Inlay-retained FDPs made from lithium-disilicate ceramic present a high clinical failure rate and therefore cannot be recommended.
The ctools open-source software package was developed for the scientific analysis of astronomical data from Imaging Air Cherenkov Telescopes (IACTs), such as H.E.S.S., VERITAS, MAGIC, and the future ...Cherenkov Telescope Array (CTA). To date, the software has been mainly tested using simulated CTA data; however, upon the public release of a small set of H.E.S.S. observations of the Crab nebula, MSH 15–52, RX J1713.7–3946, and PKS 2155–304 validation using real data is now possible. We analysed the data of the H.E.S.S. public data release using ctools version 1.6 and compared our results to those published by the H.E.S.S. Collaboration for the respective sources. We developed a parametric background model that satisfactorily describes the expected background rate as a function of reconstructed energy and direction for each observation. We used that model, and tested all analysis methods that are supported by ctools, including novel unbinned and joint or stacked binned analyses of the measured event energies and reconstructed directions, and classical On-Off analysis methods that are comparable to those used by the H.E.S.S. Collaboration. For all analysis methods, we found a good agreement between the ctools results and the H.E.S.S. Collaboration publications considering that they are not always directly comparable due to differences in the datatsets and event processing software. We also performed a joint analysis of H.E.S.S. and Fermi-LAT data of the Crab nebula, illustrating the multi-wavelength capacity of ctools. The joint Crab nebula spectrum is compatible with published literature values within the systematic uncertainties. We conclude that the ctools software is mature for the analysis of data from existing IACTs, as well as from the upcoming CTA.
To investigate αvβ3-integrin-targeted optoacoustic imaging and MRI for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma.
Human BRAF V600E-positive melanoma ...xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1.3 mg/kg/d; binimetinib, 0.6 mg/kg/d, n = 5) or placebo (n = 5), respectively. Optoacoustic imaging was performed on a preclinical system unenhanced and 5 h after i. v. injection of an αvβ3-integrin-targeted fluorescent probe. The αvβ3-integrin-specific tumor signal was derived by spectral unmixing. For morphology-based tumor response assessments, T2w MRI data sets were acquired on a clinical 3 Tesla scanner. The imaging results were validated by multiparametric immunohistochemistry (ß3 -integrin expression, CD31 -microvascular density, Ki-67 -proliferation).
The αvβ3-integrin-specific tumor signal was significantly reduced under therapy, showing a unidirectional decline in all animals (from 7.98±2.22 to 1.67±1.30; p = 0.043). No significant signal change was observed in the control group (from 6.60±6.51 to 3.67±1.93; p = 0.500). Immunohistochemistry revealed a significantly lower integrin expression (ß3: 0.20±0.02 vs. 0.39±0.05; p = 0.008) and microvascular density (CD31: 119±15 vs. 292±49; p = 0.008) in the therapy group. Tumor volumes increased with no significant intergroup difference (therapy: +107±42 mm3; control +112±44mm3, p = 0.841). In vivo blocking studies with αvβ3-integrin antagonist cilengitide confirmed the target specificity of the fluorescent probe.
αvβ3-integrin-targeted optoacoustic imaging allowed for the early non-invasive monitoring of a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma, adding molecular information on tumor receptor status to morphology-based tumor response criteria.
Focal 68Ga-DOTATATE PET lesions within the myocardium of neuroendocrine tumor (NET) patients are observed in clinical practice. We determined the frequency and characteristics of lesions that are ...consistent with cardiac metastasis and assessed the lesion detection rate of conventional imaging.
629 patients who underwent 68Ga-DOTATATE PET-CT at a supraregional comprehensive cancer center on NET were included from a consecutive registry. Inclusion criteria were: (1) focal 68Ga-DOTATATE tracer uptake within the myocardium in more than two sequential PET exams, and (2) contrast-enhanced CT. To determine the diagnostic accuracy of conventional CT imaging, a case-control cohort with a ratio of 1:3 was used. PET and CT were independently analyzed by two blinded readers. Cohen's κ was assessed for interreader agreement. Descriptive statistics were applied for frequencies and characteristics and group comparisons were analyzed using the Fisher's exact test.
The prevalence of myocardial metastases related to the registry was 2.4% (15 of 629 NET patients fulfilling the inclusion criteria), for a total of 21 myocardial 68Ga-DOTATATE foci detected. Myocardial lesions were most frequently located in the left ventricle (43%) and the septum (43%). No patient demonstrated a pericardial effusion. Patients with myocardial metastases did not differ in demographics, tumor grading, disease stage or circulating tumor markers compared to the overall registry (all p > 0.05). Higher Ki67-Indices were observed (p = 0.049) for patients with myocardial metastases. Interreader agreement for PET assessment was excellent (Cohen's κ = 1.0). CT reading showed a sensitivity of 19% (95% confidence interval: 6-43%) at a specificity of 100% (95% confidence interval: 90-100%).
68Ga-DOTATATE PET enables detection of myocardial metastatic lesions in NET patients. In contrast, standard morphologic CT imaging provides very limited sensitivity.
The Cherenkov Telescope Array (CTA) is a future gamma-ray observatory that is planned to significantly improve upon the sensitivity and precision of the current generation of Cherenkov telescopes. ...The observatory will consist of several dozens of telescopes with different sizes and equipped with different types of cameras. Of these, the FlashCam camera system is the first to implement a fully digital signal processing chain which allows for a traceable, configurable trigger scheme and flexible signal reconstruction. As of autumn 2016, a prototype FlashCam camera for the medium-sized telescopes of CTA nears completion. First results of the ongoing system tests demonstrate that the signal chain and the readout system surpass CTA requirements. The stability of the system is shown using long-term temperature cycling.
•A full-scale prototype of the FlashCam Cherenkov camera is in operation.•System level testing and characterisation in a dark room is ongoing.•The performances of the data acquisition and the signal chain have been verified.•The system is stable over long periods and robust against temperature variations.
To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal ...adenocarcinomas in rats with immunohistochemical validation.
Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group) female athymic nude rats (Hsd:RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV, %) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67).
Regorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05).
A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F-FDG-PET validated by immunohistochemistry.
To investigate 68Ga-TRAP-(RGD)3 hybrid imaging for the in vivo monitoring of αvß3-integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer.
Human breast ...cancer (MDA-MB-231) xenografts were implanted orthotopically into the mammary fat pads of n = 25 SCID mice. Transmission/emission scans (53 min to 90 min after i.v. injection of 20 MBq 68Ga-TRAP-(RGD)3) were performed on a dedicated small animal PET before (day 0, baseline) and after (day 7, follow-up) a 1-week therapy with the VEGF antibody bevacizumab or placebo (imaging cohort n = 13; therapy n = 7, control n = 6). The target-to-background ratio (TBR, VOImaxtumor/VOImeanmuscle) served as semiquantitative measure of tumor radiotracer uptake. Unenhanced CT data sets were subsequently acquired for anatomic coregistration and morphology-based tumor response assessments (CT volumetry). The imaging results were validated by multiparametric ex vivo immunohistochemistry (αvß3-integrin, microvascular density-CD31, proliferation-Ki-67, apoptosis-TUNEL) conducted in a dedicated immunohistochemistry cohort (n = 12).
68Ga-TRAP-(RGD)3 binding was significantly reduced under VEGF inhibition and decreased in all bevacizumab-treated animals (ΔTBRfollow-up/baseline: therapy -1.07±0.83, control +0.32±1.01, p = 0.022). No intergroup difference in tumor volume development between day 0 and day 7 was observed (Δvolumetherapy 134±77 μL, Δvolumecontrol 132±56 μL, p = 1.000). Immunohistochemistry revealed a significant reduction of αvß3-integrin expression (308±135 vs. 635±325, p = 0.03), microvascular density (CD31, 168±108 vs. 432±70, p = 0.002), proliferation (Ki-67, 5,195±1,002 vs. 7,574±418, p = 0.004) and significantly higher apoptosis (TUNEL, 14,432±1,974 vs. 3,776±1,378, p = 0.002) in the therapy compared to the control group.
68Ga-TRAP-(RGD)3 hybrid imaging allows for the in vivo assessment of αvß3-integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer.
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