Single Coronary Artery with Anomalous Rising of the Right Coronary Artery: A Rare Coronary Anomaly Diagnosed by 256-Multidetector Computed Tomography

Herein we report the diagnostic potential of cardiac computed tomography (cCT) to delineate the origin and course of an anomalous right coronary artery (RCA) originating from the midpart of the left anterior descended artery (LAD) in an adult with no other form of congenital heart disease. The patient was referred to our institution due to exertional dyspnea and suspected coronary artery disease. The patient underwent X-ray coronary angiography, and no high grade lesions were observed in the left coronary vessels. In the course of the mid-left-anterior-descending artery (LAD), an anomalous side branch coursing away from the left circumflex coronary artery (LCX) was observed, while a right coronary ostium could not be depicted. cCT confirmed the absence of a right coronary ostium, and the vessel originating from the mid LAD was identified as an anomalous RCA, which coursed anterior of the aorta and the pulmonary trunk

Isolation and Characterization of tumor associated MHC class I and class II peptides in Solid Renal Cell and Cholangiocellular Carcinoma

Die Immuntherapie stellt eine viel versprechende Schlüsseltechnologie in der auf den Patienten individualisierten Krebstherapie dar. Einen möglichen Ansatz liefert die Peptid-basierte Vakzinierungstherapie, deren Grundlage die Erkennung von MHC-gebundenen Epitopen auf Tumorzellen durch cytotoxische T-Zellen ist. Das Ziel dieser Arbeit bestand einerseits darin, neue Tumorassoziierte Antigene (TAA) und deren Peptide zu finden, welche für eine Peptid-basierte Vakzinierungstherapie von Patienten mit Nierenzellkarzinom (RCC) oder Cholangiozellulärem Karzinom (CCC) geeignet sein könnten. Zweitens, wurde die Rolle von MHC-II-Molekülen und –Peptiden im RCC untersucht. Aus insgesamt zwei RCCs und einem CCC konnten 88 MHC-I-Peptide isoliert und charakterisiert werden, wovon 11 Peptide aufgrund ihrer biologischen Wirkung und Eigenschaft ihrer Quellproteine als potentiell tumorassoziiert diskutiert wurden. Insbesondere ein Ubiquitin D (UBD)-Peptid wurde aufgrund seiner zusätzlichen Überexpression im RCC in den Impfcocktail aufgenommen. Aus neun weiteren RCCs wurden Eluate angefertigt, welche für zukünftige massenspektrometrische Analysen zur Verfügung stehen. Erstmals wurden mithilfe des oben genannten methodischen Ansatzes CCC-Gewebe im Rahmen einer Heilstudie untersucht und ein Impfcocktail zusammengestellt. Durch histologische und proteomische Studien am RCC konnte gezeigt werden, dass neben den bekannten MHC-II-exprimierenden Zellen auch die RCC-Tumorzellen zur MHC-II-Überexpression fähig sind. Durch Nachweis von Entzündungszellen (Makrophagen und T-Zellen) in unmittelbarer Nähe zu den MHC-II-exprimierenden Tumorzellen und durch Untersuchung des Expressionsprofils (insbesondere IFN-gamma) ist hier am ehesten von einer durch Tumorinflammation induzierten MHC-II-Überexpression in Tumorzellen auszugehen. Insgesamt konnten durch MS-Spektrenanalyse von drei RCC-Eluaten 60 MHC-II-Peptide isoliert und charakterisiert werden, wovon 6 Peptide aufgrund ihrer biologischen Wirkung und Eigenschaft ihrer Quellproteine als potentiell tumorassoziiert diskutiert wurden. In einer weiteren Studie wurden Primärzellsuspensionen aus intraoperativ entnommenen RCC-Geweben angefertigt, mit dem Ziel, diese in Langzeitkulturen überzuführen. Im Wesentlichen aufgrund von Kontaminationen, Selektionierung von Fibroblasten und spontaner Wachstumseinstellung konnte leider keine stabile Langzeitkultur realisiert werden. Die erzielten Protokolloptimierungen und die gewonnen Erfahrungen liefern eine solide Basis für mögliche zukünftige Studien. Zusammenfassend konnten im Rahmen dieser Arbeit neue Impfpeptide identifiziert werden, welche bereits im Rahmen von kontrollierten klinischen Studien für die Tumor-Vakzinierung verwendet worden sind. Darüber hinaus konnte eine Beziehung zwischen MHC-II-Überexpression in primären RCC-Zellen und den tumorinfiltrierenden Immunzellen gezeigt werden.Immunotherapy represents a key technology in patient individualized cancer therapy. A promising approach is peptide based tumor vaccination, which is fundamentally based on the recognition of MHC restricted Peptides on tumor cells by cytotoxic T cells. Aim of this work was the investigation of new tumor associated antigens (TAA) and their peptides with consecutively application in patients suffering from renal cell carcinoma (RCC) or cholangiocellular carcinoma (CCC). Above, the role of MHC II molecules and their peptides were explored for RCC. Analyzing two RCCs and one CCC, 88 MHC I restricted peptides were isolated and charatarized. 11 peptides were discussed as potential candidates for tumor vaccination due to the biological role of their source proteins. An Ubiqutin D (UBD) peptide especially was identified which was also overexpressed in tumor tissue and was used for clinical vaccination. Eluates of further nine RCC tissue probes were prepared and can be utilized for mass spectrometry analysis in future. For the first time CCC tumor tissue was explored according to the methods described above, and a vaccination cocktail consisting of both MHC I and MHC II UBD peptides was designed for tumor vaccination. Histological and proteomical studies revealed the ability of MHC II overexpression in primary RCC cells. Co-localization of tumor infiltrating immune cells (macrophages and T cells) and expression profile analysis (especially IFN-gamma) insinuating a tumor inflammation induced MHC II overexpression in tumor cells. Mass spectrometry of three RCC eluates supplied 60 MHC II restricted peptides. Six peptides were discussed as potential candidates for tumor vaccination due to the biological role of their source proteins. Above cell suspension from intraoperative removed primary RCC tissue was prepared to achieve long term culture. Mainly contamination, fibroblast selection and spontaneously growth stop impede severely the establishment of stable long term cultures. Nevertheless, protocol development and the practical experience are a solid basis for relative cell culture studies in future. In conclusion, during this work new vaccination peptides were identified and used for clinical application within clinical trials. Furthermore, a relation between MHC II overexpression in primary RCC cells and tumor infiltrating immune cells was demonstrated and new MHC II restricted peptides in RCC tumor tissue were characterized

Image quality and contrast agent exposure in cardiac computed tomography angiography prior to transcatheter aortic valve implantation procedures using different acquisition protocols

Background: ECG-gated cardiac computed tomography angiography (CCTA) has found widespread use for prosthesis sizing before transcatheter aortic valve implantation (TAVI). However, still little data exists on the optimal scan-strategy in such patients. We hypothesized that prospectively triggered CCTA can enable the visualization of aortic valve structures and peripheral arteries with lower radiation and contrast agent exposure in patients considered for TAVI compared to retrospectively gated protocols. Methods: All studies were performed using a 256 multi-detector single source CT (iCT Philips, Best, Netherlands). With the prospective protocol the whole volume from the heart to the iliofemoral arteries scanned using prospective triggering. With the retrospective protocol a first retrospectively gated scan was performed for the heart and the iliofemoral part was subsequently scanned using a second non-triggered scan. Image quality was assessed semi-quantitatively and signal-to-noise- (SNR) and contrast-to-noise-ratios (CNR) were obtained for all scans. Results: Prospective CCTA was performed in 74 and in 34 patients, respectively using non-tailored and BMI adapted scans, whereas retrospective CCTA was performed in 57 patients. Prospective scans required lower contrast agent administration compared to retrospective scans (71 ± 8 mL versus 91 ± 15 mL, p < 0.01) and resulted in lower radiation exposure (26 ± 7mSv for retrospective versus 15 ± 3mSv for non-tailored prospective versus 8 ± 4mSv for BMI-adapted prospective scans, p < 0.01). Visual image quality was better for the evaluation of aortic valve structures and similar for the assessment of iliofemoral anatomy with prospective versus retrospective scans. In addition, contrast density, SNR and CNR were higher in the ascending aorta with prospective versus retrospective CCTA (434 ± 98HU versus 349 ± 112HU; 35 ± 14 versus 24 ± 9 and 31 ± 11 versus 16 ± 7, p < 0.001 for all). Subsection analysis by heart rate groups demonstrated that both image quality and CNR were significantly higher in patients with prospective versus retrospective CCTA, irrespective of the heart rate during image acquisition. Conclusion: Prospectively triggered CCTA allows for improved visualization of aortic valve structures and peripheral arteries in patients scheduled for TAVI with simultaneously reduced contrast agent dose and radiation exposure. Therefore, this acquisition mode seems to be the preferred for the evaluation of patients considered for TAVI. Keywords: Cardiac computed tomography TAVI, Image quality, Radiation exposure, SNR, CN

HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease.

OBJECTIVES: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD). DESIGN: HMGB1, high sensitive troponin T (hsTnT) and high sensitive C-reactive protein (hsCRP) were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA). Using CCTA, we assessed 1) coronary calcification, 2) non-calcified plaque burden and 3) the presence of vascular remodeling in areas of non-calcified plaques. RESULTS: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively). By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively), whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07). By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively) was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. CONCLUSIONS: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque