Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) primarily affecting the aorta and its major branches, mainly differentiated by the onset age (>50 years GCA and <40 years TA). In addition, temporal artery involvement and polymyalgia rheumatica are typical features of GCA, but not TA. Imaging techniques are required to secure the diagnosis of large-vessel vasculitides, and to monitor the disease course. Both morphological and metabolic imaging are involved. Morphological imaging is represented mainly by computerized tomography (CT), CT angiography, magnetic resonance (MR), MR angiography, color-Doppler sonography (CDS) and high-resolution CDS. Metabolic aspects of inflammatory process in LVV can be well studied by positron emission tomography/computed tomography with [18F]deoxyglucose ([18F]FDG PET/CT). It has an important increasing role in diagnosis, extent assessment and disease activity and therapy response evaluation. In the near future the concomitant development of increasingly powerful PET/CT scanners, of new radiopharmaceuticals more specific for inflammation, and of new PET/MRI hybrid scanners probably will lead to a further new step forward in the diagnosis and clinical management of LVV.
Abstract Purpose: Early response to ABVD, assessed with interim FDG-PET (iPET), is prognostic for classical Hodgkin lymphoma (cHL) and supports the use of response adapted therapy. The aim of this study was to identify a gene-expression profile on diagnostic biopsy to predict iPET positivity (iPET+). Experimental Design: Consecutive untreated patients with stage I–IV cHL who underwent iPET after two cycles of ABVD were identified. Expression of 770 immune-related genes was analyzed by digital expression profiling (NanoString Technology). iPET was centrally reviewed according to the five-point Deauville scale (DS 1-5). An iPET+ predictive model was derived by multivariate regression analysis and assessed in a validation set identified using the same inclusion criteria. Results: A training set of 121 and a validation set of 117 patients were identified, with 23 iPET+ cases in each group. Sixty-three (52.1%), 19 (15.7%), and 39 (32.2%) patients had stage I–II, III, and IV, respectively. Diagnostic biopsy of iPET+ cHLs showed transcriptional profile distinct from iPET−. Thirteen genes were stringently associated with iPET+. This signature comprises two functionally stromal-related nodes. Lymphocytes/monocytes ratio (LMR) was also associated to iPET+. In the training cohort a 5-gene/LMR integrated score predicted iPET+ [AUC, 0.88; 95% confidence interval (CI), 0.80–0.96]. The score achieved a 100% sensitivity to identify DS5 cases. Model performance was confirmed in the validation set (AUC, 0.68; 95% CI, 0.52–0.84). Finally, iPET score was higher in patients with event versus those without. Conclusions: In cHL, iPET is associated with a genetic signature and can be predicted by applying an integrated gene-based model on the diagnostic biopsy.
To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV).Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described.Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity.Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.
The ability of second-generation YBCO coated conductor (CC) tapes to transport high current densities at high temperature, i.e., up to 77 K, and at very high magnetic fields, i.e., above 20 T, are pushing the use of these tapes in various applications, from magnet to power system technologies. An accurate study of their quench behavior is mandatory for the design and safe use of cables and magnets manufactured with this ceramic superconducting material. A new 2-D finite-element method (FEM) numerical quench model, which is called anisotropic model of YBCO CCs, was built for this purpose in the COMSOL Multiphysics environment. One of the most difficult issues in the modeling of the YBCO tapes with the FEM is their high aspect ratio due to the very small thickness of the YBCO layer, about 1 μm. In the model developed, the problem of the high aspect ratio of the tape is tackled by multiplying the tape thickness by a constant factor and then compensating the heat and electrical balance equations through the introduction of material anisotropic properties. The FEM model is validated by comparison with literature experimental data on minimum quench energy and normal zone propagation velocity.
SUMMARY Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.
