Detailed cross-sectional study of 60 superficial femoral artery occlusions: morphological quantitative analysis can lead to a new classification.

OBJECTIVE: Current clinical classification of superficial femoral artery (SFA) occlusions as defined by TASC II guidelines is limited to length and calcifications analysis on 2D angiograms, while state-of-the-art cross-sectional imaging like computed tomography angiography (CTA) and magnetic resonance angiography (MRA) provides much more detailed anatomical information than traditional invasive angiography: quantitative morphological analysis of these advanced imaging techniques could therefore be the basis of a refined classification. METHODS AND RESULTS: Forty-six patients (65% men, 68±11.6 years) that underwent lower limb CTA were retrospectively included, totalizing 60 SFA occlusions. Lesions were classified as TASC II stage A in 3% of cases, stage B in 20%, stage C in 2% and stage D in 75%. For each pathological artery, curved multiplanar reconstructions following the occluded SFA course were used to measure the total length and the mean diameter of the occluded segment. Color-coded map provided an accurate estimation of calcifications' volume. Thirty-nine percent of the occlusions were total. Mean occluded segment length was 219±107 mm (range, 14-530 mm); mean occluded segment diameter was 6.1±1.6 mm (range, 3.4-10 mm); mean calcifications' volume in the occluded segment was 1,265±1,893 mm(3) (range, 0-8,815 mm(3)), corresponding to a percentage of 17.4%±20% (range, 0-88.7%). Shrinked occluded occlusions were defined by a mean diameter under 5 mm and heavily calcified occlusions by a mean percentage of calcifications above 4%. Use of these thresholds allowed the distinction of four groups of patients: heavily calcified occlusions with preserved caliber (56%), non-calcified occlusions with preserved caliber (19%), non-calcified occlusions with small caliber (15%) and heavily calcified occlusions with small caliber (10%). CONCLUSIONS: SFA OCCLUSIONS ARE DISPARATE: this simple morphological study points out TASC II classification weaknesses for SFA occlusions, as quantitative cross-sectional imaging analysis with measurement of mean occluded diameter and percentage of calcifications can refine it. This could be particularly useful in the management of TASC II type D lesions, for which new endovascular revascularization techniques are arising, and where a CTA or MRA-based morphological classification could provide support in choosing between them..journal article2014 Aprimporte

COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord

BACKGROUND: While multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are primarily inflammatory and degenerative disorders respectively, there is increasing evidence for shared cellular mechanisms that may affect disease progression, particularly glial responses. Cyclooxygenase 2 (COX-2) inhibition prolongs survival and cannabinoids ameliorate progression of clinical disease in animal models of ALS and MS respectively, but the mechanism is uncertain. Therefore, three key molecules known to be expressed in activated microglial cells/macrophages, COX-2, CB2 and P2X7, which plays a role in inflammatory cascades, were studied in MS and ALS post-mortem human spinal cord. METHODS: Frozen human post mortem spinal cord specimens, controls (n = 12), ALS (n = 9) and MS (n = 19), were available for study by immunocytochemistry and Western blotting, using specific antibodies to COX-2, CB2 and P2X7, and markers of microglial cells/macrophages (CD 68, ferritin). In addition, autoradiography for peripheral benzodiazepine binding sites was performed on some spinal cord sections using [3H] (R)-PK11195, a marker of activated microglial cells/macrophages. Results of immunostaining and Western blotting were quantified by computerized image and optical density analysis respectively. RESULTS: In control spinal cord, few small microglial cells/macrophages-like COX-2-immunoreactive cells, mostly bipolar with short processes, were scattered throughout the tissue, whilst MS and ALS specimens had significantly greater density of such cells with longer processes in affected regions, by image analysis. Inflammatory cell marker CD68-immunoreactivity, [3H] (R)-PK11195 autoradiography, and double-staining against ferritin confirmed increased production of COX-2 by activated microglial cells/macrophages. An expected 70-kDa band was seen by Western blotting which was significantly increased in MS spinal cord. There was good correlation between the COX-2 immunostaining and optical density of the COX-2 70-kDa band in the MS group (r = 0.89, P = 0.0011, n = 10). MS and ALS specimens also had significantly greater density of P2X7 and CB2-immunoreactive microglial cells/macrophages in affected regions. CONCLUSION: It is hypothesized that the known increase of lesion-associated extracellular ATP contributes via P2X7 activation to release IL-1 beta which in turn induces COX-2 and downstream pathogenic mediators. Selective CNS-penetrant COX-2 and P2X7 inhibitors and CB2 specific agonists deserve evaluation in the progression of MS and ALS

Purinergic modulation of microglial cell activation

Microglial cells are resident macrophages in the brain and their activation is an important part of the brain immune response and the pathology of the major CNS diseases. Microglial activation is triggered by pathological signals and is characterized by morphological changes, proliferation, phagocytosis and the secretion of various cytokines and inflammatory mediators, which could be both destructive and protective for the nervous tissue. Purines are one of the most important mediators which regulate different aspects of microglial function. They could be released to the extracellular space from neurons, astrocytes and from the microglia itself, upon physiological neuronal activity and in response to pathological stimuli and cellular damage. Microglial activation is regulated by various subtypes of nucleotide (P2X, P2Y) and adenosine (A1, A2A and A3) receptors, which control ionic conductances, membrane potential, gene transcription, the production of inflammatory mediators and cell survival. Among them, the role of P2X7 receptors is especially well delineated, but P2X4, various P2Y, A1, A2A and A3 receptors also powerfully participate in the microglial response. The pathological role of microglial purine receptors has also been demonstrated in disease models; e.g., in ischemia, sclerosis multiplex and neuropathic pain. Due to their upregulation and selective activation under pathological conditions, they provide new avenues in the treatment of neurodegenerative and neuroinflammatory illnesses

Zenith Bifurcated Iliac Side Branch Device: Mid-term Results and Assessment of Risk Factors for Intraoperative Thrombosis.

The aim of this study is to evaluate the short- and mid-term results of the Zenith bifurcated iliac side branch device (ZBIS) in the treatment of common iliac artery (CIA) aneurysms, and to assess risk factors for intraoperative internal iliac artery (IIA) thrombosis. All patients who underwent endovascular treatment of either an isolated CIA aneurysm or an aortoiliac aneurysm using the ZBIS device in the departments of vascular surgery of Strasbourg (France) and Lausanne (Switzerland) between January 2010 and December 2014 were retrospectively collected. Thirty-one implantations were performed: 30 patients underwent 31 endovascular CIA aneurysm treatments with the ZBIS device. Mean operative time was 188 min. Technical success was obtained in 26 implantations (84%). In 5 implantations (16%), the final angiogram revealed an IIA thrombosis. Thirty-day mortality was 3.2%. Thirty-day morbidity was 13.3%. Mean follow-up was 15 months. Overall survival was 96% at 1 year and 89% at 2 years. In intention-to-treat analysis, primary patency of the internal iliac side branch was 84% at 1 year and 76% at 2 years (5 peroperative IIA occlusions and 1 late occlusion). Freedom from reintervention was 89% at 1 and 2 years. One case of type III endoleak and 2 cases of type II endoleaks were identified. Only type III endoleak required an additional intervention with a covered stent. Aneurysm diameter decreased in 15 implantations (48%) and remained stable in 16 implantations (52%). Clinical, radiological, and peroperative parameters were analyzed to identify risk factor for intraoperative thrombosis of the internal iliac side branch. Notion of intraoperative difficulties (any additional procedure that was not initially planned and increasing the operating time) appeared as a risk factor in multivariate analysis (P < 0.01, standard deviation 1.27, odds ratio 30.6). The main findings of our study is that the procedure can be difficult to perform in particular conditions and can lead to peroperative failure in these cases, highlighting the need for adequate patients screening. When technical success is obtained, outcomes can be considered as satisfactory