A systematic review of infected descending thoracic aortic grafts and endografts

Objective: The objective of this study was to collect and critically analyze the current evidence on the modalities and results of treatment of descending thoracic aortic surgical graft (SG) and endograft (EG) infection, which represents a rare but dramatic complication after both surgical and endovascular aortic repair. Methods: A comprehensive electronic health database search (PubMed/MEDLINE, Scopus, Google Scholar, and the Cochrane Library) identified all articles that were published up to October 2017 reporting on thoracic aortic SG or EG infection. Observational studies, multicenter reports, single-center series and case reports, case-control studies, and guidelines were considered eligible if reporting specific results of treatment of descending thoracic aortic SG or EG infection. Comparisons of patients presenting with SG or EG infection and between invasive and conservative treatment were performed. Odds ratio (OR) meta-analyses were run when comparative data were available. Results: Forty-three studies reporting on 233 patients with infected SG (49) or EG (184) were included. Four were multicenter studies including 107 patients, all with EG infection, associated with a fistula in 91% of cases, with a reported overall survival at 2 years of 16% to 39%. The remaining 39 single-center studies included 49 patients with SG infection and 77 with EG infection. Association with aortoesophageal fistula was significantly more common with EG (60% vs 31%; P = .01). In addition, time interval from index procedure to infection was significantly shorter with EG (17 +/- 21 months vs 32 +/- 61 months; P = .03). Meta-analysis showed a trend of increased 1-year mortality in patients with SG infection compared with EG infection (pooled OR, 3.6; 95% confidence interval, 0.9-14.7; P = .073). Surgical management with infected graft explantation was associated with a trend toward lower 1-year mortality compared with graft preservation (pooled OR, 0.3; 95% confidence interval, 0.1-1.0; P = .056). Conclusions: Thoracic aortic EG infection is likely to occur more frequently in association with aortoesophageal fistulas and in a shorter time compared with SG infection. Survival is poor in both groups, especially in patients with SG infection. Surgical treatment with graft explantation seems to be the preferable choice in fit patients

Intracellular cross talk and physical interaction between two classes of neurotransmitter-gated channels

Fast chemical communications in the nervous system are mediated by several classes of receptor channels believed to be independent functionally and physically. We show here that concurrent activation of P2X 2 ATP-gated channels and 5-HT 3 serotonin-gated channels leads to functional interaction and nonadditive currents (47-73% of the predicted sum) in mammalian myenteric neurons as well as in Xenopus oocytes or transfected human embryonic kidney (HEK) 293 cell heterologous systems. We also show that these two cation channels coimmunoprecipitate constitutively and are associated in clusters. In heterologous systems, the inhibitory cross talk between P2X 2 and 5-HT 3 receptors is disrupted when the intracellular C-terminal domain of the P2X 2 receptor subunit is deleted and when minigenes coding for P2X 2 or 5-HT 3 A receptor subunit cytoplasmic domains are overexpressed. Injection of fusion proteins containing the C-terminal domain of P2X 2 receptors in myenteric neurons also disrupts the functional interaction between native P2X 2 and 5-HT 3 receptors. Therefore, activity-dependent intracellular coupling of distinct receptor channels underlies ionotropic cross talks that may significantly contribute to the regulation of neuronal excitability and synaptic plasticity

Editor's Choice \u2013 Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)

2017 Clinical Practice Guidelines of the European Society for Vascular Surgery

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

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease

info:eu-repo/semantics/publishedVersio

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

The Effects of Apelin on the Electrical Activity of Hypothalamic Magnocellular Vasopressin and Oxytocin Neurons and Somatodendritic Peptide Release

Apelin, a novel peptide originally isolated from bovine stomach tissue extracts, is widely but selectively distributed throughout the nervous system. Vasopressin and oxytocin are synthesised in the magnocellular neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN), which are apelin-rich regions in the central nervous system. We made extracellular electrophysiological recordings from the transpharyngeally exposed SON of urethane-anaesthetised rats to assess the role of apelin in the control of the firing activity of identified magnocellular vasopressin and oxytocin neurons in vivo. Apelin-13 administration onto SON neurons via microdialysis revealed cell-specific responses; apelin-13 increased the firing rates of vasopressin cells, but had no effect on the firing rate of oxytocin neurons. A direct excitatory effect of apelin-13 on vasopressin cell activity is also supported by our in vitro studies showing depolarisation of membrane potential and increase in action potential firing. To assess the effects of apelin-13 on somato/dendritic peptide release we used in vitro release studies from SON explants in combination with highly sensitive and specific radioimmunoassays. Apelin-13 decrease basal (by 78%, p<0.05, n=6) and potassium-stimulated (by 57%, p<0.05, n=6) vasopressin release but had no effect on somato/dendritic oxytocin release. Taken together, our data suggest a local autocrine feedback action of apelin on magnocellular vasopressin neurons. Furthermore, these data show a marked dissociation between axonal and dendritic vasopressin release with a decrease in somato/dendritic release but an increase in electrical activity at the cell bodies, indicating that release from these two compartments can be regulated wholly independently