Magnesium 2000 postmarket evaluation : Guideline adherence and intraprocedural performance of a sirolimus-eluting resorbable magnesium scaffold

Background The Magmaris bioresorbable magnesium scaffold was successfully tested in in-vitro and in clinical premarket studies. Subsequently the Magmaris postmarket program aimed to review intraprocedural data of at least 2000 patients to assess user preferences, guideline adherence and intraprocedural performance in clinical routine. Methods This international multicentre survey encompasses data from 356 hospitals across 45 countries. As part of the certification for Magmaris implantation, each hospital had to complete consecutive post-market evaluation forms of their first 10 commercial Magmaris patients. Results From June 2016 to May 2018, data on 2018 implantations were collected. Main reasons for selecting Magmaris was patients' life expectancy (67%, n = 1359) and low or not calcified lesions, (67%, n = 1357). Magmaris was successfully deployed in 99% of cases (n = 1995), predilatation was performed in 95% (n = 1922) and post-dilatation in 87% (n = 1756). Physicians rated the overall performance and the pushability as good or very good in 96% of cases (n = 1799). Guide wire friction, trackability, and conformability were rated as good or very good in 94% of cases, and crossability in 93%. The majority of patients were scheduled to receive dual antiplatelet therapy for up to 12 months. Conclusion Generally, implantation guidelines were adhered to and theoretical advantages of the metal scaffold observed in in-vitro tests have translated into practice with good intraprocedural performance outcomes, confirming the controlled roll-out of this novel technology into clinical practice. (C) 2019 The Authors. Published by Elsevier Inc.Peer reviewe

Zero fluoroscopy catheter ablation for atrial fibrillation: a systematic review and meta-analysis

IntroductionCatheter ablation for atrial fibrillation (AF) is the most frequently performed cardiac ablation procedure worldwide. The majority of ablations can now be performed safely with minimal radiation exposure or even without the use of fluoroscopy, thanks to advances in 3-dimensional electroanatomical mapping systems and/or intracardiac echocardiography. The aim of this study was to conduct a meta-analysis to compare the effectiveness of zero fluoroscopy (ZF) versus non-zero fluoroscopy (NZF) strategies for AF ablation procedures.MethodsElectronic databases were searched and systematically reviewed for studies comparing procedural parameters and outcomes of ZF vs. NZF approaches in patients undergoing catheter ablation for AF. We used a random-effects model to derive the mean difference (MD) and risk ratios (RR) with a 95% confidence interval (CI).ResultsOur meta-analysis included seven studies comprising 1,593 patients. The ZF approach was found to be feasible in 95.1% of patients. Compared to the NZF approach, the ZF approach significantly reduced procedure time [mean difference (MD): −9.11 min (95% CI: −12.93 to −5.30 min; p < 0.01)], fluoroscopy time [MD: −5.21 min (95% CI: −5.51 to −4.91 min; p < 0.01)], and fluoroscopy dose [MD: −3.96 mGy (95% CI: −4.27 to −3.64; p < 0.01)]. However, there was no significant difference between the two groups in terms of total ablation time [MD: −104.26 s (95% CI: −183.37 to −25.14; p = 0.12)]. Furthermore, there was no significant difference in the acute [risk ratio (RR): 1.01, 95% CI: 1.00–1.02; p = 0.72] and long-term success rates (RR: 0.96, 95% CI: 0.90–1.03; p = 0.56) between the ZF and NZF methods. The complication rate was 2.76% in the entire study population and did not differ between the groups (RR: 0.94, 95% CI: 0.41–2.15; p = 0.89).ConclusionThe ZF approach is a feasible method for AF ablation procedures. It significantly reduces procedure time and radiation exposure without compromising the acute and long-term success rates or complication rates

Expansions of cytotoxic CD4+CD28− T-cells drive excess cardiovascular mortality in rheumatoid arthritis and other chronic inflammatory conditions and are triggered by CMV infection

A large proportion of cardiovascular pathology results from immune-mediated damage, including systemic inflammation and cellular proliferation, which cause a narrowing of the blood vessels. Expansions of cytotoxic CD4+ T-cells characterized by loss of CD28 (‘CD4+CD28− T-cells’ or ‘CD4+CD28null cells’) are closely associated with cardiovascular disease (CVD), in particular coronary artery damage. Direct involvement of these cells in damaging the vasculature has been demonstrated repeatedly. Moreover, CD4+CD28− T-cells are significantly increased in rheumatoid arthritis (RA) and other autoimmune conditions. It is striking that expansions of this subset beyond 1-2% occur exclusively in CMV-infected people. CMV infection itself is known to increase the severity of autoimmune diseases, in particular RA and has also been linked to increased vascular pathology. A review of the recent literature on immunological changes in cardiovascular disease, RA, and CMV infection provides strong evidence that expansions of cytotoxic CD4+CD28− T-cells in RA and other chronic inflammatory conditions are limited to CMV-infected patients and driven by CMV-infection. They are likely to be responsible for the excess cardiovascular mortality observed in these situations. The CD4+CD28− phenotype convincingly links CMV infection to cardiovascular mortality based on a direct cellular-pathological mechanism rather than epidemiological association

T Cells in Vascular Inflammatory Diseases

Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4(+) T cells termed effector memory T (T-EM cells. This expanded population of T-EM cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, natural killer cells, B cells, and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of T-EM cells is uniquely dependent on the voltage-gated potassium Kv1.3 channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic T-EM cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation

T-cell regulation in Erythema Nodosum Leprosum.

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL

Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4+CD28+ Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly

Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4+ and CD8+ cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4+CD28+ population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4+CD28+ cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4+ cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance

Autoantibodies against matrix metalloproteinase-1 in patients with localized scleroderma

Background: Localized scleroderma (LSc) is characterized by cutaneous fibrosis and various autoantibodies. Objective: To determine the presence or levels of antibodies (Abs) against matrix metalloproteinase (MMP)-1 and their clinical relevance in LSc. Methods: Anti-MMP-1 Ab was examined by ELISA (Enzyme-Linked ImmunoSorbent Assay) and immunoblotting using human recombinant MMP-1. MMP-1 collagenase activity was determined using biotinylated collagen as substrate and the amount of cleaved biotinylated fragments of collagen by MMP-1 was measured by ELISA. Results: LSc patients exhibited significantly elevated IgG anti-MMP-1 Ab levels relative to normal controls at similar level of patients with systemic sclerosis (SSc). However, IgG anti-MMP-1 Ab levels were comparable among the 3 LSc subgroups: morphea, linear scleroderma, and generalized morphea. When absorbance values higher than the mean + 2S.D. of normal controls were considered positive, IgG or IgM anti-MMP-1 Ab was found in 46% and 49% of total LSc patients and SSc patients, respectively. Anti-MMP-1 Ab was detected most frequently in morphea patients (60%), followed by linear scleroderma patients (47%) and then generalized morphea patients (25%). LSc patients positive for IgG anti-MMP-1 Ab had elevated levels of IgG anti-single-stranded DNA Ab, IgG anti-nucleosome Ab, and shorter disease duration relative to those negative. The presence of anti-MMP-1 Ab in LSc patients was confirmed by immunoblotting. IgG isolated from LSc patients\u27 sera positive for IgG anti-MMP-1 Ab by ELISA inhibited MMP-1 collagenase activity. Conclusion: These results suggest that anti-MMP-1 autoantibody is a novel autoantibody in LSc. c 2008 Japanese Society for Investigative Dermatology