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Protein Phosphatases of Pathogenic Bacteria: Function in Structure along with Virulence.
Background Chronic inflammation caused by pathogenic immune response is crucial in the pathogenesis of kidney disease. In particular, T-cell-mediated adaptive immune responses evoke pathogenic immunoinflammatory responses and contribute to kidney injury (KI). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a potent negative regulator of T-cell immune responses, protects against immunoinflammatory diseases of the arteries such as atherosclerosis and abdominal aortic aneurysm. However, the role of this molecule in kidney disease remains undetermined. Methods and Results To examine the effects of CTLA-4 overexpression on angiotensin II (AngII)-induced KI, we induced KI in CTLA-4 transgenic/apolipoprotein E-deficient (CTLA-4-Tg/Apoe-/-) mice or Apoe-/- mice fed a high-cholesterol diet by continuously infusing AngII. Overexpression of CTLA-4 ameliorated the development of AngII-induced KI and fibrosis. Moreover, CTLA-4-Tg/Apoe-/- mice had decreased expression of pro-inflammatory molecules in the kidney. Conclusions CTLA-4 overexpression has a protective effect on AngII-induced KI, and increasing CTLA-4 may be a novel therapeutic strategy to prevent the progression of kidney disease.Background Recently, the left ventricular early inflow-outflow index (LVEIO), calculated by dividing mitral E-wave velocity by the left ventricular outflow velocity time integral, has been proposed as a simple method for evaluating mitral regurgitation (MR). This study determined the optimal LVEIO threshold to assess severe MR with different etiologies and assessed its prognostic value. Methods and Results The records of 18,692 consecutive patients who underwent echocardiography were reviewed. MR was classified into 4 groups Grade 0/1, no, trivial, or mild MR; Grade 2, moderate MR; Grade 3, moderate to severe MR; and Grade 4, severe MR. The mean (±SD) LVEIO of Grades 0/1, 2, 3, and 4 was 3.6±1.4, 6.0±2.5, 7.4±3.1, and 9.5±2.8, respectively. An optimal LVEIO threshold of 5.4 was determined to distinguish moderate to severe or severe MR from non-severe MR (sensitivity 84%, specificity 91%). Kaplan-Meier survival analysis revealed high mortality in the group with LVEIO ≥5.4 (P=0.009, hazard ratio 1.833). This was found only in primary MR when separate analyses were performed according to etiology. MRTX1133 research buy Multivariate analysis revealed that LVEIO was an independent predictor for all-cause death only in primary MR. Conclusions Using appropriate thresholds, LVEIO is a simple and useful method to diagnose severe MR regardless of etiology. LVEIO can also be useful for predicting prognosis in primary MR.Background The clinical frailty scale (CFS) predicts late mortality in patients undergoing transcatheter aortic valve replacement. We evaluated the CFS and other parameters associated with 1-year mortality after balloon aortic valvuloplasty (BAV). Methods and Results Between January 2013 and May 2018, 148 patients with severe aortic stenosis (AS) who underwent BAV at the present hospital were enrolled. We recorded pre-procedural CFS grade, baseline characteristics, echocardiographic, and hemodynamic parameters. To investigate the potential risk to patients before BAV, we evaluated the Society of Thoracic Surgeons (STS) score. After patients who underwent surgical aortic valve replacement, transcatheter aortic valve replacement or repeat BAV were excluded, we investigated 1-year survival. Of 127 patients, 41 (32.3%) died ≤1 year after BAV, 8 of whom (19.5% of all-cause deaths) had cardiac deaths. Higher grade of CFS and STS score significantly correlated with 1-year mortality. Severe frailty and the high operative risk group (CFS ≥7 and STS score ≥8.7%) had an extremely poor prognosis (1-year mortality, 81.2%). Conclusions In this BAV cohort, severe frailty was a predictor of 1-year mortality in elderly patients with severe AS.Background The prognostic factors in Japanese patients with wild-type transthyretin amyloidosis (ATTRwt) have not been elucidated. Methods and Results In this study we retrospectively analyzed the clinical characteristics and outcomes of 47 patients with ATTRwt (mean (±SD) age at diagnosis 80.3±4.6 years; 41 males). Fifteen patients died within 2 years of their diagnosis. Receiver operating characteristic and Kaplan-Meier analyses revealed that the best predictors of 2-year mortality were low serum albumin (≤3.75 g/dL), elevated high-sensitivity cardiac troponin T (hs-cTnT; >0.086 ng/mL), and reduced left ventricular ejection fraction (LVEF; less then 50%). According to the total number of these 3 risk factors, patients were stratified into 4 subgroups low risk (no risk factors; n=15), intermediate-low risk (1 risk factor; n=15), intermediate-high risk (2 risk factors; n=7), and high risk (3 risk factors; n=10). The estimated 2-year survival rate of patients classified as low risk, intermediate-low risk, intermediate-high risk, and high risk was 93%, 80%, 83%, and 11%, respectively (P less then 0.001). Conclusions Low serum albumin, elevated hs-cTnT, and reduced LVEF are associated with a worse prognosis in Japanese patients with ATTRwt. The combination of these factors may be useful for predicting medium-term mortality in patients with ATTRwt.Background Myocardial viability assessment in revascularization of ischemic heart failure remains controversial. This study evaluated the prognostic utility of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in ischemic heart failure. Methods and Results This study retrospectively analyzed subjects with ischemic heart failure and left ventricular ejection fraction (LVEF) ≤35%, who underwent CMR at a single center in 2004-2014 before undergoing coronary artery bypass grafting (CABG) or optimal medical therapy (OMT). Analyses were stratified by treatment. Myocardial segments were deemed non-viable if LGE exceeded 50% wall thickness. Overall and anterior viability were assessed. Outcomes were all-cause mortality, cardiovascular (CV) mortality and major adverse CV events. Among 165 subjects (mean (±SD) age 57.5±8.5 years, 152 males), 79 underwent CABG and 86 received OMT. A greater number of non-viable segments was significantly associated with higher all-cause and CV mortality in the CABG group (adjusted hazard ratios 1.
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