Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies.

TIGIT is an immune checkpoint inhibitor expressed by effector CD4 and CD8 T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with an anti-PD(L)-1 antibody. In the current work, we demonstrate broader TIGIT expression than previously reported in healthy donors and patients with cancer with expression on γδ T cells, particularly in CMV-seropositive donors, and on tumor cells from hematologic malignancies.

Vascular age calculation and equivalent risk factors in HIV-infected patients obtained from the D:A:D risk equation.

Background: Vascular age is a concept that represents the hypothetical age of the cardiovascular system and might be an alternative way of expressing the cardiovascular risk of a patient. The Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) developed a cardiovascular risk equation from a population of HIV-infected patients, incorporating exposure to individual antiretroviral therapy drugs and traditional classic cardiovascular risk factors.

Objectives: The aim of this study was to determine the vascular age calculated from the D:A:D equation, for HIV infected patients.

[Cardiovascular disease and systemic inflammatory diseases].

More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process.

[Vascular risk in endocrine diseases other than diabetes].

Endocrinological diseases directly affect the cardiovascular system. The deleterious effects on cardiovascular function can be direct, and linked to the increase or reduction of circulating hormones. Equally, the adverse effects may be indirect; for example following the rise in blood pressure, increase or redistribution of lean mass, or increased plasma lipoproteins.

Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo.

Regulatory T cells (Tregs) are essential to prevent autoimmunity, but excessive Treg function contributes to cancer progression by inhibiting antitumor immune responses. Tregs exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-β1 (TGF-β1). On the Treg cell surface, TGF-β1 is in an inactive form bound to membrane protein GARP and then activated by an unknown mechanism.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish Society of Internal Medicine.

Background: Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients.

Cardiovascular news 2013/2014.

During 2013 and the first months of 2014, numerous studies have been published in the cardiovascular field. New guidelines have appeared for managing arterial hypertension and reducing cardiovascular risk by lowering cholesterol levels. New data have emerged on the considerable lipid-lowering efficacy of monoclonal antibodies against PCSK-9, in contrast, however, to the clinical trials directed towards raising HDL-cholesterol with nicotinic acid, which have not shown a reduction in the rate of cardiovascular complications.

[Ischaemic heart disease].

In the year 2011, cardiovascular diseases were responsible of 31.2% of total deaths in Spain. The absolute number of cases of acute coronary syndrome in this year will be approximately 115,752 cases (95%CI: 114,822-116,687).

GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.

GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1.

Metabolic syndrome and vascular risk estimation in a Mediterranean non-diabetic population without cardiovascular disease.

Aims: Vascular risk equations are tools used to help prevent cardiovascular events. Our aim was to compare the REGICOR and SCORE equations in a general population and in persons with the metabolic syndrome (MS) according to the criteria of the International Diabetes Federation.

Methods And Results: We calculated the cardiovascular risk with both equations in a random sample of 838 non-diabetic persons aged 40-65years without a history of cardiovascular disease, of whom 251 had the MS.

How to calculate vascular age with the SCORE project scales: a new method of cardiovascular risk evaluation.

Aims: In 2008, a new cardiovascular risk table from the Framingham Heart Study was published, which incorporated the new concept 'vascular age'. The aim of the present study was to determine the vascular age calculated from the two SCORE project scales and to determine the degree of agreement in vascular age between the two scales.

Methods And Results: Vascular age was calculated according to its definition, but using the SCORE scale equations (for low- and high-risk countries) instead of the Framingham equations.

Human neuroblastoma cells with MYCN amplification are selectively resistant to oxidative stress by transcriptionally up-regulating glutamate cysteine ligase.

Neuroblastoma is a sympathetic nervous system tumour whose degree of malignancy, prognosis and therapy resistance has been associated with the amplification of MYCN oncogene. However, the molecular pathway responsible for such resistance is unknown. To contribute addressing this issue, in this study, we have compared the vulnerability of four human neuroblastoma cell lines differentially amplifying MYCN, namely SK-N-BE-2 and IMR-32 (MYCN-amplified cells) and SH-SY5Y and SK-N-SH (MCYN-non-amplified cells), to H(2)O(2)-mediated apoptotic death.

Retinoic acid downregulates Rae1 leading to APC(Cdh1) activation and neuroblastoma SH-SY5Y differentiation.

In neuroblastoma cells, retinoic acid induces cell cycle arrest and differentiation through degradation of the F-box protein, Skp2, and stabilization of cyclin-dependent kinase inhibitor, p27. However, the mechanism responsible for retinoic acid-mediated Skp2 destabilization is unknown. Since Skp2 is degraded by anaphase-promoting complex (APC)(Cdh1), here we studied whether retinoic acid promotes differentiation of human SH-SY5Y neuroblastoma cells by modulating Cdh1.

Effect of population aging on the international organ donation rates and the effectiveness of the donation process.

This study analyzed the effect of population aging on organ donation for transplants in 43 countries and on the effectiveness of the donation process by comparing the results between Spain and the United States. The percentage of the population aged 65 or over accounted for 33% of the difference in the donation rates between the countries and for 91% of the variation in the rates after age adjustment. However, the level of aging of the Spanish (16.

[Cardiovascular risk percentiles avoid overestimation or underestimation of risk calculated by the SCORE risk function].

Background: Cardiovascular risk evaluation is of the utmost importance for treatment of patients with cardiovascular risk factors. There are various scales or equations and they can be adapted to a particular population to try to avoid over or under estimation of risk. We propose risk percentiles as a new method of adapting risk scoring systems to our population.

[Risk percentiles: a new adapted method for evaluating vascular risk. ERVPA study].

Background And Objective: Various cardiovascular scoring systems estimating the risk in the Spanish population are currently used. The aim of our study was to create graphs and charts of populational percentiles to assess the total burden of risk of a population and to place each subject individually in the context of their own population setting by using cardiovascular risk charts.

Subjects And Method: A cross-sectional study of 514 individuals of both sexes from a general population setting was carried out.