Epidemiology, Treatment Patterns, and Cost Analysis of Immune Thrombocytopenia in Spain between 2014 and 2020: A Population-based Study.

 Immune thrombocytopenia (ITP) is characterised by low platelet counts and often leads to bleeding, fatigue, and reduced health-related quality of life.  This observational, retrospective, population-based study using BIG-PAC® database included Spanish paediatric and adult patients with primary ITP diagnosed in primary care and hospitals between 2014 and 2020 (median follow-up: 4 years). Epidemiology, baseline/clinical characteristics, treatment trends, healthcare resources and costs were analysed.

Characteristics of patients with chronic hypoparathyroidism not adequately controlled with conventional treatment and management patterns in Spain.

Background And Objective: The current guidelines on hypoparathyroidism offer a model for treating patients but do not cover real-world situations or patient diversity. Given the lack of data regarding hypoparathyroidism, a Delphi panel was convened in Spain to establish consensus in defining the characteristics of patients with chronic hypoparathyroidism not adequately controlled with conventional treatment, as well as to investigate patterns of management.

Material And Methods: A presentation matrix provided a framework for characterizing inadequately controlled chronic hypoparathyroidism, based on four predefined patient groups: group 1 (normal biochemical levels and the patient feeling well); group 2 (abnormal biochemical levels and the patient feeling well); group 3 (normal biochemical levels and the patient feeling unwell); and group 4 (abnormal biochemical levels and the patient feeling unwell).

Characteristics of patients with chronic hypoparathyroidism not adequately controlled with conventional treatment and management patterns in Spain.

Background And Objective: The current guidelines on hypoparathyroidism offer a model for treating patients but do not cover real-world situations or patient diversity. Given the lack of data regarding hypoparathyroidism, a Delphi panel was convened in Spain to establish consensus in defining the characteristics of patients with chronic hypoparathyroidism not adequately controlled with conventional treatment, as well as to investigate patterns of management.

Material And Methods: A presentation matrix provided a framework for characterizing inadequately controlled chronic hypoparathyroidism, based on 4 predefined patient groups: group 1 (normal biochemical levels and the patient feeling well); group 2 (abnormal biochemical levels and the patient feeling well); group 3 (normal biochemical levels and the patient feeling unwell); and group 4 (abnormal biochemical levels and the patient feeling unwell).

Impaired HDL (High-Density Lipoprotein)-Mediated Macrophage Cholesterol Efflux in Patients With Abdominal Aortic Aneurysm-Brief Report.

Objective- The ability of HDL (high-density lipoprotein) to promote macrophage cholesterol efflux is considered the main HDL cardioprotective function. Abdominal aortic aneurysm (AAA) is usually characterized by cholesterol accumulation and macrophage infiltration in the aortic wall. Here, we aim to evaluate the composition of circulating HDL particles and their potential for promoting macrophage cholesterol efflux in AAA subjects.

Prognostic Values of Inflammatory and Redox Status Biomarkers on the Risk of Major Lower-Extremity Artery Disease in Individuals With Type 2 Diabetes.

Objective: Inflammation and oxidative stress play an important role in the pathogenesis of lower-extremity artery disease (LEAD). We assessed the prognostic values of inflammatory and redox status biomarkers on the risk of LEAD in individuals with type 2 diabetes.

Research Design And Methods: Plasma concentrations of tumor necrosis factor-α receptor 1 (TNFR1), angiopoietin-like 2, ischemia-modified albumin (IMA), fluorescent advanced glycation end products, protein carbonyls, and total reductive capacity of plasma were measured at baseline in the SURDIAGENE (Survie, Diabete de type 2 et Genetique) cohort.

Circulating Concentrations of Redox Biomarkers Do Not Improve the Prediction of Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus.

Background: Despite pathophysiological relevance and promising experimental data, the usefulness of biomarkers of oxidative stress for cardiac risk prediction is unclear. The aim of our study was to investigate the prognostic value of 6 biomarkers exploring different pathways of oxidative stress for predicting adverse cardiovascular outcomes in patients with type 2 diabetes mellitus beyond established risk factors.

Methods And Results: The SURDIAGENE (Survie, Diabete de type 2 et Genetique) prospective cohort study consecutively recruited 1468 patients with type 2 diabetes mellitus.

Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish Men.

Background: Animal models support dietary omega-3 fatty acids protection against abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids, known as omega-3 index, is a valid surrogate for long-term omega-3 intake. We investigated the association between the omega-3 index and the prevalence and progression of AAA.

Factor XII Contact Activation.

Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate.

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm.

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7).

Proteomics and metabolomics in biomarker discovery for cardiovascular diseases: progress and potential.

Introduction: The process of discovering novel biomarkers and potential therapeutic targets may be shortened using proteomic and metabolomic approaches.

Areas Covered: Several complementary strategies, each one presenting different advantages and limitations, may be used with these novel approaches. In vitro studies show how cells involved in cardiovascular disease react, although the phenotype of cultured cells differs to that occurring in vivo.

Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice.

Aims: To study the role of lipocalin-2 (Lcn2) and the effect of Lcn2 blockade via anti-Lcn2 antibody in the development of abdominal aortic aneurysm (AAA).

Methods And Results: Expression mRNA and protein levels of Lcn2 and its human orthologue neutrophil gelatinase-associated lipocalin (NGAL) in aortic wall samples from experimental mouse and human AAA samples, respectively, were analysed by real-time PCR and immunohistochemistry. Experimental AAA was induced by aortic elastase perfusion in wild-type mice (WT) and Lcn2-deficient mice (Lcn2-/-).

A Single In-Vial Dual Extraction Strategy for the Simultaneous Lipidomics and Proteomics Analysis of HDL and LDL Fractions.

A single in-vial dual extraction (IVDE) procedure for the subsequent analysis of lipids and proteins in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions derived from the same biological sample is presented. On the basis of methyl-tert-butyl ether (MTBE) extraction, IVDE leads to the formation of three phases: a protein pellet at the bottom, an aqueous phase with polar compounds, and an ether phase with lipophilic compounds. After sample extraction, performed within a high-performance liquid chromatography vial insert, the ether phase was directly injected for lipid fingerprinting, while the protein pellet, after evaporation of the remaining sample, was used for proteomics analysis.

Paraoxonase-1 overexpression prevents experimental abdominal aortic aneurysm progression.

Abdominal aortic aneurysm (AAA) is a permanent dilation of the aorta due to excessive proteolytic, oxidative and inflammatory injury of the aortic wall. We aimed to identify novel mediators involved in AAA pathophysiology, which could lead to novel therapeutic approaches. For that purpose, plasma from four AAA patients and four controls were analysed by a label-free proteomic approach.

Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis.

To assess the potential association between TRX-1/PRX-1 and NADPH oxidase (Nox) activity in vivo and in vitro, TRX-1/PRX-1 levels were assessed by ELISA in 84 asymptomatic subjects with known phagocytic NADPH oxidase activity and carotid intima-media thickness (IMT). We found a positive correlation between TRX-1/PRX-1 and NADPH oxidase-dependent superoxide production (r=0.48 and 0.

ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression.

Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3-5 cm) vs large AAA] using iTRAQ labelling, high-throughput nano-LC-MS/MS and a novel multi-layered statistical model.

Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis.

Background: Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown.

Label-free proteomic analysis of red blood cell membrane fractions from abdominal aortic aneurysm patients.

Purpose: To test whether red blood cell (RBC) membrane composition is modified in abdominal aortic aneurysms (AAA) patients.

Experimental Design: RBC membrane extracts from AAA patients (aortic diameter >3 cm, n = 7) and control subjects (n = 4) were analyzed by a label-free quantitative MS-based strategy, using spectral count data. Additional validation was performed by western-blot.

The human HDL proteome displays high inter-individual variability and is altered dynamically in response to angioplasty-induced atheroma plaque rupture.

Recent findings support potential roles for HDL in cardiovascular pathophysiology not related to lipid metabolism. We address whether HDL proteome is dynamically altered in atheroma plaque rupture. We used immunoaffinity purification of HDL samples from coronary artery disease patients before and after percutaneous transluminal coronary angioplasty (PTCA), a model of atheroma plaque disruption.

Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms.

Objective: To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA).

Approach And Results: Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry-based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system.

Quantitative proteomics analysis of high-density lipoproteins by stable 18O-isotope labeling.

For the large-scale study of dynamic proteomes, quantitative proteomic approaches based on stable isotope labeling and mass spectrometry (MS) have been developed as a high-throughput, reproducible, and robust alternative to conventional gel-based techniques. In this chapter, we describe in detail a quantitative proteomic strategy based on HDL isolation by affinity chromatography, in-gel trypsin digestion of protein extracts, peptide (18)O labeling, separation by off-gel isoelectric focusing, and peptide analysis on a linear ion trap mass spectrometer, followed by the application of a robust multilayered statistical model. This protocol is of universal applicability and has been successfully applied to the global characterization of the HDL proteome with some specific considerations for this particle, paving the way to the in-depth study of the protein cargo of HDL and its implication in cardiovascular diseases.

Beneficial effects of omega-3 fatty acids in the proteome of high-density lipoprotein proteome.

Background: Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs) have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode.

Erythrocytes, leukocytes and platelets as a source of oxidative stress in chronic vascular diseases: detoxifying mechanisms and potential therapeutic options.

Oxidative stress is involved in the chronic pathological vascular remodelling of both abdominal aortic aneurysm and occlusive atherosclerosis. Red blood cells (RBCs), leukocytes and platelets present in both, aneurysmal intraluminal thrombus and intraplaque haemorraghes, could be involved in the redox imbalance inside diseased arterial tissues. RBCs haemolysis may release the pro-oxidant haemoglobin (Hb), which transfers heme to tissue and low-density lipoproteins.

Cell stress proteins in atherothrombosis.

Cell stress proteins (CSPS) are a large and heterogeneous family of proteins, sharing two main characteristics: their levels and/or location are modified under stress and most of them can exert a chaperon function inside the cells. Nonetheless, they are also involved in the modulation of several mechanisms, both at the intracellular and the extracellular compartments. There are more than 100 proteins belonging to the CSPs family, among them the thioredoxin (TRX) system, which is the focus of the present paper.

Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia.

Objective: Rare mutations in the APOE gene, undetectable with the usual genotyping technique, are responsible for dominant familial dysbetalipoproteinemia (FD) and therefore could be easily misclassified as familial combined hyperlipidemia (FCHL). We aimed to identify APOE mutations associated with dominant combined hyperlipoproteinemia and to establish their frequency in subjects with a clinical diagnosis of FCHL.

Methods And Results: In 279 unrelated subjects with FCHL in whom a functional LDLR mutation was excluded, sequencing of the entire APOE gene detected 9 carriers of a rare mutation: 5 subjects (1.