Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.

The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.

Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes.

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.

Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.

KEY POINTS: T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Circulating myeloid-derived suppressor cells may be a useful biomarker in the follow-up of unvaccinated COVID-19 patients after hospitalization.

SARS-CoV-2 infection is the cause of the disease named COVID-19, a major public health challenge worldwide. Differences in the severity, complications and outcomes of the COVID-19 are intriguing and, patients with similar baseline clinical conditions may have very different evolution. Myeloid-derived suppressor cells (MDSCs) have been previously found to be recruited by the SARS-CoV-2 infection and may be a marker of clinical evolution in these patients. We have studied 90 consecutive patients admitted in the hospital before the vaccination program started in the general population, to measure MDSCs and lymphocyte subpopulations at admission and one week after to assess the possible association with unfavorable outcomes (dead or Intensive Care Unit admission). We analyzed MDSCs and lymphocyte subpopulations by flow cytometry. In the 72 patients discharged from the hospital, there were significant decreases in the monocytic and total MDSC populations measured in peripheral blood after one week but, most importantly, the number of MDSCs (total and both monocytic and granulocytic subsets) were much higher in the 18 patients with unfavorable outcome. In conclusion, the number of circulating MDSCs may be a good marker of evolution in the follow-up of unvaccinated patients admitted in the hospital with the diagnosis of COVID-19.

Study of the diagnostic efficiency of anti-ZnT8 autoantibodies for type 1 diabetes in pediatric patients.

OBJECTIVE: Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. METHODS: A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. RESULTS: Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. CONCLUSION: The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.

Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles / Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos españoles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio (AU)

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports (AU)

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69, ≥70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles / Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos españoles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio. (AU)

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports. (AU)

Expression of nutrient transporters in placentas affected by gestational diabetes: role of leptin.

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab.

BACKGROUND: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of anti-drug antibodies that reduce their effectiveness. The HLA-DQA1*05 allele has been shown to increase the risk of immunogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully investigated for newer biotherapies. OBJECTIVE: whether the presence of the HLA-DQA1*05 allele is associated with a reduction of response to ustekinumab and vedolizumab was investigated. MATERIAL AND METHODS: the impact of HLA-DQA1*05 on disease activity in 93 patients with IBD, treated with ustekinumab (n = 39) or vedolizumab (n = 54) was investigated in a retrospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn's disease) and Mayo score (ulcerative colitis). RESULTS: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedolizumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treatment groups. CONCLUSIONS: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab.

The Smallpox Vaccine in Latin America: A New Approach (1801-1804).

The Royal Philanthropic Vaccine Expedition is considered in the history of medicine as the first international health expedition aimed at the global elimination of a contagious disease: smallpox. However, the initiatives carried out in this way before the arrival of the Balmis Expedition, by surgeons from the Spanish Navy, are less well known. Thus, the main objective of this research work is to offer an overview of the different anti-variolic vaccination initiatives prior to the campaign financed by the Spanish crown from these health facilities. Using the heuristic and hermeneutic method, our article is based on primary sources contrasted with specialised literature. The results obtained are presented in a narrative style from each of the surgeons identified as decisive in the implementation of the vaccine, thus providing a divergent and unpublished historiographic approach. As the facts described show, before the arrival of Balmis the vaccine substance was introduced in those countries thanks to the initiative of various surgeons: in Puerto Rico by Francisco Oller; in Cartagena and Santa Marta in Colombia by Ángel Hidalgo; in Venezuela by Alonso Ruiz; in Cuba by Tomás Romay and Bernardo de Cózar; in the Viceroyalty of New Granada (Colombia) by Lorenzo Vergés; in Guatemala by Miguel José Monzón and José María Ledesma; in the Viceroyalty of New Spain by Alejandro García Arboleya and Antonio Serrano; in Peru by Pedro Belomo; in Río de la Plata by Cristóbal Martín de Montúfar; in the Chilean region of Coquimbo by José María Gómez; and in the Philippines by Cristóbal Regidor. Finally, it should be noted that these surgeons and the approach presented are part of a historiography based on the personal actions of professionals trained, for the most part, at the Medical-Surgical School of Cadiz.

Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles / Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos españoles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio.(AU)

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.(AU)

Human amniotic epithelial stem cells: Hepatic differentiation and regenerative properties in liver disease treatment.

The placenta and the extraembryonic tissues represent a valuable source of cells for regenerative medicine. In particular, the amniotic membrane possesses cells with stem cells characteristics that have attracted research attention. Human amniotic epithelial cells (hAECs) have unique and desirable features that position them over other stem cells, not only because of the unlimited potential supplied of, the easy access to placental tissues, and the minimal ethical and legal barriers associated, but also due to the embryonic stem cells markers expression and their ability to differentiate into the three germ layers. In addition, they are non-tumorigenic and have immunomodulatory and anti-inflammatory properties. Hepatic failure is one of the major causes of morbidity and mortality worldwide. Organ transplantation is the best way to treat acute and chronic liver failure, but there are several associated obstacles. Stem cells have been highlighted as alternative hepatocytes source because of their potential for hepatogenic differentiation. HAECs, in particular, have some properties that make them suitable for hepatocyte differentiation. In this work, we review the general characteristics of the epithelial stem cells isolated from human amniotic membrane as well as their ability to differentiate to hepatic cells. We also revise their regenerative properties, with the focus on their potential application in the liver disease treatment.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile? / Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab

Background: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of anti-drug antibodies that reduce their effectiveness. The HLA-DQA1*05 allele has been shown to increase the risk of immunogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully investigated for newer biotherapies. Objective: whether the presence of the HLA-DQA1*05 allele is associated with a reduction of response to ustekinumab and vedolizumab was investigated. Material and methods: the impact of HLA-DQA1*05 on disease activity in 93 patients with IBD, treated with ustekinumab (n = 39) or vedolizumab (n = 54) was investigated in a retrospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn’s disease) and Mayo score (ulcerative colitis). Results: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedolizumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treatment groups. Conclusions: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab (AU)

Obesity and Risk for Lymphoma: Possible Role of Leptin.

Obesity, which is considered a pandemic due to its high prevalence, is a risk factor for many types of cancers, including lymphoma, through a variety of mechanisms by promoting an inflammatory state. Specifically, over the last few decades, obesity has been suggested not only to increase the risk of lymphoma but also to be associated with poor clinical outcomes and worse responses to different treatments for those diseases. Within the extensive range of proinflammatory mediators that adipose tissue releases, leptin has been demonstrated to be a key adipokine due to its pleotropic effects in many physiological systems and diseases. In this sense, different studies have analyzed leptin levels and leptin/leptin receptor expressions as a probable bridge between obesity and lymphomas. Since both obesity and lymphomas are prevalent pathophysiological conditions worldwide and their incidences have increased over the last few years, here we review the possible role of leptin as a promising proinflammatory mediator promoting lymphomas.

Decreased Expression of Sam68 Is Associated with Insulin Resistance in Granulosa Cells from PCOS Patients.

BACKGROUND AND OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, which leads to subfertility. PCOS is the most frequent metabolic disorder in women and the major cause of infertility. Susceptibility to developing PCOS is determined by a complex interaction between environmental and genetic factors. Although different mechanisms have been proposed to explain PCOS manifestations, defects in insulin actions or in the insulin signaling pathways are central in the pathogenesis of the syndrome. However, the mechanisms (molecular players and signaling pathways) underlying its primary origin still remain an unsolved issue. Current research is increasingly focusing on the discovery of novel biomarkers to further elucidate the complex pathophysiology of PCOS. Sam68, an RNA-binding protein, is recruited to insulin signaling, mediating different insulin actions. We aimed to investigate the role of Sam68 in insulin signaling and the possible implications of Sam68 in the insulin resistance in PCOS. MATERIALS AND METHODS: Granulosa cells were taken from women with PCOS (n = 25) and healthy donors (n = 25) and, within the age range of 20 to 42 years, from GINEMED, Assisted Reproduction Centre, Seville, Spain. The Sam68 expression level was analyzed both by qPCR and immunoblot. Statistical significance was assessed by one-way ANOVA, followed by a post-hoc test. A p value of < 0.05 was considered statistically significant. RESULTS: We found that insulin stimulation increases the phosphorylation and expression level of Sam68 in granulosa cells from normal donors. The downregulation of Sam68 expression resulted in a lower activation of both the MAPK and the PI3K pathways in response to insulin. Moreover, the granulosa cells from the women with PCOS presented a lower expression of Sam68, as well as insulin receptor and insulin receptor substrate-1 (IRS-1). In these cells, the overexpression of Sam68 resulted in an increased activation of both the MAPK and the PI3K pathways in response to insulin. CONCLUSIONS: These results suggest the participation of Sam68 in insulin receptor signaling, mediating the insulin effect in granulosa cells, and they suggest the possible role of Sam68 in the insulin resistance of PCOS.