Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies. RECENT FINDINGS: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

Hipertrigliceridemia grave en Argentina: prevalencia y características clínicas / Severe Hypertriglyceridemia in Argentina: Prevalence and Clinical Characteristics

RESUMEN Introducción : La hipertrigliceridemia grave (HTGG) es un desorden metabólico con múltiples causas e implicancias tera péuticas. Se desconocen hasta la fecha las características clínicas, la prevalencia y sus posibles causas en nuestra población. Objetivo : estimar la prevalencia, describir las características clínicas y causas subyacentes de la HTGG en un hospital de tercer nivel del municipio de General Pueyrredón. Materia y métodos : Estudio descriptivo y observacional realizado con pacientes ambulatorios e internados de un hospital provincial. Se incluyeron pacientes adultos con triglicéridos (TG) mayores que 885 mg/dL (10 mmol/L) evaluados desde enero de 2018 a diciembre de 2021. Se extrajeron sus historias clínicas y, luego, se los contactó para obtener medidas antro pométricas, variables sociodemográficas, antecedentes personales y familiares, causas secundarias de hipertrigliceridemia y el tratamiento recibido. Resultados : Se analizaron 16 029 muestras; 46 presentaron HTGG, lo que representa una prevalencia total del 0,28% (IC 95% 0,20-0,40%) (IC 95% 0,20-0,40%); se incluyeron 19 participantes en el análisis. La edad media fue de 48,47 años (DE ±16); el 84,2% de ellos eran hombres. La mediana de triglicéridos fue 1821 mg/dL (rango intercuartílico 917-7000 mg/dL); 17 participantes (84,97%) presentaban hipercolesterolemia (colesterol total mayor que 200 mg/dL). Casi el 50% refirió consumo de alcohol, el 55% presentaba obesidad y el 68% diabetes tipo II. Solo 9 participantes se encontraban en tratamiento, 4 con fibratos y 5 con estatinas. Conclusión : se encontró una prevalencia del 0,28%, más alta que la esperada y reportada en series previas. Por otro lado, se destaca la subutilización de medicación para el tratamiento de esta dislipidemia grave.

ABSTRACT Background : Severe hypertriglyceridemia (SHTG) is a metabolic disorder with multiple origins and management implications. Prevalence, clinical characteristics, and its possible causes are unknown in Argentina. Objective : The aim of this study was to estimate the prevalence and describe the clinical characteristics and underlying SHTG causes in a third level hospital in the municipality of General Pueyrredón. Methods : An observational, descriptive study was performed using an electronic database from a provincial Hospital. It included adult patients with triglyceride (TG) levels above 885 mg/dL (10 mmol/L) evaluated from January 2018 to December 2021. Medical records were collected, and patients were then contacted to obtain anthropometric measurements, sociodemographic variables, personal and family history, secondary causes of hypertriglyceridemia, and treatment received. Results : Among 16 029 patients analyzed, 46 presented SHTG, representing a total prevalence of 0.28% (95% CI 0.20-0.40%). Finally, 19 participants with mean age 48.47±16 years and 84.2% men were included in the analysis. Median TG level was 1821 mg/dL (interquartile range 917-7000 mg/dL), and 17 participants (84.97%) had hypercholesterolemia (total cholesterol >200 mg/dL). Almost 50% reported alcohol consumption, 55% were obese and 68% had type II diabetes. Nine participants were under pharmacological treatment, 4 with fibrates and 5 with statins. Conclusion : A prevalence of 0.28% SHTG was found, higher than that reported in other series. Another finding was the underuse of medication for this severe dyslipidemia.

Influenza and pneumococcal vaccine prescription for adults during COVID-19 first wave in three regions of Argentina.

Immunizations for influenza and pneumococcus are effective interventions in reducing morbidity and mortality. The objective of this study was to describe the vaccination rates in volunteers from three regions of Argentina during the COVID-19 pandemic. In 2020, 3853 adults were surveyed, 61.6 % were females, 45 % were aged between 40 and 60 and 18.6 % were > 60 years old. The commonest comorbidities were hypertension (12.9 %), dyslipidemia (8.5 %), and smokers or former smokers (9.2 %). The global influenza vaccination rate was 37.7 %, pneumococcal vaccination 24.7 %, and both 17.8 %. Multivariable regression showed that the vaccination rate increased with age and the presence of comorbidities. However, in the subgroup with indications for both vaccines, 71.7 % had the influenza vaccine, 59 % had the pneumococcal vaccine, and 28.3 % received neither. Our study suggests that influenza and pneumococcal vaccine percentages in high-risk patients in Argentina remain sub-optimal. Immunizations with proven reductions in morbimortality could have also been relegated during the COVID pandemic.

Deeply in Plasticenta: Presence of Microplastics in the Intracellular Compartment of Human Placentas.

Microplastics (MPs) are defined as plastic particles smaller than 5 mm. They have been found almost everywhere they have been searched for and recent discoveries have also demonstrated their presence in human placenta, blood, meconium, and breastmilk, but their location and toxicity to humans have not been reported to date. The aim of this study was twofold: 1. To locate MPs within the intra/extracellular compartment in human placenta. 2. To understand whether their presence and location are associated with possible structural changes of cell organelles. Using variable pressure scanning electron microscopy and transmission electron microscopy, MPs have been localized in ten human placentas. In this study, we demonstrated for the first time the presence and localization in the cellular compartment of fragments compatible with MPs in the human placenta and we hypothesized a possible correlation between their presence and important ultrastructural alterations of some intracytoplasmic organelles (mitochondria and endoplasmic reticulum). These alterations have never been reported in normal healthy term pregnancies until today. They could be the result of a prolonged attempt to remove and destroy the plastic particles inside the placental tissue. The presence of virtually indestructible particles in term human placenta could contribute to the activation of pathological traits, such as oxidative stress, apoptosis, and inflammation, characteristic of metabolic disorders underlying obesity, diabetes, and metabolic syndrome and partially accounting for the recent epidemic of non-communicable diseases.

Biochemical and clinical markers of endothelial dysfunction do not outweigh traditional risk factors for the presence of diabetic retinopathy in patients with type 1 diabetes.

BACKGROUND: This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). METHODS: Patients aged ≥ 12 years completed a clinical-epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays. RESULTS: Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6-15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI. CONCLUSIONS: In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.

Estudio prospectivo sobre uso y persistencia de tratamiento hipolipidemiante en pacientes con hipercolesterolemia severa / Use and persistence of lipid-lowering therapy in patients with severe hypercholesterolemia: A prospective study

Introducción: Las estatinas son la primera línea de tratamiento en pacientes con hipercolesterolemia severa (HS). A pesar de la evidencia disponible sobre su eficacia y seguridad para prevenir eventos cardiovasculares, el correcto tratamiento sigue siendo un desafío. Materiales y métodos: Estudio observacional prospectivo diseñado para determinar mediante entrevista telefónica la presencia de factores de riesgo, seguimiento clínico anual, persistencia/uso de estatinas y aparición de nuevos eventos cardiovasculares (ECV) después de 5 años, en pacientes con HS incluidos en un programa de Detección de Hipercolesterolemia Familiar. Resultados: Se evaluó a 115 participantes, la edad media fue de 56 ± 10, siendo el 74% mujeres. El 63,4% de las mujeres y el 43% de los hombres refirió estar en seguimiento y control clínico en el último año. El 38,8% de las mujeres recibió estatinas vs. el 26,7% de los hombres y solo 22 participantes (31,8%) fueron persistentes con el tratamiento desde 2015. El 15,5% de los participantes presentó un ECV no fatal y el 3,4% fatal. En el análisis multivariado no se detectaron predictores para presentar un ECV. Conclusiones: En nuestra población con HS encontramos un alto riesgo de presentar un ECV y una dramática baja tasa de uso y persistencia al tratamiento con estatinas.(AU)

Introduction: Statins are the first line of treatment in patients with severe hypercholesterolemia (SH). However, despite the knowledge regarding its effectiveness and security for preventing cardiovascular diseases, treatment is a major challenge. Material and methods: A prospective observational study was conducted by telephone survey to determine cardiovascular risk factors, annual monitoring, statins use and persistence and new-onset cardiovascular events (CVE) after 5 years in patients with SH including in a program for detection of familial hypercholesterolemia. Results: 115 participants were analysed, the median age was 56 ±10 being 74% females. 63.4% of women and 43% of men had been correctly controlled in the last year. Patients on lipid lowering drugs stratified by sex was 38.8% in women and 26.7% in men, however, only 22 participants (31.8%) were persistence with statins since 2015.Overall, 48% of the patients presented a CVE and 3.4% died. Multivariate analysis did not reveal predictors for CVE. Conclusions: In our population with SH we found a high risk to present a CVE and a dramatic low use and persistence with the treatment.(AU)

Use and persistence of lipid-lowering therapy in patients with severe hypercholesterolemia: A prospective study. / Estudio prospectivo sobre uso y persistencia de tratamiento hipolipidemiante en pacientes con hipercolesterolemia severa.

INTRODUCTION: Statins are the first line of treatment in patients with severe hypercholesterolemia (SH). However, despite the knowledge regarding its effectiveness and security for preventing cardiovascular diseases, treatment is a major challenge. MATERIAL AND METHODS: A prospective observational study was conducted by telephone survey to determine cardiovascular risk factors, annual monitoring, statins use and persistence and new-onset cardiovascular events (CVE) after 5 years in patients with SH including in a program for detection of familial hypercholesterolemia. RESULTS: 115 participants were analysed, the median age was 56 ±10 being 74% females. 63.4% of women and 43% of men had been correctly controlled in the last year. Patients on lipid lowering drugs stratified by sex was 38.8% in women and 26.7% in men, however, only 22 participants (31.8%) were persistence with statins since 2015.Overall, 48% of the patients presented a CVE and 3.4% died. Multivariate analysis did not reveal predictors for CVE. CONCLUSIONS: In our population with SH we found a high risk to present a CVE and a dramatic low use and persistence with the treatment.

Plasticenta: First evidence of microplastics in human placenta.

Microplastics are particles smaller than five millimeters deriving from the degradation of plastic objects present in the environment. Microplastics can move from the environment to living organisms, including mammals. In this study, six human placentas, collected from consenting women with physiological pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments (ranging from 5 to 10 µm in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4 in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in terms of morphology and chemical composition. All of them were pigmented; three were identified as stained polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments, which were all used for man-made coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics and personal care products.

[Immunizations in adults with cardiovascular disease. Summary of the Consensus of the Argentine Cardiology Society]. / Inmunizaciones en adultos con cardiopatías. Resumen del Consenso de la Sociedad Argentina de Cardiología.

Cardiovascular diseases are the leading cause of death in most regions of the world, usually followed by infectious diseases. For decades, infections in general, and particularly those involving the respiratory system, have been known to be associated with an increased risk of cardiovascular and cerebrovascular events, and their consequent morbidity and mortality. Although vaccines are an excellent strategy in the prevention of infectious diseases, the proportion of immunized adults in our country is frankly deficient. Multiple barriers contribute to perpetuating this problem, within which the lack of prescription of the same by professionals who care for vulnerable populations occupies a central place. Patients with cardiovascular disease represent a particularly risky subpopulation. The spectrum of pathologies that can trigger respiratory infections is wide: development or worsening of heart failure, arrhythmias, acute coronary syndromes and cerebrovascular diseases, among the main ones. The role of immunoprophylaxis with influenza, pneumococcal and tetanus vaccine in patients with different heart diseases is addressed here, evaluating the evidence supporting its use, and placing special emphasis on practical aspects of its use, such as adverse effects, contraindications and special care situations, such as congenital heart disease in adults, heart transplantation, anticoagulation or egg allergy. Thus, this document aims to assist in decision-making for any doctor involved in the care of patients with cardiovascular disease.

Las enfermedades cardiovasculares ocupan la primera causa de muerte en la mayoría de las regiones del mundo, seguidas habitualmente por las enfermedades infecciosas. Desde hace décadas se conoce que las infecciones en general, y particularmente las que involucran el aparato respiratorio, se vinculan con un incremento en el riesgo de eventos cardiovasculares y cerebrovasculares, y su consecuente morbimortalidad. Si bien las vacunas constituyen una excelente estrategia en la prevención de enfermedades infectocontagiosas, la proporción de adultos inmunizados en nuestro país es francamente deficitaria. Múltiples barreras contribuyen a perpetuar esta problemática, dentro de las cuales la falta de prescripción de las mismas por parte de los profesionales que atienden a poblaciones vulnerables ocupa un lugar central. Los pacientes con enfermedades cardiovasculares representan una subpoblación de particular riesgo. El espectro de enfermedades que pueden originar las infecciones respiratorias es amplio: desarrollo o empeoramiento de insuficiencia cardíaca, arritmias, síndromes coronarios agudos y enfermedades cerebrovasculares, entre los principales. Se aborda aquí el rol de la inmunoprofilaxis con vacuna antigripal, antineumocócica y antitetánica en pacientes con diferentes cardiopatías, valorando la evidencia que respalda su empleo y haciendo especial hincapié en aspectos prácticos de su utilización, como efectos adversos, contraindicaciones y situaciones especiales de atención: cardiopatías congénitas del adulto, trasplante cardíaco, individuos anticoagulados o con alergia al huevo. Así, este documento tiene como objetivo asistir en la toma de decisiones a cualquier médico involucrado en el cuidado de pacientes con enfermedad cardiovascular.

Expression and antigenic analysis of the recombinant TRP36 protein from Ehrlichia canis São Paulo strain for serologic tests.

Ehrlichia canis is the main etiological agent of canine monocytic ehrlichiosis (CME), a globally canine infectious disease. In Brazil, CME is considered to be endemic, and its prevalence can reach 65% in some states. The diagnosis of ehrlichiosis is important for treatment and epidemiological purposes. The E. canis TRP36 (Tandem Repeat Protein) protein elicits the earliest acute-phase antibody response observed during the course of the disease. This study aimed to generate the recombinant TRP36 protein from E. canis São Paulo strain and to evaluate its potential as a tool for the serologic diagnosis of CME. The E. canis São Paulo isolate was cultivated in DH82 lineage cells, and its genomic DNA was obtained. The bacterial DNA fragment encoding the entire ORF of TRP36 was cloned into the pBAD/Thio-TOPO vector and transformed into Escherichia coli DH10B competent cells with the trp36-bearing plasmid for protein expression. To evaluate the protein antigenicity, 16 canine serum samples were previously tested (by PCR and the commercial SNAP®4Dx® serological test). The results were in accordance with the SNAP®4Dx® test. Experiments using this recombinant protein as an antigen, targeting the development of a serologic test based on ELISA methodology, are the next step to produce a reliable, affordable and useful diagnostic tool for CME in Brazil.

Inmunizaciones en adultos con cardiopatías. Resumen del consenso de la Sociedad Argentina de Cardiología / Immunizations in adults with cardiovascular disease. Summary of the Consensus of the Argentine Cardiology Society

Resumen Las enfermedades cardiovasculares ocupan la primera causa de muerte en la mayoría de las regiones del mundo, seguidas habitualmente por las enfermedades infecciosas. Desde hace décadas se conoce que las infecciones en general, y particularmente las que involucran el aparato respiratorio, se vinculan con un incremento en el riesgo de eventos cardiovasculares y cerebrovasculares, y su consecuente morbimortalidad. Si bien las vacunas constituyen una excelente estrategia en la prevención de enfermedades infectocontagiosas, la proporción de adultos inmunizados en nuestro país es francamente deficitaria. Múltiples barreras contribuyen a perpetuar esta problemática, dentro de las cuales la falta de prescripción de las mismas por parte de los profesionales que atienden a poblaciones vulnerables ocupa un lugar central. Los pacientes con enfermedades cardiovasculares representan una subpoblación de particular riesgo. El espectro de enfermedades que pueden originar las infecciones respiratorias es amplio: desarrollo o empeoramiento de insuficiencia cardíaca, arritmias, síndromes coronarios agudos y enfermedades cerebrovasculares, entre los principales. Se aborda aquí el rol de la inmunoprofilaxis con vacuna antigripal, antineumocócica y antitetánica en pacientes con diferentes cardiopatías, valorando la evidencia que respalda su empleo y haciendo especial hincapié en aspectos prácticos de su utilización, como efectos adversos, contraindicaciones y situaciones especiales de atención: cardiopatías congénitas del adulto, trasplante cardíaco, individuos anticoagulados o con alergia al huevo. Así, este documento tiene como objetivo asistir en la toma de decisiones a cualquier médico involucrado en el cuidado de pacientes con enfermedad cardiovascular.

Abstract Cardiovascular diseases are the leading cause of death in most regions of the world, usually followed by infectious diseases. For decades, infections in general, and particularly those involving the respiratory system, have been known to be associated with an increased risk of cardiovascular and cerebrovascular events, and their consequent morbidity and mortality. Although vaccines are an excellent strategy in the prevention of infectious diseases, the proportion of immunized adults in our country is frankly deficient. Multiple barriers contribute to perpetuating this problem, within which the lack of prescription of the same by professionals who care for vulnerable populations occupies a central place. Patients with cardiovascular disease represent a particularly risky subpopulation. The spectrum of pathologies that can trigger respiratory infections is wide: development or worsening of heart failure, arrhythmias, acute coronary syndromes and cerebrovascular diseases, among the main ones. The role of immunoprophylaxis with influenza, pneumococcal and tetanus vaccine in patients with different heart diseases is addressed here, evaluating the evidence supporting its use, and placing special emphasis on practical aspects of its use, such as adverse effects, contraindications and special care situations, such as congenital heart disease in adults, heart transplantation, anticoagulation or egg allergy. Thus, this document aims to assist in decision-making for any doctor involved in the care of patients with cardiovascular disease.

Epidemiology of early repolarization pattern in an adult general population.

Background: Early repolarization pattern (ERP) is a frequent finding in asymptomatic subjects with controversial implications regarding to its prognosis. This study aims to estimate the prevalence of ERP and its association with sociodemographic characteristics and cardiovascular risk factors among the adult population in the Southern Cone of Latin America.Methods: A sub-sample of 5398 participants of the CESCAS I study was included in the present analysis. ERP was defined as a J peak ≥0.1 mV in two or more contiguous leads with an end-QRS notch or slur on the downslope of a prominent R-wave.Results: The global prevalence of ERP was 8.1%; 11.1% in men and 5.6% in women. The prevalence in women increased with age (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.5-4.2, at >65 years, p < 0.001), current cigarette smoking (OR 1.4, 95%CI 1.0-2.0, p = 0.045) and hypercholesterolaemia (OR 1.4, 95%CI 1.0-2.0, 0 p = 0.036). Conversely, in men, ERP prevalence decreased with age (OR 0.5, 95%CI 0.3-0.9, at >65 years, p = 0.01) and obesity (OR 0.6, 95%CI 0.4-0.8, p = 0.006). We found an increasing ERP prevalence with a higher Sokolow-Lyon index in both sexes (p < 0.001). Inferior location was found in 67.9% of cases, and the most common ERP type was a "slurring" appearance without ST elevation (76.3%).Conclusions: We found an overall prevalence of ERP of 8.1% and a robust association of ERP with normal BMI and higher Sokolow-Lyon index in men and with hypercholesterolaemia, current cigarette smoking and higher Sokolow-Lyon index in women.

Relationship between inflammatory markers, glycated hemoglobin and placental weight on fetal outcomes in women with gestational diabetes.

OBJECTIVE: The aim of this study was to evaluate the relationship between inflammatory cytokines, placental weight, glycated hemoglobin and adverse perinatal outcomes (APOs) in women with gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: This was a prospective, longitudinal and observational study conducted from April 2004 to November 2005 in Bauru, Brazil. Included patients had singleton pregnancies and performed a 100 g OGTT and had the levels of C-reactive protein (CRP), interleukin (IL)-6, TNF alfa and glycated hemoglobin (HbA1c) determined at 24-28th gestation weeks. RESULTS: A total of 176 patients were included, of whom 78 had the diagnosis of GDM (44.3%). Multivariate analysis demonstrated that HbA1c, age, body mass index (BMI) and previous history of GDM were independent predictors for GDM diagnosis. ROC curve indicated that HbA1C levels ≥ 5.1% at 24-28 weeks gestation were associated with GDM. No difference was found in IL-6, tumor necrosis factor alpha (TNF-alpha) and CRP serum levels in women with and without GDM. Multivariate analysis showed that placental weight was significantly associated with APOs (p < 0.005), with a cut-off value of 610 grams as demonstrated by the ROC curve. CONCLUSION: Placental weight ≥ 610 grams and HbA1C ≥ 5.1% were found to be associated with APOs and GDM, respectively, and their evaluation should be part of prenatal care routine.

Relationship between inflammatory markers, glycated hemoglobin and placental weight on fetal outcomes in women with gestational diabetes

ABSTRACT Objective: The aim of this study was to evaluate the relationship between inflammatory cytokines, placental weight, glycated hemoglobin and adverse perinatal outcomes (APOs) in women with gestational diabetes mellitus (GDM). Subjects and methods: This was a prospective, longitudinal and observational study conducted from April 2004 to November 2005 in Bauru, Brazil. Included patients had singleton pregnancies and performed a 100 g OGTT and had the levels of C-reactive protein (CRP), interleukin (IL)-6, TNF alfa and glycated hemoglobin (HbA1c) determined at 24-28th gestation weeks. Results: A total of 176 patients were included, of whom 78 had the diagnosis of GDM (44.3%). Multivariate analysis demonstrated that HbA1c, age, body mass index (BMI) and previous history of GDM were independent predictors for GDM diagnosis. ROC curve indicated that HbA1C levels ≥ 5.1% at 24-28 weeks gestation were associated with GDM. No difference was found in IL-6, tumor necrosis factor alpha (TNF-alpha) and CRP serum levels in women with and without GDM. Multivariate analysis showed that placental weight was significantly associated with APOs (p < 0.005), with a cut-off value of 610 grams as demonstrated by the ROC curve. Conclusion: Placental weight ≥ 610 grams and HbA1C ≥ 5.1% were found to be associated with APOs and GDM, respectively, and their evaluation should be part of prenatal care routine.

Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients.

Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-1) and cytokines (IL-1ß, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-ß) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-ß (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-ß mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1ß mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1ß, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1ß and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction.

Sensibility and specificity of laser speckle contrast imaging according to Endo-PAT index in type 1 diabetes.

OBJECTIVES: To find out an normality value for microvascular response (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) based on Endo-PAT, which identifies the ones with Endothelial Dysfunction (ED) in patients with Type 1 Diabetes (T1D). METHODS: Patients with T1D, aged ≥12years underwent a clinical-epidemiological questionnaire. Fasting blood samples were obtained (lipid profile, glycemic control and levels of C-reactive protein). Vascular reactivity was assessed in the forearm through the technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH) and during iontophoresis of acetylcholine (ACh) and peripheral arterial tonometry was performed by supplying the RHI through Endo-PAT device. RESULTS: 189 patients were evaluated, 97 women (51.3%) with T1D, aged 32±13years and with a disease duration of 16 (6-21) years and mean A1c of 9.2% (±2.2). Receiver Operating Characteristics curve (ROC) analysis according to RHI showed that the Area under curve (AUC) of ACh of 10,369 Laser Speckle Perfusion Unit (LSPU) presented sensitivity and specificity of 65% and 87,5%, respectively, (p=0.002) in those patients with T1D's duration <5years. Overall, no test of vascular reactivity was able to distinguish the ideal cuttoff based on RHI. CONCLUSION: In the present study, we could find an ideal cut off value of microcirculation assessment through endothelium-dependent vasodilation to ACh using LSCI according to Endo-PAT's score, only in those under 5years of disease duration. Further prospective studies shall be conducted to evaluate its predictive cardiovascular value.

The Opportunity of Precision Medicine for Breast Cancer With Context-Sensitive Tumor Suppressor Maspin.

To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine the mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations. Unlike most other serpins that are expressed in multiple cell types, maspin is epithelial specific and has distinct roles in luminal and myoepithelial cells. Endogenously expressed maspin has been found in the nucleus and cytoplasm, and detected on the surface of cell membrane. It is also secreted free and as an exosomal cargo protein. Research in the field has led to the identification of the maspin targets and maspin-associated molecules, as well as the structural determinants of its suppressive functions. The current review discusses the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency. J. Cell. Biochem. 118: 1639-1647, 2017. © 2017 Wiley Periodicals, Inc.