Liquid Biopsy Biomarkers for Immunotherapy in Non-Small Cell Lung Carcinoma: Lessons Learned and the Road Ahead.

Over the recent years, advances in the development of anti-cancer treatments, particularly the implementation of ICIs (immune checkpoint inhibitors), have resulted in increased survival rates in NSCLC (non-small cell lung cancer) patients. However, a significant proportion of patients does not seem respond to immunotherapy, and some individuals even develop secondary resistance to treatment. Therefore, it is imperative to correctly identify the patients that will benefit from ICI therapy in order to tailor therapeutic options in an individualised setting, ultimately benefitting both the patient and the health system. Many different biomarkers have been explored to correctly stratify patients and predict response to immunotherapy, but liquid biopsy approaches have recently arisen as an interesting opportunity to predict and monitor treatment response due to their logistic accessibility. This review summarises the current data and efforts in the field of ICI response biomarkers in NSCLC patients and highlights advantages and limitations as we discuss the road to clinical implementation.

Familial combined hyperlipidaemia/polygenic mixed hyperlipidaemia. / Hiperlipemia familiar combinada/hiperlipemia mixta poligénica.

Familial combined hyperlipidaemia (FCH) is the most prevalent form of familial hyperlipidaemia with a multigenic origin and a complex pattern of inheritance. In this respect, FCH is an oligogenic primary lipid disorder due to interaction of genetic variants and mutations with environmental factors. Patients with FCH are at increased risk of cardiovascular disease and often have other associated metabolic conditions. Despite its relevance in cardiovascular prevention, FCH is frequently underdiagnosed and very often undertreated. In this review, emphasis is placed on the most recent advances in FCH, in order to increase its awareness and ultimately contribute to improving its clinical control.

Gliosarcoma: presentación de un caso y hallazgos por tomografía y resonancia magnética convencional y tractografía / Gliosarcoma: Case Report and Findings by Tomography and Conventional and DTI Magnetic Resonance Imaging

El gliosarcoma es un tumor raro del sistema nervioso central y de alto grado de malignidad. La OMS lo clasifica como variante del glioblastoma (grado IV) y es de mal pronóstico. Histológicamente se caracteriza por tener componentes gliales y mesenquimatosos. El cuadro clínico varía dependiendo de su localización y tamaño, los signos y síntomas más frecuentes son convulsiones, cefalea y déficit neurológico focal. El acercamiento diagnóstico inicial es la tomografía computarizada que aporta datos de sospecha; sin embargo, la resonancia magnética constituye el pilar diagnóstico, con importantes elementos de diagnóstico que se vuelven más significativos con el uso de secuencias funcionales como la tractografía. Se presenta un caso clínico con revisión de la literatura y los hallazgos más significativos en los estudios de imagen.

Gliosarcoma is a rare and highly malignant central nervous system tumor. It is classified by the WHO as a variant of glioblastoma (grade IV) and has a poor prognosis. Histologically it is characterized by having both glial and mesenchymal components. Clinically, it varies depending on the location and size of the tumor, the most frequent symptoms being seizures, headaches and focal neurological deficit. The initial diagnostic approach is computed tomography, which provides suspicionus data; however, magnetic resonance is the diagnostic pillar, providing important data that becomes more significant with the use of functional sequences such as tractography. A clinical case is presented with a literature review and the most significant findings in the imaging studies.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico.

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular.

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.

Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease. / Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular.

Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop. The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention. It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time. The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid, atorvastatin and ramipril approved in Spain. The purpose of this consensus document was to define and recommend, through the evidence available in the literature and clinical expert opinion, the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle. A RAND/UCLA methodology based on scientific evidence, as well as the collective judgment and clinical expertise of an expert panel was used for this assessment. As a result, a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced. The recommendations included in this document have been addressed to all those specialists, cardiologists, internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks.

[Delphi consensus on management of dyslipidaemia in patients with impaired glucose metabolism: Diana study]. / Consenso Delphi sobre el manejo de la dislipidemia en pacientes con alteración del metabolismo de la glucosa: estudio Diana.

OBJECTIVES: The aim of the present study was to develop a multidisciplinary consensus based on the Delphi system to establish clinical recommendations for the management of dyslipidaemia when hyperglycaemia is present, and the relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. METHODS: The questionnaire developed by the scientific committee included four blocks of questions about dyslipidaemia in patients with impaired glucose metabolism. The results of the first two blocks are presented here: a) management of dyslipidaemia; b) relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. RESULTS: Among the 497 experts who participated in the study, an agreement of over 90% was attained for recommending screening for dyslipidaemia in patients with diabetes or pre-diabetes and/or cardiovascular disease or a family history and/or abdominal obesity and/or hypertension. There was a high degree of agreement that a statin is the lipid-lowering treatment of choice, and that it should be switched when side effects develop. Also, the choice of statin and dose should be made according to baseline LDL cholesterol levels, the target to achieve, and the possible drug-drug interactions. CONCLUSIONS: The screening of dyslipidaemia is primarily conducted in patients with cardiovascular disease, or any major cardiovascular risk factor. When prescribing a statin, physicians mainly focus on the ability to reduce LDL cholesterol and the risk of drug interactions.

CARACTERIZACIÓN DEL ESTADO NUTRICIONAL Y LA ACTIVIDAD FÍSICA EN UNA POBLACIÓN DE PILOTOS DE ALA FIJA Y ROTATIVA EN LA CIUDAD DE BOGOTÁ (COLOMBIA) / CHARACTERIZATION OF NUTRITIONAL STATE AND PHYSICAL ACTIVITY OF A ROTATIVE PILOTS POPULATION IN BOGOTA CITY / CARACTERIZAÇÃO DO ESTADO NUTRICIONAL E ATIVIDADE FÍSICA EM UMA CIDADE DE PILOTOS ASA FIXA E ROTATIVA NA CIDADE DE BOGOTÁ (COLOMBIA)

Las enfermedades cardiovasculares, como parte de las enfermedades crónicas no transmisibles, representan un problema de salud pública a nivel mundial y uno de los factores que influyen en el desempeño y producción laboral. Dentro de los factores de riesgo, se considera tanto la nutrición y alimentación, como el patrón de actividad física. Este artículo presenta la caracterización del estado nutricional y la actividad física en una población de pilotos de avión con base en la ciudad de Bogotá. Se realizó evaluación de la composición corporal a través de técnicas antropométricas e impedanciometría; análisis del consumo de alimentos a partir de la Frecuencia de Consumo; y, evaluación del patrón de actividad física. El grupo estuvo conformado por 23 sujetos de 24 a 39 años (edad media 29,8 ± 4,5). Los resultados demostraron que el 69,6 % de los sujetos presentan sobrepeso y el 8,7% obesidad grado I. Existe asociación lineal directa entre el índice de masa corporal y la circunferencia de la cintura. La mayoría de los pilotos presenta valores de grasa corporal por encima de los parámetros normales en los rangos alto y muy alto, así como aumento en los valores de perímetro de la cintura (89,8 ± 8,31) con respecto a patrones de referencia. El consumo diario recomendado de frutas se observó en el 13% y el consumo de verduras en el 45,5% de la población total. El 39% de la población toma gaseosas de 1 a 3 veces por día y el 48% jugos industrializados de 1 a 3 veces por día. El 34,78% de los sujetos, reporta consumir embutidos y alimentos de salsamentaria de 1 a 3 veces por día. El 55,6% de la población refiere realizar actividad de intensidad moderada y el 33,3% de los pilotos actividad física vigorosa. El 66,7% de la población permanece sentada 5 a 7 horas diarias. Es evidente la necesidad de generar estrategias de prevención y/o control de factores de riesgo cardiovascular relacionados con el estado nutricional y el patrón de actividad física en esta población de pilotos de avión para optimizar su estado de salud y potenciar su actividad laboral y productiva.

Cardiovascular diseases, as part of chronic communicable diseases, represent a public healthy problem in the world and of the most influent factors in work and production performance. Nutrition and supply are considered in those risk factors. This articles show characterization of nutritional state and physical activity in a group of pilots established in Bogota city. Corporal composition was evaluated with anthropometric techniques and impedance measure; consumption of smokes based on consumption frequency; and pattern of physical activity evaluation. Group was composed 23 people between 24 and 39 years (middle age of 29,8 ± 4,5). According to results, 60,6% of those people has overweight and 8.7%, obesity grade 1. There is a lineal direct association between the corporal mass index and waist circumference. Most of pilots have corporal fat values over normal parameters in high and very high ranges, as well as increase of hip perimeter values (89,8 ± 8,31) with regard to reference patterns. The recommended daily consumption of fruits was watched in 13% and vegetables consumption in the 45,5% of the total. 39% drinks sodas 1 to 3 times at day and 48% drinks industrial juices 1 to times at day. 34% of people say consuming sausages and fast food 1 to 3 times at day. 55,6% of people refers to do activity of moderated intensity and 33,3% of pilots, vigorous physical activity. 66,7% of the group stay sits 5 to 7 hours every day. It is clear the necessity for making strategies of prevention and/or control of risk factor related with nutritional state and the pattern of physical activity in this group of airplane pilots to boost their working and productive performance.

As doenças cardiovasculares, como parte das doenças crónicas não transmissíveis, representam um problema de saúde pública a nível mundial e uno dos fatores que influenciam no desempeno e produção laboral. A nutrição e alimentação consideram-se dentro duos fatores de resgo, também o padrão de atividade física. Este texto presenta a caracterização do estado nutricional e a atividade física numa população de pilotos de aeronave que moram na cidade de Bogotá. A composição corporal foi avaliada com técnicas antropométricas e medição de impedância; análises de consumo do alimentos a partir da frequência de consumo; e avaliação do padrão de atividade física. O grupo era formado por 23 sujeitos de 24 ao 39 anos (idade media 29,8 ± 4,5). Os resultados mostraram que que o 69,6 % dos sujeitos presentam sobrepeso e o 8,7% obesidade grado 1. Ha uma associação lineal direta entre o índice de massa corporal e a circunferência da cadeira. A maioria dos pilotos presenta valores de grassa corporal por encima dos parâmetros normais nos rangos alto e muito alto, e aumento nos valores de perímetro da cintura (89,8 ± 8,31) no que respeita ao padrões de referencia. O consumo diário de frutas observou-se no 13% e o consumo de verduras no 54,5% da população total. No 39% da população pega sodas de 1 ao 3 vezes num dia. O 34,78% dos sujeitos reporta consumir embutidos e alimentos como assim de 1 ao 3 vezes por dia. O 55,6% da população dize fazer atividade de intensidade moderada e o 33,3% dos pilotos, atividade física vigorosa. O 66,7% da população fica sentada 5 ao 7 horas diárias. Ê claro que precisa-se gerar estratégias de prevenção e/ou controle de fatores de resgo cardiovascular relacionados com o estado nutricional e o padrão de atividade física nesta população de aeronave para otimizar o estado de saúde deles e potenciar a atividades laboral e produtiva deles.

[Dyslipemia in diabetics treated with statins. Results of the DYSIS study in Spian]. / Dislipemia en población diabética tratada con estatinas. Resultados del estudio DYSIS en España.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (DM2) is characterized by carrying a high cardiovascular risk. This situation underscores the importance of intensively treating the risk factors present in diabetic patients, notably dyslipemia. The treatment with cholesterol-lowering drugs may be especially effective to reduce the cardiovascular risk in diabetic patients. Therefore, LDL-cholesterol is a priority target in the lipid management of these patients. This study analyzes the alterations in the lipid profile of diabetic patients receiving treatment with statins, which therefore may contribute to persistent cardiovascular risk in such individuals. PATIENTS AND METHODS: The DYSIS (Dyslipidemia International Study) is an international, observational trial analyzing the lipid profile of patients treated with statins and followed-up on in outpatient clinics by primary care physicians and specialists. This study is referred to the data on the diabetic patients. RESULTS: Of the total patients enrolled in the DYSIS, the present study included 3703 patients, 39% being diabetics. A total of 59.2% of diabetics showed LDL-C out of goal; triglyceride elevation was observed in 43.6% and 36.4% showed low HDL-C. In diabetics patients with coronary heart disease, 31% had uncontrolled levels of all three lipid parameters. The prevalence of out of goal LDL-C in diabetic patients with metabolic syndrome was close to 60%; 39.8% had low levels of HDL-C and 46,6% high levels of triglycerides. In addition, 57% of diabetic patients with obesity showed LDL-C out of control, despite statins treatment. CONCLUSIONS: Cardiovascular diseases remain the main cause of morbidity-mortality in patients with DM2. The results of the present study show that in diabetic patients the degree of control is very limited with regard to LDL-cholesterol. More than half of diabetic patients treated with statins had LDL-cholesterol out of goal. The level of dyslipidemia control was low, despite statins treatment. Therefore, the detection of atherogenic dyslipidemia may point to the advisability of using combination therapy for dyslipidemia in diabetic patients.

[Prevalence of metabolic syndrome and its components in patients with acute coronary syndrome]. / Prevalencia del síndrome metabólico y de sus componentes en pacientes con síndrome coronario agudo.

INTRODUCTION AND OBJECTIVES: A large proportion of patients with coronary disease have metabolic syndrome, although the frequency and association of its different components are not well understood. The aim of this study was to determine the prevalence of metabolic syndrome and the combination of its components in a Spanish cohort of patients with acute coronary syndrome. METHODS: Clinical histories of 574 inpatients with acute coronary syndrome in 6 tertiary hospitals were reviewed and the presence of metabolic syndrome and its components determined by applying Adult Treatment Panel III criteria. In a second step, the components of the metabolic syndrome were analyzed, excluding those patients with diabetes mellitus. RESULTS: The metabolic syndrome was present in 50.9% of patients and was more frequent in women than in men (66.3% vs. 47.3%; P<.001). The most prevalent component was carbohydrate metabolism disorder (85.3%), followed by low high-density lipoprotein cholesterol (HDLc) levels (80.5%). In nondiabetic patients, 34.6% had metabolic syndrome and the most prevalent component was low HDLc levels (86%), followed by high blood pressure and hypertriglyceridemia and, in fourth place, impaired fasting serum glucose levels. CONCLUSIONS: The metabolic syndrome has a high prevalence in patients with an acute coronary syndrome, especially in women. The most frequent components are hyperglycemia and low HDLc levels. After excluding diabetic patients, the most prevalent diagnostic criterion of metabolic syndrome was low HDLc levels. Full English text available from: www.revespcardiol.org.

A very high prevalence of low HDL cholesterol in Spanish patients with acute coronary syndromes.

BACKGROUND: Total and low-density lipoprotein cholesterol (LDL-C) concentrations in coronary artery disease have progressively declined, although high-density lipoprotein cholesterol (HDL-C) has not always been evaluated. The prevalence and related factors of low HDL-C in a cohort of Spanish patients with acute coronary syndromes (ACS) were assessed. METHODS: Clinical and laboratory data registered at admission and at discharge of 648 patients admitted to coronary care units of 6 Spanish hospitals for ACS between January 2004 and September 2007 were analyzed. RESULTS: Low HDL-C (HDL-C < 1.04 mmol/L) was observed in 367 (56.6%) patients. Male gender, smoking, hypertension, diabetes, high body mass index, and triglycerides were related to low HDL-C. Female gender was the strongest protective factor against low HDL-C (0.619; 95% confidence interval [CI]: 0.410-0.934; P = 0.022), whereas high triglycerides (1.653; 95% CI: 1.323-2.064; P < 0.001) followed by previous ischemic disease (1.504; 95% CI: 1.073-2.110; P = 0.018) were the strongest factors associated with low HDL-C. One-third of patients were taking statins at admission, but only 2% were on fibrate therapy. A large increase in statin therapy, but not in other hypolipemiant drug therapy, between admission and discharge was noted in the whole cohort and among patients with low HDL-C. CONCLUSION: Spanish patients with ACS have a very high prevalence of low HDL-C. Male gender, high triglycerides, and previous ischemic disease are strong, independent factors associated with this disorder. As low HDL-C remains almost completely untreated in ACS, strategies to enhance the treatment of this lipoprotein abnormality are urgently required.

Ethanol beverages containing polyphenols decrease nuclear factor kappa-B activation in mononuclear cells and circulating MCP-1 concentrations in healthy volunteers during a fat-enriched diet.

AIMS: Different epidemiological studies have demonstrated that some ethanol containing beverages intake could be associated with a reduction of cardiovascular mortality, effect attributed in part to its antioxidant properties. Nuclear factor-kappa B (NF-kappaB) is a redox sensitive transcription factor implicated in the pathogenesis of atherosclerosis. We have examined the effect of four different ethanol containing beverages on the activation of NF-kappaB in peripheral blood mononuclear cells (PBMC) and circulating concentrations of monocyte chemoattractant protein-1 (MCP-1) in healthy volunteers receiving a fat-enriched diet. METHODS AND RESULTS: Sixteen volunteers received 16 g/m(2) of ethanol in form of red wine, spirits (vodka, rum, and brandy) or no ethanol intake along with a fat-enriched diet during 5 days and all of them took all alcohols at different periods. NF-kappaB activation (electrophoretic mobility shift assay) and circulating MCP-1 levels (ELISA) were examined in blood samples taken before and after 5 days of ethanol intake. Subjects receiving a fat-enriched diet had increased NF-kappaB activation in PBMC at day 5. Furthermore, MCP-1 levels were increased in plasma at day 5. Red wine intake and some ethanol beverages containing polyphenols (brandy and rum) prevented NF-kappaB activation and decreased MCP-1 release. CONCLUSION: Consumption of moderate amounts of alcoholic drinks containing polyphenols decreases NF-kappaB activation in PBMCs and MCP-1 plasma levels during a fat-enriched diet. Our results provide additional evidence of the anti-inflammatory effects of some ethanol containing beverages, further supporting the idea that its moderate consumption may help to reduce overall cardiovascular mortality.

[Tables of coronary risk evaluation adapted to the Spanish population: the DORICA study]. / Tablas de evaluación del riesgo coronario adaptadas a la población española. Estudio DORICA.

BACKGROUND AND OBJECTIVE: Independent risk factors (smoking, hypertension, hypercholesterolemia and diabetes mellitus) are direct causes of coronary heart disease and are common in the population. Considering all independent factors together seems to be more appropriate to estimate the global risk of coronary heart disease. The objective of this paper was to estimate the global risk of coronary heart disease based on the Framingham function, adapted to the prevalence of risk factors in Spain. SUBJECTS AND METHOD: The prevalence of risk factors in the Spanish population was estimated based on pooled analysis of regional cross-sectional random population surveys. Prevalence estimates and incidence rate of coronary events were replaced in the Framingham equation accordingly. Risk probability for 10 years was estimated and risk tables were designed using a gradual color coding system according to an increasing risk. RESULTS: The estimated attributable fraction (AF) for hypertension in the Spanish population was 26.7% for men and 22.9% women; that for hypercholesterolemia was 15.7% and 12.7% for men and women, respectively. Smoking was identified in the third position of the ranking order for males (AF 13.13%) and fourth for the female group (AF 3.71%). The prevalence of obesity was 13.2% for men and 17.5% for women. AF for obesity among men was 4% and it was 5% for women. CONCLUSIONS: An adaptation of the Framingham equation according to the prevalence of independent risk factors and incidence of coronary events in the Spanish population is useful to build instruments to estimate the 10-year global risk of coronary heart disease while a specific function based on a well-designed cohort study in not available in Spain.

Síndrome post colecistectomía: un mito? / Post colecistectomy syndrome: a myth?

Se estudiaron 621 pacientes operados de enero de 1979 a diciembre de 1982, a todos los pacientes se les hizo el diagnóstico previo de colecistitis por clínica, radiología y/o ultrasonografía; se les realizó colecistectomía simple con colangiografía transoperatoria trans-cística. La evolución no fue satisfactoria en 122 pacientes (19.6%). Estos pacientes se estudiaron en forma complementaria para determinar si el cuadro clínico que presentaron se relacionaba con la exéresis vesicular y por lo tanto con la ausencia de sus funciones. Después de analizar los resultados de los estudios complementarios encontramos una serie de padecimientos ya existentes, pero enmascarados por el cuadro de colecistitis, que fueron los que aparentemente causaban la sintomatología que motivó la cirugía. En esta serie no se encontró el llamado SPC, y las alteraciones que presentaron los pacientes fueron ocasionadas por otra patología