Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14, 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatmen

Primary Melanoma of the Small Intestine with a Metastatic Lymph Mass in the Inguinal Canal: A Case Report

Objectives: We report a case of primary melanoma of the small intestine. Primary intestinal melanoma (PIM) is an extremely rare neoplasm for which the cause is unknown. Materials and methods: A 67-year-old man was admitted to our department due to abdominal pain, constipation, a large, hard inguinal mass and severe anaemia. Results: After laboratory data, imaging techniques and histopathological examination, the diagnosis was confirmed. A surgical resection of the intestinal neoplasm, treatment with BRAF inhibitors and radiation therapy to the inguinal mass were performed. Conclusion: PIM is rare and it is usually difficult to establish its exact origin

Vericiguat, nuevo pilar en el tratamiento de la insuficiencia cardiaca con fracción de eyección reducida

Heart failure with reduced ejection fraction (HFrEF) is associated with high morbidity and mortality, conditioned by multiple hospitalizations. Vericiguat has currently beenshown to be effective and safe in patients with a recent decompensation. We present a series of three cases using vericiguat in different clinical scenarios: an elderly patient with dilated cardiomyopathy of ischemic origin, a patient with alcoholic cardiomyopathy and polyvalvular heart disease, and a young patient with idiopathic cardiomyopathy. In the 3 cases vericiguat was effective and safe. This medication has been tested and monitored in other studies and we consider it plays an important role in the therapeutic armamentarium of this population, although it is necessary to accumulate more clinical experience.La insuficiencia cardiaca con fracción de eyección reducida (ICFEr) se asocia con una elevada morbimortalidad, condicionada por múltiples hospitalizaciones. Actualmente vericiguat ha mostrado ser eficaz y seguro en pacientes con una descompensación reciente. Presentamos una serie de tres casos clínicos usando vericiguat en diferentes perfiles clínicos: paciente de edad avanzada con miocardiopatía dilatada de origen isquémico, paciente con miocardiopatía de origen enólico y enfermedad polivalvular y paciente joven con miocardiopatía de origen idiopático. En los 3 casos el vericiguat mostró resultados eficaces y seguros. Este fármaco ha sido monitorizado en otros estudios y creemos que constituye un arma terapéutica importante para pacientes con ICFEr, aunque es necesario acumular mayor experiencia clínica

Deterioro cognitivo posquirúrgico a largo plaza tras cirugía cardiaca

Objetivos: Evaluar de forma longitudinal el Deterioro Cognitivo Postquirúrgico (DCP) a largo plazo en pacientes tras cirugía cardíaca, analizar el perfil cognitivo obtenido e identificar los factores de riesgo involucrados. Material y Métodos: Estudio prospectivo de 70 pacientes sometidos a cirugía cardíaca (36 con……..). Se recogieron los datos sociodemográficos y clínicos y se realizó evaluación longitudinal neuropsicológica (pre y postquirúrgica a los 1, 6 y 12 meses) para caracterizar el DCP (Proyecto Neuronorma). Se evaluaron las funciones ejecutivas (Test del Trazo, Test de Stroop), memoria (Test de Recuerdo libre y selectivamente facilitado), fluidez verbal (Semántica y Fonológica) y función visuoespacial (Orientación de Líneas. Se valoró también depresión y ansiedad (escalas de Hamilton). Resultados: Se comprobó la presencia de DCP en los dos grupos de pacientes (p>0.05-p>0.001, mayor en el grupo con CEC), que fue máximo a los 6 meses de la intervención, pero aún significativo a los 12 meses. El deterioro cognitivo se asoció con variables intraoperatorias (baja saturación de oxígeno intraoperatoria y tiempo de bypass cardiopulmonar prolongado) y con factores de riesgo cardiovasculares (tabaquismo, insuficiencia cardíaca, hipertrofia ventricular izquierda, diabetes mellitus, enfermedad coronaria de 3 vasos y arteriopatía periférica) como factores predictivos. Conclusión: Los resultados indican la prevalencia del deterioro cognitivo postquirúrgico (DCP) al año de la intervención en ambos grupos, siendo mayor en el grupo con CEC. El DCP se caracteriza por un deterioro multidominio significativo en atención, funciones ejecutivas y fluencia verbal. Se describen los factores intraoperatorios y cardiovasculares significativos en el DCP, planteando la necesidad de establecer protocolos para su detección así como su prevención.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Physical functional performance and prognosis in patients with heart failure: a systematic review and meta-analysis

Background: Patients with Heart Failure (HF) show impaired functional capacities which have been related to their prognosis. Moreover, physical functional performance in functional tests has also been related to the prognosis in patients with HF. Thus, it would be useful to investigate how physical functional performance in functional tests could determine the prognosis in patients with HF, because HF is the leading cause of hospital admissions for people older than 65 years old. This systematic review and meta-analysis aims to summarise and synthesise the evidence published about the relationship between physical functional performance and prognosis in patients with HF, as well as assess the risk of bias of included studies and the level of evidence per outcome. Methods: Major electronic databases, such as PubMed, AMED, CINAHL, EMBASE, PEDro, Web of Science, were searched from inception to March 2020 for observational longitudinal cohort studies (prospective or retrospective) examining the relationship between physical functional performance and prognosis in patients with HF. Results: 44 observational longitudinal cohort studies with a total of 22,598 patients with HF were included. 26 included studies reported a low risk of bias, and 17 included studies showed a moderate risk of bias. Patients with poor physical functional performance in the Six Minute Walking Test (6MWT), in the Short Physical Performance Battery (SPPB) and in the Gait Speed Test showed worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance. However, there was a lack of homogeneity regarding which cut-off points should be used to stratify patients with poor physical functional performance from patients with good physical functional performance. Conclusion: The review includes a large number of studies which show a strong relationship between physical functional performance and prognosis in patients with HF. Most of the included studies reported a low risk of bias, and GRADE criteria showed a low and a moderate level of evidence per outcome

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure

[Abstract] Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.Ministerio de Salud, Servicios Sociales e Igualdad; PI13/02542Ministerio de Salud, Servicios Sociales e Igualdad; PI11/01661Red de Investigación Cardiovascular (España), RD12/0042/003

Expression of sterol regulatory element-binding proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study

[Abstract] Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.Instituto de Salud Carlos III; PI13/02542Instituto de Salud Carlos III; PI11/01661Red de Investigación Cardiovascular; RD12/0042/003

De-Intensification of Antidiabetic Treatment Using Canagliflozin in Patients with Heart Failure and Type 2 Diabetes: Cana-Switch-HF Study

Canagliflozin is a sodium-glucose co-transporter 2 inhibitor that reduces glycemia as well as the risk of cardiovascular events. Our main objective was to analyze antidiabetic treatment de-intensification and the glycemic efficacy of replacing antidiabetic agents (excluding metformin) with canagliflozin in patients with heart failure and type 2 diabetes with poor glycemic control. In this observational, retrospective, real-world study, we selected patients treated with metformin in combination with ≥2 non-insulin antidiabetic agents or metformin in combination with basal insulin plus ≥1 non-insulin antidiabetic agent. Non-insulin antidiabetic agents were replaced with canagliflozin. Patients were followed-up on at three, six, and 12 months after the switch and a wide range of clinical variables were recorded. A total of 121 patients were included. From baseline to 12 months, the number of antidiabetic agents (3.1 ± 1.0 vs. 2.1 ± 0.8, p < 0.05), basal insulin dose (20.1 ± 9.8 vs. 10.1 ± 6.5 units, p < 0.01), and percentage of patients who used basal insulin (47.9% vs. 31.3%, p < 0.01) decreased. The proportion of patients who used diuretics also declined significantly. In addition, we observed improvement in glycemic control, with an increase in the proportion of patients with glycated hemoglobin <7% from 16.8% at three months to 63.5% at 12 (p < 0.001). Canagliflozin use was also beneficial in terms of body weight, blood pressure, heart failure status, functional class, and cardiovascular-renal risk. There were also reductions in the number of emergency department visits and hospitalizations for heart failure. Moreover, canagliflozin was well-tolerated, with a low rate of drug-related discontinuation. Mounting evidence from randomized controlled trials and real-world studies point to the beneficial profile of sodium-glucose co-transporter type 2 inhibitors such as canagliflozin in patients with heart failure.This work was supported by PI15/00256 from the Institute of Health “Carlos III” (ISCIII), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Maria Isabel Queipo-Ortuño was supported by the “Miguel Servet Type II” program (CPI18/00003, ISCIII, Spain, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER) and by the “Nicolas Monardes” research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Bruno Ramos Molina was supported by the “Miguel Servet Type I” program (CP19/00098, ISCIII, Spain, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER). Lidia Sanchez-Alcoholado was the recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain). Aurora Laborda-Illanes was the recipient of a predoctoral grant, PFIS-ISCIII (FI19-00112), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain.Ye

Primeros resultados de la caracterización del contenido estomacal de juveniles 0+ de atún rojo Thunnus thynnus

Stomach contents from 19 dead young bluefin tuna were analyzed in the framework of the SELFDOTT project (From capture based to SELF-sustained aquaculture and Domestication Of bluefin tuna, Thunnus thynnus). The fish were captured close to Cartagena (Murcia- Spain) between the 3rd and the 16th of October 2008, using the «curricán» method (a Spanish term meaning to fish by trailing a baited line along behind a boat). The first stomach analyses show that cephalopods are the main prey (53% in weight 49% in number), followed by fishes (28%, 24%) and crustaceans (2%, 27%). The main prey species is the squid Illex coindetti.Proyecto SELFDOT