Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

SmartLab 2.0 en prevención cardiovascular de dislipemia aterogénica / SmartLab 2.0 in cardiovascular prevention of atherogenic dyslipidemia

Objetivo: Implementación en el sistema informático de laboratorio (SIL) de un algoritmo bioquímico automatizado para la identificación en analíticas de rutina de pacientes con dislipemia aterogénica y derivación prioritaria a la unidad de día de diabetes. Material y métodos: Se diseñó en el SIL el algoritmo: HBA1c>9,3 +TG>150mg/dl +cHDL <40mg/dl +LDL/ApoB es<1,3. Se inserta un comentario alertando al médico peticionario del diagnóstico de dislipemia aterogénica y se procede a la derivación prioritaria desde el laboratorio a la unidad de día de diabetes en los casos necesarios. Resultados: En el periodo de un año se han identificado a un total de 899 pacientes con HBA1c>7 y criterio de dislipemia aterogénica. De ellos, 203 pacientes procedentes de atención primaria con HbA1c>9,3 se derivaron al hospital de día de diabetes. Conclusiones: El refuerzo de la prevención cardiovascular es necesario a todos los niveles. El laboratorio clínico debe jugar un papel fundamental en el diagnóstico de las dislipemias. La detección temprana de los pacientes con alto riesgo cardiovascular es primordial y la colaboración entre las distintas unidades clínicas es fundamental para garantizar la seguridad del paciente.(AU)

Introduction: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. Objective: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. Material and methods: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. Results: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. Conclusions: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.(AU)

SmartLab 2.0 in cardiovascular prevention of atherogenic dyslipidemia. / SmartLab 2.0 en prevención cardiovascular de dislipemia aterogénica.

INTRODUCTION: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. OBJECTIVE: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. MATERIAL AND METHODS: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. RESULTS: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. CONCLUSIONS: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.

Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models.

Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers by blocking the tumor cell's ability to produce glutamine-derived nutrients. Starting from the known GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide, we describe the medicinal chemistry evolution of a series from lipophilic inhibitors with suboptimal physicochemical and pharmacokinetic properties to cell potent examples with reduced molecular weight and lipophilicity, leading to compounds with greatly improved oral exposure that demonstrate in vivo target engagement accompanied by activity in relevant disease models.

Discovery of potent inhibitors of the lysophospholipase autotaxin.

The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active site of ATX together with occupying the LPA 'exit' channel.

The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase.

We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity.

Trombosis subaguda de stent en paciente con púrpura trombocitopénica idiopática tratado con inmunoglobulina intravenosa / Subacute stent thrombosis in a patient with idiopathic thrombocytopenic purpura treated with intravenous immunoglobulin

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Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; MIM 600513) has been associated with mutations in the genes coding for the alfa-4 (CHRNA4), beta-2 (CHRNB2), and alpha-2 (CHRNA2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) and for the corticotropin-releasing hormone (CRH). A four-generation ADNFLE family with six affected members was identified. All affected members presented the clinical characteristics of ADNFLE. Interictal awake and sleep EEG recordings showed no epileptiform abnormalities. Ictal video-EEG recordings showed focal seizures with frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed a c.859G>A transition (Val287Met) within the second transmembrane domain, identical to that previously described in a Scottish ADNFLE family. To our knowledge, this is the third family reported presenting a mutation in CHRNB2. The clinical phenotype appears similar to that described with mutations in CHRNA4, suggesting that mutations in these two subunits lead to similar functional alterations of the nAChR.

Prognostic significance of ischemic mitral regurgitation after non-Q-wave acute myocardial infarction.

BACKGROUND AND AIM OF THE STUDY: The development of mitral regurgitation (MR) soon after acute myocardial infarction (AMI) is a recognized and frequent complication. Its negative impact on survival has been observed after Q-wave AMI, even when of a mild degree, and independently of left ventricular systolic function. Few data exist regarding MR after non-Q-wave AMI (nQ AMI), however. Hence, the study aim was to investigate the incidence, clinical predictors and prognostic implications of MR in the setting of nQ AMI. METHODS AND RESULTS: A total of 99 consecutive patients (37 men, 62 women; mean age 72 +/- 13 years) who suffered a nQ AMI was studied. All patients underwent echocardiography during the first week after the nQ AMI. MR was detected in 34 patients (17 men, 17 women; mean age 76 +/- 10 years). Events during follow up were coded as death, AMI, unstable angina, or heart failure. The in-hospital outcome was not significantly different between patients with and without MR. The mean follow up period was 663 +/- 574 days. In the univariate analysis, freedom from hospital survival was significantly greater in patients without MR. However, multivariate analysis showed that MR was not an independent predictor of cardiovascular hospitalization or death. CONCLUSION: The incidence of MR is high among patients with nQ AMI but, unlike results found with Q-wave AMI, its presence does not add any prognostic significance to other known negative factors in the setting of nQ AMI.

Morphological determinants of subaortic stenosis in hypertrophic cardiomyopathy: insights from real-time 3-dimensional echocardiography.

Real-time 3-dimensional echocardiography allows a comprehensive evaluation of left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy. The anterior segment of the anterior mitral leaflet is essential in the development of the LVOT pressure gradient.

[Cardiac hamartoma. Case report and literature review]. / Hamartoma intracardíaco. Caso clínico y revisión de la bibliografía.

Primary cardiac tumors are infrequent and usually benign. They can manifest as dyspnea, chest pain, palpitations, sudden death, peripheral embolism, cyanosis, or general symptoms. They are sometimes an incidental finding in an asymptomatic patient. We describe a 33-year-old man who was seen because of dyspnea and palpitations. Transthoracic echocardiography revealed, on the lateral wall of the left ventricle, an intramyocardial mass that was successfully resected surgically. The pathologic diagnosis was hamartoma of mature cardiac myocytes. We discuss the usefulness of imaging techniques for identifying cardiac masses.

Hamartoma intracardíaco. Caso clínico y revisión de la bibliografía / Cardiac hamartoma. Case report and literature review

Los tumores cardíacos primarios son infrecuentes y habitualmente benignos. Pueden manifestarse con disnea, dolor torácico, palpitaciones, muerte súbita, embolia periférica, cianosis o síndrome constitucional. A veces es un hallazgo casual en un individuo asintomático. Presentamos el caso de 1 paciente de 33 años que consultó por disnea y palpitaciones. El ecocardiograma transtorácico reveló una masa intramiocárdica en la pared lateral del ventrículo izquierdo. Fue extirpada quirúrgicamente con éxito. El diagnóstico anatomo-patológico fue de hamartoma de células miocárdicas maduras. Se discute la utilidad de las pruebas de imagen en el estudio y la definición de las masas cardíacas

Primary cardiac tumors are infrequent and usually benign.They can manifest as dyspnea, chest pain, palpitations, sudden death, peripheral embolism, cyanosis, orgeneral symptoms. They are sometimes an incidental finding in an asymptomatic patient. We describe a 33-yearoldman who was seen because of dyspnea and palpitations. Transthoracic echocardiography revealed, on the lateral wall of the left ventricle, an intramyocardial mass that was successfully resected surgically. The pathologic diagnosis was hamartoma of mature cardiac myocytes. We discuss the usefulness of imaging techniques for identifying cardiac masses