Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis.

BACKGROUND: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. METHODS: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. RESULTS: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). CONCLUSIONS: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Imnuno-Oncología: Recuento Histórico y Fundamentos Básicos / Imnuno-Oncology: Historical Recount and Basic Fundamentals

El sistema inmune cumple un rol fundamental en la defensa contra microorganismos y células anómalas. Históricamente, el concepto de vigilancia inmunológica se fundamenta en el control de múltiples funciones incluyendo la regulación de células cancerígenas a través de diversos mecanismos, en los cuales están involucrados: células, moléculas y tejidos del sistema inmune. El objetivo de analizar la respuesta inmune frente al cáncer, es entender los mecanismos de presentación del antígeno y los mecanismos desencadenados por el sistema adaptativo e innato que participan en la destrucción del tumor a expensas de un proceso inflamatorio agudo que podría llevar al control o destrucción del cáncer. La propuesta de esta revisión es resumir y esquematizar los aspectos cardinales de los diferentes procesos inmunológicos que participan en la fisiopatología de las enfermedades malignas, así como los mecanismos que emplea el sistema inmune para la defensa del cáncer.

The Inmune System plays an essential role in the defense of the organism against microorganisms and alters cells. Historically, the concept of immune surveillance its based in the control of multiple functions including the regulation of cancer cells through diverse mechanisms such as cells, molecules and tissue from the immune system. Therefore, it is important to understand the mechanisms of antigen presentation and other mechanisms of the innate and adaptive system which participate in the defense of the organism against the tumor. This process is enhancing by an inflammatory acute process that could lead to the control or de destruction of the tumor. The purpose of this review is to develop the cardinal aspects of the immunologic process that take part in the defense against malignant diseases, and also to explain its mechanisms.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Litiasis vesical gigante / Giant bladder calculus

Las litiasis vesicales de gran tamaño son infrecuentes. Se manifiestan clínicamente por sepsis urinaria a repetición, polaquiuria y estranguria. Se presenta un nuevo caso de litiasis vesical gigante, así como aspectos de su diagnóstico y tratamiento. La paciente de 64 años de edad, asistió a la consulta y refirió padecer de infecciones urinarias reiteradas, incontinencia por urgencia miccional y dolor posmiccional en hipogastrio y uretra. Tenía el antecedente de haber sido operada, siete meses atrás, de un prolapso uterino total por vía vaginal. En el cultivo de orina se aisló Escherichia coli y, en el ultrasonido abdominal, se detectó una litiasis vesical de gran tamaño, la cual se confirmó en la radiografía simple de la pelvis. Se le realizó la cistolitotomía retropúbica, extrayéndose una litiasis de 9 x 6 x 5 cm de tamaño y 186 g de peso. La paciente evolucionó favorablemente con la desaparición total de los síntomas. La litiasis vesical gigante es rara, pero se debe sospechar en pacientes con síntomas urinarios sépticos e irritativos bajos persistentes. El ultrasonido del tracto urinario y la radiografía simple de la pelvis, son suficientes para establecer el diagnóstico de certeza. La cistolitotomía continúa siendo el tratamiento de elección de esta afección.

Giant bladder calculi are uncommon. Their clinical manifestations are recurrent urinary sepsis, polachiuria and strangury. A new case is presented of giant bladder calculus, as well as aspects of its diagnosis and treatment. A 64-year-old female patient attended consultation and stated that she suffered from recurrent urinary infection, urinary urgency incontinence and hypogastric and urethral post-miction pain. Seven months before she had undergone surgery for total uterine prolapse via the vagina. Escherichia coli was isolated from the urine culture, and abdominal ultrasonography revealed a large bladder calculus, which was confirmed by simple pelvic radiography. Retropubic cystolithotomy resulted in the removal of a 9 x 6 x 5 cm, 186 g calculus. The patient evolved favorably with total disappearance of all symptoms. Giant bladder calculus is a rare condition which should be suspected in patients with persistent irritative symptoms of lower urinary sepsis. Urinary-tract ultrasonography and simple pelvic radiography are sufficient to establish the certainty diagnosis. Cystolithotomy continues to be the treatment of choice for this condition.

Evaluación de estudios clínicos de recuperación de la función endotelial con fármacos hipotensores

El endotelio cumple un papel crucial en el mantenimiento de la integridad del sistema cardiovascular, a través de sus funciones vasodilatadoras, antitrombóticas y antiaterogénicas. La disfunción endotelial ha sido implicada en la génesis de importantes enfermedades como la hipertensión arterial, la aterosclerosis, la enfermedad arterial coronaria, la insuficiencia cardiaca crónica, la diabetes mellitus, etc. Varios métodos clínicos han sido descritos para valorar la función endotelial; entre los mejor estandarizados están el de la respuesta vasomotora coronaria a la infusión de acetilcolina o bradicinina en arterias de conducción evaluada por pletismografía, y la vasodilatación dependiente de flujo (VDF) en arterias de conducción del antebrazo, valorada por el cambio en el diámetro de la arteria braquial de frente a la hiperemia reactiva, determinado por eco-doppler. En el presente artículo revisamos los diferentes estudios dirigidos a investigar el efecto de diferentes drogas hipotensoras en la recuperación de la función endotelial en pacientes con hipertensión esencial, enfermedad arterial coronaria e insuficiencia cardíaca crónica. Los inhibidores de la enzima convertidora de la angiotensina (ECA-I) son los fármacos que con más consistencia ejercen un efecto beneficioso en la recuperación de la función vasodilatadora dependiente de endotelio. Existen diferencias en la capacidad de mejorar la función endotelial entre los diferentes componentes

Factores de riesgo clásicos y emergentes para enfermedades cardiovasculares / Classic and emerging risk factors for cardiovascular diseases

Las enfermedades cardiovasculares han experimentado un incremento epidémico en los países del tercer mundo durante las últimas décadas. Las causas son multifactoriales y se asocian con un aumento em la expectativa de vida y con cambios en los hábitos nutricionales y estilos de vida. Los países desarrollados, que hace cuarenta años sufrieron una situación similar, identificaron y están combatiendo los factores de riesgo clásicos (hipertensión arterial, tabaquismo, obesidad,inactividad física, dislipidemia, diabetes mellitus). Esto les ha permitido disminuir la prevalencia de accidentes cerebrovasculares y enfermedad cardiaca coronaria. Sin embargo, los resultados epidemiológicos de estos rígidos programas de control de los factores de riesgo fueron los esperados, por lo que han comenzado a identificar y estudiar los denominados factores de riesgo emergentes (infección, inflamación, hiperhomocisteinemia, deficit de ácido fólico y vitaminas antioxidantes, Síndrome X metabólico, hiperinsulinismo y resistencia a la insulina), los cuales estarían contribuyendo a la génesis y manifestaciones de las enfermedades cardiovasculares. En latinoamérica, por sus particulares condiciones étnicas, nutricionales y culturales, se vuelve inprescindible la realización de investigaciones observacionales, clínicas y básicas que permitan definir el peso específico de cada uno de los factores de riesgo clásicos y emergentes en nuestras poblaciones. La necesidad de optimizar los limitados recursos disponibles demanda de estrategias de intervención efectivas, las cuales deben priorizar bajo nuestras propias condiciones sociales, económicas y culturales, aquellos factores de mayor riesgo y que sean posibles de transformarse