[Acute ischemic stroke in cancer patients. A case-control study]. / Accidente cerebrovascular isquémico en pacientes con cáncer. Un estudio caso-control.

One in 10 patients with ischemic stroke has comorbid cancer. Our goal was to compare stroke patients with cancer against those without cancer in terms of clinical and radiological features, and the underlying mechanism. We conducted a retrospective case-control study in patients admitted with ischemic stroke between July 2013 and September 2018. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls only of ischemic stroke. Age, gender, vascular risk factors (VRF), pattern of ischemic lesion in neuroimaging, etiology and clinical outcome were compared between groups. Fifty-seven cases were identified, 61% were male (n = 35), and mean age was 75 ± 11. Fiftytwo had known oncologic disease at the onset of stroke. Most of them had solid tumors (91%, n = 52), and 54% (n = 31) had a non-metastatic tumor at the time of stroke. Prevalence of common VRF between groups was not significantly different. Previous deep venous thrombosis and pulmonary thromboembolism were more frequent in the cancer cohort (8% vs. 1%, p = 0.01). The average NIHSS was 3.8 ± 4 in the cancer group and 9 ± 7 in the control group (p = 0.01). Small artery disease as the etiology of stroke was significantly less common in the cancer group (2% vs. 26%, p = 0.001). Regarding neuroimaging, the embolic pattern was more frequent in patients with cancer (82% vs. 35%, p = 0.001). In these patients recurrence and mortality at 90 days was three and six times higher (10% vs. 3%, and 18% vs. 3%. p = 0.08 and 0.001, respectively).

Aproximadamente uno de cada 10 pacientes que sufre un accidente cerebrovascular isquémico (ACVi) padece cáncer concomitantemente. Nuestro objetivo fue evaluar características clínicoradiológicas del ACVi en pacientes con cáncer y compararlas con otros sin cáncer. Fue un estudio caso-control retrospectivo que incluyó pacientes con ACVi entre julio 2013 y septiembre 2018. Los casos tenían diagnóstico de cáncer y ACVi, y los controles solamente ACVi. Se comparó edad, sexo, factores de riesgo vascular, patrones radiológicos de lesiones, etiología y evolución clínica entre ambos grupos. Hubo 57 casos, 61% (n = 35) eran varones. La edad media fue 75 ± 11 años, sin diferencias en prevalencia de factores de riesgo vascular. En los casos hubo más pacientes con antecedentes de trombosis venosa profunda y/o tromboembolismo pulmonar (8% vs. 1%, p = 0.01). En 52 se conocía la presencia del cáncer antes del ACVi. El 91% se trató de tumores sólidos (n = 52) y en 54% el tumor no presentaba metástasis. El puntaje NIHSS promedio fue 3.8 ± 4 en los casos, y 9 ± 7 en los controles (p = 0.01). Las lesiones de pequeña arteria fueron menos frecuentes en los casos (2% vs. 26%, p = 0.001). Las lesiones de aspecto embólico fueron más comunes entre los casos (82% vs. 35%, p = 0.001). Aquellos con cáncer tuvieron menor NIHSS, menor frecuencia de lesiones de pequeña arteria, y mayor frecuencia de lesiones de aspecto embólico. La recurrencia a 90 días fue 3 veces mayor y la mortalidad 6 veces mayor en pacientes con cáncer (10% vs. 3%, y 18% vs. 3%. p = 0.08 y 0.001 respectivamente).

Accidente cerebrovascular isquémico en pacientes con cáncer. Un estudio caso-control / Acute ischemic stroke in cancer patients. A case-control study

Resumen Aproximadamente uno de cada 10 pacientes que sufre un accidente cerebrovascular isquémico (ACVi) padece cáncer concomitantemente. Nuestro objetivo fue evaluar características clínicoradiológicas del ACVi en pacientes con cáncer y compararlas con otros sin cáncer. Fue un estudio caso-control retrospectivo que incluyó pacientes con ACVi entre julio 2013 y septiembre 2018. Los casos tenían diagnóstico de cáncer y ACVi, y los controles solamente ACVi. Se comparó edad, sexo, factores de riesgo vascular, patrones radiológicos de lesiones, etiología y evolución clínica entre ambos grupos. Hubo 57 casos, 61% (n = 35) eran varones. La edad media fue 75 ± 11 años, sin diferencias en prevalencia de factores de riesgo vascular. En los casos hubo más pacientes con antecedentes de trombosis venosa profunda y/o tromboembolismo pulmonar (8% vs. 1%, p = 0.01). En 52 se conocía la presencia del cáncer antes del ACVi. El 91% se trató de tumores sólidos (n = 52) y en 54% el tumor no presentaba metástasis. El puntaje NIHSS promedio fue 3.8 ± 4 en los casos, y 9 ± 7 en los controles (p = 0.01). Las lesiones de pequeña arteria fueron menos frecuentes en los casos (2% vs. 26%, p = 0.001). Las lesiones de aspecto embólico fueron más comunes entre los casos (82% vs. 35%, p = 0.001). Aquellos con cáncer tuvieron menor NIHSS, menor frecuencia de lesiones de pequeña arteria, y mayor frecuencia de lesiones de aspecto embólico. La recurrencia a 90 días fue 3 veces mayor y la mortalidad 6 veces mayor en pacientes con cáncer (10% vs. 3%, y 18% vs. 3%. p = 0.08 y 0.001 respectivamente).

Abstract One in 10 patients with ischemic stroke has comorbid cancer. Our goal was to compare stroke patients with cancer against those without cancer in terms of clinical and radiological features, and the underlying mechanism. We conducted a retrospective case-control study in patients admitted with ischemic stroke between July 2013 and September 2018. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls only of ischemic stroke. Age, gender, vascular risk factors (VRF), pattern of ischemic lesion in neuroimaging, etiology and clinical outcome were compared between groups. Fifty-seven cases were identified, 61% were male (n = 35), and mean age was 75 ± 11. Fiftytwo had known oncologic disease at the onset of stroke. Most of them had solid tumors (91%, n = 52), and 54% (n = 31) had a non-metastatic tumor at the time of stroke. Prevalence of common VRF between groups was not significantly different. Previous deep venous thrombosis and pulmonary thromboembolism were more frequent in the cancer cohort (8% vs. 1%, p = 0.01). The average NIHSS was 3.8 ± 4 in the cancer group and 9±7 in the control group (p = 0.01). Small artery disease as the etiology of stroke was significantly less common in the cancer group (2% vs. 26%, p = 0.001). Regarding neuroimaging, the embolic pattern was more frequent in patients with cancer (82% vs. 35%, p = 0.001). In these patients recurrence and mortality at 90 days was three and six times higher (10% vs. 3%, and 18% vs. 3%. p = 0.08 and 0.001, respectively).

[Clinical predictors of hemorrhagic transformation in non lacunar ischemic stroke]. / Predictores clínicos de transformación hemorrágica en accidente cerebrovascular isquémico no lacunar.

Hemorrhagic transformation is a complex phenomenon where brain tissue bleeds, which could be associated or not to an increase in the neurological deficit after the acute ischemic stroke. The aim of our study was to evaluate clinical predictors of hemorrhagic transformation in patients with non-lacunar ischemic stroke. We performed a prospective analysis of the clinical records and images of patients with non-lacunar ischemic stroke. Demographics, vascular risk factors, previous medications and the information of the event in patients with and without hemorrhagic transformation were here compared. We included in this study 747 patients with non-lacunar stroke, the mean age was 77 ± 11 years and 61% were females. In the univariate analysis, the age, a history of hypertension, atrial fibrillation, chronic kidney disease and the previous use of oral anticoagulation resulted statistically significant. In the multivariate analysis of logistic regression adjusted by age and vascular risk factors: the age > 80 years (OR 3.6, CI 95% 1.8-7.6), the pulse pressure > 60 mmHg at admission (OR 5.3, CI 95% 3.2-9.1), the chronic kidney disease (OR 3, CI 95% 2.5-3.8) and the presence of previous atrial fibrillation (OR 3.5, CI 95% 2.1-6.1) were associated with and increased risk of hemorrhagic transformation. The predictors of hemorrhagic transformation in our cohort showed a relationship with severe vascular illness. The identification of these patients could influence therapeutic decisions that could increase the risk of hemorrhagic transformation.

Predictores clínicos de transformación hemorrágica en accidente cerebrovascular isquémico no lacunar / Clinical predictors of hemorrhagic transformation in non lacunar ischemic stroke

La transformación hemorrágica es un fenómeno complejo en el que el tejido cerebral isquémico sangra; este proceso puede asociarse o no a un deterioro del estado neurológico inicial. El objetivo de nuestro estudio fue evaluar los predictores clínicos de trasformación hemorrágica en los pacientes con accidente cerebrovascular isquémico no lacunar. Se analizaron las historias clínicas y las imágenes de pacientes con infarto cerebral no lacunar incluidos prospectivamente en un programa de prevención secundaria. Se compararon datos demográficos, factores de riesgo vascular, medicación previa y datos del evento de los pacientes con transformación hemorrágica y sin ella. Se incluyeron 747 pacientes, la edad promedio fue de 77 ± 11 años, 61% mujeres. En el análisis univariado, la edad, el antecedente de hipertensión arterial, la fibrilación auricular, la insuficiencia renal crónica y la anticoagulación oral previa se relacionaron significativamente con la presencia de transformación hemorrágica. En el análisis multivariado de regresión logística ajustado por edad y factores de riesgo vascular, resultaron predictores de transformación hemorrágica: la edad > 80 años (OR 3.6; IC 95% 1.8-7.6), la presión de pulso > 60 mmHg al ingreso (OR 5.3; IC 95% 3.2-9.1), la insuficiencia renal crónica (OR 3; IC 95% 2.5-3.8) y el antecedente de fibrilación auricular (OR 3.5; IC 95% 2.1-6.1). En nuestra cohorte los predictores clínicos de conversión hemorrágica del infarto cerebral muestran una relación con la gravedad de la enfermedad vascular. La identificación de estos pacientes influenciaría en la toma de decisiones terapéuticas que pudieran incrementar el riesgo de transformación hemorrágica.

Hemorrhagic transformation is a complex phenomenon where brain tissue bleeds, which could be associated or not to an increase in the neurological deficit after the acute ischemic stroke. The aim of our study was to evaluate clinical predictors of hemorrhagic transformation in patients with non-lacunar ischemic stroke. We performed a prospective analysis of the clinical records and images of patients with non-lacunar ischemic stroke. Demographics, vascular risk factors, previous medications and the information of the event in patients with and without hemorrhagic transformation were here compared. We included in this study 747 patients with non-lacunar stroke, the mean age was 77 ± 11 years and 61% were females. In the univariate analysis, the age, a history of hypertension, atrial fibrillation, chronic kidney disease and the previous use of oral anticoagulation resulted statistically significant. In the multivariate analysis of logistic regression adjusted by age and vascular risk factors: the age > 80 years (OR 3.6, CI 95% 1.8-7.6), the pulse pressure > 60 mmHg at admission (OR 5.3, CI 95% 3.2-9.1), the chronic kidney disease (OR 3, CI 95% 2.5-3.8) and the presence of previous atrial fibrillation (OR 3.5, CI 95% 2.1-6.1) were associated with and increased risk of hemorrhagic transformation. The predictors of hemorrhagic transformation in our cohort showed a relationship with severe vascular illness. The identification of these patients could influence therapeutic decisions that could increase the risk of hemorrhagic transformation.

[Medication adherence to secondary prevention for coronary artery disease]. / Adherencia a la prevención secundaria de la enfermedad coronaria.

We compared the use of evidence-based secondary prevention drugs for coronary artery disease at hospital discharge and 3 years of follow-up in a group of patients associated to an integrated network of health services. We conducted a retrospective group study that included 125 patients under 80 years of age who were hospitalized for acute coronary syndrome. McNemar's test was used to compare values at baseline and 3 years. The mean age of of participants was 63.7 years (SD ± 10.08) and 65.6% (95% CI 56.6-73.9) of male sex. The average follow-up time was 2.94 years (SD ± 0.25). The use of secondary prevention drugs for coronary heart disease decreased at 3 years of follow-up: anti-platelet 97.6 to 88.0% (p = 0.012), beta-blockers 94.4 to 84.8% (p = 0.021) and statins 83.7 to 91.2% (p = 0.035). Patients medicated with a combination of anti-platelet, beta blockers and statins showed a decrease from 86.4 to 66.3% (p < 0.0001). It is necessary to study the causes for the decreased adherence to long-term cardio-protective drugs.

Adherencia a la prevención secundaria de la enfermedad coronaria / Medication adherence to secondary prevention for coronary artery disease

Se comparó la adherencia a la prevención secundaria de enfermedad coronaria mediante el uso indicado de fármacos de probada eficacia, al momento del egreso hospitalario y a 3 años de seguimiento, en una cohorte de pacientes afiliados al Plan de Salud del Hospital Italiano. Se realizó un estudio de cohorte retrospectivo que incluyo 125 pacientes menores de 80 años de edad, afiliados a una red integrada de salud, con internación por síndrome coronario agudo. En el análisis se utilizó el test de McNemar. La edad media de los participantes fue 63.7 años (DS 10.08) y el 65.6% (IC95% 56.6-73.9) fue de sexo masculino. El 76.8% (IC95% 68.4-83.9) presentó como evento calificante un síndrome coronario agudo sin elevación del segmento ST. El tiempo de seguimiento promedio fue 2.94 años (DS 0.25). Se observó que el uso de drogas de probada eficacia en la prevención secundaria de enfermedad coronaria descendió entre el momento del egreso hospitalario y los 3 años de seguimiento: antiagregantes de 97.6 a 88.0% (p = 0.012); beta-bloqueantes de 94.4 a 84.8% (p = 0.021); estatinas 91.2 a 83.7% (p = 0.035). Uso combinado de antiagregantes, betabloqueantes y estatinas de 86.4 a 66.3% (p < 0.0001). Es necesario estudiar las causas de la disminución de la adherencia a drogas cardioprotectoras a largo plazo.

We compared the use of evidence-based secondary prevention drugs for coronary artery disease at hospital discharge and 3 years of follow-up in a group of patients associated to an integrated network of health services. We conducted a retrospective group study that included 125 patients under 80 years of age who were hospitalized for acute coronary syndrome. McNemar´s test was used to compare values at baseline and 3 years. The mean age of of participants was 63.7 years (SD ± 10.08) and 65.6% (95% CI 56.6-73.9) of male sex. The average follow-up time was 2.94 years (SD ± 0.25). The use of secondary prevention drugs for coronary heart disease decreased at 3 years of follow-up: anti-platelet 97.6 to 88.0% (p = 0.012), beta-blockers 94.4 to 84.8% (p = 0.021) and statins 83.7 to 91.2% (p = 0.035). Patients medicated with a combination of anti-platelet, beta blockers and statins showed a decrease from 86.4 to 66.3% (p < 0.0001). It is necessary to study the causes for the decreased adherence to long-term cardio-protective drugs.

Adherencia a la prevención secundaria de la enfermedad coronaria / Medication adherence to secondary prevention for coronary artery disease

Se comparó la adherencia a la prevención secundaria de enfermedad coronaria mediante el uso indicado de fármacos de probada eficacia, al momento del egreso hospitalario y a 3 años de seguimiento, en una cohorte de pacientes afiliados al Plan de Salud del Hospital Italiano. Se realizó un estudio de cohorte retrospectivo que incluyo 125 pacientes menores de 80 años de edad, afiliados a una red integrada de salud, con internación por síndrome coronario agudo. En el análisis se utilizó el test de McNemar. La edad media de los participantes fue 63.7 años (DS 10.08) y el 65.6% (IC95% 56.6-73.9) fue de sexo masculino. El 76.8% (IC95% 68.4-83.9) presentó como evento calificante un síndrome coronario agudo sin elevación del segmento ST. El tiempo de seguimiento promedio fue 2.94 años (DS 0.25). Se observó que el uso de drogas de probada eficacia en la prevención secundaria de enfermedad coronaria descendió entre el momento del egreso hospitalario y los 3 años de seguimiento: antiagregantes de 97.6 a 88.0% (p = 0.012); beta-bloqueantes de 94.4 a 84.8% (p = 0.021); estatinas 91.2 a 83.7% (p = 0.035). Uso combinado de antiagregantes, betabloqueantes y estatinas de 86.4 a 66.3% (p < 0.0001). Es necesario estudiar las causas de la disminución de la adherencia a drogas cardioprotectoras a largo plazo.(AU)

We compared the use of evidence-based secondary prevention drugs for coronary artery disease at hospital discharge and 3 years of follow-up in a group of patients associated to an integrated network of health services. We conducted a retrospective group study that included 125 patients under 80 years of age who were hospitalized for acute coronary syndrome. McNemar´s test was used to compare values at baseline and 3 years. The mean age of of participants was 63.7 years (SD ± 10.08) and 65.6% (95% CI 56.6-73.9) of male sex. The average follow-up time was 2.94 years (SD ± 0.25). The use of secondary prevention drugs for coronary heart disease decreased at 3 years of follow-up: anti-platelet 97.6 to 88.0% (p = 0.012), beta-blockers 94.4 to 84.8% (p = 0.021) and statins 83.7 to 91.2% (p = 0.035). Patients medicated with a combination of anti-platelet, beta blockers and statins showed a decrease from 86.4 to 66.3% (p < 0.0001). It is necessary to study the causes for the decreased adherence to long-term cardio-protective drugs.(AU)

Adherencia a la prevención secundaria de la enfermedad coronaria. / [Medication adherence to secondary prevention for coronary artery disease].

We compared the use of evidence-based secondary prevention drugs for coronary artery disease at hospital discharge and 3 years of follow-up in a group of patients associated to an integrated network of health services. We conducted a retrospective group study that included 125 patients under 80 years of age who were hospitalized for acute coronary syndrome. McNemars test was used to compare values at baseline and 3 years. The mean age of of participants was 63.7 years (SD ± 10.08) and 65.6

(95

CI 56.6-73.9) of male sex. The average follow-up time was 2.94 years (SD ± 0.25). The use of secondary prevention drugs for coronary heart disease decreased at 3 years of follow-up: anti-platelet 97.6 to 88.0

(p = 0.012), beta-blockers 94.4 to 84.8

(p = 0.021) and statins 83.7 to 91.2

(p = 0.035). Patients medicated with a combination of anti-platelet, beta blockers and statins showed a decrease from 86.4 to 66.3

(p < 0.0001). It is necessary to study the causes for the decreased adherence to long-term cardio-protective drugs.

Is it possible to apply secondary stroke prevention guidelines to very old populations?

The aging population is an undeniable reality which must be faced by all health systems all over the world. Among people over 80 years old, increase in stroke incidence, high mortality rates and adverse outcomes are problems of major public concern. Lack of evidence-based data to guide rational decision making on vascular risk factors management to avoid recurrence in elderly stroke patients increases the areas of uncertainty, and sometimes favors medical inertia at the time of taking care of this growing elderly population.

Protocolo de efectividad de un programa de prevención secundaria de eventos coronarios / Effectiveness assessment of a program for secondary prevention of coronary events

A pesar de los avances farmacológicos en el tratamiento de la cardiopatía isquémica se observan dificultades para alcanzar los objetivos terapéuticos en la práctica clínica. Con el propósito de superarlas se ha propuesto implementar en el Hospital Italiano de Buenos aires (HIBA) un programa de prevención secundaria. El objetivo de este artículo es describir cómo será la implementación del programa y su protocolo de evaluación. Material y Métodos: estudio cuasiexperimental con control histórico: cohorte prospectiva intervenida comparada con una cohorte retrospectiva control. El período de seguimiento será de 3 años. Serán elegibles pacientes de 18 a 79 años,afiliados al Plan de Salud, que hayan ingresado en unidad coronaria del HIBa por síndrome coronario agudo con elevación del segmento ST o sin ella.Durante el programa, el equipo de salud trabajará con los pacientes aplicando técnicas cognitivo-conductuales para lograr cambios en el estilo de vida, estimulará el autocuidado por parte de los pacientes y coordinará su atención para favorecer la continuidad del cuidado. Se implementarán intervenciones según el caso clínico: terapia antitabáquica, ejercicio, educación nutricional, tratamiento de obesidad/sobrepeso, monitoreo del control de factores de riesgo cardiovascular modificables y de la adherencia a tratamientos farmacológicos. La efectividad del Programa se evaluará mediante un indicador compuesto de calidad de atención. Conclusiones: considerando que un gran número de pacientes con enfermedad coronaria no logra alcanzar las metas terapéuticas, es necesario desarrollar un programa basado en un equipo multidisciplinario y centrado en las necesidades del paciente. La efectividad a largo plazo de este programa en nuestro centro debe ser evaluada.

Recent respiratory infection predicts atherothrombotic stroke: case-control study in a Buenos Aires healthcare system.

BACKGROUND AND PURPOSE: Increasing evidence links infections to atherosclerosis. Case-control and cohort studies have found that infections, especially respiratory and dental, are associated with coronary heart disease. However, data on the association of infections with cerebrovascular disease are limited, especially beyond Europe and the United States. We assessed the relationship between recent infections and atherothrombotic disease in a South American cohort. METHODS: We conducted a case-control study of 105 cases and 354 control subjects in a Buenos Aires healthcare system matched by age (mean age, 73.2+/-12.3 and 72.9+/-12.8 years), sex, and major cardiovascular risk factors. Cases were patients hospitalized with atherothrombotic ischemic stroke from December 2006 to October 2007. Control subjects were randomly assigned from an electronic outpatient database. Data from the preceding year on inpatient and ambulatory respiratory, urinary and abdominal infections as well as peripheral white blood cell count were collected. RESULTS: Infections were more frequent in cases than control subjects (29% versus 13%; OR, 2.6; 95% CI, 1.4 to 4.5; P=0.0004); however, this was driven by community-acquired respiratory tract infections (19% versus 6%; OR, 3.9; 95% CI, 1.9 to 8; P<0.001) because there were no differences between cases and control subjects for other types of infection. Respiratory tract infections were the most prevalent type of infection during the 3 months before an atherothrombotic ischemic event, occurring more in cases compared with control subjects (17% versus 4%; OR, 5; 95% CI, 2.2 to 11.3; P<0.001). In multivariable analysis adjusting for major vascular risk factors, history of respiratory infection in the prior year was associated more with cases than control subjects (OR, 4.9; 95% CI, 2.3 to 10.2;P<0.001). White blood cell count was slightly higher in cases versus control subjects (7602+/-2058 versus 7121.6+/-1947, P=0.01). CONCLUSIONS: In this South American cohort, recent respiratory tract infections were significantly associated with atherothrombotic stroke, suggesting that prompt identification and treatment of individuals with or at risk for these infections may mitigate the burden from this type of stroke.

In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes.

The antitumor activity of the organometallic ruthenium(II)-arene complexes, RuCl(2)(eta(6)-arene)(PTA), (arene = p-cymene, toluene, benzene, benzo-15-crown-5, 1-ethylbenzene-2,3-dimethylimidazolium tetrafluoroborate, ethyl benzoate, hexamethylbenzene; PTA = 1,3,5-triaza-7-phosphaadamantane), abbreviated RAPTA, has been evaluated. In vitro biological experiments demonstrate that these compounds are active toward the TS/A mouse adenocarcinoma cancer cell line whereas cytotoxicity on the HBL-100 human mammary (nontumor) cell line was not observed at concentrations up to 0.3 mM, which indicates selectivity of these ruthenium(II)-arene complexes to cancer cells. Analogues of the RAPTA compounds, in which the PTA ligand is methylated, have also been prepared, and these prove to be cytotoxic toward both cell lines. RAPTA-C and the benzene analogue RAPTA-B were selected for in vivo experiments to evaluate their anticancer and antimetastatic activity. The results show that these complexes can reduce the growth of lung metastases in CBA mice bearing the MCa mammary carcinoma in the absence of a corresponding action at the site of primary tumor growth. Pharmacokinetic studies of RAPTA-C indicate that ruthenium is rapidly lost from the organs and the bloodstream.