Adipose tissue-derived mesenchymal stromal cells for treating chronic kidney disease: A pilot study assessing safety and clinical feasibility.

BACKGROUND: Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD. METHODS: AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. RESULTS: No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15-9.57) at baseline to 0.54 g/day (range, 0.01-2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs. CONCLUSION: Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

RATIONALE: Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. OBJECTIVE: Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. METHODS AND RESULTS: Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×106 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography (P=0.0167 versus baseline) and cardiac MRI (P=0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P=0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class (P=0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire (P<0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy. CONCLUSIONS: Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777.

[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. / Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio.

BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio / Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction

Background: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. Aim: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. Material and Methods: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. Results: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. Conclusions: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Chorion Mesenchymal Stem Cells Show Superior Differentiation, Immunosuppressive, and Angiogenic Potentials in Comparison With Haploidentical Maternal Placental Cells.

UNLABELLED: Mesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine. SIGNIFICANCE: This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine.

[Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy]. / Resultados a largo plazo del trasplante intracoronario de células mononucleares de médula ósea autólogas en pacientes con cardiopatía dilatada de diversa etiología.

BACKGROUND: Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. AIM: To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. PATIENTS AND METHODS: Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. RESULTS: No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p < 0.01). The treated group showed a non-significant increase in left ventricular ejection fraction at long-term follow-up (from 26.75 ± 4.85% to 34.90 ± 8.57%, p = 0.059 compared to baseline). There were no changes in left ventricular volumes. We observed no improvement of these variables in the control group. CONCLUSIONS: Intracoronary transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.

Resultados a largo plazo del trasplante intracoronario de células mononucleares de médula ósea autólogas en pacientes con cardiopatía dilatada de diversa etiología / Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy

Background: Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. Aim: To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Patients and Methods: Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. Results: No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p < 0.01). The treated group showed a non-significant increase in left ventricular ejection fraction at long-term follow-up (from 26.75 ± 4.85% to 34.90 ± 8.57%, p = 0.059 compared to baseline). There were no changes in left ventricular volumes. We observed no improvement of these variables in the control group. Conclusions: Intracoronary transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.

[Stem cells for the treatment of cardiovascular diseases. An update]. / Estado actual de la terapia con células madre en el tratamiento de las cardiopatías.

Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the capacity to regenerate, repair or substitute damaged tissue, allowing the reestablishment of its function. Stem cells can also modulate apoptosis, angiogenesis, fibrosis and inflammation, favoring the endogenous regenerative process initiated by the damaged tissue. These capacities have been corroborated in several animal models of cardiovascular diseases with positive results. In humans, therapies with bone marrow mononuclear stem cells, mesenchymal stem cells and cardiac stem cells are safe. Most randomized clinical trials in patients with myocardial infarction or cardiomyopathies of different etiologies have reported benefits on ventricular function, quality of life and even over mortality of treated patients. This article reviews the state of art of stem cell therapy in cardiovascular diseases, focusing on the most common cellular types used in patients with acute myocardial infarction and chronic cardiomyopathies of different etiologies.

Estado actual de la terapia con células madre en el tratamiento de las cardiopatías / Stem cells for the treatment of cardiovascular diseases. An update

Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the capacity to regenerate, repair or substitute damaged tissue, allowing the reestablishment of its function. Stem cells can also modulate apoptosis, angiogenesis, fibrosis and inflammation, favoring the endogenous regenerative process initiated by the damaged tissue. These capacities have been corroborated in several animal models of cardiovascular diseases with positive results. In humans, therapies with bone marrow mononuclear stem cells, mesenchymal stem cells and cardiac stem cells are safe. Most randomized clinical trials in patients with myocardial infarction or cardiomyopathies of different etiologies have reported benefits on ventricular function, quality of life and even over mortality of treated patients. This article reviews the state of art of stem cell therapy in cardiovascular diseases, focusing on the most common cellular types used in patients with acute myocardial infarction and chronic cardiomyopathies of different etiologies.

Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure.

Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently been reported that BM-MSCs derived from uraemic patients failed to confer functional protection in a similar model. This suggests that autologous BM-MSCs are not suitable for the treatment of CKD. In the present study, we have explored the potential of MSCs derived from adipose tissue (AD-MSCs) as an alternative source of MSCs for the treatment of CKD. We have isolated AD-MSCs and evaluated their effect on the progression of CKD. Adult male SD (Sprague-Dawley) rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×10(6) AD-MSCs or MSC culture medium alone. The therapeutic effect was evaluated by plasma creatinine measurement, structural analysis and angiogenic/epitheliogenic protein expression. AD-MSCs were detected in kidney tissues from NPX animals. This group had a significant reduction in plasma creatinine levels and a lower expression of damage markers ED-1 and α-SMA (α-smooth muscle actin) (P<0.05). In addition, treated rats exhibited a higher level of epitheliogenic [Pax-2 and BMP-7 (bone morphogenetic protein 7)] and angiogenic [VEGF (vascular endothelial growth factor)] proteins. The expression of these biomarkers of regeneration was significantly related to the improvement in renal function. Although many aspects of the cell therapy for CKD remain to be investigated, we provide evidence that AD-MSCs, a less invasive and highly available source of MSCs, exert an important therapeutic effect in this pathology.

El trasplante intracoronario de células mononucleares de médula ósea se asocia a mejoría la función ventricular izquierda, en pacientes con cardiopatía dilatada de diferente etiología: Proyecto INNOVA Chile N°205-4350 / Autologous bone marrow cell transplantation improves ejection fraction in patients with dilated cardiomyopathy of diverse etiologies: Proyecto innova chile n° 205-4350

Introducción: Estudios recientes indican que el trasplante intracoronario de células mononucleares de médula ósea (BMCs) autólogas, mejoran la fracción de eyección (FEVI) y otros marcadores clínicos en pacientes con insuficiencia cardíaca (IC). Objetivo: Evaluar la seguridad y eficacia de la administración intracoronaria de BMCs autólogas, en pacientes con insuficiencia cardíaca (IC) en fase dilatada, de diferente etiología y en óptimas condiciones de tratamiento médico. Método: De 23 pacientes consecutivos que cumplieron con los criterios de inclusión, 12 fueron asignados a trasplante intracoronario de BMCs autólogas, recibiendo una dosis media de 8.19+/-4.43 x 10(6) células CD34+ (Grupo trasplantado). Los pacientes restantes sólo recibieron terapia estándar (Grupo control). Todos los pacientes fueron evaluados mediante Electrocardiograma, Ecocardiografía, Holter ECG, RMN Cardíaca, Test de esfuerzo, Potenciales Ventriculares Tardíos, Variabilidad de Frecuencia Cardíaca y evaluación clínica a los 0, 3, 6 y 12 meses. La capacidad funcional (CF) fue evaluada clínicamente y por cuestionarios de calidad de vida. Elanálisis estadístico fue realizado mediante Test Anova, y test de Bonferroni. Resultados: El grupo trasplantado presentó un aumento significativo de la FEVI a los 6 meses (26.75+/-4.85 vs 37.82+/-6.97 por ciento, p=0.001) mejoría que se mantuvo a los 12 meses (26.75+/-4.85 vs 37.27+/-7.51 por ciento, p=0.002). Hubo una mejora significativa de la CF en el grupo trasplantado a los 6 y 12 meses (p<0.001). No hubo cambios significativos en los volúmenes de ventrículo izquierdo, así como en las restantes variables estudiadas. En el grupo control no observamos cambios de estas variables. No hubo complicaciones en relación al trasplante de BMCs. Conclusión: En pacientes con IC severa y baja FEVI, el trasplante intracoronario de células BMCs au-tólogas, se asoció a una mejoría significativa de la FEVI y la CF, a los 6 y 12 meses. Adicionalmente, no observamos ...

Background: Recent studies indicate that intra-coronary delivery of autologous bone marrow mono-nuclear cells (BMCs) improves the ejection fraction (LVEF) and other clinical markers in patients with heart failure (HF). Aim: To evaluate the safety and efficacy of intraco-ronary delivery of autologous BMCs in patients with HF in dilated phase under optimal medical treatment. Method: Of 23 consecutive patients who met the inclusion criteria, 12 were assigned to autologous BMCs intracoronary transplantation, receiving a mean dose of 8.19+/-4.43 x 106 CD34+ cells (BMCs group). The remaining patients received only standard therapy (control group). All patients were evaluated by Electrocardiogram, Echocardiography, Holter Monitoring, Cardiac Magnetic Resonance Imaging, Stress Testing, Ventricular Late potetials, Heart Rate Variability, and regular clinical examination at baseline and at follow-up (3, 6 and 12 months). Repeated measures ANOVA and Bonferroni testing were used for statistic analysis. Results: The BMCs group presented a significant increase in EF at sixth months (26.75+/-4.85 vs. 37.82+/-6.97 per cent, p=0.001) and 12 months post-transplant (26.75+/-4.85 vs. 37.27+/-7.51 per cent, p=0.002). There was a significant improvement in functional (NYHA) in the transplanted group at 6 and 12 months (p<0.001). There were no significant changes concerning left ventricular volumes, heart rate variability and exercise stress testing. We observed no improvement of these variables in the control group. There were no complications related to the BMCs transplant. Conclusions: Intracoronary infusion of auto-logous BMCs, in addition to standard therapy, was associated with significant improvement of left ventricular function at 12 months in patients with HF. We observed no complications relative to the procedure.

[ln-hospital mortality after ST-segment elevation myocardial infarction according to reperfusion therapy]. / Mortalidad intrahospitalaria en hombres y mujeres según terapias de reperfusión en infarto agudo del miocardio con supradesnivel del ST.

BACKGROUND: Primary angioplasty is considered the best reperfusion therapy in the treatment of ST-segment elevation myocardial infarction (STEMI). However, thrombolysis is the reperfusion method most commonly used, due to its wide availability, reduced costs and ease of administration. AIM: To compare in-hospital mortality in STEMI patients according to reperfusion therapy. MATERIAL AND METHODS: Patients admitted to Chilean hospitals participating in the GEMI network, from 2001 to 2005, with STEMI were included. They were divided in three groups: a) treated with thrombolytics, b) treated with primary angioplasty, c) without reperfusion procedure. In-hospital mortality according to gender, was analyzed in each group, using a logistic regression method, to assess risk factors associated with mortality. RESULTS: We included 3,255 patients. Global mortality was 9.9% (7.5% in men and 16.7% in women, p<0.001). Mortality in patients treated with thrombolytics, was 10.2% (7.6% in men and 18.7% in women, p<0.01). The figure for patients treated with primary angioplasty, was 4.7% (2.5% in men and 13% in women, p<0.01), and in patients without reperfusion, was 11.6% (9.8% in men and in 15.4% women, p<0.01). In each group women were older, had a higher prevalence of hypertension and a higher percentage of Killip 3-4 infarctions. Logistic regression showed that angioplasty, compared with no reperfusion, was associated with a reduced mortality only in men. The use of thrombolytics in women was associated with a higher mortality. CONCLUSIONS: Primary angioplasty was the reperfusion therapy associated to the lower mortality in STEMI. Use of thrombolytics in women was associated with a higher mortality rate than in non reperfused women.

Mortalidad intrahospitalaria en hombres y mujeres según terapias de reperfusión en infarto agudo del miocardio con supradesnivel del ST / ln-hospital mortality after ST-segment elevation myocardial infarction according to reperiusion therapy

Primary angioplasty is considered the best reperiusion therapy in the treatment of ST-segment elevation myocardial infarction (STEMI). However, thrombolysis is the reperiusion method most commonly used, due to its wide availability, reduced costs and ease of administration. Aim: To compare inhospital mortality in STEMI patients according to reperiusion therapy. Material and Methods: Patients admitted to Chilean hospitals participating in the GEMI network, from 2001 to 2005, with STEMI were included. They were divided in three groups: a) treated with thrombolytics, b) treated with primary angioplasty, c) without reperiusion procedure. Inhospital mortality according to gender, was analized in each group, using a logistic regression method, to assess risk factors associated with mortality. Results: We included 3,255 patients. Global mortality was 9.9 percent (7.5 percent in men and 16.7 percent in women, p <0.001). Mortality in patients treated with thrombolytics, was 10.2 percent (7.6 percent in men and 18.7 percent in women, p <0.01). The figure for patients treated with primary angioplasty, was 4.7 percent (2.5 percent in men and 13 percent in women, p <0.01), and in patients without reperiusion, was 11.6 percent (9.8 percent in men and in 15.4 percent women, p <0.01). In each group women were older, had a higher prevalence of hypertension and a higher percentage of Killip 3-4 infarctions. Logistic regression showed that angioplasty, compared with no reperiusion, was associated with a reduced mortality only in men. The use oí thrombolytics in women was associated with a higher mortality. Conclusions: Primary angioplasty was the reperiusion therapy associated to the lower mortality in STEMI. Use of thrombolytics in women was associated with a higher mortality rate than in non reperfused women.

[Usefulness of thrombolytic therapy with low doses of streptokinase in acute myocardial infarction]. / Utilidad de la terapia trombolítica con estreptokinasa a dosis baja en infarto agudo del miocardio.

BACKGROUND: The optimal dose of Streptokinase in the treatment of acute myocardial infarction is not well established. Apparently, the thrombolytic efficacy would not increase with doses over 750,000 units. AIM: To compare the effectiveness and safety of treatment with low doses of Streptokinase, ranging from 500,000 to 750,000 units, in patients with ST elevation acute myocardial infarction. PATIENTS AND METHODS: From September 1993 to September 1998, the GEMI register of patients with acute myocardial infarction, was carried out in 37 hospitals, incorporating 4,938 patients. Of these, 1,631 patients received streptokinase. According to the administered dose of Streptokinase, patients were divided in two groups: 1,465 patients who received 1.5 millions U in 60 minutes (classical therapy group), and 166 patients with ischemic chest discomfort and either ST-segment elevation or left bundle-branch block on the electrocardiogram, who received 500,000 to 750,000 U streptokinase administered in no more than 30 minutes, with heparin, within 0 to 6 hours of symptom onset. Successful reperfusion, mortality, complications, and hospital outcome was evaluated in both groups. RESULTS: The low dose group of patients had a better reperfusion criteria profile. No differences between groups were observed in patient evolution, mortality, maximum Killip classification, post myocardial infarction heart failure, ischemic complications, arrhythmias or mechanical complications. CONCLUSIONS: These results suggest that streptokinase in low doses is at least as effective as classical therapy, in the treatment of ST elevation acute myocardial infarction.

[Reduction of myocardial infarction mortality in Chilean hospitals]. / Reducción de la mortalidad por infarto del miocardio en hospitales chilenos.

BACKGROUND: The characteristics of patients with acute myocardial infarction (MI) admitted to 37 Chilean hospitals (GEMI Registry Group), have been analyzed in the period 1993-1995 and 1997-1998. AIM: To report the changes in hospital mortality between these 2 periods, with a particular emphasis on the impact of treatment. PATIENTS AND METHODS: Between 1993-1995 we collected information from 2,957 patients and between 1997-1998 we registered 1,981 patients with MI. Analysis of the changes in mortality between periods was adjusted by demographic variables, coronary risk factors, MI location, Killip class on admission and the different therapeutic strategies utilized. The effects of different treatments on hospital mortality were adjusted by the previously determined mortality risk variables. RESULTS: Hospital mortality decreased from 13.3% to 10.8% between both periods (Odds Ratio (OR) 0.78, confidence intervals (95%) (CI) 0.65-0.93). A significant reduction in mortality was observed among patients below 60 years of age, in men, in diabetics and in subjects with an infarction classified as Killip class over II. The use of beta blockers (OR 0.65, CI 0.42-0.99) and intravenous nitrates (OR 0.78, CI 0.61-0.99) and the lower use of calcium channel blockers (OR 0.72, CI 0.60-0.87) were significantly associated with a lower mortality. The administration of angiotensin converting enzyme inhibitors was associated with a 29.3% mortality reduction (OR 0.69, CI 0.47-1.02). CONCLUSIONS: There has been a significant reduction in the mortality rate for MI in Chilean hospitals during the 2 registry periods analyzed, which was significant among some high risk patients and was related to treatment changes, according to evidence based guidelines.

La punción biopsia prostática transrectal guiada por ecografía, el PSA y el tacto rectal en la detección del cáncer de próstata / Prostate cancer: transrectal US guided biopsy, digital rectal examination and prostatic specific antigen

El cáncer de próstata tiene una incidencia creciente en varones sexagenarios, cuyo diagnóstico se basa en el tacto rectal, el PSA y la punción biopsia. Para contrastar nuestro grupo de pacientes biopsiados en 1999, con aquellos de otros servicios privados, examinados retrospectivamente nuestro archivo de historias clínicas, los datos de servicios de patología, de laboratorios y del Registro Regional de Tumores. De 1089 estudios ecográficos prostáticos separamos 49 con historia clínica completa, tabulando edad, tacto, histología, tomas, volúmen y ecogenicidad de la próstata, inflamación y niveles de PSA. Obtuvimos diagnósticos de 227 punciones del medio privado, edades, y cantidades de PSA efectuadas en laboratorios, y los datos del Registro Regional de Tumores. Tratamos nuestros datos con test de "t", ANOVA de una vía y regresiones con técnica "forward stepwise". Vimos relación entre PSA y número de muestras (p=0,2231) y entre tacto rectal y cáncer (p=0,1678). Las restantes variables mostraron entre ellas p<0,05. No obtuvimos pendiente de regresión en ninguno de los modelos planteados. Nuestra serie mostró nueve pacientes con cáncer de próstata, cuatro de ellos con PSA por debajo de 4 ng/ml. Diagnosticamos cáncer en el 18 por ciento de nuestros biopsiados. La incidencia de cáncer prostático aumentó, al menos, 81 por ciento en la década, cuyo diagnóstico temprano se ha incrementado por el PSA y por la ecografía. No deberían excluirse a candidatos a biopsia sólo por un PSA normal. No encontramos regresión entre PSA y cáncer en nuestras series, ni entre volúmen y cáncer y vimos relación entre tacto y cáncer. Presumimos que cada uno de los 62 cánceres de próstata diagnosticados durante 1999 puede haber insumido $3.744 al sistema

La punción biopsia prostática transrectal guiada por ecografía, el PSA y el tacto rectal en la detección del cáncer de próstata / Prostate cancer: transrectal US guided biopsy, digital rectal examination and prostatic specific antigen

El cáncer de próstata tiene una incidencia creciente en varones sexagenarios, cuyo diagnóstico se basa en el tacto rectal, el PSA y la punción biopsia. Para contrastar nuestro grupo de pacientes biopsiados en 1999, con aquellos de otros servicios privados, examinados retrospectivamente nuestro archivo de historias clínicas, los datos de servicios de patología, de laboratorios y del Registro Regional de Tumores. De 1089 estudios ecográficos prostáticos separamos 49 con historia clínica completa, tabulando edad, tacto, histología, tomas, volúmen y ecogenicidad de la próstata, inflamación y niveles de PSA. Obtuvimos diagnósticos de 227 punciones del medio privado, edades, y cantidades de PSA efectuadas en laboratorios, y los datos del Registro Regional de Tumores. Tratamos nuestros datos con test de "t", ANOVA de una vía y regresiones con técnica "forward stepwise". Vimos relación entre PSA y número de muestras (p=0,2231) y entre tacto rectal y cáncer (p=0,1678). Las restantes variables mostraron entre ellas p<0,05. No obtuvimos pendiente de regresión en ninguno de los modelos planteados. Nuestra serie mostró nueve pacientes con cáncer de próstata, cuatro de ellos con PSA por debajo de 4 ng/ml. Diagnosticamos cáncer en el 18 por ciento de nuestros biopsiados. La incidencia de cáncer prostático aumentó, al menos, 81 por ciento en la década, cuyo diagnóstico temprano se ha incrementado por el PSA y por la ecografía. No deberían excluirse a candidatos a biopsia sólo por un PSA normal. No encontramos regresión entre PSA y cáncer en nuestras series, ni entre volúmen y cáncer y vimos relación entre tacto y cáncer. Presumimos que cada uno de los 62 cánceres de próstata diagnosticados durante 1999 puede haber insumido $3.744 al sistema (AU)