HIF-1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end-stage Chagas disease patients.

Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% of Trypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads to ventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end-stage Chagas disease patients. Although the pathophysiology of Chagas disease has been addressed for decades by numerous groups, the cardiac immunologic mechanisms involved in the progression of clinical manifestation are still unknown. Growing evidence demonstrates that hypoxia-inducible factor (HIF)-1α plays indispensable roles in driving immune response by triggering the expression of CD73 purinergic ecto-enzyme. Purinergic system controls the duration and magnitude of purine signals directed to modulate immune cells through the conversion of extracellular ATP (microbicide/proinflammatory) to the immunoregulatory metabolite adenosine. In the present work, we described that infiltrating leukocytes within cardiac explants from patients with end-stage Chagas cardiomyopathy up-regulated HIF-1α and CD73 expression. Moreover, the number of HIF-1α+ and CD73+ leukocytes positively correlated with the myocarditis severity and the local parasite load. Furthermore, we demonstrated a direct relationship between tissue parasite persistence and the influx of immune cells to the infected hearts, which ultimately determine the severity of the myocarditis. These findings provide evidence that CD73-dependent regulatory pathways are locally triggered in the myocardium of patients with end-stage Chagas disease.

Experiencia preliminar con el uso del soporte vital extracorpóreo como puente al trasplante pulmonar / Preliminary Experience of the Use of Extracorporeal Life Support as a Bridge to Lung Transplantation

Introducción: Diversos estudios han demostrado los beneficios del soporte vital extracorpóreo en pacientes críticos con patologías cardiorrespiratorias. El objetivo del presente trabajo consiste en evaluar la experiencia preliminar con el uso del soporte vital extracorpóreo en pacientes con enfermedad pulmonar avanzada, en lista de espera para trasplante pulmonar. Material y métodos: Se realizó un análisis retrospectivo y descriptivo de los pacientes que recibieron soporte vital extracorpóreo como puente al trasplante o a la candidatura para trasplante, entre agosto 2010 y julio 2015. Se analizaron los resultados según: exclusión de la lista de espera, candidatos a trasplante y trasplantes realizados. Se describen complicaciones y causas de mortalidad, tiempos de soporte vital extracorpóreo, asistencia respiratoria mecánica e internación post-trasplante. Se incluyeron 23 pacientes, edad promedio 36 ± 17 años, 61% mujeres. Los diagnósticos principales fueron fibrosis quística (34.8%), fibrosis pulmonar idiopática (30.4%) y fibrosis pulmonar secundaria (13.0%). Resultados: El tiempo medio con soporte vital extracorpóreo fue 14.4 ± 11.7 días; y se realizó veno-venoso en 14 pacientes, veno-arterial en 4, arterio-venoso 3 casos y veno-arterio-venoso en 2. Ocho pacientes no calificaron como candidatos al trasplante y se excluyeron de la lista de espera. Fueron aceptados como puente al trasplante 15 pacientes; 8 fallecieron bajo soporte vital extracorpóreo y 7 lograron ser trasplantados. Post trasplante, un paciente falleció y 6 fueron externados superando el año de supervivencia. Conclusión: En nuestra serie, el 46.7% de los candidatos lograron acceder al trasplante pulmonar bajo soporte vital extracorpóreo. La implementación de un programa de soporte vital extracorpóreo como puente al trasplante pulmonar efectivo requiere acceso a nuevas tecnologías y desarrollo de experiencia por parte del equipo.

Introduction: Several studies have demonstrated that the use of extracorporeal life support (ECLS) improves the recovery of critically ill patients with cardiorespiratory diseases. The purpose of this study was to evaluate a preliminary experience on the use of ECLS as a bridge to lung transplantation. Methods: We conducted a retrospective and descriptive analysis of patients who received ECLS as a bridge to lung transplantation between August 2010 and July 2015. ECLS results were analyzed according to the final status: excluded from the waiting list, confirmed transplant candidacy and transplanted patients. Complications and cause of mortality were evaluated, as well as the length of ECLS, time on mechanical ventilation, length of stay and survival. Twenty-three patients were included, mean age 36±17 years, 61% were female. The most common diagnoses were cystic fibrosis (34.8%), idiopathic pulmonary fibrosis (30.4%) and secondary pulmonary fibrosis (13.0%). Results: Mean time on ECLS was 14.4±11.7 days; veno-venous support was implemented in 14 patients, veno-arterial support in 4 cases, arterio-venous in 3, and veno-arterio-venous in 2. During ECLS, 8 patients did not qualify as candidates for transplantation. Fifteen patients were accepted as candidates for lung transplant, 8 of them died during ECLS, and 7 were transplanted. After transplant, one patient died and 6 were discharged from the hospital. Conclusion: The use of ECLS provided a successful bridge to lung transplantation in 46.7% of the patients. The implementation of an effective ECLS program requires of the conjunction between the technological advances and the development of the center's experience.

Preliminary Experience of the Use of Extracorporeal Life Support as a Bridge to Lung Transplantation

Introduction: Several studies have demonstrated the benefits of extracorporeal life support in critically ill patients with cardiorespiratory diseases. The purpose of this study was to evaluate the preliminary experience of the use of extracorporeal life support in patients with advanced pulmonary disease on the waiting list for lung transplantation. Materials and Methods: We conducted a retrospective and descriptive analysis of patients who received extracorporeal life support as a bridge to lung transplantation or to lung transplantation candidacy between August 2010 and July 2015. Results were analyzed according to: exclusion from the waiting list, transplant candidates and number of transplants performed. We described complications and causes of mortality, and duration of extracorporeal life support, mechanical respiratory assistance and post-transplant hospitalization. Twenty-three patients were included, with a mean age of 36 ± 17 years; 61% were female. The most common diagnoses were cystic fibrosis (34.8%), idiopathic pulmonary fibrosis (30.4%) and secondary pulmonary fibrosis (13.0%). Results: Mean time on extracorporeal life support was 14.4 ± 11.7 days; veno-venous support was implemented in 14 patients, veno-arterial support in 4 cases, arterio-venous in 3, and veno-arterio-venous in 2. Eight patients did not qualify as candidates for transplantation and were excluded from the waiting list. 15 patients were accepted as a bridge for lung transplant; 8 of them died while receiving extracorporeal life support, and 7 were transplanted. After the transplantation, one patient died and 6 were discharged from the hospital with more than one year survival. Conclusion: In our series, 46.7% of candidates had access to lung transplantation under extracorporeal life support. The implementation of an effective extracorporeal life support program as a bridge to lung transplantation requires the access to new technologies and the development of the Center's team experience.

Trasplante cardiorenal combinado en la enfermedad cardíaca y renal avanzada / Combined cardiorenal transplant in heart and advanced renal disease

Introducción: la insuficiencia renal (IR) es predictor de morbimortalidad postrasplante cardíaco (TxC). El trasplante cardiorenal (TxCR) combinado en candidatos a TxC con enfermedad renal severa, es una opción terapéutica. Nuestro objetivo es evaluar los resultados y seguimiento del TxCR en un único Centro. Material y métodos: Entre febrero de 1993 y diciembre de 2014 se realizaron 442 TxC. Desde el año 2006 se efectuaron TxCR con único donante en 20 pacientes (p). Los criterios de selección fueron: IR con ClCr ≤ 40 mil/min o requerimiento de diálisis en candidatos a TxC. Todos los p recibieron timoglobulina e inmunosupresión con tacrolimus, micofenolato mofetil y esteroides. La mediana de seguimiento fue 46 meses (7-96). Resultados: Edad media 58±7 años y 85% eran hombres. La creatinina (Cr) media 3,1+-2,5 mg/ dl y ClCr 27,5+10 mil/min. Requirieron diálisis 3p en el período pre trasplante y 4p se encontraban en diálisis crónica. Etiología de miocardiopatías dilatadas: coronaria 10p, no coronaria 9p y reTxC 1p; nefropatías: nefroangioesclerosis 5p, síndrome cardiorenal 10p, diabetes 2p, glomerulopatía 1p, poliquistosis 1p y nefritis tóxica 1p. La Cr a 30 días y a 1 año del TxCR fue 1,2+-0,4 mm/dl y 1,1+-0,2 mg/dl respectivamente. La mortalidad hospitalaria fue de 3/20p (15%), 2p por sepsis y 1p por falla del injerto cardíaco. Mortalidad alejada 5/17p (29%), 4p por sepsis y 1p por sarcoma hepatocelular. La supervivencia a 1 y 3 años fue del 76 y 72%. Conclusiones: En nuestra serie el TxCR fue un tratamiento seguro y eficaz en candidatos a TxC y con ClCr < 40 mil/min.

Introduction: renal failure (RF) is a post cardiac transplantation predictor of morbimortality. The combined cardiorenal transplant (CCRTx) in cardiac transplantation (CTx) candidates with chronic renal disease is a therapeutic option. Our aim was to evaluate the CCRTx follow up outcomes in a single Centre. Methods: Between 2/1993 and 12/2014 we performed 442 CTx. Since 2006, 20 patients (p) underwent CCRTx using allografts from the same donor. The inclusion criteria were: RF with CrCl ≤ 40 mil/min or dialysis requirement in CTx candidates. All p received Thymoglobulin and immunosuppression with tacrolimus, mycophenolate mofetil and steroids.Median follow up: 46 months (7-96). Results: Mean age: 58±7 years, 85% were male. Mean Creatinine (Cr): 3,1+-2,5 mg/dl and ClCr 27,5+10 mil/min. Three p required dialysis during the pre-transplantation phase and 4 p were under chronic dialysis. Etiologies: cardiomyopathies: coronary 10 p, noncoronary 9 p and re CTx, 1 p; nephropathies: nephroangiosclerosis 5 p, cardiorenal syndrome 10 p, diabetes 2 p, glomerulopathy 1 p, polycystosis 1 p and toxic nephritis 1 p. At 30 days and 1 year post CCRTx, Cr was 1,2+-0,4 mg/dl and 1,1+-0,2 mg/dl respectively. In-hospital mortality was 3/20 p (15%), 2 p due to sepsis and 1 p due to cardiac graft failure. Late mortality 5/17 p (29 %), 4p due to sepsis and 1 p due to liver sarcoma. Survival at 1 and 3 years was 76 and 72%, respectively. Conclusions: In our series CCRTx was a safe and effective treatment for CTx candidates with CrCl < 40 ml/min.

Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in chagas disease patients.

BACKGROUND: This report describes a real-time PCR (Q-PCR) strategy to quantify Trypanosoma cruzi (T. cruzi) DNA in peripheral blood samples from Chagas disease patients targeted to conserved motifs within the repetitive satellite sequence. METHODOLOGY/PRINCIPAL FINDINGS: The Q-PCR has a detection limit of 0.1 and 0.01 parasites/mL, with a dynamic range of 10(6) and 10(7) for Silvio X10 cl1 (T. cruzi I) and Cl Brener stocks (T. cruzi IIe), respectively, an efficiency of 99%, and a coefficient of determination (R(2)) of 0.998. In order to express accurately the parasitic loads: (1) we adapted a commercial kit based on silica-membrane technology to enable efficient processing of Guanidine Hydrochloride-EDTA treated blood samples and minimize PCR inhibition; (2) results were normalized incorporating a linearized plasmid as an internal standard of the whole procedure; and (3) a correction factor according to the representativity of satellite sequences in each parasite lineage group was determined using a modified real-time PCR protocol (Lg-PCR). The Q-PCR strategy was applied (1) to estimate basal parasite loads in 43 pediatric Chagas disease patients, (2) to follow-up 38 of them receiving treatment with benznidazole, and (3) to monitor three chronic Chagas heart disease patients who underwent heart-transplantation and displayed events of clinical reactivation due to immunosupression. CONCLUSION/SIGNIFICANCE: All together, the high analytical sensitivity of the Q-PCR strategy, the low levels of intra- and inter-assay variations, as well as the accuracy provided by the Lg-PCR based correction factor support this methodology as a key laboratory tool for monitoring clinical reactivation and etiological treatment outcome in Chagas disease patients.

Cardiopatía isquémica con severo deterioro de la función ventricular: alternativas quirúrgicas / Ischemic cardiomyopathy with poor ventricular function: surgical options

El objetivo de este estudio fue evaluar los resultados de la cirugía de revascularización miocárdica y el trasplante cardíaco ortotópico en pacientes con cardiomiopatía isquémica y fracción de eyección de ventrículo izquierdo menor o igual 25 por ciento. Noventa y cuatro pacientes, con edad media de 55,4 ñ 20 años (27-74), 87 (92 por ciento) de sexo masculino, fueron evaluados por el Servicio de Trasplante e Insuficiencia Cardíaca. Se analizaron dos grupos: 48 pacientes (51 por ciento) pertenecientes al grupo de cirugía de revascularización miocárdica y 46 (49 por ciento) al grupo de trasplante cardíaco ortotópico (17 por ciento, 8 pacientes; p= 0,09). No hubo diferencias en la mortalidad hospitalaria y la supervivencia a 3 años en ambos grupos. Ambos métodos mejoraron la clase funcional de disnea y la función ventricular izquierda. La cirugía de revascularización miocárdica debería ser considerada el método de primera elección. Los pacientes con pobre clase funcional de disnea, mayor diámetro diastólico de ventrículo izquierdo y menor fracción de eyección no son buenos candidatos para la revascularización miocárdica. La cantidad de territorios viables predijo la mejoría de la función ventricular