Mixed T Helper1/T Helper2/T Cytotoxic Profile in Subjects with Chronic Chagas Disease with Hypersensitivity Reactions to Benznidazole.

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

Evidence of Continued CD4+ and CD8+ T Cell Activity After SARS-COV-2 Clearance in a Late COVID-19 Pneumonia Heart Transplant Patient.

We have studied an unvaccinated heart transplant 64-year-old patient admitted for low-grade fever, dry cough, general malaise, and bilateral interstitial infiltrates, after two months of a diagnosis of coronavirus disease 2019 (COVID-19) bilateral pneumonia. A bronchoalveolar lavage and transbronchial biopsy were performed. Bacterial, mycotic and viral infections were ruled out including repeated reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diffuse thickening of alveolar septa with fibrosis and infiltration of lymphocytes and macrophages into the alveolar septa with aggregates of CD4+ and CD8+ T cells with positive immunolabelling for granzyme B were observed, indicating a continuing cytotoxic process that might have induced proliferation and fibrosis. An intense ongoing immunopathological cellular reaction, potentially triggered by SARS-CoV-2 overcoming the anti-inflammatory and immunomodulatory effects of the immunosuppressive drugs is suggested by these findings, opening to debate the usual approach of minimizing immunosuppression after COVID-19 in transplant patients when presence of SARS-CoV-2 has been ruled out.

Trasplante cardíaco en miocardiopatía chagásica: 23 años de experiencia en un centro de referencia / Heart Transplantation in Chagas Cardiomyopathy: 23-Year Follow-Up in a Referral Center

RESUMEN Introducción: La enfermedad de Chagas afecta aproximadamente a 6 millones de personas en América Latina. El 25 a 35% evoluciona hacia la Miocardiopatía Chagásica (MCh). Una opción terapéutica en sus estadios avanzados es el trasplante cardíaco (TxC). Objetivos: Comparar la supervivencia de pacientes con TxC por MCh frente a otras etiologías. Analizar la incidencia de la reactivación (Ra) de enfermedad de Chagas y su impacto en la supervivencia en este subgrupo de pacientes. Material y métodos: Se evaluaron retrospectivamente pacientes con TxC entre agosto 1998 y marzo 2021. Se analizó la supervivencia mediante curvas de Kaplan-Meier y log rank test. El diagnóstico de Ra se realizó mediante métodos moleculares, prueba de Strout en sangre periférica, tejido miocárdico y/o cutáneo. Resultados: De 606 pacientes con TxC, 39 (6,4%) presentaban MCh. Seguimiento medio 4,4 años (Rango Intercuartilo 1,2-8,6). Edad subgrupo MCh 51 años (RIC 45-60). Hombres 28 (72%). Se documentó Ra en el 38,5% de los pacientes. Supervivencia a 1, 5 y 10 años en TxC por MCh con Ra versus no Ra: 85%, 76% y 61% versus 72%, 55% y 44% (p = 0,3). Supervivencia a 1, 5 y 10 años en TxC por MCh versus TxC por otras causas: 79%, 65% y 50% versus 79%, 62% y 47% (p = 0,5). Conclusión: En nuestra serie no se encontró diferencia estadísticamente significativa en la supervivencia de los pacientes trasplantados cardíacos por MCh en comparación con aquellos trasplantados por otras causas; así como tampoco entre los pacientes que reactivaron la enfermedad de Chagas y los que no lo hicieron.

ABSTRACT Background: Chagas disease affects about 6 million people in Latin America, and 25 to 35% progress to Chagas cardiomyopathy (ChCM). Heart transplantation (HTx) is a therapeutic option in advanced stages. Objectives: The aim of this study is to compare survival of patients with HTx due to ChCM versus those transplanted for other etiologies and to analyze the incidence of Chagas disease reactivation (Ra) and its impact on survival in this group of patients. Methods: Patients undergoing HTx between August 1998 and March 2021 were retrospectively evaluated. Survival was analyzed using Kaplan-Meier curves and the log-rank test. The diagnosis of Ra was performed by molecular methods, Strout's test in peripheral blood, myocardial tissue or skin tissue. Results: Of 606 patients with Htx, 39(6,4%) presented ChCM. Median follow up was 4.4 years (interquartile range 1.2-8.6). Median age of the subgroup with ChCM was 51 years (IQR 45-60) and 28 were men (72%). Reactivation was documented in 38.5% of the patients. Survival at 1, 5 and 10 years in HTx recipients due to ChCM and Ra versus no Ra was 85%, 76% and 61% versus 72%, 55% and 44%, respectively (p = 0.3). Survival at 1, 5 and 10 years in HTx recipients due to ChCM versus HTx for other causes was 79%, 65% and 50% versus 79%, 62% and 47%, respectively (p = 0.5). Conclusion: In our series we did not find statistically significant differences in survival of heart transplant recipients due to ChCM versus those transplanted due to other reasons. Survival in patients with Chagas disease reactivation and those without reactivation was also similar.

[Ischemic cardiogenic shock and short-term mechanical circulatory support as bridge to transplantation]. / Shock cardiogénico en infarto agudo de miocardio y soporte circulatorio puente al trasplante.

Cardiogenic shock (CS) has a high mortality rate and often requires advanced therapies such as mechanical circulatory support (MCS) and heart transplantation (HT). Those patients who presented an acute myocardial infarction (AMI) with CS and required support through MCS as bridge to HT were retrospectively analyzed in a single Center. Between January 1997 and June 2020, 524 patients received HT, 203 for ischemic-cardiomyopathy, 103 were in emergency waiting list. Eleven patients met the inclusion criteria (mean age 53 ± 11 years old; men 73%). Five primary angioplasties and 2 emergency myocardial revascularization surgeries were performed. Four patients had coronary anatomy not subject to revascularization. All received inotropic and vasopressor treatment and required intra-aortic balloon pump (IABP). Subsequently, two required support with a left univentricular centrifugal pump (BioMedicus®, Medtronic) and two with peripheral veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (Maquet®, Getinge Group). The median between AMI and HT was 15 days (range 7-21) and the mean age of the donors 28 ± 11 years. All had extensive AMI (necrotic amount 35 ± 5%) with histopathological signs of transmural necrosis and reperfusion injury. The median follow-up was 9 years (range 1-15). None died in hospitalization or during the first year after transplantation. Survival at 5 and 10 years was 73% and 55%. Emergency HT may be the best option for selected patients with acute myocardial infarction and cardiogenic shock refractory to conventional therapy.

El shock cardiogénico (SC) presenta una elevada mortalidad y puede requerir de terapéuticas avanzadas como la asistencia circulatoria mecánica (ACM) y el trasplante cardíaco (TC). Se analizaron en forma retrospectiva, en un único centro, aquellos pacientes que presentaron un infarto agudo de miocardio (IAM), SC y requirieron ACM puente al TC. Entre enero 1997 y junio 2020, 524 pacientes recibieron un TC, 203 por cardiopatía isquémica, 103 en lista de emergencia. Se incluyeron once pacientes con los criterios mencionados (edad media 53 ± 11 años; hombres 73%). Se realizaron 5 angioplastias primarias y 2 cirugías de revascularización miocárdica de urgencia. Cuatro pacientes presentaban anatomía coronaria no pasible de revascularización. Todos recibieron tratamiento inotrópico y vasopresor y requirieron soporte con balón de contrapulsación intra aórtico (BCIA). Dos requirieron el implante de bomba centrífuga univentricular izquierda (BioMedicus®, Medtronic) y 2 de oxigenador de membrana extracorpóreo veno-arterial (ECMO-VA) periférico (Maquet®, Getinge Group). La mediana entre IAM y TC fue 15 días (rango 7-21) y la edad de los donantes 28 ± 11 años. Todos presentaron un IAM extenso (monto necrótico 35 ± 5%) con signos histopatológicos de necrosis transmural e injuria de reperfusión. La mediana de seguimiento fue 9 años (rango 1-15). Ninguno falleció en la internación ni durante el primer año post trasplante. La supervivencia a los 5 y 10 años fue 73% y 55%. El TC en situación de emergencia ha demostrado ser, en nuestro medio, la mejor opción en aquellos pacientes con IAM y SC refractario a la terapia convencional.

Shock cardiogénico en infarto agudo de miocardio y soporte circulatorio puente al trasplante / Ischemic cardiogenic shock and short-term mechanical circulatory support as bridge to Transplantation

Resumen El shock cardiogénico (SC) presenta una elevada mortalidad y puede requerir de terapéuticas avanzadas como la asistencia circulatoria mecánica (ACM) y el trasplante cardíaco (TC). Se analizaron en forma retrospectiva, en un único centro, aquellos pacientes que presentaron un infarto agudo de miocardio (IAM), SC y requirieron ACM puente al TC. Entre enero 1997 y junio 2020, 524 pacientes recibieron un TC, 203 por cardiopatía isquémica, 103 en lista de emergencia. Se incluyeron once pacientes con los criterios mencionados (edad media 53 ± 11 años; hombres 73%). Se realizaron 5 angioplastias primarias y 2 cirugías de revascularización miocárdica de urgencia. Cuatro pacientes presentaban anatomía coronaria no pasible de revascularización. Todos recibieron tratamiento inotrópico y vasopresor y requirieron soporte con balón de contrapulsación intra aórtico (BCIA). Dos requirieron el implante de bomba centrífuga univentricular izquierda (BioMedicus®, Medtronic) y 2 de oxigenador de membrana extracorpóreo veno-arterial (ECMO-VA) periférico (Maquet®, Getinge Group). La mediana entre IAM y TC fue 15 días (rango 7-21) y la edad de los donantes 28 ± 11 años. Todos presentaron un IAM extenso (monto necrótico 35 ± 5%) con signos histopatológicos de necrosis transmural e injuria de reperfusión. La mediana de seguimiento fue 9 años (rango 1-15). Ninguno falleció en la internación ni durante el primer año post trasplante. La supervivencia a los 5 y 10 años fue 73% y 55%. El TC en situación de emergencia ha demostrado ser, en nuestro medio, la mejor opción en aquellos pacientes con IAM y SC refractario a la terapia convencional.

Abstract Cardiogenic shock (CS) has a high mortality rate and often requires advanced therapies such as mechanical circulatory support (MCS) and heart transplantation (HT). Those patients who presented an acute myocardial infarction (AMI) with CS and required support through MCS as bridge to HT were retrospectively analyzed in a single Center. Between January 1997 and June 2020, 524 patients received HT, 203 for ischemic-cardiomyopathy, 103 were in emergency waiting list. Eleven patients met the inclusion criteria (mean age 53 ± 11 years old; men 73%). Five primary angioplasties and 2 emergency myocardial revasculariza tion surgeries were performed. Four patients had coronary anatomy not subject to revascularization. All received inotropic and vasopressor treatment and required intra-aortic balloon pump (IABP). Subsequently, two required support with a left univentricular centrifugal pump (BioMedicus®, Medtronic) and two with peripheral veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (Maquet®, Getinge Group). The median between AMI and HT was 15 days (range 7-21) and the mean age of the donors 28 ± 11 years. All had extensive AMI (necrotic amount 35 ± 5%) with histopathological signs of transmural necrosis and reperfusion injury. The median follow-up was 9 years (range 1-15). None died in hospitalization or during the first year after transplantation. Survival at 5 and 10 years was 73% and 55%. Emergency HT may be the best option for selected patients with acute myocardial infarction and cardiogenic shock refractory to conventional therapy.

Chagas disease: Historic perspective.

This review is a perspective on the history of Chagas disease, and it adopts a novel approach from literary studies, historical documents and the science and epidemiology of the nature of the disease. From this analysis, comes the review's working definition of the Contact Zone (CZ): "the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships, which usually involve coercive conditions, radical inequality and intolerable conflict." In the Patient-Physician CZ, we verified the triple transition phenomena: the American trypanosomiasis shifted from a rural, acute, and vectorial transmitted disease to an urban, chronic and non-vectorial disease. In the Academic CZ, we describe the original disagreements which denied the existence of the disease and the current controversies about pathogenic mechanisms and etiological treatment. From the News from Latin America, and in the Original CZ, we will review the evolution of different forms of transmission. As in any good story, research across broad disciplines is necessary to reveal historical perspectives, scientific approaches, and the epidemiology of the disease, which has a prequel of 9000 years and an open ending: thus, we explore across the Global CZ, with its multiple and unexpected actors.

Clinical characteristics and outcome of 107 adult patients with chronic Chagas disease and parasitological cure criteria.

BACKGROUND: The cure in adult patients with chronic Chagas disease and the relationship between parasitological and clinical evolution is still under debate. The aim of this study was to analyze the clinical, epidemiological and progression features of the disease in a patient population who became serologically negative either spontaneously or post-etiological treatment. METHODS: We included 107 patients over 20 years old with three different confirmed reactive anti-Trypanosoma cruzi serologic tests on admission, and a minimum of two years of follow-up. Patients were assigned to clinical groups according to Kuschnir. Change of clinical group was considered a heart disease progression criterion, and seronegative conversion of two or three as parasitological cure criterion. RESULTS: From 107 patients with parasitological cure, 82 had received treatment (77%) and 25 became spontaneously seronegative (23%). Forty-six (43%) and 61 (57%) patients had two and three negative serological tests, respectively. No differences in clinical groups, ECG, echocardiogram and heart disease progression were found in patients who became negative spontaneously or post-treatment. The clinical progression and ECG changes were observed in 5/107 (5%) and 11/107 (10%) respectively, in a mean of 10 years follow-up. CONCLUSIONS: Adults with chronic Chagas disease can cure, mostly post-etiological treatment, but also spontaneously, showing a favourable clinical outcome.

Comparison of prevalence, clinical course, and pathological findings of left ventricular systolic impairment versus normal systolic function in patients with hypertrophic cardiomyopathy.

Impaired left ventricular systolic function (ILVSF) in hypertrophic cardiomyopathy (HC) is a risk factor for sudden death and a determinant of high mortality. We determined its prevalence, clinical parameters, long-term outcome, and pathologic findings of explanted hearts. We retrospectively analyzed 382 patients with HC; ILVSF was characterized by LV ejection fraction <50% at rest and was identified in 24 patients (6.3%). Patients with ILVSF were younger than patients with normal SF (43.5 ± 14.1 vs 55.3 ± 20.4 years, p = 0.001) and had larger LV end-diastolic cavity diameter (53.2 ± 12.2 vs 43.8 ± 6.2 mm, p = 0.001), larger left atrium (51.2 ± 6.5 vs 44.3 ± 8 mm, p <0.001), and lower fractional shortening (30.7 ± 11.1% vs 45.5% ± 10.3%, p <0.001). A combined end point (heart failure death or heart transplantation) was considered. Median follow-up was 3 years (1.2 to 6.3). Fourteen patients with ILVSF (58.3%) had the end point compared to 3 (0.8%) with normal SF (p <0.001). In explanted hearts, fibrosis represented 30.5 ± 12.5% of the left ventricle; we observed a direct correlation between fibrosis and ventricular dilation (r = 0.794, p = 0.001) and an inverse correlation between fibrosis and ejection fraction (r = -0.623, p = 0.023). Number and length density of small arterioles (<50 µm in diameter) were significantly decreased. In conclusion, ILVSF in HC has a poor prognosis and is associated with fibrosis and selective decreased development of small arterioles.

Cardiomyocyte hypertrophy, oncosis, and autophagic vacuolization predict mortality in idiopathic dilated cardiomyopathy with advanced heart failure.

OBJECTIVES: The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities. BACKGROUND: There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated. METHODS: In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes. RESULTS: CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality. CONCLUSIONS: CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.

Heart transplantation in rapidly progressive end-stage heart failure associated with celiac disease.

Celiac disease is characterised by chronic immune-mediated malabsorption in genetically susceptible individuals induced by gluten proteins present in wheat, barley and rye. It occurs in adults and children at rates approaching 1% of the population. Cardiomyopathy associated with celiac disease is infrequent. The authors present here a first case of a severe progressive dilated cardiomyopathy that required heart transplantation in young woman with celiac disease.

Open lung biopsy for diffuse disease in patients with and without previously transplanted solid organs.

BACKGROUND: Studies on whether surgical lung biopsy (SLB) modifies the treatment of patients with diffuse lung disease are conflicting, and information is limited on whether it alters treatment in solid-organ transplant recipients. Our objective was to determine and compare the rate of treatment change after SLB for diffuse lung disease in patients with and without a history of solid-organ transplantation. METHODS: Patients undergoing SLB for diffuse lung disease between March 2004 and March 2009 were identified. A retrospective review was performed. RESULTS: Sixty patients had SLB. Thirty-four patients (57%) had solid-organ transplantation. Twenty of 60 patients (33%) had a change in treatment as a result of the findings of the SLB. No significant differences in the treatment change rate were found between the transplant and nontransplant groups (10 of 34 versus 10 of 26; p = 0.46). Transplant patients were more likely to be on mechanical ventilation at the time of SLB (12 of 34 versus 3 of 26; p = 0.03). Mechanical ventilatory support at the time of SLB was associated with increased postoperative complications (odds ratio, 6.20; 95% confidence interval [CI], 1.70 to 22.66; p = 0.006) and in-hospital mortality (odds ratio, 9.75; 95% CI, 2.54 to 37.38; p = 0.001). Being on mechanical ventilation (hazard ratio, 3.91; 95% CI, 1.40 to 10.93; p = 0.009), a diagnosis of cancer (hazard ratio, 13.20; 95% CI, 2.87 to 60.78; p = 0.001), and a history of solid-organ transplantation (hazard ratio, 5.52; 95% CI, 1.08 to 28.14; p = 0.04) were independent predictors of survival. CONCLUSIONS: Surgical lung biopsy changes treatment in one third of patients, with no significant difference between patients without transplantation and solid-organ transplant recipients. Patients who undergo SLB while on mechanical ventilation have a significantly increased risk of postoperative complications and death.

Myocarditis as a form of relapse in two patients with adult Still's disease.

Still's disease is a subset of juvenile idiopathic arthritis (JIA) that usually presents with intermittent fever, rash, and arthritis. Extra-articular flares can occur several years after disease onset. We report two cases of adult Still's disease with myocarditis after several years of being in remission. A 34-year-old Caucasian man with history of systemic juvenile arthritis in remission since age 13 was admitted in hospital with 10 days history of fever, odynophagia, and arthralgias. Chest X-ray and cardiac ultrasound showed cardiac enlargement. An endomyocardial biopsy revealed acute myocarditis. He was treated with methylprednisolone and intravenous gammaglobulin, with improvement of his general condition and cardiac parameters. A 16-year-old Caucasian male patient with history of systemic JIA in remission for the last 7 years was admitted with 7 days history of fever, odynophagia, arthralgias, and myalgias. Two days after admission, he developed chest pain and pericardial rubbing was found on examination. Cardiac ultrasound showed left ventricular dilatation with impaired systolic function, and posterior, inferior and apical-septal wall hypokinesia. Blood test showed elevated creatine phosphokinase levels. He was treated with IV methylprednisolone with normal follow-up cardiac ultrasound. Cardiac involvement in patients with systemic JIA can be the first symptom of disease reactivation, even after many years of disease remission.

The impact of socioeconomic conditions on chronic Chagas disease progression.

INTRODUCTION AND OBJECTIVES: The extent to which a patient's socioeconomic conditions determine the persistence or control of chronic Chagas disease has not been previously investigated. The aim of this study was to evaluate the effect of socioeconomic conditions on clinical and serologic measures of disease progression. METHODS: Data on the following socioeconomic variables were obtained by questioning as part of medical history taking at admission: birth in a rural area, time of residence in endemic and urban areas (in years), overcrowding index (i.e. number of inhabitants/number of bedrooms), absence of toilet facilities, years of education, employed or unemployed, and health insurance coverage (i.e. private contributory medical insurance cover). The study endpoints for the Cox regression analysis were: consistently negative results on serologic tests and on tests for markers of cardiomyopathy progression by the end of the study. RESULTS: The study included 801 Argentine patients (mean age 42 years) who were followed up for a mean of 10 years between 1990 and 2005. After adjustment for age and antiparasitic treatment, negative seroconversion was associated with a short time of residence in an endemic area (hazard ratio [HR]=0.97; 95% confidence interval [CI], 0.96-0.99; P=.004), a low overcrowding index (HR=0.82; 95% CI, 0.70-0.97; P=.022) and medical insurance cover (HR=1.46; 95% CI, 1.01-2.09; P=.04). After adjustment for age, sex, ECG abnormalities and antiparasitic treatment, a low rate of cardiomyopathy progression was associated with more years of education (HR=0.88; 95% CI, 0.80-0.97; P=.01) and higher medical insurance cover (HR=0.49; 95% CI, 0.30-0.81; P=.005). CONCLUSIONS: Socioeconomic conditions had a significant effect on chronic Chagas disease progression which was independent of antiparasitic treatment and clinic characteristics.

The heavy chain variable segment gene repertoire in chronic Chagas' heart disease.

Patients chronically infected with Trypanosoma cruzi develop chronic Chagas' heart disease (cChHD). Their Ab response is suspected to be involved in the cardiac pathogenesis. Reactivity of serum Abs from these patients has been extensively studied but little is known about the diversity of the in vivo IgG repertoire. We analyzed 125 variable H chain (VH) genes and compared it to repertoires from healthy individuals, and patients with autoimmune processes and other infections. VH were from plasma cells isolated from heart tissue of three cChHD patients and from a Fab combinatorial library derived from bone marrow of another cChHD patient. The role of the parasite in shaping the Ab repertoire was assessed analyzing VH genes before and after panning against T. cruzi Ag. Among recovered VH genes, a significantly increased representation of VH4 was observed. Plasma cells at the site of cardiac infiltration showed an increased VH1 usage. CDR3 lengths were similar to the ones found in the healthy repertoire and significantly shorter than in other infections. VH derived from anti-T. cruzi Fab and plasma cells showed a higher proportion of hypermutated genes, 46.9% and 43.75%, respectively, vs 30.9% of the cChHD patient repertoire, pointing to the role of parasite Ags in the shaping of the humoral response in Chagas' disease. No histological evidence of germinal center-like structures was observed in heart tissue. In accordance, VH analysis of heart plasmocytes revealed no evidence of clonal B cell expansion, suggesting that they migrated into heart tissue from secondary lymphoid organs.

El impacto de las condiciones socioeconómicas en la evolución de la enfermedad de Chagas crónica / The impact of socioeconomic conditions on chronic Chagas disease progression

Introducción y objetivos. Las condiciones socioeconómicas del huésped no han sido evaluadas como determinantes de la persistencia o el control de la enfermedad de Chagas crónica. El objetivo fue valorar el impacto de las condiciones socioeconómicas sobre la evolución clínica y serológica. Métodos. Las variables socioeconómicas en estudio fueron obtenidas por interrogatorio como parte de la historia clínica de ingreso: nacimiento en área rural, tiempo de residencia en área endémica y urbana (años), índice de hacinamiento (número de habitantes/número de dormitorios), ausencia de instalaciones sanitarias, años de educación, ocupación/desocupación y cobertura social (planes de asistencia médica por aportación privada). La negativización de las pruebas serológicas y los indicadores de progresión de la cardiopatía al concluir el estudio fueron los puntos finales de evaluación para el análisis de regresión de Cox. Resultados. Se incluyó a 801 pacientes, de 42 años de edad y 10 años de seguimiento promedio, en Argentina, entre los años 1990 y 2005. Un aumento de la seroconversión negativa, ajustada para edad y tratamiento etiológico, se asoció con un menor tiempo de residencia en área endémica (hazard ratio [HR] = 0,97 [0,96-0,99]; p = 0,004), menor índice de hacinamiento (HR = 0,82 [0,70-0,97]; p = 0,022) y mayor cobertura social (HR = 1,46 [1,01-2,09]; p = 0,04). Una disminución de la progresión de la cardiopatía, ajustada para edad, sexo, electrocardiograma anormal y tratamiento etiológico, se observó en pacientes con más años de educación (HR = 0,88 [0,80-0,97]; p = 0,01) y con cobertura social (HR = 0,49 [0,30-0,81]; p = 0,005). Conclusiones. Las condiciones socioeconómicas mostraron un significativo impacto sobre la evolución de la enfermedad de Chagas crónica independientemente del tratamiento antiparasitario y las características clínicas (AU)

Introduction and objectives. The extent to which a patient’s socioeconomic conditions determine the persistence or control of chronic Chagas disease has not been previously investigated. The aim of this study was to evaluate the effect of socioeconomic conditions on clinical and serologic measures of disease progression. Methods. Data on the following socioeconomic variables were obtained by questioning as part of medical history taking at admission: birth in a rural area, time of residence in endemic and urban areas (in years), overcrowding index (ie, number of inhabitants/number of bedrooms), absence of toilet facilities, years of education, employed or unemployed, and health insurance coverage (ie, private contributory medical insurance cover). The study endpoints for the Cox regression analysis were consistently negative results on serologic tests and on tests for markers of cardiomyopathy progression by the end of the study. Results. The study included 801 Argentine patients (mean age, 42 years) who were followed up for a mean of 10 years between 1990 and 2005. After adjustment for age and antiparasitic treatment, negative seroconversion was associated with a short time of residence in an endemic area (hazard ratio [HR] = 0.97; 95% confidence interval [CI], 0.96-0.99; P=.004), a low overcrowding index (HR=0.82; 95% CI, 0.70-0.97; P=.022) and medical insurance cover (HR=1.46; 95% CI, 1.01-2.09; P=.04). After adjustment for age, sex, ECG abnormalities, and antiparasitic treatment, a low rate of cardiomyopathy progression was associated with more years of education (HR=0.88; 95% CI, 0.80-0.97;P=.01) and higher medical insurance cover (HR=0.49; 95% CI, 0.30-0.81; P=.005). Conclusions. Socioeconomic conditions had a significant effect on chronic Chagas disease progression which was independent of antiparasitic treatment and clinic characteristics (AU)

Trypanosoma cruzi DNA in cardiac lesions of Argentinean patients with end-stage chronic chagas heart disease.

The extent of inflammation, fibrosis, and progression of chronic Chagas heart disease (cChHD) was associated with persistence of parasite DNA in cardiac lesions of necropsies or explants from Argentinean cChHD patients. A Trypanosoma cruzi-based polymerase chain reaction showed a positive result in 1) 15% of cardiac sections with less than 10 mononuclear inflammatory cells/high-power field (440x) (MNC/HPF), 89% with 10-19 MNC/HPF, and 100% with more than 20 MNC/HPF (P < 0.0001); 2) 33% with less than 10% fibrosis, 79% with 10-19% fibrosis, and 100% with more than 20% fibrosis (P < 0.01); 3) 25% of specimens from patients classified in Kuschnir groups 0 and I, 70% in group II and 90% in group III (P < .001); and 4) 45% and 90% of the specimens from cChHD patients without or with heart failure, respectively (P < 0.01). These findings stress the role of the parasite in pathogenesis and disease progression of cChHD.

Analysis of the presence of Trypanosoma cruzi in the heart tissue of three patients with chronic Chagas' heart disease.

It is still unclear to what extent myocarditis-associated, chronic Chagas' heart disease is due to persisting Trypanosoma cruzi. In the present study, we have analyzed tissue samples from the hearts of three patients with this disease. In situ hybridization provided little evidence for the presence of intact T. cruzi even at sites of strong inflammation. Nevertheless, micromanipulation techniques detected remnants of both T. cruzi kinetoplast DNA and nuclear DNA. Trypanosoma cruzi DNA was also detected in single macrophages dissected directly from frozen heart tissue sections. Thus, this analysis demonstrates that T. cruzi kinetoplast DNA and nuclear DNA are widely dispersed in the heart tissue, although in low amounts. Since we rarely detected intact T. cruzi parasites during the chronic phase of Chagas' heart disease, we can exclude heart tissue as a major parasite reservoir.

Valor pronóstico de los anticuerpos anti-glicolípidos de músculo esquelético en la angina inestable / Prognostic value of anti-skeletal muscle glycolipid antibodies in unstable angina

Se estudió si la determinación del nivel de anticuerpos anti-glicolípidos de músculo esquelético, un marcador de rechazo agudo en el trasplante cardíaco, podía representar un predictor de pronóstico adverso durante la hospitalización de pacientes con angina inestable como ocurre con el aumento de las troponinas cardíacas T e I. Se investigó la presencia y título de anticuerpos anti-glicolípidos de músculo esuqlético, por el método ELISA en el suero de 50 pacientes con angina inestable, al momento de la admisión y 24 h después. El descenso en el título de anticuerpos a las 24 h fue un predictor de la ocurrencia de eventos cardíacos adversos (muerte, infarto agudo de miocardio, revascularización de urgencia y angina refractaria) durante la hospitalización, especialmente en pacientes con antecedentes de infarto de miocardio previo, y es aparentemente para este grupo un mejor predictor de evolución que la determinación de las troponinas cardíacas T e I

Valor pronóstico de los anticuerpos anti-glicolípidos de músculo esquelético en la angina inestable / Prognostic value of anti-skeletal muscle glycolipid antibodies in unstable angina

Se estudió si la determinación del nivel de anticuerpos anti-glicolípidos de músculo esquelético, un marcador de rechazo agudo en el trasplante cardíaco, podía representar un predictor de pronóstico adverso durante la hospitalización de pacientes con angina inestable como ocurre con el aumento de las troponinas cardíacas T e I. Se investigó la presencia y título de anticuerpos anti-glicolípidos de músculo esuqlético, por el método ELISA en el suero de 50 pacientes con angina inestable, al momento de la admisión y 24 h después. El descenso en el título de anticuerpos a las 24 h fue un predictor de la ocurrencia de eventos cardíacos adversos (muerte, infarto agudo de miocardio, revascularización de urgencia y angina refractaria) durante la hospitalización, especialmente en pacientes con antecedentes de infarto de miocardio previo, y es aparentemente para este grupo un mejor predictor de evolución que la determinación de las troponinas cardíacas T e I (AU)

Mixomas cardíacos: estudio clínico - patológico y seguimiento alejado de 31 casos resecados quirurgicamente / Cardiac myxomas: clinic - pathologic study and remote follow-up of 31 cases surgically resected

Introducción: Los tumores cardíacos representan una patología de escasa prevalencia con inclusión de los denominados mixomas (Mx) cardíacos que constituyen el 60 por ciento de aquellos. Por tal razón no existe en nuestro medio una casuística con un número suficiente como para extraer conocimientos útiles para el enfoque diagnóstico y terapéutico. Las manifestaciones clínicas y sus formas de presentación son usualmente proteiformes. Objetivos: El objetivo principal del presente trabajo fue estudiar las distintas formas de presentación y las principales características clínicas de los tumores mixomatosos cardíacos, así como la evolución hospitalaria y alejada de un grupo de 31 pacientes (pts) sometidos a cirugía de resección de Mx. De manera adicional se analizaron los hallazgos anatomopatológicos y las probabilidades de recidiva y embolia tumoral. Material y métodos: Entre julio de 1992 y diciembre de 1999 se identificaron 31 pts portadores de Mx. Se estudió la evolución hospitalaria y alejada de los pts operados. En un subgrupo de pts con Mx se realizó el análisis del patrón de ploidía del ADN tumoral con el objeto de identificar pts con posibilidad de recidiva y/o embolias tumorales. Resultados: La incidencia de los Mx en nuestra población operada (total de casos 14440) de diversos tipos de cirugía cardiovascular fue de 0,21 por ciento, y 0,027 por ciento del total (112280) de historias clínicas más frecuentes fueron: los síntomas constitucionales ( 74,2 por ciento), la disnea (45,16 por ciento) y los episodios embólicos (41,93 por ciento). De las características anatomopatológicas analizadas sólo el diámetro menor más pequeño de los Mx se correlacionó en forma independiente con embolia tumoral (p=0,007)...(TRUNCADO)