miguel vicco

Background Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease (“conditions of interest”). Methods Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was anal...

La variabilidad de la frecuencia cardíaca (FC) y de la presión arterial (PA) se evalúan por lo general mediante Holter y monitorización ambulatoria de la presión arterial (MAPA). Estos exámenes no se encuentran disponibles generalmente en el medio hospitalario. Objetivo: Evaluar los parámetros de la función barorrefleja determinada por electrocardiograma basal y durante la realización de la maniobra de Valsalva (MV), con los indicadores de variabilidad de FC por Holter y PA por MAPA. Métodos: Estudio transversal, observacional. Se incluyeron prospectivamente pacientes adultos, sin enfermedades ni utilización de fármacos que modifiquen la FC o la PA. Se realizó electrocardiograma (ECG) basal de 10 s. La respuesta cronotrópica se evaluó mediante MV estandarizada registrada en ECG. Se realizaron MAPA y Holter de 12 horas. Resultados: Se estudiaron 50 pacientes, observándose que el SDNN del ECG de 10 s y la variación de la FC intra/previa a la MV podrían resultar de utilidad para estima...

Introduction: chronic Chagas heart disease (CCHD) is the most common manifestation of American Trypanosomiasis, causing about 50,000 deaths annually. Several factors bear correlation with the severity of CCHD. However, to our knowledge, the assessment on the contribution of major cardiovascular risk factors (CRF), such as hypertension and atherogenic dyslipidemia (AD) to CCHD severity is scarce, despite their well-established role in coronary artery disease, heart failure and stroke. Objective: to explore the potential relationship of blood pressure and AD with the clinical profile of patients with CCHD. Methods: we performed a cross-sectional study in T. cruzi seropositive patients categorized according to a standard CCHD classification. All individuals were subjected to complete clinical examination. Autoantibodies induced by T. cruzi were assessed by ELISA. Results: we observed that Atherogenic index (AI) levels rose significantly in relation to the severity of the CCHD stage, wi...

La presencia de anticuerpos inducidos por Trypanosoma cruzi se relaciona con el perfil clínico de personas con miocardiopatía chagásica crónica.Materiales y Métodos: Realizamos un trabajo observacional transversal con 177 personas seropositivas a T. cruzi. En base a la clasificación de Storino et al se conformaron los siguientes grupos: I) 65 individuos con estudios radiológicos, electrocardiográficos y ecocardiográficos normales; II) 65 pacientes con alteraciones electrocardiográficas pero sin insuficiencia cardiaca; y III) 47 personas con insuficiencia cardiaca y/o miocardiopatía dilatada por ecocardiograma transtorácico. Se determinó la escala de Boston para insuficiencia cardiaca y se evaluaron los anticuerpos contra los antígenos ribosomal p2β y B13 mediante ELISA.Resultados: La muestra se conformó con 91 hombres y 86 mujeres de 52.73±12.32 años. La valoración de la escala de Boston para la predicción de insuficiencia cardiaca sistólica presentó un área debajo de la curva de 85.7% para un criterio de 7 puntos (p=0.026). En relación a los anticuerpos inducidos por T. cruzi, observamos que el anticuerpo anti-B13 fue mayor en los individuos con fracción de eyección disminuida (p<0.001). La correlación entre anti-B13 y la escala de Boston mostró una fuerte asociación (Spearman´s=0.76; p<0.001). Por su parte, anti-p2β, a pesar de no relacionarse a los grupos clínicos de la miocardiopatía chagásica, se correlacionaron inversamente con las concentraciones de triglicéridos y el índice aterogénico. Éste índice fue mayor en los individuos del grupo III.Conclusiones: Nuestros resultados sugieren que anti-p2β y anti-B13 se relacionan al perfil clínico de las personas con enfermedad de Chagas.Fil: Peverengo, Luz María. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodeles Antonelli, Luz María. Universidad Nacional del Litoral. Facultad de Ciencias Médicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prochetto, Estefanía Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bertona, Daiana. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Poato, Alexia Ayelén. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Cabrera, Gabriel Gustavo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vicco, Miguel Hernán. Universidad Nacional del Litoral. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The difficulties encountered in achieving treatments for chronic Chagas disease have promoted the investigation of new therapeutic strategies. In this study, we used two murine models of Trypanosoma cruzi chronic infection to determine the usefulness of applying a therapeutic vaccine alone or followed by benznidazole (Bz) chemotherapy. A vaccine formulation based on an N-terminal fragment of Trans-sialidase (TS) and Immunostimulant Particle Adjuvant (ISPA) - TSNt-ISPA was obtained. Firstly, the immunogenicity and protective capacity of TSNt-ISPA was demonstrated as a prophylactic formulation in an acute model of infection. Later, the formulation was assessed as a therapeutic vaccine alone or combined with (Bz) using two models of chronic infection. BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 T. cruzi strains were not treated as control or treated only with the therapeutic vaccine TSNt-ISPA, with a combined treatment TSNt-ISPA+Bz (Bz applied after the vaccine), or only with Bz. The vaccination schedule consisted of TSNt-ISPA administration at 110, 120, and 130 days post-infection (pi) and Bz administration was performed daily from 140 to 170 days pi. At 273 days pi, electrocardiographic (ECG) parameters, heart parasite load, myocarditis, and heart fibrosis were assessed. In both models, therapeutic administration of TSNt-ISPA reduced ECG alterations and the cardiac tissue damage observed in the chronic phase. Moreover, vaccine treatment significantly decreased heart parasite load in both Sylvio X10/4 and Tulahuen cl2 infected mice. The combined treatment, but not Bz or vaccine administration alone, allowed to restore ECG parameters in Tulahuen cl2 infected mice. The results indicate the usefulness of the therapeutic TSNt-ISPA formulation in BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 strain. For the mice infected with T. cruzi Tulahuen cl2 strain, the combined treatment with the vaccine and Bz had a more positive effect on the course of heart disease than the individual treatments with the vaccine or Bz alone.

Objective. To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. Methods. Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. Results. 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed c...

Potential activation of β2 adrenergic receptors (β2AR) by specific autoreactive antibodies (Abs) that arise during the host reaction to Trypanosoma cruzi, could contribute to the elevated prevalence of metabolic disturbances described in patients with chronic Chagas disease (CCD). This study aimed to determine the prevalence of anti-β2AR Abs in patients with CCD, as well as the correlation of these Abs with the presence of glucose and lipid metabolism disturbances, in order to explore their association with an insulin resistance profile. Additionally, we tested the functional effects of anti-β2AR Abs employing an in vitro bioassay with neuroendocrine cells expressing β2AR. A clinical and metabolic evaluation including an OGTT was performed in 80 CCD patients and 40 controls. Anti-β2AR Abs were measured by an in-house-developed ELISA, and the β2 adrenergic activity of affinity-purified IgG fractions from patient’ sera were assayed in CRE-Luc and POMCLuc transfected AtT-20 cells. A hi...

Resumen En la comunidad médica existen opiniones muy dispares frente al aborto. Nos proponemos analizar las premisas filosóficas que enmarcan la opinión de los médicos respecto a la legalización del aborto y corroborar cómo varían según la pertenencia generacional de los profesionales; así como establecer qué rol juega la objeción de conciencia para lograr un equilibrio ante la variedad de posturas existentes. Se realizaron entrevistas a médicos y a estudiantes de medicina interrogando si les parecía correcto o no legalizar el aborto y las razones en las cuales basaban sus posturas . Los médicos más jóvenes fueron quienes se mostraron a favor de la legalización en mayor proporción con argumentos brindados con una perspectiva en salud pública. Ante tan variadas posturas e idiosincrasias que conviven en el ámbito médico, la objeción de conciencia se erige como un instrumento legal necesario para proteger la integridad moral de cada persona.

The use of chimeric molecules fusing several antigenic determinants is a promising strategy for the development of low-cost, standardized and reliable kits to determine specific antibodies. In this study, we designed and assessed a novel recombinant chimera that complements the performance of our previously developed chimera, CP1 [FRA and SAPA antigens (Ags)], to diagnose chronic Chagas disease. The new chimeric protein, named CP3, is composed of MAP, TcD and TSSAII/V/VI antigenic determinants. We compared the performance of both chimeric Ags using a panel of 67 Trypanosoma cruzi-reactive sera and 67 non-reactive ones. The sensitivity of CP3 vs CP1 was 100 and 90.2%, and specificity was 92.5 and 100%, respectively. The mixture of CP1 + CP3 achieved 100% of sensitivity and specificity. More importantly, an additional subset of 17 sera from patients with discordant results of conventional serological methods was analysed; the CP1 + CP3 mixture allowed us to accurately classify 14 of t...

The development of vaccines against Trypanosoma cruzi remains in an exploratory stage. Despite several antigen candidates have been evaluated, a comparison among the performance of the immunogens cannot be carried out because the available reports differ in formulations and infection model. In this work, we compared the protective capacity of seven T. cruzi antigens in the same model of five new antigens and two well-established candidates. Materials & methods: We evaluated highly immunogenic proteins that contain tandem repeats (FRA [flagelar repetitive protein], Tc3, Tc6); enzymes involved in metabolic pathways critical for parasite survival (cytosolic tryparedoxin peroxidase and tryparedoxin peroxidase); and enzymes involved in parasite invasion (trans-sialidase [TS] and cruzipain). All these antigens were formulated with Freund's adjuvant and protection against the parasite infection was assessed in BALB/c mice. Tc3, cytosolic tryparedoxin peroxidase, cruzipain and TS showed...

Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control.Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes. After a challenge with T. cruzi, TSf-immunized mice showed 90% survival and low parasitemia as compared with 40% survival and high parasitemia in PBS-immunized mice.In relation to the regulatory/suppressor arm of the immune system, after T. cruzi infection TSf-immunized mice showed an increase ...

SUMMARY Introduction: chronic Chagas heart disease (CCHD) is the most common manifestation of American Trypanosomiasis, causing about 50,000 deaths annually. Several factors bear correlation with the severity of CCHD. However, to our knowledge, the assessment on the contribution of major cardiovascular risk factors (CRF), such as hypertension and atherogenic dyslipidemia (AD) to CCHD severity is scarce, despite their well-established role in coronary artery disease, heart failure and stroke. Objective: to explore the potential relationship of blood pressure and AD with the clinical profile of patients with CCHD. Methods: we performed a cross-sectional study in T. cruziseropositive patients categorized according to a standard CCHD classification. All individuals were subjected to complete clinical examination. Autoantibodies induced by T. cruzi were assessed by ELISA. Results: we observed that Atherogenic index (AI) levels rose significantly in relation to the severity of the CCHD st...

Autoantibodies cross-reacting with the β1 adrenergic receptor (anti-β1AR and anti-p2β) and cardiac myosin antigens (anti-B13), have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure. We conducted a cross-sectional study of 155 T. cruzi-seropositive patients and 26 age- and gender-matched healthy controls. They were categorized in three stages of CCHD. Serum antibodies were measured by specific immunoassays. Symptomatic individuals showed increased levels of anti-β1AR and anti-B13, while anti-p2β antibodies were similar between groups. A composite logistic regression model including anti-B13, anti-β1AR antibody levels and age, was able to predict systolic heart failure yielding an area under the curve...

Summary Objective: several scores were developed in order to improve the determination of community acquired pneumonia (CAP) severity and its management, mainly CURB-65 and SACP score. However, none of them were evaluated for risk assessment of in-hospital mortality, particularly in individuals who were non-immunosuppressed and/or without any comorbidity. In this regard, the present study was carried out. Methods: we performed a cross-sectional study in 272 immunocompetent patients without comorbidities and with a diagnosis of CAP. Performance of CURB- 65 and SCAP scores in predicting in-hospital mortality was evaluated. Also, variables related to death were assessed. Furthermore, in order to design a model of in-hospital mortality prediction, sampled individuals were randomly divided in two groups. The association of the variables with mortality was weighed and, by multiple binary regression, a model was constructed in one of the subgroups. Then, it was validated in the other subgr...

Introduction: ascites is one of the most common complications of cirrhosis associated with a high rate of mortality. Although several scores have been developed in order to assess the prognosis of the disease, they were designed for predicting liver transplantation requirements and mortality in the short term, but not while in hospital. The aim of this study was to weigh risk factors for in-hospital mortality in adult patients with ascites due to alcoholic cirrhosis. Material and methods: we performed a cross-sectional study in 180 adult patients with diagnosis of cirrhosis with portal hypertension associated with high alcohol intake. The diagnosis of cirrhosis was made by liver echography and portal hypertension was defined by clinical features plus serum-ascites albumin gradient. Sampled individuals were subjected to complete clinical examination. Child Pugh and the MELD scores were applied in all the patients. Results: nineteen patients died while in-hospital. Mortality was assoc...

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipe...

Studies indicate that Trypanosoma cruzi is capable of inducing immunological disturbances such as decreased expression of molecules involved in T-cell survival and costimulation for antigen-driven T-cell responses. On the other hand, several reports have described that BCG vaccination induces a T-helper 1-type immune response with protective effects in different pathologies. In this regard, we evaluated whether BCG vaccination coexists with a better clinical and immunological profile of chronic Chagas heart disease (CCHD). We performed a cross-sectional study in T. cruzi seropositive patients categorized according the BCG vaccine background and to the well-established CCHD classification provided by Storino et al. All individuals were subjected to a complete clinical examination. All patients presented detectable levels of autoantibodies anti-p2β, anti-B13, anti-FRA and antiparasite homogenate immunoglobulins, which were unrelated to age and sex distribution or blood pressure values. Comparisons according to BCG vaccination revealed that individuals who had not been vaccinated presented higher values of antibodies, and patients without BCG vaccine had an OR of 6.1 (95 % CI 1.23-29.25, p = 0.02) for globally dilated cardiomyopathy with reduced ejection fraction (Hosmer and Lemeshow test of 5.2 p = 0.73). Our results suggest that BCG vaccination coexists with a better clinical and immunological profile of CCHD, associated with lower cardiac involvement.

Introduccion: La decision de internar a un paciente con neumonia es guiada por la utilizacion de escalas pronosticas siendo las mas frecuentes el Indice de Severidad de Neumonia de Fine et al  y la escala CURB-65 de la Sociedad Britanica de Torax. Objetivo: Evaluar la aplicabilidad y concordancia entre dichas escalas en la clasificacion de los pacientes en grupos de riesgo. Metodos: Se realizo un estudio descriptivo, retrospectivo, y observacional. Se revisaron las historias clinicas de pacientes internados en el Servicio de Clinica Medica del Hospital J. B. Iturraspe desde 1997 al 2008, mayores de 15 anos con neumonia. Se clasificaron en bajo y alto riesgo, considerandose de alto riesgo los pacientes con un puntaje de CURB 65 de ≥2 y clase de Fine ≥IV. Resultados: Se incluyeron 235 pacientes, 117 mujeres y 118 hombres; la media de edad fue de 54 ± 20 anos. En la evolucion clinica, un 20% requirio internacion en terapia intensiva y un 7,7% asistencia respiratoria mecanica. La mortalidad fue de 3,4%. La concordancia entre escalas fue de 0,58 (p<0.05). La mortalidad comparada entre los grupos fue mayor en los pacientes de alto riesgo segun el CURB-65 (p=0,008) pero no hubo diferencias al utilizar el score de Fine, que si identifico mejor como de alto riesgo a los pacientes que presentaron insuficiencia respiratoria. Conclusion: La concordancia fue moderada, no encontrandose un mejor desempeno del score de Fine en relacion al CURB 65 en la categorizacion de riesgo, siendo esta ultima mas sencilla de utilizar.