Instituto FLENI

CABA, Argentina

Instituto FLENI

CABA, Argentina
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Perez-Millan M.I.,CONICET | Berner S.I.,Hospital Santa Lucia | Luque G.M.,CONICET | De Bonis C.,Servicio de Neurocirugia | And 3 more authors.
Pituitary | Year: 2013

The role of angiogenesis in human pituitary tumor progression is questioned. Our aim was to characterize the morphologic changes that occur in the vasculature of pituitary adenomas, in correlation with the expression of nestin, a protein found in endothelial cells of newly formed vessels of developing organs. We also evaluated the relation of angiogenic markers and nestin with Ki-67 index. Immunohistochemical studies were performed on paraffin embedded samples of 47 pituitary adenomas and six normal pituitaries. We determined microvessel density (number of CD31+ or CD34+ vessels per square millimetre), vascular area (cumulative area occupied by vessels), average vessel size, and further classified vessels as small (<100 μm2) or large (>100 μm2). We correlated the above parameters with nestin expression and Ki-67 index. Lower vascular area compared to normal tissue was found in adenomas (p < 0.05). Interestingly, pituitary adenomas had significantly more small vessels than control pituitaries (p < 0.04 for CD31 and CD34). In tumors many capillaries were positive for nestin, while scarce staining was detected in controls, so that nestin positive area was significantly higher in tumors. Furthermore, nestin area correlated positively with the % of small vessels. Ki-67 correlated neither with vascular area nor with nestin expression. In human pituitary tumors there was a predominance of small capillaries in correlation with increased expression of the progenitor marker nestin. We suggest that angiogenesis is an active process in these tumors, in spite of their low total vascular area when compared to normal pituitaries. © 2012 Springer Science+Business Media, LLC.


Penas-Steinhardt A.,University of Buenos Aires | Barcos L.S.,University of Buenos Aires | Barcos L.S.,National University of Luján | Belforte F.S.,University of Buenos Aires | And 10 more authors.
PLoS ONE | Year: 2012

Subclinical low-grade systemic inflammation has been associated with obesity, insulin resistance and metabolic syndrome (MS). Recent studies have highlighted the role of gut microbiota in these disorders. The toll-like receptor 4 (TLR4) plays a key role in the innate immune response activation. We studied two polymorphisms (+3725G/C and 11350G/C) in the 3′ untranslated region (3′UTR) of the TLR4 gene that may alter its expression and their association with metabolic disorders related to systemic inflammation. We cloned the 3′UTR into a luciferase reporter system and compared wild-type 3′UTR (WT) and +3725C variant (MUT) constructs luciferase activities. MUT construct reduced the reporter gene activity by 30% compared to WT (P = 0.0001). To evaluate the association between these polymorphisms with biochemical and clinical overweight related variables, we conducted a population cross-sectional study in 966 men of Argentine general population. Considering smoking as a confounding variable that causes systemic inflammation, we studied these possible effects in both, smokers and nonsmokers. The 11350G/C polymorphism was not detected in our sample whereas the CC genotype of +3725 polymorphism was associated with lean subjects (p = 0.011) and higher Adiponectin levels (p = 0.021). Subjects without any NCEP/ATP III MS component were associated with this genotype as well (p = 0.001). These results were strengthened in nonsmokers, in which CC genotype was associated with lean subjects (p = 0.003) and compared with G carriers showed significantly lower BMI (25.53 vs. 28.60 kg/m2; p = 0.023) and waist circumference (89.27 vs. 97.51 cm; p = 0.025). None of these associations were found in smokers. These results showed that +3725C variant has a functional effect down-regulating gene expression and it could be considered as a predictive factor against overweight, particularly in nonsmokers. Considering the role of TLR4 in inflammation, these findings would suggest that the presence of +3725C variant could predict a lower prevalence of chronic metabolic disorders. © 2012 Penas-Steinhardt et al.


Filippatos G.,National and Kapodistrian University of Athens | Khan S.S.,Northwestern University | Ambrosy A.P.,Duke University | Cleland J.G.F.,Imperial College London | And 14 more authors.
European Journal of Heart Failure | Year: 2015

Aims The clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF. Methods Data collection for the registry will be conducted at ?300 sites located in ?40 countries. Comprehensive data including demographics, clinical presentation, co-morbidities, treatment patterns, quality of life, in-hospital and post-discharge outcomes, and health utilization and costs will be collected. Enrolment of ?20 000 adult patients hospitalized with new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year period is planned with subsequent 3 years follow-up. Perspective The REPORT-HF registry will explore the clinical characteristics, management, and outcomes of HF worldwide. This global research programme may have implications for the formulation of public health policy and the design and conduct of international clinical trials. © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.


Bevacqua R.J.,Hospital General Of Agudos Dr Jose Maria Ramos Mejia | Perrone S.V.,Instituto FLENI | Perrone S.V.,Instituto Argentino Of Diagnostico Y Tratamiento | Perrone S.V.,Hospital Alta Complejidad En Red El Cruce Dr Nestor Carlos Kirchner | And 2 more authors.
Insuficiencia Cardiaca | Year: 2013

Over the last decade has witnessed extensive progress in basic and clinical research in the field of pulmonary arterial hypertension (PAH). International PAH registries have achieved much to advance our understanding of the epidemiology, demographics, etiology, clinical course, hemodynamics, disease management and treatment outcomes of PAH. Therapies available to target the pathophysiology of PAH have expanded considerably and more options are expected in the near future. However, the long-term prognosis for patients with PAH remains poor. Recent evidence suggests that World Health Organization functional (WHO) class I or II patients have significantly better long-term survival rates than WHO functional class III-IV patients, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programs have an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH. © 2013 Silver Horse.


Perrone S.V.,Instituto FLENI | Ronderos R.,Instituto Cardiovascular Buenos Aires | Ronderos R.,Institute Cardiologia La Plata | Embon M.,Instituto FLENI | Zuelgaray J.G.,Instituto Argentino Of Diagnostico Y Tratamiento S A
Insuficiencia Cardiaca | Year: 2010

We present a case of a 36 years-old female patient who presents palpitations and dyspnea, with heart failure due to non-compacted cardiomyopathy and severe left ventricular systolic deterioration. Due to the absence of improvement instead of full medical tolerated treatment, we decided to install cardiac resynchronization therapy device with an implantable cardioverter defibrillator device. One year after placement of the device, the patient is asymptomatic with clear improvement of echocardiographic parameters. © 2010 Silver Horse.


Carosella V.C.,Instituto FLENI | Mastantuono C.,Sanatorio Dr. Julio Mendez | Golovonevsky V.,Sanatorio Dr. Julio Mendez | Cohen V.,Sanatorio Dr. Julio Mendez | And 4 more authors.
Revista Argentina de Cardiologia | Year: 2014

Introduction In patients with aortic stenosis and planned aortic valve replacement, an accurate stratification of surgical risk is mandatory to offer the best individual option. Preoperative risk scores have recovered a leading role in the assessment of these patients. Objectives The aim of this study was to perform a prospective, multicentric validation of the ArgenSCORE and compare its performance with the EuroSCORE I and the EuroSCORE II. Methods A total of 250 adult patients undergoing aortic valve replacement at four centers of the City of Buenos Aires were included in the study from February 2008 to December 2012. The ArgenSCORE was compared with the EuroSCORE I and the EuroSCORE II, evaluating model discrimination with the area under the ROC curve and calibration comparing the relation between observed mortality and predicted mortality. Results The mean age of the validation population (n = 250) was 68.62 ± 13.3 years and overall mortality of 3.6%. The ArgenSCORE showed good discrimination power (area under the ROC curve of 0.82) and a good predictive capacity to allocate risk (relation between observed mortality: 3.6% vs. predicted mortality: 3.39%; p = 0.471). The EuroSCORE I showed poor discrimination power (area under the ROC curve of 0.62) and risk overestimation (relation between observed mortality: 3.6% vs. predicted mortality: 5.58%; p < 0.0001). The EuroSCORE II showed an acceptable discrimination power (area under the ROC curve of 0.76), though lower than that of the ArgenSCORE, but a significant underestimation of predicted risk (relation between observed mortality: 3.6% vs. predicted mortality: 1.64%; p < 0.0001). Conclusions The ArgenSCORE evidenced adequate ability to predict mortality in patients undergoing AVR surgery. This local model demonstrated good discrimination power and better calibration compared to the European models, as the EuroSCORE I overestimated and the EuroSCORE II underestimated predicted risk.


Giorgi M.A.,Instituto FLENI | Cohen Arazi H.,Instituto FLENI | Gonzalez C.D.,Instituto FLENI | Di Girolamo G.,Instituto FLENI
Expert Opinion on Pharmacotherapy | Year: 2011

Introduction: Clinical nonresponse to clopidogrel has been associated with variability in response.This has led to the development of other P2Y12 receptor inhibitors, such as prasugrel and ticagrelor, with different pharmacokinetic characteristics that influence their pharmacodynamics.Areas covered: Clopidogrel response variability is attributable to its complex pharmacokinetics and is vulnerable to genetic polymorphisms in genes involved in absorption, metabolism and drug-drug interactions (i.e., proton pump inhibitors).Prasugrel which has a simpler metabolism, leading to greater bioavailability, seems to be less affected by genetic or drug-drug interactions and achieves a greater antiplatelet effect.Ticagrelor is the most novel compound approved with a simpler metabolism.Both prasugrel and ticagrelor reached their antiplatelet effect faster and to a much greater extent than clopidogrel.All these differences observed in kinetics explain, to some degree, the efficacy and safety profile observed in clinical trials for these molecules associated with other antiplatelet agents (aspirin, gpIIb/IIIa inhibitors) and anticoagulants.Expert opinion: Clopidogrel is still the best standard of care.However, the pharmacokinetic advantages of both prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for the appropriate subject. © 2011 Informa UK, Ltd.


Despite the progress made in the treatment of heart failure, it remains associated with high morbidity and mortality. Several studies link elevated heart rate to cardiac remodeling and increased morbidity and mortality with a higher incidence of cardiovascular events. But is the heart rate an independent risk factor in patients with heart failure? Doesthe reduction in heart rate in patients with heart failure may provide additional benefit added to the recommended therapeutic with beta receptor blockers? The study SHIFT (Systolic Heart failure Treatment with the If inhibitor ivabradine Trial) allowed us to evaluate the effects of ivabradine versus placebo in patients with heart failure due to left ventricular dysfunction with a baseline heart rate> 70 beats/minute in functional class II to IV of the New York Heart Association. This study showed that the addition of ivabradine in patients with low ejection fraction, heart rate ≥ 70 beats per minute and sinus rhythm is associated with a significant reduction in mortality. SHIFT study contributed to a shift in the way we see the heart failure to show us that we have more than the intervention on the renin-angiotensin-aldosterone and the adrenergic system that is highly beneficial for our patients and our health system. © 2010 Silver Horse.


Mazzei J.A.,University of Buenos Aires | Caneva J.O.,Hospital Universitario | Perrone S.V.,Instituto FLENI | Melero M.J.,University of Buenos Aires | And 2 more authors.
Medicina | Year: 2011

The term pulmonary hyper- tension includes a heterogeneous group of disorders which produce an obstructive remodeling of the lung vessels characterized by a steady rise in pulmonary arterial pressure. The ensuing morbidity and mortality of this disease result from the failure of the right ventricle to compensate this increase in the after-load. The conditions to achieve an optimum treatment of pulmonary hypertension patients are: a clinical presumption and early diagnosis, an adequate stratification based on the underlying causes and the different vascular territories involved, the response to therapy and the degree of severity, the selection of the different therapeutic alternatives and their timely indication. These recommendations are aimed at the general practitioner and their objective is to facilitate the early detection, diagnosis and treatment of pulmonary hypertension patients, representing a major change in the prognosis. Moreover, as the diagnostic evaluation requires complementary tests that are not usually available in all medical centers, they can also be used as the basis to request a timely referral to institutions with the adequate complexity.


Carosella V.C.,Instituto FLENI | Grancelli H.,Instituto FLENI | RodriGUEZ W.,Instituto FLENI | Sellanes M.,Instituto FLENI | And 4 more authors.
Revista Argentina de Cardiologia | Year: 2011

During the last decades, several risk assessment models have been applied to predict the risk of mortality after cardiac surgery; however, none of them have been developed in Latin American populations. These models have inferior performance when applied to patient groups other than the ones on whom they were developed. Objectives To perform external and temporal validation of a local risk score for cardiac surgery [Argentinean System for Cardiac Operative Risk Evaluation (ArgenSCORE)] and compare it to the EuroSCORE. Material and Methods A total of 5268 consecutive adult patients undergoing cardiac surgery were included from June 1994 to December 2009. The risk model was developed through logistic regression on the data of 2903 patients who underwent cardiac surgery between June 1994 and December 1999 at a center. Prospective internal validation was performed on 708 patients between January 2000 and June 2001. External and temporal validation of the recalibrated model were performed between February 2000 and December 2009, evaluating model discrimination and calibration in patients operated on at four centers different from the one where the score had been originally developed. The method was also compared to the EuroSCORE. Results The external validation was performed on 1657 patients, mean age was 62.8±13.3 years and global mortality was 4.58%. The ArgenSCORE showed both good discriminatory power with an area under the ROC curve of 0.80 and predictive capacity for risk assessment in all patients (observed mortality 4.58% vs. expected mortality 4.54%; p=0.842). The EuroSCORE showed good discriminatory power (area under the ROC curve of 0.79) but overestimated the risk (observed mortality 4.58% vs. expected mortality 5.23%; p <0.0001). Conclusions The ArgenSCORE showed an adequate capacity to predict in-hospital mortality in cardiac surgery 10 years after being developed. The score can be applied to populations with similar geographic characteristics, showing a better performance compared to an established international risk stratification model.

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