Introducción a los espacios fibrados

Traballo Fin de Grao en Matemáticas. Curso 2019-2020En este trabajo se definen los espacios fibrados, haciendo un pequeño estudio de los localmente triviales para abordar como ejemplo el fibrado de las referencias lineale

Epicardial Fat and Hepatic Steatosis as Cardiovascular Risk Markers

El tejido adiposo epicardico (TAE) es un tejido metabólicamente activo que ha cobrado gran interés en la última década como marcador de riesgo cardiovascular. El TAE se relaciona con la producción de citoquinas proinflamatorias y de ácidos grasos libres, con la promoción de un estado de hipercoagulabilidad, y con numerosos factores de riesgo cardiometabólico. Existe una íntima relación entre las arterias coronarias y el TAE, no solo anatómica, sino en cuanto a aspectos fisiológicos bidireccionales de regulación paracrina. Además, numerosos estudios han encontrado una relación entre el TAE y la presencia de disfunción endotelial, ateromatosis no obstructiva, estrés oxidativo, fibrilación auricular, y disfunción diastólica. En paralelo, existe una estrecha relación entre la esteatosis hepática (la enfermedad hepática crónica más frecuente), la ateromatosis coronaria, y el riesgo cardiovascular. Una de las características interesantes de la esteatosis hepática y diferenciales con respecto a la enfermedad coronaria es su carácter dinámico y, en cierta medida, reversible. A pesar de las asociaciones descriptas con la ateromatosis y con el riesgo cardiovascular, y de su evaluación sencilla a partir de métodos de imagen no invasivos, la grasa epicárdica y el hígado graso no alcohólico son raramente considerados como marcadores de riesgo en la práctica clínica.Epicardial adipose tissue (EAT) is a metabolically active tissue which has raised great interest in the last decade as a cardiovascular risk marker. It is related with the production of proinflammatory cytokines and free fatty acids, the promotion of a state of hyper-coagulability and with numerous cardiometabolic risk factors. Between EAT and coronary arteries, there is not only an intimate anatomical association, but also bidirectional physiological aspects of paracrine regulation. In addition, several studies have found a relationship between EAT and endothelial dysfunction, non-obstructive atheromatosis, oxidative stress, atrial fibrillation and diastolic dysfunction. Parallel to these findings, there is a tight association between hepatic steatosis (the most prevalent chronic hepatic disease), coronary atheromatosis and cardiovascular risk. One of the interesting and differential characteristics of hepatic steatosis with respect to coronary artery disease is its dynamic, and to a certain point reversible, character. Despite their association with atheromatosis and cardiovascular risk, and simple assessment from non-invasive imaging methods, epicardial fat and non-alcoholic fatty liver are seldom considered as risk markers in clinical practice.Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arufe, Diego. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Epicardial Fat and Hepatic Steatosis as Cardiovascular Risk Markers

Epicardial adipose tissue (EAT) is a metabolically active tissue which has raised great interest in the last decade as a cardiovascularrisk marker. It is related with the production of proinflammatory cytokines and free fatty acids, the promotion of a state of hypercoagulabilityand with numerous cardiometabolic risk factors. Between EAT and coronary arteries, there is not only an intimateanatomical association, but also bidirectional physiological aspects of paracrine regulation. In addition, several studies have founda relationship between EAT and endothelial dysfunction, non-obstructive atheromatosis, oxidative stress, atrial fibrillation anddiastolic dysfunction.Parallel to these findings, there is a tight association between hepatic steatosis (the most prevalent chronic hepatic disease), coronaryatheromatosis and cardiovascular risk. One of the interesting and differential characteristics of hepatic steatosis with respectto coronary artery disease is its dynamic, and to a certain point reversible, character.Despite their association with atheromatosis and cardiovascular risk, and simple assessment from non-invasive imaging methods,epicardial fat and non-alcoholic fatty liver are seldom considered as risk markers in clinical practice.El tejido adiposo epicárdico (TAE) es el depósito graso visceral intratorácico localizado entre el miocardio y el pericardio, en íntimo contacto con las arterias coronarias en todo su trayecto. Considerado históricamente como un simple depósito de energía, el TAE es un tejido metabólicamente activo que ha cobrado gran interés en la última década como marcador de riesgo cardiovascular. Tanto el TAE como el tejido adiposo visceral abdominal, de mismo origen embriológico, se relacionan con la producción de citoquinas proinflamatorias y de ácidos grasos libres (AGL), con la promoción de un estado de hipercoagulabilidad, y con numerosos factores de riesgo cardiometabólico. En particular, los pacientes diabéticos evidencian un mayor volumen de TAE, con un perfil metabólicamente más activo y proinflamatorio independientemente de los otros factores de riesgo cardiovasculare

Development of new non-viral systems for genetic modification of senescent cells

Senescence is a process characterized by a prolonged irreversible cell-cycle arrest. The accumulation of senescent cells in tissues is related to aging and to the development of age-related diseases. Recently, gene therapy has emerged as a powerful tool for treating age-associated diseases by the transference of specific genes into the target cell population. However, the high sensitivity of senescent cells significantly precludes their genetic modification via classical viral and non-viral systems. Niosomes are self-assembled non-viral nanocarriers that exhibit important advantages due to their elevated cytocompatibility, versatility, and cost-efficiency, arising as a new alternative for genetic modification of senescent cells. In this work, we explore for the first time the use of niosomes for genetic modification of senescent umbilical cord-derived mesenchymal stem cells. We report that niosome composition greatly affected transfection efficiency; those formulations prepared in medium with sucrose and containing cholesterol as helper lipid being the most suitable to transfect senescent cells. Moreover, resulting niosome formulations exhibited a superior transfection efficiency with a markedly less cytotoxicity than the commercial reagent Lipofectamine. These findings highlight the potentiality of niosomes as effective vectors for genetic modification of senescent cells, providing new tools for the prevention and/or treatment of age-related diseases

Isolated Intrapulmonary Vascular Dilatations and the Risk of Developing Hepatopulmonary Syndrome in Liver Transplant Candidates

Background: The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series. Aims: To assess the development of hepatopulmonary syndrome (HPS) in patients with isolated IPVD and to evaluate outcomes of IPVD and HPS among patients evaluated for liver transplantation (LT). Material and methods: Data from a prospective cohort of patients evaluated for LT with standardized screening for HPS were analyzed. IPVDs were defined as the presence of microbubbles in the left atrium > 3 cycles following right atrial opacification. HPS was defined as the presence of IPVD and hypoxemia (Alveolar-arterial gradient ≥ 15 mmHg) in the absence of concomitant cardiopulmonary disease. Results: A total of 104 patients with negative contrast-enhanced echocardiogram (CE) were compared to 63 patients with IPVD and 63 patients with HPS. Only four patients were categorized as ‘severe’ HPS based on degree of hypoxemia (defined as PaO2 0.5). Conclusions: Patients with IPVD appear to have a substantial risk of developing oxygenation impairment over time and progress to HPS. In our cohort, survival in patients with HPS and isolated IPVD is not different when compared to those without IPVDs

Successful orthotopic liver transplantation and delayed delivery of a healthy newborn in a woman with fulminant hepatic failure during the second trimester of pregnancy

Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient’s and fetus’ immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby’s lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby’s growths until the attainment of a viable gestational age was feasible despite the mother’s fulminant hepatic failure and liver transplant surgery

Outbreak of hepatitis A in a post-vaccination era: High rate of co-infection with sexually transmitted diseases

Introduction and objectives: After hepatitis A (HAV) mandatory immunization in 2005 in Argentina, the incidence of HAV declined drastically. However, several new autochthonous cases of HAV have been reported since 2017. We aimed to evaluate the clinical and epidemiological characteristics and possible transmission routes of affected patients. Patients or Materials and methods: We performed a cross-sectional study of patients residing in Argentina with acute hepatitis A between 30.06.2017 and 31.12.2018. Results: 66 cases of HAV were registered. Fifty-six patients (86%) were males, with a mean age of 34 ± 12 years old. The most likely routes of transmission were sexual intercourse of men with men, reported by 31 patients. Additionally, 23% and 26% of patients tested positive for HIV and syphilis, respectively. In total, 35% of patients required hospitalization. When assessing outcomes, 79% had a mild presentation and 21% had a severe/fulminant presentation: one patient underwent liver transplantation, and one patient died. Conclusions: Our study describes that during the study period, HAV infection affected predominantly young adults, particularly men who have sex with men. An elevated proportion of them was diagnosed with a concomitant sexually transmitted disease, and several patients had a severe presentation of the disease

Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC

Introduction and Objectives: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. Patients and Methods: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). Results: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. Conclusions: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists

Direct-acting antivirals and Hepatocellular Carcinoma: No evidence of higher wait-list progression or posttransplant recurrence

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT

Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay

Introduction and Objectives: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. Materials and Methods: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. Results: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. Conclusions: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032)