Systematic review and meta-analysis on the adverse events of rimonabant treatment: Considerations for its potential use in hepatology

<p>Abstract</p> <p>Background</p> <p>The cannabinoid-1 receptor blockers have been proposed in the management of obesity and obesity-related liver diseases (fatty liver as NAFLD or NASH). Due to increasing number of patients to be potentially treated and the need to assess the advantage of this treatment in terms of risk/benefit, we analyze the side events reported during the treatment with rimonabant by a systematic review and meta-analysis of all randomized controlled studies.</p> <p>Methods</p> <p>All published randomized controlled trials using rimonabant <it>versus </it>placebo in adult subjects were retrieved. Relative risks (RR) with 95% confidence interval for relevant adverse events and number needed to harm was calculated.</p> <p>Results</p> <p>Nine trials (n = 9635) were considered. Rimonabant 20 mg was associated with an increased risk of adverse event (RR 1.35; 95%CI 1.17-1.56), increased discontinuation rate (RR 1.79; 95%CI 1.35-2.38), psychiatric (RR 2.35; 95%CI 1.66-3.34), and nervous system adverse events (RR 2.35; 95%CI 1.49-3.70). The number needed to harm for psychiatric adverse events is 30.</p> <p>Conclusion</p> <p>Rimonabant is associated with an increased risk of adverse events. Despite of an increasing interest for its use on fatty liver, the security profile and efficacy it is needs to be carefully assessed before its recommendation. At present the use of rimonabant on fatty liver cannot be recommended.</p

Prophylactic Activated Recombinant Factor VII in Liver Resection and Liver Transplantation: Systematic Review and Meta-Analysis

Intraoperative blood loss is a frequent complication of hepatic resection and orthotopic liver transplantation. Recombinant activated coagulation factor VII (rFVIIa) is a coagulation protein that induces hemostasis by directly activating factor X. There is no clear information about the prophylactic value of rFVIIa in hepatobiliary surgery, specifically in liver resection and orthotopic liver transplantation. The aim of this study was to assess the effect of rFVIIa prophylaxis to prevent mortality and bleeding resulting from hepatobiliary surgery.Relevant randomized trials were identified by searching The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index. Randomized clinical trials comparing different rFVIIa prophylactic schemas against placebo or no intervention to prevent bleeding in hepatobiliary surgery were included. Adults undergoing liver resection, partial hepatectomy, or orthotopic liver transplantation were included. Dichotomous data were analyzed calculating odds ratios (ORs) and 95% confidence intervals (CIs). Continuous data were analyzed calculating mean differences (MD) and 95% CIs.Four randomized controlled trials were included. There were no significant differences between rFVIIa and placebo for mortality (OR 0.96; 95% CI 0.35-2.62), red blood cell units (MD 0.32; 95% CI -0.08-0.72) or adverse events (OR 1.55; 95% CI 0.97-2.49).The available information is limited, precluding the ability to draw conclusions regarding bleeding prophylaxis in hepatobiliary surgery using rFVIIa. Although an apparent lack of effect was observed in all outcomes studied, further research is needed

Aspectos prácticos de medicina basada en evidencias

Si se considera a la historia como algo más queun depósito de anécdotas o cronología, puedeproducir una transformación decisiva de laimagen que tenemos actualmente de la ciencia.Ya desde 1962 Thomas S. Kuhn remarcaba laimportancia del cambio y transformación de losparadigmas en el campo científico considerandocomo paradigma a un modelo o patrón aceptado.En esta aplicación común, el paradigma funcionapermitiendo la renovación de ejemplos cada unode los cuales podría servir para reemplazarlo. Enciencia un paradigma es raramente un objetopara renovación, en lugar de ello, tal y como unadecisión judicial aceptada en el derecho común,es un objeto para una mayor articulación yespecificación, en condiciones nuevas o másrigurosas1. El desarrollo de la Medicina Basada enEvidencias (MBE) surge como un nuevoparadigma que busca responder a las nuevas&nbsp;necesidades, sociales, económicas y culturalescontemporáneas

Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new <it>in vitro </it>model of NASH.</p> <p>Methods</p> <p>HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured.</p> <p>Results</p> <p>FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species.</p> <p>Conclusions</p> <p>The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH.</p

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6% (CI 3.7–5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14−25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P 30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). Conclusions: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIFC had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.Fil: Mendizabal, Manuel. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Ridruejo, Ezequiel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Centro de Educación Médica e Investigaciones Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piñero, Federico. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Anders, Margarita. Hospital Alemán; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Padilla, Martín Jesus. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Toro, Luis G.. Fundación de Medellín y Rionegro; ColombiaFil: Torre, Aldo. Instituto Nacional de Ciencias Médicas y Nutrición; MéxicoFil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; ArgentinaFil: Urzúa, Alvaro. Universidad de Chile; ChileFil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Silveyra, María Dolores. Sanatorio Anchorena; ArgentinaFil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; BrasilFil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Peralta, Mirta. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pages, Josefina. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: García, Sandro Ruiz. Hospital de Víctor Lazarte Echegaray; PerúFil: Gutierrez Lozano, Isabel. Centro Médico ABC; MéxicoFil: Macias, Yuridia. IMSS Hospital General Regional No. 1 “Dr. Carlos Mc Gregor Sánchez”; MéxicoFil: Cocozzella, Daniel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Hospital Italiano de La Plata; ArgentinaFil: Chavez Tapia, Norberto. Medica Sur Clinic & Foundation; MéxicoFil: Tagle, Martín. Clínica Anglo-Americana; PerúFil: Dominguez, Alejandra. Hospital Padre Hurtado; ChileFil: Varón, Adriana. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Fundación Cardio Infantil; ColombiaFil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo del IESS; EcuadorFil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga”; MéxicoFil: Bustios, Carla. Fundación Cardio Infantil; ColombiaFil: Conte, Damián. Hospital Privado de Córdoba; ArgentinaFil: Escajadillo, Nataly. Universidad Austral; ArgentinaFil: Rubinstein, Fernando Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; BrasilFil: Tenorio, Laura. Hospital Nacional Edgardo Rebagliati Martins; Per

Systematic review and meta-analysis on the adverse events of rimonabant treatment: Considerations for its potential use in hepatology

<p>Abstract</p> <p>Background</p> <p>The cannabinoid-1 receptor blockers have been proposed in the management of obesity and obesity-related liver diseases (fatty liver as NAFLD or NASH). Due to increasing number of patients to be potentially treated and the need to assess the advantage of this treatment in terms of risk/benefit, we analyze the side events reported during the treatment with rimonabant by a systematic review and meta-analysis of all randomized controlled studies.</p> <p>Methods</p> <p>All published randomized controlled trials using rimonabant <it>versus </it>placebo in adult subjects were retrieved. Relative risks (RR) with 95% confidence interval for relevant adverse events and number needed to harm was calculated.</p> <p>Results</p> <p>Nine trials (n = 9635) were considered. Rimonabant 20 mg was associated with an increased risk of adverse event (RR 1.35; 95%CI 1.17-1.56), increased discontinuation rate (RR 1.79; 95%CI 1.35-2.38), psychiatric (RR 2.35; 95%CI 1.66-3.34), and nervous system adverse events (RR 2.35; 95%CI 1.49-3.70). The number needed to harm for psychiatric adverse events is 30.</p> <p>Conclusion</p> <p>Rimonabant is associated with an increased risk of adverse events. Despite of an increasing interest for its use on fatty liver, the security profile and efficacy it is needs to be carefully assessed before its recommendation. At present the use of rimonabant on fatty liver cannot be recommended.</p

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO