Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

Unlabelled: With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis.

Methods: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472).

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.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.

Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic.

Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project.

[Adrenal insufficiency in cirrhotic patients].

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

Introduction: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis.

Aim: We evaluated the effect of food intake on LS in patients with different degrees of liver disease.

Patients And Methods: We evaluated 24 patients (F≤1, n=11 and F> 1, n=13).

Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.

HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis.

Induced maturation of human immunodeficiency virus.

Unlabelled: HIV-1 assembles at the plasma membrane of virus-producing cells as an immature, noninfectious particle. Processing of the Gag and Gag-Pol polyproteins by the viral protease (PR) activates the viral enzymes and results in dramatic structural rearrangements within the virion--termed maturation--that are a prerequisite for infectivity. Despite its fundamental importance for viral replication, little is currently known about the regulation of proteolysis and about the dynamics and structural intermediates of maturation.

In vitro analysis of human immunodeficiency virus particle dissociation: gag proteolytic processing influences dissociation kinetics.

Human immunodeficiency virus particles undergo a step of proteolytic maturation, in which the main structural polyprotein Gag is cleaved into its mature subunits matrix (MA), capsid (CA), nucleocapsid (NC) and p6. Gag proteolytic processing is accompanied by a dramatic structural rearrangement within the virion, which is necessary for virus infectivity and has been proposed to proceed through a sequence of dissociation and reformation of the capsid lattice. Morphological maturation appears to be tightly regulated, with sequential cleavage events and two small spacer peptides within Gag playing important roles by regulating the disassembly of the immature capsid layer and formation of the mature capsid lattice.

An unreported case of pancreatic panniculitis in a liver transplant patient.

Pancreatic panniculitis is an uncommon condition that can occur in association with pancreatic disease. Most of the cases reported to date were associated with acute or chronic pancreatitis and pancreas cancer. Recently, development has been described in kidney transplant patients and secondarily to allograft pancreatitis in a pancreas-kidney transplant recipient.

[Efficacy of the association of a single dose of hepatitis B hyperimmune gammaglobulin and entecavir in the prophylaxis of hepatitis B after liver transplantation: experience of a single center in Argentina].

The present study reports the effectiveness of the association of a single dose of hepatitis B immunoglobulin (HBIg) associated to entecavir in the prophylaxis of hepatitis B in patients who have undergone liver transplantation. Six patients that had been transplanted because of hepatitis B liver disease were retrospectively evaluated. Three of them developed non-oncological complications related to liver cirrhosis, two had hepatocellular carcinoma and another one had fulminant HBV hepatitis.

[Cost analysis of liver transplantation in a community hospital: association with the Model for End-stage Liver Disease, a prognostic index to prioritize the most severe patients].

Introduction: The aim of the present study was to investigate the impact of the Model for End-stage Liver Disease (MELD) on transplantation costs.

Material And Methods: We included all patients who received a liver transplant for end-stage liver disease between 2006 and 2010. The study period encompassed the day of transplantation until hospital discharge.

Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy.

Human immunodeficiency virus type 1 (HIV-1) buds from the cell as an immature particle requiring subsequent proteolysis of the main structural polyprotein Gag for morphological maturation and infectivity. Visualization of the viral envelope (Env) glycoprotein distribution on the surface of individual HIV-1 particles with stimulated emission depletion (STED) superresolution fluorescence microscopy revealed maturation-induced clustering of Env proteins that depended on the Gag-interacting Env tail. Correlation of Env surface clustering with the viral entry efficiency revealed coupling between the viral interior and exterior: Rearrangements of the inner protein lattice facilitated the alteration of the virus surface in preparation for productive entry.

An expanded model of HIV cell entry phenotype based on multi-parameter single-cell data.

Background: Entry of human immunodeficiency virus type 1 (HIV-1) into the host cell involves interactions between the viral envelope glycoproteins (Env) and the cellular receptor CD4 as well as a coreceptor molecule (most importantly CCR5 or CXCR4). Viral preference for a specific coreceptor (tropism) is in particular determined by the third variable loop (V3) of the Env glycoprotein gp120. The approval and use of a coreceptor antagonist for antiretroviral therapy make detailed understanding of tropism and its accurate prediction from patient derived virus isolates essential.

[Usefulness of transient elastography (Fibroscan®) in the assessment of fibrosis in patients with chronic liver disease].

The prognosis and management of chronic liver disease largely depends on the extent and progression of liver fibrosis. Unfortunately, liver biopsy, an invasive and painful technique with several limitations, continues to be the gold standard for the staging and grading of fibrosis. Therefore, accurate noninvasive tests for liver injury are urgently needed.

A SNAP-tagged derivative of HIV-1--a versatile tool to study virus-cell interactions.

Fluorescently labeled human immunodeficiency virus (HIV) derivatives, combined with the use of advanced fluorescence microscopy techniques, allow the direct visualization of dynamic events and individual steps in the viral life cycle. HIV proteins tagged with fluorescent proteins (FPs) have been successfully used for live-cell imaging analyses of HIV-cell interactions. However, FPs display limitations with respect to their physicochemical properties, and their maturation kinetics.

Takotsubo Cardiomyopathy: A Cardiac Syndrome Mimicking Acute Myocardial Infarction in a Liver Transplant Recipient.

Takotsubo cardiomyopathy (TTC) is a rare clinical syndrome defined as a profound but reversible left ventricular dysfunction in the absence of coronary artery disease. We describe the clinical features and management of TC manifesting in the postoperative period in a patient undergoing liver transplantation. Two days after surgery, the patient developed clinical features of acute myocardial infarction.

Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.

Background: Current antiretroviral therapy against human immunodeficiency virus (HIV-1) reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection.

A simple fluorescence based assay for quantification of human immunodeficiency virus particle release.

Background: The assembly and release of human immunodeficiency virus (HIV) particles from infected cells represent attractive, but not yet exploited targets for antiretroviral therapy. The availability of simple methods to measure the efficiency of these replication steps in tissue culture would facilitate the identification of host factors essential for these processes as well as the screening for lead compounds acting as specific inhibitors of particle formation. We describe here the development of a rapid cell based assay for quantification of human immunodeficiency virus type 1 (HIV-1) particle assembly and/or release.