Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters.

Objective: Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking.

Design: Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis.

Results: In the derivation cohort, 100/405 patients died during a median 8.

Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis.

Background & Aims: Pegylated interferon is still the backbone of hepatitis C treatment and may cause thrombocytopenia, leading to dose reductions, early discontinuation, and eventually worse clinical outcome. We assessed associations between interferon-induced thrombocytopenia and bleeding complications, interferon dose reductions, early treatment discontinuation, as well as SVR and long-term clinical outcome.

Methods: All consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis (Ishak 4-6) who initiated interferon-based therapy between 1990 and 2003 in 5 large hepatology units in Europe and Canada were included.

[Reversibility of hepatic fibrosis].

Although chronic hepatitis has a diverse aetiology, development of hepatic fibrosis is the universal outcome. Cirrhosis is considered to be the universal end-stage of chronic liver disease. Patients with cirrhosis are at increased risk for liver failure and hepatocellular carcinoma.

High-mobility group box 1 and the receptor for advanced glycation end products contribute to lung injury during Staphylococcus aureus pneumonia.

Introduction: Staphylococcus (S.) aureus has emerged as an important cause of necrotizing pneumonia. Lung injury during S.

Selective expansion of human natural killer cells leads to enhanced alloreactivity.

In allogeneic stem cell transplantation (SCT), natural killer (NK) cells lacking their cognate inhibitory ligand can induce graft-versus-leukemia responses, without the induction of severe graft-versus-host disease (GVHD). This feature can be exploited for cellular immunotherapy. In this study, we examined selective expansion of NK cell subsets expressing distinct killer immunoglobulin-like receptors (KIRs) within the whole human peripheral blood NK cell population, in the presence of HLA-Cw3 (C1) or Cw4 (C2) transfected K562 stimulator cells.

The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection.

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis-related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis.

Combining findings from gaze and electroencephalography recordings to study timing in a visual tracking task.

Electroencephalography (EEG) and gaze data have traditionally been separated in neurocognitive studies because of the artefacts that even small controlled eye movements produce. Study of gaze control in a visual tracking task provides information about an individual's prospective control. By including gaze events in the EEG analysis, we studied prospective control and its neural correlates during deceleration in a visual tracking task.

Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation.

Protease-activated receptor-2 (PAR2) is abundantly expressed in the pulmonary compartment. House dust mite (HDM) is a common cause of allergic asthma and contains multiple PAR2 agonistic proteases. The aim of this study was to determine the role of PAR2 in HDM-induced allergic lung inflammation.

Is there sufficient evidence to recommend antiviral therapy in hepatitis C?

While patients with chronic hepatitis C virus (HCV) infection are treated in order to prevent liver-related morbidity and mortality, we rely on sustained virological response (SVR) as a virological biomarker to evaluate treatment efficacy in both clinical practice as well as in drug development. However, conclusive evidence for the clinical benefit of antiviral therapy or validity of SVR as surrogate marker, as derived from trials randomizing patients to a treatment or control arm, is lacking. In fact, the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial recently showed an increased mortality rate among interferon-treated patients compared to untreated controls.

Reversed phase free ion selective radiotracer extraction (RP-FISRE): a new tool to assess the dynamic stabilities of metal (-organic) complexes, for complex half-lives spanning six orders of magnitude.

This paper introduces reversed phase free ion selective radiotracer extraction (RP-FISRE) as a new tool to assess the stability of metal complexes, as illustrated by the assessment of the stability of [(177)Lu]Lu-DOTA-octreotate. To this end, the TUDelft-developed FISRE, where the released metal is column-retained and the complex eluted, was changed into RP-FISRE, where the complex is column-retained and the released metal is eluted. This change in the approach allows for studies to be performed with high stability complexes.

Single-size thermometric measurements on a size distribution of neutral fullerenes.

We present measurements of the velocity distribution of electrons emitted from mass-selected neutral fullerenes, performed at the intracavity free electron laser FELICE. We make use of mass-specific vibrational resonances in the infrared domain to selectively heat up one out of a distribution of several fullerene species. Efficient energy redistribution leads to decay via thermionic emission.

Three-dimensional co-cultures of human endothelial cells and embryonic stem cell-derived pericytes inside a microfluidic device.

Organs-on-chips are microengineered in vitro tissue structures that can be used as platforms for physiological and pathological research. They provide tissue-like microenvironments in which different cell types can be co-cultured in a controlled manner to create synthetic organ mimics. Blood vessels are an integral part of all tissues in the human body.

Structures of the dehydrogenation products of methane activation by 5d transition metal cations.

The activation of methane by gas-phase transition metal cations (M(+)) has been studied extensively, both experimentally and using density functional theory (DFT). Methane is exothermically dehydrogenated by several 5d metal ions to form [M,C,2H](+) and H2. However, the structure of the dehydrogenation product has not been established unambiguously.

Treatment of HCV infection by targeting microRNA.

Background: The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122). Miravirsen is a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function.

Methods: In this phase 2a study at seven international sites, we evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection.

Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122.

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte-derived microRNAs in serum and liver injury in patients with chronic hepatitis C.

Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner.

Rupture of a vulnerable atherosclerotic plaque causes thrombus formation and precipitates cardiovascular diseases. In addition to the thrombogenic content of a plaque, also the hemodynamic microenvironment plays a major role in thrombus formation. How the altered hemodynamics around a plaque promote pathological thrombus formation is not well understood.

Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.

Context: Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.

Objective: To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.

Design, Setting, And Patients: An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6).

Longitudinal study of looming in infants with high-density EEG.

A rapidly approaching object provides information about the object's approach and how imminent a collision is. Prospective control when responding to a looming virtual object approaching on a direct collision course was studied longitudinally in 10 infants aged 5/6 and 12/13 months. Different characteristics of the looming-related visual evoked potential (VEP) responses from infants' brain electrical recordings (EEG) were explored and compared between the infants at these different ages.

Scaling laws for photoelectron holography in the midinfrared wavelength regime.

Midinfrared strong-field laser ionization offers the promise of measuring holograms of atoms and molecules, which contain both spatial and temporal information of the ion and the photoelectron with subfemtosecond temporal and angstrom spatial resolution. We report on the scaling of photoelectron holographic interference patterns with the laser pulse duration, wavelength, and intensity. High-resolution holograms for the ionization of metastable xenon atoms by 7-16  μm light from the FELICE free electron laser are presented and compared to semiclassical calculations that provide analytical insight.

BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function.

The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential.

Fast-track practice in cardiac surgery: results and predictors of outcome.

Objectives: Various studies have shown different parameters as independent risk factors in predicting the success of fast-track postoperative management in cardiac surgery. In the present study, we evaluated our 7-year experience with the fast-track protocol and investigated the preoperative predictors of successful outcome.

Methods: Between 2004 and 2010, 5367 consecutive patients undergoing cardiac surgery were preoperatively selected for postoperative admission in the postanaesthesia care unit (PACU) and were included in this study.

Influence of erroneous patient records on population pharmacokinetic modeling and individual bayesian estimation.

Background: Observational data sets can be used for population pharmacokinetic (PK) modeling. However, these data sets are generally less precisely recorded than experimental data sets. This article aims to investigate the influence of erroneous records on population PK modeling and individual maximum a posteriori Bayesian (MAPB) estimation.

[The 'paper-based' preoperative evaluation: non-optimal health care].

A nationwide preoperative assessment guideline was introduced in the Netherlands in 1997 at the advice of the Health Council of the Netherlands. The preoperative assessment should entail an appropriate interview, a physical examination, additional tests, risk assessment and informing the patient. Dutch and several international guidelines recommend a complete assessment under the responsibility of the anaesthesiologist.