Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon.

Interleukin (IL)28-B polymorphism has been related to interferon response in the treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is still poorly understood. We aimed to investigate the effect of IL28-B polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%), treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to virological, serological and biochemical response.

Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation.

Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function.

Cerebrospinal fluid penetration of tigecycline.

We report, in a clinical setting, the tigecycline concentration and area under the concentration-time curve (AUC) - both in blood and in cerebrospinal fluid (CSF) - of a patient with a ventriculo-atrial shunt infection. Tigecycline weakly penetrates CSF the CSF-to-serum concentration ratio was 0.079 and CSF-to-serum AUC(0-12) ratio was 0.

Effect of large arteries on blood pressure variability.

Blood pressure (BP) variability is generally considered to be due to neurogenic influences on arterioles modulating peripheral resistance, as well as variations in stroke volume (SV). However, for a given change in peripheral resistance or SV, the degree of BP variability is modulated by the stiffness of large conduit arteries. Recent epidemiological evidence shows that cardiovascular risk is not only related to the average arterial pressure, but also to the degree of diurnal variability.

Lumped parameter model of cardiovascular-respiratory interaction.

The aim of this work was to develop a lumped parameter model of the cardiovascular system and to couple it with a model of respiratory mechanics. In comparison to existing models, modifications and additions have been implemented to include a model of the upper limb vasculature employing the electrical analogy of hemodynamic variables. The model prediction of respiratory effects on arterial pressure was compared with in vivo invasive measurement of blood pressure in patients.

Application of cardiovascular models in comparative physiology and blood pressure variability.

The usefulness of cardiovascular models is determined by their intended function with respect to elucidating underlying hemodynamic concepts and to enable simulations that will assist in understanding the effects of specific parameters. Models can take different forms, including mock circulatory constructs with physical components, mathematical representations of parameter space relations employing constitutive equations, or closed form representations of electrical circuit analogs described in the time or frequency domain. This investigation describes the use of cardiovascular models based on electrical analogs of mechanical hydrodynamic systems to elucidate two different physiologic concepts: (i) the use of distributed vascular impedance to investigate comparative physiology of optimal design and features related to body size across a broad range of animal species; (ii) use of lumped parameter models to assess the role of arterial stiffness in blood pressure variability.

Pharmacokinetics of anidulafungin in two critically ill patients with septic shock undergoing CVVH.

Candidemia is associated with high mortality rate especially in critically ill (ICU) patients with septic shock and echinocandins such as anidulafungin are recommended as first-line treatment. Available pharmacokinetic studies of anidulafungin in healthy volunteers and in patients with renal or hepatic impairment showed that no dose adjustment is needed even in patients receiving standard intermittent haemodialysis. However, few data are available with continuous veno-venous haemofiltration (CVVH).

Carotid-femoral pulse wave velocity assessment using novel cuff-based techniques: comparison with tonometric measurement.

Background: Carotid-femoral pulse wave velocity, a predictor of cardiovascular outcome, is conventionally measured using a tonometer sequentially placed upon the carotid and femoral arteries, gated using an electrocardiogram. Leg cuff detection of the femoral pulse removes the need for signal gating, reduces the time required for a single measurement, but gives different pulse wave velocity values to tonometric analysis. A novel algorithm to correct for the transit time and distance related to the additional femoral segment was applied to the cuff-based approach in this study.

Ultra performance liquid chromatography PDA method for determination of tigecycline in human plasma.

: A simple ultra performance liquid chromatography with photodiode array method for the quantification of human plasma concentrations of tigecycline was developed and validated. Quinaxoline, used as an internal standard, was added to 500 μL of plasma before adding 1 mL of protein precipitation solution. The extracts were dried in a vacuum centrifuge system at 60°C and reconstituted with 60 μL of water and acetonitrile (95:5, vol/vol), and 5 μL was injected onto an ACQUITY UPLC H-Class system.

Determination of central blood pressure by a noninvasive method (brachial blood pressure and QKD interval): a noninvasive validation.

Objective: We validated against invasive measurements a measure of central SBP based on the QKD interval. The present objective is a comparison to the SphygmoCor device.

Materials And Methods: A first cohort was used to redefine an algorithm for estimating ascending aorta SBP (cSBP) with respect to SphygmoCor.

Development and validation of an UPLC-PDA method to quantify daptomycin in human plasma and in dried plasma spots.

Quantification of daptomycin in plasma samples may be useful in optimizing therapy especially in special patients' population. Nevertheless, therapeutic drug monitoring of daptomycin is still limited probably for the low number of laboratories which perform this analysis and for high shipment costs. We developed and validated a new UPLC-PDA method to quantify daptomycin in plasma and in dried plasma spots (DPS) collected on dried sample spots devices (DSSD).

Incidence of upper aerodigestive tract cancer after liver transplantation for alcoholic cirrhosis: a 10-year experience in an Italian center.

Introduction: The aim of this study was to evaluate the incidence, clinical characteristics, treatment, and outcome of de novo tumors (DNT) of the upper aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver transplantation (OLT).

Methods: Among 225 consecutive OLT performed between January 2002 and January 2012, a total of 205 patients received a first liver allograft. Eleven (4.

Incidence, management, and results of hepatic artery stenosis after liver transplantation in the era of donor to recipient match.

Introduction: Hepatic artery stenosis (HAS) is an important complication after liver transplantation. However, studies are not conclusive in terms of definition, incidence, best treatment, and timing of intervention. The aim of this study was to evaluate the incidence of SSHA that occurred in a single center over the past 12 years, pointing out diagnostic and therapeutic strategies.

High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis.

Objectives: To analyse the determinants of raltegravir CSF penetration, including the pharmacogenetics of drug transporters located at the blood-brain barrier or blood-CSF barrier.

Methods: Plasma and CSF raltegravir concentrations were determined by a validated HPLC coupled with mass spectrometry method in adults on raltegravir-based combination antiretroviral therapy undergoing a lumbar puncture. Single nucleotide polymorphisms in the genes encoding drugs transporters (ABCB1 3435, SLCO1A2, ABCC2 and SLC22A6) and the gene encoding hepatocyte nuclear factor 4 α (HNF4α) were determined by real-time PCR.

Development and validation of a new UPLC-PDA method to quantify linezolid in plasma and in dried plasma spots.

Linezolid is an oxazolidinone antibiotic used for the treatment of pneumonia and uncomplicated and complicated skin and soft tissues infections caused by Gram positive bacteria. It is also used as second line agent in multi-drug resistant tuberculosis. Therapeutic drug monitoring (TDM) of linezolid represents a valid tool in clinical practice to optimize therapy, especially in critically ill patients.

Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients.

Functional variants rs7270101 and rs1127354 of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of no functional rs6051702 polymorphism. Since a simultaneous evaluation of the three ITPA SNPs for hemolytic anemia has not yet been investigated, we aimed to understand the contribution of each SNPs and its potential clinical use to predict anemia in HCV treated patients.

Determination of telaprevir in plasma of HCV-infected patients by HPLC-UV.

Telaprevir is a direct acting antiviral agent, used with pegylated interferon and ribavirin for the management of chronic hepatitis C virus (HCV) genotype 1 infection, in patients not responding to therapy with pegylated interferon and ribavirin only. Although 75% of patients achieve a sustained virological response after treatment with telaprevir, adverse drug-drug interactions and undesirable events often occur. Therefore, telaprevir monitoring is pivotal to improve the management of HCV infection.

Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice.

Nitric oxide (NO) can modulate arterial stiffness by regulating both functional and structural changes in the arterial wall. Tissue transglutaminase (TG2) has been shown to contribute to increased central aortic stiffness by catalyzing the cross-linking of matrix proteins. NO S-nitrosylates and constrains TG2 to the cytosolic compartment and thereby holds its cross-linking function latent.

Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010.

Pharmacokinetics of caspofungin increased dosage in a patient on rifampin-containing anti-tubercular treatment.

We describe a patient treated with caspofungin and rifampin; after increasing the dosage of the former (70 mg/day) we observed an unexpectedly lower plasma exposure (AUC0-24 79.5 μg/ml*h vs. 108.