Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the i…

Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy

A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or inter…

Isolation, characterization, differentiative properties of human mesenchymal stem cells isolated from the sub-endocardial layer of post-infarct chronic heart failure-affected patients

Mesenchymal stem cells (MSC) are pluripotent cells which reside in several adult organs, including heart, even if heart regeneration in vivo is still a poorly comprised phenomenon. Contrasting literature reports suggest that several efforts should be made to better characterize resident or migrating MSC populations (for both markers expression and immunogenic potential) prior to their effective use for regenerative medicine applications in heart diseases. We developed a new protocol to obtain human sub-endocardial MSC (HSE-MSC) from post-infarct hearts explanted from chronic heart failure (CHF) patients undergoing heart transplantation. We characterized HSE-MSC by immunocytochemistry (ICC) …

Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B

Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population.128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisa…

Practice guidelines for the treatment of hepatitis C: recommendations from an AISF/SIMIT/SIMAST Expert Opinion Meeting.

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies.

The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017

Abstract Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + …

FOLLICULAR HELPER T-CELLS POPULATE THE INTRAHEPATIC INFILTRATES OF HCV GENOTYPE-1 CHRONICALLY INFECTED PATIENTS AND PREDICT THE ACHIEVEMENT OF VIROLOGICAL RESPONSE FOLLOWING IFN-BASED TREATMENT

Extending the usefulness of extraembryonic mesenchymal stem cellsin regenerative medicine: expression of novel markers, immunoregulatory molecules, and novel differentiation capacities.

Mesenchymal stem cells (MSC) are considered promising tools in regenerative medicine applications. Even if they are already applied clinically, their extended characterization is being increasingly viewed as a needed feature, in order to avoid contrasting results when translating “in vitro” experiments to “in vivo” approaches. We recently demonstrated in human MSC isolated from the umbilical cord matrix (HEMSC) the expression of novel markers indicative of their stemness, as well as differentiative and immune properties [1]. HEMSC were cultured and subject to multiple molecular and morphological analyses to determine the expression of markers of interest. Undifferentiated HEMSC expressed im…

HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype…

Prevalence and features of delirium in older patients admitted to rehabilitation facilities

Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected i…

Oxidative stress induces myeloperoxidase expression by HUVEC and chronic heart failure endocardial endothelial cells. Active contribution of endothelium to an inflammatory heart disease.

In vitro and in vivo detection of end-products of MPO-driven oxidative and nitrosative stress in human endocardial endothelial cells from patients affected by chronic heart failure

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design This is a cross-sectional study nested in the "Delirium Day" study, a nationwide Italian point-prevalence study. Setting and participants Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholine…

HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS

Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) …

Oxidative stress-driven expression of myeloperoxidase in endothelial cells results in accumulation of markers of oxidative and nitrosative stress in vitro and in vivo

Endothelial cells (ECs), are able to manage with higher concentrations of ROS as well as reactive nitrogen species, respect to the other cell types. The unbalance between oxidizing species and antioxidant cellular defences has been implicated in the pathogenesis of cardiovascular diseases. While the role of MPO in the oxidative burst is well established, the effects of this enzyme on endothelial biology have only recently come to light. MPO can interact with endothelial –derived NO causing its depletion and favouring its conversion to nitrogen dioxide radical, a compound responsible of protein nitration generating 3-nitrotyrosine. Moreover, MPO is the only enzyme capable to form hypoclorous…

Peginterferon alfa-2b and Ribavirin: Effective in Patients With Hepatitis C Who Failed Interferon alfa/Ribavirin Therapy

Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy.This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 microg/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could ent…

Liver stiffness, a non-invasive marker of liver disease: a core study group report

The ability to evaluate liver stiffness non-invasively in clinical practice by measuring transient elastography using FibroScan® has resulted in considerable interest and enthusiasm. A core study group, organized by the Italian Association for the Study of the Liver, has assessed the usefulness of FibroScan® in the diagnosis and management of liver disease in clinical practice. The group concluded that FibroScan® is a valuable, non-invasive technique and have developed a consensus report form for registering transient elastography results. In this article, we report the findings of the study group.

Liver follicular helper T-cells in chronic hepatitis C

Smoke exposure affects gelatinase A and B activity levels in two lung epithelial cell lines