Novel Therapies in HBV Infection

Current treatments for chronic hepatitis B are able to provide a sustained suppression of the viral replication (i.e., persistent undetectability of HBV DNA). This leads to improvement of liver fibrosis and reduction of clinical complications. However, hepatitis B surface antigen (HBsAg) persists in most patients, probably justifying a still increased risk of hepatocellular carcinoma. Indeed, obtaining a complete and sterilizing cure with elimination of the covalently closed circular DNA (cccDNA) or silencing its activity is still a holy grail. New molecules are under evaluation to suppress viral replication acting on multiple phases of the HBV cycle or improve specific immune response against HBV. Molecules acting on HBV cycle have already showed encouraging results, such as entry inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators (CAMs), nucleic acid polymers (NAPs). Also, promising results have been observed with immune-modulators, therapeutic vaccines, and other immune-based approaches. Among these, toll-like (TLR) or anti-programmed receptor agonists antibody 1 of the cell death protein (PD1) (e.g., nivolumab) are most promising. This paper describes newer drugs appearing on the horizon, including antiviral drugs targeting different steps of the HBV life cycle and therapeutic approaches based on immune-modulation

Left ventricular diastolic filling alterations in subjects with mitral valve prolapse: a Doppler echocardiographic study

To assess left ventricular diastolic filling in mitral valve prolapse (MVP), we studied 22 patients with idiopathic MVP and 22 healthy controls matched for sex, age, body surface area and heart rate. A two-dimensional, M-mode and Doppler echocardiographic examination was performed to exclude any cardiac abnormalities. The two groups had similar diastolic and systolic left ventricular volumes, left ventricle mass and ejection fraction. Doppler measurements of mitral inflow were: E and A areas (the components of the total flow velocity-time integral in the early passive period of ventricular filling, E; and the late active period of atrial emptying, A), the peak E and A velocities (cm.s-1), acceleration and deceleration half-times (ms) of early diastolic rapid inflow, acceleration time of early diastolic flow (AT), total diastolic filling time (DFT) (ms), and the deceleration of early diastolic flow (cm.s-2). From these measurements were calculate: peak A/E ratio (A/E), E area/A area, the early filling fraction, the atrial filling fraction, AT/DFT ratio. All the Doppler measurements reported are the average of three cardiac cycles selected at end expiration. The mean peak A velocity, A/E velocity ratio, deceleration half time and atrial filling fraction were each significantly higher for subjects presenting a MVP (60 +/- 12 cm.s-1 vs 49 +/- 14, P < 0.008; 98 +/- 13% vs 64 +/- 12%, P < 0.0001; 120 +/- 36 ms vs 92 +/- 11, P < 0.002; 0.45 +/- 0.14 vs 0.36 +/- 0.08, P < 0.02

Rapid left ventricular filling in untreated hypertensive subjects with or without left ventricular hypertrophy

In this study, independent contribution of age, HR, BMI, casual and ambulatory blood pressure, LVM and LVEF in evaluating diastolic filling have been investigated in 34 never-treated hypertensive patients and in 15 healthy normotensive subjects. All the subjects were free from coronary artery disease, valvular disease, heart failure, renal disease and psychiatric problems. All the hypertensive subjects (never treated) were subgrouped according to presence or absence of LVH. The PFR decreased significantly and tPFR increased significantly in hypertensive patients in comparison with normotensive subjects and they did not change in the presence vs absence of LVH. The PFR was inversely correlated with BMI, age, 24-h mean SBP and with 24-h DBP. In multiple regression analysis, PFR decreased with BMI, age, 24-h mean SBP and DBP but not with LVMI. These results suggest that BMI, age and 24-h mean blood pressure were the major determinants of PFR abnormalities in hypertensive patients

Methodological matters on an Alzheimer's dementia trial: is a double-blind randomized controlled study design sufficient to draw strong conclusions on treatment?

Letter to Edito

Evidence-based practice needs stronger prognostic scores for the prediction of recurrent stroke.

Comment on: Prediction of recurrent stroke and vascular death in patients with transient ischemic attack or nondisabling stroke: a prospective comparison of validated prognostic scores. [Stroke. 2010

Optimized search strategy for detecting scientifically strong studies on treatment through PubMed

Our study was designed to optimize the search strategies based on the work of Haynes et al. for detecting randomized controlled trials (RCTs) through PubMed. In particular, we aimed to improve precision for broad and narrow searches on interventional studies. We used in addition to the string suggested by the Hedge Team the following: {NOT ((animals [mh] NOT humans [mh]) OR (review [pt] OR meta-analysis [pt]))} and tested its effectiveness. The search was carried out on a year's worth of articles from the PubMed database. We analyzed 35,590 bibliographic citations about four relevant major topics in internal medicine (hypertension, diabetes, heart failure, and hepatitis). Precision, percentage gain between the Hedge Team search strategies and the new one were computed and reported in the text. Moreover, a pooled analysis was carried out in terms of absolute precision difference. We observed better precision for both broad and narrow searches. However, effective gain resulted only for broad searches. In this case, bibliographic citation recall effectively reduced (-24 to -35 % retrieved citation with a gain of 32-54 %) without loss of information. The search strategy improved broad searches regarding each of the four considered topics. We think this new search strategy, based on a previous work of the Hedge team, could be a step forward and can save some time by researchers

Hypoadiponectinemia: A Link between Visceral Obesity and Metabolic Syndrome

Metabolic syndrome (MetS) represents a combination of cardiometabolic risk factors, including visceral obesity, glucose intolerance or type 2 diabetes, elevated triglycerides, reduced HDL cholesterol, and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the “epidemic” obesity, with a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. At present, there is a growing interest on the role of visceral fat accumulation in the occurrence of MetS. In this review, the effects of adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of the MetS have been also emphasized. Accordingly, the “hypoadiponectinemia” has been proposed as the most interesting new hypothesis to explain the pathophysiology of MetS

Daily Rhythmicity of Behavior of Nine Species of South American Feral Felids in Captivity

The authors analyzed the daily activity rhythms of the domestic cat and of eight of the ten feral felid species that are indigenous to South America. All species showed daily rhythmicity of activity in captivity under a natural light-dark cycle. The robustness of the rhythmicity varied from species to species, but the grand mean of 34% was within the range of robustness previously described for mammalian species ranging in size from mice to cattle. There was not a sharp division between diurnal and nocturnal felids. Instead, what was found was a gradient of diurnality going from the predominantly nocturnal margay (72% of activity counts during the night) to the predominantly diurnal jaguarundi (87% of activity counts during the day) with the remaining species lying in between these two extremes. The ecological implications of temporal niche variations are discussed