Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.     

Two hugging balloons at high pressures successfully dilate a lesion refractory to routine coronary angioplasty.

A small portion of lesions are refractory to coronary angioplasty even when very high pressures are used. This leads to a failed angioplasty and emergent bypass surgery. We successfully attempted the technique of hugging balloons or two polyethelene terephthalate (PET) balloons inflated simultaneously side by side which successfully dilated a lesion which would not dilate using standard techniques. This technique successfully dilated the lesion as the geometry of two balloons inflated side by side is different from one balloon. Two balloons inflated side by side consists of two outer semi-circles and a central trapezoidal square area. This altered geometric configuration may be important in successfully dilating a lesion refractory to standard dilating techniques. Higher pressures can be attained with smaller balloons as the burst pressure is higher in smaller balloons compared to larger balloons.     

Prevalence and correlates of multiple organ damage in referred treated hypertensives: data from the ETODH study

This study, carried out in a large cohort of treated essential hypertensives attending an out-patient hospital hypertension clinic, extends previous observations by showing that a clustering of two or three markers of organ damage (OD) has a higher prevalence than a single organ involvement. These findings call for a systematic evaluation of cardiac and extracardiac OD in treated hypertensive patients referred to a specialist setting.     

Impaired Cotranslational Processing as a Mechanism for Type I Antithrombin Deficiency

Most secretory proteins, including antithrombin (AT), aresynthesized with a signal peptide, which is cleaved before the mature protein is exported from the cell. The signal peptide is important inthe process whereby nascent protein is recognized as requiring subsequent modification within the endoplasmic reticulum (ER). We haveidentified a novel mutation, 2436TC L(-10)P, which affects the central hydrophobic domain of the AT signal peptide, in a probandpresenting with venous thrombotic disease and type I AT deficiency. Weinvestigated the basis of the phenotype by examining expression inmammalian cells of a range of variant AT cDNAs with mutations affectingthe -10 residue. Glycosylated AT was secreted from COS-7 cellstransfected with wild-type AT, -10L deletion, -10V or -10M variants,but not variants with P, T, R, or G at -10. Cell-free expression ofwild-type and variant AT cDNAs was then performed in the presence ofcanine pancreatic microsomes, as a substitute for ER. Variant ATproteins with P, T, R, or G at residue -10 did not undergoposttranslational glycosylation, and their susceptibility to trypsindigestion suggested they had not been translocated into microsomes. Ourresults suggest that the ability of AT signal peptide to direct theprotein to ER for cotranslational processing events appears to becritically dependent on maintaining the hydrophobic nature of theregion including residue -10. The investigations have defined impairedcotranslational processing as a hitherto unrecognized cause ofhereditary AT deficiency.     

Metabolomics Approach in Allergic and Rheumatic Diseases

Metabolomics is the analysis of the concentration profiles of low molecular weight compounds present in biological fluids. Metabolites are nonpeptide molecules representing the end products of cellular activity. Therefore, changes in metabolite concentrations reveal the range of biochemical effects induced by a disease or its therapeutic intervention. Metabolomics has recently become feasible with the accessibility of new technologies, including mass spectrometry and high-resolution proton nuclear magnetic resonance, and has already been applied to several disorders. Indeed, it has the advantage of being a nontargeted approach for identifying potential biomarkers, which means that it does not require a preliminary knowledge of the substances to be studied. In this review, we summarize the main studies in which metabolomic approach was used in some allergic (asthma, atopic dermatitis) and rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) to explore the feasibility of this technique as a novel diagnostic tool in these complex disorders.     

Dispersal of male Aedes aegypti in a coastal village in southern Mexico

Most Aedes aegypti dispersal studies have focused on females because of their central role in dengue virus transmission. Only a few mark-release-recapture (MRR) studies provided insights into male Ae. aegypti dispersal. To fill this knowledge gap, we conducted five male Ae. aegypti MRR experiments in a coastal village in southern Mexico. Small and large male cohorts were marked with fluorescent dusts, released outside buildings, and recaptures were carried out by using backpack aspirators. Recapture rates ranged between 0.35% and 6.55% and median distance traveled was 12-166 meters. A statistically significant difference in median distance traveled with large males dispersing farther than small ones was detected only in one experiment (MRR5: U = 3.5, P < 0.01). Male dispersal data will be useful for constructing and estimating parameter values and validating models that will be used to plan the most effective release strategies for genetically modified male Ae. aegypti.