Ophthalmological complications in hepatitis C virus infection: Side effect of interferon therapy or a direct role of HCV?

Several clinical studies have demonstrated that retinopathy and ophthalmic complications are features that appear mostly as side effects in HCV patients undergoing interferon (IFN) therapy. Here we underline that HCV itself is also able to modulate genes involved in ocular pathologies. Presently an in vitro model of ocular tissue derived cells infected with HCV is missing. The establishment of such in vitro models would be helpful to better understand the mechanisms through which HCV induces optical pathologies in order to specifically target the causes of ocular disease.     

Gestación gemelar con feto muerto intraútero en el segundo trimestre

Nowadays, twin gestation is increased due to advances in assisted reproduction. Unquestionably, these pregnancies have an increased risk of foetal and maternal disorders. Single foetal death has a different incidence depending on gestational age; in the first trimester between 10-70%, in the second and third trimester it is a rare event, 0.5-7%.     

Transcoronary concentration gradients of circulating microRNAs in heart failure

Aims

Circulating levels of microRNAs (miRNAs) are emergent promising biomarkers for cardiovascular disease. Altered expression of miRNAs has been related to heart failure (HF) and cardiac remodelling. We measured the concentration gradients across the coronary circulation to assess their usefulness to diagnose HF of different aetiologies.

Methods and results

Circulating miRNAs were measured in plasma samples simultaneously obtained from the aorta and the coronary venous sinus in patients with non‐ischaemic HF (NICM‐HF, n = 23) ischaemic HF (ICM‐HF, n = 41), and in control patients (n = 11). A differential modulation of circulating levels of miR‐423, ‐34a, ‐21‐3p, ‐126, ‐199 and ‐30a was found across the aetiology groups. Interestingly, a positive transcoronary gradient was found for miR‐423 (P < 0.001) and miR‐34a (P < 0.001) only in the ICM‐HF group. On the contrary, a positive gradient was found for miR‐21‐3p (P < 0.001) and miR‐30a (P = 0.030) only in the NICM‐HF group. Finally, no significant variations were observed in the transcoronary gradient of miR‐126 or miR‐199.

Conclusions

The present findings suggest that circulating levels of miRNAs are differentially expressed in patients with HF of different aetiologies. The presence of a transcoronary concentration gradient suggests a selective release of miRNAs by the failing heart into the coronary circulation. The presence of aetiology‐specific transcoronary concentration gradients in HF patients might provide important information to better understand their role in HF, and suggests they could be useful biomarkers to distinguish HF of different aetiologies.

     

Lipoprotein abnormalities in patients with extra-coronary arteriosclerosis

Serum levels of lipids, lipoproteins and apolipoproteins A-I and B were evaluated in 102 patients (75 males and 27 females; ages 58 +/- 8 and 61 +/- 7 years (mean +/- SD), respectively) with arteriosclerosis of the lower limbs of supra-aortic trunks. Compared to findings in 64 healthy, age-matched control subjects, male patients in both groups had significantly higher serum triglyceride levels (+42%, P less than 0.05), while female patients with lower limb arteriosclerosis showed significantly increased cholesterol and triglyceride concentrations (+19%, P less than 0.01 and +82%, P less than 0.05, respectively). LDL-triglycerides were also increased in all patients. HDL-cholesterol was significantly decreased in male patients with arteriosclerosis of the lower limbs (-27%, P less than 0.01) and the supra-aortic trunks (-28%, P less than 0.01), and in females of both groups (-26%, P less than 0.01 and -20%, P less than 0.01, respectively); in terms of percent, HDL2-cholesterol was reduced 2-fold compared to HDL3-cholesterol. Patient apolipoprotein A-I and B levels were unchanged. In male and female patients, correlations between triglycerides and HDL-cholesterol as well as HDL2-cholesterol were negative, but not significant; on the other hand, both correlations were negative and significant in male controls, while only the correlation between triglycerides and HDL2-cholesterol was negative and significant in the female controls. Since HDL-cholesterol, and in particular HDL2-cholesterol, concentrations seem closely related to the intravascular catabolism of triglyceride-rich lipoproteins, the absence of a significant correlation between these parameters in the patients suggests a possible alteration in this metabolic process.     

Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice

An amphotropic retroviral vector, LgAL(delta Mo + PyF101) containing a human adenosine deaminase (ADA) cDNA was used to optimize procedures for the lasting genetic modification of the hematopoietic system of mice. The highest number of retrovirally infected cells in the hematopoietic tissues of long-term reconstituted mice was observed after transplantation of bone marrow (BM) cells that had been cocultured in the presence of both interleukin-1 alpha (IL-1 alpha) and IL-3. A significantly lower number was detected when IL-1 alpha was omitted from such cocultures. The yield of cells that generate spleen colony-forming cells (CFU-S) in the BM of lethally irradiated recipients (MRA-CFU-S) significantly improved on inclusion of the adherent cell fraction of cocultures in the transplant. Retroviral integration patterns in MRA-CFU-S-derived spleen colonies showed that an MRA-CFU-S can produce many CFU-S during BM regeneration. Expression of hADA was detected in the circulating white blood cells of long-term reconstituted animals, demonstrating that the LgAL(delta Mo + PyF101) vector is capable of directing the sustained expression of hADA, and in approximately 35% of the transduced MRA-CFU-S-derived spleen colonies. These results should facilitate the development of gene therapy protocols for the treatment of severe combined immunodeficiency caused by a lack of functional ADA.     

Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis

Purpose

To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE).

A Short Review of the Non-invasive Transcutaneous Pericranial Electrical Stimulation Techniques and their Application in Headache

Purpose of Review

In this short review, the most common non-invasive neuromodulatory techniques will be described, along with their advantages and disadvantages and their application in headache. Available preventive treatments can be unhelpful or may have unpleasant side effects; moreover, the rate of response to preventive drugs does not exceed 50%, lower in chronic migraine; alternative options would be welcome. Though the concept of neuromodulation was originally developed with invasive methods, newer non-invasive techniques are appearing.

Recent Findings

The novel neuromodulatory techniques have been developed with encouraging results: compared with traditional pharmacotherapy, advantages of non-invasive neuromodulation include reduced incidence of adverse effects, improved adherence, and safety and ease of use. The results are encouraging for acute or preventive treatment of different kinds of headache.

Summary

A variety of neuromodulatory approaches is expanding fastly and has opened new possibilities for treatment of patients suffering from many forms of headache, especially those who have failed traditional pharmacotherapy. The non-invasive treatments can be seen as supplementing traditional management in refractory patients. Current study results are encouraging but preliminary and larger and more rigorous trials are needed to clarify benefit and mode of action.

     

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.