Swine Influenza A(H3N2) Virus Infection in Immunocompromised Man,Italy, 2014

Because swine influenza virus infection is seldom diagnosed in humans, its frequency might be underestimated. We report a immunocompromised hematologic patient with swine influenza A(H3N2) virus in 2014 in Italy. Local pigs were the source of this human infection.     

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.     

Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34+-selected hematopoietic stem cell transplant for acute lymphoblastic leukemia

We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones. Antiviral treatment with foscarnet and ganciclovir was successful but prolonged treatment was required to prevent relapses. We hypothesize that this complication was more related to an immune reconstitution process than to an immune-deficient state post-grafting. We conclude that CMV retinitis is a late complication of HSCT that can occur despite satisfactory immune reconstitution. Usually, it is responsive to antiviral therapy. Dilated fundoscopic examination is essential both for examining patients with reduced visual acuity and for screening asymptomatic patients.     

Improvement of prognosis in idiopathic dilated cardiomyopathy: role of early diagnosis and optimized medical treatment. Study Group on Heart Muscle Diseases

BACKGROUND: The aim of this study was to assess the extent to which a more widespread use of new effective treatments for heart failure associated with earlier detection of the disease may have contributed to enhancing the prognosis of idiopathic dilated cardiomyopathy (IDC) patients over the past 20 years. METHODS: Heart transplant-free survival curves were analyzed in 343 IDC patients, prospectively enrolled from January 1, 1978 to June 30, 1997 in the Heart Muscle Disease Registry of the Cardiology Department in Trieste (94 enrolled between 1978 and 1987, Group 1; 249 between 1988 and 1997, Group 2). At enrollment, 91 patients had no heart failure symptoms (NoHF), whereas the remaining 252 showed HF of recent (HF < or = 6 months, n = 132) or non-recent (HF > 6 months, n = 120) onset. RESULTS: In comparison to Group 1, Group 2 was treated more frequently with ACE-inhibitors and beta-blockers (p < 0.0001) and showed a better long-term survival (p = 0.0034), resulting from a reduction of death for refractory HF or need for heart transplant (p = 0.011). Conversely, the risk of sudden death did not significantly differ between the two groups. NoHF, HF > 6 months and HF < or = 6 months groups were similarly treated with ACE-inhibitors and beta-blockers. Long-term survival was better in patients without HF than in those with overt HF (p = 0.0015). As compared to Group HF > 6 months, Group HF < or = 6 months had a poorer one-year prognosis (p = 0.045), related to the presence of a subgroup of patients with refractory HF and need for heart transplant, but showed a better survival rate over the following years (p = 0.015). Over the two subsequent decades of enrollment, a significant improvement in patient survival was observed within Groups NoHF (p = 0.03) and HF > 6 months (p = 0.01), but not in Group HF < or = 6 months. CONCLUSIONS: Over the past 20 years, the increasing use of ACE-inhibitors and beta-blockers in IDC was associated with a significant improvement in long-term survival, resulting from a reduction in mortality for refractory heart failure or need for heart transplant. In addition, early diagnosis may have contributed significantly to enhancing the prognosis of IDC, since the benefits of medical therapy were lower in patients identified and treated in advanced stages of the disease. Moreover, early diagnosis was shown to be useful in recognizing patients with recent onset of heart failure who are not responders to aggressive medical treatments and urgently need heart transplant.     

Inhibition of influenza A virus replication by resveratrol

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.     

Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens.

The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine on extracellular dopamine concentrations in the nucleus accumbens shell and core by means of microdialysis with vertically implanted concentric probes. Doses selected were in the range of those known to sustain drug self-administration in rats. Morphine, at 0.2 and 0.4 mg/kg, and cocaine, at 0.5 mg/kg, increased extracellular dopamine selectivity in the shell. Higher doses of cocaine (1.0 mg/kg) and the lowest dose of amphetamine tested (0.125 mg/kg) increased extracellular dopamine both in the shell and in the core, but the effect was significantly more pronounced in the shell compared with the core. Only the highest dose of amphetamine (0.250 mg/kg) increased extracellular dopamine in the shell and in the core to a similar extent. The present results provide in vivo neurochemical evidence for a functional compartmentation within the nucleus accumbens and for a preferential effect of psychostimulants and morphine in the shell of the nucleus accumbens at doses known to sustain intravenous drug self-administration.