1,721,037 research outputs found

    Dynamic of mixed HCV infection in plasma and PBMC of HIV/HCV patients under treatment with Peg-IFN/ribavirin

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    The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG

    Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use

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    Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1â6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance

    Surgical site infections after elective neurosurgery: a survey of 1747 patients.

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    OBJECTIVE: To evaluate the incidence and risk factors of postsurgical site infections (SSIs) in elective neurosurgical procedures in patients treated with an ultrashort antibiotic protocol. METHODS: In this consecutive series of 1747 patients treated with elective neurosurgery and ultrashort prophylactic antibiotic therapy at the Fondazione Istituto Nazionale Neurologico "Carlo Besta" in Milan, the rate of SSIs was 0.7% (13 patients). When only clean neurosurgery was considered, there were 11 such SSIs (1.52%) in 726 craniotomies and one SSI (0.15) in 663 spinal operations. The antibiotic protocol was prolonged in every case of external communication as cerebrospinal fluid leaks or external drainages. RESULTS: The infection rate of the whole series was low (0.72%), and a risk factor identified for SSIs in clean neurosurgery was longer surgery duration. The relative risk estimate was 12.6 for surgeries lasting 2 hours and 24.3 for surgeries lasting 3 or more hours. Patients aged older than 50 years had a lower risk of developing SSI with a relative risk of 0.23 when compared with patients aged younger than 50 years. CONCLUSION: The present series reports a low incidence of SSIs for elective neurosurgery, even for high-risk complex craniotomies performed for tumor removal. Given that an antibiotic protocol prolongation was used to pretreat any early signs of infection and external communication, the protocol was appropriate for the case mix. The two identified risk factors (surgical duration > 2 hours and middle-aged patients [16-50 yr]) may be indicators of other factors, such as the level of surgical complexity and poor neurological outcome. Copyright © by the Congress of Neurological Surgeons

    Raised serum beta 2 microglobulin levels in different stages of human immunodeficiency virus infection

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    Serum β2 microglobulin (β2-M) levels were determined in patients with Acquired Immunodeficiency Syndrome (AIDS), AIDS Related Complex (ARC), Persistent Generalized Lymphadenopathy (PGL), healthy intravenous drug addicts (IVDA) and heterosexual controls. Seventy-eight out of 79 AIDS patients (98.7%) exhibited elevated β2-M levels. High levels of β2-M were also found in 83 of 100 (83%) of PGL/ARC patients and in 24 of 56 (42.8%) healthy IVDA. Patients with AIDS had significantly higher mean β2-M levels when compared with all other groups. The mean levels of PGL/ARC patients were significantly higher than those of healthy IVDA and the mean levels for healthy IVDA significantly differ from those of the heterosexual controls. After 2-24 months of follow up three out of four PGL/ARC patients whose serum β2-M was greater than 8.0 mg/l developed AIDS

    Rate of cirrhosis progression reduced in HIV/HCV co-infected non-responders to anti-HCV therapy

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    This is a retrospective longitudinal follow-up study of 25 HIV/HCV positive cirrhotic patients not responding to peg-IFN plus ribavirin, and 25 untreated controls matched for age ( 5 years), gender and Child-Pugh score. The primary endpoint of the study was the incidence of cirrhosis progression (CP) defined as the occurrence of at least one of the following events: death, ascites, jaundice, encephalopathy, gastrointestinal bleeding and hepatocellular carcinoma (HCC). During the median follow-up of 54 months (34-89), four treated (16%) and 13 untreated patients (52%) experienced CP (p=0.02). Poisson's regression model showed that the independent predictors of CP were Peg-IFN therapy (p=0.016), positive HIV-RNA (p=0.024), and altered ALP values (p=0.012). Peg-IFN therapy seems to slow down the rate of cirrhosis progression also in HIV/HCV co-infected patients nonresponders to anti-HCV therapy, in comparison with untreated patients
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