Regulating STING in health and disease.

The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named "STimulator of INterferon Genes (STING)". STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases

Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: A multicenter longitudinal study

© 2017 Borba et al. Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil. Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR). Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load) on RVR achievement. Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV) genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL) and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group). Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir) and the baseline viral load had an influence on the RVR rate (odds ratio [OR] =0.011; 95% confidence interval [CI]: 0.001–0.119; P<0.001/OR =13.004; 95% CI: 1.522–111.115; P=0.019, respectively). Conclusion: In this longitudinal multicenter cohort study conducted from the Brazilian perspective, differences were found in the RVR rates, favoring telaprevir over boceprevir for genotype 1 HCV-infected patients. In addition, the baseline viral load was associated with RVR achievement in both evaluated groups. As RVR is also reported in the literature as a predictor of the sustained virological response (SVR), further analyses of RVR as predictor of SVR outcomes should be further evaluated in Brazil

Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cl&aacute;udia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Cl&iacute;nicas, Federal University of Paran&aacute;, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paran&aacute;, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paran&aacute; between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR). Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load) on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV) genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6&nbsp;years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (&ge;800,000&nbsp;IU/mL) and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group). Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir) and the baseline viral load had an influence on the RVR rate (odds ratio [OR] =0.011; 95% confidence interval [CI]: 0.001&ndash;0.119; P&lt;0.001/OR =13.004; 95% CI: 1.522&ndash;111.115; P=0.019, respectively).Conclusion: In this longitudinal multicenter cohort study conducted from the Brazilian perspective, differences were found in the RVR rates, favoring telaprevir over boceprevir for genotype 1 HCV-infected patients. In addition, the baseline viral load was associated with RVR achievement in both evaluated groups. As RVR is also reported in the literature as a predictor of the sustained virological response (SVR), further analyses of RVR as predictor of SVR outcomes should be further evaluated in Brazil. Keywords: hepatitis C, rapid virological response, protease inhibitors, telaprevir, boceprevir, multicente

Efficacy and safety of amphotericin B lipid-based formulations—A systematic review and meta-analysis

© 2016 Blackwell Verlag GmbH Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid® infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile