Central nervous system vasculitis in a patient with HIV infection: a diagnostic challenge

Univ Fed Sao Paulo, Dept Neurol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Doencas Infecciosas, Rua Napoleao Barros,715, BR-04023900 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Radiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Doencas Infecciosas, Rua Napoleao Barros,715, BR-04023900 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Radiol, Sao Paulo, SP, BrazilWeb of Scienc

Tempo de opção

Background & Aims: There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). Methods: 1078 patients with bridging fibrosis (n = 552) or cirrhosis (n = 526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/ mm3, Hb >12/13 g/dl) and liver function (Albumin >3.3 g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. Results: Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR) = 1.51, 95% CI 1.31- 2.00, p = 0.005), (B) subtype 1b (OR = 1.63, 95% CI 1.18-2.24, p = 0.0029), (C) alpha-fetoprotein <10 ng/ml (OR = 2.50, 95% CI 1.87-3.36, p <0.0001) and (D) any prior response other than null (OR = 3.29, 95% CI 2.40-4.52, p <0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. Conclusions: Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pre-treatment counselling.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Final results of the telaprevir access program: Fibroscan values predict safety and efficacy in hepatitis c patients with advanced fibrosis or cirrhosis

Background: Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods: 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results: Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intentionto- treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions: FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. © 2015 Lepida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.7595% CI 0.58-0.99p=0.045) and to early treatment interruption due to SAE (PR 0.3695% CI 0.20-0.68p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.0695% CI 1.02-1.10p<0.001) and occurrence of liver cirrhosis (PR 2.0695% CI 1.11-3.83p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.Univ Sul Santa Catarina, Fac Med, Dept Ciencias Biol & Saude & Ciencias Sociais Apl, Disciplina Doencas Infecciosas, Av Pedra Branca 25, BR-88137270 Palhoca, SC, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Div Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Estado Rio de Janeiro, Dept Clin Med, Disciplina Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Serv Infectol, Vitoria, ES, SpainUniv Sao Paulo, Fac Med Ribeirao Preto, Div Gastroenterol, Ribeirao Preto, SP, BrazilInst Infectol Emilio Ribas, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Doencas Infecciosas & Parasitarias, Sao Paulo, SP, BrazilSecretaria Estadual Saude, Unidade Mista Saude, Unimista 508 509, Brasilia, DF, BrazilUniv Sao Paulo, Inst Med Trop Sao Paulo, Lab Virol, LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p 465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, RJ, BrazilCtr Referencia & Treinamento DST Aids, Sao Paulo, SP, BrazilCDH, Rio De Janeiro, RJ, BrazilHosp Fed Servidores Estado Rio de Janeiro HFSE, Setor Gastrohepatol, Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Clin Med, Div Gastroenterol, Sao Paulo, SP, Brazil| Univ Fed do Maranhao UFMA, HUPD, Ctr Pesquisa Clin, Sao Luis, MA, BrazilUniv Fed Estado Rio de Janeiro UNIRIO, Disciplina Clin Med & Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Rio do Grande Sul UFRGS, Dept Med Interna, Porto Alegre, RS, BrazilUniv Fed Espirito Santo, Ambulatorio HIV AIDS Hepatites Virais, Vitoria, ES, BrazilSMS, Ctr Orientacao & Aconselhamento, Foz Do Iguacu, PR, BrazilUniv Estado Rio de Janeiro UERJ, Serv Gastroenterol, Rio De Janeiro, RJ, BrazilIMT, Lab Virol LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Photodynamic therapy for root canals infected with Enterococcus faecalis

Objective: The aim of this study was to investigate the effects of photodynamic therapy (PDT) on endodontic pathogens by evaluating the decrease in numbers of Enterococcus faecalis colonies in the canals of extracted human teeth. Background Data: Failure in endodontics is usually related to inadequate cleaning and disinfection of the root canal system. This is due to the establishment of microorganisms in areas where the instruments and chemical agents used during root canal preparation cannot eliminate them. PDT is a complementary therapeutic method that could be used to eliminate these remaining bacteria. PDT is a process in which radiation acts on a dye that is applied to the target organism, resulting in bacterial death. Materials and Methods: Forty-six uniradicular teeth had their canals contaminated with bacteria and were incubated for 48 h at 35 degrees C. After that, the teeth were divided into a control group (CG) and a test group (TG). The 23 CG teeth did not undergo any intervention, whereas in the TG the teeth received a solution of 0.0125% toluidine blue for 5 min followed by irradiation using a 50-mW diode laser (Ga-Al-As) at a wavelength of 660 nm. Bacterial samples were taken before and after irradiation. In each of the samples, the number of colony-forming units (CFU) was counted. Results: The mean decrease in CFU was 99.9% in the TG, whereas in the CG an increase of 2.6% was observed. Conclusion: PDT was effective as a bactericidal agent in Enterococcus faecalis-contaminated root canals

Postoperative Ileus: Pathophysiology, Prevention and Treatment

Background: Continuous long-term treatment is recommended to reduce the hepatitis B virus (HBV) viral load. However, as a consequence, resistance mutations can emerge and be transmitted to other individuals. the polymerase (POL) gene overlaps the surface (S) gene. Thus, during treatment, mutations in the POL gene may lead to changes in hepatitis B surface antigen (HBsAg). the purpose of this study was to evaluate the frequency of lamivudine and vaccine escape mutations in HBsAg-positive blood donors from the city of Santos and in untreated HBV mono-infected patients from the city of São Paulo, Brazil.Methods: HBV DNA was extracted from 80 serum samples, of which 61 were from volunteer blood donors and 19 were from untreated HBV patients. A fragment of the POL/S genes containing 593 base pairs was amplified using nested PCR. Thirty four were PCR-positive and sequencing was performed using an ABI Prism 3130 Genetic Analyzer. Alignments and mutation mapping were performed using BioEdit software.Results: HBV DNA from 21 blood donors and 13 untreated patient samples were characterized using nucleotide sequencing PCR products from the POL/S genes. We were able to detect one sample with the resistance mutation to lamivudine rtM204V + rtL180M (2.94%), which was found in a volunteer blood donor that has never used antiviral drugs. the other samples showed only compensatory mutations, such as rtL80F (5.88%), rtL80V (2.94%), rtL82V + rtV207L (2.94%), rtT128P (5.88%), rtT128N/S (2.94%) and rtS219A (5.88%). We found modifications in the S gene in 14 of the 34 samples (41.16%). the mutations detected were as follows: sM133L + sI195T (2.94%), sI195M (2.94%), sP120T (2.94%), sY100S/F (2.94%), sY100C (17.64%), sI/T126P + sQ129P (2.94%), sM198I + sF183C (2.94%) and sS210R (5.88%).Conclusions: Our results suggest the transmission of lamivudine-resistant forms. Thus, the evaluation of HBV-infected subjects for lamivudine resistance would improve treatment regime. Moreover, the mutations in the S gene may impair HBsAg antigenicity and contribute to HBsAg failure detection and vaccine escape