Performances of HTLV serological tests in diagnosing HTLV infection in high-risk population of São Paulo, Brazil

Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from S?o Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.     

Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients

BACKGROUND/AIMS: This study assessed the safety and antiviral effects of telaprevir (VX-950) in combination with peginterferon alfa-2a and ribavirin. METHODS: Twelve treatment-nai ve patients with chronic genotype 1 hepatitis C virus infection received telaprevir (750mg q8h), peginterferon alfa-2a (180mug/week), and ribavirin (1000 or 1200mg/day) for 28 days. Patients could then start off-study treatment with peginterferon alfa-2a and ribavirin for up to 44 weeks, at the discretion of the investigator and patient. RESULTS: The combination of telaprevir, peginterferon alfa-2a, and ribavirin was well tolerated, with no serious adverse events or treatment discontinuations. Rash or pruritus occurred in 5 of the 12 patients; all cases resolved either during or after the end of telaprevir treatment. All 12 patients had undetectable HCV RNA levels by day 28 (rapid viral response, RVR). Eight patients completed 44 weeks of off-study peginterferon alfa-2a and ribavirin treatment. Eight patients achieved a sustained viral response (SVR), including one patient who received only 22 weeks of treatment. CONCLUSIONS: The combination of telaprevir, peginterferon alfa-2a, and ribavirin was generally well tolerated. Events of pruritus and rash resolved during or after end of telaprevir dosing. All 12 patients achieved an RVR.     

Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification

Aims: Among various hypotheses proposed for pathological tissue calcification,recent evidence supports the possibility that self-replicatingcalcifying nanoparticles (CNPs) can contribute to such calcification.These CNPs have been detected and isolated from calcified humantissues, including blood vessels and kidney stones, and arereferred to as nanobacteria. We evaluated calcific aortic valvesfor the presence of CNP. Methods and results: Calcific aortic valves were obtained from 75 patients undergoingsurgical valve replacement. The control group was formed byeight aortic valves corresponding to patients with heart transplants.In the microbiology laboratory, valves were screened for CNPusing a 4–6 weeks specific culture method. The culturefor CNP was positive in 48 of the 75 valves with aortic stenosis(64.0%) in comparison with zero of eight (0%) for the controlgroup (P = 0.0005). The observation of cultures by way of scanningelectron microscopy highlighted the resemblance in size andmorphology of CNP. Conclusion: Self-replicating calcific nanometer-scale particles, similarto those described as CNP from other calcific human tissues,can be cultured and visualized from calcific human aortic valves.This finding raises the question as to whether CNP contributeto the pathogenesis of the disease or whether they are onlyinnocent bystanders.     

R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log(10) IU/mL. Synergy was observed between R1626 and peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions. Conclusion: A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa-2a +/- ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa-2a and ribavirin is underway.     

Recommendations for the diagnosis and treatment of latent and active tuberculosis in patients with inflammatory joint diseases treated with tumour necrosis factor alpha inhibitors

The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-alpha) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test.     

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin.Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/ day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin).Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 lU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin.Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.     

Acceso radial frente a femoral después de una intervención coronaria percutánea en infarto agudo de miocardio con elevación del segmento ST. Resultados de mortalidad a 30 días y a 1 año

Introduction and objectives

Little attention has been given to the effect of vascular access site on mortality, while an increasing body of evidence is showing that radial access has much more benefit than femoral access for ST-segment elevation myocardial infarction patients. We aimed to assess the influence of vascular access site on mortality at 30 days and at 1 year in ST-segment elevation myocardial infarction patients.

Methods

We included all patients with ST-segment elevation myocardial infarction who had undergone primary angioplasty at 2 Galician hospitals between 2008 and 2010. We performed 2 multivariate regression models for each endpoint (30-day and 1-year mortality). The only difference between these models was the inclusion or not of the vascular access site (femoral vs radial). For each of the 4 models we calculated the Hosmer-Lemeshow test and the C-index. We also tested the interaction between hemodynamic instability and vascular access.

Results

We included 1461 patients with a mean age of 64. Of these patients, 86% had radial access and 7.4% had hemodynamic instability. All-cause mortality was 6.8% (100/1461) at 30 days and 9.3% (136/1461) at 1 year. Vascular access site follows hemodynamic instability and age in terms of effect on mortality risk, with an odds ratio of 5.20 (95% confidence interval, 2.80-9.66) for 30-day mortality. A similar effect occurs for 1-year mortality. The C-index slightly improves (without achieving statistical significance) with the inclusion of the vascular access site.

Conclusions

Vascular access site should be taken into account when predicting mortality after a primary percutaneous coronary intervention.Full English text available from:www.revespcardiol.org/en