Anca Streinu-Cercel

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

BACKGROUND & AIMS Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA <15IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. RESULTS The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, -35.5% to -19.6%; p<0.001]). CONCLUSIONS EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR. LAY SUMMARY The combination of elbasvir/grazoprevir for 12weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations. CLINICAL TRIAL REGISTRATION Clinical trials.gov Identifier: NCT02358044.

Surveillance of pneumococcal diseases in Central and Eastern Europe.

ABSTRACT Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine vaccination. Pneumococcal conjugate vaccines (e.g. PCV7, PCV13) provide protection from invasive pneumococcal disease as well as non-invasive infection (pneumonia, acute otitis media), and decrease vaccine-type nasopharyngeal colonisation, thus reducing transmission to unvaccinated individuals. PCVs have also been shown to reduce the incidence of antibiotic-resistant pneumococcal disease. Surveillance for pneumococcal disease is important to understand local epidemiology, serotype distribution and antibiotic resistance rates. Surveillance systems also help to inform policy development, including vaccine recommendations, and monitor the impact of pneumococcal vaccination. National pneumococcal surveillance systems exist in a number of countries in Central and Eastern Europe (such as Croatia, Czech Republic, Hungary, Poland, Romania and Slovakia), and some have introduced PCVs (Czech Republic, Hungary, Kazakhstan, Russia, Slovakia and Turkey). Those countries without established programs (such as Kazakhstan, Russia and Ukraine) may be able to learn from the experiences of those with national surveillance systems. The serotype distributions and impact of PCV13 on pediatric pneumococcal diseases are relatively similar in different parts of the world, suggesting that approaches to vaccination used elsewhere are also likely to be effective in Central and Eastern Europe. This article briefly reviews the epidemiology of pneumococcal disease, presents the latest surveillance data from Central and Eastern Europe, and discusses any similarities and differences in these data as well the potential implications for vaccination policies in the region.

Microbiologic Safety of the Transareolar Approach in Breast Augmentation

BACKGROUND In aesthetic breast augmentation, especially by the transareolar approach, there is increasing concern regarding the occurrence of capsular contracture and its potential correlation with intraoperative implant contamination from putative endogenous breast flora of the nipple and lactiferous ducts. However, detectable bacteria cannot be considered synonymous with established resident microflora. OBJECTIVES The authors sought to elucidate the existence of endogenous breast flora and assess the microbiologic safety of transareolar breast augmentation. METHODS In this prospective study (BREAST-MF), the authors collected microbiologic samples from the breast skin, ductal tissue, and parenchyma of 39 consecutive female patients who underwent breast procedures in a plastic surgery clinic. Swabs collected pre-, intra-, and postoperatively were processed for bacterial and fungal growth. Positive cultures underwent identification through VITEK and MALDI-TOF, as well as antimicrobial susceptibility testing. RESULTS Staphylococcus species accounted for 95 of 106 (89.6%) positive results from native breast skin, 15 of 18 (83.3%) positive results from decontaminated breast skin, and 4 of 4 (100%) positive results from the breast parenchyma. Methicillin resistance was present in 26.4% of S. epidermidis, 25.3% of S. hominis, and 71.4% of S. haemolyticus strains. CONCLUSIONS During transareolar breast augmentation, in the nipple-areola region it is more likely to find bacteria populating the skin, rather than endogenous breast flora, as previously considered. Appropriate preoperative decontamination is essential for minimizing the risk of postoperative infections. LEVEL OF EVIDENCE 3: Risk.

Neurocognitive impairment screening in Romanian HCV infected patients

Background Neurocognitive impairment can occur in HCV infected patients. A series of studies have shown that patients with HCV may experience diminished attention and concentration, or suffer from severe cognitive deficits, such as disorientation and fluctuating consciousness. We performed a study to determine if there are neurocognitive differences or dissimilarities in the quality of life between a control group and a group of HCV infected patients.

The role of sonication in the microbiological diagnosis of implant-associated infections – the experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Balş”, Bucharest

The role of sonication in the microbiological diagnosis of implant-associated infections – the experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest Raluca Mihăilescu, Daniela Tălăpan, Olga Dorobăț, Alexandru Rafila, Emilia Capraru, Daniela Munteanu, Anca Streinu-Cercel, Oana Streinu-Cercel, Vlad Predescu, Florian Purghel, Cătălin Cârstoiu, Razvan Ene, Dana Mihaela Jianu, Cristina Popescu, Victoria Aramă, Adrian Streinu-Cercel

Entecavir as specific antiviral therapy in selected cases of severe acute hepatitis B.

The role of specific antiviral treatment in severe acute hepatitis B has been subject to debate during the past few years. We present clinical findings in a series of three cases of severe acute hepatitis B and one case of acute hepatitis B treated with entecavir during 2007-2009, with interesting evolution. Entecavir appeared to improve the clinical evolution in the reported cases. Two of the patients displayed HBsAg to HBsAb seroconversion while another patient went into an inactive HBsAg carrier state. In the case of mild acute hepatitis B, the liver enzymes had returned to normal, symptomatology had receded but HBsAg had remained positive. Without data on viral load, we were unable to determine whether the patient had entered an inactive HBsAg carrier state or had continued into the services of another medical unit, for treatment of chronic HBV infection. We also discuss into detail a case which displayed transient initial HBe seroconversion at 1 week, followed by seroreversion to positive HBeAg and negative HBeAb at week 3, and a new seroconversion at week 7. We assess the possible roles of precore mutations, antibody-dependent cellular cytotoxicity, coinfection with Epstein Barr virus and the function of Kupffer cells.

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy.

INTRODUCTION Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. METHODS A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann-Whitney-Wilcoxon test for non-parametric variables. Pearsons chi-squared test was used for correlation analysis. RESULTS A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17-63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19-65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. CONCLUSIONS The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy.

Nasopharyngeal bacterial colonization in children – study hypothesis

Background With monthly reports of decreased bacterial susceptibility to antibiotics and the soaring incidence of invasive infections, it becomes increasingly important to assess bacterial colonization, as this can easily constitute a reservoir for infection. Entering the community for kindergarten and school training is an important step for children, particularly since this may be associated with a change in the microbiota.

Response to “Commentary on: Microbiologic Safety of the Transareolar Approach in Breast Augmentation”

We thank Dr Bartsich for providing valuable input on our previously reported work1 and we agree with her conclusion: the breast cannot be considered a sterile site.2 As the human body includes 10 times more bacterial cells than human cells,3 it is virtually impossible for any particular bodily compartment which communicates with the exterior to be sterile.4 Therefore, we agree that flora from the surrounding skin can transiently colonize the nipple ducts, as we have …

Comparison of Kaposi disease outlines in patients with and without HIV infection in two tertiary care hospitals in Bucharest, Romania

Methods A retrospective study on KD was performed in two academic centers, tertiary-care hospitals with national addressability in Romania. Two groups were comparatively studied: HIV-infected patients diagnosed in the National Institute for Infectious Diseases “Prof.Dr. Matei Bals” (HIV-positive group), and non-HIV patients diagnosed in the first Clinic of Dermatology, Colentina Clinical Hospital (HIV-negative group). The statistical analysis was performed using IBM SPSS Statistics v.22 (Chicago, USA).