Explore the vast range of titles available.

In this randomized, controlled trial conducted at Danish cardiac centers, intravenous antibiotic therapy was compared with partial oral antibiotic therapy for the treatment of bacterial endocarditis. The outcomes were similar in the two groups.

The 5-year outcomes from the Partial Oral Treatment of Endocarditis (POET) trial show continued effectiveness of oral antibiotic therapy as compared with intravenous antibiotic therapy for endocarditis.

We isolated the barley stem rust resistance genes Rpg5 and rpg4 by map-based cloning. These genes are colocalized on a 70-kb genomic region that was delimited by recombination. The Rpg5 gene consists of an unusual structure encoding three typical plant disease resistance protein domains: nucleotide-binding site, leucine-rich repeat, and serine threonine protein kinase. The predicted RPG5 protein has two putative transmembrane sites possibly involved in membrane binding. The gene is expressed at low but detectable levels. Posttranscriptional gene silencing using VIGS resulted in a compatible reaction with a normally incompatible stem rust pathogen. Allele sequencing also validated the candidate Rpg5 gene. Allele and recombinant sequencing suggested that the probable rpg4 gene encoded an actin depolymerizing factor-like protein. Involvement of actin depolymerizing factor genes in nonhost resistance has been documented, but discovery of their role in gene-for-gene interaction would be novel and needs to be further substantiated.

Purpose Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. Methods This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. Results Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor ( n  = 21, 8%) and non-poor ( n  = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4–34.8) and 5.4 (95% CI 4.1–7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7–7.0, p  < 0.01). Conclusion Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. Trial registry POET ClinicalTrials.gov number, NCT01375257.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

This letter describes outcomes of the POET trial at a median follow-up of 3.5 years. The authors found that in patients with endocarditis on the left side of the heart, a change from intravenous antibiotic treatment to early oral antibiotic treatment was not associated with delayed treatment failure.

Introduction Highly effective oral antivirals (OAV) have been licensed for use in Chronic Hepatitis B (CHB). Efficacy of Tenofovir (TDF) and Entecavir (ETV) monotherapy has been demonstrated in randomised controlled trials. However, there may be a role for de novo combination therapy to reduce the development of resistance. For this reason, the authors offer patients combination therapy with TDF and Lamivudine (LAM) irrespective of whether they are OAV-naïve or experienced. In this study the authors test the hypothesis that combination therapy is superior to TDF monotherapy as assessed by viral suppression and ALT normalisation. Methods A retrospective prospective study of 185 patients (male=135), from a single centre, was performed. Viral suppression, was defined as <80 IU/ml and ALT normalisation <40 IU/l. Our real life data was compared with a published meta-analysis on the use of all treatments for HBV, but which reports TDF as the most potent OAV.1 Results Median age of patients was 45 (range 18–81). 74% were eAg negative prior to starting TDF and LAM. Median ALT at baseline was 46 (range 12–1141). 86 patients were treatment naïve prior to commencing combination therapy. Of 99 patients previously exposed to OAV's, 65 were partial responders and 34 virally suppressed when switching to TDF and LAM. 125/185 patients had completed 12 months and 84, 24 months of combination therapy. Overall viral suppression was recorded in 84% and 94% at 12 and 24 months respectively and ALT normalisation was seen in 67% and 74% at 12 and 24 months respectively. In the OAV-naïve group viral suppression was 81% compared with 84% in the OAV-experienced and ALT normalisation was 56% and 72% respectively in these groups at 12 months. In the published meta-analysis, viral suppression was 91% and ALT normalisation 67% at 12 months in a treatment naïve group. Comparing real life with published data showed no statistical significance for viral suppression and normalisation of ALT for combination versus monotherapy (p=0.12 and p=0.2 respectively). Conclusion These data highlight the efficacy of TDF in generating and sustaining viral suppression and ALT normalisation at 12 months and beyond. Combination OAV therapy versus TDF monotherapy does not show superiority. Furthermore, there is no reported resistance with TDF to date, but data are limited to 4-year follow-up. Given that OAV resistance may occur over many years, combination OAV may still have a role in the treatment of CHB, however larger randomised controlled trials are needed to determine this.

Introduction Bone Mineral Density (BMD) loss has been reported in chronic liver disease. In Chronic Hepatitis B (CHB) patients, Tenofovir Disoproxil Fumarate (TDF) is recommended as a first line therapy, in accordance with EASL guidelines. Concerns regarding the long-term safety of TDF have been raised, in particular changes in BMD in HIV patients, but limited data exist on similar changes in HBV treated patients. The aim of this study was to determine the impact of TDF on BMD in an ethnically diverse HBV infected population undergoing long-term treatment with this agent. Methods In a single centre, CHB patients treated with TDF for a minimum 12 months were prospectively offered a dual x-ray absorptiometry scan. BMD loss was defined by WHO criteria; T-score <−2.5 (osteoporosis) and between −1 and −2.5 (osteopenia). 83 consecutive patients were included (64 males), median age 45 (range 26–64). A control group, 27 patients with CHB (19 males), median age 32 (range 20–61), with no TDF exposure were also examined. Data on ethnicity, BMI, gender, fibrosis stage, comorbidities and drug history were recorded in all subjects. Results BMD loss was present in 45% of the treatment group (osteopenia 84%, osteoporosis 16%) and in 48% of the control group (osteopenia 85%, osteoporosis 15%). There was no difference in BMD loss when comparing both groups (p=0.45). In the ethnically diverse population studied, there was increased BMD loss in the non-White population (48%, treated group; 50%, controls) compared with the white population (33%, treated group; 40%, controls). By univariate analysis age, gender, fibrosis stage, comorbidities were all significant (p=<0.05, all variables), but particularly ethnicity (p=0.009). At multivariate analysis only ethnicity, BMI and male gender met statistical significance (p<0.015, <0.017 and <0.018 respectively), but not TDF. Conclusion This results demonstrate the prevalence of reduced BMD in CHB patients of diverse ethnicity, independent of TDF treatment. This cross-sectional study does not exclude the potential for BMD loss with TDF and further longitudinal studies are required to determine its effect on bone over time. Other factors also contribute to BMD loss, namely ethnicity and BMI, and should be given due consideration when selecting a treatment option.

Introduction Pegylated-Interferon a (PEG-IFNα) therapy provides sustained immune control and is associated with HBsAg loss and improved survival. Despite this, the immune mechanisms and timing of immunomodulatory effects remain ill-defined. Recent data has reported changes in a subset of NK cells in HBeAg negative disease which may predict response. This study evaluated the effects of PEG-IFNα on the innate immune response in eAg positive patients, a cohort known to respond favourably to interferon. Methods Paired PBMC samples were compared pre and during PEG-IFNα therapy from 16 patients. Changes in innate immune responses were evaluated at two on-treatment intervals, 12 and 24 weeks. The number, phenotype and function of NK cell populations were assessed. The expression of TNF related apoptosis inducing ligand (TRAIL) and the production of interferon γ (IFNγ) on the NK cell population was determined with flow cytometry. Changes in the innate response were correlated with HBsAg quantification (Abbott ARCHITECT). Results PEG-IFNα increased the CD56bright NK cell population (CD56/CD16) by threefold (mean fold change; MFC 3.02, p=0.01) in all patients. This was associated with an overall decline in HBsAg 0.42 log and HBV DNA 2.5 log. Further increase in CD56bright NK cells was noted from 12 to 24 weeks (MFC 2.3 vs 3.7). Consistent with this, HBsAg decline was also more marked at 24 weeks (mean decline log 0.13 vs 0.70). In the absence of HBsAg decline, there was no upregulation of CD56bright NK cells. Upregulation of TRAIL expression was noted on this CD56bright NK subset by more than twofold (MFC 2.44, p=0.009), this effect was more dramatic at 12 weeks (MFC 2.12 vs 2.72). A twofold increase in IFNγ producing CD56bright NK cells was observed, (MFC 2.39, p=0.03); again this effect was more marked at 12 weeks (MFC 2.61 vs 2.01). Conclusion These data highlight the effects of PEG-IFNα on the innate immune response in eAg positive CHB. An upregulation of CD56bright NK cells, their expression of TRAIL and IFNγ production presage a decline in HBsAg and HBV DNA. These changes observed at 12 weeks, are not reflected in concurrent HBsAg decline, but may predict sustained immune control in the longer term with a more marked HBsAg decline at 24 weeks.

Introduction Chronic hepatitis B (CHB) is a dynamic disease process with patients moving between disease phases over time. The majority of young adults infected with CHB are exposed to the virus perinatally or in the early years of life. Despite this, the extent of liver disease in this group remains ill-defined, as are the indications and timing of treatment. The aim of this study was to elucidate the extent of liver disease in a cohort of patients identified for a newly established young adult viral hepatitis clinic. Methods Only young adults who underwent liver biopsy for the assessment of CHB were included in the study. 70 patients (male=49), median age 26 (range 16–30), were examined. Data on ethnicity, BMI and eAg status were collated. Longitudinal data including viral load and ALT were recorded for 6–18 months prior to each patient undergoing liver biopsy. Normal ALT levels in the group were defined as;<30 IU/l males, <19 IU/l females in accordance with the Prati criteria. These clinical parameters were evaluated for their utility in predicting fibrosis stage (FS); fibrosis score 0–6, in accordance with the modified Ishak score. Disease severity in the young adult group, defined as FS, was compared with that reported in 51 consecutive CHB patients (>30 years), (male=45), median age 43 (range 32–71), undergoing liver biopsy for disease assessment. Results 38/70 of the young adults were eAg positive; median ALT over the course of follow-up was 61 (range 11–1050). 14 were Caucasian, 38 Asian and 18 Afro-Caribbean. Median BMI was 22.7 (range 17.9–35.6). By univariate analysis male gender and eAg positive disease were significant in predicting more marked disease with a higher FS (p≥0.05), but abnormal ALT and non-Caucasians in particular demonstrated marked significance (p=0.0002 and p=0.001 respectively). When evaluating the level of liver disease in young adults compared with that found in the 51 older CHB patients, there was no statistical difference between the FS reported in the two groups, presence of fibrosis (p=0.93); presence of moderate to severe fibrosis (p=0.6), demonstrating a trend towards higher FS with older age. However, normal ALT over the course of follow-up in the young adult group, was significantly associated with no fibrosis (p=.001). Conclusion These data highlight the importance of formal disease assessment in this age group, as comparable levels of liver fibrosis are present in young adults as in older patients. However, closer scrutiny with assessment of ALT according to Prati criteria may identify patients with milder disease. This study emphasises the advantages of a young adult clinic in providing greater focus on CHB in this age group, enabling the early and timely intervention with therapeutic options where indicated.