Kornumholt7727

OBJECTIVES Incomplete SLE (iSLE) patients display symptoms typical for SLE but have insufficient criteria to fulfil the diagnosis. Biomarkers are needed to identify iSLE patients that will progress to SLE. IFN type I activation, B-cell-activating factor (BAFF) and B-cell subset distortions play an important role in the pathogenesis of SLE. The aim of this cross-sectional study was to investigate whether B-cell subsets are altered in iSLE patients, and whether these alterations correlate with IFN scores and BAFF levels. METHODS iSLE patients (n = 34), SLE patients (n = 41) with quiescent disease (SLEDAI ≤4) and healthy controls (n = 22) were included. Proportions of B-cell subsets were measured with flow cytometry, IFN scores with RT-PCR and BAFF levels with ELISA. RESULTS Proportions of age-associated B-cells were elevated in iSLE patients compared with healthy controls and correlated with IgG levels. In iSLE patients, IFN scores and BAFF levels were significantly increased compared with healthy controls. Also, IFN scores correlated with proportions of switched memory B-cells, plasma cells and IgG levels, and correlated negatively with complement levels in iSLE patients. CONCLUSION In this cross-sectional study, distortions in B-cell subsets were observed in iSLE patients and were correlated with IFN scores and IgG levels. Since these factors play an important role in the pathogenesis of SLE, iSLE patients with these distortions, high IFN scores, and high levels of IgG and BAFF may be at risk for progression to SLE. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective adjunctive therapy for Parkinson disease. Studies have shown improvement of motor function but often exclude patients older than 75 yr. OBJECTIVE To determine the safety and effectiveness of STN DBS in patients 75 yr and older. METHODS A total of 104 patients (52 patients >75 yr old, 52 patients  less then 75 yr old) with STN DBS were paired and retrospectively analyzed. The primary outcome was change in Unified Parkinson Disease Rating Scale (UPDRS) subscale III at 1 yr postoperatively, OFF medication. Secondary outcomes were changes in UPDRS I, II, and IV subscales and levodopa equivalents. Complications and all-cause mortality were assessed at 30 d and 1 yr. RESULTS Both cohorts had significant improvements in UPDRS III at 6 mo and 1 yr with no difference between cohorts. Change in UPDRS III was noninferior to the younger cohort. The cohorts had similar worsening in UPDRS I at 1 yr, no change in UPDRS II, similar improvement in UPDRS IV, and similar levodopa equivalent reduction. There were similar numbers of postoperative intracerebral hemorrhages (2/52 in each cohort, more severe in the older cohort) and surgical complications (4/52 in each cohort), and mortality in the older cohort was similar to an additional matched cohort not receiving DBS. CONCLUSION STN DBS provides substantial motor benefit and reduction in levodopa equivalents with a low rate of complications in older patients, which is also noninferior to the benefit in younger patients. STN DBS remains an effective therapy for those over 75 yr. Copyright © 2020 by the Congress of Neurological Surgeons.Although epigenetic factors may influence the expression of defense genes in plants, their role in antiviral responses and the impact of viral adaptation and evolution in shaping these interactions are still poorly explored. We used two isolates of turnip mosaic potyvirus (TuMV) with varying degrees of adaptation to Arabidopsis thaliana to address these issues. One of the isolates was experimentally evolved in the plant and presented increased load and virulence relative to the ancestral isolate. The magnitude of the transcriptomic responses was larger for the evolved isolate and indicated a role of innate immunity systems triggered by molecular patterns and effectors in the infection process. Several transposable elements (TEs) located in different chromatin contexts and epigenetic-related genes were also affected. Correspondingly, mutant plants having loss or gain of repressive marks were, respectively, more tolerant and susceptible to TuMV, with a more efficient response against the ancestral isolate. In wild-type plants both isolates induced similar levels of cytosine methylation changes, including in and around TEs and stress-related genes. Results collectively suggested that apart from RNA silencing and basal immunity systems, DNA methylation and histone modification pathways may also be required for mounting proper antiviral defenses and that the effectiveness of this type of regulation strongly depends on the degree of viral adaptation to the host. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND There are several guidelines that recommend pneumococcal vaccination (PPSV23 and/or PCV13) in adults with a history of cardiovascular disease (established heart failure, coronary disease, cerebrovascular disease) or at a very-high risk of cardiovascular disease. However, there is no Randomized Controlled Trial (RCT) systematic review that evaluates the impact of vaccination on all-cause mortality compared to no vaccination in this particular population. EN4 OBJECTIVE To conduct a systematic review and meta-analysis of the impact of pneumococcal vaccination in the referred population. METHODS We searched CENTRAL and MEDLINE for relevant RCTs and observational studies. Data were screened, extracted, and appraised by two independent reviewers. We pooled results using a random-effects model, and used Hazard Ratios (HR) with 95% Confidence Intervals (CI) to assess measure of effect. The primary outcome was all-cause mortality and we assessed the confidence in the evidence using the GRADE framework. RESULTS No RCTs were found. Seven observational studies were included for analyses. Pooled results from five studies enrolling a total of 163,756‬ participants showed a significant decrease in all-cause mortality (HR 0.78, 95% CI 0.73 to 0.83, very-low confidence), without statistically significant heterogeneity (Chi2 test P = 0.21; I2 = 32%). CONCLUSIONS Pneumococcal vaccination was associated with a 22% decrease of all-cause mortality in patients with cardiovascular disease or at a very high-cardiovascular risk. However, limitations due to study design and the serious risk of bias in three of the included studies leads to a decreased level of result confidence. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.Importance Bacterial vaginosis is common and is caused by a disruption of the microbiological environment in the lower genital tract. In the US, reported prevalence of bacterial vaginosis among pregnant women ranges from 5.8% to 19.3% and is higher in some races/ethnicities. Bacterial vaginosis during pregnancy has been associated with adverse obstetrical outcomes including preterm delivery, early miscarriage, postpartum endometritis, and low birth weight. Objective To update its 2008 recommendation, the USPSTF commissioned a review of the evidence on the accuracy of screening and the benefits and harms of screening for and treatment of bacterial vaginosis in asymptomatic pregnant persons to prevent preterm delivery. Population This recommendation applies to pregnant persons without symptoms of bacterial vaginosis. Evidence Assessment The USPSTF concludes with moderate certainty that screening for asymptomatic bacterial vaginosis in pregnant persons not at increased risk for preterm delivery has no net benefit in preventing preterm delivery. The USPSTF concludes that for pregnant persons at increased risk for preterm delivery, the evidence is conflicting and insufficient, and the balance of benefits and harms cannot be determined. Conclusions and Recommendation The USPSTF recommends against screening for bacterial vaginosis in pregnant persons not at increased risk for preterm delivery. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant persons at increased risk for preterm delivery. (I statement).Importance Preterm delivery results in adverse outcomes; identifying and treating bacterial vaginosis may reduce its occurrence. Objective To update the evidence on screening and treatment of asymptomatic bacterial vaginosis in pregnancy for the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, and trial registries through May 29, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through December 31, 2019. Study Selection Fair- or good-quality English-language studies evaluating diagnostic accuracy of tests feasible within primary care; randomized clinical trials (RCTs); nonrandomized controlled intervention studies (for harms only); or meta-analyses of metronidazole or clindamycin. Data Extraction and Synthesis Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures SensitivitImportance Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food. Objective To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden. Design, Setting, and Participants All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017. Exposures Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by aga small but statistically significant increased mortality risk.Importance Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone. Objective To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS. Design, Setting, and Participants ANNOUNCE was a confirmatory, phase 3, double-blind, randomized trial conducted at 110 sites in 25 countries from September 2015 to December 2018; the final date of follow-up was December 5, 2018. Eligible patients were anthracycline-naive adults with unresectable locally advanced or metastatic STS, an Eastern Cooperative Oncology Group performance status of 0 to 1, and cardiac ejection fraction of 50% or greater. Interventions Patients were randomized 11 to receive doxorubicin, 75 mg/m2 (day 1), combined with olaratumab (n = 258), 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles, or placebo (n = 251) on days 1 and 8 for up to 8 21-day cycles, followed by olaratumab/placebo monotherapy.