Comparison of PREDICTS atherosclerosis biomarker changes after initiation of new treatments in patients with SLE

Objective Patients with SLE have an increased risk ofatherosclerosis (ATH) that is not adequately explainedby traditional risk factors. We previously described thePredictors of Risk for Elevated Flares, Damage Progression,and Increased Cardiovascular disease in PaTients withSLE (PREDICTS) atherosclerosis-risk panel, which includesproinflammatory HDL (piHDL), leptin, soluble tumournecrosis factor-like weak inducer of apoptosis (sTWEAK)and homocysteine, as well as age and diabetes. A highPREDICTS score confers 28-fold increased odds forfuture atherosclerosis in SLE. The aim of this study is todetermine whether PREDICTS biomarkers are modifiable bycommon lupus therapies.Methods This prospective observational study includedSLE subjects started on new lupus treatments. Leptin,sTWEAK, homocysteine and antioxidant function of HDLwere measured at baseline (prior to drug initiation), 6weeks and 12 weeks.Results 16 subjects started mycophenolate (MMF), 18azathioprine (AZA) and 25 hydroxychloroquine (HCQ).In MMF-treated subjects, HDL function progressivelyimproved from 2.23 ± 1.32 at baseline to 1.37±0.81at 6 weeks (p=0.02) and 0.93±0.54 at 12 weeks(p=0.009). sTWEAK levels also improved in MMF-treatedsubjects from 477.5±447.1 to 290.3±204.6 pg/mLafter 12 weeks (p=0.04), but leptin and homocysteinelevels were not significantly changed. In HCQ-treatedsubjects, only HDL function improved from 1.80±1.29 atbaseline to 1.03±0.74 after 12 weeks (p=0.05). Therewere no changes in the AZA group. MMF treatmentwas still associated with significant improvements inHDL function after accounting for potential confounderssuch as total prednisone dose and changes in diseaseactivity. Overall, the mean number of high-risk PREDICTSbiomarkers at week 12 significantly decreased in theentire group of patients started on a new lupus therapy(2.1±0.9 to 1.8±0.9, p=0.02) and in the MMF-treatedgroup (2.4±0.8 vs 1.8±0.9, p=0.003), but not in theAZA or HCQ groups. In multivariate analysis, the odds ofhaving a high PREDICTS atherosclerosis risk score at 12weeks were lower with MMF treatment (OR 0.002, 95%CI 0.000 to 0.55, p=0.03).Conclusions 12 weeks of MMF therapy improves theoverall PREDICTS atherosclerosis biomarker profile.Further studies will determine whether biomarkerchanges reflect decreases in future cardiovascularevents

Mixed Spatial and Movement Representations in the Primate Posterior Parietal Cortex

The posterior parietal cortex (PPC) of humans and non-human primates plays a key role in the sensory and motor transformations required to guide motor actions to objects of interest in the environment. Despite decades of research, the anatomical and functional organization of this region is still a matter of contention. It is generally accepted that specialized parietal subregions and their functional counterparts in the frontal cortex participate in distinct segregated networks related to eye, arm and hand movements. However, experimental evidence obtained primarily from single neuron recording studies in non-human primates has demonstrated a rich mixing of signals processed by parietal neurons, calling into question ideas for a strict functional specialization. Here, we present a brief account of this line of research together with the basic trends in the anatomical connectivity patterns of the parietal subregions. We review, the evidence related to the functional communication between subregions of the PPC and describe progress towards using parietal neuron activity in neuroprosthetic applications. Recent literature suggests a role for the PPC not as a constellation of specialized functional subdomains, but as a dynamic network of sensorimotor loci that combine multiple signals and work in concert to guide motor behavior

High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids.

BackgroundPatients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population.ObjectiveTo examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis.MethodsCarotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed.ResultsLeptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present.ConclusionsHigh leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis

Association of metabolic syndrome and change in Unified Parkinson\u27s Disease Rating Scale scores.

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p \u3c 0.0001), were more likely to be male (75.3% vs 57.0%; p \u3c 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p \u3c 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865

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Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145507/1/cld728.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145507/2/cld728_am.pd

BC Data ScoutTM: A New Tool To Investigate Datasets For Health Research

Introduction BC’s Ministry of Health (MOH) maintains many administrative databases with rich information and analytical potential. Researchers are keen to use these data for both discovery and applied research. Historically, limited views of data availability and populations therein have supported study feasibility. Therefore, we developed BC Data ScoutTM, a cohort browser. Objectives and Approach We developed a cohort browser service to provide information to researchers planning a study using MOH data. The objective was to create a tool that is simple to use, provides quick results and is free to users to encourage its use. A better understanding of the data available can improve study quality and expand the user-base by giving researchers access to information not previously available during the planning stages. The tool will be evaluated by examining the number of requests received and a user satisfaction survey. Plans are in place to expand into additional data sources and extend query sophistication. Results The BC Data ScoutTM online tool provides cohort information in the form of highly aggregated, approximate results to researchers planning a study. It was developed by the MOH, the BC SUPPORT Unit and Population Data BC (PopData) and was launched in February 2018. The service is delivered by PopData. BC Data ScoutTM offers province-wide information for query, is accessible to a wide group of eligible researchers, and has data availability from the year 2000 onwards. Four types of MOH data are available for query: hospital data; physician data; pharmaceutical data; and demographics. In addition to determining study feasibility, the aggregate reports also help to further refine a full data access request and provide enough information to complete and strengthen a funding application. Conclusion/Implications BC Data ScoutTM will be beneficial for researchers planning to request data. This preliminary information may increase the chances of meaningful research studies to obtain funding, and the production of relevant, high-quality research results. BC will be among the first jurisdictions across Canada to offer this type of feasibility service

Effect of daily chlorhexidine bathing on hospital-acquired infection

BACKGROUND Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs). METHODS We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine– impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis. RESULTS A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period. CONCLUSIONS Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no