Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015; 13: 1245-53. Summary. Background: Hospitalized patients with cirrhosis are at increased risk for venous thromboembolism (VTE). The benefits and risks of pharmacological thromboprohylaxis in these patients have not been well studied. Objectives: To examine the safety and efficacy of pharmacological VTE prophylaxis in hospitalized cirrhotic patients. Patients/Methods: Retrospective cohort study of patients with cirrhosis hospitalized at an academic tertiary care referral center over a 5-year period. Results: Six hundred hospital admissions accounting for 402 patients were included. VTE prophylaxis was administered during 296 (49%) admissions. Patients receiving VTE prophylaxis were older (59 years vs. 55 years, P < 0.001), had longer lengths of stay (9.6 days vs. 6.8 days, P = 0.002), and lower Model for End-Stage Liver Disease scores (13.2 vs. 16.1, P < 0.001). In-hospital bleeding events (8.1% vs. 5.5%, P = 0.258), gastrointestinal bleeding events (3.0% vs. 3.2% P = 0.52), new VTE events (2.37% vs. 1.65%, P = 0.537), and mortality (8.4% vs. 7.3%, P = 0.599) were similar in the two groups. VTE prophylaxis did not reduce the risk of VTE (odds ratio 0.94, 95% confidence interval 0.23-3.71), and patients receiving unfractionated heparin, but not low molecular weight heparin, were at increased risk for in-hospital bleeding events (odds ratio 2.38, 95% confidence interval 1. 15-4.94 vs. 0.87, 0.37-2.05, respectively). Conclusion: The rate of VTE in this cohort of hospitalized cirrhotic patients was low and was unaffected by pharmacological thromboprophylaxis. Unfractionated heparin was associated with an increased risk for in-hospital bleeding, suggesting that if thromboprophylaxis is indicated, low molecular weight heparin may be favored.

Purpose-Gleason grade 4/5 prostate cancer is a determinant for recurrence following radical prostatectomy. Monoamine oxidase-A is over expressed in grade 4/5 compared to grade 3 cancer. Monoamine oxidase-A is also expressed by normal basal cells and in vitro studies suggest that its function is to repress secretory differentiation. Therefore, monoamine oxidase-A in grade 4/5 cancer might reflect dedifferentiation to a basal cell-like phenotype. We investigated whether monoamine oxidase-A expression correlates with another basal cell protein, CD44, in high grade cancer and whether either is associated with an aggressive phenotype.Materials and Methods-A total of 133 grade 4/5 archival cancers from a cohort previously used to evaluate the prognostic significance of histomorphological variables were scored for monoamine oxidase-A and CD44 immunohistochemical labeling. Spearman rank correlations of the proteins, and histomorphological and clinical variables were determined. The univariate and multivariate value of each variable as a determinant of biochemical recurrence was assessed by logistic regression.Results-Monoamine oxidase-A expression correlated with CD44. Neither was prognostic for biochemical recurrence. However, monoamine oxidase-A expression positively correlated with preoperative serum prostate specific antigen and the percent of grade 4/5 cancer.Conclusions-Concurrent expression of monoamine oxidase-A and CD44 suggests that grade 4/5 cancer may be basal cell-like in nature, despite the absence of other classic basal cell biomarkers such as cytokeratins 5 and 14, and p63. The correlation of monoamine oxidase-A expression with prostate specific antigen and the percent of grade 4/5 cancer suggests that monoamine oxidase-A may contribute to growth of high grade cancer and that antidepressant drugs that target monoamine oxidase-A may have applications in treating prostate cancer. Keywordsprostate; monoamine oxidase; neoplasm recurrence, local; adenocarcinoma; CD44 protein, humanThe presence of Gleason grades 4 and/or 5 cancer in primary adenocarcinoma of the prostate is associated with a poor outcome following radical prostatectomy. 1 The primary determinant of failure to cure prostate cancer by surgery is the percent of Gleason grade 4/5 present in the largest (index) cancer. 2 Individuals in whom cancer is composed entirely of Gleason grade 3 have a greater than 95% chance of being cured by surgery. In contrast, for approximately every 10% increase in the percent of grade 4/5 cancer present at surgery there is a 10% biochemical The functions of MAO-A in the nervous system have been extensively studied and inhibitors of its activity have therapeutic value in neurological diseases. 4 However, MAO-A actions in other tissues are not as well understood. In studies to reveal the biological role of MAO-A in prostate cancer we observed that MAO-A is also highly expressed in basal but not in secretory cells of the normal prostatic epithelium. 5 Furthermore, using a primary cell culture model we noted that...

Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

Six months of spaceflight may be sufficient to cause transient changes in left atrial structure and atrial electrophysiology that increase the risk of AF. However, there was no definite evidence of increased supraventricular arrhythmias and no identified episodes of AF.

Background and Aims Patients with familial hypercholesterolemia (FH) may be at increased risk of statin-associated muscle symptoms since they require long-term treatment with high-intensity statin therapy. We sought to determine 1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms - solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056 – also increase the risk of statin-associated muscle symptoms in FH patients, and 2) the natural history and management for FH patients with statin-associated muscle symptoms. Methods We queried electronic records (2004–2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment LDL-C 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy. Results The risk of muscle symptoms was associated with age (OR 1.6, [95% CI 1.2, 2.2]), BMI in non-African-Americans (0.90 [0.83, 0.97]), and hypertension (0.4, [0.2, 0.9]). Simvastatin most commonly employed and most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy (“eventually tolerant”) and 29% (n = 28) never reestablished statin therapy (“never tolerant”). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually-tolerated statins, and “eventually tolerant” patients achieved lower treated LDL-C levels (“eventually tolerant” 127 vs “never tolerant” 192 mg/dL, p < 0.001). “Never tolerant” patients also developed muscle symptoms on non-statins (16% vs. 50%, p = 0.003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (OR 1.40, [95% CI 0.74–2.64]). Conclusion Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never re-established statin therapy. Such patients developed muscle symptoms even on non-statin lipid lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship of FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

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Multiplexed detection assays that analyze a modest number of nucleic acid targets over large sample sets are emerging as the preferred testing approach in such applications as routine pathogen typing, outbreak monitoring, and diagnostics. However, very few DNA testing platforms have proven to offer a solution for mid-plexed analysis that is high-throughput, sensitive, and with a low cost per test. In this work, an enhanced genotyping method based on MassCode technology was devised and integrated as part of a high-throughput mid-plexing analytical system that facilitates robust qualitative differential detection of DNA targets. Samples are first analyzed using MassCode PCR (MC-PCR) performed with an array of primer sets encoded with unique mass tags. Lambda exonuclease and an array of MassCode probes are then contacted with MC-PCR products for further interrogation and target sequences are specifically identified. Primer and probe hybridizations occur in homogeneous solution, a clear advantage over micro- or nanoparticle suspension arrays. The two cognate tags coupled to resultant MassCode hybrids are detected in an automated process using a benchtop single quadrupole mass spectrometer. The prospective value of using MassCode probe arrays for multiplexed bioanalysis was demonstrated after developing a 14plex proof of concept assay designed to subtype a select panel of Salmonella enterica serogroups and serovars. This MassCode system is very flexible and test panels can be customized to include more, less, or different markers.

Although statins are well tolerated, their widespread use has raised awareness of rare adverse events. For example, the United States Food and Drug Administration (FDA) has issued product label warnings about statin-associated myopathy, incident diabetes, and cognitive impairment. Additional statin-associated adverse effects include proteinuria, transaminitis, and hemorrhagic stroke. The underlying pathophysiology of these adverse events remains unclear, and thus little guidance exists on addressing these issues at the bedside. Although statin-associated myopathy is common, many patients eventually tolerate a statin-albeit at less than ideal doses. Incident diabetes remains difficult to predict, but high statin potency, increasing age, and preexisting diabetes risk factors may predispose patients. Cognitive impairment-described mostly in case reports-may resolve after discontinuation of the offending statin. Rosuvastatin is linked to dose-dependent proteinuria. Elevated transaminases are reversible and unlikely to cause severe consequences. History of cerebrovascular disease increases the risk of hemorrhagic stroke on statin therapy. Overall, a thorough understanding of statin-associated adverse events will help health care providers manage patients who develop these complications. Here, we review the evidence for several statin-associated adverse effects and the implications for clinical practice.