Rivaroxaban for the Treatment of Pulmonary Embolism

With the advent of new oral anticoagulants (NOACs) for the treatment of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE), a new era of oral anticoagulation for patients with venous thromboembolism (VTE) has begun. Rivaroxaban is the first NOAC to receive regulatory approval for the acute and continued treatment of DVT and PE, and for the secondary prevention of VTE. Here, the clinical trials of rivaroxaban in patients with VTE are reviewed, and the clinical use of rivaroxaban for patients with PE is discussed. Even though rivaroxaban will facilitate the therapeutic management of PE, its use in specific clinical situations needs further study

Hemostasis and inflammation: two of a kind?

Hemostasis is a defense mechanism to stop bleeding. Activated by vessel wall injury, it consists of intertwined activation of platelets and the coagulation cascade, tightly controlled by natural anticoagulants and the fibrinolytic system

TreatmentPatterns:An R package to facilitate the standardized development and analysis of treatment patterns across disease domains

Background and objectives: There is an increasing interest to use real-world data to illustrate how patients with specific medical conditions are treated in real life. Insight in the current treatment practices helps to improve and tailor patient care, but is often held back by a lack of data interoperability and a high-level of required resources. We aimed to provide an easy tool that overcomes these barriers to support the standardized development and analysis of treatment patterns for a wide variety of medical conditions. Methods: We formally defined the process of constructing treatment pathways and implemented this in an open-source R package TreatmentPatterns (https://github.com/mi-erasmusmc/TreatmentPatterns) to enable a reproducible and timely analysis of treatment patterns. Results: The developed package supports the analysis of treatment patterns of a study population of interest. We demonstrate the functionality of the package by analyzing the treatment patterns of three common chronic diseases (type II diabetes mellitus, hypertension, and depression) in the Dutch Integrated Primary Care Information (IPCI) database. Conclusion: TreatmentPatterns is a tool to make the analysis of treatment patterns more accessible, more standardized, and more interpretation friendly. We hope it thereby contributes to the accumulation of knowledge on real-world treatment patterns across disease domains. We encourage researchers to further adjust and add custom analysis to the R package based on their research needs.</p

Prediction of coronary artery disease using urinary proteomics

Aims: Coronary artery disease (CAD) is multifactorial, caused by complex pathophysiology, and contributes to a high burden of mortality worldwide. Urinary proteomic analyses may help to identify predictive biomarkers and provide insights into the pathogenesis of CAD. Methods and results: Urinary proteome was analysed in 965 participants using capillary electrophoresis coupled with mass spectrometry. A proteomic classifier was developed in a discovery cohort with 36 individuals with CAD and 36 matched controls using the support vector machine. The classifier was tested in a validation cohort with 115 individuals who progressed to CAD and 778 controls and compared with two previously developed CAD-associated classifiers, CAD238 and ACSP75. The Framingham and SCORE2 risk scores were available in 737 participants. Bioinformatic analysis was performed based on the CAD-associated peptides. The novel proteomic classifier was comprised of 160 urinary peptides, mainly related to collagen turnover, lipid metabolism, and inflammation. In the validation cohort, the classifier provided an area under the receiver operating characteristic curve (AUC) of 0.82 [95% confidence interval (CI): 0.78–0.87] for the CAD prediction in 8 years, superior to CAD238 (AUC: 0.71, 95% CI: 0.66–0.77) and ACSP75 (AUC: 0.53 and 95% CI: 0.47–0.60). On top of CAD238 and ACSP75, the addition of the novel classifier improved the AUC to 0.84 (95% CI: 0.80–0.89). In a multivariable Cox model, a 1-SD increment in the novel classifier was associated with a higher risk of CAD (HR: 1.54, 95% CI: 1.26–1.89, P \u3c 0.0001). The new classifier further improved the risk reclassification of CAD on top of the Framingham or SCORE2 risk scores (net reclassification index: 0.61, 95% CI: 0.25–0.95, P = 0.001; 0.64, 95% CI: 0.28–0.98, P = 0.001, correspondingly). Conclusion: A novel urinary proteomic classifier related to collagen metabolism, lipids, and inflammation showed potential for the risk prediction of CAD. Urinary proteome provides an alternative approach to personalized prevention

Staphylococcus aureus and Neutrophil Extracellular Traps: The Master Manipulator Meets Its Match in Immunothrombosis

Over the past 10 years, neutrophil extracellular traps (NETs) have become widely accepted as an integral player in immunothrombosis, due to their complex interplay with both pathogens and components of the coagulation system. While the release of NETs is an attempt by neutrophils to trap pathogens and constrain infections, NETs can have bystander effects on the host by inducing uncontrolled thrombosis, inflammation, and tissue damage. From an evolutionary perspective, pathogens have adapted to bypass the host innate immune response. Staphylococcus aureus (S. aureus), in particular, proficiently overcomes NET formation using several virulence factors. Here we review mechanisms of NET formation and how these are intertwined with platelet activation, the release of endothelial von Willebrand factor, and the activation of the coagulation system. We discuss the unique ability of S. aureus to modulate NET formation and alter released NETs, which helps S. aureus to escape from the host’s defense mechanisms. We then discuss how platelets and the coagulation system could play a role in NET formation in S. aureus-induced infective endocarditis, and we explain how targeting these complex cellular interactions could reveal novel therapies to treat this disease and other immunothrombotic disorders

A young star-forming galaxy at z = 3.5 with an extended Ly\,α\alpha halo seen with MUSE

Spatially resolved studies of high redshift galaxies, an essential insight into galaxy formation processes, have been mostly limited to stacking or unusually bright objects. We present here the study of a typical (L$^{*}$, M$_\star$ = 6 $\times 10^9$ $M_\odot$) young lensed galaxy at $z=3.5$, observed with MUSE, for which we obtain 2D resolved spatial information of Ly$\alpha$ and, for the first time, of CIII] emission. The exceptional signal-to-noise of the data reveals UV emission and absorption lines rarely seen at these redshifts, allowing us to derive important physical properties (T$_e\sim$15600 K, n$_e\sim$300 cm$^{-3}$, covering fraction f$_c\sim0.4$) using multiple diagnostics. Inferred stellar and gas-phase metallicities point towards a low metallicity object (Z$_{\mathrm{stellar}}$ = $\sim$ 0.07 Z$_\odot$ and Z$_{\mathrm{ISM}}$ $<$ 0.16 Z$_\odot$). The Ly$\alpha$ emission extends over $\sim$10 kpc across the galaxy and presents a very uniform spectral profile, showing only a small velocity shift which is unrelated to the intrinsic kinematics of the nebular emission. The Ly$\alpha$ extension is $\sim$4 times larger than the continuum emission, and makes this object comparable to low-mass LAEs at low redshift, and more compact than the Lyman-break galaxies and Ly$\alpha$ emitters usually studied at high redshift. We model the Ly$\alpha$ line and surface brightness profile using a radiative transfer code in an expanding gas shell, finding that this model provides a good description of both observables.Comment: 19 pages, 15 figures, accepted in MNRA

Epidemiologic observations guiding clinical application of a urinary peptidomic marker of diastolic left ventricular dysfunction

Hypertension, obesity, and old age are major risk factors for left ventricular (LV) diastolic dysfunction (LVDD), but easily applicable screening tools for people at risk are lacking. We investigated whether HF1, a urinary biomarker consisting of 85 peptides, can predict over a 5-year time span mildly impaired diastolic LV function as assessed by echocardiography. In 645 white Flemish (50.5% women; 50.9 years [mean]), we measured HF1 by capillary electrophoresis coupled with mass spectrometry in 2005-2010. We measured early (E) and late (A) peak velocities of the transmitral blood flow and early (e') and late (a') mitral annular peak velocities and their ratios in 2009-2013. In multivariable-adjusted analyses, per 1-standard deviation increment in HF1, e' was -0.193 cm/s lower (95% confidence interval: -0.352 to -0.033; P = .018) and E/e' 0.174 units higher (0.005-0.342; P = .043). Of 645 participants, 179 (27.8%) had LVDD at follow-up, based on impaired relaxation in 69 patients (38.5%) or an elevated filling pressure in the presence of a normal (74 [43.8%]) or low (36 [20.1%]) age-specific E/A ratio. For a 1-standard deviation increment in HF1, the adjusted odds ratio was 1.37 (confidence interval, 1.07-1.76; P = .013). The integrated discrimination (+1.14%) and net reclassification (+31.7%) improvement of the optimized HF1 threshold (-0.350) in discriminating normal from abnormal diastolic LV function at follow-up over and beyond other risk factors was significant (P ≤ .024). In conclusion, HF1 may allow screening for LVDD over a 5-year horizon in asymptomatic people

The Lyman alpha Reference Sample: Extended Lyman alpha Halos Produced at Low Dust Content

We report on new imaging observations of the Lyman alpha emission line (Lya), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample (LARS). We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Lya, Halpha, and the far ultraviolet continuum. We show that Lya is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20 percent radius, RP20, Lya radii are larger than those of Halpha by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Lya-to-FUV radii is 2.9. This suggests that much of the Lya light is pushed to large radii by resonance scattering. Defining the "Relative Petrosian Extension" of Lya compared to Halpha, \xi_ext = RP20_Lya / RP20_Ha, we find \xi_ext to be uncorrelated with total Lya luminosity. However \xi_ext is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Lya photons throughout the interstellar medium and drive a large extended Lya halo.Comment: Published in ApJ Letters ~~ 6 pages using emulateapj, 4 figures ~~ Higher-resolution, larger, nicer jpeg versions of Figures 1 and 2 can be found here: http://xayes.org/pub/press_lars.htm

Blood pressure and renal function responses in workers exposed to lead for up to six years

The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the blood pressure (BP) and renal function (RF) responses for up to 6 years in the workers without previous occupational lead exposure. BP was the average of five consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 μg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 μg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92–6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p ≥.51 and p ≥.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were −0.25/−0.12 mm Hg (CI: −0.94 to 0.44/−0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p ≥.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to −0.70 mL/min/1.73 m2 (CI: −1.70 to 0.30 mL/min/1.73 m2) and −1.06 mL/min/1.73 m2 (−2.16 to 0.03 mL/min/1.73 m2). In conclusion, the BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.</p