Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Cerebrospinal fluid leak after microvascular reconstruction of large craniofacial defects with orbital exenteration

Abstract Objectives: To assess risk factors for cerebrospinal fluid (CSF) leak after microvascular reconstruction of extensive cranio-orbitofacial resection with orbital exenteration (CFOE). Study Design: Retrospective Case Series Methods: 70 consecutive patients at a tertiary hospital underwent 76 procedures with microvascular reconstruction of CFOE defects. Patients were stratified by extent of skull base exposure and presence or absence of dural resection. Patients with exposure of the orbital apex and roof alone were classified as minimal skullbase exposure (MSE, n=32). Those with exposure beyond the orbital apex and roof were classified as significant skullbase exposure (SSE, n=38), including those with dural resection (n=23). The main outcome measure was incidence of postoperative CSF leak according to univariate and multivariate analysis of risk factors. Results: Five patients developed a postoperative CSF leak, and 3 required operative management. All 5 were SSE with dural resection and had middle fossa exposure, previous radiation and 4 had previous surgery. None of the MSE group or SSE without dural resection or SSE with anterior fossa exposure alone developed a CSF leak. Multivariate analysis revealed middle fossa exposure to be the only significant predictor of CSF leak (p=0.03). The overall complication rate was 31.6%. Major complications were greater in the SSE group (p=0.05). Conclusion: Middle fossa exposure increases the risk of CSF leak in microvascular reconstruction of CFOE defects.https://jdc.jefferson.edu/otoposters/1003/thumbnail.jp

Contrast-enhanced ultrasound-guided Sentinel lymph node biopsy of the ocular conjunctiva.

OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy (SLNB) has been utilized for cutaneous melanoma and other malignancies arising from the eye and ocular adnexa. Currently, SLNB requires blue dyes and/or radiopharmaceuticals; both of which have significant shortcomings. This study sought to evaluate the feasibility of SLNB with the use of real-time, contrast-enhanced ultrasound (CEUS) as an alternative technique for tumors arising in the conjunctiva. STUDY DESIGN: Prospective feasibility study in a porcine model. METHODS: Twelve experiments were performed on six non-tumor-bearing Yorkshire swine. An ultrasound contrast agent, Sonazoid (GE Healthcare, Oslo, Norway), (99m) technetium ((99m) Tc), and methylene blue (MB) (Covidien, Mansfield, MA) were injected in the ocular conjunctiva. Sentinel lymph nodes (SLNs) were localized with CEUS and findings were compared to that of MB and (99m) Tc. Fisher exact test was used. RESULTS: Contrast-enhanced SLNs were identified within an average of 6.2 minutes from time of injection of Sonazoid. A total of 17 SLNs were identified by at least one of the three techniques. Correlation between Sonazoid and (99m) Tc was 94.1% (16/17 SLNs). Correlation between (99m) Tc and MB was 88.2% (15/17). One SLN that was positive for (99m) Tc but negative for Sonazoid and was considered to be a false positive (1/17); findings were similar for MB (1/17). Differences between the three techniques were not significant (P = .886). CONCLUSIONS: CEUS-guided injection of conjunctiva for SLNB is technically feasible and correlates well with standard detection techniques. This technique shows promise for rapid, real-time, intraoperative imaging for SLNB, using a widely available imaging modality and avoiding the need for radiopharmaceuticals. LEVEL OF EVIDENCE: N

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

Isolation of flow and nonflow correlations by two- and four-particle cumulant measurements of azimuthal harmonics in √sNN = 200 GeV Au+Au collisions

A data-driven method was applied to Au+Au collisions at √sNN = 200 GeV made with the STAR detector at RHIC to isolate pseudorapidity distance η-dependent and η-independent correlations by using two- and four-particle azimuthal cumulant measurements. We identified a η-independent component of the correlation, which is dominated by anisotropic flow and flow fluctuations. It was also found to be independent of η within the measured range of pseudorapidity |η| 0.7