Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention

On the growth of linear perturbations

We consider the linear growth of matter perturbations in various dark energy (DE) models. We show the existence of a constraint valid at $z=0$ between the background and dark energy parameters and the matter perturbations growth parameters. For $\Lambda$CDM $\gamma'_0\equiv \frac{d\gamma}{dz}_0$ lies in a very narrow interval $-0.0195 \le \gamma'_0 \le -0.0157$ for $0.2 \le \Omega_{m,0}\le 0.35$. Models with a constant equation of state inside General Relativity (GR) are characterized by a quasi-constant $\gamma'_0$, for $\Omega_{m,0}=0.3$ for example we have $\gamma'_0\approx -0.02$ while $\gamma_0$ can have a nonnegligible variation. A smoothly varying equation of state inside GR does not produce either $|\gamma'_0|>0.02$. A measurement of $\gamma(z)$ on small redshifts could help discriminate between various DE models even if their $\gamma_0$ is close, a possibility interesting for DE models outside GR for which a significant $\gamma'_0$ can be obtained.Comment: 8 pages, 8 figures. Results unchanged; clarifying sentence added; one reference adde

Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven) for perioperative volume replacement in children undergoing cardiac surgery: a propensity-matched analysis

Introduction: Six percent hydroxyethyl starch (HES) 130/0.4 is considered an alternative to human albumin (HA) and crystalloids for volume replacement in children undergoing cardiac surgery. In this large propensity-matched analysis, we aimed to assess the efficacy and safety of replacing HA with HES for intraoperative volume therapy in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We retrospectively reviewed our database, including children who underwent cardiac surgery between January 2002 and December 2010. Four percent HA was used until 2005; it was replaced by HES thereafter. Demographic data, intra- and postoperative blood loss and blood component transfusions were recorded, together with the incidence of postoperative complications and mortality. We performed a propensity-matched analysis using 13 possible confounding factors to compare children who received either HES or HA intraoperatively. The primary objectives included the effects of both fluids on intraoperative fluid balance (difference between fluids in and fluids out (efficacy)) and blood loss and exposure to allogeneic blood products (safety). Secondary safety outcomes were mortality and the incidence of postoperative renal dysfunction. Results: Of 1,832 children reviewed, 1,495 were included in the analysis. Intraoperative use of HES was associated with a less positive fluid balance. Perioperative blood loss, volume of red blood cells and fresh frozen plasma administered, as well as the number of children who received transfusions, were also significantly lower in the HES group. No difference was observed regarding the incidence of postoperative renal failure requiring renal replacement therapy or of morbidity and mortality. Conclusions: These results confirm that the use of HES for volume replacement in children during cardiac surgery with CPB is as safe as HA. In addition, its use might be associated with less fluid accumulation. Further large studies are needed to assess whether the reduction in fluid accumulation could have a significant impact on postoperative morbidity and mortality

Nonminimal Couplings in the Early Universe: Multifield Models of Inflation and the Latest Observations

Models of cosmic inflation suggest that our universe underwent an early phase of accelerated expansion, driven by the dynamics of one or more scalar fields. Inflationary models make specific, quantitative predictions for several observable quantities, including particular patterns of temperature anistropies in the cosmic microwave background radiation. Realistic models of high-energy physics include many scalar fields at high energies. Moreover, we may expect these fields to have nonminimal couplings to the spacetime curvature. Such couplings are quite generic, arising as renormalization counterterms when quantizing scalar fields in curved spacetime. In this chapter I review recent research on a general class of multifield inflationary models with nonminimal couplings. Models in this class exhibit a strong attractor behavior: across a wide range of couplings and initial conditions, the fields evolve along a single-field trajectory for most of inflation. Across large regions of phase space and parameter space, therefore, models in this general class yield robust predictions for observable quantities that fall squarely within the "sweet spot" of recent observations.Comment: 17pp, 2 figs. References added to match the published version. Published in {\it At the Frontier of Spacetime: Scalar-Tensor Theory, Bell's Inequality, Mach's Principle, Exotic Smoothness}, ed. T. Asselmeyer-Maluga (Springer, 2016), pp. 41-57, in honor of Carl Brans's 80th birthda

Observational evidence for cosmological coupling of black holes and its implications for an astrophysical source of dark energy

Observations have found black holes spanning ten orders of magnitude in mass across most of cosmic history. The Kerr black hole solution is however provisional as its behavior at infinity is incompatible with an expanding universe. Black hole models with realistic behavior at infinity predict that the gravitating mass of a black hole can increase with the expansion of the universe independently of accretion or mergers, in a manner that depends on the black hole's interior solution. We test this prediction by considering the growth of supermassive black holes in elliptical galaxies over $0<z\lesssim2.5$. We find evidence for cosmologically coupled mass growth among these black holes, with zero cosmological coupling excluded at 99.98% confidence. The redshift dependence of the mass growth implies that, at $z\lesssim7$, black holes contribute an effectively constant cosmological energy density to Friedmann's equations. The continuity equation then requires that black holes contribute cosmologically as vacuum energy. We further show that black hole production from the cosmic star formation history gives the value of $\Omega_{\Lambda}$ measured by Planck while being consistent with constraints from massive compact halo objects. We thus propose that stellar remnant black holes are the astrophysical origin of dark energy, explaining the onset of accelerating expansion at $z \sim 0.7$.Comment: 10 pages, 3 figures, published in ApJ Letter

Recommendations from the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS)

Background: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality following surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. Objective: To develop consensus recommendations for anemia management in surgical patients. Methods: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. Results: The panel recommends that all patients be screened for anemia prior to surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. Conclusions: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients

Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule

Overexpression of Bcl-2 protein occurs via both t(14;18)-dependent and independent mechanisms and contributes to the survival and chemoresistance of non-Hodgkin lymphomas. HA14–1 is a nonpeptidic organic small molecule, which has been shown to inhibit the interaction of Bcl-2 with Bax, thereby interfering with the antiapoptotic function of Bcl-2. In this study, we sought to determine the in vitro efficacy of HA14–1 as a therapeutic agent for non-Hodgkin lymphomas expressing Bcl-2. Assessment of cell viability demonstrated that HA14–1 induced a dose- (IC50 = 10 μM) and time-dependent growth inhibition of a cell line (SudHL-4) derived from a t(14;18)-positive, Bcl-2-positive, non-Hodgkin lymphoma. HA14–1 effectively induced apoptosis via a caspase 3-mediated pathway but did not affect either the p38 MAPK or p44/42 MAPK pathways. Western blot analyses of Bcl-2 family proteins and other cell cycle-associated proteins were performed to determine the molecular sequelae of HA14–1-induced apoptosis. The results show down-regulation of Mcl-1 but up-regulation of p27kip1, Bad, Bcl-xL, and Bcl-2 proteins, without change in Bax levels during HA14–1-mediated apoptosis. Our findings further elucidate the cellular mechanisms accompanying Bcl-2 inhibition and demonstrate the potential of Bcl-2 inhibitors as therapeutic agents for the treatment of non-Hodgkin lymphomas

Observational Evidence for Cosmological Coupling of Black Holes and its Implications for an Astrophysical Source of Dark Energy

Observations have found black holes spanning 10 orders of magnitude in mass across most of cosmic history. The Kerr black hole solution is, however, provisional as its behavior at infinity is incompatible with an expanding universe. Black hole models with realistic behavior at infinity predict that the gravitating mass of a black hole can increase with the expansion of the universe independently of accretion or mergers, in a manner that depends on the black hole’s interior solution. We test this prediction by considering the growth of supermassive black holes in elliptical galaxies over 0 < z ≲ 2.5. We find evidence for cosmologically coupled mass growth among these black holes, with zero cosmological coupling excluded at 99.98% confidence. The redshift dependence of the mass growth implies that, at z ≲ 7, black holes contribute an effectively constant cosmological energy density to Friedmann’s equations. The continuity equation then requires that black holes contribute cosmologically as vacuum energy. We further show that black hole production from the cosmic star formation history gives the value of ΩΛ measured by Planck while being consistent with constraints from massive compact halo objects. We thus propose that stellar remnant black holes are the astrophysical origin of dark energy, explaining the onset of accelerating expansion at z ∼ 0.7