Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure.</p> <p>Methods</p> <p>A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay.</p> <p>Discussion</p> <p>The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure.</p> <p>Trial Registration</p> <p>Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01143909">NCT01143909</a></p

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

Non-equilibrium Superconductivity and Quasiparticle Dynamics studied by Photo Induced Activation of Mm-Wave Absorption (PIAMA)

We present a study of non-equilibrium superconductivity in DyBa2Cu3O7-d using photo induced activation of mm-wave absorption (PIAMA). We monitor the time evolution of the thin film transmissivity at 5 cm-1 subject to pulsed infrared radiation. In addition to a positive bolometric signal we observe a second, faster, decay with a sign opposite to the bolometric signal for T>40 K. We attribute this to the unusual properties of quasi-particles residing near the nodes of an unconventional superconductor, resulting in a strong enhancement of the recombination time.Comment: 4 pages, REVTeX, Submitted to Phys. Rev. Letter

Towards the prevention of acute lung injury: a population based cohort study protocol

<p>Abstract</p> <p>Background</p> <p>Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets.</p> <p>Methods/Design</p> <p>In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups.</p> <p>Discussion</p> <p>This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials.</p

Nanoscale mechanical control of surface electrical properties of manganite films with magnetic nanoparticles

Mechanical control of electrical properties in complex heterostructures, consisting of magnetic FeOx nanoparticles on top of manganite films, is achieved using atomic force microscope AFM based methods. Under applied pressure of the AFM tip, drop of the electrical conductivity is observed inducing an electrically insulating state upon a critical normal load. Current and surface potential maps suggest that the switching process is mainly governed by the flexoelectric field induced at the sample surface. The relaxation process of the electrical surface potential indicates that the diffusion of oxygen vacancies from the bulk of the manganite films towards the sample surface is the dominant relaxation mechanism. The magnetic FeOx nanoparticles, staying attached to the sample surface after the rubbing, protect the underlying manganite films and provide stability of the observed resistive switching effect. The employed mechanical control gives a new freedom in the design of resistive switching devices since it does not depend on the film thickness, and biasing is not neede