Do I really need this transthoracic ECHO? An over-utilized test in trauma and surgical intensive care units.

INTRODUCTION: Clinical use of transthoracic echocardiogram (TTE) in intensive care units (ICU) has dramatically increased without clear guidance on validated assessment indications, appropriateness, and patient value. METHODS: A retrospective analysis of consecutive TTEs performed among patients admitted to a tertiary trauma/surgical ICU over 2.5 years was performed. A bivariate analysis and Poisson regression was used to compare patients who received a TTE. Sensitivity analysis was performed to assess patient factors that predict change in management based on TTE. An abnormal exam was defined as having at least one of the following: ejection fraction < 55%, wall motion, pericardial effusion, pericardial effusion, or other significant abnormality including filling defect. The effect on management was derived from clinical course. We hypothesize that these studies are usually normal and rarely lead to changes in clinical management. RESULTS: 912 TTEs were performed in 806 patients. The median age was 68 years (IQR 57, 77) and 63.5% were male. Syncope (21.7%) or hypotension/hypovolemia (20.5%) were the most common indications for a TTE. In total, 39.4% TTEs were abnormal and only 7.6% resulted in a change in management. Predictive factors associated with an abnormal exam included: age >50, serum troponin ≥0.1 ng/ml, abnormal ECG, and clinical suspicion of heart failure or acute myocardial infarction. A troponin cutoff level <0.25 ng/mL was the most reliable factor to predict no change in management after TTE with a negative predictive value of 94.3% (95% CI 93.1, 95.3). CONCLUSION: TTE is commonly used for patient assessment in critically ill surgical patients but the majority of exams are normal without change in clinical management. Certain patient factors, such as troponin level, may help distinguish which patients would benefit from this diagnostic test. Given the considerable cost associated with TTE and the minimal effect on management, guidelines on appropriate use would provide improved patient value.

Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding Through Model Cell Membranes and in vivo Toxicity.

INTRODUCTION: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications. METHODS AND MATERIALS: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC). RESULTS AND DISCUSSION: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed in vivo to determine how AuNP curvature and uptake influence cell health. In contrast, in vivo toxicity tested in embryonic zebrafish showed rapid toxicity of the 5 nm AuNPs, with significant 24 hpf mortality occurring at concentrations ≥20 mg/L, whereas the 10 nm and 20 nm AuNPs showed no significant mortality throughout the five-day experiment. CONCLUSION: By combining information from membrane models using SFG spectroscopy with in vivo toxicity studies, a better mechanistic understanding of how nanoparticles (NPs) interact with membranes is developed to understand how the physiochemical features of AuNPs drive nanoparticle-membrane interactions, cellular uptake, and toxicity.

A facile route to tailoring peptide-stabilized gold nanoparticles using glutathione as a synthon.

The preparation of gold nanoparticles (AuNPs) of high purity and stability remains a major challenge for biological applications. This paper reports a simple synthetic strategy to prepare water-soluble peptide-stabilized AuNPs. Reduced glutathione, a natural tripeptide, was used as a synthon for the growth of two peptide chains directly on the AuNP surface. Both nonpolar (tryptophan and methionine) and polar basic (histidine and dansylated arginine) amino acids were conjugated to the GSH-capped AuNPs. Ultracentrifugation concentrators with polyethersulfone (PES) membranes were used to purify precursor materials in each stage of the multi-step synthesis to minimize side reactions. Thin layer chromatography, transmission electron microscopy, UV-Visible, 1H-NMR, and fluorescence spectroscopies demonstrated that ultracentrifugation produces high purity AuNPs, with narrow polydispersity, and minimal aggregation. More importantly, it allows for more control over the composition of the final ligand structure. Studies under conditions of varying pH and ionic strength revealed that peptide length, charge, and hydrophobicity influence the stability as well as solubility of the peptide-capped AuNPs. The synthetic and purification strategies used provide a facile route for developing a library of tailored biocompatible peptide-stabilized AuNPs for biomedical applications.

The Impact of Surface Ligands and Synthesis Method on the Toxicity of Glutathione-Coated Gold Nanoparticles.

Gold nanoparticles (AuNPs) are increasingly used in biomedical applications, hence understanding the processes that affect their biocompatibility and stability are of significant interest. In this study, we assessed the stability of peptide-capped AuNPs and used the embryonic zebrafish (Danio rerio) as a vertebrate system to investigate the impact of synthesis method and purity on their biocompatibility. Using glutathione (GSH) as a stabilizer, Au-GSH nanoparticles with identical core sizes were terminally modified with Tryptophan (Trp), Histidine (His) or Methionine (Met) amino acids and purified by either dialysis or ultracentrifugation. Au-GSH-(Trp)2 purified by dialysis elicited significant morbidity and mortality at 200 µg/mL, Au-GSH-(His)2 induced morbidity and mortality after purification by either method at 20 and 200 µg/mL, and Au-GSH-(Met)2 caused only sublethal responses at 200 µg/mL. Overall, toxicity was significantly reduced and ligand structure was improved by implementing ultracentrifugation purifications at several stages during the multi-step synthesis and surface modification of Au-GSH nanoparticles. When carefully synthesized at high purity, peptide-functionalized AuNPs showed high biocompatibility in biological systems.