Multicenter evaluation of the Quantra with the QStat Cartridge in adult patients undergoing liver transplantation.

Blood loss and transfusion of blood products are key concerns during liver transplantation. Whole-blood viscoelastic testing devices have been used to monitor hemostatic function and guide the transfusion of blood products in this patient population. The Quantra System with the QStat Cartridge is a new point-of-care, closed-system viscoelastic testing device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance.

Initial clinical experience with the Quantra QStat System in adult trauma patients.

Background: Whole blood viscoelastic testing (VET) devices are routinely used in a variety of clinical settings to assess hemostasis. The Quantra QStat System is a cartridge-based point of care VET device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The objective of this study was to assess the ability of the Quantra QStat System to detect coagulopathies in trauma patients.

Multicenter Evaluation of the Quantra QPlus System in Adult Patients Undergoing Major Surgical Procedures.

Background: The management of perioperative bleeding and the optimization of the available therapies are subjects of significant clinical interest. Clinical guidelines recommend the use of whole blood viscoelastic testing devices to target the utilization of blood products during major surgical procedures. The Quantra QPlus System is a new cartridge-based viscoelastic testing device based on an innovative ultrasound technology.

Comparison of Coagulation Parameters in Arterial and Venous Blood in Cardiac Surgery Measured Using the Quantra System.

Objective: Perioperative coagulation testing often is performed with arterial samples even though device reference ranges typically are established in venous samples. Although limited studies exist comparing coagulation parameters across sampling sites, viscoelastic testing devices have demonstrated some differences. The objective of this study was to compare coagulation parameters determined using the Quantra System for venous and arterial samples.

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

Background: In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile.

Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level.

A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36 months.

Utility of high density lipoprotein particle concentration in predicting future major adverse cardiovascular events among patients undergoing angiography.

Background: HDL-C is recognized to be inversely associated with cardiovascular (CV) risk. However, attenuation of the association of HDL-C with CV risk may occur after adjustment for other lipoprotein parameters and in various disease states, especially in the setting of acute coronary syndrome (ACS). Recently, the number of HDL particles (HDL-P) has been suggested to improve CV risk prediction.

Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

Background: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation.

Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy.

Objective: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerotic cardiovascular disease. Patients with SLE have adverse lipoprotein variables, but little is known about how these change with treatment and disease activity. The nuclear magnetic resonance LipoProfile test contains a glycoprotein signal-termed GlycA, an inflammatory marker, which has not been evaluated in SLE.

Effect of PCSK9 Inhibition by Alirocumab on Lipoprotein Particle Concentrations Determined by Nuclear Magnetic Resonance Spectroscopy.

Background: In patients with discordance between low-density lipoprotein (LDL) cholesterol and LDL particle (LDL-P) concentrations, cardiovascular risk more closely correlates with LDL-P.

Methods And Results: We investigated the effect of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, on lipoprotein particle concentration and size in hypercholesterolemic patients, using nuclear magnetic resonance spectroscopy. Plasma samples were collected from patients receiving alirocumab 150 mg every 2 weeks (n=26) or placebo (n=31) during a phase II, double-blind, placebo-controlled trial in patients (LDL cholesterol ≥100 mg/dL) on a stable atorvastatin dose.

A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.

Background: RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA.

Methods: Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI).

Is ambulatory laparoscopic Roux-en-Y gastric bypass associated with higher adverse events?

Objective: To determine the impact of length of stay upon 30-day outcomes.

Background: It has been recommended the goal length of stay (LOS) after laparoscopic Roux-en-Y gastric bypass (LRYGB) should be 1 day to improve resource utilization. This study's aim was to assess LRYGB outcomes by LOS.

Effect of ethnicity on weight loss among adolescents 1 year after bariatric surgery.

Aim: To investigate whether or not bariatric surgery weight outcomes vary by ethnicity in a large, nationally representative sample of adolescents.

Methods: The Bariatric Outcomes Longitudinal Database was used for analysis and contains data on surgeries performed on adolescents from 2004 to 2010 from 423 surgeons at 360 facilities across the United States Adolescents (n = 827) between 11 and 19 years old who underwent either gastric bypass or adjustable gastric banding surgery were included in the analysis. Outcome measures included changes in anthropometric measurements [weight (kg) and body mass index] from baseline to 3 (n = 739), 6 (n = 512), and 12 (n = 247) mo after surgery.

Influence of ethnicity on the efficacy and utilization of bariatric surgery in the USA.

Background: Ethnic disparities in patterns of utilization and outcomes after Roux-en-Y gastric bypass surgery (RYGB) were examined from Bariatric Outcomes Longitudinal Database.

Methods: Descriptive statistics were used for demographics of Whites, Blacks, or Hispanics undergoing RYGB with 1 year of follow-up, between June 2007 and October 2011. Multivariate logistic and normal regression models, controlling for baseline characteristics, examined relationships between race and outcomes.

Risk factors associated with mortality after Roux-en-Y gastric bypass surgery.

Objective: We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery.

Background: Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.

Risk stratification of serious adverse events after gastric bypass in the Bariatric Outcomes Longitudinal Database.

Background: There is now sufficient demand for bariatric surgery to compare bariatric surgeons and bariatric centers according to their postsurgical outcomes, but few validated risk stratification measures are available to enable valid comparisons. The purpose of this study was to develop and validate a risk stratification model of composite adverse events related to Roux-en-Y gastric bypass (RYGB) surgery.

Methods: The study population included 36,254 patients from the Bariatric Outcomes Longitudinal Database (BOLD) registry who were 18-70 years old and had RYGB between June 11, 2007, and December 2, 2009.

Changes in weight and co-morbidities among adolescents undergoing bariatric surgery: 1-year results from the Bariatric Outcomes Longitudinal Database.

Background: Bariatric surgery is 1 of the few effective treatments of morbid obesity. However, the weight loss and other health-related outcomes for this procedure in large, diverse adolescent patient populations have not been well characterized. Our objective was to analyze the prospective Bariatric Outcomes Longitudinal Database (BOLD) to determine the weight loss and health related outcomes in adolescents.

Early outcomes of bariatric surgery in patients with metabolic syndrome: an analysis of the bariatric outcomes longitudinal database.

Background: Metabolic syndrome (MetS) complicating obesity is endemic in the United States.

Study Design: Bariatric Outcomes Longitudinal Database, the national database for the American Society for Metabolic and Bariatric Surgery Bariatric Surgery Center of Excellence Program, was queried to identify patients undergoing bariatric surgery from June 2007 through November 2010. MetS was defined as the presence of hypertension, diabetes, and dyslipidemia at presentation for bariatric surgery.

Venous thromboembolism after bariatric surgery performed by Bariatric Surgery Center of Excellence Participants: analysis of the Bariatric Outcomes Longitudinal Database.

Background: Venous thromboembolism (VTE) is an uncommon complication of bariatric surgery but a leading cause of postoperative mortality. Studying the factors predictive of low-incidence complications requires the analysis of large cohorts. The Bariatric Outcomes Longitudinal Database, the world's largest prospective database for bariatric surgery, has provided a suitable medium for analyzing low-frequency events.

Phenoxyacetic acids as PPARδ partial agonists: synthesis, optimization, and in vivo efficacy.

A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.

Early postoperative outcomes of metabolic surgery to treat diabetes from sites participating in the ASMBS bariatric surgery center of excellence program as reported in the Bariatric Outcomes Longitudinal Database.

Objective: Small case series suggest bariatric surgery may be an effective treatment for type 2 diabetes mellitus in patients who do not meet body weight criteria for morbid obesity (body mass index [BMI], <35 kg/m), but large multi-institutional series, which allow better assessment of the safety and efficacy of treatment, have not been reported.

Methods: Data from 66,264 research-consented patients with a primary bariatric surgery encounter in the Bariatric Outcomes Longitudinal Database from June 2007 to June 2009 were queried to identify patients with a BMI > or =30 but <35 kg/m2 (1.2%, n = 794) and diabetes requiring any medication (29%).

Baseline data from American Society for Metabolic and Bariatric Surgery-designated Bariatric Surgery Centers of Excellence using the Bariatric Outcomes Longitudinal Database.

Background: The Bariatric Outcomes Longitudinal Database (BOLD) is a registry of self-reported bariatric surgery patient information from the American Society for Metabolic and Bariatric Surgery Bariatric Surgery Center of Excellence participants. The present study was undertaken to define the baseline characteristics of the patients with data entered into BOLD.

Methods: The data submitted by >800 surgeons and >450 facilities using BOLD before May 20, 2009, were analyzed.

Increased hepatic oxidative metabolism distinguishes the action of Peroxisome proliferator-activated receptor delta from Peroxisome proliferator-activated receptor gamma in the ob/ob mouse.

Background: The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear receptor superfamily. The PPAR family consists of three members: PPARalpha, PPARgamma, and PPARdelta. PPARdelta controls the transcription of genes involved in multiple physiological pathways, including cellular differentiation, lipid metabolism and energy homeostasis.

Discovery of a novel class of PPARdelta partial agonists.

Anthranilic acid GW9371 was identified as a novel class of PPARdelta partial agonist through high-throughput screening. The design and synthesis of SAR analogues is described. GSK1115 and GSK7227 show potent partial agonism of the PPARdelta target genes CPT1a and PDK4 in skeletal muscle cells.

Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the beta-ketoacyl reductase reaction.

GSK837149A has been identified as a selective inhibitor of human fatty acid synthase (FAS). The compound was first isolated as a minor impurity in a sample found to be active against the enzyme in a high-throughput screening campaign. The structure of this compound was confirmed by NMR and MS studies, and evaluation of the newly synthesized molecule confirmed its activity against FAS.