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. The aim of this multicenter prospective observational study was to evaluate the Quantra System against the ROTEM delta device in monitoring coagulation and fibrinolysis in patients undergoing liver transplantation. One hundred twenty-five (125) adult subjects (above 18 y old) were enrolled across 5 medical centers in the US. Blood samples were collected at a minimum of 3-time points: preincision (baseline), during the anhepatic phase, and after the start of reperfusion. Performance was assessed as the correlation of equivalent measurements from the QStat Cartridge and ROTEM delta INTEM, EXTEM, and FIBTEM assays. In addition, a clinical concordance analysis was performed to assess the agreement between the 2 devices related to the detection of fibrinolysis. The correlation between the 2 viscoelastic testing devices was strong, with r -values ranging between 0.88 and 0.95, and the overall agreement with respect to detecting fibrinolysis was 90.3% (CI, 86.9%-93.2%). The results indicate that the Quantra with the QStat Cartridge provides comparable information as the ROTEM delta in the assessment of hemostatic function during a liver transplant. Quantra's simplicity of use and availability of rapid results may provide clinicians with a faster, more convenient means to assess coagulation and fibrinolysis status in the operating room and critical care setting.

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. METHODS: A multicenter observational study was conducted on adult subjects at two level 1 trauma centers. For each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products and/or antifibrinolytics. Samples were analyzed on the Quantra in parallel to ROTEM delta. The QStat cartridge provides measures of Clot Time (CT), Clot Stiffness (CS), Fibrinogen and Platelet Contributions to clot stiffness (FCS and PCS), and Clot Stability to Lysis (CSL). Data analyses included linear regression of Quantra and ROTEM parameters and an assessment of the concordance of the two devices for the assessment of hyperfibrinolysis. RESULTS: A total of 56 patients were analyzed. 42% of samples had a low QStat CS value suggestive of an hypocoagulable state. The low stiffness values could be attributed to either low PCS, FCS or combination. Additionally, 13% of samples showed evidence of hyperfibrinolysis based on the QStat CSL parameter. Samples analyzed with ROTEM assays showed a lower prevalence of low CS and hyperfibrinolysis based on EXTEM and FIBTEM results. The correlation of CS, FCS and CT versus equivalent ROTEM parameters was strong with r-values of 0.83, 0.79 and 0.79, respectively. DISCUSSION: This first clinical experience with the Quantra in trauma patients showed that the QStat Cartridge was strongly correlated with ROTEM parameters and that it could detect coagulopathies associated with critical bleeding. LEVEL OF EVIDENCE: Diagnostic test, Level II.

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. The aim of this study was to evaluate this new system in a surgical population. METHODS: Two hundred seventy-seven adult subjects were enrolled in a multicenter, prospective observational study consisting primarily of patients undergoing cardiac and major orthopedic surgeries. Samples were obtained at multiple time points for testing on the Quantra QPlus System, the rotational thromboelastometry (ROTEM) delta, and standard coagulation tests. Quantra measurements included Clot Time (CT), Heparinase Clot Time (CTH), Clot Time Ratio (CTR), Clot Stiffness (CS), Fibrinogen (FCS), and Platelet (PCS) Contributions to CS. Data analyses included assessment of the concordance of Quantra parameters with a series of clinical composite indexes formed on the basis of standard coagulation tests in 3 domains representing increased, decreased, and normal/subclinical coagulation function. Linear regression and receiver operator characteristic (ROC) analyses of Quantra parameters with corresponding parameters from ROTEM assays were also performed. RESULTS: The accuracy (overall percent agreement or ratio of true positives and true negatives over the entire population) between the Quantra and the composite indexes was between 72% and 98% depending on the specific parameter. Linear regression analysis indicated that the correlation between ROTEM delta and Quantra was very strong with r values ranging between 0.84 and 0.89. Results from ROC analysis demonstrated sensitivities and specificities in the 80%-90% range when QPlus parameters were used to discriminate ROTEM threshold values currently used in goal-directed treatment algorithms. CONCLUSIONS: This study demonstrated that the Quantra QPlus System is strongly correlated with a well-established viscoelastic testing device and its parameters effectively represent the results from multiple standard laboratory assays. The Quantra has been designed to operate at the point of care with the potential to provide rapid and comprehensive results to aid in the management of coagulopathic patients.

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. DESIGN: Prospective, observational study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 30 adult patients undergoing cardiac surgery. INTERVENTIONS: Paired arterial and venous samples were obtained at 2 of the following time points: baseline, during bypass, or after protamine reversal of heparin. Quantra measurements included Clot Time (CT), Heparinase Clot Time (CTH), Clot Time Ratio (CTR), Clot Stiffness (CS), and Fibrinogen (FCS) and Platelet (PCS) Contributions to clot stiffness. MEASUREMENTS AND MAIN RESULTS: The relationship and agreement between matched data pairs were established and statistical analysis was performed via paired t tests. CTR, CS, FCS, and PCS were unaffected by the sampling site, whereas CT and CTH demonstrated statistically significant differences between arterial and venous samples (p < 0.001). Arterial clot times were prolonged relative to the venous ones with a mean percent error of 14.2 % and 11.9 %, respectively. These results are in general agreement with those reported for other viscoelastic testing devices. CONCLUSIONS: This study demonstrates that Quantra clot stiffness-based parameters (CS, FCS, PCS) are unaffected by sampling site, whereas the clot time parameters (CT and CTH) show good correlation in the presence of a bias. CTR, a ratio of CT and CTH, also is unaffected.

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. METHODS: NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. RESULTS: Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). CONCLUSIONS: The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008-13, this study was not registered in clinicaltrials.gov.

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. Patients who achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL-C cohort. CVD-related costs included all health plan paid amounts related to CVD events or lipid management. Cost effectiveness was assessed through incremental cost-effectiveness ratios, defined as difference in total costs across the cohorts divided by difference in CVD events, measured over follow-up. Each cohort included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up. Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and had fewer CVD events during follow-up compared to patients in the LDL-C cohort. This led to greater pharmacy costs and lower medical costs over time. Incremental cost-effectiveness ratio estimates ranged from $23,131 per CVD event avoided at 12 months to $3,439 and -$4,555 at 24- and 36-month follow-up, suggesting a high likelihood that achieving LDL-P <1,000 nmol/l is cost effective. In conclusion, LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with greater clinical and economic benefit seen over longer time horizons and with the increased use of generic statins.

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. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses. METHODS: Nuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48). RESULTS: GlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset. CONCLUSIONS: High levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients.

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. METHODS AND RESULTS: Patients (n=2999) in the Intermountain Heart Collaborative Study who underwent angiography and had lipoprotein particle measurements determined by nuclear magnetic resonance (NMR) spectroscopy were studied. Multivariable Cox hazard regression was utilized to evaluate the association of HDL-C, HDL-P, and HDL-P subclasses with future major adverse CV events (MACE: death, myocardial infarction, heart failure, and stroke). Patients averaged 64±12years, 66% male, 26% diabetic, and 42% ACS. At angiography, 65% of patients were diagnosed with coronary artery disease (CAD). HDL-C and HDL-P averaged 41±13mg/dL and 28±8µmol/L, respectively. HDL-P (HR=0.903, p=0.001), but not HDL-C (HR=0.947, p=0.102) was significantly associated with MACE. In a model that included all HDL-P subclasses, both small (HR=0.862, p<0.0001) and medium (HR=0.922, p=0.020) were associated with CV risk, but not large HDL-P (HR=1.0042, p=0.185). Small HDL-P continued to be associated with all of the individual components of MACE, but not stroke. CONCLUSION: In this study of patients undergoing angiography, HDL-P was a strong, independent predictor of future MACE, with the smaller HDL-P accounting for this association.

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). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance. RESULTS: On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1ß, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all). CONCLUSIONS: GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.

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. We assessed patients longitudinally to determine how lipoproteins and GlycA change with active SLE. METHODS: Sera from selected clinical visits of patients in the Hopkins Lupus Cohort were analyzed for lipoprotein and GlycA levels. Univariate and multivariate analyses were performed to evaluate lipoprotein variables and their relationship to ethnicity, disease activity, prednisone use, and hydroxychloroquine (HCQ) therapy. RESULTS: Fifty-two patients were included over 229 visits. Adverse changes in lipoprotein variables with disease activity were demonstrated. For each point increase in the Systemic Lupus Erythematosus Disease Activity Index, there was a decrease in high-density lipoprotein (HDL) even after adjusting for corticosteroid use. Prednisone was associated with higher very low-density lipoprotein, low-density lipoprotein, HDL, and triglycerides. HCQ was associated with more favorable variables. GlycA levels were higher than in normal populations and increased with disease activity. CONCLUSION: Adverse changes in lipoprotein profiles were associated with SLE activity and prednisone therapy. This gives insight into mechanisms of atherosclerosis in SLE. Favorable lipoprotein variables occurred in those taking HCQ. GlycA increased with disease activity and was higher than in healthy populations.

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. In this post hoc analysis, percentage change in concentrations of LDL-P, very-low-density lipoprotein particles, and high-density lipoprotein particles from baseline to week 12 was determined by nuclear magnetic resonance. Alirocumab significantly reduced mean concentrations of total LDL-P (-63.3% versus -1.0% with placebo) and large (-71.3% versus -21.8%) and small (-54.0% versus +17.8%) LDL-P subfractions and total very-low-density lipoprotein particle concentrations (-36.4% versus +33.4%; all P<0.01). Total high-density lipoprotein particles increased with alirocumab (+11.2% versus +1.4% with placebo; P<0.01). There were greater increases in large (44.6%) versus medium (17.7%) or small high-density lipoprotein particles (2.8%) with alirocumab. LDL-P size remained relatively unchanged in both groups; however, very-low-density and high-density lipoprotein particle sizes increased to a significantly greater extent with alirocumab. CONCLUSIONS: Alirocumab significantly reduced LDL-C and LDL-P concentrations in hypercholesterolemic patients receiving stable atorvastatin therapy. These findings may be of particular relevance to patients with discordant LDL-C and LDL-P concentrations. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01288443.

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. T tests were used for continuous variables and Pearson chi-square test for categorical variables. RESULTS: Study patients (108,333) were79 % White, 12 % Black, and 9 % Hispanic. Fewer Black males underwent surgery (15 %) compared to Whites or Hispanics (∼22 %). Blacks compared to Whites were younger (42.7 ± 10.6 vs. 46.4 ± 11.6 years), heavier BMI (50 ± 9.1 vs. 47.4 ± 8.0 kg/m(2)), and more often hypertensive (57 vs. 52 %). Other comorbidities were higher in Whites. Thirty-day mortality rate was equivalent (0.23-0.26 %), but serious adverse events were higher for Blacks (3.65 %) versus Whites (3.19 %) and Hispanics (2.01 %). At 1 year, weight and comorbidity burden declined significantly but less in Blacks despite adjustment for baseline characteristics. CONCLUSIONS: Fewer Black males underwent RYGB. Despite a smaller percent decline in BMI and comorbidities in Blacks, all races benefitted significantly from RYGB. Influence of other factors such as diet, culture, and genetics needs to be investigated further.

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. METHODS: Data were obtained from the BOLD (Bariatric Outcomes Longitudinal Database) for 51,788 laparoscopic gastric bypass (LRYGB) procedures performed between 2007 and 2010. Logistic regression models were used to evaluate age, sex, race, body mass index, insurance status, comorbidities, and LOS as predictors for 30-day mortality, serious complications, and readmissions. RESULTS: Overall patient demographics were as follows: median age, 45 years; median body mass index, 46.3 kg/m; % female, 78.6; % white, 77.8; % private insurance, 86.2; and % comorbidities more than 5 (39.1%). Overall, 30-day outcomes included mortality, 0.1%; serious complications, 0.5%; and readmissions, 3.8%. median LOS was 2 days, and the distribution of LOS was as follows [n (%)]: 0 (1.0), 1 (18.4), 2 (59.0), 3 (17.5), and 4 (4.1). Using the median LOS 2 days as reference, the logistic regression analysis revealed that ambulatory LOS of was significantly associated with increased risk of 30-day mortality (odds ratio: 13.02; P < 0.0001) as was LOS 1 day (odds ratio: 2.02; P < 0.0552). For LOS of 0 day, there was a trend toward an increase in the rate of 30-day serious complications (odds ratio: 1.9; P < 0.16). There was no significant trend between LOS status and 30-day readmission rates. CONCLUSIONS: In this large, prospective, clinical database, LOS of 1 day or less for LRYGB patients was significantly associated with an increased risk of 30-day mortality and a trend toward increased risk of 30-day serious complications.

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 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers. METHODS: Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed. RESULTS: The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P<0.0001), increasing age (P<0.005), male gender (P<0.001), pulmonary hypertension (P<0.0001), congestive heart failure (P=0.0008), and liver disease (P=0.038). When the RYGB risk score was applied, a significant trend (P<0.0001) between increasing risk score and mortality rate is found. CONCLUSIONS: Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.

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. RESULTS: A year after patients underwent either gastric bypass (51%) or adjustable gastric banding (49%) surgery, mean estimated weight loss for all ethnic groups differed by a maximum of only 1.5 kg, being 34.3 kg (95%CI: 30.0-38.5 kg) for Hispanics, 33.8 kg (95%CI: 27.3-40.3 kg) for non-Hispanic blacks, and 32.8 kg (95%CI: 30.9-34.7 kg) for non-Hispanic whites. No overall pairwise group comparisons were significant, indicating that no ethnic group had better weight loss outcomes than did another. CONCLUSION: Bariatric surgery substantially reduces the weight of severely obese adolescents at 1 year post-procedure with little variation by ethnicity and/or gender. These results suggest that bariatric surgery is a safe and reasonable treatment for all severely obese adolescents with the appropriate indications.

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. The BOLD data are collected from 423 surgeons at 360 facilities in the United States. METHODS: The main outcome measures included the anthropometric and co-morbidity status at baseline (n = 890) and at 3 (n = 786), 6 (n = 541), and 12 (n = 259) months after surgery. Adolescents (75% female; 68% non-Hispanic white, 14% Hispanic, 11% non-Hispanic black, and 6% other) aged 11 to 19 years were included in the present analyses. RESULTS: The overall 1-year mean weight loss for those who underwent gastric bypass surgery was more than twice that of those who underwent adjustable gastric band surgery (48.6 versus 20 kg, P < .001). Similar results were found for all other anthropometric changes and comparisons within 1 year between surgery types (P < .001). In general, the gastric bypass patients reported more improvement than the adjustable gastric band patients in co-morbidities at 1 year after surgery. A total of 45 readmissions occurred among gastric bypass patients and 10 among adjustable gastric band patients, with 29 and 8 reoperations required, respectively. CONCLUSIONS: The weight loss at 3, 6, and 12 months after surgery is approximately double in adolescent males and females who underwent gastric bypass surgery versus those who underwent adjustable gastric band surgery. Bariatric surgery can safely and substantially reduce weight and related co-morbidities in morbidly obese adolescents for ≥1 year.

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. This population was randomly divided into a 50% testing sample and a 50% validation sample. The testing sample was used to identify significant predictors of 90-day composite adverse events and estimate odds ratios, while the validation sample was used to assess model calibration. After validating the fit of the risk stratification model, the testing and validation samples were combined to estimate the final odds ratios. RESULTS: The 90-day composite adverse event rate was 1.48%. The risk stratification model of 90-day composite adverse events included age (40-64, ≥ 65), indicators for male gender, body mass index (50-59.9, ≥ 60), obesity hypoventilation syndrome, back pain, diabetes, pulmonary hypertension, ischemic heart disease, functional status, and American Society of Anesthesiology classes 4 or 5. Our final gastric bypass model was predictive (c-statistic = .68) of serious adverse events 90 days after surgery. CONCLUSIONS: With additional validation, this risk model can inform both the patient and surgeon about the risks of bariatric surgery and its different procedures, as well as enable valid outcomes comparisons between surgeons and surgical programs.

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. Ninety-day and 1-year outcomes were assessed to determine early outcomes in bariatric surgery patients with MetS. RESULTS: Among 186,576 research-consented patients, 23,106 (12%) were diagnosed with MetS. Patients with MetS were more likely to be male (35% vs 20%; p < 0.0001), older (mean age 54 vs 44 years; p < 0.0001), and Caucasian (81% vs 74%; p < 0.0001). Of the 23,106 MetS patients, more underwent gastric bypass (RYGB) (62%) compared with gastric banding (32%), sleeve gastrectomy (4.5%), and biliopancreactic diversion with duodenal switch (BPD/DS)(1.5%). MetS patients had an increase in serious complications (2.4% vs 1.0%; p < 0.0001), readmissions (6.2% vs 4.7%; p < 0.0001), and mortality (0.3% vs 0.1%; p < 0.0001) within 90 days of operation. After adjusting for sex, age, and body mass index, RYGB patients with MetS had an increased risk of 90-day serious complications compared to RYGB patients without MetS (odds ratio 1.43; 95% CI, 1.27 to 1.61; p < 0.0001). The 12-month remission rate of diabetes was least for gastric banding (28%) compared with the other procedures (RYGB 62%, sleeve gastrectomy 52%, BPD/DS 74%). CONCLUSIONS: Patients with MetS undergoing bariatric surgery showed dramatic improvement in diabetes 1-year after surgery; however, an adverse 90-day outcome was more common.

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.

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. METHODS: The data in the Bariatric Outcomes Longitudinal Database from 73,921 research-consented patients who had undergone bariatric surgery by a participant in the American Society for Metabolic and Bariatric Surgery Bariatric Surgery Center of Excellence program before September 22, 2009, were analyzed for VTE events within 90 days after surgery. RESULTS: The overall risk of VTE within 90 days after surgery was .42%, and 73% of these events occurred after discharge, most within 30 days after surgery. The risk of VTE was greater in the patients undergoing gastric bypass than in those undergoing adjustable gastric banding (.55% versus .16%). VTE was more frequent when the procedure was performed using an open than a laparoscopic approach (1.54% versus .34%). Patients with a VTE event were older (+4.9 yr), had had a greater preoperative body mass index (+3.9 kg/m(2)), and were more likely to have a history of VTE (16.5% versus 3.7%). The risk of VTE was greater in men (hazard ratio 2.32, 95% confidence interval 1.81-2.98) and in patients with an inferior vena cava filter (hazard ratio 7.66, 95% confidence interval 4.55-12.91). CONCLUSION: The overall risk of VTE was low in the population treated by participants in the Bariatric Surgery Center of Excellence program, where clinical pathways to prevent VTE have been mandated. Analysis of this large study population allowed the identification of patient characteristics correlating with increased risk of postoperative VTE and the variable effectiveness of VTE prophylaxis methods.