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Background The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease. Objective To characterize platelet function according to VTE phenotypes. Patients/Methods In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select clinical and platelet biomarkers that distinguish between VTE phenotypes. Results PFA-200 results did not differ between VTE phenotypes. LTA from DVT+PE subjects showed lowest maximum aggregation after epinephrine and adenosine diphosphate compared to iPE and iDVT. Lower % of PAC-1-positive platelets after in-vitro trigger were present in DVT+PE and iPE compared to iDVT. TG in PRP had lower peak height and velocity in DVT+PE and iPE against iDVT. The results of LASSO regression for the distinction between DVT+PE vs iDVT identified 18 variables (AUC =0.93) of which 72% were platelet biomarkers. For distinction between iPE and iDVT, 10 variables were selected (AUC = 0.96) of which 50% were platelet-related. Obesity was the only variable weakly discriminating between DVT+PE vs iPE (AUC = 0.66). Conclusion This explorative study suggests an important distinction between PE-related phenotypes and iDVT when considering clinical and platelet function data. Lower platelet-dependent TG along with reduced platelet reactivity suggest higher platelet degranulation in PE-dependent phenotypes compared to iDVT.

Purpose: To review the safety of hepatic radioembolization (RE) in patients with high (>= 10%) hepatopulmonary shunt fraction (HPSF) using various prophylactic techniques. Materials and Methods: A review was conducted of 409 patients who underwent technetium 99m-labeled macroaggregated albumin scintigraphy before planned RE. Estimated pulmonary absorbed radiation doses based on scintigraphy and hepatic administered activity were calculated. Outcomes from dose reductions and adjunctive catheter-based prophylactic techniques used to reduce lung exposure were assessed. Results: There were 80 patients with HPSF >= 10% who received RE treatment (41 resin microspheres for metastases, 39 glass microspheres for hepatocellular carcinoma). Resin microspheres were used in 17 patients according to consensus guideline-recommended dose reduction; 38 patients received no dose reduction because the expected lung dose was

Background and objectives Successful long-term dieting appears to be difficult, and part of its difficulty might be explained by processes related to classical appetitive conditioning. Increasing the speed of extinction of appetitive responses to food cues and decreasing the magnitude of returns of these responses could help increase the long-term effectiveness of weight loss attempts. Two extinction techniques hypothesized to slow down rapid reacquisition of conditioned appetitive responses were investigated: the provision of 1) occasional reinforced extinction trials (OR) and 2) unpaired unconditioned stimuli (USs) during extinction (UNP). Methods After acquisition, participants (N = 90) received one of three extinction trainings: OR, UNP, or normal extinction (control), followed by a reacquisition phase. Their desire to eat, US expectancy, and salivation were measured. Effects of impulsivity on different phases of appetitive conditioning were also assessed. Results It was found that both extinction techniques were successful in reducing the rate of reacquisition of US expectancies. Participants in the OR condition also demonstrated a slower extinction of US expectancies and desires to eat. However, the reacquisition of conditioned desires was not affected by either extinction technique. Impulsivity did not moderate responses during acquisition or extinction, but appeared to slow down the reacquisition of conditioned desires. Limitations US expectancies and eating desires were not completely extinguished, and a few differences in baseline responses caused difficulty in interpreting some of the findings. Conclusions It is concluded that the provision of occasional reinforced extinction trials and unpaired USs seem promising techniques to slow down reacquisition, but that additional studies are needed.

An exacerbated physiological response to stress is associated with the development of stress-related disorders (e.g., depression and anxiety disorders). Recently, it has been proposed that individuals with high expectancies of being able to deal with stressful situations will activate regulatory mechanisms during the anticipation of the stressful event that would improve stress regulation. To test this hypothesis, 52 women in young adulthood (M = 21.06; SD = 2.58) anticipated and performed a laboratory-based stress task after receiving positive or negative bogus feedback on their abilities to deal with stressful events. Heart rate variability and salivary cortisol were assessed throughout the experimental protocol. Participants receiving positive bogus feedback (i.e., High Expectancy group) showed a more positive anticipatory cognitive stress appraisal (i.e., they anticipated the stress task as less threatening/challenging, and they perceived that they were more able to deal with it), and they showed a lower cortisol response to stress. Moreover, a more positive anticipatory cognitive stress appraisal was associated with better anticipatory stress regulation (indexed as less decrease in heart rate variability), leading to a lower cortisol response. Our results indicate that people with positive expectancy initiate mechanisms of anticipatory stress regulation that enhance the regulation of the physiological stress response. Expectancy and anticipatory stress regulation may be key mechanisms in the development and treatment of stress-related disorders.

Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘ c ' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘ c ' 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.

Background Epidemiologic evidence for the association between types of fatty acid and risk of type 2 diabetes is inconsistent This may in part be due to the limitations of fatty acid measurement methods Objective The objective was to use 3 different measures of fatty acid to estimate the prospective association between fatty acid composition and development of incident diabetes Design We analyzed 199 cases of clinically incident diabetes and 184 noncases aged 40-79 y at baseline in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study Fatty acids were derived from a food frequency questionnaire (FFQ) and measured in plasma phospholipid (P FA) and erythrocyte membrane phospholipid (Ery FA) fractions by gas chromatography Results There were stronger associations with diabetes risk with the use of objectively measured tatty acids (P FA and Ery-FA) than with the FFQ in analyses adjusted for age sex and potential confounders Positive associations with diabetes were greater in magnitude with the use of P FA than with Ery FA (highest lowest tertiles) for example the palmitic acid odds ratios (ORs) were 247 (95% CI 1 37 4 46) and 1 96 (95% CI 1 10 3 49) respectively Inverse associations with diabetes were also stronger with the use of P FA than with Ery FA for example the OR for linoleic acid was 050 (95% CI 028 0 91) compared with 0 77 (95% CI 043 1 37) respectively Conclusions The objective measurement of fatty acids with the use of either P-FA or Ery-FA identifies important associations with diabetes Incidence that may be missed when assessed by FFQ Fatty acids measured in P-FA appear to be more strongly associated with diabetes incidence These findings endorse the use of objective measurement of fatty acids for nutritional-epidemiologic studies and the apparently stronger findings for the plasma fraction should be confirmed in larger studies and in different populations Am J Clin Nutr 2010 92 1214-22

Objective Current data suggest that individual genetic predisposition may influence the magnitude of cytokine response and the degree of organ dysfunction after cardiopulmonary bypass. Lipoprotein lipase S447X polymorphism has been shown to be protective against atherosclerosis. The aim of the study was to investigate the effect of lipoprotein lipase S447X polymorphism on cytokine release and early outcome after cardiopulmonary bypass. Methods Forty patients who underwent coronary artery bypass grafting with cardiopulmonary bypass were included. Genotyping for lipoprotein lipase S447X polymorphism was performed by polymerase chain reaction. Levels of interleukins 6 and 8 were measured before induction and 6, 24, and 72 hours after operation by enzyme-linked immunosorbent assay. Clinical data were collected prospectively. Daily assessment of organ dysfunction was done according to the cardiac surgery scoring (CASUS) system. Results The allele frequency of lipoprotein lipase S447X stop codon was 17.5%. S447X carriers revealed significantly lower interleukin 8 levels at the sixth and 24th postoperative hours than the noncarrier group ( P = .005 and P = .041, respectively). Patients in the S447X carrier group had significantly shorter ventilation times than the noncarrier group ( P = .048). Also, the S447X carrier group revealed significantly lower postoperative 6-hour lactate levels, operative day, and postoperative day 1 organ dysfunction scores than the other group ( P = .001, .005 and .002, respectively). Conclusion Lipoprotein lipase S447X stop codon mutation is associated with lower levels of interleukin 8 after coronary artery bypass grafting. Identification of high-risk patients for cardiopulmonary bypass–related systemic inflammation by detecting lipoprotein lipase S447X stop codon polymorphism may improve early postoperative outcome, especially in patients with limited organ reserves.

Role of patient factors in therapy resistance to antiproteinuric intervention in nondiabetic and diabetic nephropathy. Reduction of proteinuria is a prerequisite for successful long-term renoprotection. To investigate whether individual patient factors are determinants of antiproteinuric efficacy, we analyzed individual responses to different modes of antiproteinuric intervention in nondiabetic and diabetic patients, obtained in prior studies comparing the efficacy of various pharmacological regimens. The individual antiproteinuric response to angiotensin-converting enzyme (ACE) inhibition positively correlated to the response to angiotensin type I (AT1) receptor blockade in diabetic (r = 0.67, P < 0.01, N = 16) as well as nondiabetic patients (r = 0.75, P < 0.01, N = 12). This corresponded to the correlations for antihypertensive efficacy between ACE inhibition and AT1 receptor blockade in diabetic (r = 0.73, P < 0.001) as well as nondiabetic patients (r = 0.55, P < 0.05). Remarkably, the antiproteinuric response to ACE inhibition also correlated positively to the antiproteinuric response to indomethacin (r = 0.63, P < 0.05, N = 9). Thus, patients responding favorably to one class of antiproteinuric drugs also respond favorably to other classes of available drugs, supporting a main role for individual patient factors in responsiveness or resistance to antiproteinuric intervention. In the search for strategies to improve response in these high risk patients, combination-treatment (combining different drugs, and combining drugs with dietary measures like sodium and protein restriction), and the use of higher doses may provide more fruitful strategies to optimize renoprotection than shifting to other classes of the available drugs.