Screening for variants in TPMT did not reduce the proportions of patients with hematologic ADRs during thiopurine treatment for IBD. However, there was a 10-fold reduction in hematologic ADRs among variant carriers who were identified and received a dose reduction, compared with variant carriers who did not, without differences in treatment efficacy. ClinicalTrials.gov number: NCT00521950.
In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL.
Summary. Background: The coagulopathy in cirrhosis is associated with thrombosis and bleeding. Objectives: To gain better insights into the coagulopathy in patients with cirrhosis, we evaluated plasma thrombin generation and whole blood clot formation in a cross-sectional study. Methods: Blood was collected from 73 patients with allcause cirrhosis (Child-Pugh-A n = 52, B n = 15, C n = 6) and 20 healthy controls. Activity of the coagulation pathways was measured with assays for factor (F) VIIa and FIXa-antithrombin and FXa-antithrombin complexes, respectively. Thrombin generation by calibrated automated thrombography was determined in platelet-poor plasma using a 1 or 5 pM tissue factor trigger with/without thrombomodulin. ROTEM measurements were performed in whole blood triggered with 35 pM tissue factor without/with 175 ng mL À1 tissue plasminogen activator (the latter refered to as 'tPA-ROTEM'). Results: We observed an increased generation of FVIIa and a moderately elevated amount of FIXa (in complex with antithrombin) without apparent increase in FX activation in patients with cirrhosis. In accordance with this prothrombotic state, markers of thrombin generation potential were also increased upon increasing severity of cirrhosis.In the whole blood clotting assay we observed delayed clot formation and decreased clot strength associated with increased severity of cirrhosis. No significant differences were found for tPA-ROTEM parameters of clot degradation. Conclusion: These results indicate that cirrhosis patients have an overall procoagulant plasma milieu but a decreased whole blood clot formation capacity with an apparently unaltered resistance to clot lysis.
In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus A 0 on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus A 0 for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. A 0 status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after A 0 supplementation. Furthermore, compared with controls, serum concentrations of P-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplemention; however, after A 0 supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus A 0 supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or A 0 may have the potential to play a role in the treatment of CD. Key Words:Crohn's disease-Nutritional supplementation-Antioxidants-N-3 fatty acids-Randomized double-blind placebocontrolled trial.
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