From January 2008 through December 2008 Patients were enrolled at 393 sites in 15 countries. Hospitalized patients for whom discharge within 48 hours after randomization had not been anticipated were excluded from the analysis. Additional exclusion requirements were the need for long-term or short-term use of a PPI, an H2-receptor antagonist, sucralfate, or misoprostol; preexisting erosive esophagitis or esophageal or gastric variceal disease or previous nonendoscopic gastric surgery; receipt of clopidogrel or another thienopyridine for a lot more than 21 times before randomization; receipt of oral anticoagulation therapy that could not really be safely discontinued for the duration of the study; or latest fibrinolytic therapy.Four of the genes with significant mutation frequencies, TP53, ATM, MYD88, and NOTCH1, have already been described previously in chronic lymphocytic leukemia. 3A in the Supplementary Appendix). 3C in the Supplementary Appendix).19 Finally, we detected a recurrent frameshift mutation in the C-terminal PEST domain of NOTCH1 in 4 patients that was identical to that recently reported in other investigations of chronic lymphocytic leukemia.5,6 This mutation is connected with unmutated IGHV and a poor prognosis,5,6 and it is predicted to trigger impaired degradation of NOTCH1, resulting in pathway activation. Five of the genes with significant mutation frequencies don’t have established roles in chronic lymphocytic leukemia. Strikingly, the next most regularly mutated gene inside our cohort was splicing factor 3b, subunit 1 , with missense mutations occurring in 14 of 91 individuals .
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