The efficacy of low-dose warfarin initiation (3 mg versus 5 mg) in newly diagnosed venous thromboembolism patients among a population with a high prevalence of warfarin-sensitive haplotype of the VKORC1 gene: a randomized controlled trial.

OBJECTIVES: The fact that a lower warfarin maintenance dose is required by Asian populations is well-known. Currently, the American College of Chest Physicians recommends commencing warfarin at a dose between 5 and 10 mg for venous thromboembolism (VTE). However, the optimal initiating dose in Asians is unknown. This study aimed to evaluate the efficacy of a 3 mg versus a 5 mg of warfarin initiating dose and a corresponding nomogram in patients with VTE. METHODS: Eligible patients were randomized to receive 3 mg or 5 mg per day warfarin for the first 2 days of treatment. The subsequent dose was adjusted according to the warfarin nomogram. The primary outcome was the number of patients who achieved an INR 2.0-3.0 within 8 days. RESULTS: Fifty-six patients were enrolled. There was no significant difference in baseline characteristics between the groups. Seventeen (60.7%) patients in the 3-mg group and 22 (78.6%) patients in the 5-mg group achieved a therapeutic INR within 8 days (p = 0.146). However, there were significantly more patients in the 5-mg group who achieved the target INR on day 5 (53.6% vs 25.0%, p = 0.029). Furthermore, VKORC1-1639G > A was associated with an increased likelihood to achieve the target INR within 5 days (OR 3.81, 95%CI 1.19-12.16, p = 0.021). CONCLUSIONS: The efficacy of a 3 mg warfarin starting dose with subsequent dose adjustment was similar to that of 5 mg on day 8 after warfarin initiation. However, a 5 mg initiating dose resulted in more patients who achieved therapeutic INR on day 5.

Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

OBJECTIVES: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. MATERIALS AND METHODS: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. RESULTS: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. CONCLUSIONS: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.