Intravenous unfractionated heparin dosing in obese patients using anti-Xa levels.

There is limited guidance on intravenous dosing of unfractionated heparin in obese patients. The purpose of this study was to determine the efficacy and safety of a standard unfractionated heparin (UFH) protocol in obese patients based on total body weight (TBW) or adjusted body weight (ABW) to reach two consecutive therapeutic anti-Xa levels. This was a retrospective observational cohort study conducted in a large academic medical center. Adults received a standard UFH protocol between January 1, 2013 to December 31, 2015. Inclusion criteria included age ≥ 18 years of age, weight ≥ 100 kg with a BMI ≥ 30 kg/m2, and received intravenous UFH. Patients were excluded if they received an alternative UFH protocol, received < 24 h of the standard UFH protocol, or had inadequate compliance to protocol. Out of the 131 patients included, 109 patients reached two consecutive therapeutic UFH levels within 96 h. The average time to two consecutive therapeutic UFH levels was 29.4 h and 27.6 h in patients dosed by TBW and ABW, respectively (95% CI - 4.63 to 8.11; P = 0.93). Safety outcomes included major bleeding, overt bleeding, or death events between patients dosed by TBW compared to ABW, (p = 0.61, p = 1.0, p = 1.0, respectively). Dosing intravenous UFH based on TBW or ABW resulted in similar times to therapeutic anti-Xa levels and safety outcomes. The data provided suggests using either TBW or ABW in obese patients is as effective and safe to use.

Design and synthesis of isosteviol triazole conjugates for cancer therapy.

One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using "click" chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low µM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development.