Evaluation of methotrexate clearance with an enteral urine alkalinization protocol for patients receiving high-dose methotrexate.

PURPOSE: High-dose methotrexate is a cytotoxic agent used to treat several malignancies. Urine alkalinization with sodium bicarbonate and hyperhydration are given with methotrexate to prevent drug precipitation in the kidneys. Due to a nationwide intravenous sodium bicarbonate shortage, an enteral-based urine alkalinization protocol was instituted. This study compared outcomes and adverse effects between the previously used intravenous and newly implemented enteral protocols. METHODS: Single center retrospective cohort study comparing parenteral and enteral urine alkalinization for patients that received methotrexate doses ≥ 500 mg/m2 between 1 April 2016 and 1 October 2018. The primary endpoint was time to methotrexate clearance. Secondary outcomes included length of stay, time to administration of methotrexate, amount of sodium bicarbonate utilized, toxicities of methotrexate, and protocol-associated adverse effects. RESULTS: There were 67 patients included in the study for a total of 195 infusions. The average time to methotrexate clearance between the two cohorts was similar (parenteral 88 h vs. enteral 98 h p = 0.06). Likewise, length of stay was not different between the two cohorts (p = ns). The enteral cohort methotrexate's doses were initiated faster and received significantly less intravenous sodium bicarbonate when compared to the parenteral cohort (p = 0.04). Rates of acute kidney injury, neutropenia, hepatotoxicity, and mucositis were similar between the two groups. There were higher rates of diarrhea and low serum bicarbonate values in the enteral cohort. CONCLUSION: This study supports the ability to conserve intravenous sodium bicarbonate by using an enteral-based urine alkalization regimen for HD methotrexate, with no difference in outcomes or toxicity.

Multicenter comparison of high-dose cytarabine-based regimens versus liposomal daunorubicin and cytarabine (CPX-351) in patients with secondary acute myeloid leukemia.

Liposomal daunorubicin/cytarabine (CPX-351) gained FDA approval for secondary AML after demonstrating improved outcomes over daunorubicin and cytarabine (7 + 3). A number of study limitations prompted a comparison of safety/efficacy of CPX-351 against regimens containing a purine analogue and high-dose cytarabine (HIDAC). This retrospective study compared complete response rates with/without count recovery (CR/CRi) between HIDAC-based regimens and CPX-351 in 169 patients with newly diagnosed sAML. The CR/CRi rate was 62.7% in the HIDAC-based therapy arm vs. 47.9% in the CPX-351 arm (p = 0.002 [one-sided for non-inferiority]). Median time to absolute neutrophil and platelet count recovery was shorter after HIDAC-based therapy (18 and 23 days, respectively) compared to CPX-351 (36 and 38 days; p < 0.001). Median overall survival was 9.8 months in the HIDAC-based group and 9.14 months in the CPX-351 group. 30-day mortality was greater with CPX-351 (8.5%) compared to HIDAC-based (1.3%; p = 0.039). These results reveal comparable efficacy and favorable safety with HIDAC-based regimens.

Effective treatment of refractory intracranial hypertension after traumatic brain injury with repeated boluses of 14.6% hypertonic saline.

OBJECT: Normal intracranial pressure (ICP) and cerebral perfusion pressure (CPP) have been identified as favorable prognostic factors in the outcome of patients with traumatic brain injuries (TBIs). Osmotic diuretics and hypertonic saline (HTS) are commonly used to treat elevated ICP in patients with TBI; however, sustained effects of repeated high-concentration HTS boluses for severely refractory ICP elevation have not been studied. The authors' goal in this study was to determine whether repeated 14.6% HTS boluses were efficacious in treating severely refractory intracranial hypertension in patients with TBI. METHODS: In a prospective cohort study in a neurocritical care unit, adult TBI patients with sustained ICP > 30 mm Hg for more than 30 minutes after exhaustive medical and/or surgical therapy received repeated 15-minute boluses of 14.6% HTS over 12 hours through central venous access. RESULTS: Response to treatment was evaluated in 11 patients. Within 5 minutes of bolus administration, mean ICP decreased from 40 to 33 mm Hg (30% reduction, p < 0.05). Intracranial pressure-lowering effects were sustained for 12 hours (41% reduction, p < 0.05) with multiple boluses (mean number of boluses 7 ± 5.5). The mean CPP increased 22% and 32% from baseline at 15 and 30 minutes, respectively (p < 0.05). The mean serum sodium level (SNa) at baseline was 155 ± 7.1 mEq/L, and after multiple boluses of 14.6% HTS, S(Na) at 12 hours was 154 ± 7.1 mEq/L. The mean heart rate, systolic blood pressure, blood urea nitrogen, and creatinine demonstrated no significant change throughout the study. CONCLUSIONS: The subset of TBI patients with intracranial hypertension that is completely refractory to all other medical therapies can be treated effectively and safely with repeated boluses of 14.6% HTS rather than a one-time dose.

The methylerythritol phosphate pathway contributes to carotenoid but not phytol biosynthesis in Euglena gracilis.

The biosynthesis of diadinoxanthin and beta-carotene in Euglena gracilis was examined using [1-13C]-D-glucose and [5,5-2H2]-1-deoxy-D-xylulose. In contrast to previous studies on isoprenoid biosynthesis in E. gracilis, the results demonstrate a role for the methylerythritol phosphate (MEP) pathway, along with the mevalonate pathway, in carotenoid biosynthesis. Interestingly, the MEP pathway is not involved in the biosynthesis of phytol, a result not previously observed for other chloroplast-containing organisms.