PURPOSE Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown. METHODS Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). RESULTS No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

Red wine polyphenols (RWPPs) were obtained from red wine by absorption and elution from a resin column. Red wine (375 mL/d), white wine (375 mL/d), RWPPs (1 g/d, equivalent to 375 mL red wine/d) in capsules, RWPPs (1 g/d) dissolved in white wine, or a control alcoholic drink (40 g ethanol/d) was given to groups of 6-9 healthy men for 2 wk. Plasma LDL was separated by ultracentrifugation and desalted by dialyzing against a phosphate buffer without EDTA. In the copper-catalyzed peroxidation of LDL (copper-diene assay), the mean lag time increased by 17.8 min after red wine, 14.2 min after RWPP capsules, and 11.7 min after RWPPs in white wine. These groups also showed decreases in thiobarbituric acid-reactive substances, lipid peroxides, and conjugated dienes and increases in plasma and LDL polyphenols. The only change with white wine was an increase in thiobarbituric acid-reactive substances; there were no changes after the control drink. In a second study, RWPPs (1 and 2 g/d) and vitamin E [1000 IU (671 mg)/d] were given for 2 wk. In the copper-diene assay the addition of 10 micromol EDTA/L abolished the increased lag time of 17.7 min seen with 1 g RWPP/d and changed the increased lag time from 13.2 to 4.5 min seen with 2 g RWPP/d. Vitamin E increased lag time by 67.6 min with dialysis without EDTA and by 50.5 min with EDTA. When the column method was used for desalting LDL, all 3 treatments produced an increase in lag time. The failure of some authors to obtain antioxidant effects with the consumption of red wine may be due to the differing techniques.

Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.

The linear relationship between work accomplished (W(lim)) and time to exhaustion (t(lim)) can be described by the equation: W(lim) = a + CP x t(lim). Critical power (CP) is the slope of this line and is thought to represent a maximum rate of ATP synthesis without exhaustion, presumably an inherent characteristic of the aerobic energy system. The present investigation determined whether the choice of predictive tests would elicit significant differences in the estimated CP. Ten female physical education students completed, in random order and on consecutive days, five all-out predictive tests at preselected constant-power outputs. Predictive tests were performed on an electrically-braked cycle ergometer and power loadings were individually chosen so as to induce fatigue within approximately 1-10 mins. CP was derived by fitting the linear W(lim)-t(lim) regression and calculated three ways: 1) using the first, third and fifth W(lim)-t(lim) coordinates (I135), 2) using coordinates from the three highest power outputs (I123; mean t(lim) = 68-193 s) and 3) using coordinates from the lowest power outputs (I345; mean t(lim) = 193-485 s). Repeated measures ANOVA revealed that CPI123 (201.0+/-37.9W) > CPI135 (176.1+/-27.6W) > CPI345 (164.0+/-22.8W) (P<0.05). When the three sets of data were used to fit the hyperbolic Power-t(lim) regression, statistically significant differences between each CP were also found (P<0.05). The shorter the predictive trials, the greater the slope of the W(lim)-t(lim) regression; possibly because of the greater influence of 'aerobic inertia' on these trials. This may explain why CP has failed to represent a maximal, sustainable work rate. The present findings suggest that if CP is to represent the highest power output that an individual can maintain "for a very long time without fatigue" then CP should be calculated over a range of predictive tests in which the influence of aerobic inertia is minimised.

These results suggest that supplementation with all three macular carotenoids potentially offered advantages over preparations lacking MZ, both in terms of MPOD response and visual performance enhancement.