A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed-effects model. Thirty five trials with a total of 1029 AML (n = 814) and MDS (n = 215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p < 0.01). No difference in CR was noted between the new (56.7%) and relapsed/refractory AML (60.1%) (p > 0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p < 0.05). Remarkably, the CR rate of CAG was significantly higher than those of non-CAG regimens (odds ratio 2.43). CAG regimen was well tolerated, with cardiotoxicity in 2.3% and early death in 5.2% of the cases. In conclusion, CAG regimen was an effective and safe regimen for the treatment of AML, and may be more effective than non-CAG regimens. Randomized controlled trials are strongly recommended to evaluate its efficacy and safety in comparison with the current standard treatment

TOTAL ANTIOXIDANT CAPACITY AND FRAILTY IN OLDER MEN

Frailty, a clinical syndrome characterized by multisystem dysregulation, has been associated with high levels of oxidative stress. We investigated the association between serum total antioxidant capacity (TAC) and frailty in older men. This cross-sectional study included 581 men (age 60-90 years) enrolled in the Geelong Osteoporosis Study. Frailty comprised at least three of unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. Serum TAC was measured by quantitative colorimetric determination and expressed as uric acid equivalents (mM). Relationships between TAC (in SD units) and frailty were explored using multivariable logistic regression models. Sociodemographic, anthropometric, and lifestyle variables were tested as potential confounders and effect modifiers. A sensitivity analysis excluded participants (n = 145) in the upper quartile of TAC, who were likely to have hyperuricemia. Fifty (8.6%) men were frail. There was evidence that higher TAC levels were associated with increased likelihood of frailty (OR 1.34, 95% confidence interval [CI; 0.99, 1.80]), and this was attenuated after adjustment for age and body mass index (BMI; OR 1.26, 95% CI [0.93,1.71]). No effect modifiers or other confounders were identified. The sensitivity analysis revealed a positive association between TAC and frailty, before and after accounting for age and BMI (adjusted OR 1.79, 95% CI [1.01, 3.17] p = .038). These results suggest a positive association between TAC levels and frailty, supporting the hypothesis that this biomarker could be useful in identifying individuals at risk of frailty. We speculate that a milieu of heightened oxidative stress in frailty may elevate the oxidative stress regulatory set point, raising antioxidant activity. This warrants further investigation

The association between a fracture risk tool and frailty: Geelong Osteoporosis Study

BACKGROUND: Frailty is characterised by age-related declines in physical, psychological and social functioning. Features of frailty overlap with risk factors for fragility fractures. The aim of this study was to investigate the association between the fracture risk assessment tool (FRAX®) and frailty. METHODS: In cross-sectional analysis, frailty status was determined for participants aged 60-90 yr at 15-year follow-up of the Geelong Osteoporosis Study, using a modified Fried frailty phenotype. Using the FRAX on-line tool, scores for hip and major osteoporotic fracture (MOF) were calculated with and without bone mineral density (BMD). Using the area under Receiver Operating Characteristic (AUROC) curves, and FRAX scores calculated at the baseline visit for these participants, we investigated the association of FRAX and frailty 15 years later. RESULTS: Forty-seven of 303 women (15.5%) and 41 of 282 men (14.5%) were frail at the 15-year visit. There was a gradient of increasing median FRAX scores from robust to frail. For example, for women, median MOF-FRAX without BMD increased from 5.9 for the robust to 7.5 for the pre-frail and 14.0 for the frail (p < 0.001). In secondary analyses, an association was observed between FRAX and frailty over 15 years, with the highest AUROC for women being 0.72 for MOF-FRAX with BMD, and for men, 0.76 hip-FRAX without BMD. CONCLUSION: An association was observed between FRAX and frailty where frail men and women had higher FRAX-scores compared to the other groups. Preliminary data suggest that FRAX, with or without BMD, may be useful in enhancing the information on frailty. Further research using larger datasets will be required to explore this