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Objective Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2–3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Methods and Results Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE −/− background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. Conclusions These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals.

Introduction: Immature platelet fraction (IPF) is a new laboratory parameter, representing a fraction of young platelets in peripheral blood count which is known to correlate with thrombopoiesis. IPF can be reported in absolute numbers or expressed as percentage (IPF%) of total platelet count. IPF% can be used to differentiate individuals at higher risk for bleeding among patients suffering from immune thrombocytopenia and to predict recovery of blood counts after stem cell transplantation (SCT). Moreover, IPF% was also reported to predict the development of sepsis in patients admitted to the general intensive care unit. This study was aimed to prospectively evaluate the value of IPF% as a predictor of clinical outcome and/or mortality in patients susceptible to sepsis. Methods: Two different patient populations at high risk for life-threatening infection, i.e., patients presenting with fever and neutropenia and adults admitted to the general intensive care unit (ICU) of a tertiary health care center for various reasons apart from neutropenic fever were prospectively studied. IPF was measured using the Sysmex XE-2100 analyzer during the first 24 hours of hospitalization. In addition, C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were tested in some of the patients. All patients were monitored and their vital signs, renal function, hemodynamic and respiratory state, as well as final outcome were recorded. For patients with neutropenic fever, the infectious pathogen was listed, whenever identified. Treating physicians were blinded to IPF% results to ensure that clinical decisions were not affected by consideration of this parameter. Results: One hundred and four adults with neutropenic fever and 138 additional adults admitted to the ICU were included in the study. A median age of patients admitted to ICU and those with neutropenic fever was 53 (range 17-88) and 55 (range 18-85) years; males composed 58% and 60% of the cohorts, respectively. A mean IPF% in patients admitted to ICU was significantly higher than that determined in neutropenic patients (8.6 vs 6.8). IPF% levels during the first 24 hours of admission, predicted mortality (p = 0.037) for patients admitted to ICU but not for patients presenting with neutropenic fever. In patients admitted to ICU, high IPF% was also associated with length of stay in the unit, poor hemodynamic status, and death. Neither IL-6 plasma level nor CRP correlated with these clinical outcomes. APACHE-II score (a known disease severity scale in ICU patients) and IPF% were not correlated by Pearson test (p=0.09). Conclusion: IPF% is a valuable biomarker for predicting prognosis in ICU patients independent of APACHE-II score. This study suggests that the validity of IPF% as a predictor of outcome depends on the bone marrow (BM) capacity. In patients with normal bone marrow admitted to ICU, IPF% correlates with the significance of stress and severity of the disease. In patients presenting with neutropenic fever, BM reserve is impaired due to chemotherapy. Larger studies are needed to evaluate the role of IPF% in different patient populations and to determine its application to patients with impaired BM reserves such as immunocompromised patients and those at older age. Disclosures No relevant conflicts of interest to declare.