The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood

Background

Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS).

Objective

We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4–6 years of age.

Materials and methods

Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500–1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine.

Results

No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA.

Conclusion

Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4–6 years of age or were too small to be statistically significant in the current sample.

     

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2-/- neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2-/- bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.     

Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non–Small-Cell Lung Cancer

Background

Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non–small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC.