The use of statins was associated with a protective effect in patients with severe sepsis, as demonstrated by a significant reduction in mortality compared with patients not receiving statins.

Hematological deficiencies increase with aging including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age, was associated with decreased numbers of side population (SP) hematopoietic stem cells (HSC) and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N=100 subjects). In addition, BM from cadavers (N=36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of IGF-1, SDF-1 and IL-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM and as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with decreased number of SP stem cells and IGF- 1 and SDF-1 levels with aging. This data further raises a more general question as to the role of adipose cells in the regulation of tissue stem cells.

To determine the relation between the serum cyclosporine concentration and the risk of acute graft-versus-host disease (GVHD), we studied 179 recipients of bone marrow grafts from HLA-identical sibling donors who received prophylaxis with cyclosporine, either by itself or combined with methotrexate. Cyclosporine was given either orally or intravenously at full doses from the day before transplantation until day 50; it was then tapered off and discontinued on day 180. Trough concentrations of serum cyclosporine were measured by radioimmunoassay. The relation between patients' characteristics and the risk of acute GVHD was analyzed with a relative-risk regression model. In 66 patients (37 percent), grades II to IV of acute GVHD developed 7 to 66 days (median, 13) after transplantation. The trough cyclosporine concentration for a given week was significantly associated with the risk that acute GVHD would develop during the following week. The relative risks were 0.7 (i.e., there was a 30 percent reduction in risk) for every increase of 100 ng per milliliter in cyclosporine concentration and 1.0, 0.60, and 0.20 for concentrations of less than 100, 100 to 199, and 200 or more ng per milliliter, respectively (P less than 0.01). A patient's age, prophylaxis regimen, and year of transplantation also influenced the risk of acute GVHD significantly. These data indicate that low cyclosporine concentrations can be a cause of treatment failure and that concentrations should be monitored in recipients of marrow transplants.

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