Recommendations from the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS)

Background: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality following surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. Objective: To develop consensus recommendations for anemia management in surgical patients. Methods: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. Results: The panel recommends that all patients be screened for anemia prior to surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. Conclusions: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients

Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2=0.51, P<0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2±0.34% (value is the mean±S.D.) increased Hct to 28.3±0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3–7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P

Limits on active to sterile neutrino oscillations from disappearance searches in the MINOS, Daya Bay, and bugey-3 experiments

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^2 2θμe are set over 6 orders of magnitude in the sterile mass-squared splitting Δm^2 41. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm^2 41 < 0.8 eV^2 at 95% CLs

BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell–Cell Fusion

The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus&ndash;cell and cell&ndash;cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell&ndash;cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell&ndash;cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell&ndash;cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype

Role of endogenous gastrin in gastroprotection

Gastrin has a potent influence on gastric acid secretion and mucosal growth but its role in mucosal integrity has been little studied. This study investigated in rats whether gastrin protects the gastric mucosa against the damage by 100% ethanol and what are the possible mechanisms of this protection. Exogenous gastrin-17 (0.6–5.0 pmol/kg) injected subcutaneously (s.c.) reduced dose dependently ethanol-induced mucosal damage and the dose decreasing the ethanol lesions by 50% was about 1.8 pmol/kg. The protection afforded by gastrin-17 was accompanied by a dose-dependent increase in gastric blood flow and these effects were almost completely abolished by the pretreatment with specific CCK B (L-365,260) but not CCK A receptor antagonist (loxiglumide). Endogenous gastrin released by intragastric (i.g.) peptone meal or s.c. injection of gastrin-releasing peptide prevented the formation of acute ethanol-induced lesions and these effects were also abolished by the pretreatment with L-365,260 but not by loxiglumide. The inhibition of nitric oxide (NO) synthase, by N G-nitro- l-arginine methyl ester almost completely eliminated both the protective and hyperemic effects of gastrin-17 and the addition of l-arginine (but not d-arginine) to N G-nitro- l-arginine-methyl ester restored, in part, these effects of gastrin-17. Deactivation of sensory nerves with capsaicin did not influence the protective or hyperemic effects of gastrin-17. We conclude that both exogenous and endogenous gastrin exert its protective activity against ethanol damage of gastric mucosa and this effect is mediated through the interaction with specific CCK B receptors and arginine-NO pathway, but does not involve sensory nerves