; for the French Society of Emergency Medicine Collaborators Group IMPORTANCE An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. OBJECTIVE To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones. DESIGN, SETTINGS, AND PARTICIPANTS International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death. EXPOSURES Measurement of qSOFA, SOFA, and SIRS. MAIN OUTCOMES AND MEASURES In-hospital mortality. RESULTS Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P < .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis. CONCLUSIONS AND RELEVANCE Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting.

In CAP-suspected patients visiting the emergency unit, early CT scan findings complementary to chest radiograph markedly affect both diagnosis and clinical management. Clinical trial registered with www.clinicaltrials.gov (NCT 01574066).

No abstract

No abstract

The production of red blood cells is tightly regulated by erythropoietin (Epo). The phosphoinositide 3-kinase (PI 3-kinase) pathway was previously shown to be activated in response to Epo. We studied the role of this pathway in the control of Epo-induced survival and proliferation of primary human erythroid progenitors. We show that phosphoinositide 3 (PI 3)-kinase associates with 4 tyrosine-phosphorylated proteins in primary human erythroid progenitors, namely insulin receptor substrate-2 (IRS2), Src homology 2 domain-containing inositol 5-phosphatase (SHIP), Grb2-associated binder-1 (Gab1), and the Epo receptor (EpoR). Using different in vitro systems, we demonstrate that 3 alternative pathways independently lead to Epo-induced activation of PI 3-kinase and phosphorylation of its downstream effectors, Akt, FKHRL1, and P70S6 kinase: through direct association of PI 3-kinase with the last tyrosine residue (Tyr479) of the Epo receptor (EpoR), through recruitment and phosphorylation of Gab proteins via either Tyr343 or Tyr401 of the EpoR, or through phosphorylation of IRS2 adaptor protein. The mitogenactivated protein (MAP) kinase pathway was also activated by Epo in erythroid progenitors, but we found that this process is independent of PI 3-kinase activation. In erythroid progenitors, the functional role of PI 3-kinase was both to prevent apoptosis and to stimulate cell proliferation in response to Epo stimulation. Finally, our results show that PI 3-kinase-mediated proliferation of erythroid progenitors in response to Epo occurs mainly through modulation of the E3 ligase SCF SKP2 , which, in turn, downregulates p27 Kip1 IntroductionThe production of red blood cells is tightly regulated by the cytokine erythropoietin (Epo), which supports the survival and proliferation of erythroid progenitors. 1 Epo binding to its cognate receptor activates the receptor-associated Janus kinase-2 (Jak2) tyrosine kinase. 2 The Epo receptor (EpoR) is tyrosine phosphorylated 3 and recruits several Src homology-2 (SH2) domain-containing proteins, thereby leading to the activation of different intracellular signaling pathways. 4 One of these pathways involves phosphoinositide 3-kinase (PI 3-kinase). PI 3-kinase products phosphoinositide 3,4 bisphosphate (PI(3,4)P2) and phosphoinositide 3,4,5-trisphosphate (PI(3,4,5)P3) are major intracellular second messengers acting as mediators between the plasma membrane and intracellular signaling molecules. The class IA family of PI 3-kinases consists of a regulatory subunit (p85) and a catalytic subunit (p110). 5 PI 3-kinase plays a central role in controlling cell survival and cell cycle progression in different systems. 6 In the erythroid lineage, PI 3-kinase is required for the protection of erythroid cells from apoptosis 7 and is involved in Epo-induced mitogenic responses. 8 We and others have previously shown that PI 3-kinase is associated through its SH2 domains with the activated EpoR. [9][10][11] The last tyrosine residue (Tyr479) in the EpoR cytoplasmic domain was further shown to ...