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Background: According to World Health Organization estimates, sepsis accounts for 60%-80% of lost lives per year in childhood. Measures appropriate for resource-scarce and resource- abundant settings alike can reduce sepsis deaths. In this regard, the World Federation of Pediatric Intensive Care and Critical Care Societies Board of Directors announces the Global Pediatric Sepsis Initiative, a quality improvement program designed to improve quality of care for children with sepsis. Objectives: To announce the global sepsis initiative; to justify some of the bundles that are included; and to show some preliminary data and encourage participation. Methods: The Global Pediatric Sepsis Initiative is developed as a Web-based education, demonstration, and pyramid bundles/ checklist tool (http://www. wfpiccs.org). Four health resource categories are included. Category A involves a nonindustrialized setting with mortality rate <5 yrs and >30 of 1,000 children. Category B involves a nonindustrialized setting with mortality rate <5 yrs and <30 of 1,000 children. Category C involves a developing industrialized nation. In category D, developed industrialized nation are determined and separate accompanying administrative and clinical parameters bundles or checklist quality improvement recommendations are provided, requiring greater resources and tasks as resource allocation increased from groups A to D, respectively.Results: In the vanguard phase, data for 361 children (category A, n = 34; category B, n = 12; category C, n = 84; category D, n = 231) were successfully entered, and quality-assurance reports were sent to the 23 participating international centers. Analysis of bundles for categories C and D showed that reduction in mortality was associated with compliance with the resuscitation (odds ratio, 0.369; 95% confidence interval, 0.188-0.724; p < .0004) and intensive care

The World Federation of Pediatric Intensive and Critical Care Societies (WFPICCS) is an international body that brings together international expertise, experience, and influence to improve the outcomes of children suffering from life-threatening illness and injury. Its mission is educational, scientific, and charitable in nature. WFPICCS is committed to a global environment, in which all children have access to intensive and critical care of the highest standard. It exists to find ways of improving the care of critically ill children throughout the world, and making that knowledge available to those who care for such children. As in an ideal world all children should have access to state of the art critical care services, this is unlikely to happen anytime soon. Faced with this reality, the member societies of the WFPICCS will strive to develop the best model and provide the best care for critically ill and injured children worldwide. The challenge is to find the appropriate role that we need to (and can effectively) play in decreasing both unnecessary death and suffering for children. Clearly, we cannot achieve these goals on our own, hence WFPICCS visualizes close cooperation and collaboration with other agencies offering care to critically ill or injured children such as the World Health Organization, World Federation of Societies of Intensive and Critical Care Medicine, International Pediatric Associations, and regional organizations and programs to achieve our objectives. We feel that this document while imperfect is a good starting point and hope that it will stimulate more discussion to guide the agenda of the federation for years to come. © 2009 The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment outcome. Therefore, novel therapeutic strategies are needed to improve prognosis. Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL). Here we demonstrate FLT3 expression in infants with MLL (n = 41) to be significantly higher compared to both infant (n = 8; P < .001) and noninfant patients with ALL (n = 23; P = .001) carrying germline MLL genes. Furthermore, leukemic cells from infants with MLL were significantly more sensitive to the Fms-like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than noninfant ALL cells, and at least as sensitive as internal tandem duplication-positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However, measuring FLT3 phosphorylation in infants with MLL expressing varying levels of wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand-independent FLT3 activation. This suggests that infant MLL cells displaying activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors such as PKC412. However, at concentrations of PKC412 minimally required to fully inhibit FLT3 phosphorylation, the cytotoxic effects were only fractional. Thus, PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of FLT3 inhibition alone but may involve inhibition of multiple other kinases by this drug.

MAGE-2 is expressed in many tumors, including melanoma, laryngeal tumors, lung tumors and sarcomas, but not in healthy tissue, with the exception of testis. Thus, MAGE-2-derived peptides that bind to HLA class I molecules and elicit cytotoxic T lymphocyte (CTL) responses could be of significant therapeutic importance. In this study, we show that several MAGE-2-derived peptides bind with high affinity to HLA-A*0201. Three of them form complexes with HLA-A*0201 that are stable at 37 degrees C and are immunogenic in HLA-A*0201Kb transgenic mice. Moreover, CTLs against 2 of them (M2 112-120, and M2 157-166) specifically recognize cells that express both the MAGE-2 protein and HLA-A*0201Kb. These 2 peptides are processed and presented in the context of HLA-A*0201. Therefore, these peptides are candidate components in peptide-based vaccines for the treatment and prevention of several types of MAGE-2-expressing cancers.