In children who suffer out of hospital cardiac arrest, targeted hypothermia at 33.0 C confers no benefit when compared to targeted normothermia at 36.8 C. Level of evidence: 2B (RCT with wide CIs)Appraised by: Andrew Claxton Citation: Moler FW, Silverstein FS, Holubkov R and the THAPCA Trial Investigators. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng

BACKGROUND-Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after inhospital cardiac arrest are limited.

A substantial proportion of children with TBI had unmet or unrecognized health care needs during the first year after injury. It is recommended that pediatricians be involved in the post-acute care follow-up of children with TBI to ensure that the injured child's needs are being addressed in a timely and appropriate manner. One of the recommendations that trauma center providers should make on hospital discharge is that the parent/primary caregiver schedule a visit with the child's pediatrician regardless of the post-acute services that the child may be receiving. Because unmet and unrecognized need was highest for cognitive services, it is important to screen for cognitive dysfunction in the primary care setting. Finally, because the health care needs of children with TBI change over time, it is important for pediatricians to monitor their recovery to ensure that children with TBI receive the services that they need to restore their health after injury.

Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor-induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell-derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and IntroductionDuring steady state conditions, adhesive interactions between the bone marrow (BM) stromal cells and primitive hematopoietic cells mostly result in stem cell retention, in a noncycling and nonmotile mode. However, low levels of progenitor cells are continuously released from the BM to the blood circulation as part of homeostasis. This process is dramatically amplified during emergency situations because of damage and cell death, as part of host defense and repair, in response to stress signals, including cytokines such as granulocyte colony-stimulating factor (G-CSF). Repetitive G-CSF stimulations are commonly used in the clinic, mimicking emergency situations to harvest stem and progenitor cells from the circulation for transplantation protocols. 1,2 The BM reservoir of immature and maturing leukocytes is dynamic, replenishing the blood with new cells on demand. These dynamic changes are achieved through a complex interplay between the immune and nervous systems, the bones and the BM microenvironment, involving cytokines, chemokines, proteolytic enzymes, and adhesion molecules. 3 In particular, oscillations in BM levels of stromal cell-derived factor 1 (SDF-1; transiently increased and subsequently degraded) and CXC chemokine receptor-4 (CXCR4) activation play a crucial role in promoting progenitor cell egress. 4,5 The cytokine hepatocyte growth factor (HGF) and its receptor c-Met control complex biologic programs known as "invasive growth" and tumor spreading. 6 Reactive oxygen species (ROS) are constantly generated during intracellular metabolism and in response to cytokines. Although excess ROS can cause oxidative damage to DNA, moderate levels have important roles in cell signaling, regulating different physiologic and pathologic cellular processes, including cell-cycle progression, migration, and invasion. 7 Finally, redox signaling has emerged as an important regulator of hematopoietic stem cell (HSC) self-renewal and lifespan. 8,9 The Forkhead Box, class O (FOXO) family of Forkhead transcription factors is a regulator of oxidative stress. 10 Loss of FOXO function in HSCs results in increased ROS levels, defective maintenance of quiescence, and reduced long-term repopulating ability. 11,12 FOXOs are a direct substrate of the protein kinase Akt, a mammalian target of rapamycin inhibition (mTOR) target, 13 which inactivates them by phosphorylation. 14 In this study, we demonstrate that c-Met expression levels on immature and maturing leukocytes in the BM reservoir are dynamic and dramatically increased when urgent requirements for enhanced leukocyte production and recruitment emerge. Moreover, full c-Me...

Patients with higher 6-hr Glasgow Coma Scale scores were more likely to survive. Adjusting for severity of injury, survival was associated with maximum systolic blood pressure >or=135 mm Hg, suggesting that supranormal blood pressures are associated with improved outcome. Mannitol administration was associated with prolonged LOS, yet conferred no survival advantage. We suggest reevaluation of blood pressure targets and mannitol use in children with severe traumatic brain injury.

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Caregivers are more likely to report family burden problems when child functioning is poorer and health care needs are unmet. Improved identification and provision of services is a potentially modifiable factor that may decrease family burden after pediatric traumatic brain injury.

Mutations in the kinase domain of ALK (anaplastic lymphoma kinase) have recently been shown to be important for the progression of the childhood tumour neuroblastoma. In the present study we investigate six of the putative reported constitutively active ALK mutations, in positions G1128A, I1171N, F1174L, R1192P, F1245C and R1275Q. Our analyses were performed in cell-culture-based systems with both mouse and human ALK mutant variants and subsequently in a Drosophila melanogaster model system. Our investigation addressed the transforming potential of the putative gain-of-function ALK mutations as well as their signalling potential and the ability of two ATP-competitive inhibitors, Crizotinib (PF-02341066) and NVP-TAE684, to abrogate the activity of ALK. The results of the present study indicate that all mutations tested are of an activating nature and thus are implicated in tumour initiation or progression of neuroblastoma. Importantly for neuroblastoma patients, all ALK mutations used in the present study can be blocked by the inhibitors, although some mutants exhibited higher levels of drug sensitivity than others.