What's new in Shock? May 2013.

This month’s issue of Shock offers several articles with a focus on biomarkers as well as basic reports related to mechanisms and treatment of shock-related conditions. Four clinical articles address different aspects of biomarkers in trauma and sepsis. Based on the observation that cardiac events are common during intensive care unit stays for trauma patients, De’Ath et al. (1) compared biomarkers for myocardial ischemia and inflammatory cytokines to the incidence of acute cardiac events (ACEs) in trauma patients. They found that there was an association-specific cytokines at admission, or 24 or 72 h into the intensive care unit stay was associated with an increased incidence of ACEs as were admission levels of heart-specific fatty acidYbinding protein and troponin I; however, patients with elevations in both proinflammatory cytokines and biomarkers were at the highest risk for ACEs. This suggests that monitoring these parameters may help in the prediction of cardiac complications in trauma patients. Another important target of injury in trauma and sepsis is the vascular endothelium. Skibsted et al. (2) previously showed in a single-center study that endothelial biomarkers appear to correlate with the severity of sepsis; therefore, they now report the results of a multicenter trial to validate these preliminary findings. They studied 63 patients with sepsis, 61 with severe sepsis, and 42 with septic shock. All endothelial biomarkers studied correlated with severity of sepsis, but Fms-like tyrosine kinase 1 (sFlt-1) had the strongest correlation with severity score, and sFlt-1 and plasminogen activator inhibitor showed the strongest correlation with mortality. These results further support the important role for endothelial dysfunction in sepsis and suggest that sFlt-1 may be a useful biomarker for the severity of sepsis. Two of the clinical studies this month address coagulation alterations as predictors of the severity of sepsis or mortality in trauma patients. Fukushima et al. (3) evaluated the relationship between von Willebrand factor propeptide and the enzyme that cleaves it to make mature VWF (ADAMTS13) with severity of sepsis in 27 patients with severe sepsis or septic shock and thrombocytopenia. This ratio was significantly elevated in septic patients and correlated significantly with severity scores and tumor necrosis factor ! levels as well as with acute kidney injury. Although these results suggest that this ratio is a good marker for severity in thrombocytopenic patients, it would be interesting to see if changes in the ratio might predict the development of thrombocytopenia. The final clinical study by Whittaker et al. (4) compared markers of coagulopathy to mortality in 803 pediatric trauma patients. Although early coagulopathy was only mildly correlated with mortality in patients without traumatic brain injury (TBI), it was associated with a fourfold increase in mortality in patients with TBI. They conclude that early correction of coagulopathy could decrease mortality in pediatric patients with TBI, but it is not clear that coagulopathy is truly the cause of mortality of just a marker. This could possibly be addressed by using the animal model reported by Darlington et al. (5). They developed a rat model of acute coagulopathy of trauma. They induced trauma by injuring the intestines, liver, and leg skeletal muscle and fracturing the right femur and characterized the complex changes in coagulation. Given the results of Whittaker et al. (4), it would be interesting to add TBI to this model. Continuing in the theme of traumatic injury, Song et al. (6) tested the effect of early resuscitation with a hypertonic solution consisting of either a bolus of hypertonic hydroxyl ethyl starch (HHES) or continuous infusion of hypertonic saline (HTS) in crush injury in rats. Rats resuscitated with HHES showed improved blood pressure, serum electrolytes, and acidbase balance and kidney function, resulting in improved 72-h survival. These improvements were not seen with HTS, but rather they observed a worsening of acid-base balance in the HTS group. They conclude that HHES is superior for resuscitation in this type of injury, especially in situations in which electrolyte or acid-base balance is of concern. Ischemic preconditioning is an important means for protecting a tissue from an elective ischemic stress such as often occurs in surgery. Recent evidence suggests that endoplasmic reticulum (ER) stress may be an important mechanism for producing ER stress. Thus, Grall et al. (7) compared the contribution of ER stress to myocardial preconditioning produced by either brief bouts of myocardial ischemia (IPost) or remote ischemia to a hindlimb (RIP). Only IPost increased myocardial markers of ER stress. In addition, an inhibitor of the ER stress response abrogated the preconditioning caused by IPost but not RIP. These results support a role for ER stress in preconditioning by IPost, but indicate that a separate mechanism is responsible in the case of remote ischemia. The final research report in this month’s issue from Bosmann et al. (8) investigates the cellular source of interleukin 23 (IL-23) in the lung of endotoxemic mice. Interleukin 23 mRNA was increased 10-fold in lung homogenates after endotoxin, and the protein was elevated in bronchoalveolar lavage fluid. Interleukin 23Ydeficient mice showed decreased IL-17 production and CD11c-depleted mice produced less IL-23, indicating a role for alveolar macrophages in this pathway. In the tradition of a spirited and open exchange of ideas, this month’s issue of Shock offers three letters to the editor and two responses. The first letter from Luyer et al. (9) comments on an article by Levy et al. (10). Levy et al. (10) had reported on the