What's new in Shock, June 2010?

This month’s edition of SHOCK presents a diverse range of outstanding clinical and basic science investigations, with topics including prediction of morbidity and mortality after trauma, burns, and sepsis through physiological, inflammatory, cellular, and genetic patterns; stem cell cardioprotection; hemorrhage control through nerve stimulation; models of sepsis exploring modulation by toll-like receptor (TLR) agonists, microvascular fluid leak, immune cell receptor regulation, and gastric mucosal barrier disruption; pancreatic injury following abdominal compartment syndrome; vasopressin and anaphylaxis; and the anti-inflammatory effects of oxygen therapy and peroxisome proliferator-activated receptor + agonists. High-mobility group box protein 1 (HMGB1) is a nonhistone nuclear protein that is described as an Balarmin[ or damageassociated molecular pattern molecule, as its extracellular release from dead and dying cells signals damage to the innate immune system and the need for tissue repair (1). It is a known ligand for TLR2 and TLR4 and the receptor for advanced glycation end-products (RAGE), forming highly inflammatory complexes, and a potent mediator of sepsis. In an interesting clinical study presented by Lantos et al. (2), plasma levels of HMGB1 were examined in 26 adult burn patients requiring mechanical ventilation for the first 5 days after admission. Levels of HMGB1 were significantly greater on the first day of admission in nonsurviving patients and those who developed sepsis. Levels of HMGB1 seemed to peak on the day of admission and were correlated with burn surface area, suggesting it as a valuable early marker of both sepsis and mortality, with a cutoff of 16 ng/mL being highly specific of the latter. In addition, significantly greater levels of IL-10 throughout the study period were also found in these at-risk patients. Their results indicate that a postburn immune response featuring elevated HMGB1 and IL-10 levels is associated with increased mortality. Continuing the theme of inflammation and danger-associated molecular patterns, early expression profiles of complement regulatory proteins and C5a receptor (CD88) are characterized in leukocytes after multiple trauma in the study by Amara et al. (3). These host-protective components of the complement system include CD55 (delay accelerating factor), which inhibits formation and promotes breakdown of C3a convertase, CD59 (membrane attack complex inhibitor), and CD46 (a cofactor membrane protein). They used flow cytometry to show CD55 expression to be upregulated in neutrophils and monocytes within several hours of admission, whereas both CD46 and CD88 are significantly downregulated after injury, and to negatively correlate with injury severity. The subject of early identification of patients at risk is explored further at the genomic level in the study by Wen et al. (4). They examined a population of 238 trauma patients for three biallelic single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-1b gene, in a work that followed from this group’s previous study into IL-1b response in these different haplotypes (5). Levels of IL-1b were measured after ex vivo LPS stimulation of blood samples, with response levels found to correlate with distinct polymorphisms. A particular set of SNPs was found to be associated with a greater LPS-induced IL-1b response and to correspond with a significantly greater risk of sepsis in these patients. Although further studies are needed in patients of different ethnicity, these intriguing results point to the future use of SNPs to analyze risk and fashion new treatments to the needs of individual patients. For potential use in the assessment of hemorrhagic trauma patients, early prediction of central hypovolemia through noninvasive analysis of heart period variability parameters is explored in the notable investigation by Ryan et al. (6). Healthy volunteers underwent application of lower body negative pressure during noninvasive monitoring of blood pressure and stroke volume, with these changes simultaneously compared with analysis of heart period variability by linear and nonlinear metrics. Although overall group means of several parameters were highly correlated with the induced decline in stroke volume, dynamic changes in individuals proved difficult to predict using these analyses. Their results highlight the importance and challenge of validating predictive measurements at an individual-patient level. The meta-analysis reported by Siempos et al. (7) provides compelling data regarding predictors of increased mortality in intensive-care patients diagnosed with ventilator-associated pneumonia. They reviewed a total of 26 studies conducted over the last 15 years and identify significant and potentially correctable risk factors for increased mortality including sepsis, shock, inappropriate antimicrobial choice, and delay in treatment greater than 24 h after diagnosis, as well as significantly greater mortality when nonfermenting gram-negative bacteria or Acinetobacter baumannii were isolated. These findings emphasize the importance of early accurate diagnosis and appropriate treatment in ventilator-associated pneumonia cases to improve outcomes. Kelly et al. (8) explore the importance and the differential effects of the TNF receptors (TNFRs) 1 and 2 on mesenchymal stem cells (MSCs) used as cardioprotective pretreatment