IntroductionMany studies have shown that monocyte human leukocyte antigen-DR (mHLA-DR) expression may be a good predictor for mortality in severe septic patients. On the contrary, other studies found mHLA-DR was not a useful prognostic marker in severe sepsis. Few studies have taken changes of mHLA-DR during treatment into consideration. The objective of this study was to estimate the prognostic value of changes of mHLA-DR to predict mortality in severe sepsis.MethodsIn this prospective observational study, mHLA-DR was measured by flow cytometry in peripheral blood from 79 adult patients with severe sepsis. mHLA-DR levels were determined on day 0, 3, 7 after admission to the surgical intensive care unit (SICU) with a diagnosis of severe sepsis. ΔmHLA-DR3 and ΔmHLA-DR7 were defined as the changes in mHLA-DR value on day 3 and day 7 compared to that on day 0. Data were compared between 28-day survivors and non-survivors. Receiver operating characteristic (ROC) curves were plotted to measure the performance and discriminating threshold of ΔmHLA-DR3, ΔmHLA-DR7, ΔmHLA-DR7-3, mHLA-DR0, mHLA-DR3 and mHLA-DR7 in predicting mortality of severe sepsis.ResultsROC curve analysis showed that ΔmHLA-DR3 and ΔmHLA-DR7 were reliable indicators of mortality in severe sepsis. A ΔmHLA-DR3 value of 4.8% allowed discrimination between survivors and non-survivors with a sensitivity of 89.0% and a specificity of 93.7%; similarly, ΔmHLA-DR7 value of 9% allowed discrimination between survivors and non-survivors with a sensitivity of 85.7% and a specificity of 90.0%. Patients with ΔmHLA-DR3 ≤4.8% had higher mortality than those with ΔmHLA-DR3 > 4.8% (71.4% vs. 2.0%, OR 125.00, 95% CI 13.93 to 1121.67); patients with ΔmHLA-DR7 ≤9% had higher mortality than those with ΔmHLA-DR7 > 9% (52.9% vs. 2.0%, OR 54.00, 95% CI 5.99 to 486.08). The mean change of mHLA-DR significantly increased in the survivor group with the passage of time; from day 0 to day 3 and day 7, changes were 6.45 and 16.90 (P < 0.05), respectively.ConclusionsThe change of mHLA-DR over time may be a reliable predictor for mortality in patients with severe sepsis.

IntroductionSevere sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis.MethodsWe performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis.ResultsA total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded.ConclusionsThe use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis.Trial registrationClinicalTrials.gov NCT00711620.

ΔIVC shows limited ability for predicting fluid responsiveness in distinct ventilator settings. In patients with TV ≥8 mL/kg and PEEP ≤5 cm H2O, ΔIVC was an accurate predictor of fluid responsiveness, while in patients with TV <8 mL/kg or PEEP >5 cm H2O, ΔIVC was a poor predictor. Thus, intensivists must be cautious when using ΔIVC.

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The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients.