***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In this prospect i ve study of 45 patients , we tested the hypothesis that markedly elevated levels of plasma von Willebr and antigen ( vWf-Ag ) a marker of endothelial cell injury , might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome . Acute lung injury was quantified on a four-point scoring system . At the time of entry into the study , none of the 45 patients had evidence of lung injury . Subsequently , 15 patients developed lung injury and 30 patients did not develop lung injury . The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury ( 588 + /- 204 vs. 338 + /- 196 , percentage of control , P less than 0.01 ) . Furthermore , a plasma vWf-Ag level greater than or equal to 450 was 87 % sensitive and 77 % specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis . In addition , the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80 % for acute lung injury . Also , a plasma vWf-Ag level greater than 450 had a positive predictive value of 80 % for identifying nonsurvivors . Thus , in patients with nonpulmonary sepsis , an elevated level of plasma vWf-Ag is a useful , early biochemical marker of endothelial injury and it has both predictive and prognostic value Introduction The endothelial specific angiopoietin (Ang)-Tie2 lig and -receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis . Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage , whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function . Here , we examine whether circulating Ang-1 and /or Ang-2 independently predict mortality in a cohort of critically ill medical patients . Methods Circulating vascular endothelial growth factor ( VEGF ) , Ang-1 and Ang-2 were prospect ively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay ( IRMA ) and ELISA , respectively . Survival after 30 days was the primary outcome studied . Results Median serum Ang-2 concentrations were increasingly higher across the following groups : healthy controls , patients without sepsis , patients with sepsis and patients with septic shock . In contrast , Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls . Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen ( FiO2 ) , tissue hypoxia , Sequential Organ Failure Assessment ( SOFA ) and Physiology and Chronic Health Evaluation II ( APACHE II ) score . Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival . Conclusions A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients . Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness . Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU Abstract Angiogenesis is a key component of the repair mechanisms triggered by tissue injury . Vascular endothelial growth factor ( VEGF ) is an important mediator of angiogenesis , as it acts directly and specifically on endothelial cells . VEGF produced locally in regenerating tissue may spill over into the systemic circulation , and measuring levels of circulating VEGF may allow monitoring of angiogenesis . To determine whether circulating VEGF is increased after severe injury , we measured concentrations of VEGF in serial serum sample s of 23 mechanical burn patients , 55 patients with multiple trauma and 56 healthy normal controls , using a newly established ELISA assay . In burn patients , serum VEGF was increased on day 1 ( 369.4 ± 88.0 pg/ml ) and on day 3 ( 452.0 ± 65.3 pg/ml ) , reached highest levels on day 14 ( 1809.5 ± 239.7 pg/ml ) and was still elevated on day 21 post-burn ( 1339.8 ± 208.7 pg/ml ) ( mean ± SEM , p<0.01 ) , when compared with healthy controls ( 82.2 ± 10.8 pg/ml ( mean ± SEM ) ) . Likewise , in trauma patients , serum VEGF showed a trend towards elevated values on the day of admission ( 186.9 ± 43.9 pg/ml ) and on day 3 after injury ( 193.2 ± 62.1 pg/ml ) . Thereafter , serum VEGF increased further ( day 7 , 507.0 ± 114.7 pg/ml ) , peaked on day 14 ( 742.4 ± 151.8 pg/ml ) and was still elevated on day 21 after injury ( 693.1 ± 218.6 pg/ml ( mean ± SEM , p<0.01 ) ) . No significant correlation was observed between peak serum VEGF and initial severity of mechanical ( Injury Severity Score ) or burn injury ( percentage of body surface burned ) . However , in both burn and trauma patients , the subgroup of patients with uncomplicated healing showed significantly higher increases of serum VEGF than the subgroup who developed severe complications during the post-traumatic course , such as sepsis , adult respiratory distress syndrome or multiple organ failure ( p<0.05 ) . Thus , markedly enhanced levels of serum VEGF are present one to three weeks after trauma or burn injury . Further , occurrence of severe complications during the post-traumatic period is associated with lesser increases of serum VEGF Objective : To measure plasma levels of  angiopoietin-1 ( Ang-1 ) ,  angiopoietin-2 ( Ang-2 ) , and vascular endothelial growth factor ( VEGF )  early after trauma and to determine their clinical significance . Background : Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells . Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury . Little is known about the role of angiopoietins and VEGF early after trauma . Methods :  Blood specimens  from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma sample s assayed for Ang-1 , Ang-2 , VEGF , markers of endothelial activation , protein C pathway , fibrinolytic system , and complement . Base deficit was used as a measure of tissue hypoperfusion . Data were collected prospect ively . Results : Blood sample s were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation .  Plasma levels of Ang-2 , but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion . Furthermore , plasma levels of Ang-2 correlated with markers of endothelial activation , coagulation abnormalities , and activation of the complement cascade and were associated with worse clinical outcome . Conclusions : Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion . High levels of Ang-2 were associated with an activated endothelium , coagulation abnormalities , complement activation , and worse clinical outcome . These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma Introduction Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis . We investigated the association between biomarkers of endothelial cell activation and sepsis severity , organ dysfunction sequential organ failure assessment ( SOFA ) score , and death . Methods This is a prospect i ve , observational study including adult patients ( age 18 years or older ) presenting with clinical suspicion of infection to the emergency department ( ED ) of an urban , academic medical center between February 2005 and November 2008 .  Blood was sample d during the ED visit and biomarkers of endothelial cell activation , namely soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , plasminogen activator inhibitors -1 ( PAI-1 ) , sE-selectin , soluble intercellular adhesion molecule ( sICAM-1 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) , were assayed . The association between biomarkers and the outcomes of sepsis severity , organ dysfunction , and in-hospital mortality were analyzed . Results A total of 221 patients were included : sepsis without organ dysfunction was present in 32 % , severe sepsis without shock in 30 % , septic shock in 32 % , and 6 % were non-infected control ED patients . There was a relationship between all target biomarkers ( sFlt-1 , PAI-1 , sE-selectin , sICAM-1 , and sVCAM-1 ) and sepsis severity , P < 0.05 . We found a significant inter-correlation between all biomarkers , including the strongest correlations between sFlt-1 and sE-selectin ( r = 0.55 , P < 0.001 ) , and between sFlt-1 and PAI-1 ( 0.56 , P < 0.001 ) . Among the endothelial cell activation biomarkers , sFlt-1 had the strongest association with SOFA score ( r = 0.66 , P < 0.001 ) , the highest area under the receiver operator characteristic curve for severe sepsis of 0.82 , and for mortality of 0.91 . Conclusions Markers of endothelial cell activation are associated with sepsis severity , organ dysfunction and mortality . An improved underst and ing of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis OBJECTIVE Soluble adhesion molecules are regarded to be markers of inflammation , endothelial activation , or damage . The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients . DESIGN Prospect i ve and descriptive study over 5 days . SETTING Clinical investigation in a surgical intensive care unit of a university hospital . PATIENTS Thirty critically ill patients ( Acute Physiology and Chronic Health Evaluation [ APACHE ] II score of > 15 points ) , with sepsis secondary to postoperative complications , were included in this study . Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospect ively studied . INTERVENTIONS All patients were treated by the st and ard protocol s of our intensive care unit , which did not differ between the groups . The patients received continuous analgesia-sedation and mechanical ventilation . Intensivists caring for the patients were not involved in the study and were blinded to data analysis . MEASUREMENTS AND MAIN RESULTS Hemodynamic parameters were extensively monitored in all patients . From arterial blood sample s , plasma concentrations of soluble adhesion molecules ( endothelial leukocyte adhesion molecule-1 , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , granule membrane protein-140 ) were measured on the day of admission ( i.e. , baseline values ) and during the following 5 days . Three of the younger patients and six of the elderly patients died during the study period ( p < .05 ) . Oxygen delivery and consumption , and the other hemodynamic data , were without group differences throughout the study . Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups . These concentrations increased further during the first 2 to 3 days in both groups , with a significantly higher increase in the elderly patients ( endothelial leukocyte adhesion molecule-1 to 179 + /- 32 ng/mL ; intercellular adhesion molecule-1 to 1695 + /- 158 ng/mL ; vascular cell adhesion molecule-1 to 1395 + /- 212 ng/mL ; and granule membrane protein-140 to 888 + /- 119 ng/mL ) . In the younger patients , concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5 . In the elderly patients , these concentrations remained significantly higher until the end of the study . CONCLUSIONS The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium . Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules , particularly in the elderly critically ill patient ObjectiveS epsis and systemic inflammatory response syndrome ( SIRS ) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation . This study was design ed to compare cerebrospinal fluid ( CSF ) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood – CSF barrier or from local production . Design Prospect i ve observational study . Setting University hospital medical intensive 
    Output:
    
Overall , published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis , supporting the critical role of EC activation in sepsis .
Conclusions Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans , and variably correlated to other clinical ly-important outcomes .