Outcomes In Sepsis Patients Research Articles

The Monitoring and Management of Severe Traumatic Brain Injury in the United Kingdom: Is there a Consensus?: A National Survey.

To survey the current practice of monitoring and management of severe traumatic brain injury (TBI) patients in the critical care units across the United Kingdom. A structured telephone interview was conducted with senior medical or nursing staff of all the adult neurocritical care units. Thirty-one neurocritical care units that managed adult patients with severe TBI were identified from the Risk Adjustment in Neurocritical Care (RAIN) study and the Society of British Neurological Surgeons. Intracranial pressure (ICP) monitoring was used in all the 31 institutions. Cerebral perfusion pressure was used in 30 of the 31 units and a Cerebral perfusion pressure target of 60 to 70 mm Hg was the most widely used target (25 of 31 units). Transcranial Doppler was used in 12 units (39%); brain tissue oxygen (PbtO(2)) was used in 8 (26%); cerebral microdialysis was used in 4 (13%); jugular bulb oximetry in 1 unit; and near-infrared spectrometry was not used in any unit. Continuous capnometry was used in 28 (91%) units for mechanically ventilated patients. Mannitol was the most commonly used agent for osmotherapy to treat intracranial hypertension. We identified that there was no clear consensus and considerable variation in practice in the management of TBI patients in UK neurocritical care units. A protocol-based management has been shown to improve outcome in sepsis patients. Given the magnitude of the problem, we conclude that there is an urgent need for international consensus guidelines for management of TBI patients in critical care units.

Effect of admission hyperglycemia in sepsis patients with or without a history of diabetes

Introduction Hyperglycemia is common and often multifactorial in critically ill patients. The association of hyperglycemia with adverse outcome has repeatedly been established in a variety of settings. The objective of this study was to investigate whether hyperglycemia on admission to the ICU impacts presentation and outcome of sepsis patients and whether this effect is different for patients with a history of diabetes mellitus. Methods A two-center, prospective observational cohort study was conducted including all consecutive critically ill patients admitted to the ICU between January 2011 and July 2013. Sepsis patients were identified using strict clinical and diagnostic criteria. The first glucose measurement within a time window of 4 hours before up to 4 hours after ICU admission was categorized into euglycemia (71 to 140 mg/dl), mild hyperglycemia (141 to 200 mg/dl) or severe hyperglycemia (>200 mg/ dl), patients with hypoglycemia were excluded. A multivariable Cox proportional hazard model was used to determine the effect of admission hyperglycemia on mortality corrected for covariates. Results Of the 1,059 patients admitted with sepsis, 526 (55.8%) had admission glucose levels within the normal range, 270 (25.5%) had mild hyperglycemia and 202 (19.1%) severe hyperglycemia. Patients with severe hyperglycemia were older, had higher APACHE IV scores and were more often diabetics compared with euglycemic patients. Shock on admission was more common in patients admitted with euglycemia. Crude mortality increased with increased admission glucose and a Cox regression analysis showed increased risk for 30day (HR = 1.67, CI = 1.24 to 2.23), 60-day (HR = 1.42, CI = 1.08 to 1.87) and 90-day (1.31, CI = 1.02 to 1.70) mortality in patients admitted with severe hyperglycemia compared with euglycemia. The association between mortality and severe hyperglycemia on admission was only present in patients without known diabetes but not in patients with a history of diabetes (30-day mortality HR = 1.67, CI = 1.15 to 2.43 vs. 1.84, CI = 0.97 to 3.49). Severe hyperglycemia was associated with a blunted proinflammatory cytokine response (IL-6 and IL-8) on admission in patients without, but not in patients with diabetes. Conclusion Severe hyperglycemia on admission is associated with increased 30-day, 60-day and 90-day mortality in sepsis patients without a history of diabetes mellitus.

Effects of Sequence Variations in Innate Immune Response Genes on Infectious Outcome in Trauma Patients: A Comprehensive Review.

Infectious complications, sepsis, and multiple organ dysfunction syndrome (MODS) remain important causes for morbidity and mortality in patients who survive the initial trauma. Increasing evidence suggests that genetic variants, particularly single nucleotide polymorphisms (SNPs), are critical determinants for interindividual differences in both inflammatory responses and clinical outcome in sepsis patients. Although the effect of SNPs on sepsis and MODS has been studied in many populations and diseases, this review aimed to summarize the current knowledge on the effect of SNPs on infectious complication specifically in trauma patients. A review of available literature was performed in PubMed database. The following genes have been studied in populations of trauma patients: CD14, HMGB1, IFNG, IL1A, IL1B, IL1RN, IL4, IL6, IL8, IL10, IL17F, IL18, MBL2, MASP2, FCN2, TLR1, TLR2, TLR4, TLR9, TNF, LTA, GR, MYLK, NLRP3, PRDX6, RAGE, HSPA1B, HSPA1L, HSP90, SERPINE1, IRAK1, IRAK3, VEGFA, LY96, ANGPT2, LBP, MicroRNA, and mtDNA. In this review, we discuss the genes of the Pattern Recognition Receptors, Signal Transducing Adaptor Proteins, and Inflammatory Cytokines of the innate immune system. A number of genetic variations have so far been studied in cohorts of trauma patients. Studies are often unique and numbers sometimes small. No definitive conclusions can be reached at this time about the influence of specific sequence variations on outcome in trauma patients.

Association between hemodynamic presentation and outcome in sepsis patients.

We aimed to compare outcomes of sepsis patients according to their hemodynamic presentation: cryptic shock (CS), cryptic to overt shock (COS), and overt shock (OS). We analyzed the sepsis registry for adult patients who presented to the emergency department (ED) of a tertiary hospital and met the criteria for severe sepsis or septic shock between August 2008 and March 2012. We classified the patients as having CS, COS, or OS. "Cryptic shock" was defined as severe sepsis with a lactate level of 4 mmol/L or greater and normotension, "COS" was defined as initial CS that progressed to septic shock within 72 h, and "OS" was defined as septic shock on ED arrival. The primary outcome was in-hospital mortality. We performed a multivariable logistic regression analysis to assess variables related to in-hospital mortality and a multivariable Cox regression analysis to assess predictive factors for progression to OS in patients who initially showed CS. A total of 591 patients were included. We assigned 187 (31.6%) patients to the CS group, 157 (26.6%) patients to the COS group, and 247 (41.8%) patients to the OS group. There was a significant difference in unadjusted in-hospital mortality among groups (7.0% in the CS group, 27.4% in the COS group, and 21.9% in the OS group; P < 0.01). Multivariable analysis showed an odds ratio (OR) for in-hospital mortality of 0.17 (95% confidence interval, 0.07 - 0.40; P < 0.01) for the CS group and 0.83 (95% confidence interval, 0.46 - 1.49; P = 0.54) for the COS group compared with the OS group. A higher blood lactate concentration and respiratory failure were significant risk factors for progression to OS. In conclusion, CS without deterioration to hypotension during initial treatment showed significantly lower mortality than OS. The mortality from CS that progressed to apparent hypotension, however, was comparable to the mortality associated with OS.

Adrenomedullin: its double-edged sword during sepsis slices yet again.

In this first issue of Intensive Care Medicine Experimental, two related studies describe the effects of antibodies directed against adrenomedullin (ADM), a vasoactive peptide that is released from various tissues during systemic inflammation, in murine sepsis. ADM, derived from a larger precursor peptide (pro-ADM), is released into the circulation during systemic inflammation, and the highest plasma concentrations are measured in patients with septic shock [1]. With a plasma half-life of approximately 20 min, it exerts multiple effects of which the most relevant appears to be vasodilation [2]. The consequent clinical sequelae of increased ADM concentrations are far from clear. While elevated ADM levels are associated with impaired outcome in sepsis patients [1] and the measurement of the circulating pro-peptide of ADM might serve as a marker to assess disease severity and predict mortality [3], administration of exogenous ADM actually improved outcome in animal models of septic shock [4]. Intriguingly, in this issue of Intensive Care Medicine Experimental, two studies demonstrate beneficial effects of anti-ADM antibodies administered in a murine cecal ligation and puncture (CLP) model [5,6]. These studies represent the first attempts at antibody targeting of the ADM cascade in vivo. Struck et al. [5] describe the development of monoclonal antibodies directed against various epitopes of ADM and their ability to attenuate sepsis-induced mortality in severe murine sepsis (100% control group mortality within 2 to 3 days). The severity of this model means that any longterm deleterious or beneficial effects of the antibody remain unknown. Notably, all antibodies directed against ADM improved survival. Of interest, the antibody against the N-terminal moiety of ADM prevented mortality most effectively, while it inhibited ADM agonistic activity by only 25%. Wagner et al. [6] performed a more mechanistic study into the effects of HAM1101, the antibody targeted against the N-terminal part of ADM, in a resuscitated murine CLP model. They show that HAM1101 improves vasoactive responsiveness to catecholamines, attenuates systemic inflammation, and improves kidney function. The beneficial effects on the kidneys are likely attributable to reduced iNOS expression and nitrotyrosine formation in HAM1101-treated animals. The effects on inflammatory parameters are surprising as ADM itself has also been reported to inhibit inflammation [7]. In summary, previous work has established that high endogenous levels of ADM correlate with poor outcomes and that exogenous administration improved outcomes, while now it is reported that antagonism of ADM using antibodies improves outcome in an animal sepsis model.

Delayed assessment of serum lactate in sepsis is associated with an increased mortality rate

Lactate assessment early in the resuscitation of sepsis has been recommended as a diagnostic biomarker. An abnormal lactate, independent of blood pressure, is an indication for aggressive fluid resuscitation and its normalization is a recommended endpoint of resuscitation. The objective of this study was to evaluate the effect of the timing of lactate assessment on patient outcomes in sepsis.

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Introduction: Cryptic septic shock may show poor outcomes despite the setting of normal hemodynamic indices. Patients with cryptic septic shock often undergo severe tissue hypoperfusion and progressing to overt septic shock within several hours in emergency department (ED). We performed the study to compare clinical characteristics and outcomes of sepsis patients with cryptic shock, cryptic to overt shock, and overt shock. Methods: We analyzed the sepsis registry from August 2008 to March 2012 for adult patients presenting to an ED of a tertiary urban hospital and meeting the criteria for severe sepsis or septic shock. We classified enrolled patients as cryptic shock (CS) group, cryptic to overt shock (COS) group, and overt shock (OS group), defined as sepsis with a lactate ≥ 4 mmol/L and normotension, initially cryptic shock progressed to overt shock within 72 hours, and sepsis with overt hypotension on ED arrival, respectively. The primary outcome was in-hospital mortality. Results: A total 758 patients were included. Of the eligible patients, 212 patients were assigned to the CS group, 145 patients to the COS group, and 401 patients to the OS group. There was significant difference in in-hospital mortality (9.0% in the CS group, 26.2% in the COS group, and 17.2% in the OS group, p<0.001). Compared with the OS group, adjusted odds ratio (OR) for in-hospital mortality was 0.40 (95% confidence interval [CI], 0.20 – 0.81; p=0.011) in the CS group and 1.02 (95% CI 0.57 – 1.85; p=0.93) in the COS group. Among patients who initially showed cryptic shock (the CS and COS group), a higher blood lactate concentration and respiratory failure were significant risk factors for progression to overt septic shock. Conclusions: Cryptic septic shock without deterioration to hypotension during initial treatment showed significantly lower mortality than overt septic shock. The mortality of cryptic septic shock, however, was comparable to overt septic shock when it progressed to apparent hypotension. Prevention and early management of hypotension are critical strategies for improving survival of patients with cryptic septic shock.

Neutrophil Related Data Obtained From Newly Developed Automatic Hematology Analyzer Sysmex XN-2000 Can Provide Useful Informations For The Discrimination Of Sepsis Patients

Background In addition to classical biomarkers of sepsis such as C-reactive protein (CRP), lactic acid, and procalcitonin (PCT), new parameters such as immature granulocytes (IG), which can be obtained from automated hematology analyzers without any additional cost, have been recently proposed as biomarkers for the early detection of sepsis and the evaluation of its severity. Recently launched automatic hematology analyzer Sysmex XN-2000 (Sysmex, Kobe, Japan) can provide 36 routine items as well as 57 items of cell population data (CPD) which reflect detailed status of cells examined. In this study, we evaluated the clinical relevance of CPD items as a biomarker for the diagnosis of sepsis, discrimination of sepsis severity, and prediction of outcome in sepsis patients. Methods A total of 280 normal controls (NCs) and 130 patients diagnosed as bacterial sepsis were enrolled in this study. The sepsis patients were classified into uncomplicated sepsis (N=29) and complicated sepsis (N=101, defined as severe sepsis and and septic shock) depending on the sepsis severity at the time of sampling. A total of 93 items (36 routine and 53 CPD) were obtained from the Sysmex XN-2000 automatic hematology analyzer and the results were compared between NC and sepsis group at first and between uncomplicated and complicated sepsis group later. In items with significant differences between 2 groups, receiver operating characteristics (ROC) analysis was performed to evaluate discrimination power of the item between 2 groups. In addition, the results of 93 items were compared between survivors and non-survivors after 28 days from the time of sampling, and ROC analysis was also performed to compare the prediction power of the 28-day mortality of each item which showed significant differences between 2 groups. Results Among the total 93 items, a total of 21 items showed area under the curve (AUC) more than 0.900 for the discrimination of sepsis patients from NCs. These include routine items such as hematocrit (best cutoff values ≤ 37.2%, AUC 0.964), hemoglobin (≤ 11.7 g/dL AUC 0.961), IG (≥ 0.5%, AUC 0.961), CV of RDW (&gt; 13.7%, AUC 0.951), proportion of lymphocytes (≤ 18.5%, AUC 0.941) and neutrophils (&gt; 72.2%, AUC 0.914). Notably, CPD items NE-SFL (defined as the fluorescent light intensity of the neutrophil area on the WDF scattergram) and NE-WY (defined as the fluorescent light distribution width of the neutrophil area on the WDF scattergram) showed comparative AUC of 0.909 (&gt; 51.6 for NE-SFL) and 0.905 (&gt; 641.0 for NE-WY). However, for the discrimination of sepsis severity, the overall performance of all items was relatively poor and only 3 red blood cell CPD items such as RET-UPP (defined as the count in the upper area of the RET scattergram, ≤ 2.0%, AUC of 0.662), reticulocyte hemoglobin (&gt;33.2 pg, AUC of 0.633), and MacroR (defined as the macrocytic RBC ratio, &gt; 4.60%, AUC of 0.607) and only 1 granulocyte CPD item NE-SFL (&gt; 57.6, AUC of 0.603) showed AUC more than 0.600. The performance of classical sepsis biomarkers was also not satisfactory (AUC of 0.695, 0.543, and 0.537 for lactic acid, CRP, and PCT). For the prediction of 28-day mortality, the overall performance of all items was also not good and only 4 routine items such as CV of RDW (&gt; 15.4%, AUC of 0.766), platelet counts (&lt; 54,000/µL, AUC of 0.677), absolute number of neutrophils (&gt; 12,120/µL, AUC of 0.665), absolute number of reticulocytes (&gt; 2.89 x 106/µL, AUC of 0.650), and 1 CPD item RET-TNC (defined as the count in the TNC area of the RET scattergram, &gt; 125.00, AUC of 0.692) showed AUC of more than 0.650. These results were not superior compared with those from classical sepsis biomarkers (AUC of 0.712, 0.547, and 0.592 for lactic acid, CRP, and PCT). Conclusion IG%, the proportion of neutrophils, and 2 granulocytic CPD items (NE-SFL and NE-WY) could discriminate sepsis patients from normal controls when their values increase (which means neutrophil immaturity or activation). Several CPD items showed similar performance compared with lactic acid and slightly better performance than CRP and PCT for the discrimination of sepsis severity and prediction of 28-day mortality. Therefore, it can be speculated that the CPD items of neutrophil immaturity or activation can contribute partly to the discrimination of sepsis patients from NCs, but these items do not discriminate sepsis severity and predict 28-day mortality in sepsis patients as the classical sepsis biomarkers do not. Disclosures: No relevant conflicts of interest to declare.

An extended leukocyte differential count (16 types of circulating leukocytes) using the cytodiff flow cytometric system can provide information for the discrimination of sepsis severity and prediction of outcome in sepsis patients

The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter, Miami, FL) was recently developed for performing leukocyte differential counts in up to 16 leukocyte subpopulations. We compared these leukocyte subpopulation levels among patients with three stages of sepsis (uncomplicated sepsis, severe sepsis, septic shock), especially focused on the discrimination of complicated sepsis from uncomplicated sepsis. We examined a total of 181 samples with sepsis who were admitted to the surgical intensive care unit. In addition, we examined samples obtained from 60 normal healthy volunteers. Both the proportions and absolute numbers of each cell type in the four groups were obtained using the CytoDiff flow cytometric system and compared. Mature neutrophils and immature granulocytes failed to discriminate patients with complicated sepsis from those with uncomplicated sepsis although their absolute numbers were increased compared with normal controls. In contrast, almost all lymphocyte subpopulations and CD16(-) monocytes decreased significantly in patients with complicated sepsis compared with uncomplicated sepsis. Among them, only B lymphocytes showed independent ability to discriminate two groups. Both B lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic impact on overall survival when their absolute numbers decreased. Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with increasing sepsis severity. Among them, only B lymphocytes showed independent ability to discriminate patients with complicated sepsis from those with uncomplicated sepsis. Both B lymphocytes and CD16 (-) monocytes show a significant adverse prognostic impact on overall survival outcomes in sepsis patients when their absolute numbers are decreased.

An extended leukocyte differential count (16 types of circulating leukocytes) using the cytodiff flow cytometric system can provide informations for the discrimination of sepsis severity and prediction of outcome in sepsis patients.

Background: The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter, Miami, FL, USA) was recently developed for performing leukocyte differential counts in up to 16 leukocyte subpopulations. We compared these leukocyte subpopulation levels among patients with three stages of sepsis (uncomplicated sepsis, severe sepsis, septic shock), especially focused on the discrimination of complicated sepsis from uncomplicated sepsis. Methods: We examined a total of 181 samples with sepsis who were admitted to the surgical intensive care unit. In addition, we examined samples obtained from 60 normal healthy volunteers. Both the proportions and absolute numbers of each cell type in the four groups were obtained using the CytoDiff flow cytometric system and compared. Results: Mature neutrophils and immature granulocytes failed to discriminate patients with complicated sepsis from those with uncomplicated sepsis although their absolute numbers were increased compared with normal controls. In contrast, almost all lymphocyte subpopulations and CD16(-) monocytes decreased significantly in patients with complicated sepsis compared with uncomplicated sepsis. Among them, only B lymphocytes showed independent ability to discriminate two groups. Both B lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic impact on overall survival when their absolute numbers decreased. Conclusions: Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with increasing sepsis severity. Among them, only B lymphocytes showed independent ability to discriminate patients with complicated sepsis from those with uncomplicated sepsis. Both B lymphocytes and CD16(-) monocytes show a significant adverse prognostic impact on overall survival outcomes in sepsis patients when their absolute numbers are decreased. © 2013 Clinical Cytometry Society.

Activation of factor VII-activating protease in human inflammation: a sensor for cell death

IntroductionCell death is a central event in the pathogenesis of sepsis and is reflected by circulating nucleosomes. Circulating nucleosomes were suggested to play an important role in inflammation and were demonstrated to correlate with severity and outcome in sepsis patients. We recently showed that plasma can release nucleosomes from late apoptotic cells. Factor VII-activating protease (FSAP) was identified to be the plasma serine protease responsible for nucleosome release. The aim of this study was to investigate FSAP activation in patients suffering from various inflammatory diseases of increasing severity.MethodsWe developed ELISAs to measure FSAP-C1-inhibitor and FSAP-α2-antiplasmin complexes in plasma. FSAP-inhibitor complexes were measured in the plasma of 20 adult patients undergoing transhiatal esophagectomy, 32 adult patients suffering from severe sepsis and 8 from septic shock and 38 children suffering from meningococcal sepsis.ResultsWe demonstrate plasma FSAP to be activated upon contact with apoptotic and necrotic cells by an assay detecting complexes between FSAP and its target serpins α2-antiplasmin and C1-inhibitor, respectively. By means of that assay we demonstrate FSAP activation in post-surgery patients, patients suffering from severe sepsis, septic shock and meningococcal sepsis. Levels of FSAP-inhibitor complexes correlate with nucleosome levels and correlate with severity and mortality in these patients.ConclusionsThese results suggest FSAP activation to be a sensor for cell death in the circulation and that FSAP activation in sepsis might be involved in nucleosome release, thereby contributing to lethality.

Experimental Validation of a Theoretical Model of Cytokine Capture Using a Hemoadsorption Device

Sepsis, a systemic inflammatory response in the presence of an infection, is characterized by overproduction of inflammatory mediators called cytokines. Removal of these cytokines using an extracorporeal hemoadsorption device is a potential therapy for sepsis. We are developing a cytokine adsorption device (CAD) filled with microporous polymer beads and have previously published a mathematical model which predicts the time course of cytokine removal by the device. The goal of this study was to show that the model can experimentally predict the rate of cytokine capture associated with key design and operational parameters of the CAD. We spiked IL-6, IL-10, and TNF into horse serum and perfused it through an appropriately scaled-down CAD and measured the change in concentration of the cytokines over time. These data were fit to the mathematical model to determine a single model parameter, Gamma( i ), which is only a function of the cytokine-polymer interaction and the cytokine effective diffusion coefficient in the porous matrix. We compared Gamma( i ) values, which by definition should not change between experiments. Our results indicate that the Gamma( i ) value for a specific cytokine was statistically independent of all other parameters in the model, including initial cytokine concentration, flow rate, serum reservoir volume, CAD size, and bead size. Our results also indicate that competitive adsorption of cytokines and other middle-molecular weight proteins, which is neglected in the model, does not affect the rate of removal of a given cytokine. The model of cytokine capture in the CAD developed in this study will be integrated with a systems model of sepsis to simulate the progression of sepsis in humans and to develop a therapeutic CAD design and intervention protocol that improves patient outcomes in sepsis.

Lipopolysaccharide Binding Protein, Soluble-Intercellular Adhesion Molecule-1, Procalcitonin, and Protein C Activity and Clinical Outcome in Systemic Inflammatory Response Syndrome (SIRS) or Sepsis Patients

BACKGROUND: Biochemical markers may be used in diagnosis, prognostic and monitoring treatment and therapy for sepsis patients. In this study we used Lipopolysacharide Binding Protein (LBP), serum-Intercellular Adhesion Molecule-1 (ICAM-1), Procalcitonin (PCT) and protein C activity. LBP is related to lipopolysachharide or gram-negative bacterial endotoxin which bound to LBP and induced inflammatory response. ICAM-1 is associated with endothelial dysfunction in response to systemic inflammatory and septic condition. PCT increased in bacterial infection and in severe systemic inflammatory. Role of Protein C is protecting the intravascular system to systemic inflammation, sepsis and the concomitant intravascular coagulopathy. The aim of this study was to examine the associations between levels of serum LBP, sICAM-1, PCT, and protein C activity with the clinical outcome of SIRS or sepsis patients.METHODS: We included 19 post surgery patients with SIRS criteria from intensive care unit (ICU) and evaluated the level of LBP serum with Chemiliuminescent Enzyme Immunoassay (Diagnostic Product Co.), ICAM-1 with ELISA (R&amp;D System), PCT with immunochromatography (BRAHMS), protein C activity with chromogenic method (Dade Behring). We performed the samples serially at the first admission of patients and after 72 hours. Data were analysed by non-parametric with Wilcoxon test and Mann-Whitney test. Correlation study between biomarkers calculated by Kendall’s tau and Spearman’s rho.RESULTS: Of 19 patients, 9 (47,4%) died and 10 (52,6%) surviving. The level of LBP serum decreased after 72 hours in surviving-sepsis patients, and increased in nonsurviving sepsis patients with significant different levels at 72 hours examination (P&lt;0.05). The level of soluble-ICAM-1 which was high in the first admission showed in non-surviving sepsis patients, but the difference levels was not significant between surviving and non-surviving patients (P&gt;0.05). In all patients were found high level of PCT serum since the first admission examination, decreasing levels were occurred significantly in surviving patients after 72 hours (P&lt;0.05) where high PCT levels were found in non-surviving patients after 72 hours. The median level of plasma protein C activity was low at the first admission especially in non-surviving sepsis patients, the decreasing level was not significantly different after 72 hours (P&gt;0.05) both in surviving and non-surviving patients.CONCLUSIONS: Increasing level of LBP and PCT in sepsis patients showed that those biomarkers useful for predict the clinical outcome in sepsis patients. Decreasing protein C activity level was not a good predictor in worsening clinical outcomes. Soluble ICAM-1 level was not a good marker for predict risk of sepsis severity. LBP and PCT tests were more useful in serially testing from the first admission of sepsis patients, those tests are more faster than bacterial culture.KEYWORDS: Sepsis, SIRS, Lipopolysachharide Binding Protein, soluble- Intercellular Adhesion Molecule-1, Procalcitonin, Protein C

Difference in Protein Markers According to the Survival of Sepsis Patients using Protein Chips

Background; Several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. Therefore, we sought to identify the proteomic biomarkers, with wsing proteomic tools, that differed according to the outcome of sepsis patients. Methods; Upon admission to the ICU, blood samples were obtained from the 16 patients with sepsis who were enrolled in this study. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI –TOF MS) was used to identify the markers that could predict the outcome of sepsis. Results; We found six peaks, by using cation and anion chips, that statistically differed between those patients who died and those who survived. Conclusion; The biomarkers we found by using proteomic tools may help predi ct the prognosis and also plan the treatment of sepsis. (Tuberc Respir Dis 2006; 61: 41-45)

Determinants of Mortality in Patients with Severe Sepsis

To evaluate the relative importance of predictors of in-hospital mortality in severe sepsis and compare the performance of generic and disease-specific mortality prediction models. The author used data from all 826 patients receiving placebo in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial. After a variety of clinical factors were examined for their univariate association with in-hospital mortality, logistic regression models incorporating successively more inclusive sets of predictors were created and compared. For each model, discrimination was assessed and the relative contribution of each model component to overall model explanatory power evaluated. The accuracy of using the Acute Physiology and Chronic Health Evaluation (APACHE) II score in isolation as an indicator of "high risk" was assessed by comparing model predictions from APACHE-only models to those of disease-specific models. Age, a number of laboratory values, and APACHE II score were significant univariate predictors of mortality. In multivariable models, age and laboratory values contributed the most information to model predictions; the contribution of the APACHE II score, in particular, the acute physiology component, was modest at best. A risk model including only the total APACHE II score had a c-statistic of 0.686, whereas the best performing disease-specific model had a c-statistic of 0.787. Use of the APACHE II score alone to establish high risk versus low risk resulted in misclassification of 26% of patients. Individual severe sepsis patient outcomes depend on an array of clinical predictors. Models incorporating sepsis disease-specific risk factors may predict mortality more accurately than generic ICU severity measures.