Dunja Mihajlovic

Endocan is useful biomarker of survival and severity in sepsis.

INTRODUCTION Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. MATERIALS AND METHODS 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. RESULTS Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure. CONCLUSIONS Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores.

Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis

Background: Biomarkers of endothelial dysfunction are not recommended for routine laboratory investigation of the outcome prognosis and prediction of the course of sepsis. Methods: A total of 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Development of multiorgan dysfunction syndrome (MODS) in the first 48 hours was assessed. Differences between groups of patients with sepsis were assessed by Mann-Whitney U test and by Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. Results: Level of thrombomodulin was significantly higher in group of patients with MODS than without MODS (P = .015). Levels of antithrombin (P = .026) and protein C (P = .035) were significantly lower in patients with MODS. Level of thrombomodulin was the strongest predictor in MODS development in first 48 hours (P = .028). Conclusion: The level of thrombomodulin not only was able to distinguish the severity of sepsis but also was a significant predictor of MODS development.

Endogenous thrombin potential as marker of procoagulant response that can be useful in early stage of sepsis

&NA; Sepsis is associated with complex procoagulant and anticoagulant changes that modify inflammatory response. Identification of coagulation markers that can differentiate useful procoagulant response from adverse alteration of clotting mechanism in patient with sepsis. In total, 150 patients who fulfilled criteria for diagnosis of sepsis were included in this study. Patients were categorized in two groups according to sepsis severity in the first 24 h from intensive care unit admission: sepsis and septic shock. In total, 28-day mortality was assessed. Platelet count, activated partial thromboplastin time, prothrombin time, D-dimer, fibrinogen, protein C, protein S, antithrombin levels, and endogenous thrombin potential were determined within first 24 h from ICU admission. Differences between groups of septic patients were assessed by Mann–Whitney U test. Categorical variables were compared using &khgr;2 test. Receiver operating characteristic curves were plotted to determine predictive values of variables for sepsis severity prediction. Activated partial thromboplastin time and prothrombin time were significantly prolonged with higher D-dimer, lower fibrinogen, and natural anticoagulant levels (protein C, protein S, and antithrombin) in patients with more severe form of the disease and worse outcome (P < 0.05). Endogenous thrombin potential [area under the curve (AUC) %] was significantly decreased in patients with more severe form of sepsis (66.01 ± 41.51 vs. 83.21 ± 28.83; AUC 0.76) and in patients with worse outcome (67.66 ± 37.79 vs. 81.79 ± 32.15; AUC 0.68; P < 0.05). Evaluation of initial thrombin generation is useful to distinguish between beneficial coagulation activation and hazardous haemostatic alteration, and to predict multiorgan dysfunction development and poor outcome in septic patients.

Use of presepsin and procalcitonin for prediction of SeptiFast results in critically ill patients

Purpose There is a need for identification of marker that could lead physicians to take the right step towards laboratory techniques for documentation of infection. The aim of this study was to investigate whether presepsin and procalcitonin (PCT) levels in patients with suspected sepsis could predict blood culture (BC) and SeptiFast (SF) results. Material and methods 100 patients were included in our study. PCT, C‐reactive protein (CRP), and presepsin levels were determined. Differences between groups of patients were assessed by Mann‐Whitney U test. Categorical variables were compared using chi‐square test. Receiver operating characteristic (ROC) curves were plotted to determine predictive values of biomarkers for prediction of positive SF results. Results PCT (70.9 ± 106.36 vs. 16.35 ± 26.79) and presepsin (4899.73 ± 5207.81 vs. 1751.59 ± 2830.62) were significantly higher in patients with positive SF in contrast to patients with negative SF. There was no significant difference between patients who had positive and negative BC for PCT and presepsin values. PCT and presepsin showed a similar performance in predicting positive SF results with AUC of 0.75 for PCT and 0.73 for presepsin. Conclusion Presepsin can serve as good predictor of bacteremia detected by SF and it should be included with PCT in protocols for sepsis diagnosing. HighlightsSeptiFast is expensive method for sepsis detection.Presepsin is a good predictor of bacteremia detected by SeptiFast.Presepsin should be included with PCT in protocols for sepsis diagnosing.

O bloqueio do plano transverso abdominal subcostal pode melhorar a analgesia após colecistectomia laparoscópica

BACKGROUND AND GOAL OF STUDY After laparoscopic cholecystectomy, patients have moderate pain in the early postoperative period. Some studies shown beneficial effects of subcostal transversus abdominis plane block on reducing this pain. Our goal was to investigate influence of subcostal transversus abdominis plane block on postoperative pain scores and opioid consumption. MATERIALS AND METHODS We have randomized 76 patients undergoing laparoscopic cholecystectomy to receive either subcostal transversus abdominis plane block (n=38) or standard postoperative analgesia (n=38). First group received bilateral ultrasound guided subcostal transversus abdominis plane block with 20mL of 0.33% bupivacaine per side before operation and tramadol 1mg.kg-1IV for pain breakthrough (≥6). Second group received after operation tramadol 1mg.kg-1/6h as standard hospital analgesia protocol. Both groups received acetaminophen 1g/8h IV and metamizole 2.5g/12h. Pain at rest was recorded for each patient using NR scale (0-10) in period of 10min, 30min, 2h, 4h, 8h, 12h and 16h after the surgery. RESULTS AND DISCUSSION We obtained no difference between groups according age, weight, intraoperative fentanyl consumption and duration of surgery. Subcostal transversus abdominis plane block significantly reduced postoperative pain scores compared to standard analgesia in all periods after surgery. Tramadol consumption was significantly lower in the subcostal transversus abdominis plane (24.29±47.54g) than in the standard analgesia group (270.2±81.9g) (p=0.000). CONCLUSION Our results show that subcostal transversus abdominis plane block can provide superior postoperative analgesia and reduction in opioid requirements after laparoscopic cholecystectomy.

APRIL and sTACI could be predictors of multiorgan dysfunction syndrome in sepsis

ABSTRACT Although the role of B cells in sepsis immunoregulation has become an interesting topic, there is lack of data on the role of B cell function regulators in prediction of multiorgan dysfunction syndrome (MODS). The aim of this study was to evaluate the prognostic value of A Proliferation Inducing Ligand (APRIL) and soluble Transmembrane Activator and CAML Interactor Protein (sTACI), the main B cell function regulators, in prediction of MODS development within the first 48 h after admission to intensive care unit, among septic patients. We included 112 patients with sepsis, treated at Clinic for Infectious Diseases and Emergency Center, Clinical Center of Vojvodina, Novi Sad, Serbia. Plasma concentrations of APRIL and sTACI were determined at the admission and potential development of MODS was confirmed in the first 48 h. Concentrations of APRIL (p = 0.003) and sTACI (p<0.001) were higher in patients who developed MODS (n = 30). ROC curve analysis showed that AUC for sTACI (AUC = 0.764) was greater than that for procalcitonin (AUC = 0.719) and APRIL (AUC = 0.673) in MODS development prediction. Multivariate regression analysis showed that sTACI, as an anti-inflammatory biomarker stimulating the apoptosis of B cells, was the only independent predictor of MODS, beside SOFA score. Elevated level of sTACI could be the alarm for the increased B cell apoptosis and development of immune paralysis. Including these biomarkers into predictive scores specific for septic patients may potentially improve their sensitivity and specificity. Measurement of their concentrations dynamics could contribute to better assessment of sepsis evolution and timely introduction of immunomodulatory therapy.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers

INTRODUCTION The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. METHODS One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. RESULTS A significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. CONCLUSION In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

The role of TNF-α superfamily members in immunopathogenesis of sepsis

Background Members of TNF&agr; superfamily, A proliferation inducing ligand (APRIL), B‐cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B‐cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome. Materials and methods A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations. Results Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUCAPRIL = 0.982, AUCBAFF = 0.873, AUCsTACI = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049). Conclusions Concentrations of observed TNF&agr; superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis. Higher concentrations of anti‐inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti‐inflammatory response in septic patients with worse outcome. HighlightsHigh concentrations of TNF‐&agr; superfamily members point to prompt activation of B cells in sepsis.APRIL, BAFF and sTACI are good predictors of septic shock and lethal outcome in sepsis.Their concentrations correlate well with SOFA, but do not correlate with PCT.Lower BAFF and higher sTACI concentrations suggest increased apoptosis of B cells in septic shock.sTACI is an anti‐inflamatory cytokine that had the highest AUC in outcome prediction.

Ischemic Lesion on Computed Tomography after Subarachnoid Hemorrhage: Good Correlation With Angiographic Vasospasm and Worse Outcome

Objective:The aim of our study was to evaluate the frequency of angiographic vasospasm and computed tomography (CT) detectable cerebral ischemia after subarachnoid hemorrhage, the relationship between these events, and the impact on outcome. Patients and Methods:We prospective enrolled 54 patients with subarachnoid hemorrhage treated from March 2011 to January 2013. CT and CT angiography of brain were obtained on the ninth day of rupture regardless of neurological status. The control brain CT and CT angiography were obtained earlier if clinical symptoms implied delayed cerebral ischemia. The outcome was assessed after 6 months using the extended Glasgow Outcome scale scale. Results:Fifty-four percent of the patients recruited had CT angiography vasospasm and 46% had cerebral ischemia on CT scans. Our study shows a strong correlation between angiographic vasospasm and cerebral ischemia visible on CT (P=0.001) and severity of vasospasm and frequency of ischemia (P=0.03). Twenty percent of the patients showed ischemia with no demonstrable vasospasm confirming multiple cause of delayed cerebral ischemia. Logistic regression model has shown the strong impact of angiographic vasospasm (P=0.004, odds ratio=6.85; 95% confidence interval, 1.83-26.65) and arterial hypertension (P=0.02, odds ratio=4.32; 95% confidence interval, 1.16-16.01) on the development of cerebral ischemia. Angiographic vasospasm (P=0.01) and cerebral ischemia (P=0.005) were associated with worse 6-month outcome. Conclusion:A strong association exists between angiographic vasospasm and cerebral ischemia on CT although some ischemia occurs in area without vasospasm.