S100B protein (S100B) has been described as a marker of brain injury. Various cytokines also increase in the cerebrospinal fluid (CSF) of patients with severe traumatic brain injury (TBI). Thus, we investigated early changes in the concentrations of CSF S100B and various cytokines after TBI and evaluated the relations of both S100B and cytokines to intracranial pressure (ICP) and prognosis. Twenty-three patients with severe TBI and a Glasgow Coma Scale score of 8 or less on admission were included in this study. CSF and serum samples were obtained on admission and at 6, 12, 24, 48, 72, and 96 h after injury. CSF concentrations of S100B and CSF and serum concentrations of five cytokines (IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10) were measured and compared. The CSF S100B concentration was increased for 6 h after injury and decreased thereafter. The CSF concentrations of IL-6 and IL-8 peaked within 6 h after injury; other cytokines (IL-1beta, TNF-alpha, and IL-10) were elevated for 24 h after injury and gradually decreased thereafter. Peak CSF S100B concentrations correlated significantly with ICP determined at the time CSF samples were taken (r = 0.729, P < 0.0001). For the cytokines investigated, only the peak CSF IL-1beta concentration correlated significantly and positively with the peak CSF S100B concentration (r = 0.397, P < 0.005). Peak CSF concentrations of S100B (1649 +/- 415 microg/L, mean +/- SEM) and IL-1beta (16.5 +/- 3.3 pg/mL) in the 6 patients with high ICP were significantly higher than those (233 +/- 67 microg/L, 7.6 +/- 1.7 pg/mL, respectively) in the 17 patients with low ICP (P < 0.05). The CSF S100B concentration (1231 +/- 378 microg/L) in eight patients with an unfavorable outcome was significantly higher than that (267 +/- 108 microg/L) in 15 patients with a favorable outcome (P < 0.05). The CSF IL-1beta concentration (14.8 +/- 3.4 pg/mL) in eight patients with an unfavorable outcome tended to be higher than that (7.3 +/- 1.5 pg/mL) in 15 patients with a favorable outcome (P = 0.057). CSF concentrations of S100B and cytokines peak within 24 h after severe TBI and decrease gradually thereafter. CSF S100B and IL-1beta may be useful as predictors of outcome in cases of severe TBI.

BackgroundGut under severe insult is considered to have an important role in promoting infection and multiple organ dysfunction syndrome from the viewpoint of altered intestinal epithelium, immune system and commensal bacteria. There are few reports, however, about the relationship between gut flora and septic complications.MethodsWe analyzed gut flora in patients with systemic inflammatory response syndrome (SIRS) and evaluated key bacteria and their cutoff values for infectious complications and mortality by using classification and regression trees (CART). Eighty-one SIRS patients with a serum C-reactive protein level higher than 10 mg/dL treated in the intensive care unit (ICU) for more than 2 days were included for the study. We quantitatively evaluated nine types of bacteria in fecal samples by plate or tube technique. Two hundred seventy-one samples were analyzed using CART and logistic regression.ResultsThe dominant factors for complication of enteritis were the minimum number of total obligate anaerobes and the maximum number of Staphylococcus and Enterococcus. The dominant factors for complication of bacteremia were the minimum numbers of total obligate anaerobes and total facultative anaerobes. The dominant factors for mortality were the numbers of total obligate anaerobes and total facultative anaerobes and age.ConclusionsA decrease in total obligate anaerobes and an increase in pathogenic bacteria in the gut are associated with septic complications and mortality in patients with SIRS. The altered gut flora may be a potential prognostic marker in SIRS patients.

Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5–76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in “the presence of bacteria in tracheal aspirate” group (11/22, 50.0%) than in “the absence of bacteria in tracheal aspirate” group (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the presence of bacteria in tracheal aspirate was significantly associated with the presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may be one important factor associated with NET formation. NETs may play a pivotal role in the biological defense against the dissemination of pathogens from the respiratory tract to the bloodstream in potentially infected patients.

Table of contentsP001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP effluxR. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. EllisP002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez GallegoP003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsisF. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. TuzunP004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopeniaR. Riff, O. Naamani, A. DouvdevaniP005 - Analysis of neutrophil by hyper spectral imaging - A preliminary reportR. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. ShimazuP006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgeryS. Ono, T. Kubo, S. Suda, T. Ueno, T. IkedaP007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational studyT. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. ShimazuP008 - Comparison of bacteremia and sepsis on sepsis related biomarkersT. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. OnoP009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purificationT. Taniguchi, M. OP010 - Validation of a new sensitive point of care device for rapid measurement of procalcitoninC. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. LottP011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive proteinM. M. Meili, P. S. SchuetzP012 - Do we need a lower procalcitonin cut off?H. Hawa, M. Sharshir, M. Aburageila, N. SalahuddinP013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteriaV. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. MichaloudisP014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiberA. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. ImaizumiP015 - Diagnostic usefullness of combination biomarkers on ICU admissionM. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-AlcantaraP016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patientsN. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. NeeP017 - Extracellular histone H3 levels are in...

In our previous study of patients with early-phase severe traumatic brain injury (TBI), the anti-inflammatory interleukin (IL)-10 concentration was lower in cerebrospinal fluid (CSF) than in serum, whereas proinflammatory IL-1beta and tumor necrosis factor (TNF)-alpha concentrations were higher in CSF than in serum. To clarify the influence of additional injury on this disproportion between proinflammatory and anti-inflammatory mediators, we compared their CSF and serum concentrations in patients with severe TBI with and without additional injury. All 35 study patients (18 with and 17 without additional injury) had a Glasgow Coma Scale score of 8 or less upon admission. With the exception of additional injury, clinical characteristics did not differ significantly between groups. CSF and serum concentrations of two proinflammatory mediators (IL-1beta and TNF-alpha,) and three anti-inflammatory mediators (IL-1 receptor antagonist [IL-1ra], soluble TNF receptor-I [sTNFr-I], and IL-10) were measured and compared at 6 h after injury. CSF concentrations of proinflammatory mediators were much higher than the corresponding serum concentrations in both patient groups (P < 0.001). In contrast, serum concentrations of anti-inflammatory mediators were much higher than the paired CSF concentrations in patients with additional injury (P < 0.001), but serum concentrations were lower than or equal to the corresponding CSF concentrations in patients without additional injury. CSF concentrations of IL-1beta, IL-1ra, sTNFr-I, and IL-10 were significantly higher (P < 0.01 for all) in patients with high intracranial pressure (ICP; n = 11) than in patients with low ICP (n = 24), and were also significantly higher (P < 0.05 for all) in patients with an unfavorable outcome (n = 14) than in patients with a favorable outcome (n = 21). These findings indicate that increased serum concentrations of anti-inflammatory mediators after severe TBI are mainly due to additional extracranial injury. We conclude that anti-inflammatory mediators in CSF may be useful indicators of the severity of brain damage in terms of ICP as well as overall prognosis of patients with severe TBI.