Systemic Inflammatory Response Syndrome Patients Research Articles

Systemic inflammation worsens outcomes in emergency surgical patients

Acute care surgeons are uniquely aware of the importance of systemic inflammatory response and its influence on postoperative outcomes; concepts like damage control have evolved from this experience. For surgeons whose practice is mostly elective, the significance of such systemic inflammation may be underappreciated. This study sought to determine the influence of preoperative systemic inflammation on postoperative outcome in patients requiring emergent colon surgery. Emergent colorectal operations were identified in the American College of Surgeons National Surgical Quality Improvement Program 2008 dataset. Four groups were defined by the presence and magnitude of the inflammatory response before operation: no inflammation, systemic inflammatory response syndrome (SIRS), sepsis, or severe sepsis/septic shock. Thirty-day survival was analyzed by Kaplan-Meier method. A total of 3,305 patients were identified. Thirty-day survival was significantly different (p < 0.0001) among the four groups; increasing magnitudes of preoperative inflammation had increasing probability of mortality (p < 0.0001). Hazard ratios indicated that, compared with patients without preoperative systemic inflammation, the relative risk of death from SIRS was 1.9 (p < 0.0001), from sepsis was 2.5 (p < 0.0001), and from severe sepsis/septic shock was 6.7 (p < 0.0001). Operative time of <150 minutes was associated with decreased risk of morbidity (odds ratio = 0.64; p < 0.0001). Upregulation of the systemic inflammatory response is the primary contributor to death in emergency surgical patients. In SIRS or sepsis patients, operations <2.5 hours are associated with fewer postoperative complications. These results further reinforce the concept of timely surgical intervention and suggest a potential role for damage control operations in emergency general surgery. II, prognostic study.

Mo1918 Sirolimus use is Associated With Increased Risk for Cardiovascular Events Following Liver Transplantation

N-Acetylcysteine (NAC) improves transplant-free survival (TFS) in patients with non-acetaminophen (APAP) acute liver failure (ALF) when administered in early stages of hepatic encephalopathy (HE). The mechanisms of this benefit are unknown. We hypothesized that NAC may improve TFS by ameliorating the surge of pro-inflammatory cytokines leading to the systemic inflammatory response syndrome (SIRS). Objectives. To determine the effects of NAC administration on serum cytokine concentrations, and to relate cytokine concentrations to outcome, progression of HE, and the SIRS in patients with non-APAP-induced ALF. Methods. Serum samples from 90 patients from the randomized, placebo-controlled ALF Study Group NAC Trial were analyzed. Samples from 45 patients in each group were assayed, and serum cytokine concentrations were determined in multiplex SearchLight® ELISA assays by ThermoFisher. Proand anti-inflammatory cytokines representing activation of Th1 (IL2, IFNγ, TNFα), Th2 (IL-4,6,10,13), and Treg (IL-17,23) classes of T-helper cells were chosen for assay. Results. The number of SIRS components on admission was a predictor of 21 day mortality (p=0.02 by ANOVA). Predictors of TFS in univariate analysis included NAC administration (p=0.005), admission bilirubin (p<0.001), INR (p=0.085), grade 1 vs. 2 HE (p<0.02) and higher admission IL-17 concentrations (p=0.02). However, there were no differences in any serum cytokine concentrations or in SIRS in patients treated with NAC vs. placebo. Stepwise multivariable logistic analysis identified each of these factors as independent predictors of TFS (p<0.0001). IL-17 levels were higher in patients with grade 2 vs. 1 HE (p<0.01) and in those who progressed to grade 3/4 HE (p<0.02). Patterns of elevated cytokines were observed, with levels of Th1 cytokines highly related (r=0.75, p<0.0001), and levels of proand anti-inflammatory cytokines also related (eg., IL-6 and IL-10; r=0.48, p<0.001). IL-6 and IL-10 concentrations were both related to number of SIRS on admission (p<0.01 and p<0.001) and inversely related to mean arterial pressure (r=-0.35 and -0.34, respectively; p<0.001 for both). Conclusions. NAC does not improve TFS by ameliorating the surge of pro-inflammatory cytokines in patients with non-APAPinduced ALF. However, specific proand anti-inflammatory cytokine concentrations are associated with outcome, HE grade, and the SIRS. IL-17 may have an important role in HE progression and outcome.

Mo1917 Relationship of Serum Cytokine Concentrations to Outcome, Complications and N-Acetylcysteine Treatment in Patients With Non-Acetaminophen-Induced Acute Liver Failure

N-Acetylcysteine (NAC) improves transplant-free survival (TFS) in patients with non-acetaminophen (APAP) acute liver failure (ALF) when administered in early stages of hepatic encephalopathy (HE). The mechanisms of this benefit are unknown. We hypothesized that NAC may improve TFS by ameliorating the surge of pro-inflammatory cytokines leading to the systemic inflammatory response syndrome (SIRS). Objectives. To determine the effects of NAC administration on serum cytokine concentrations, and to relate cytokine concentrations to outcome, progression of HE, and the SIRS in patients with non-APAP-induced ALF. Methods. Serum samples from 90 patients from the randomized, placebo-controlled ALF Study Group NAC Trial were analyzed. Samples from 45 patients in each group were assayed, and serum cytokine concentrations were determined in multiplex SearchLight® ELISA assays by ThermoFisher. Proand anti-inflammatory cytokines representing activation of Th1 (IL2, IFNγ, TNFα), Th2 (IL-4,6,10,13), and Treg (IL-17,23) classes of T-helper cells were chosen for assay. Results. The number of SIRS components on admission was a predictor of 21 day mortality (p=0.02 by ANOVA). Predictors of TFS in univariate analysis included NAC administration (p=0.005), admission bilirubin (p<0.001), INR (p=0.085), grade 1 vs. 2 HE (p<0.02) and higher admission IL-17 concentrations (p=0.02). However, there were no differences in any serum cytokine concentrations or in SIRS in patients treated with NAC vs. placebo. Stepwise multivariable logistic analysis identified each of these factors as independent predictors of TFS (p<0.0001). IL-17 levels were higher in patients with grade 2 vs. 1 HE (p<0.01) and in those who progressed to grade 3/4 HE (p<0.02). Patterns of elevated cytokines were observed, with levels of Th1 cytokines highly related (r=0.75, p<0.0001), and levels of proand anti-inflammatory cytokines also related (eg., IL-6 and IL-10; r=0.48, p<0.001). IL-6 and IL-10 concentrations were both related to number of SIRS on admission (p<0.01 and p<0.001) and inversely related to mean arterial pressure (r=-0.35 and -0.34, respectively; p<0.001 for both). Conclusions. NAC does not improve TFS by ameliorating the surge of pro-inflammatory cytokines in patients with non-APAPinduced ALF. However, specific proand anti-inflammatory cytokine concentrations are associated with outcome, HE grade, and the SIRS. IL-17 may have an important role in HE progression and outcome.

Selenium Supplementation in the Critically Ill

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 µg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.

Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation

The outcome of patients undergoing surgical or interventional therapy is unfavourably influenced by severe systemic inflammation. We assessed the impact of a systemic inflammatory response syndrome (SIRS) on the outcome after transcatheter aortic valve implantation (TAVI). One hundred and fifty-two high-risk patients (mean age: 80.5 ± 6.5 years, mean logistic EuroSCORE: 30.4 ± 8.1%) with symptomatic severe aortic stenosis underwent TAVI. Proinflammatory cytokines [interleukin-6 (IL-6) and interleukin-8 (IL-8)], and acute phase reactants [C-reactive protein (CRP) and procalcitonin (PCT)] were measured at baseline and 1, 4, 24, 48, 72 h, and 7 days after TAVI. Sixty-one of 152 patients developed SIRS during the first 48 h after TAVI. Systemic inflammatory response syndrome patients were characterized by leucocytosis ≥12 × 10(9)/L (83.6 vs. 12.1%; P < 0.001), hyperventilation (80.3 vs. 35.2%; P < 0.001), tachycardia (37.7 vs. 9.9%; P < 0.001), and fever (31.1 vs. 3.3%; P < 0.001) compared with patients without SIRS. Furthermore, the occurrence of SIRS was characterized by a significantly elevated release of IL-6 and IL-8 with subsequent increase in the leucocyte count, CRP, and PCT. Major vascular complications [odds ratio (OR) 5.1, 95% confidence interval (CI): 1.3-19.6; P = 0.018] and the number of ventricular pacing runs (OR 1.7, 95% CI: 1.1-2.8; P = 0.025) were independent predictors of SIRS. The occurrence of SIRS was related to 30-day and 1-year mortality (18.0 vs. 1.1% and 52.5 vs. 9.9%, respectively; P < 0.001) and independently predicted 1-year mortality risk (hazard ratio: 4.3, 95% CI: 1.9-9.9; P < 0.001). SIRS may occur after TAVI and is a strong predictor of mortality. The development of SIRS could be easily identified by a significant increase in the leucocyte count shortly after TAVI.

Serum decoy receptor 3, a potential new biomarker for sepsis

BackgroundSepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS. MethodsSerum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, was quantitatively measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11±2.58ng/ml vs 2.62±1.46ng/ml, and 0.91±0.56ng/ml, respectively, p<0.001). The areas under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870–0.950), 0.992 (0.984–1.000) and 0.896 (0.820–0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r=0.556, p=0.005). ConclusionThe serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity.

Toll-like receptors expression and interferon-γ production by NK cells in human sepsis

IntroductionDuring the course of infection, natural killer (NK) cells contribute to innate immunity by producing cytokines, particularly interferon-gamma (IFN-γ). In addition to their beneficial effects against infection, NK cells may play a detrimental role during systemic inflammation, causing lethality during sepsis. Little is known on the immune status of NK cells in patients with systemic inflammatory response syndrome (SIRS) or sepsis in terms of cell surface markers expression and IFN-γ production.MethodsWe investigated 27 sepsis patients and 11 patients with non-infectious SIRS. CD56bright and CD56dim NK cell subsets were identified by flow cytometry and Toll-like receptor (TLR)2, TLR4, TLR9, CX3CR1, CD16 and CD69 expression were analyzed, as well as ex vivo IFN-γ production by NK cells in whole blood samples.ResultsWe first showed that in NK cells from healthy controls, TLR2 and TLR4 expression is mainly intracellular, similarly to TLR9. Intracellular levels of TLR2 and TLR4, in both CD56bright and CD56dim NK cell subsets from sepsis patients, were increased compared to healthy subjects. In addition, the percentage of CD69+ cells was higher among NK cells of sepsis patients. No difference was observed for TLR9, CX3CR1, and CD16 expression. The ex vivo stimulation by TLR4 or TLR9 agonists, or whole bacteria in synergy with accessory cytokines (IL-15+IL-18), resulted in significant production of IFN-γ by NK cells of healthy controls. In contrast, for SIRS and sepsis patients this response was dramatically reduced.ConclusionsThis study reports for the first time an intracellular expression of TLR2 and TLR4 in human NK cells. Surface TLR4 expression allows discriminating sepsis and SIRS. Furthermore, during these pathologies, NK cells undergo an alteration of their immune status characterized by a profound reduction of their capacity to release IFN-γ.

Comparison of the Effects of Different Intravenous Fat Emulsions in Patients With Systemic Inflammatory Response Syndrome and Sepsis

In this study, the authors aimed to compare the effects that a medium- and long-chain triglyceride (MCT/LCT) fat infusion and a fish oil-based (ω-3) fat infusion for parenteral nutrition (PN) had on systemic inflammation, cytokine response, and hepatic steatosis in mixed intensive care unit (ICU) patients. This was a single-center, placebo-controlled, randomized clinical trial in a university hospital. Four patient groups, including systemic inflammatory response syndrome (SIRS) and sepsis patients, were assigned to receive PN employing the MCT/LCT fat infusion or the fish oil-based fat infusion over 7 days. Blood biochemistry and liver steatosis were evaluated. Twenty sepsis and 20 SIRS patients were included in this study. There was no statistically significant difference in terms of biochemical values and Acute Physiology and Chronic Health Evaluation II scores between the different feeding groups. Sepsis groups who received MCT/LCT revealed higher grades of liver steatosis by ultrasound on days 7 and 10 (P < .05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 values in sepsis group 1 (S1) were higher than in sepsis group (S2) on day 7, whereas IL-1 values were higher on days 3, 7, and 10 in group S1 than in group S2. Conversely, IL-10 values on days 3 and 7 were significantly higher in group S2. Fish oil-based fat emulsions might have anti-inflammatory and hepatoprotective effects in hyperinflammatory disease such as sepsis.

What’s New in Shock, December 2011?

What’s New in Shock, December 2011?

Effects of nutritional status in patients of systemic inflammatory response syndrome on its prognosis

Objective To investigate influence of nutritional status on prognosis in patients with systemic inflammatory response syndrome (SIRS). Methods Retrospective analysis for clinical data of 533 patients who hospitalized at the Internal Medicine Department of Beijing Social Welfare Hospital and the Emergency Department of Chaoyang Hospital, Beijing during 2005 to 2010 were performed. All the patients were divided into SIRS (323 cases) and non-SIRS (210 cases) groups based on diagnostic criteria of SIRS and pyemia, and groups of the survival (431 cases) and the dead ( 102 cases) based on their end outcomes.Patients of SIRS were further divided into sub-groups of pyemia (287 cases) and non-pyemia (36 cases)based on their infection status. The Acute Physiology and Chronic Health Evaluation Ⅱ ( APACHE Ⅱ ),serum levels of prealbumin ( PAB), albumin ( ALB), total cholesterol (CHOL) and C-creative protein (CRP) were measured for all the patients on the 1st, 3rd, 7th days after admission, before discharge and prior to death, respectively. Results Scores of APACHE Ⅱ were significantly higher in SIRS and the dead groups than those in non-SIRS and the survival groups (P ＜0. 05 ). Serum level of albumin was significantly lower in SIRS and the dead groups than that in non-SIRS and the survival groups on the 7th day after admission (SIRS vs. non-SIRS: F=9.812, P=0.035; the dead vs. the survival: F =45.285, P=0. 003). Change in serum level of prealbumin was the same as the level of albumin, with significant difference between various groups since the 3rd day after admission ( P ＜ 0. 05 ). Significant time effects could be found in the dead and survival groups (for the dead group: F = 19. 188, P = 0. 000; and for the survival group: F = 47. 250, P ＜ 0. 01 ). Multiple regression analysis showed that serum levels of prealbumin and total cholesterol correlated with scores of APACHE Ⅱ[with a regression formula of scores of APACHE Ⅱ = 52.032-21.407 PAB-8.971 CHOL (R2 =0.801, F=48.016, P =0.023)]. Logistic regression analysis showed that low level of prealbumin and high scores of APACHE Ⅱ both were predictors for survival of SIRS patients, with an overall accuracy of 77. 1 percent, 73.5 percent for survival and 79. 5 percent for death prediction. Conclusions Severe malnutrition can be found in patients with SIRS and serum level of prealbumin can be used to evaluate their nutritional status and severity of the disease. High scores of APACHE Ⅱ combined with low serum level of prealbumin can predict prognosis of the patients. Key words: Sepsis; Systemic inflammatory response syndrome; Prognosis

The role of tissue factor in systemic inflammatory response syndrome

Tissue factor (TF) is a major initiator of extrinsic pathway of blood coagulation. A dual role of TF in the extensive crosstalk between blood coagulation and inflammation has recently become apparent. The majority of the cases of systemic inflammatory response syndrome, disseminated intravascular coagulation, and sepsis are accompanied by hyperactivation of TF in circulating monocytes and damaged tissue. Systemic Gram-negative infection induces expression of TF by vascular cells. In addition to extrinsic coagulation pathway, TF induces proinflammatory signaling cascade originating from activation of protease-activated receptors. Because TF-activated proteolytic cascade is placed in a nexus between coagulation and inflammation, early modulation of TF activity presently becomes a tempting experimental therapeutic strategy in systemic inflammatory response syndrome patients.

Dynamic changes in plasma levels of urokinase type plasminogen activator and urokinase type plasminogen activator receptor in patients with systemic inflammatory response syndrome

To study the dynamic changes in plasma levels of urokinase type plasminogen activator (uPA) and urokinase type plasminogen activator receptor (uPAR) and their influence on prognosis in patients with systemic inflammatory response syndrome (SIRS). In this study, a prospective clinical case control study was adopted. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS: SIRS patients (n=50) and non-SIRS patients (n=35). SIRS patients were again divided into SIRS group (n=26) and SIRS complicated by multiple organ dysfunction syndrome (MODS) group (n=24) by their severity, and survival group (n=35) and non-survival group (n=15) by their outcome . The control group comprised of 30 healthy blood donors. Venous blood samples of about 2 ml were collected at the time when non-SIRS patients were admitted, and blood samples were collected in SIRS patients on 1,3, 5 and 7 days when SIRS was diagnosed, and in the healthy control group blood samples were collected when they visited the General Health Check-up Division at our hospital. Plasma levels of uPA and uPAR were measured by enzyme-linked immunosorbent assay (ELISA), and relationship between plasma level of uPAR and acute physiology and chronic health evaluation II(APACHEII) score was analyzed using Pearson correlation. The plasma levels of uPA and uPAR in patients of SIRS and MODS were obviously higher compared with non-SIRS and healthy controls [uPA (μg/L): 1.208±0.264, 1.120±0.276 vs. 0.744±0.190, 0.782±0.257; uPAR (μg/L): 3.704±1.018, 4.970±1.284 vs. 1.892±0.476, 1.823± 0.797, all P<0.01]. The plasma level of uPAR in MODS group was obviously higher than that of SIRS group (P<0.01). The plasma level of uPA (μg/L) in non-survival group was markedly elevated on 5 days and 7 days compared to survival group (5 days: 1.177±0.185 vs. 0.856±0.223, 7 days: 1.377±0.185 vs. 0.836±0.223, both P<0.01). The plasma level of uPAR (μg/L) in patients of non-survival group was obviously higher compared with survival group on 1, 3, 5 and 7 days (1 day: 5.301±1.410 vs. 3.888±1.015, 3 days: 4.017±0.898 vs. 2.994±0.638, 5 days: 5.032±1.238 vs. 2.536±1.017, 7 days: 5.232±1.238 vs. 3.536±1.017, all P<0.01). Correlation analysis showed that there was positive correlation between uPAR level and APACHEII score (r=0.640, P<0.01). Coagulopathy is present in SIRS patients, the plasma levels of uPA and uPAR are high in patients with SIRS, and the increase of uPAR in patients with SIRS indicates a poor prognosis.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome

Objectives This study was intended to investigate the value of suPAR, C-reactive protein (CRP) and procalcitonin (PCT) in the determination and prognosis of systemic inflammatory response syndrome (SIRS) patients. Methods The study was performed among patients with at least two SIRS criteria. PCT, CRP and suPAR were analyzed from the blood specimens taken. Results Eighty-five patients were enrolled in the SIRS group (44 bacteremia, 20 urinary tract infection, 12 pneumonia and 9 non-infection), and 53 individuals in the control group. A significant correlation was determined between suPAR, PCT and CRP values in both groups (P < 0.0001). A suPAR cutoff value of 2.8 ng/mL was associated with an NPV of 87% and PPV of 91%, with 92% sensitivity and 85% specificity. A relatively high suPAR level that might predict fatality was also determined in fatal cases (P = 0.001). Conclusion suPAR possesses high sensitivity and specificity levels in terms of differential diagnosis, and high suPAR levels can predict fatality.

High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation

To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS). Prospective, placebo-controlled, randomized, single-blinded phaseII study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age >18years, and Acute Physiology and Chronic Health Evaluation (APACHE)II ≥15 (n=35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000μg Se followed by continuous infusion of 1,600μg Se per day for 10days. Blood samples were analyzed before randomization (day0) then at days3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints. SOFA score decreased significantly in the selenite group at day10 (1.3±1.2 versus 4.6±2.0, p=0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p=0.04), and hospital-acquired pneumonia was lower after ICU discharge (p=0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day7 (0.62±0.24 versus 0.28±0.14U/mL, p=0.001) in the selenite group. No adverse events attributable to selenite were observed. Daily infusion of 1,600μg Se (as selenite), following an initial bolus of 2,000μg, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU.

Prognostic significance of urokinase-type plasminogen activator and its receptor in patients with systemic inflammatory response syndrome.

This study aimed to determine the plasma levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), D-dimer, IL-6 and TNF-α and observe the relations among uPA, uPAR, D-dimer, IL-6 and TNF-α in patients with systemic inflammatory response syndrome (SIRS). A prospective, clinical case-control study was conducted in patients with SIRS at age of more than 55 years old treated during 2008-2010 at Wuhan Central Hospital. Venous blood samples were collected by routine venipuncture. Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS: SIRS patients from intensive care units (n=50), and non-SIRS patients from medical wards (n=35). Thirty healthy blood donors who visited the General Health Check-up Division at Wuhan Central Hospital served as controls. Excluded from the study were (1) those patients with pregnancy; (2) those with cancer; (3) those died after admission into the ICU in 7 days; (4) those received cardiopulmonary resuscitation; (5) those who had previous blood system diseases; and (6) those with SIRS before admission into the ICU. The levels of uPA, uPAR, D-D, IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed using SPSS version 17.0 and expressed as mean ± standard. Student's t test and the Mann-Whitney U test were used in the analysis. The relations of uPA, uPAR and D-dimer, IL-6 TNF-α levels were analyzed using Spearman's rank-order correlation coefficient test. The plasma levels of uPA, uPAR, D-dimer,IL-6 and TNF-α in the patients with SIRS were obviously higher than those in the non-SIRS patients and controls (P<0.001). Correlation analysis showed a positive correlation between uPAR and IL-6 levels (r=0.395, P=0.004) and between uPAR and TNF-α levels (r=0.606, P<0.001), but no correlation between uPAR and D-dimer levels (r=0.069, P=0.632). No correlation was observed between uPA, D-dimer, IL-6 and TNF-α levels (P>0.05). The establishment of ROC curve was based on the levels of uPAR, D-dimer, IL-6 and TNF-α in 24 hours for the diagnosis of multiple organ dysfunction syndrome (MODS), and the ROC areas under the curve were 0.76, 0.58, 0.86 and 0.83, respectively. uPA and uPAR play a major role in patients with SIRS in the process of coagulation disorder, but the mechanism of SIRS is not the same. uPAR may play a central role in the development of SIRS to MODS.

Correlation between Complicated Diverticulitis and Visceral Fat

The aim of this study was to examine the relationship of complications related to diverticulitis and visceral obesity. The study was based on a retrospective case note review conducted at the Hanyang University Hospital. Patients were diagnosed with diverticulitis based on clinical symptoms and abdominal computed tomography (CT) findings and divided into two groups: those admitted with complicated diverticulitis and those with a simple diverticulitis episode. We compared the body mass index (BMI) and degree of visceral obesity, measured by abdominal CT. The study included 140 patients, 87 (62.1%) were simple diverticulitis and 53 (37.9%) were complicated diverticulitis. In the complicated diverticulitis group, 9 (6.4%) cases were recurrent, 29 (20.7%) were perforation or abscess patients, and 28 (20%) were patients with systemic inflammatory response syndrome (SIRS). Of the SIRS patients, 13 were involved in other complication groups. When comparing in the two groups, the complicated diverticulitis group had a significantly higher visceral fat area (128.57 cm2 vs 102.80 cm2, P = 0.032) and a higher ratio of visceral fat area/subcutaneous fat area (0.997 vs 0.799, P = 0.014). Visceral obesity is significantly associated with complications of diverticulitis.

Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients

The expression of Fc receptors for IgG (FcγRs) on neutrophils, including CD16, CD32 and CD64, may be modulated in response to sepsis. We investigated the expression of FcγRs on neutrophils and procalcitonin (PCT) as biomarkers of sepsis among critically ill patients. This prospective study was conducted in a 24-bed respiratory intensive care unit between July 2007 and June 2008. Critically ill patients requiring mechanical ventilation were enrolled and categorized into three groups: those with systemic inflammatory response syndrome (SIRS), those with severe sepsis and those with septic shock. Expression of FcγRs on neutrophils was quantitatively measured by flow cytometry immediately after enrolment of the patient. Serum PCT levels were also measured. Receiver operating characteristic (ROC) curves were used to evaluate the performance of FcγR expression and PCT as biomarkers of sepsis. Sixty-six patients were enrolled, including 11 with SIRS, 31 with severe sepsis and 24 with septic shock. Nineteen healthy volunteers served as normal controls. CD64 was upregulated, CD16 was downregulated and CD32 remained unchanged during sepsis. CD64 expression and the ratio of CD64/CD16 increased significantly with the severity of sepsis. However, serum PCT levels were not significantly different between SIRS and severe sepsis patients. CD64, CD64/CD16 and PCT all significantly predicted sepsis, septic shock and bacteraemia. As assessed using ROC curves, CD64 was better than PCT for differentiating SIRS from severe sepsis and septic shock. CD64 and CD64/CD16 were associated with mortality. CD64 and CD16 were differentially modulated by sepsis. CD64, CD64/CD16 and PCT may be biomarkers of sepsis. CD64 was better than PCT for identifying patients who required treatment with antibiotics.

Peripheral photoplethysmography variability analysis of sepsis patients

Sepsis is associated with impairment in autonomic regulatory function. This work investigates the application of heart rate and photoplethysmogram (PPG) waveform variability analysis in differentiating two categories of sepsis, namely systemic inflammatory response syndrome (SIRS) and severe sepsis. Electrocardiogram-derived heart period (RRi) and PPG waveforms, measured from fingertips (Fin-PPG) and earlobes (Ear-PPG), of Emergency Department sepsis patients (n=28) with different disease severity, were analysed by spectral technique, and were compared to control subjects (n=10) in supine and 80° head-up tilted positions. Analysis of covariance (ANCOVA) was applied to adjust for the confounding factor of age. Low-frequency (LF, 0.04-0.15Hz), mid-frequency (MF, 0.09-0.15Hz) and high-frequency (HF, 0.15-0.60Hz) powers were computed. The normalised MF power in Ear-PPG (MFnu(Ear)) was significantly reduced in severe sepsis patients with hyperlactataemia (lactate>2mmol/l), compared to SIRS patients (P<0.05). Moreover, in a group of normal controls, MFnu(Ear) was not altered by head-up tilting (P>0.05), suggesting that there may be a link between 0.1Hz ear blood flow oscillation and tissue metabolic changes in sepsis, in addition to autonomic factors. The study highlighted the value of PPG spectral analysis in the non-invasive assessment of peripheral vascular regulation in sepsis patients, with potential implications in monitoring the progression of sepsis.

Direct Hemoperfusion Using Immobilized Polymyxin B in Patients with Rapidly Progressive Interstitial Pneumonias: A Retrospective Study

Background: Rapidly progressive interstitial pneumonia (IP), including acute exacerbation of IP, has a high mortality rate. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) was recently identified as an effective treatment for sepsis-associated acute respiratory distress syndrome. However, little is known about the effectiveness of PMX-DHP for rapidly progressive IP. Objectives: The present study investigates whether PMX-DHP is safe and effective against rapidly progressive IP. Methods: We retrospectively examined the effects of PMX-DHP in 33 consecutive patients with rapidly progressive IP who were resistant to steroid pulse therapy. Patients were hospitalized at Nagasaki University Hospital between 2006 and 2009. Results: Seventy-two hours after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–153 mm Hg) had significantly improved. One week after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–227 mm Hg), the alveolar-arterial difference of oxygen (median 371–177 mm Hg) and the number of positive criteria for systemic inflammatory response syndrome had significantly improved, despite the ineffectiveness of corticosteroid pulse therapy. The serum level of monocyte chemotactic protein 1 was significantly decreased immediately after PMX-DHP. Conclusions: PMX-DHP was safe and effective in improving oxygenation and systemic inflammatory response syndromein patients with rapidly progressive IP. The beneficialeffects of PMX-DHP may be at least partially due to the inhibition of monocyte activation.

Vitamin B12: the forgotten micronutrient for critical care

To analyse the anti-inflammatory and antioxidant properties of vitamin B12 and evaluate current evidence on vitamin B12 status in the critically ill with systemic inflammation. Data on vitamin B12 status of intensive care unit patients are scarce. Cobalamins could potentially be useful agents for inhibiting nitric oxide synthase and nitric oxide production, controlling nuclear factor-kappa B activation, and restoring optimal bacteriostasis and phagocytosis in which transcobalamins play a proven role. The antioxidant properties of vitamin B12, with a glutathione-sparing effect, are secondary to stimulation of methionine synthase activity and reaction with free oxygen or nitrogen radicals. Large parenteral doses are routinely administered for cyanide poisoning, with only mild, reversible side-effects. Current evidence suggests that high-dose parenteral vitamin B12 may prove an innovative approach to treat critically ill systemic inflammatory response syndrome patients, especially those with severe sepsis/septic shock. In this setting, vitamin B12 and transcobalamins could modulate systemic inflammation contributing to the anti-inflammatory cascade and potentially improve outcome. Despite evidence from animal studies, so far there are no clinical intervention trials that have studied vitamin B12 as a pharmaconutrient strategy for critical care. Well designed animal and clinical studies are required to clarify several outstanding questions on the optimal posology, safety, and efficacy of high-dose vitamin B12 in the critically ill.