Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis

Background Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. the aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction.Methods A total of 41 patients were prospectively enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. A total of 17 healthy volunteers were included as a control group. Patients were admitted to the Intensive Care Units and Emergency Rooms of Hospital São Paulo ( Federal University of São Paulo) and Hospital Santa Marcelina, São Paulo, Brazil. Toll- like receptor ( TLR) 2, TLR4, CD11b, CD11c and CD66b expression on neutrophil surfaces and oxidative metabolism measured by non- fluorescent dichlorofluorescein ( DCFH) oxidation in neutrophils and monocytes, using whole blood, were evaluated using flow cytometry. Organ dysfunction was measured using the sepsis- associated organ failure assessment ( SOFA) score.Results TLR2 expression on neutrophils was found to be downregulated in septic shock patients compared to healthy volunteers ( p = 0.05). No differences were found in CD11b and CD11c expression. CD66b expression was increased in the patient group compared to the control group ( p = 0.01). Neutrophil and monocyte oxidative burst was increased in septic patients compared to the control group at baseline and after stimulation with phorbol myristate acetate ( PMA), formylmethionylleucyl- phenylalanine ( fMLP), lipopolysaccharide ( LPS) and Staphylococcus aureus ( p 7 was higher than in patients with SOFA scores < 7, both in neutrophils and monocytes. However, oxidative burst in patients with sepsis was as high as in septic shock.Conclusion Surface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered. ROS generation is upregulated both in neutrophils and monocytes in septic patients, and it is differently modulated depending on the stage of the disease and the stimuli used.Universidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Intens Care Unit, São Paulo, BrazilHosp St Marcelina, Intens Care Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Intens Care Unit, São Paulo, BrazilWeb of Scienc

Rate and time to develop first central line-associated bloodstream infections when comparing open and closed infusion containers in a Brazilian Hospital

The objective of the study was to determine the effect of switching from an open (glass or semi-rigid plastic) infusion container to a closed, fully collapsible plastic infusion container (Viaflex®) on rate and time to onset of central lineassociated bloodstream infections (CLABSI). An open-label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in three intensive care units in Brazil. The CLABSI rate using open infusion containers was compared to the rate using a closed infusion container. Probability of acquiring CLABSI was assessed over time and compared between open and closed infusion container periods; three-day intervals were examined. A total of 1125 adult ICU patients were enrolled. CLABSI rate was significantly higher during the open compared with the closed infusion container period (6.5 versus 3.2 CLABSI/1000 CL days; RR=0.49, 95%CI=0.26- 0.95, p=0.031). During the closed infusion container period, the probability of acquiring a CLABSI remained relatively constant along the time of central line use (0.8% Days 2-4 to 0.7% Days 11-13) but increased in the open infusion container period (1.5% Days 2-4 to 2.3% Days 11-13). Combined across all time intervals, the chance of a patient acquiring a CLABSI was significantly lower (55%) in the closed infusion container period (Cox proportional hazard ratio 0.45, p= 0.019). CLABSIs can be reduced with the use of full barrier precautions, education, and performance feedback. Our results show that switching from an open to a closed infusion container may further reduce CLABSI rate as well as delay the onset of CLABSIs. Closed infusion containers significantly reduced CLABSI rate and the probability of acquiring CLABSI

Upregulation of reactive oxygen species generation and phagocytosis, and increased apoptosis in human neutrophils during severe sepsis and septic shock

We evaluated neutrophil activation by measuring its phagocytic ability and oxidative burst activity in 16 patients with sepsis and 16 healthy volunteers. We also focused on neutrophil apoptosis as a regulatory mechanism of the inflammatory response. Neutrophil phagocytosis was evaluated by the detection of propidium iodide (PI)-labeled Staphylococcus aureus added to whole blood. Reactive oxygen species (ROS) formation was quantified by measuring the oxidation of 2',7' dichlorofluorescein diacetate (DCFH-DA) at baseline and after cell stimulation with phorbol myristate acetate (PMA), and bacterial cells (killed S. aureus) or products (lipopolysaccharide [LPS] and N-formyl-methionyl-leucylphenylalanine [FMLP]). Apoptosis was assessed in neutrophils stained with annexin V and Pl. Neutrophil phagocytic ability was increased in patients with sepsis compared with healthy controls (median geometric mean fluorescence intensity [GMFI] was 101.9 and 54.7, respectively; P = 0.05). ROS formation was enhanced in patients with sepsis compared with healthy volunteers at baseline (median GMFI 275.6 and 52.1, respectively; P < 0.001), and after stimulation with S. aureus (median GMFI 2395.8 and 454.9, respectively; P < 0.001), PMA (median GMFI 1120.6 and 307.5, respectively; P = 0.003), FMLP (median GMFl 792.4 and 123.2, respectively; P < 0.001), and LPS (median GMFI 624.8 and 144.8, respectively; P < 0.001). Early neutrophil apoptosis was increased in patients with sepsis compared with healthy volunteers (median 11.3% and 9.1%, respectively; P = 0.03). These data demonstrate that neutrophil function is enhanced in patients with sepsis. Additionally, circulating neutrophils from patients with sepsis presented with increased early apoptosis, which may be consequence of a regulatory mechanism of the inflammatory response

Device-associated infection rates in intensive care units of Brazilian hospitals: findings of the International Nosocomial Infection Control Consortium

Objectives. To measure device-associated infection (DAI) rates, microbiological profiles, bacterial resistance, extra length of stay, and attributable mortality in intensive care units (ICUs) in three Brazilian hospitals that are members of the International Nosocomial Infection Control Consortium (INICC). Methods. Prospective cohort surveillance of DAIs was conducted in five ICUs in three city hospitals in Brazil by applying the definitions of the U. S. Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System (CDC-NNIS). Results. Between April 2003 and February 2006, 1 031 patients hospitalized in five ICUs for an aggregate 10 293 days acquired 307 DAIs, a rate of 29.8% or 29.8 DAIs per 1 000 ICU days. The ventilator-associated pneumonia (VAP) rate was 20.9 per 1 000 ventilator-days; the rate for central venous catheter-associated bloodstream infections (CVC-BSI) was 9.1 per 1 000 catheter-days; and the rate for catheter-associated urinary tract infections (CAUTI) was 9.6 per 1 000 catheter-days. Ninety-five percent of all Staphylococcus aureus DAIs were caused by methicillin-resistant strains. Infections caused by Enterobacteriaceae were resistant to ceftriaxone in 96.7% of cases, resistant to ceftazidime in 79.3% of cases, and resistant to piperacillin-tazobactam in 85.7% of cases. Pseudomonas aeruginosa DAIs were resistant to ciprofloxacin in 71.3% of cases, resistant to ceftazidime in 75.5% of cases, and resistant to imipenem in 27.7% of cases. Patients with DAIs in the ICUs of the hospitals included in this study presented extra mortality rates of 15.3% (RR 1.79, P = 0.0149) for VAP, 27.8% (RR 2.44, P = 0.0004) for CVC-BSI, and 10.7% (RR 1.56, P = 0.2875) for CAUTI. Conclusion. The DAI rates were high in the ICUs of the Brazilian hospitals included in this study. Patient safety can be improved through the implementation of an active infection control program comprising surveillance of DAIs and infection prevention guidelines. These actions should become a priority in every country

Neutrophil reactive oxygen species (ROS) generation in patients across the continuum of sepsis

ROS generation was measured by 2',7'dichlorofluorescein (DCFH) metabolism. Neutrophils were gated based on FSC versus SSC parameters and the expression of CD14 on cell surface. ROS generation was analyzed in histograms and expressed as the geometric mean fluorescence intensity (GMFI). *p < 0.01 compared to healthy volunteers; #p < 0.05 compared to the severe sepsis group; §p < 0.05 compared to the septic shock group.<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Correlation between formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species (ROS) generation and sepsis-associated organ failure assessment (SOFA) score in neutrophils and monocytes in patients with severe sepsis and septic shock

<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Correlation between neutrophil and monocyte oxidative metabolism in septic patients at baseline (A) and after stimuli with phorbol myristate acetate (PMA) (B), formyl-methionyl-leucyl-phenylalanine (fMLP) (C), lipopolysaccharide (LPS) (D) and (E)

<p><b>Copyright information:</b></p><p>Taken from "Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis"</p><p>http://ccforum.com/content/12/1/R25</p><p>Critical Care 2008;12(1):R25-R25.</p><p>Published online 13 Feb 2008</p><p>PMCID:PMC2374621.</p><p></p

Creative Responses to Separation: Israeli and Palestinian Joint Activism in Bil\u27in

This article examines creative ways in which Israeli and Palestinian activists engage with each other and the powers seeking to separate them in their nonviolent struggles for a just and lasting peace. Using the geopolitical theory of territoriality, the article briefly examines a number of administrative, physical, and psychological barriers facing joint activism and the strategies activists use to counteract them. Drawing on nonviolent theory and practice, the article analyzes how activists exert power through the creative use of symbols and practices that undermine the legitimacy of occupation policies. Based on fieldwork conducted in 2004-05 and July 2006, the article explores the implications of this activism on conceptions of identity, and strategies for restarting a moribund peace process. The relative \u27success\u27 of sustained joint action in Bil\u27in can provide scholars and policymakers with innovative approaches for addressing some of the outstanding issues needing to be addressed by official negotiators. Although government bodies are more constrained than activists, the imaginative means of engaging with the system- and the reframing of issues through the redeployment of \u27commonplaces\u27-can perhaps provide inspiration, if not leverage, for thinking outside of the box