WorldWideScience

Sample records for controls microbial sepsis

  1. Sepsis and septic shock

    Science.gov (United States)

    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  2. Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

    Science.gov (United States)

    Hasibuan, B. S.

    2018-03-01

    Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

  3. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    OBJECTIVE: To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis. DESIGN: A prospective study of mortality in patients with sepsis whose serum levels of sL-selectin were measured on admission to an intensive care unit (ICU) and 4 days later. Follow-up data......, and 3 and 12 months after admission. Serum sL-selectin levels were significantly lower in the patients than in the controls. Sepsis nonsurvivors had significantly lower levels than survivors. Efficiency analysis and receiver operation characteristics showed that the ideal cutoff point for s......L-selectin as a test for sepsis survival was 470 ng/ml. The accumulated mortality in patients with subnormal sL-selectin levels on admission was significantly increased. No correlation was found between clinical or paraclinical markers, including SAPS II and sL-selectin, and no relationship to the microbial diagnosis...

  4. Possible Causes of Ileal Injury in Two Models of Microbial Sepsis and Protective Effect of Phytic Acid

    Directory of Open Access Journals (Sweden)

    Rasha Rashad Ahmed

    2010-03-01

    Full Text Available Background: Sepsis related-multiple organ dysfunction is associatedwith ileum injury. We aimed to determine the causes ofileal injury in two models of microbial sepsis resulted from infectionwith Aeromonas hydrophila or its endotoxin. We alsoevaluated the protective effect of phytic acid.Methods: Thin sections of ileum from 60 Swiss male mice incontrol, bacteria-infected or lipopolysaccharides (LPS andbacteria-infected or LPS-infected co-administered with phyticacid were subjected to histopathological and TdT-mediateddUTP nick-end labeling (TUNEL assay for apoptotic cellsdetection while ultra thin sections were stained with uranylacetate and lead citrate for cytological changes examination.Also, ileum images were exposed to the image analysis softwareto determine some related morphometric measures.Results: Necrosis and apoptosis were observed in ileum injuryin both examined sepsis models. The ileum injury was moresevere in LPS model. Phytic acid showed the ability to attenuateileum injury in Aeromonas hydrophila and its endotoxinmodels of sepsis after four weeks administration where itssupplementation significantly minimized the histopathologicaland cytological complications and morphometric alterationsresulted from the injury.Conclusion: The protective effects of phytic acid may becaused by increased mucous secretion, decreased apoptoticindex, attenuating the inflammatory and lymphocytic cellscount or increasing the renewal of the crypt cells and villousepithelial cells proliferation.

  5. Diagnosis and management of sepsis

    Science.gov (United States)

    Arifin

    2018-03-01

    Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

  6. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study.

    Directory of Open Access Journals (Sweden)

    Mohammod Jobayer Chisti

    Full Text Available In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children.In this retrospective case-control study SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50 with those without severe sepsis (controls = 354. Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline.The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001. In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons.We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.

  7. Glucocorticosteroids for sepsis

    DEFF Research Database (Denmark)

    Volbeda, M; Wetterslev, J; Gluud, C

    2015-01-01

    INTRODUCTION: Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light...... for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary......-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. CONCLUSION: Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results...

  8. Severe maternal sepsis in the UK, 2011-2012: a national case-control study.

    Directory of Open Access Journals (Sweden)

    Colleen D Acosta

    2014-07-01

    Full Text Available In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK.A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2-5.2 per 10,000 maternities; 71 (19.5% women developed septic shock; and five (1.4% women died. Genital tract infection (31.0% and the organism Escherichia coli (21.1% were most common. Women had significantly increased adjusted odds ratios (aORs of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82-2.51, were primiparous (aOR = 1.60; 95% CI 1.17-2.20, had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01-1.94, had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11-17.97, or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32-4.70, pre-labour cesarean (aOR = 3.83; 95% CI 2.24-6.56, or cesarean after labour onset (aOR = 8.06; 95% CI 4.65-13.97. Median time between delivery and sepsis was 3 d (interquartile range = 1-7 d. Multiple pregnancy (aOR = 5.75; 95% CI 1.54-21.45 and infection with group A streptococcus (aOR = 4.84; 2.17-10.78 were associated with progression to septic shock; for 16 (50% women with a group A streptococcal infection there was <2 h-and for 24 (75% women, <9 h-between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%.For each maternal sepsis death, approximately 50 women have life-threatening morbidity from sepsis. Follow-up to ensure infection is eradicated is important. The

  9. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  10. Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Robert Chase Cockrell

    2018-02-01

    Full Text Available Sepsis, a manifestation of the body's inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical "sepsis," and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems. In this work, we consider the human immune system to be a random dynamical system, and investigate its potential controllability using an agent-based model of the innate immune response (the Innate Immune Response ABM or IIRABM as a surrogate, proxy system. Simulation experiments with the IIRABM provide an explanation as to why single/limited cytokine perturbations at a single, or small number of, time points is unlikely to significantly improve the mortality rate of sepsis. We then use genetic algorithms (GA to explore and characterize multi-targeted control strategies for the random dynamical immune system that guide it from a persistent, non-recovering inflammatory state (functionally equivalent to the clinical states of systemic inflammatory response syndrome (SIRS or sepsis to a state of health. We train the GA on a single parameter set with multiple stochastic replicates, and show that while the calculated results show good generalizability, more advanced strategies are needed to achieve the goal of adaptive personalized medicine. This work evaluating the extent of interventions needed to control a simplified surrogate model of sepsis provides insight into the scope of the clinical challenge, and can serve as a guide on the path towards true "precision control" of

  11. Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation.

    Science.gov (United States)

    Cockrell, Robert Chase; An, Gary

    2018-02-01

    Sepsis, a manifestation of the body's inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical "sepsis," and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems. In this work, we consider the human immune system to be a random dynamical system, and investigate its potential controllability using an agent-based model of the innate immune response (the Innate Immune Response ABM or IIRABM) as a surrogate, proxy system. Simulation experiments with the IIRABM provide an explanation as to why single/limited cytokine perturbations at a single, or small number of, time points is unlikely to significantly improve the mortality rate of sepsis. We then use genetic algorithms (GA) to explore and characterize multi-targeted control strategies for the random dynamical immune system that guide it from a persistent, non-recovering inflammatory state (functionally equivalent to the clinical states of systemic inflammatory response syndrome (SIRS) or sepsis) to a state of health. We train the GA on a single parameter set with multiple stochastic replicates, and show that while the calculated results show good generalizability, more advanced strategies are needed to achieve the goal of adaptive personalized medicine. This work evaluating the extent of interventions needed to control a simplified surrogate model of sepsis provides insight into the scope of the clinical challenge, and can serve as a guide on the path towards true "precision control" of sepsis.

  12. [Chromatographic mass spectrometric determination of low-molecular-weight aromatic compounds of microbial origin in the serum from patients with sepsis].

    Science.gov (United States)

    Beloborodova, N V; Arkhipova, A S; Beloborodov, D M; Boĭko, N B; Mel'ko, A I; Olenin, A Iu

    2006-02-01

    The investigation quantitatively determined the content of low-molecular-weight aromatic compounds of microbial origin in the sera of 34 individuals by chromatographic mass spectrometry. An "Agilent Technogies 6890N" gas chromatograph with a 5973 mass selective detector was applied; chromatographic separation of components was effected on an Hp-5MS quartz capillary column. Aromatic small molecules originating from microbes (SMOM) were determined in the sera of 7 patients with sepsis. The diagnosis of sepsis was documented by the presence of the systemic inflammation syndrome and by that of bacteriemia and/or artificial ventilation-associated pneumonia along with the level of procalcitonin of higher than 10 ng/ml. The levels of aromatic SMOM were compared in 10 healthy donors, 8 preoperative cardiosurgical patients, and 9 patients with different abnormalities without sepsis treated in an intensive care unit (ICU). Serum phenylacetic and 3-phenylpropionic acids were found to be prevalent in the healthy donors and postoperative cardiosurgical patients. In ICU patients with different complications without sepsis, more than half the compounds under study were undetectable, the others were found in very low concentrations, which may be accounted for by antibiotic therapy. At the same time, almost the whole spectrum of the test compounds (other than 3-phenylpropionic acid) with the highest concentrations of 3-phenyllactic, p-hydroxyphenylacetic, 3-(p-hydroxyphenyl)lactic and 2-hydroxybutanic acids, was detectable in septic patients receiving a more intensive therapy. The differences were statistically significant (by the Mann-Whitney U-test; p < 0.05). By taking into account the potentially high biological activity of the test compounds, studies are to be continued in this area.

  13. Clinical management of sepsis.

    Science.gov (United States)

    Lam, S M; Lau, A Cw; Lam, R Pk; Yan, W W

    2017-06-01

    Sepsis is a common cause of hospital admission worldwide and contributes significantly to morbidity and mortality. The definition of sepsis has evolved from the 1991 American College of Chest Physicians/Society of Critical Care Medicine definition based on the criteria of systemic inflammatory response syndrome, to the 2016 Sepsis-3 definition that incorporates the Sequential Organ Failure Assessment score. The landmark trial on protocolised early goal-directed therapy was published in 2001, but three subsequent multicentre randomised controlled trials (ProCESS, ARISE, and ProMISe) in 2014-2015 did not confirm a survival benefit with protocolised care. Over the years, there has been considerable improvement in sepsis outcome and management that hinges on early detection; timely source control; prompt, appropriate, and correctly dosed antibiotics; aggressive fluid resuscitation; and shock reversal. These are all directed by repeated bedside assessment. This article summarises recent developments and landmark trials that should guide current sepsis management.

  14. Severe maternal sepsis in the UK, 2011-2012: a national case-control study.

    Science.gov (United States)

    Acosta, Colleen D; Kurinczuk, Jennifer J; Lucas, D Nuala; Tuffnell, Derek J; Sellers, Susan; Knight, Marian

    2014-07-01

    In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2-5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82-2.51), were primiparous (aOR = 1.60; 95% CI 1.17-2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01-1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11-17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32-4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24-6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65-13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1-7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54-21.45) and infection with group A streptococcus (aOR = 4.84; 2.17-10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors' Summary.

  15. Evaluation of efficacy of skin cleansing with chlorhexidine in prevention of neonatal nosocomial sepsis - a randomized controlled trial.

    Science.gov (United States)

    Gupta, Basudev; Vaswani, Narain Das; Sharma, Deepak; Chaudhary, Uma; Lekhwani, Seema

    2016-01-01

    The aim of this study was to evaluate the efficacy of skin cleansing with chlorhexidine (CHD) in the prevention of neonatal nosocomial sepsis - a randomized controlled trial. This study design was a randomized controlled trial carried out in a tertiary care center of north India. About 140 eligible neonates were randomly allocated to either the subject area group (wiped with CHD solution till day seven of life) or the control group (wiped with lukewarm water). The primary outcome studied was to determine the decrease in the incidence of neonatal nosocomial sepsis (blood culture proven) in the intervention group. Out of 140 enrolled neonates, 70 were allocated to each group. The ratio of positive blood culture among the CHD group was 3.57%, while the ratio of positive blood culture among the control group was 6.85%. There was trending towards a reduction in blood culture proven sepsis in the intervention group, although the remainder was not statistically significant. A similar decreasing trend was observed in rates of skin colonization, duration of hospital stay, and duration of antibiotic treatment. CHD skin cleansing decreases the incidence of blood culture sepsis and could be an easy and cheap intervention for reducing the neonatal sepsis in countries where the neonatal mortality rate is high because of sepsis.

  16. Microbial control of pollution

    Energy Technology Data Exchange (ETDEWEB)

    Fry, J C; Gadd, G M; Herbert, R A; Jones, C W; Watson-Craik, I A [eds.

    1992-01-01

    12 papers are presented on the microbial control of pollution. Topics covered include: bioremediation of oil spills; microbial control of heavy metal pollution; pollution control using microorganisms and magnetic separation; degradation of cyanide and nitriles; nitrogen removal from water and waste; and land reclamation and restoration.

  17. Sepsis and Septic Shock Strategies.

    Science.gov (United States)

    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. THE STUDY OF SERUM PROCALCITONIN LEVEL IN CORRELATION WITH SEPSIS

    Directory of Open Access Journals (Sweden)

    Girish M

    2016-09-01

    Full Text Available BACKGROUND Sepsis refers to the systemic response to serious infection. It can be response to the infection caused by any class of microorganism. The presence of bacteraemia is an indicator of disseminated infection and generally indicates a poorer prognosis when associated with localised disease. This study was undertaken to study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. AIM To study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. MATERIALS AND METHODS Fifty patients of age more than 18 years with sepsis admitted in KMC Hospitals, Mangalore, from August 2008 to June 2010 were subjects in the study after due permission from institution and informed consent from the patients. Diagnosis of sepsis was made according to criteria by ACCP/SCCM definition for sepsis. Definitive aetiological diagnosis requires isolation of microorganism from the blood and local site of infection, Gram stain and culture of the material from the primary site of infection for the microbial aetiology was taken. Other appropriate laboratory investigations depending upon requirement were done as mentioned in the investigations. RESULTS Out of total 50 patients, 23 patients were in group of sepsis, 14 were in group of severe sepsis while 13 had septic shock. Maximum number of the study patients were in the age group of 51-60 years. 52% of the study patients were male and 48% were female. Most common symptom in patients with sepsis was fever. Most common sign in the patient with sepsis is tachycardia followed by high temperature and then tachypnoea. Most common source of sepsis was respiratory infection followed by UTI. CONCLUSION Our data suggest the possibility that the addition of Procalcitonin into the standard workup of critically ill patients with suspected sepsis could increase diagnostic certainty and improve patient management.

  19. Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

    Science.gov (United States)

    Acosta, Colleen D.; Kurinczuk, Jennifer J.; Lucas, D. Nuala; Tuffnell, Derek J.; Sellers, Susan; Knight, Marian

    2014-01-01

    Background In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. Methods and Findings A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was anyone with suspected sepsis. Signs of severe sepsis in peripartum women, particularly with confirmed or suspected group A streptococcal infection, should be regarded as an obstetric emergency. Please see later in the article for the Editors' Summary PMID:25003759

  20. Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α.

    Science.gov (United States)

    Shalova, Irina N; Lim, Jyue Yuan; Chittezhath, Manesh; Zinkernagel, Annelies S; Beasley, Federico; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Rapisarda, Annamaria; Chen, Jinmiao; Duan, Kaibo; Yang, Henry; Poidinger, Michael; Melillo, Giovanni; Nizet, Victor; Arnalich, Francisco; López-Collazo, Eduardo; Biswas, Subhra K

    2015-03-17

    Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1α (HIF1α) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. I costi della sepsi in Italia

    Directory of Open Access Journals (Sweden)

    C. Lucioni

    2001-09-01

    Full Text Available The aim of this study is to evaluate additional hospitalisation costs and intangible costs (mortality in patients with sepsis (intended as severe sepsis or sepsis shock in Italy. The evaluation is based on clinical data from the Italian Sepsis Study, a prospective, multicentre study conducted in 99 Intensive Care Units (ICUslocated across Italy. Each ICU enrolled the first two (or three patients admitted each month, during the year April 1993 to March 1994. In particular, data collected included the Average Length Of Stay (ALOS in ICU and later in the regular ward, and the mortality within four weeks and in hospital. Out of the 2,946 patients enrolled, 2,641 never developed sepsis and were considered as the control group (comparability was confirmed based on gender, age, and comorbidity. The additional (respective to the control group ALOSs of the patients with sepsis were valued in monetary terms using per diem full costs, inflated to 2000: 1,033.43 Euro for l day in ICU (published data and 299.54 Euro for l day in the regular ward (estimated data based on published materials. Statistical significance was tested with Student t test. The hospitalisation cost of a patient with sepsis (21,571.88 Euro is significantly higher (+86% than that patient without sepsis (11,590.84 Euro, due to a longer (+ 163% stay in the expensive ICU, not balanced by shorter stay in the regular ward. Also intangible costs are significantly higher: the risk for an ICU patient with sepsis to die in hospital is 3 times higher than that of an ICU patient without sepsis. In particular, those patients developing sepsis after admission are more costly and with a higher mortality risk.

  2. Clavanin bacterial sepsis control using a novel methacrylate nanocarrier

    Directory of Open Access Journals (Sweden)

    Saúde ACM

    2014-10-01

    Full Text Available Amanda CM Saúde,1 Alicia S Ombredane,1 Osmar N Silva,1 João ARG Barbosa,1,2 Susana E Moreno,3 Ana Claudia Guerra Araujo,4 Rosana Falcão,4 Luciano P Silva,4 Simoni C Dias,1 Octávio L Franco1,3 1Programa de Pós Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, FD, Brazil; 2Laboratório de Biofísica-Departamento de Biologia Celular-IB, Universidade de Brasília – UNB, DF, Brazil; 3Universidade Católica Dom Bosco – UCDB, Campo Grande, MS, Brazil; 4Empresa Brasileira de Pesquisa Agropecuária – EMBRAPA – Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil Abstract: Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w. Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and

  3. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

    Science.gov (United States)

    Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2009-06-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.

  4. Improving Outcomes in Patients With Sepsis.

    Science.gov (United States)

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

  5. Much Ado About the New Definitions of Sepsis

    Directory of Open Access Journals (Sweden)

    Copotoiu Sanda-Maria

    2016-04-01

    Full Text Available Following the publication of the new definition of sepsis (Sepsis-3, a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1, and subsequently revised in 2001 (Sepsis-2, the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs, that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.

  6. Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis.

    Science.gov (United States)

    Sarmiento, Elisa J; Moore, Justin Xavier; McClure, Leslie A; Griffin, Russell; Al-Hamdan, Mohammad Z; Wang, Henry E

    2018-04-21

    While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM 2.5 ) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM 2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM 2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM 2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM 2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m³; p = 0.28) and mean one-year PM 2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m³; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM 2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85⁻1.32). Similarly, there were no associations between one-year PM 2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78⁻1.18). In the REGARDS cohort, PM 2.5 air pollution exposure was not associated with risk of sepsis.

  7. Sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Gordon, Anthony C; De Backer, Daniel

    2016-01-01

    Sepsis is a major growing global burden and a major challenge to intensive care clinicians, researchers, guideline committee members and policy makers, because of its high and increasing incidence and great pathophysiological, molecular, genetic and clinical complexity. In spite of recent progress......, short-term mortality remains high and there is growing evidence of long-term morbidity and increased long-term mortality in survivors of sepsis both in developed and developing countries. Further improvement in the care of patients with sepsis will impact upon global health. In this narrative review...... and subsequent outcomes are to be improved in patients with sepsis....

  8. Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

    Science.gov (United States)

    Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

    2017-08-09

    Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

  9. Hemostasis and endothelial damage during sepsis.

    Science.gov (United States)

    Johansen, Maria Egede

    2015-08-01

    as infection severity. In the second study of the thesis, the role of endothelial damage during sepsis was explored. Levels of biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin (sTM), respectively) were determined in a cohort of 1103 critically ill patients. The results showed that only high levels of sTM were associated with a markedly increased risk of 90-day mortality, as well as multi-organ failure. The finding suggests that profound damage to the endothelium is centrally involved in the pathogenesis of death in sepsis. Thus, the endothelium may be a target for new interventions against sepsis. In the third study, we investigated, using a randomized controlled trial, how mild induced hypothermia (cooling to 32-34°C for 24 hours, MIH) influenced sepsis-related coagulopathy using TEG; functional coagulopathy improved in patients exposed to the intervention compared with the control group. This improvement of coagulopathy parameters during MIH persisted after rewarming. These results not only add to the understanding of the effect of hypothermia on the hemostatic system, but indicate that MIH reduces sepsis-related coagulopathy assessed by TEG. Overall, this thesis emphasizes that the role of the hemostatic system during sepsis is not only complex, but centrally involved in disease severity and prognosis. The endothelium seems to play a central role in the morbidity and mortality of sepsis, which cannot be explained simply by the presences of organ failure. Thus, restoring the broken endothelium and reducing coagulopathy appears to be essential in order to significantly improve sepsis out-comes. MIH could be a promising intervention in sepsis, in part due to the improvement of the coagulopathy. Despite the increased focus on the hemostatic system during sepsis, it seems that continued research on restoring disrupted hemostasis - including endothelial damage - is needed.

  10. Epidemiology of Adult-population Sepsis in India: A Single Center 5 Year Experience.

    Science.gov (United States)

    Chatterjee, Sharmila; Bhattacharya, Mahuya; Todi, Subhash Kumar

    2017-09-01

    Sepsis is a major worldwide cause of morbidity and mortality. Most sepsis epidemiologic data are from the Western literature. Sparse data from India describe the epidemiology of infection rather than sepsis which is a host response to infection. This study describes the epidemiology of sepsis in the Intensive Care Unit (ICU) of an Indian tertiary care hospital. A prospective study conducted between June 2006 and May 2011. All consecutively admitted patients during the 5 year study >=18 years of age were included and data obtained from hospital in-patient records. Variables measured were the incidence of severe sepsis, ICU, hospital, and 28-day mortality, the median length of ICU stay, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score, infection site, and microbial profile. There were 4711 admissions during the study with 282 (6.2%, 95% confidence interval 2.3, 13.1) admissions with severe sepsis. ICU mortality, hospital mortality, and 28-day mortality were 56%, 63.6%, and 62.8%, respectively. Predominant infection site was respiratory tract. The most common organisms were Gram-negative microbes. The most common microbe was Acinetobacter baumanni. Median APACHE II score on admission was 22 (interquartile range 16-28) and median length of ICU stay was 8 days. Severe sepsis attributable mortality was 85%. Severe sepsis is common in Indian ICUs and is mainly due to Gram-negative organisms. ICU mortality is high in this group and care is resource intensive due to increased length of stay.

  11. Sepsis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Sepsis KidsHealth / For Parents / Sepsis What's in this article? ... When to Call the Doctor Print What Is Sepsis? Sepsis is when the immune system responds to ...

  12. Sepsis

    Science.gov (United States)

    ... mild sepsis, but the mortality rate for septic shock is nearly 50 percent. Also, an episode of severe sepsis may ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  13. Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

    Science.gov (United States)

    Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

    2014-11-01

    Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

  14. Think Sepsis. Time Matters. PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This 60 second public service announcement is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  15. The effect of bacterial sepsis severity on triglyceride value

    Science.gov (United States)

    Fahila, R.; Kembaren, T.; Rahimi, A.

    2018-03-01

    Sepsis can increase the amount of triglyceride as well as change the functional and structural components of lipoproteins. The triglyceride level is directly proportional to the severity of sepsis and associated with a systemic inflammatory response. The study aims to determine the correlation between the severity of bacterial sepsis with triglyceride value. An observational study with case control design from January2017 to March 2017 in 30 sepsis and 30 non-sepsis patients at H. Adam Malik General Hospital Medan. We examined Procalcitonin (PCT) and triglyceride level on the 1st, 3rd and 5th day and then analyzed using MannWhitney to assess their correlation.The triglyceride value in the sepsis group was 120 ± 5.1 mg/dl on day 1, non-sepsis 117.53 ± 36.37mg/dl. However, on the fifth day, the sepsis group of triglyceride values was 124.2±50.29mg/dl and the non-sepsis group triglyceride values 134.03±68.12mg/dl. There was no specific connection between the severity of sepsis and triglyceride value in a patient with sepsis.

  16. Increased plasma zonulin in patients with sepsis.

    Science.gov (United States)

    Klaus, Daniel A; Motal, Michael C; Burger-Klepp, Ursula; Marschalek, Corinna; Schmidt, Elisabeth M; Lebherz-Eichinger, Diana; Krenn, Claus G; Roth, Georg A

    2013-01-01

    Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

  17. MICRONUTRIENT THERAPY FOR SEPSIS

    Directory of Open Access Journals (Sweden)

    Agung Prasetiyo

    2015-05-01

    Full Text Available Micronutrients are nutrients which are needed by the body to perform the function of body. The amounts is less than 100% μg per day and consist of vitamins and minerals. It cannot be synthesized in the body. Research in the US mentioned that the rate prevalence of sepsis is tended to be increased 8.7 % annually. In sepsis, nutrition is one of the important component which could drive the success treatment. Micronutrient, especially a vitamin which is soluble in fats, it would be toxic if the number exceed the capability of body to receive it. Although there are guidance and mutual agreement about sepsis using, it still need to concern on micronutrient which potentially giving bad effect. In sepsis case, micronutrients also determine the success of treatment due to redistribution of vitamin and trace element from circulation to the tissue which involved in the proteins formation and immune system. The conclusions of the latest 7 experiments and 4 random controlled studies of multi-centre support the micronutrients supplementation because it can decrease mortality rate. However, it still need to be aware to the toxicity of fat soluble micronutrient if the doses are excessive.

  18. Post–Acute Care Use and Hospital Readmission after Sepsis

    Science.gov (United States)

    Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

    2015-01-01

    Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P Readmission rates at 7, 30, and 90 days were higher postsepsis (P readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with adverse readmission outcomes. PMID:25751120

  19. Serum amyloid A in the diagnosis of feline sepsis.

    Science.gov (United States)

    Troìa, Roberta; Gruarin, Marta; Foglia, Armando; Agnoli, Chiara; Dondi, Francesco; Giunti, Massimo

    2017-11-01

    Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.

  20. A novel paradigm links mitochondrial dysfunction with muscle stem cell impairment in sepsis.

    Science.gov (United States)

    Chatre, Laurent; Verdonk, Franck; Rocheteau, Pierre; Crochemore, Clément; Chrétien, Fabrice; Ricchetti, Miria

    2017-10-01

    Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life threatening condition associated with multiple organ failure. Survivors may display long-term disability with muscle weakness that remains poorly understood. Recent data suggest that long-term myopathy in sepsis survivors is due to failure of skeletal muscle stem cells (satellite cells) to regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is linked to unusual mitochondrial dysfunctions, characterized by a dramatic reduction of the mitochondrial mass and hyperactivity of residual organelles. Survivors maintain the impairment of satellite cells, including alterations of the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and mitochondrial function in satellite cells, and in fine their regenerative potential. Injection of MSCs in turn increases the force of isolated muscle fibers and of the whole animal, and improves the survival rate. These effects occur in the context of reduced inflammation markers that also raised during sepsis. Targeting muscle stem cells mitochondria, in a context of reduced inflammation, may represent a valuable strategy to reduce morbidity and long-term impairment of the muscle upon sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Gene Network for Identifying the Entropy Changes of Different Modules in Pediatric Sepsis

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2016-12-01

    Full Text Available Background/Aims: Pediatric sepsis is a disease that threatens life of children. The incidence of pediatric sepsis is higher in developing countries due to various reasons, such as insufficient immunization and nutrition, water and air pollution, etc. Exploring the potential genes via different methods is of significance for the prevention and treatment of pediatric sepsis. This study aimed to identify potential genes associated with pediatric sepsis utilizing analysis of gene network and entropy. Methods: The mRNA expression in the blood samples collected from 20 septic children and 30 healthy controls was quantified by using Affymetrix HG-U133A microarray. Two condition-specific protein-protein interaction networks (PINs, one for the healthy control and the other one for the children with sepsis, were deduced by combining the fundamental human PINs with gene expression profiles in the two phenotypes. Subsequently, distinct modules from the two conditional networks were extracted by adopting a maximal clique-merging approach. Delta entropy (ΔS was calculated between sepsis and control modules. Results: Then, key genes displaying changes in gene composition were identified by matching the control and sepsis modules. Two objective modules were obtained, in which ribosomal protein RPL4 and RPL9 as well as TOP2A were probably considered as the key genes differentiating sepsis from healthy controls. Conclusion: According to previous reports and this work, TOP2A is the potential gene therapy target for pediatric sepsis. The relationship between pediatric sepsis and RPL4 and RPL9 needs further investigation.

  2. Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model.

    Science.gov (United States)

    Cockrell, Chase; An, Gary

    2017-10-07

    Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models. We present a novel investigatory and analytical approach, derived from how HPC resources and simulation are used in the physical sciences, to identify the epistemic boundary conditions of the study of clinical sepsis via the use of a proxy agent-based model of systemic inflammation. Current predictive models for sepsis use correlative methods that are limited by patient heterogeneity and data sparseness. We address this issue by using an HPC version of a system-level validated agent-based model of sepsis, the Innate Immune Response ABM (IIRBM), as a proxy system in order to identify boundary conditions for the possible behavioral space for sepsis. We then apply advanced analysis derived from the study of Random Dynamical Systems (RDS) to identify novel means for characterizing system behavior and providing insight into the tractability of traditional investigatory methods. The behavior space of the IIRABM was examined by simulating over 70 million sepsis patients for up to 90 days in a sweep across the following parameters: cardio-respiratory-metabolic resilience; microbial invasiveness; microbial toxigenesis; and degree of nosocomial exposure. In addition to using established methods for describing parameter space, we

  3. The Microcirculation is Preserved in Emergency Department Low‐acuity Sepsis Patients Without Hypotension

    DEFF Research Database (Denmark)

    Skibsted, Simon; Filbin, Michael; Hou, Peter

    2014-01-01

    -acuity sepsis patients. The hypothesis was that patients with sepsis, but without hypotension, will demonstrate signs of flow abnormalities compared to noninfected control patients. Methods This was a prospective, observational study in a convenience sample of patients with sepsis and noninfected controls...

  4. Systematic review of use of β-blockers in sepsis.

    Science.gov (United States)

    Chacko, Cyril Jacob; Gopal, Shameer

    2015-01-01

    We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  5. Opportunities for microbial control of pulse crop pests

    Science.gov (United States)

    The insect pest complex in U.S. pulse crops is almost an “orphan” in terms of developed microbial control agents that the grower can use. There are almost no registered microbial pest control agents (MPCA) for the different pulse pests. In some cases a microbial is registered for use against specifi...

  6. An international sepsis survey: a study of doctors' knowledge and perception about sepsis

    Science.gov (United States)

    Poeze, Martijn; Ramsay, Graham; Gerlach, Herwig; Rubulotta, Francesca; Levy, Mitchel

    2004-01-01

    Background To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. Methods The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. Results The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. Conclusion There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently. PMID:15566585

  7. Procalcitonin ? Assisted Antibiotic Strategy in Sepsis

    OpenAIRE

    Tr?sy, Domonkos; Moln?r, Zsolt

    2017-01-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help f...

  8. Viewpoint on the current status of researches on sepsis

    Directory of Open Access Journals (Sweden)

    Zheng-guo WANG

    2012-11-01

    Full Text Available Sepsis is a common complication after severe trauma and burn, and also one of the main causes of death. Recently, although some new progresses were seen in antibiotic therapy, the mortality of sepsis is still on the rise, and the death rate as a result of sepsis is higher than a total of that of prostate cancer, breast cancer and AIDS. Therefore, sepsis has obviously become one of the serious ailments threatening human health. The present paper introduced the international definition of sepsis, severe sepsis and septic shock, the current researches on diagnosis and therapy, and proposed that we should not only pay attention to pathogenesis and treatment, but also to sepsis prevention in sepsis researches, and we should try to find out the breakthrough in the interaction and dynamic balance between human being and pathogenic factors. Researches on the strategies to revert strong toxicity of infectious agents to non-toxic or weak pathogenic factors, and to conduct further research concerning biological characteristics of microorganisms and mechanism of drug resistance in order to render them to lose the drug resistance ability, or to increase its sensitivity to the drugs. The above suggested approaches might form the future strategies for preventing and controlling sepsis.

  9. Sepsis Induces a Dysregulated Neutrophil Phenotype That Is Associated with Increased Mortality

    Directory of Open Access Journals (Sweden)

    Jaimin M. Patel

    2018-01-01

    Full Text Available Background. Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis. Methods. This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals. Patients had sequential bloods for the ex vivo assessment of NETosis in response to phorbol-myristate acetate (PMA using a fluorometric technique and chemotaxis using time-lapse video microscopy. Continuous data was tested for normality, with appropriate parametric and nonparametric tests, whilst categorical data was analysed using a chi-squared test. Correlations were performed using Spearman’s rho. Results. Ex vivo NETosis was reduced in patients with severe sepsis, compared to patients with sepsis and controls (p=0.002. PMA NETosis from patients with septic shock was reduced further (p<0.001 compared to controls. The degree of metabolic acidosis correlated with reduced NETosis (p<0.001, and this was replicated when neutrophils from healthy donors were incubated in acidotic media. Reduced NETosis at baseline was associated with an increased 30-day (p=0.002 and 90-day mortality (p=0.014 in sepsis patients. These findings were accompanied by defects in neutrophil migration and delayed apoptosis. Resolution of sepsis was not associated with the return to baseline levels of NETosis or migration. Conclusions. Sepsis induces significant changes in neutrophil function with the degree of dysfunction corresponding to the severity of the septic insult which persists beyond physiological recovery from sepsis. The changes induced lead to the failure to effectively contain and eliminate the invading pathogens and contribute to sepsis

  10. Community-onset sepsis and its public health burden: a systematic review.

    Science.gov (United States)

    Tsertsvadze, Alexander; Royle, Pam; Seedat, Farah; Cooper, Jennifer; Crosby, Rebecca; McCarthy, Noel

    2016-05-18

    Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries (North America, Australasia, and North/Western Europe). Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand-searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95 % CIs) were ascertained by type of sepsis (non-severe, severe, and septic shock). Ten cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64-514), severe sepsis (range: 40-455), and septic shock (range: 9-31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one case-control and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR = 2.60, 95 % CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR = 1.33, 95 % CI: 1.13, 1.56) and smoking tobacco (OR = 1.85, 95 % CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and

  11. Sepsis and meningitis in hospitalized children: performance of clinical signs and their prediction rules in a case-control study.

    Science.gov (United States)

    Verbakel, Jan Y; MacFaul, Roderick; Aertgeerts, Bert; Buntinx, Frank; Thompson, Matthew

    2014-06-01

    Feverish illness is a common presentation to acute pediatric services. Clinical staff faces the challenge of differentiating the few children with meningitis or sepsis from the majority with self-limiting illness. We aimed to determine the diagnostic value of clinical features and their prediction rules (CPR) for identifying children with sepsis or meningitis among those children admitted to a District General Hospital with acute febrile illness. Acutely ill children admitted to a District General Hospital in England were included in this case-control study between 2000 and 2005. We examined the diagnostic accuracy of individual clinical signs and 6 CPRs, including the National Institute for Clinical Excellence "traffic light" system, to determine clinical utility in identifying children with a diagnosis of sepsis or meningitis. Loss of consciousness, prolonged capillary refill, decreased alertness, respiratory effort, and the physician's illness assessment had high positive likelihood ratios (9-114), although with wide confidence intervals, to rule in sepsis or meningitis. The National Institute for Clinical Excellence traffic light system, the modified Yale Observation Scale, and the Pediatric Advanced Warning Score performed poorly with positive likelihood ratios ranging from 1 to 3. The pediatrician's overall illness assessment was the most useful feature to rule in sepsis or meningitis in these hospitalized children. Clinical prediction rules did not effectively rule in sepsis or meningitis. The modified Yale Observation Scale should be used with caution. Single clinical signs could complement these scores to rule in sepsis or meningitis. Further research is needed to validate these CPRs.

  12. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

    2016-02-23

    Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock

  13. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  14. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  15. A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

    Science.gov (United States)

    Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J

    2017-10-01

    Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P

  16. Antimicrobial Materials for Advanced Microbial Control in Spacecraft Water Systems

    Science.gov (United States)

    Birmele, Michele; Caro, Janicce; Newsham, Gerard; Roberts, Michael; Morford, Megan; Wheeler, Ray

    2012-01-01

    Microbial detection, identification, and control are essential for the maintenance and preservation of spacecraft water systems. Requirements set by NASA put limitations on the energy, mass, materials, noise, cost, and crew time that can be devoted to microbial control. Efforts are being made to attain real-time detection and identification of microbial contamination in microgravity environments. Research for evaluating technologies for capability enhancement on-orbit is currently focused on the use of adenosine triphosphate (ATP) analysis for detection purposes and polymerase chain reaction (peR) for microbial identification. Additional research is being conducted on how to control for microbial contamination on a continual basis. Existing microbial control methods in spacecraft utilize iodine or ionic silver biocides, physical disinfection, and point-of-use sterilization filters. Although these methods are effective, they require re-dosing due to loss of efficacy, have low human toxicity thresholds, produce poor taste, and consume valuable mass and crew time. Thus, alternative methods for microbial control are needed. This project also explores ultraviolet light-emitting diodes (UV-LEDs), surface passivation methods for maintaining residual biocide levels, and several antimicrobial materials aimed at improving current microbial control techniques, as well as addressing other materials presently under analysis and future directions to be pursued.

  17. Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial.

    Science.gov (United States)

    Serce, Ozge; Benzer, Derya; Gursoy, Tugba; Karatekin, Guner; Ovali, Fahri

    2013-12-01

    Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly. Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer. The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis (NEC) or sepsis in very low birth weight infants. A prospective, double blind, placebo controlled trial was conducted in preterm infants (≤ 32 GWs, ≤ 1500 g birth weight). They were randomized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo, starting with the first feed until discharged. Necrotizing enterocolitis (NEC) or sepsis and NEC or death. Birth weight and gestational age of the study (n = 104) and the control (n = 104) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks, respectively. Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group (9.6% vs 7.7%, p = 0.62; 28.8% vs 23%, p = 0.34). Time to reach 100 mL/kg/day of enteral feeding (11.9 ± 7 vs 12.6 ± 7 days, p = 0.37) was not different between the groups. Saccharomyces boulardii did not decrease the incidence of NEC or sepsis. © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

    Science.gov (United States)

    Kumar, S; Gupta, E; Kaushik, S; Kumar Srivastava, V; Mehta, S K; Jyoti, A

    2018-04-01

    Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis. © 2018 The Foundation for the Scandinavian Journal of Immunology.

  19. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  20. Diagnosis of post-traumatic sepsis according to "Sepsis guidelines": a cross-sectional survey of sepsis in a trauma intensive care unit

    Directory of Open Access Journals (Sweden)

    Hao TANG

    2016-04-01

    Full Text Available Objective  To investigate the prevalence and risk factors of post-traumatic sepsis, and to evaluate the rationality of the 1992, 2001 and 2012 international sepsis definitions in diagnosing post-traumatic sepsis in a trauma intensive care unit (ICU in China. Methods  A one-day cross-sectional survey of trauma patients who met the inclusion criteria was conducted from 8:00 a.m., June 16, 2014 to 8:00 a.m., June 17, 2014 in the trauma ICU of Daping Hospital. The survey data included demographic information, clinical characteristics, pertinent scores (APACHE Ⅱ, SOFA, GCS, ISS and injury mechanism. According to the definition of sepsis as depicted in the 1992, 2001, and 2012 "International Guideline of Sepsis", the patients were divided into A, B and C groups. The infection site, infection pathogens, and key medical treatment were recorded, the infection identified, and the 28day mortality recorded. A positive pathogen culture of respiratory and urinary tracts, blood, cerebrospinal fluid, and wound secretion was adopted as the diagnostic "gold standard" for septic infection. The diagnostic sensitivity and specificity of the three versions of the guidelines were statistically analyzed and the diagnostic feasibility of each definition was assessed. Results  A total of 30 trauma patients were enrolled, twenty-three patients met the 1992 sepsis criteria, 22 met the 2001 criteria, and 20 met the 2012 criteria. The prevalence rates were 76.7%, 73.3%, and 66.7%, respectively, and there was no significant statistical difference. Four patients died within 28 days, which was in line with the diagnostic criteria of the three versions of the sepsis criteria. The 28-day mortality in the three sepsis guidelines groups was 17.4%, 18.2%, and 25.0%, respectively, indicating no statistical difference. By adopting culture-positive pathogens as the "gold standard" of septic infection, the diagnostic sensitivity and specificity of the group A was 77.8% and 25

  1. Quality of Life of Severe Sepsis Survivors After Hospital Discharge Calidad de vida de sobrevivientes de sepsis grave después del alta hospitalar Qualidade de vida de sobreviventes de sepse grave após alta hospitalar

    Directory of Open Access Journals (Sweden)

    Ligia Marcia Contrin

    2013-06-01

    Full Text Available AIMS: to evaluate the quality of life in severe sepsis survivors, using specific QoL questionnaires: the EuroQol-5 Dimensions and the Visual Analogue Scale (EQ-VAS. METHOD: This case-control study was performed in patients discharged from a teaching hospital after being admitted to the ICU with severe sepsis. Medical records from 349 patients were retrieved from the hospital sepsis registry. Each patient with sepsis was considered as a case. Patients who were admitted immediately after the sepsis episode were considered as controls, provided that they did not have sepsis and survived the ICU admission. This specific study population included 100 patients. RESULTS: The sepsis group showed higher mortality at 1 year compared with critically ill patients. However, the control group showed no sepsis. Older patients (>60 years in the sepsis group had a significantly higher prevalence of problems. There were no differences in EQ-VAS between respondents from both groups. CONCLUSIONS: After discharge from ICU, sepsis survivors of sepsis had a higher mortality rate than critically ill patients without sepsis. Older patients with sepsis had more moderate and severe problems in all five quality of life dimensions evaluated. OBJETIVO: Evaluación de la calidad de vida de los sobrevivientes de sepsis grave con los instrumentos EuroQol-5D y la Escala Analógica Visual (EQ-VAS. MÉTODO: Estudio caso-control anidado en pacientes que recibieron alta de la unidad de cuidados intensivos (UCI de un hospital de enseñanza después de la admisión con sepsis grave. La selección fue realizada a partir del registro de sepsis conteniendo 349 pacientes y cada paciente con sepsis fue considerado como un caso y el que fue hospitalizado inmediatamente después fue seleccionado como control, desde que no tuviera sepsis y hubiera sobrevivido a la hospitalización en la UCI y la sepsis, totalizando 100 sujetos. RESULTADOS: El grupo de sepsis mostró una mayor mortalidad a 1 a

  2. Control of Pecan Weevil With Microbial Biopesticides.

    Science.gov (United States)

    Shapiro-Ilan, David I; Cottrell, Ted E; Bock, Clive; Mai, Kim; Boykin, Debbie; Wells, Lenny; Hudson, William G; Mizell, Russell F

    2017-12-08

    The pecan weevil, Curculio caryae (Horn) (Coleoptera: Curculionidae), is a key pest of pecans Carya illinoinensis ([Wangenh.] K. Koch) (Fagales: Juglandaceae). Control recommendations rely on broad spectrum chemical insecticides. Due to regulatory and environmental concerns, effective alternatives for C. caryae control must be sought for pecan production in conventional and organic systems. We explored the use of microbial biopesticides for control of C. caryae in Georgia pecan orchards. Three experiments were conducted. The first investigated an integrated microbial control approach in an organic system at two locations. Three microbial agents, Grandevo (based on byproducts of the bacterium Chromobacterium subtsugae Martin, Gundersen-Rindal, Blackburn & Buyer), the entomopathogenic nematode Steinernema carpocapsae (Weiser), and entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin, were applied to each treatment plot (0.6 ha) at different times during the season. A second experiment compared the effects of S. carpocapsae and B. bassiana applied as single treatments relative to application of both agents (at different times); survival of C. caryae was assessed approximately 11 mo after larvae were added to pots sunk in an organic pecan orchard. In a conventional orchard (with 1.0 ha plots), the third experiment compared Grandevo applications to a commonly used regime of chemical insecticides (carbaryl alternated with a pyrethroid). All experiments were repeated in consecutive years. The combined pest management tactic (experiment 1) reduced C. caryae infestation relative to non-treated control plots in both locations in 2014 and one of the two locations in 2015 (the other location had less than 1% infestation). In experiment 2, no differences among combined microbial treatments, single-applied microbial treatments or different numbers of application were observed, yet all microbial treatments reduced C. caryae survival relative to the control. In the third

  3. Systematic review of use of β-blockers in sepsis

    Directory of Open Access Journals (Sweden)

    Cyril Jacob Chacko

    2015-01-01

    Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  4. Antioxidant protection of statins in acute kidney injury induced by sepsis

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos

    2014-10-01

    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  5. The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.

    Science.gov (United States)

    Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre

    2017-04-01

    Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.

  6. Role of microRNAs in sepsis.

    Science.gov (United States)

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2017-07-01

    MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time. MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives. MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.

  7. Anaesthetic management of patients with severe sepsis.

    Science.gov (United States)

    Eissa, D; Carton, E G; Buggy, D J

    2010-12-01

    Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

  8. Microbial control of arthropod pests of tropical tree fruits.

    Science.gov (United States)

    Dolinski, Claudia; Lacey, Lawrence A

    2007-01-01

    A multitude of insects and mites attack fruit crops throughout the tropics. The traditional method for controlling most of these pests is the application of chemical pesticides. Growing concern on the negative environmental effects has encouraged the development of alternatives. Inundatively and inoculatively applied microbial control agents (virus, bacteria, fungi, and entomopathogenic nematodes) have been developed as alternative control methods of a wide variety of arthropods including tropical fruit pests. The majority of the research and applications in tropical fruit agroecosystems has been conducted in citrus, banana, coconut, and mango. Successful microbial control initiatives of citrus pests and mites have been reported. Microbial control of arthropod pests of banana includes banana weevil, Cosmopolites sordidus Germar (Coleoptera: Curculionidae) (with EPNs and fungi) among others Oryctes rhinoceros (L.) is one of the most important pests of coconut and one of the most successful uses of non-occluded virus for classical biological control. Key pests of mango that have been controlled with microbial control agents include fruit flies (Diptera: Tephritidae) (with EPNs and fungi), and other pests. Also successful is the microbial control of arthropod pests of guava, papaya and pineapple. The challenge towards a broader application of entomopathogens is the development of successful combinations of entomopathogens, predators, and parasitoids along with other interventions to produce effective and sustainable pest management.

  9. Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

    Science.gov (United States)

    Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

    2017-11-01

    OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

  10. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  11. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6.

    Science.gov (United States)

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance.

  12. Plasma procalcitonin concentrations are increased in dogs with sepsis

    Science.gov (United States)

    Goggs, Robert; Milloway, Matthew; Troia, Roberta; Giunti, Massimo

    2018-01-01

    Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1–164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2–63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis. PMID:29682292

  13. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis.A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated.No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  14. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  15. A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

    Science.gov (United States)

    Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik

    2015-08-28

    Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Personalized identification of differentially expressed pathways in pediatric sepsis.

    Science.gov (United States)

    Li, Binjie; Zeng, Qiyi

    2017-10-01

    Sepsis is a leading killer of children worldwide with numerous differentially expressed genes reported to be associated with sepsis. Identifying core pathways in an individual is important for understanding septic mechanisms and for the future application of custom therapeutic decisions. Samples used in the study were from a control group (n=18) and pediatric sepsis group (n=52). Based on Kauffman's attractor theory, differentially expressed pathways associated with pediatric sepsis were detected as attractors. When the distribution results of attractors are consistent with the distribution of total data assessed using support vector machine, the individualized pathway aberrance score (iPAS) was calculated to distinguish differences. Through attractor and Kyoto Encyclopedia of Genes and Genomes functional analysis, 277 enriched pathways were identified as attractors. There were 81 pathways with Ppathways with Ppathway clusters and four sample clusters. Thus, in the majority pediatric sepsis samples, core pathways can be detected as different from accumulated normal samples. In conclusion, a novel procedure that identified the dysregulated attractors in individuals with pediatric sepsis was constructed. Attractors can be markers to identify pathways involved in pediatric sepsis. iPAS may provide a correlation score for each of the signaling pathways present in an individual patient. This process may improve the personalized interpretation of disease mechanisms and may be useful in the forthcoming era of personalized medicine.

  17. Construction and management of ARDS/sepsis registry with REDCap.

    Science.gov (United States)

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

    2014-09-01

    The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

  18. T-cell proliferative responses following sepsis in neonatal rats.

    Science.gov (United States)

    Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

    2003-01-01

    Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

  19. Non-invasive ventilation in HIV positive patients with sepsis and ...

    African Journals Online (AJOL)

    Method: We conducted an observational prospective cohort study for the NIV arm (in the first half of 2016) with a retrospective chart review for the controls that focused on HIV positive patients with sepsis and hypoxaemic respiratory failure. 77 consecutive HIV positive patients with sepsis and respiratory distress meeting the ...

  20. Active Detoxification in the Treatment of Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    O. M. Shevtsova

    2009-01-01

    Full Text Available Objective: to evaluate the efficiency of extracorporeal detoxification techniques in patients with abdominal sepsis. Subjects and methods. Three hundred and seventy-nine patients with acute generalized peritonitis were examined. Extracorporeal detoxifying techniques were used during conventional therapy in Group 1 (n=319; the other patients received only traditional therapy (a control group. The time course of changes in the parameters of toxemia, a hemostasiogram, and an immunogram were examined. Results. The study indicated significantly reduced endotoxemia and better blood aggregation resulting from the use of plasmapheresis, cryoplasmasorption, and plasmasorption, as well as stimulated immunity when the above techniques were combined with autoblood photomodification and extracorporeal immunopharmacotherapy in patients with abdominal sepsis. In severe abdominal sepsis and infectious-toxic shock, there was regression of multiple organ dysfunction and lower mortality when venovenous hemofiltration was applied. Conclusion. A differential approach to using active detoxifying techniques is needed, by taking into account the severity of the disease. Key words: abdominal sepsis, detoxifying techniques.

  1. Unrevealing culture-negative severe sepsis

    OpenAIRE

    de Prost, Nicolas; Razazi, Keyvan; Brun-Buisson, Christian

    2013-01-01

    Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.

  2. The costs and cost-effectiveness of an integrated sepsis treatment protocol.

    Science.gov (United States)

    Talmor, Daniel; Greenberg, Dan; Howell, Michael D; Lisbon, Alan; Novack, Victor; Shapiro, Nathan

    2008-04-01

    Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institution's integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Beth Israel Deaconess Medical Center. Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. In-hospital treatment costs were collected using the hospital's detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of approximately $8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of $11,274 per life-year saved and a cost of $16,309 per quality-adjusted life year gained. In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

  3. Engineering microbial consortia for controllable outputs

    Energy Technology Data Exchange (ETDEWEB)

    Lindemann, Stephen R.; Bernstein, Hans C.; Song, Hyun-Seob; Fredrickson, Jim K.; Fields, Matthew W.; Shou, Wenying; Johnson, David R.; Beliaev, Alexander S.

    2016-03-11

    Much research has been invested into engineering microorganisms to perform desired biotransformations; nonetheless, these efforts frequently fall short of expected results due to the unforeseen effects of biofeedback regulation and functional incompatibility. In nature, metabolic function is compartmentalized into diverse organisms assembled into resilient consortia, in which the division of labor is thought to lead to increased community efficiency and productivity. Here, we consider whether and how consortia can be designed to perform bioprocesses of interest beyond the metabolic flexibility limitations of a single organism. Advances in post-genomic analysis of microbial consortia and application of high-resolution global measurements now offer the promise of systems-level understanding of how microbial consortia adapt to changes in environmental variables and inputs of carbon and energy. We argue that when combined with appropriate modeling framework that predictive knowledge generates testable hypotheses and orthogonal synthetic biology tools, such understanding can dramatically improve our ability to control the fate and functioning of consortia. In this article, we articulate our collective perspective on the current and future state of microbial community engineering and control while placing specific emphasis on ecological principles that promote control over community function and emergent properties.

  4. Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article

    Directory of Open Access Journals (Sweden)

    Kayambu Geetha

    2011-10-01

    Full Text Available Abstract Background Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. Methods/Design A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252 will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care. The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test. Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. Discussion The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12610000808044

  5. CDC Vital Signs–Think Sepsis. Time Matters.

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This podcast is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  6. Letter to editor Platelet volume evaluation in patients with sepsis ...

    African Journals Online (AJOL)

    I have read the article published by Guclu et al. with a great interest.1 They examined platelet indices in patients with sepsis. Mean platelet volume (MPV) and platelet distribution width (PDW) were significantly higher in patients with sepsis than in controls. MPV and PDW were significantly higher in patients with severe ...

  7. Distribution characteristics of liquid sequestration in rats with sepsis

    Directory of Open Access Journals (Sweden)

    Bin LI

    2012-03-01

    Full Text Available Objective To investigate the distribution characteristics of organs with liquid sequestration during fluid resuscitation in rats with sepsis. Methods Fifty male Wistar rats were randomly divided into five groups: control group (n=10, sepsis group (n=10, crystalloid group (n=10, albumin group (n=10, and artificial colloid (HAES group (n=10. The sepsis model was reproduced by cecal ligation and puncture. The mean arterial pressure was monitored with carotid artery intubation. Twelve hours after fluid infusion by micro-infusion pump via the femoral vein, tissues from the heart, liver, lungs, kidney (right, and small intestine were harvested to observe the pathological changes and calculate the tissue water content. Results The water content of every visceral tissue was higher in the sepsis group than in the control group (P < 0.05; the water content in the heart, liver, and lung tissues was higher in the albumin group than in the crystalloid group (P < 0.05. The water content in both albumin and crystalloid groups was higher than that in the sepsis group (P < 0.05. Moreover, the water content in the heart, liver, and lungs in the HAES group was lower than that in the crystalloid and albumin groups (P < 0.05. Cellular injuries were more severe in the heart, liver, and lungs than in the intestine and kidney in the crystalloid group and albumin group under electron-microscope. Conclusion Liquid sequestration exists mainly in the lungs, heart, and liver of rats with sepsis during fluid resuscitation. The phenomenon is less evident in the kidney and small intestine. Artificial colloid can reduce capillary leak with a good volume expansion effect.

  8. A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

    Science.gov (United States)

    Watkins, Richard R; Haller, Nairmeen; Wayde, Melinda; Armitage, Keith B

    2017-01-01

    We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

  9. Advances in sepsis-associated liver dysfunction

    Directory of Open Access Journals (Sweden)

    Dawei Wang

    2014-07-01

    Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.

  10. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    Science.gov (United States)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  11. Effects of paraoxonase, arylesterase, ceruloplasmin, catalase, and myeloperoxidase activities on prognosis in pediatric patients with sepsis.

    Science.gov (United States)

    Ayar, Ganime; Atmaca, Yasemin Men; Alışık, Murat; Erel, Özcan

    2017-05-01

    The present study aimed to investigate the levels of paraoxonase (PON), stimulated paraoxonase (SPON), arylesterase (ARE), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase (CAT) in pediatric sepsis and to explore their effects on the prognosis of sepsis. Patients diagnosed with sepsis (n=33) and healthy controls (n=30) were included. PON, SPON, ARE, CLP, MPO, and CAT activities were measured in the sepsis and control groups. Additionally, the parameters were compared between survivors and non-survivors in the sepsis group. The levels of hemoglobin, white blood cell, platelet, lactate, and C-reactive protein were measured in the blood samples drawn from the patients with sepsis at diagnosis, at the 48th hour, and on day 7. The pediatric risk of mortality and pediatric logistic organ dysfunction scores of the patients were used for the estimation of severity of disease. Lower ARE (153.24 vs. 264.32U/L; p<0.001), lower CLP (80.58 vs. 97.98U/L; p=0.032), lower MPO (91.24 vs. 116.55U/L; p=0.023), and higher CAT levels (256.5 vs.145.5kU/L; p=0.003) were determined in the sepsis group as compared to the control group. There was no difference between the groups in terms of PON or SPON levels. No difference was determined between the survivors and non-survivors in terms of any of the parameters. The present study determined that ARE, CLP, CAT, and MPO levels are different between the pediatric patients with sepsis and healthy controls. ARE level can be a potent biomarker for sepsis in critical patients in intensive care units. Further studies with larger samples are required to demonstrate the value of these parameters as prognostic biomarkers in pediatric sepsis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

    Science.gov (United States)

    Alessi, Lauren J; Warmus, Holly R; Schaffner, Erin K; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M

    2018-03-01

    Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods are organized in a plan-do-study-act cycle. During the "plan" phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the "do" phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45-8.2% and mortality range of 8.2-25% (Table 2). 1-5 . Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement.

  13. Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

    Science.gov (United States)

    Navar-Boggan, A M; Halsey, N A; Golden, W C; Escobar, G J; Massolo, M; Klein, N P

    2010-09-01

    Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, Pimmunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (Pimmunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

  14. Perioperative treatment of patients with sepsis

    DEFF Research Database (Denmark)

    Ibsen, Michael; Perner, Anders

    2013-01-01

    Key elements in the initial resuscitation and stabilization of the patient with sepsis are fluid therapy, vasopressor or inotropic support, administration of adequate antibiotics and source control. This review will primarily discuss fluid, vasopressor and antibiotic therapy because these have been...

  15. Procalcitonin - Assisted Antibiotic Strategy in Sepsis.

    Science.gov (United States)

    Trásy, Domonkos; Molnár, Zsolt

    2017-05-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help fast and accurate diagnosis biomarkers have been measured for decades. Procalcitonin (PCT) is one of the most studied, but the results are conflicting. Sepsis means a very loose cohort of a large heterogeneous patient population, hence defining certain cut off values for PCT to differentiate between different severities of the disease is almost impossible. Clinicians first have to understand the pathophysiological background of sepsis to be able to interpret correctly the PCT results. Nevertheless, PCT has been shown to have the best sensitivity and specificity to indicate infection, antibiotic appropriateness and stopping therapy. In this article we will focus on some important aspects of pathophysiology and advice on how to implement that in the everyday clinical practice. We believe that this multimodal evaluation of the clinical picture together with PCT results can be a useful tool to make the most out of the PCT results, and do the best for patients on the ICU.

  16. Changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis

    International Nuclear Information System (INIS)

    Wang Jinjiang

    2007-01-01

    Objective: To investigate the importance of determination of changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis. Methods: Serum PCT (with double-sandwich immunofluorescence assay) and IL-6 (with ELISA) levels were measured repeatedly in 130 patients with sepsis on d1, d3, d5, d7 after admission. Values in 130 healthy individuals were also measured as control. Results: The serum levels of PCT and IL-6 in the patients with sepsis of admission were significantly higher than those in controls. The levels dropped markedly in the survivors by d7. Among the septic patients, the levels in the succumbed patients were significantly higher those in the survivors (P<0.05). Conclusion: Serum PCT and IL-6 values appeared to be of prognostic value in patients with sepsis. (authors)

  17. Sepsis neonatal cervicomaxilofacial (1996 a 2005 Neonatal cervicomaxillofacial sepsis (1996-2005

    Directory of Open Access Journals (Sweden)

    Zoila del S. López Díaz

    2007-12-01

    Full Text Available Se realiza un estudio retrospectivo y longitudinal de la sepsis cervicomaxilofacial en los neonatos ingresados en nuestra unidad de cuidados intensivos en un período de 10 años. Encontramos una incidencia promedio de 1,20 por cada 100 ingresos, y el predominio del grupo de edades entre 7 y 27 días de vida (sepsis tardía, del sexo femenino y del color blanco de la piel. La celulitis facial fue ocasionada por trauma obstétrico y fue el diagnóstico más frecuente. No encontramos relación entre la presencia de sepsis y la edad gestacional, el conteo de Apgar o el peso al nacer, pues en el mayor número de niños estos resultados estuvieron dentro de límites normales. El tratamiento más utilizado fue la antibioticoterapia con asociación de 2 o más antibióticos, y entre estas la más socorrida fue la asociación de penicilina y gentamicina. Cuando la sepsis tuvo una repercusión sistémica muy grave, se utilizó además inmunoglobulinoterapia. La evolución fue satisfactoria en el 100 % de los casos, la mayoría de los cuales necesitó internación hospitalaria hasta los 7 días. No hubo fallecidos.A retrospective and longitudinal study of cervicomaxillofacial sepsis in the neonates admitted in our intensive care unit in a period of 10 years was conducted. An average incidence of 1.20 per 100 admissions, as well as the predominance of white female infants aged 7-27 days old (late sepsis were observed. Facial cellulitis was caused by obstetric trauma and it was the most frequent diagnosis. No relation between the presence of sepsis and gestational age, Apgar score, or birth weight, was found, since in most of the children these results were within the normal limits. The most used treatment was the antibiotic therapy with the association of 2 or more antibiotics. The combination of penicillin and gentamicin was the most common treatment. In those cases, among whom the sepsis had a very severe systemic repercussion, immunoglobulin therapy was

  18. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need

  19. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock: A comparative retrospective study.

    Science.gov (United States)

    Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

    2018-03-01

    While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases.This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission.In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EFshock.

  20. Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

    Science.gov (United States)

    Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

    2016-11-15

    Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

  1. Premise for Standardized Sepsis Models.

    Science.gov (United States)

    Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin

    2018-06-05

    Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

  2. Disruption of Brain-Heart Coupling in Sepsis

    NARCIS (Netherlands)

    Admiraal, Marjolein M.; Gilmore, Emily J.; Van Putten, Michel J.A.M.; Zaveri, Hitten P.; Hirsch, Lawrence J.; Gaspard, Nicolas

    2017-01-01

    Purpose: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-Associated brain dysfunction. Methods: Fifty-Two patients with sepsis were prospectively identified, categorized as comatose (N

  3. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality.

    Science.gov (United States)

    Wiens, Matthew O; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Ndamira, Andrew; Larson, Charles P

    2012-01-01

    Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.

  4. Sepsis-Induced Cardiomyopathy: Mechanisms and Treatments

    Directory of Open Access Journals (Sweden)

    Yan-Cun Liu

    2017-08-01

    Full Text Available Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (SIC, defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of SIC involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for SIC include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of SIC and hope to provide further insights to researchers and create a new road for the therapy of sepsis.

  5. Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

    Science.gov (United States)

    Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

    2016-01-01

    Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

  6. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings

  7. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee

  8. Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study

    Directory of Open Access Journals (Sweden)

    Grazyna Anna Hoser

    2012-10-01

    Full Text Available The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell populations were examined: white blood cell count (WBC, monocytes, lymphocytes:
    CD3+, CD4+ and CD8+ T cells, B cells, and NK cells. In both studied groups (i.e. IAS and PDS, the
    WBC was elevated. However, it was significantly higher in the IAS group than in the PDS group. The difference
    was due to a lower granulocyte count, as well as a lower monocyte count in PDS. We found no significant
    correlation between the total lymphocyte number and CD3+CD8+ T cells in either form of sepsis. Similarly, we
    observed no correlation between the total lymphocyte number and the NK cells subset in IAS. However, the
    numbers of CD3+CD8+ and NK cells correlated similarly in both types of sepsis. Both studied types of sepsis
    induced profound lymphocytopenia, with marked loss of CD8+ T cells and the NK cells. However, the similar
    relation between them, which was independent of the infection type, suggests that the NK and CD3+CD8+ cells
    have shared mechanisms of regulation. The primary site of infection has an impact on the global immune reaction.
    These alternations include especially myeloid cells: granulocytes and monocytes which disappear from peripheral
    blood during PDS, but increase in IAS.
    The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell

  9. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis.

    Science.gov (United States)

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with

  10. Procalcitonin as an adjunctive biomarker in sepsis

    Directory of Open Access Journals (Sweden)

    Mahua Sinha

    2011-01-01

    Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

  11. Fatores de risco para o desenvolvimento de sepse neonatal precoce em hospital da rede pública do Brasil Risk factors for early-onset neonatal sepsis in Brazilian public hospital short-title: early-onset neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Ana Paula Goulart

    2006-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O conhecimento dos fatores de risco associados à sepse neonatal precoce em unidade de neonatologia, inserida na realidade de nosso sistema de saúde, no sentido de se detectar, prevenir e adotar medidas específicas e reduzir as taxas de mortalidade nessa faixa etária. O objetivo deste estudo foi determinar os fatores de risco associados a sepse neonatal precoce em hospital de referência em neonatologia ligado à rede pública de saúde. MÉTODO: Foi realizado um estudo observacional, prospectivo, tipo caso-controle. Foram incluídos os recém-nascidos com diagnóstico de sepse precoce e como controle, recém-nascidos sem infecção neonatal nascido na mesma data do recém-nascido considerado como caso. Foram incluídos 50 casos e três controles para cada caso, resultando em amostra total de 200 pacientes. Foi considerada estatisticamente significativa a associação quando p BACKGROUND AND OBJECTIVES: The determination of the risk factors to early-onset neonatal sepsis in our country is essential to prevent and reduce the mortality associated with this syndrome. Thus, the objective of this study was to determine the frequency and associated risk factors to early-onset neonatal sepsis in public hospital in Southern Brazil. METHODS: Observational, case-control study. Were included neonates with diagnostic of early-onset neonatal sepsis and as controls, neonates without neonatal infection. Were included 50 cases and 3 controls for each case resulting in a total sample of 200 patients. Associations were considered significant when p < 0.05. RESULTS: The sepsis frequency was 50.3 per 1000 born-alive. Risk factors associated to the development of neonatal sepsis were prematurity (OR 9.33; p < 0.001, low birth weight (OR 11.74; p < 0.001, maternal infection (OR 2.28; p = 0.009, mother with history of previous infant with neonatal sepsis (OR 6.43; p = 0.035 and rupture of the membranes more than 18 hours before delivery

  12. Sepsis attenuates the anabolic response to skeletal muscle contraction.

    Science.gov (United States)

    Steiner, Jennifer L; Lang, Charles H

    2015-04-01

    Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.

  13. Genotyping of PPAR-γ gene polymorphism in Egyptian neonates affected with sepsis disease and its severity

    Directory of Open Access Journals (Sweden)

    Rabah M. Shawky

    2018-07-01

    Full Text Available Background: Peroxisome Proliferator-Activated Receptor gamma (PPARγ is a ligand-dependent transcription factor involved in inflammatory process. PPAR-γ gene was mentioned as having a modulating role in the pathological status of sepsis.The present study aimed to make a correlation between The Pro12Ala polymorphism in PPAR-γ gene and occurrence of neonatal sepsis and its severity among a sample of Egyptian neonates suffering sepsis. Subjects and methods: This case-control study included 30 neonates (11 females and19 males newly admitted with neonatal sepsis at the intensive care unit (NICU (mean age 10.3 days ± 6.23. The control group included 50 age and sex matched neonates (23 females and 27 males (mean age 10.20 days ± 5.36 days. All the neonates (preterm and full term included were with clinical signs and laboratory data consistent with neonatal sepsis. Genotyping for PPARγ gene region harboring the Pro12Ala variant locus were carried out using Tetra ARMS technique. Results: About 56.7% of the patients group was homozygote (GG for polymorphic locus (coding for Alanine/Alanine while 30% was heterozygote for polymorphic locus (CG (coding for Proline/Alanine and up to 13.3% was homozygote for the polymorphic locus (CC (coding for Proline/Proline. Compared to the control group where homozygotes for CC were the most prevalent (90% and the CG were 10% with absence of GG genotypes. There was a strong statistical significant difference between patients and the normal control group as regards prevalence of PPAR-γ gene polymorphism in occurrence of neonatal sepsis and its severity. Also, there were strong relation between genotype GG and low birth weight, neonatal fever, prematurity and depressed neonatal reflexes. Conclusion: PPAR-γ gene has been suggested to be a candidate gene for neonatal sepsis. Therefore, Pro12Ala polymorphism might be useful in predicting the risk factor of neonatal sepsis and its severity. Keywords: Sepsis, PPAR

  14. Red cell distribution width and its association with mortality in neonatal sepsis.

    Science.gov (United States)

    Martin, Snehal L; Desai, Saumil; Nanavati, Ruchi; Colah, Roshan B; Ghosh, Kanjaksha; Mukherjee, Malay B

    2018-01-08

    Neonatal sepsis is a major cause of mortality in the developing countries. However, with current severity scores and laboratory parameters, predicting outcomes of neonatal sepsis is a serious challenge. Red cell distribution width (RDW) is a readily available pragmatic means to predict outcomes of various comorbidities in adults and children, without causing any additional blood loss. However, its utility in neonates remains unexplored. Hence, the objective of the present study was to evaluate the association of RDW with neonatal sepsis and its role as a predictive marker for mortality. This Prospective observational study was carried out in a Level IIIB NICU for a period of 3 years. It involved comparison of RDW values of septic neonates with those of controls (matched for gestational age and birth weight) with an equal allocation ratio. A total of 251 septic neonates along with 251 controls >28 weeks of gestational age were enrolled. The RDW was derived from complete blood count done within first 6 hours of life. After arranging the RDW (median; interquartile range (IQR)), the values were categorized as those above the 50th percentile i.e. ≥20% and those below the 50th percentile i.e. rates of the above two groups were assessed using the Kaplan-Meier curve and the log rank test. RDW levels were significantly higher among the neonatal sepsis cases (19.90%) as compared to the controls (18.90%) with a p value of < .001. RDW was significantly higher amongst the nonsurvivors than survivors (p < .003). Kaplan-Meier curve showed that septic neonates having RDW values ≥20% had significantly increased mortality (p < .02) with a hazard ratio of 0.5. High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis.

  15. Sepsis Associated Encephalopathy

    Directory of Open Access Journals (Sweden)

    Neera Chaudhry

    2014-01-01

    Full Text Available Sepsis associated encephalopathy (SAE is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

  16. Syndrome Evaluation System (SES) versus Blood Culture (BACTEC) in the Diagnosis and Management of Neonatal Sepsis--A Randomized Controlled Trial.

    Science.gov (United States)

    Bhat, B Vishnu; Prasad, P; Ravi Kumar, Venkata Banda; Harish, B N; Krishnakumari, K; Rekha, Anand; Manjunath, G; Adhisivam, B; Shruthi, B

    2016-05-01

    To compare the clinical outcome of a multiplex polymerase chain reaction (PCR) based molecular diagnostic method -- Syndrome Evaluation System (SES) directed treatment strategy vs. standard of care (blood culture) directed treatment strategy for neonatal sepsis. This randomized controlled trial (RCT) included 385 neonates with sepsis who were randomized into two groups -- SES and control (BACTEC). Both tests were performed for all the neonates. However, in the SES group, the results of SES test were revealed to the treating clinicians, while in the control group, SES results were withheld. Two ml of blood was drawn from each baby. One aliquot was sent for blood culture, whereas the remaining aliquot was sent for SES. Babies were then administered empirical IV antibiotics and given supportive care. Further antibiotic changes, if required were done in SES and control groups based on their respective reports. The microbiological profile, immediate outcome, duration of hospital stay, number of antibiotics used and readmission within a month in both groups were compared. SES was better than BACTEC in identifying the causative organism in both the groups (68 % vs. 18 % in SES group and 72 % vs. 18 % in control group). SES had 100 % concordance with blood culture by BACTEC. Detection of bacteria and fungi were four and ten-fold higher respectively with SES when compared to BACTEC culture. Microbiological diagnosis was rapid with SES compared to BACTEC (7 h vs. 72 h). Treatment based on SES resulted in significantly less mortality (3 % vs. 18 %). Readmission rate, duration of hospital stay and change in antibiotics were also significantly less in SES group. This new molecular based diagnostic system (SES) helps in rapid and accurate diagnosis of neonatal sepsis and reduces mortality and morbidity in affected neonates.

  17. What?s New in Paediatric Sepsis

    OpenAIRE

    Farrell, Deborah; Nadel, Simon

    2016-01-01

    Severe sepsis and septic shock remains a leading cause of mortality and morbidity in children. There is ongoing uncertainty regarding the optimal treatment pathways however the initial management of sepsis is crucial. This article is designed to be an informal and personal review of recent developments in paediatric sepsis over the past 3?years.

  18. Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

    International Nuclear Information System (INIS)

    Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

    2006-01-01

    To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

  19. Sepsis: at-risk patients, clinical manifestations and management

    African Journals Online (AJOL)

    As sepsis progresses to septic shock, the risk of dying increases ... Jantjie Taljaard's current fields of interests are general internal medicine, antibiotic stewardship, HIV/HBV co-infection, drug-related .... infections (infection control) and stress.

  20. Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

    Science.gov (United States)

    Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

    2017-09-01

    To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

  1. Estrogen protects the liver and intestines against sepsis-induced injury in rats.

    Science.gov (United States)

    Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

    2005-09-01

    Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

  2. Role of leucocytes cell population data in the early detection of sepsis.

    Science.gov (United States)

    Urrechaga, Eloísa; Bóveda, Oihane; Aguirre, Urko

    2018-03-01

    The cell population data (CPD) parameters reported by XN analyser (Sysmex, Kobe, Japan) reflect the size and internal structure of leucocytes. We aimed to assess the clinical utility of these parameters as biomarkers for the early diagnosis of sepsis. The study group (G1) included 586 controls (no quantitative or morphological alterations in the complete blood count) and 137 patients diagnosed with sepsis. The reliability of the model was evaluated using a validation group (G2) of 212 controls and 60 patients with sepsis. The optimal cut-off for the diagnosis of sepsis and the OR for CPD were established using a univariate logistic regression. A multivariate logistic regression model was then created. The OR and area under the curve were recorded. A risk stratification scale (neutrophils and monocytes (NEMO)) for diagnosing sepsis was established on the basis of the coefficients of the multivariate model. MO-X and neutrophils fluorescence intensity (NE-SFL) were found to be the most relevant of the CPD in predicting sepsis applying multivariate analysis to G1.NEMO score was composed using the above-mentioned CPD and subsequently stratified into three risk groups: mild (≤3), moderate (4≤NEMO≤5) and high (≥6). The OR for patients with a score of 4-5 was 10 and 249 for a score of ≥6. When applied to G2, the positive predictive value was 84.8 % and the negative predictive value was 96.0%. CPD are potentially useful for the early diagnosis of sepsis. Their values were used to compose in NEMO score can help in rapid and reliable decision making. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. β-hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice.

    Science.gov (United States)

    Supinski, Gerald S; Callahan, Leigh A

    2014-06-01

    Infections induce severe respiratory muscle weakness. Currently there are no treatments for this important clinical problem. We tested the hypothesis that β-hydroxy-β-methylbutyrate (HMB) would prevent sepsis-induced diaphragm weakness. Four groups of adult male mice were studied: controls (saline-injected), sepsis (intraperitoneal lipopolysaccharide), sepsis+HMB (injected intravenously), and HMB. Diaphragm force generation and indices of caspase 3, calpain, 20S proteasomal subunit, and double-stranded RNA-dependent protein kinase (PKR) activation were assessed after 24h. Sepsis elicited large reductions in diaphragm specific force generation at all stimulation frequencies. Endotoxin also activated caspase 3, calpain, the 20S proteasomal subunit and PKR in the diaphragm. HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, but did not prevent calpain activation. Most importantly, HMB administration significantly attenuated sepsis-induced diaphragm weakness, preserving muscle force generation at all stimulation frequencies (pHMB may prove to be an important therapy in infected patients, with the potential to increase diaphragm strength, to reduce the duration of mechanical ventilation and to decrease mortality in this patient population. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Lipoproteins/peptides are sepsis-inducing toxins from bacteria that can be neutralized by synthetic anti-endotoxin peptides.

    Science.gov (United States)

    Martinez de Tejada, Guillermo; Heinbockel, Lena; Ferrer-Espada, Raquel; Heine, Holger; Alexander, Christian; Bárcena-Varela, Sergio; Goldmann, Torsten; Correa, Wilmar; Wiesmüller, Karl-Heinz; Gisch, Nicolas; Sánchez-Gómez, Susana; Fukuoka, Satoshi; Schürholz, Tobias; Gutsmann, Thomas; Brandenburg, Klaus

    2015-09-22

    Sepsis, a life-threatening syndrome with increasing incidence worldwide, is triggered by an overwhelming inflammation induced by microbial toxins released into the bloodstream during infection. A well-known sepsis-inducing factor is the membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS), signalling via Toll-like receptor-4. Although sepsis is caused in more than 50% cases by Gram-positive and mycoplasma cells, the causative compounds are still poorly described. In contradicting investigations lipoproteins/-peptides (LP), lipoteichoic acids (LTA), and peptidoglycans (PGN), were made responsible for eliciting this pathology. Here, we used human mononuclear cells from healthy donors to determine the cytokine-inducing activity of various LPs from different bacterial origin, synthetic and natural, and compared their activity with that of natural LTA and PGN. We demonstrate that LP are the most potent non-LPS pro-inflammatory toxins of the bacterial cell walls, signalling via Toll-like receptor-2, not only in vitro, but also when inoculated into mice: A synthetic LP caused sepsis-related pathological symptoms in a dose-response manner. Additionally, these mice produced pro-inflammatory cytokines characteristic of a septic reaction. Importantly, the recently designed polypeptide Aspidasept(®) which has been proven to efficiently neutralize LPS in vivo, inhibited cytokines induced by the various non-LPS compounds protecting animals from the pro-inflammatory activity of synthetic LP.

  5. Pediatric Sepsis Guidelines: Summary for resource-limited countries

    Science.gov (United States)

    Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish

    2010-01-01

    Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908

  6. The Microcirculation System in Critical Conditions Caused by Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    S. L. Kan

    2011-01-01

    Full Text Available Objective: to evaluate the microcirculation system in critical conditions caused by abdominal sepsis for a further differentiated approach to intensive care. Subjects and methods. Twenty-four patients with abdominal sepsis (mean age 42.9±0.9 years were examined; a control group consisted of 35 apparently healthy individuals (mean age 40.1±2.1 years. Over 11 days, the microcirculatory bed was evaluated by cutaneous laser Doppler flowmetry by means of a ЛАКК-02 laser capillary blood flow analyzer made in the Russian Federation (LAZMA Research-and-Production Association, by using a basic light guide for percutaneous microcirculation studies. Results. Throughout the study, tissue blood perfusion remained in the patients with sepsis due to the higher effect of mainly active components of vascular tone regulation on the microvascular bed. In a poor outcome, there was a reduction in both active and passive regulatory effects on tissue perfusion chiefly due to local (myogenic factors. Conclusion. The findings suggest that the patients with sepsis have microcirculatory regulation changes aimed at maintaining tissue perfusion. A follow-up of the microcirculation may be useful in choosing intensive care tactics and predicting disease outcome. Key words: sepsis, microcirculation, microvascular bed, micro blood flow, tissue perfusion.

  7. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    Science.gov (United States)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  8. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    Science.gov (United States)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  9. The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.

    Science.gov (United States)

    Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio; Whiteson, Katrine

    2018-06-27

    The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae , Enterococcus , and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R 2 = 0.48, P PERMANOVA R 2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding

  10. Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Shaw, J.H.; Durkot, M.J.

    1985-01-01

    The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2- 3 H]glycerol and [1- 14 C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1- 13 C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. The authors conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis

  11. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality

    Directory of Open Access Journals (Sweden)

    Larson CP

    2012-11-01

    Full Text Available Matthew O Wiens,1 Elias Kumbakumba,2 Niranjan Kissoon,3 J Mark Ansermino,4 Andrew Ndamira,2 Charles P Larson51School of Population and Public Health, University of British Columbia, Vancouver, Canada; 2Department of Pediatrics, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Pediatrics, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 4Department of Anesthesia, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 5Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, CanadaAbstract: Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.Keywords: children, pediatric sepsis, developing countries

  12. Experimental sepsis impairs humoral memory in mice.

    Directory of Open Access Journals (Sweden)

    Christian Pötschke

    Full Text Available Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.

  13. Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

    Science.gov (United States)

    Motzkus, Christine A; Luckmann, Roger

    2017-09-01

    Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

  14. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    Science.gov (United States)

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  15. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    Science.gov (United States)

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Serum Neutrophil Gelatinase-Associated Lipocalin in Infants and Children with Sepsis-Related Conditions with or without Acute Renal Dysfunction

    Directory of Open Access Journals (Sweden)

    Mohammed Farouk M. Afify

    2016-01-01

    Full Text Available Purpose To validate serum neutrophil gelatinase-associated lipocalin (NGAL as an early biomarker for acute kidney injury (AKI in sepsis-related conditions and its predictive and prognostic values. Patients and Methods This study included 65 patients, who were clinically evaluated for sepsis, severe sepsis, or septic shock, and 20 apparently healthy served as controls. Patients were divided into two groups: Group I (AKI-sepsis: 65 newly admitted patients diagnosed as sepsis, who were further divided into three subgroups according to the severity: systemic inflammatory response syndrome, severe sepsis, and septic shock, and Group II (control group: 20 apparently healthy subjects matched for age and sex, serum creatinine and serum NGAL concentrations were estimated initially within 24 hours of admission and after 72 hours of admission in all patients and control groups. Results Serum NGAL increased significantly with increasing severity of renal impairment. Receiver-operating characteristic analysis suggested that serum NGAL cutoff value of 40 ng/mL within the first 24 hours of admission is highly specific and sensitive for predicting AKI, with sensitivity of 90.9% and specificity of 75.8%. Conclusion We concluded that early measurement of serum NGAL level in sepsis can serve as a clinically useful marker for early prediction of AKI and for grading of its severity.

  17. Sepsis patients' renal manifestation on contrast-enhanced CT

    International Nuclear Information System (INIS)

    Sasaguri, K.; Yamaguchi, K.; Nakazono, T.; Mizuguchi, M.; Irie, H.

    2016-01-01

    Aim: To evaluate renal volume and attenuation changes in patients with sepsis on contrast-enhanced computed tomography (CT) with respect to the severity of sepsis. Materials and methods: Forty-four patients with sepsis who underwent CT before and after the onset of sepsis were retrospectively analysed. Renal volume and CT attenuation value of the renal cortex on contrast-enhanced CT were measured for each patient and changes in renal volume and CT attenuation value from before to after the onset of sepsis were calculated. The changes were correlated with the severity of sepsis (Sepsis-related Organ Failure Assessment [SOFA] score). The time course of the renal volume and CT attenuation changes were also evaluated. Results: Renal volume increased by 17.6% and CT attenuation value decreased by 19% after the onset of sepsis with statistically significant differences (p<0.001 for both renal volume and CT attenuation changes). The renal volume and CT attenuation changes had significant correlations with the SOFA score (r=0.36, p=0.018 and −0.43, p=0.005, respectively). The time course of the renal volume and CT attenuation changes seemed to be gradual compared to that of the SOFA score and to lag behind the peak of the SOFA score. Conclusion: In patients with sepsis, the renal volume increases and the CT attenuation value decreases in proportion to the severity of sepsis. The changes may lag behind the peak of severity of sepsis and can be observed for a relatively long time after a patient's recovery from sepsis. - Highlights: • The renal volume increases and the renal enhancement on contrast-enhanced CT decreases in patients with sepsis. • The degrees of these changes are correlated with severity of sepsis. • These changes may lag behind the peak of severity of sepsis and last for a long time after a patient's recovery from sepsis.

  18. Advances in sepsis-associated liver dysfunction

    OpenAIRE

    Wang, Dawei; Yin, Yimei; Yao, Yongming

    2014-01-01

    Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In additi...

  19. [Value of sepsis single-disease manage system in predicting mortality in patients with sepsis].

    Science.gov (United States)

    Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D

    2018-04-03

    Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90

  20. Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial.

    Science.gov (United States)

    Janz, David R; Bastarache, Julie A; Rice, Todd W; Bernard, Gordon R; Warren, Melissa A; Wickersham, Nancy; Sills, Gillian; Oates, John A; Roberts, L Jackson; Ware, Lorraine B

    2015-03-01

    This trial evaluated the efficacy of acetaminophen in reducing oxidative injury, as measured by plasma F2-isoprostanes, in adult patients with severe sepsis and detectable plasma cell-free hemoglobin. Single-center, randomized, double-blind, placebo-controlled phase II trial. Medical ICU in a tertiary, academic medical center. Critically ill patients 18 years old or older with severe sepsis and detectable plasma cell-free hemoglobin. Patients were randomized 1:1 to enteral acetaminophen 1 g every 6 hours for 3 days (n = 18) or placebo (n = 22) with the same dosing schedule and duration. F2-Isoprostanes on study day 3, the primary outcome, did not differ between acetaminophen (30 pg/mL; interquartile range, 24-41) and placebo (36 pg/mL; interquartile range, 25-80; p = 0.35). However, F2-isoprostanes were significantly reduced on study day 2 in the acetaminophen group (24 pg/mL; interquartile range, 19-36) when compared with placebo (36 pg/mL; interquartile range, 23-55; p = 0.047). Creatinine on study day 3, a secondary outcome, was significantly lower in the acetaminophen group (1.0 mg/dL; interquartile range, 0.6-1.4) when compared with that in the placebo (1.3 mg/dL; interquartile range, 0.83-2.0; p = 0.039). There was no statistically significant difference in hospital mortality (acetaminophen 5.6% vs placebo 18.2%; p = 0.355) or adverse events (aspartate aminotransferase or alanine aminotransferase > 400; acetaminophen 9.5% vs placebo 4.3%; p = 0.599). In adults with severe sepsis and detectable plasma cell-free hemoglobin, treatment with acetaminophen within 24 hours of ICU admission may reduce oxidative injury and improve renal function. Additional study is needed to confirm these findings and determine the effect of acetaminophen on patient-centered outcomes.

  1. Sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Rhodes, Andrew; Venkatesh, Bala

    2017-01-01

    Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countri...

  2. Is hypertriglyceridemia a prognostic factor in sepsis?

    Directory of Open Access Journals (Sweden)

    Cetinkaya A

    2014-02-01

    Full Text Available Ali Cetinkaya,1 Abdulsamet Erden,1 Deniz Avci,1 Hatice Karagoz,1 Samet Karahan,1 Mustafa Basak,1 Kadir Bulut,1 Vedat Gencer,1 Hasan Mutlu2 1Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey; 2Medical Oncology Department, Acibadem Kayseri Hospital, Kayseri, Turkey Introduction: Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality in patients with severe sepsis. Materials and methods: Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results: The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.49±11.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31 in the non-survivor group and 19% (6/31 in the survivor group. There was a significant difference regarding TG values between groups (P=0.039. Discussion: It was observed in this study that patients in the intensive care unit with sepsis had high

  3. Uterine Sarcoma Presenting with Sepsis from Clostridium perfringens Endometritis in a Postmenopausal Woman

    Directory of Open Access Journals (Sweden)

    Mary J. Kao

    2018-01-01

    Full Text Available Clostridium perfringens is an anaerobic gram positive rod that is found in normal vaginal and cervical flora in 1–10% of healthy women. Uterine infection with Clostridium perfringens is seen rarely but is often related to underlying uterine pathology and can progress quickly to sepsis. Early recognition of sepsis, prompt treatment with antibiotics, and source control with surgical management allow for optimal chance of recovery. We present a case of a postmenopausal woman who presented with sepsis, vaginal bleeding, and back pain who was found to have Clostridium perfringens infection in the setting of undifferentiated uterine sarcoma.

  4. Therapeutic effects of compound hypertonic saline on rats with sepsis

    Directory of Open Access Journals (Sweden)

    Fang Dong

    2014-09-01

    Full Text Available Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

  5. The German Quality Network Sepsis: study protocol for the evaluation of a quality collaborative on decreasing sepsis-related mortality in a quasi-experimental difference-in-differences design.

    Science.gov (United States)

    Schwarzkopf, Daniel; Rüddel, Hendrik; Gründling, Matthias; Putensen, Christian; Reinhart, Konrad

    2018-01-18

    While sepsis-related mortality decreased substantially in other developed countries, mortality of severe sepsis remained as high as 44% in Germany. A recent German cluster randomized trial was not able to improve guideline adherence and decrease sepsis-related mortality within the participating hospitals, partly based on lacking support by hospital management and lacking resources for documentation of prospective data. Thus, more pragmatic approaches are needed to improve quality of sepsis care in Germany. The primary objective of the study is to decrease sepsis-related hospital mortality within a quality collaborative relying on claims data. The German Quality Network Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study protocol describes the conduction and evaluation of the start-up period of the GQNS running from March 2016 to August 2018. Democratic structures assure participatory action, a study coordination bureau provides central support and resources, and local interdisciplinary quality improvement teams implement changes within the participating hospitals. Quarterly quality reports focusing on risk-adjusted hospital mortality in cases with sepsis based on claims data are provided. Hospitals committed to publish their individual risk-adjusted mortality compared to the German average. A complex risk-model is used to control for differences in patient-related risk factors. Hospitals are encouraged to implement a bundle of interventions, e.g., interdisciplinary case analyses, external peer-reviews, hospital-wide staff education, and implementation of rapid response teams. The effectiveness of the GQNS is evaluated in a quasi-experimental difference-in-differences design by comparing the change of hospital mortality of cases with sepsis with organ dysfunction from a retrospective baseline period (January 2014 to December 2015) and the intervention period (April 2016 to March 2018) between the participating hospitals and all other German

  6. Radiologic findings of neonatal sepsis

    International Nuclear Information System (INIS)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong

    1997-01-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment

  7. Radiologic findings of neonatal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

    1997-06-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.

  8. Post operative infection and sepsis in humans is associated with deficient gene expression of gammac cytokines and their apoptosis mediators.

    LENUS (Irish Health Repository)

    White, Mary

    2011-06-28

    Abstract Introduction Lymphocyte homeostasis is dependent on the γc cytokines. We hypothesised that sepsis in humans is associated with differential gene expression of the γc cytokines and their associated apoptosis mediators. Methods The study population consisted of a total of 60 patients with severe sepsis, 15 with gram negative bacteraemia, 10 healthy controls and 60 patients undergoing elective lung resection surgery. Pneumonia was diagnosed by CDC NNIC criteria. Gene expression in peripheral blood leukocytes (PBLs) of interleukin (IL)-2, 7, 15 and interferon (IFN)-γ, Bax, Bim, Bcl-2 was determined by qRT-PCR and IL-2 and IL-7 serum protein levels by ELISA. Gene expression of IL-2, 7 and IFN-γ was measured in peripheral blood leukocytes (PBL), cultured in the presence of lipopolysacharide (LPS) and CD3 binding antibody (CD3ab) Results IL-2 gene expression was lower in the bacteraemia group compared with controls, and lower still in the sepsis group (P < 0.0001). IL-7 gene expression was similar in controls and bacteraemia, but lower in sepsis (P < 0.0001). IL-15 gene expression was similar in the three groups. Bcl-2 gene expression was less (P < 0.0001) and Bim gene expression was greater (P = 0.0003) in severe sepsis compared to bacteraemic and healthy controls. Bax gene expression was similar in the three groups. In lung resection surgery patients, post-operative pneumonia was associated with a perioperative decrease in IL-2 mRNA (P < 0.0001) and IL-7 mRNA (P = 0.003). IL-2 protein levels were reduced in sepsis and bacteraemia compared to controls (P = 0.02) but similar in pneumonia and non-pneumonia groups. IL-7 protein levels were similar in all groups. In cultured PBLs, IFN-γ gene expression was decreased in response to LPS and increased in response to CD3ab with sepsis: IL-7 gene expression increased in response to LPS in controls and to CD3ab with sepsis; Bcl-2 gene expression decreased in response to combined CD3ab and IL-2 with sepsis

  9. Effect of bacterial sepsis on gluconeogenic capacity in the rat

    International Nuclear Information System (INIS)

    Holman, J.M. Jr.; Saba, T.M.

    1988-01-01

    Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [ 14 C]alanine to [ 14 C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting

  10. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

    Directory of Open Access Journals (Sweden)

    Stefania Battista

    2016-01-01

    Full Text Available The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism. Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L, calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  12. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

    Science.gov (United States)

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  13. Brain infection following experimental Staphylococcus aureus sepsis in pigs

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Iburg, Tine Moesgaard; Nielsen, Ole Lerberg

    2010-01-01

    Introduction: Sepsis is a major problem in humans and both the incidence and mortality is increasing. Multiple microabcesses can be found in the brain of septic patients. Staphylococcus aureus is one of the most common causes of sepsis and brain abscesses. S. aureus is also a frequent cause...... of spontaneous porcine pyemia including endocarditis and associated brain lesions. We present a porcine model of haematogenous S. aureus induced brain infection. Materials and Methods: Twelve pigs received an intravenous injection of S. aureus of 108 CFU/kg body weight once at 0h or twice at 0h and 12h. Four...... pigs were kept as controls. The pigs were euthanized in groups of four at either 6, 12, 24 or 48 h post infection. The brain was collected from all the animals and examined histologically. Results: All the inoculated pigs developed sepsis and 7 out of 12 animals had microabscesses in the prosencephalon...

  14. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis.

    Science.gov (United States)

    Alcayaga-Miranda, Francisca; Cuenca, Jimena; Martin, Aldo; Contreras, Luis; Figueroa, Fernando E; Khoury, Maroun

    2015-10-16

    Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB

  15. Plasminogen activators in inflammation and sepsis.

    Science.gov (United States)

    Pechlaner, Ch

    2002-01-01

    Mortality of severe sepsis remains at 40% to 50%. Intensive efforts over the past two decades have only marginally improved outcome. Improving outcome in sepsis depends on understanding its pathophysiology, which involves triggers, responses of the organism, and dysfunction. Stress, injury, or infection trigger host responses, including local and systemic orchestrated mechanisms. Dysfunction and outcome depend on both trigger and response. Blood coagulation, inflammation, immunity, and fibrinolysis are critical components of the organism's responses. Understanding their role in sepsis pathophysiology is the key to effective treatment. Relevant studies were identified by a systematic literature search, complemented by manual search of individual citations. Using PubMed, 'sepsis' yields more than 62,000 references, 'plasminogen activators' more than 21,000. The selection of citations was guided by preference for reviews that expand important threads of argumentation. Single original studies were included when relevant to critical points. This analytical review describes the essential elements of pathophysiology and the current status of sepsis treatment. Based on this context, an emerging therapeutic option will be discussed: plasminogen activators.

  16. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Directory of Open Access Journals (Sweden)

    Leena B Mithal

    Full Text Available Early onset sepsis (EOS is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2 were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12; presumed sepsis (PS, n = 30; and no sepsis (controls, n = 30. Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™. In addition, placental histopathologic data were linked to biomarker results.cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP, serum amyloid A (SAA, haptoglobin (Hp, serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01. SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01 and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  17. May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

    Science.gov (United States)

    Segre, Elisabetta; Pigozzi, Luca; Lison, Davide; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Suppo, Umberto; Turvani, Fabrizio; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

    2014-10-01

    Thrombopoietin (TPO), a growth factor primarily involved in regulating thrombopoiesis, has been recently implicated in the pathogenesis of sepsis. TPO levels are, indeed, greatly increased in patients with sepsis compared to control subjects, and correlate with sepsis severity. The aim of this study was to evaluate TPO as predictive biomarker of sepsis and of sepsis severity in patients entering the emergency department (ED) with systemic inflammatory response syndrome (SIRS). This was a prospective observational study. Ours is a sub-study of the 'Need-speed trial', a multi-center observational study involving six Italian centers affiliated to the GREAT Italian Network. TPO was measured by ELISA. We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of whom had severe sepsis and three septic shock. TPO was significantly higher in patients with sepsis than with SIRS. In addition, TPO was higher in patients with severe sepsis than with sepsis, and in patients with septic shock than with severe sepsis, although these differences did not reach the statistical significance. Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

  18. Regulators of Intestinal Epithelial Migration in Sepsis.

    Science.gov (United States)

    Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

    2018-02-08

    The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

  19. Seasonal Variation in the Emergency Department Prevalence Of Sepsis

    LENUS (Irish Health Repository)

    McNevin, C

    2018-05-01

    The incidence and mortality of sepsis and severe sepsis in hospitalised patients is seasonal and consistently highest during the winter. The primary aim of this study was to measure the seasonal variation in the prevalence of emergency department (ED) patients with sepsis. This cross-sectional study was performed over two four-week periods in the summer and in the winter, respectively. The clinical records of all patients presenting to the ED during the study periods were retrospectively screened to determine if they met the criteria for “uncomplicated” sepsis and severe sepsis or septic shock. The prevalence of “uncomplicated” sepsis was higher in the winter (43.9 per 1000) compared to the summer (30.7 per 1000). The prevalence of severe sepsis or septic shock was also higher in the winter (17.7 per 1000) compared to the summer (11.7 per 1000). This quantitatively demonstrates the increased ED burden of sepsis in the winter that can be used to inform healthcare planning and resource allocation.

  20. Molecular diagnosis of microbial aetiologies using SepsiTest™ in the daily routine of a diagnostic laboratory.

    Science.gov (United States)

    Haag, Heike; Locher, Franziska; Nolte, Oliver

    2013-08-01

    A universal PCR and sequencing test, SepsiTest™ (Molzym, Germany) was evaluated for its applicability during daily diagnostic routine in a privately operated laboratory. In total, 96 specimens originating from 66 patients under suspect of infectious endocarditis, infections of joints, encephalitis/meningitis, systemic infections and infections of unknown genesis were PCR analysed and compared to culture results. Samples comprised cultured and non-cultured blood, synovial fluid, synovial tissue, heart valves, pacemakers, spinal tissue, cerebrospinal fluid, and swabs. PCR and culture were concordant in 26 negative and 8 positive cases (51.5%). A group of 25 patients was culture-negative but PCR-positive (37.9%). In at least 14 of these, common and/or rare aetiologies were identified, while for 4 patients the results of 16S PCR could not be unequivocally linked with the underlying disease. Benefits and limitations of the molecular test are discussed with special emphasis on technical and economic issues. In conclusion, SepsiTest™ proved to be a valuable tool for the diagnosis of aetiologies, particularly in cases of culture-negative patients who are under strong suspicion for an infection. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care.

    Science.gov (United States)

    Onwuneme, Chike; Carroll, Aoife; Doherty, Dermot; Bruell, Heike; Segurado, Ricardo; Kilbane, Mark; Murphy, Nuala; McKenna, Malachi J; Molloy, Eleanor J

    2015-10-01

    This study aimed to assess vitamin D status, and its determinants, in paediatric patients with suspected sepsis who were admitted to a paediatric intensive care unit (PICU). We also investigated the association between vitamin D status and clinical outcomes. Serum 25-hydroxy vitamin D (25OHD) and clinical determinants were prospectively assessed in children with suspected sepsis (<12 years old) admitted to the PICU. The relationship between 25OHD and clinical outcomes was evaluated. Vitamin D status was also assessed in control children of a similar age. We enrolled 120 children with suspected sepsis admitted to the PICU and 30 paediatric controls. 25OHD was <50 nmol/L in 59% of the children admitted to the PICU and 25OHD was lower than in the controls (47 ± 29 vs 66 ± 26 nmol/L, p < 0.001). After adjusting for potential confounders, 25OHD was strongly associated with culture positive sepsis (p < 0.001), the paediatric index of mortality (p = 0.026) and the duration of mechanical ventilation (p = 0.008). There was a negative correlation between 25OHD and C-reactive protein (CRP): each 0.1% decrease in 25OHD increased CRP (p = 0.04). Children admitted to the PICU with suspected sepsis had lower 25OHD than controls and inadequate 25OHD status was associated with confirmed sepsis and poor outcomes. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  2. Thromboelastography in patients with severe sepsis

    DEFF Research Database (Denmark)

    Haase, Nicolai; Ostrowski, Sisse Rye; Wetterslev, Jørn

    2015-01-01

    PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156......) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox...... bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding....

  3. A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

    Science.gov (United States)

    Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

    2017-08-23

    An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Sepsis: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Eliézer Silva

    2008-01-01

    Full Text Available Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.

  5. Sepsis and Shock Response Team: Impact of a Multidisciplinary Approach to Implementing Surviving Sepsis Campaign Guidelines and Surviving the Process.

    Science.gov (United States)

    Grek, Ami; Booth, Sandra; Festic, Emir; Maniaci, Michael; Shirazi, Ehsan; Thompson, Kristine; Starbuck, Angela; Mcree, Chad; Naessens, James M; Moreno Franco, Pablo

    The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.

  6. Urine metabolomics in neonates with late-onset sepsis in a case-control study

    Science.gov (United States)

    Sarafidis, Kosmas; Chatziioannou, Anastasia Chrysovalantou; Thomaidou, Agathi; Gika, Helen; Mikros, Emmanouel; Benaki, Dimitra; Diamanti, Elisavet; Agakidis, Charalampos; Raikos, Nikolaos; Drossou, Vasiliki; Theodoridis, Georgios

    2017-04-01

    Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

  7. Sepsis is a preventable public health problem.

    Science.gov (United States)

    Kempker, Jordan A; Wang, Henry E; Martin, Greg S

    2018-05-06

    There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.

  8. Long term health-related quality of life in survivors of sepsis in South West Wales: an epidemiological study.

    Science.gov (United States)

    Battle, Ceri E; Davies, Gareth; Evans, Phillip A

    2014-01-01

    Survivors of sepsis report persistent problems that can last years after hospital discharge. The main aim of this study was to investigate long-term health-related quality of life in survivors of SIRS and sepsis compared with Welsh normative data, controlling for age, length of stay and pre-existing conditions. The second aim was to investigate any differences in long-term health-related quality of life specifically with the patients categorised into three groups; SIRS, uncomplicated sepsis and severe sepsis/septic shock. A prospective study design was used in order to investigate all sepsis patients either presenting to the Emergency Department or admitted to the Intensive Care Unit of a regional trauma centre. Baseline demographics, clinical characteristics and outcomes were collected and surviving patients were sent a SF-12v2 survey at between six months to two years post-hospital discharge. Quality of life was significantly reduced in all patients when compared to local normative data (all pquality of life were more pronounced in severe sepsis/septic shock patients when compared to uncomplicated sepsis and SIRS patients, when controlling for age, pre-existing conditions, hospital and ICU length of stay. This is the first observational study to specifically focus on the different groups of SIRS and sepsis patients to assess long-term quality of life. Local population norms were used for comparison, rather than UK-wide norms that fail to reflect the intricacies of a country's population.

  9. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    Science.gov (United States)

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  10. The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

    Science.gov (United States)

    Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley

    2018-05-01

    In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult

  11. Inadequate exercise as a risk factor for sepsis mortality.

    Science.gov (United States)

    Williams, Paul T

    2013-01-01

    Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0

  12. Sepsis and cytomegalovirus: foes or conspirators?

    Science.gov (United States)

    Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H

    2015-06-01

    Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

  13. Preventing intensive care admissions for sepsis in tropical Africa (PICASTA): an extension of the international pediatric global sepsis initiative: an African perspective.

    Science.gov (United States)

    Pollach, Gregor; Namboya, Felix

    2013-07-01

    The Global Sepsis Initiative recommends prevention of sepsis through immunizations, vitamins, breast feeding, and other important interventions. In our study, we consider a second set of proposals for preventing intensive care admissions for sepsis in tropical Africa, which have been specifically designed to further prevent ICU admissions for sepsis in the group A nation hospital setting. To reduce admissions with severe sepsis in an ICU of a group A nation through the identification of challenges leading to preventable, foreseeable, or nosocomial sepsis specific to our setting. Malawi is one of the poorest countries in the world. Lacking the ability to comply with standard sepsis treatment, we conducted over 4 years several studies, audits, and surveys to identify challenges leading to preventable pediatric sepsis in our setting. We developed a method to identify malnourished children through a "gatekeeper" in the theaters without any equipment, tried to implement the World Health Organization's Safe Surgery Campaign checklist, evaluated our educational courses for the districts to improve the quality of referrals, looked into the extreme fasting times discovered in our hospital, trained different cadres in the districts to deal with peripartal and posttraumatic sepsis, and identified the needs in human resources to deal with pediatric sepsis in our setting. Six foci were identified as promising to work on in future. Focus 1: Preventing elective operations and procedures in malnourished children in the hospital and in the district: 134 of 145 nurses (92.4%) and even 25 of 31 African laymen (80.6%) were able to identify malnourished children with their own fingers. Focus 2: Preventing sepsis-related problems in emergencies through the implementation of the Safe Surgery Campaign checklist: only 100 of 689 forms (14.5%) were filled in due to challenges in ownership, communication responsibility, and time constraints. Focus 3: Preventing sepsis through the reduction

  14. Surviving the first hours in sepsis: getting the basics right (an intensivist's perspective).

    Science.gov (United States)

    Daniels, Ron

    2011-04-01

    Severe sepsis is a major cause of morbidity and mortality, claiming between 36 000 and 64 000 lives annually in the UK, with a mortality rate of 35%. International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles. In 2010, the Campaign published results from its improvement programme showing that, although an absolute mortality reduction of 5.4% was seen over a 2 year period in line with increasing compliance with the Bundles, reliability was not achieved and Bundle compliance reached only 31%. This article explores current challenges in sepsis care and opportunities for further improvements. Basic care tasks [microbiological sampling and antibiotic delivery within 1 h, fluid resuscitation, and risk stratification using serum lactate (or alternative)] are likely to benefit patients most, yet are unreliably performed. Barriers include lack of awareness and robust process, the lack of supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex life-saving tasks (such as early goal-directed therapy) demands greater awareness, faster recognition and initiation of basic care, and more effective collaboration between clinicians and nurses on the front line, in critical care and in specialist support services, such as microbiology and infectious diseases. Organizations such as Survive Sepsis, the Surviving Sepsis Campaign and the Global Sepsis Alliance are working to raise awareness and promote further improvement initiatives. Future developments will focus on sepsis biomarkers and microarray techniques to rapidly screen for pathogens, risk stratification using genetic profiling, and the development of novel therapeutic agents targeting immunomodulation.

  15. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  16. MicroRNA's are novel biomarkers in sepsis

    DEFF Research Database (Denmark)

    Søndergaard, Edith Smed; Alamili, Mahdi; Coskun, Mehmet

    2015-01-01

    Purpose: Sepsis is one of the leading causes of death after admission to the intensive care unit (ICU). The discovery of small non-coding microRNAs (miRs) and their correlation to sepsis has gained increasing interest. Our aim was to systematically review the literature examining the association ...... searching the computational target prediction databases. Conclusion: Various miRs are associated with sepsis, but no corresponding predictor genes were found....

  17. Treatment of patients with severe sepsis using Ulinastatin and Thymosin α1: a prospective, randomized, controlled pilot study

    Institute of Scientific and Technical Information of China (English)

    CHEN Hao; HE Ming-yan; LI Yu-min

    2009-01-01

    Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin (UTI) plus Thymosin α1 (Tα1) for improving organ function and reducing mortality in patients with severe sepsis.Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tα1 (defined as Group A), 55 patients were given a placebo (defined as Group B). Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ), multiple organ failure (MOF) and the Glasgow Coma Scores (GCS) on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4+/CD8+ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive

  18. N-acetylcysteine for sepsis and systemic inflammatory response in adults.

    Science.gov (United States)

    Szakmany, Tamas; Hauser, Balázs; Radermacher, Peter

    2012-09-12

    Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial. We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis. We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review. We included only randomized controlled trials (RCTs) in the meta-analysis. We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability. Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful

  19. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Guoda Ma

    2014-01-01

    Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P=0.622 for genotype; P=0.629 for allele. However, stratification by subtypes (sepsis, septic shock, and severe sepsis revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014 for allele and P=0.012, for genotype. Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P=0.002. In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P<0.001. Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

  20. Diagnosis trajectories of prior multi-morbidity predict sepsis mortality

    DEFF Research Database (Denmark)

    Beck, Mette Kristina; Jensen, Anders Boeck; Nielsen, Annelaura Bach

    2016-01-01

    Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease histo...... of disease history to scoring based on within-admission clinical measurements emphasizing the value of long term data in novel patient scores that combine the two types of data.......Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease history...... recurrent trajectories of time-ordered co-morbidities had significantly increased sepsis mortality compared to those who did not follow a trajectory. We identified trajectories which significantly altered sepsis mortality, and found three major starting points in a combined temporal sepsis network: Alcohol...

  1. Neonatal sepsis: Highlighting the principles of diagnosis and management

    Directory of Open Access Journals (Sweden)

    Melantha Coetzee

    2017-07-01

    Full Text Available Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal sepsis to be 8.5 - 10%, with late-onset sepsis accounting for most of these infections. The diagnosis of neonatal sepsis is not always straightforward, and the initiation and continuation of antimicrobials in these situations relies on good clinical judgment. The need for empirical antimicrobials is driven by the existence of risk factors for early-onset sepsis and clinical symptoms and signs of late-onset sepsis. Antimicrobial stewardship programmes should be in place to guide clinicians to either stop, change, or continue antimicrobials. Institution-specific knowledge of the most common pathogens and the antimicrobial susceptibility pattern is important to prevent the emergence of further antimicrobial resistance.

  2. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  3. Diagnostic methods in sepsis: the need of speed

    Directory of Open Access Journals (Sweden)

    Fernando Rodrigues Coelho

    2012-08-01

    Full Text Available OBJECTIVE: Sepsis is a common condition encountered in hospital environments. There is no effective treatment for sepsis, and it remains an important cause of death at intensive care units. This study aimed to discuss some methods that are available in clinics, and tests that have been recently developed for the diagnosis of sepsis. METHODS: A systematic review was performed through the analysis of the following descriptors: sepsis, diagnostic methods, biological markers, and cytokines. RESULTS: The deleterious effects of sepsis are caused by an imbalance between the invasiveness of the pathogen and the ability of the host to mount an effective immune response. Consequently, the host's immune surveillance fails to eliminate the pathogen, allowing it to spread. Moreover, there is a pro-inflammatory mediator release, inappropriate activation of the coagulation and complement cascades, leading to dysfunction of multiple organs and systems. The difficulty achieve total recovery of the patient is explainable. There is an increased incidence of sepsis worldwide due to factors such as aging population, larger number of surgeries, and number of microorganisms resistant to existing antibiotics. CONCLUSION: The search for new diagnostic markers associated with increased risk of sepsis development and molecules that can be correlated to certain steps of sepsis is becoming necessary. This would allow for earlier diagnosis, facilitate patient prognosis characterization, and prediction of possible evolution of each case. All other markers are regrettably constrained to research units.

  4. Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Seoh Wei Teh

    2018-02-01

    Full Text Available Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

  5. Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

    Science.gov (United States)

    Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

    2018-02-13

    Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

  6. A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

    Science.gov (United States)

    Raschke, Robert A; Groves, Robert H; Khurana, Hargobind S; Nikhanj, Nidhi; Utter, Ethel; Hartling, Didi; Stoffer, Brenda; Nunn, Kristina; Tryon, Shona; Bruner, Michelle; Calleja, Maria; Curry, Steven C

    2017-01-01

    Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

  7. High Levels of Methylarginines Were Associated With Increased Mortality in Patients With Severe Sepsis

    DEFF Research Database (Denmark)

    Mortensen, Karoline Myglegard; Itenov, Theis Skovsgaard; Haase, Nicolai

    2016-01-01

    Introduction: Nitric oxide (NO) likely plays a pivotal role in the pathogenesis of sepsis. Arginine is a substrate for NO, whereas the methylated arginines—asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)—are endogenous by-products of proteolysis that inhibit NO production....... We investigated if high-plasma levels of ADMA, SDMA, and arginine/ADMA ratio were associated with 90-day mortality in patients with severe sepsis or septic shock. Methods: We included 267 adult patients admitted to intensive care unit with severe sepsis or septic shock. The patients had previously...... been included in the randomized controlled trial “Scandinavian Starch for Severe Sepsis and Septic Shock (6S).” ADMA, SDMA, and arginine/ADMA ratio were measured in plasma. The risk of death within 90 days was estimated in multivariate Cox regression analyses adjusted for gender, age >=65 years, major...

  8. Procalcitonin, MR-Proadrenomedullin, and Cytokines Measurement in Sepsis Diagnosis: Advantages from Test Combination

    Directory of Open Access Journals (Sweden)

    Silvia Angeletti

    2015-01-01

    Full Text Available Background. Elevated cytokines levels correlate with sepsis severity and mortality but their role in the diagnosis is controversial, whereas Procalcitonin (PCT has been largely used. Recently, the mid-regional proadrenomedullin (MR-proADM has been combined with PCT for diagnosis optimization. In this study the combined measurement of PCT, MR-proADM, and cytokines in patients with sepsis was evaluated. Methods. One hundred and four septic patients and 101 controls were enrolled. Receiver operating characteristic (ROC analysis and multiple logistic regression were used to evaluate applicant markers for sepsis diagnosis. Markers with best Odds Ratio (OR were combined, and the posttest probability and a composite score were computed. Results. Based upon ROC curves analysis, PCT, MR-proADM, IL-6, IL-10, TNF-α, and MCP-1 were considered applicant for sepsis diagnosis. Among these PCT, MR-proADM , IL-6, and TNF-α showed the best OR. A better posttest probability was found with the combination of PCT with MR-proADM and PCT with IL-6 or TNF-α compared to the single marker. A composite score of PCT, MR-proADM, and TNF-α showed the best ROC curve in the early diagnosis of sepsis. Conclusion. The combination of PCT with other markers should expedite diagnosis and treatment of sepsis optimizing clinical management.

  9. The Effectiveness of Combined Use of Antioxidant and Glutamine in Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    V. V. Nazaretyan

    2017-01-01

    Full Text Available Aim of the study: the effectiveness of concomitant use of antioxidant therapy with antioxidant 2-ethyl-6- methyl-3-hydroxypyridine succinate (mexidol and intensive nutritional support with glutamine in patients with abdominal sepsis (AS. Materials and methods. 170 patients with abdominal sepsis (AS involved in the study were separated into two groups. Patients of group 1 (control group, n=70 received basic treatment. Patients from group 2 (n=100 were divided into 2 subgroups. Patients from the subgroup 21 (n=70, in additon to the basic treatment, received intravenously, by drop infusion, mexidol (2000 mg per day and dipeptiven (27.5 g per day, patients from subgroup 22 (n=30 additionally to that received per os glutamine. Survival analysis was carried out according to the Kaplan-Meier method with using of the Cox's F-test and Mantel-Cox test for testing of statistical hypotheses. Results. Treatment outcomes analysis showed that in the basic group 2, mortality was lower than in the control group 1. A statistically significant increase of cumulative part in the survivors was revealed using mexidol and glutamine. Conclusion. Concomitant intravenous administration of medications had positive effects on treatment outcomes. Following on from the analysis results, we may suggest that the pair mexidol + dipeptiven interrupts the cascade of development of abdominal sepsis and contributes to avoiding a critical condition during sepsis.

  10. RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

    NARCIS (Netherlands)

    FISHER, C. J.; DHAINAUT, J. F. A.; Opal, S. M.; Pribble, J. P.; BALK, R. A.; SLOTMAN, G. J.; IBERTI, T. J.; RACKOW, E. C.; SHAPIRO, M. J.; GREENMAN, R. L.; REINES, H. D.; SHELLY, M. P.; THOMPSON, B. W.; LABRECQUE, J. F.; Catalano, M. A.; KNAUS, W. A.; Sadoff, J. C.; ASTIZ, M.; CARPATI, C.; BONE, R. C.; FREIDMAN, B.; MURE, A. J.; BRATHWAITE, C.; SHAPIRO, E.; MELHORN, L.; TAYLOR, R.; KEEGAN, M.; OBRIEN, J.; SCHEIN, R.; PENA, M.; WASSERLOUF, M.; OROPELLO, J.; BENJAMIN, E.; DELGUIDICE, R.; EMMANUEL, G.; LIE, T.; Anderson, L.; Marshall, J.; DEMAJO, W.; ROTSTEIN, O.; FOSTER, D.; Abraham, E.; MIDDLETON, H.; Perry, C.; LEVY, H.; FRY, D. E.; SIMPSON, S. Q.; CROWELL, R. E.; Neidhart, M.; Stevens, D.; COFFMAN, T.; NARASIMHAM, N.; MERRICK, D. K.; BERGQUIST, W.; MATZEL, K. E.; HUEBLER, M.; Foulke, G. E.; ALBERTSON, T. E.; WALBY, W. F.; ALLEN, R. P.; Baughman, R.; HASSELGREN, P. O.; Fink, M. P.; FAVORITO, F.; THOMPSON, B. T.; CORBIN, R.; SHELLHORSE, G. Y.; FRAZIER, A.; White, S.; GARRARD, C.; ACOURT, C.; STORER, S.; GERVICH, D. H.; FOSHE, D.; BRASE, R.; BAGDAHN, A.; COONEY, R.; Smith, J. S.; MARTIN, L. F.; Vincent, J. L.; Friedman, G.; Berlot, G.; FLETCHER, J. R.; WILLIAMS, M. D.; WRIGHT, T. F.; Johnson, S.; FEILD, C.; WOLF, K.; MACINTYRE, N.; DUBIN, H. G.; DURKIN, M. R.; DUBIN, P. K.; STAUBACH, K. H.; FEIN, A. M.; SCHULMAN, D. B.; NIEDERMAN, M. S.; CHALFIN, D. B.; van Leeuwen, P. A. M.; Boermeester, M. A.; Schneider, A. J.; BANDER, J.; IMM, A.; BERNARD, G.; Nelson, L.; Stroud, M.; SAFCSAK, K.; CERRA, F.; RINDAL, J.; Mann, H.; HALPERN, N.; SILVERSTEIN, J.; ALICEA, M.; Sibbald, W. J.; MARTIN, C. M.; RUTLEDGE, F. S.; PETTI, K.; RUSSELL, J. A.; KRUGER, R.; DRUMMOND, A.; LANGE, P.; SEIFERT, T.; DUROCHER, A.; TENAILLON, A.; BOITEAU, R.; LHERM, T.; Lowry, S. F.; Coyle, S. M.; Barie, P. S.; DEMARIA, E.; SNYDMAN, D. R.; SCHWAITZBERG, S. D.; NASRAWAY, S. A.; GRINDLINGER, J.; SUMMER, W.; DEBOISBLANC, B.; WAHL, M.; ALESTIG, K.; GROSSMAN, J.; MAKI, D.; PAZ, H. L.; Weiner, M.; BIHARI, D.; Campbell, D.; BLEICHNER, G.; DAHN, M. S.; LANGE, M. P. A.; Hall, J.; POHLMAN, A.; WENZEL, R. P.; GROSSERODE, M.; COSTIGAN, M.; MILESKI, W.; WEIGELT, J.; YESTON, N.; IRIZARRY, C.; Ross, J.; ROBBINS, J.; NIGHTINGALE, P.; OWEN, K.; SANDSTEDT, S.; Berg, S.; SIMON, G. L.; SENEFF, M. G.; CONRY, K. M.; ZIMMERMAN, J. L.; Dellinger, R. P.; Johnston, R.; ALLEE, P.; GRANDE, P. O.; MYHRE, E.; DHAINAUT, J. F.; HAMY, I.; Mira, J. P.; HARMON, J.; White, J.; MCKIE, L.; SILVERMAN, H.; TUMA, P.; Bennett, D.; PORTER, J. C.; LAURELL, M. H.; Jacobs, S.; ASH, S.; Stiles, D. M.; PRIOR, M. J.; KNATTERUD, G.; TERRIN, M.; KUFERA, J.; WILKENS, P.; RA, K.; MONROE, L.; SPRUNG, C.; HAMILTON, C. M.; MATTHAY, R.; MCCABE, W.; TONASCIA, J.; WIEDEMAN, H.; Wittes, J.; CAMPION, G. V.; CROFT, C. R.; LUSTICK, R.; LOOKABAUGH, J.; GORDON, G. S.; NOE, L.; BLOEDOW, D.; SMITH, C. G.; BRANNON, D.; KUSH, R.; NG, D.; MOORE, E.; BAZEMORE, K.; GALVAN, M.; Wagner, D.; HARRELL, F.; STABLEIN, D.

    1994-01-01

    Objective.-To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhlL-1ra) in the treatment of sepsis syndrome. Study Design.-Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population.-A total of 893 patients with

  11. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Designing a Pediatric Severe Sepsis Screening Tool

    Directory of Open Access Journals (Sweden)

    Robert eSepanski

    2014-06-01

    Full Text Available We sought to create a screening tool with improved predictive value for pediatric severe sepsis and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric Emergency Department (ED. Gold standard severe sepsis cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over two months. The tool’s identification of severe sepsis was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating curve (ROC characteristics. Age-specific normal and abnormal values for heart rate (HR and respiratory rate (RR were empirically derived from 143,603 children seen in a second pediatric ED over three years. Univariate analyses were performed for each measure in the tool to assess its association with severe sepsis and to characterize it as an early or late indicator of severe sepsis. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly three-fold improvement over the original ICCPS tool. False positive Systemic Inflammatory Response Syndrome (SIRS identifications were nearly six-fold lower.

  13. Trends in microbial control techniques for poultry products.

    Science.gov (United States)

    Silva, Filomena; Domingues, Fernanda C; Nerín, Cristina

    2018-03-04

    Fresh poultry meat and poultry products are highly perishable foods and high potential sources of human infection due to the presence of several foodborne pathogens. Focusing on the microbial control of poultry products, the food industry generally implements numerous preventive measures based on the Hazard Analysis and Critical Control Points (HACCP) food safety management system certification together with technological steps, such as refrigeration coupled to modified atmosphere packaging that are able to control identified potential microbial hazards during food processing. However, in recent years, to meet the demand of consumers for minimally processed, high-quality, and additive-free foods, technologies are emerging associated with nonthermal microbial inactivation, such as high hydrostatic pressure, irradiation, and natural alternatives, such as biopreservation or the incorporation of natural preservatives in packaging materials. These technologies are discussed throughout this article, emphasizing their pros and cons regarding the control of poultry microbiota and their effects on poultry sensory properties. The discussion for each of the preservation techniques mentioned will be provided with as much detail as the data and studies provided in the literature for poultry meat and products allow. These new approaches, on their own, have proved to be effective against a wide range of microorganisms in poultry meat. However, since some of these emergent technologies still do not have full consumer's acceptability and, taking into consideration the hurdle technology concept for poultry processing, it is suggested that they will be used as combined treatments or, more frequently, in combination with modified atmosphere packaging.

  14. Microbial control of seawater by microfiltration

    Directory of Open Access Journals (Sweden)

    Wilmer Soler T

    2010-08-01

    Full Text Available Recent scientific literature presents seawater as a potential aid to solve a variety of health diseases in animals and human beings because by means of its mineral and trace elements content. In Colombia, Nicaragua and Spain it is collected in a natural way from de shore and drunk; however, this can represent a health risk because of the problems related to chemical and microbiological contamination. Microbial control of seawater allows the improvement of its microbiological quality. Objective: to compare the efficiency of three microbial control methods: microfiltration, solar exposition and quarantine. Methodology: 30 samples were collected in 20-liter high density polyethylene containers in three different places in the Colombian Atlantic coast. Results: 15 samples out of 30 showed the presence of bacteria such as E. coli and halophiles bacteria like Vibrio and Aeromonas. Microfiltration through ceramic filters of 0.5 µm produces disinfection in 100% of the samples but the quarantine for five months and solar disinfection are effective in 66 and 21% respectively. The latter requires certain weather conditions to achieve disinfection and it only allows managing small quantities of water. Dicussion: Considering chemical contamination in some places which cannot be controlled through disinfection methods, the collection of water offshore in clean places is suggested and then microfiltration treatment should be performed.

  15. Biomarkers, Trauma, and Sepsis in Pediatrics: A Review

    Directory of Open Access Journals (Sweden)

    Marianne Frieri

    2016-01-01

    Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species

  16. Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

    Directory of Open Access Journals (Sweden)

    Mahshid Talebi-Taher

    2014-06-01

    Full Text Available Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP, Erythrocyte Sedimentation Rate (ESR, procalcitonin (PCT, and Interleukin-6 (IL-6 to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98% and negative predictive value (98.6% and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI. On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

  17. Role of β1 Integrin in Tissue Homing of Neutrophils During Sepsis

    Science.gov (United States)

    Sarangi, Pranita P.; Hyun, Young-Min; Lerman, Yelena V.; Pietropaoli, Anthony P.; Kim, Minsoo

    2012-01-01

    Aberrant activation of neutrophils during sepsis results in the widespread release of pro-inflammatory mediators, leading to multi-organ system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multi organ system failure and death. One of the pivotal components of neutrophil migration during inflammation is the expression of surface integrins. In this study, we show that administration of a cyclic analog of RGD peptide (Arg-Gly-Asp) significantly reduced the number of tissue-invading neutrophils and the degree of sepsis-induced lethality in mice as compared to control peptide. Secondly, β1 integrin (CD29) was highly up-regulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of β1 integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of β1 integrin is important for modulating neutrophil trafficking during sepsis, and that therapeutics designed against β1 integrins may be beneficial. PMID:22683734

  18. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  19. SIGNALING MECHANISMS IN SEPSIS-INDUCED IMMUNE DYSFUNCTION

    OpenAIRE

    Hasan, Zirak

    2013-01-01

    Sepsis and subsequent organ failure remain the major cause of mortality in intensive care units in spite of significant research efforts. The lung is the most vulnerable organ affected by early hyper-inflammatory immune response in septic patients. On the other hand, the septic insult induces immune dysfunction in later phases of sepsis which in turn increases susceptibility to infections. The aim of this thesis was to investigate early and late inflammatory mechanisms in abdominal sepsis ind...

  20. The impact of hospital-onset Clostridium difficile infection on outcomes of hospitalized patients with sepsis.

    Science.gov (United States)

    Lagu, Tara; Stefan, Mihaela S; Haessler, Sarah; Higgins, Thomas L; Rothberg, Michael B; Nathanson, Brian H; Hannon, Nicholas S; Steingrub, Jay S; Lindenauer, Peter K

    2014-07-01

    To examine the impact of hospital-onset Clostridium difficile infection (HOCDI) on the outcomes of patients with sepsis. Most prior studies that have addressed this issue lacked adequate matching to controls, suffered from small sample size, or failed to consider time to infection. Retrospective cohort study. We identified adults with a principal or secondary diagnosis of sepsis who received care at 1 of the institutions that participated in a large multihospital database between July 1, 2004 and December 31, 2010. Among eligible patients with sepsis, we identified patients who developed HOCDI during their hospital stay. We used propensity matching and date of diagnosis to match cases to patients without Clostridium difficile infections and compared outcomes between the 2 groups. Of 218,915 sepsis patients, 2368 (1.08%) developed HOCDI. Unadjusted in-hospital mortality was significantly higher in HOCDI patients than controls (25% vs 10%, P Clostridium difficile infections was 5.1 days longer than controls (95% confidence interval: 4.4-5.8) and the median-adjusted cost increase was $4916 (P Clostridium difficile infection was associated with increased mortality, LOS, and cost. Our results can be used to assess the cost-effectiveness of prevention programs and suggest that efforts directed toward high-risk patient populations are needed. © 2014 Society of Hospital Medicine.

  1. Improved Early Detection of Sepsis in the ED With a Novel Monocyte Distribution Width Biomarker.

    Science.gov (United States)

    Crouser, Elliott D; Parrillo, Joseph E; Seymour, Christopher; Angus, Derek C; Bicking, Keri; Tejidor, Liliana; Magari, Robert; Careaga, Diana; Williams, JoAnna; Closser, Douglas R; Samoszuk, Michael; Herren, Luke; Robart, Emily; Chaves, Fernando

    2017-09-01

    Sepsis most often presents to the ED, and delayed detection is harmful. WBC count is often used to detect sepsis, but changes in WBC count size also correspond to sepsis. We sought to determine if volume increases of circulating immune cells add value to the WBC count for early sepsis detection in the ED. A blinded, prospective cohort study was conducted in two different ED populations within a large academic hospital. Neutrophil and monocyte volume parameters were measured in conjunction with routine CBC testing on a UniCel DxH 800 analyzer at the time of ED admission and were evaluated for the detection of sepsis. There were 1,320 subjects in the ED consecutively enrolled and categorized as control subjects (n = 879) and those with systemic inflammatory response syndrome (SIRS) (n = 203), infection (n = 140), or sepsis (n = 98). Compared with other parameters, monocyte distribution width (MDW) best discriminated sepsis from all other conditions (area under the curve [AUC], 0.79; 95% CI, 0.73-0.84; sensitivity, 0.77; specificity, 0.73; MDW threshold, 20.50), sepsis from SIRS (AUC, 0.74; 95% CI, 0.67-0.84), and severe sepsis from noninfected patients in the ED (AUC, 0.88; 95% CI, 0.75-0.99; negative predictive value, 99%). The added value of MDW to WBC count was statistically significant (AUC, 0.89 for MDW + WBC vs 0.81 for WBC alone; P sepsis compared with WBC count alone at the time of admission in the ED. ClinicalTrials.gov; No.: NCT02232750; URL: www.clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. Potentially modifiable factors contributing to sepsis-associated encephalopathy.

    Science.gov (United States)

    Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

    2017-08-01

    Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

  3. Sepsis Within 30 Days of Geriatric Hip Fracture Surgery.

    Science.gov (United States)

    Bohl, Daniel D; Iantorno, Stephanie E; Saltzman, Bryan M; Tetreault, Matthew W; Darrith, Brian; Della Valle, Craig J

    2017-10-01

    Sepsis after hip fracture typically develops from one of the 3 potential infectious sources: urinary tract infection (UTI), pneumonia, and surgical site infection (SSI). The purpose of this investigation is to determine (1) the proportion of cases of sepsis that arises from each of these potential infectious sources; (2) baseline risk factors for developing each of the potential infectious sources; and (3) baseline risk factors for developing sepsis. The National Surgical Quality Improvement Program database was searched for geriatric patients (aged >65 years) who underwent surgery for hip fracture during 2005-2013. Patients subsequently diagnosed with sepsis were categorized according to concomitant diagnosis with UTI, SSI, and/or pneumonia. Multivariate regression was used to test for associations while adjusting for baseline characteristics. Among the 466 patients who developed sepsis (2.4% of all patients), 157 (33.7%) also had a UTI, 135 (29.0%) also had pneumonia, and 36 (7.7%) also had SSI. The rate of sepsis was elevated in patients who developed UTI (13.0% vs 1.7%; P sepsis (21.0% vs 3.8%; P Sepsis occurs in about 1 in 40 patients after geriatric hip fracture surgery. Of these septic cases, 1 in 3 is associated with UTI, 1 in 3 with pneumonia, and 1 in 15 with SSI. The cause of sepsis is often unknown on clinical diagnosis, and this distribution of potential infectious sources allows clinicians for direct identification and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Polarization of microglia and its role in bacterial sepsis.

    Science.gov (United States)

    Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe

    2017-02-15

    Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Citations for Randomized Controlled Trials in Sepsis Literature: The Halo Effect Caused by Journal Impact Factor.

    Directory of Open Access Journals (Sweden)

    Zhongheng Zhang

    Full Text Available Citations for randomized controlled trials (RCT are important for the dissemination of study results. However, predictors of citations for RCTs have not been investigated. The study aimed to investigate the predictors of citations for RCTs in sepsis literature. RCTs that investigated the efficacy of treatment strategies on clinical outcomes in sepsis patients were included, and publication dates were restricted to the period from 2000 to 2016. Risk of bias was assessed using the Cochrane handbook for systematic reviews and interventions. A multivariable linear regression model was built to investigate the independent variables associated with total citations. In total, 160 RCTs met our inclusion criteria and were included for analysis. The median of total citations was 28.5 (IQR: 6-76. The journal impact factor (IF for articles was 6.312 (IQR: 3.143-7.214. The dependent variable was transformed by the square root to improve normality and meet the assumption of homoscedasticity. The journal IF (coefficient: 0.2; 95% CI: 0.16, 0.25 was independently associated with total citations. Large samples were associated with more total citations (coefficient: 0.0026; 95% CI: 0.0013, 0.0039. The study demonstrated that the journal IF was a major determinant of the RCT's total citation number.

  6. Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

    Science.gov (United States)

    Jafarzadeh, S Reza; Thomas, Benjamin S; Marschall, Jonas; Fraser, Victoria J; Gill, Jeff; Warren, David K

    2016-01-01

    To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Assessment of Clinical Criteria for Sepsis

    Science.gov (United States)

    Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

    2016-01-01

    IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected

  8. Effects of Ecballium elaterium on brain in a rat model of sepsis-associated encephalopathy

    Science.gov (United States)

    Arslan, Demet; Ekinci, Aysun; Arici, Akgul; Bozdemir, Eda; Akil, Esref; Ozdemir, Hasan Huseyin

    2017-01-01

    ABSTRACT Despite recent advances in antibiotic therapy, sepsis remains a major clinical challenge in intensive care units. Here we examined the anti-inflammatory and antioxidant effects of Ecballium elaterium (EE) on brain, and explored its therapeutic potential in an animal model of sepsis-associated encephalopathy (SAE) [induced by cecal ligation and puncture (CLP)]. Thirty rats were divided into three groups of 10 each: control, sepsis, and treatment. Rats were subjected to CLP except for the control group, which underwent laparatomy only. The treatment group received 2.5 mg/kg EE while the sepsis group was administered by saline. Twenty-four hours after laparotomy, animals were sacrificied and the brains were removed. Brain homogenates were prepared to assess interleukin 1beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total antioxidant capacity (TAC), and total oxidant status (TOS). Brain tissue sections were stained by hematoxylin and eosin (H&E) to semi-quantitatively examine the histopathologic changes such as neuron degeneration, pericellular/perivascular edema and inflammatory cell infiltration in the cerebral cortex. We found a statistically significant reduction in brain tissue homogenate levels of TNF-α 59.5 ± 8.4/50.2 ± 6.2 (p = 0.007) and TOS 99.3 ± 16.9/82.3 ± 7.8 (p = 0.01) in rats treated with EE; although interleukin 6 levels were increased in the treatment group compared to the sepsis group, this was not statistically significant. Neuronal damage (p = 0.00), pericellular/perivascular edema and inflammatory cell infiltration (p = 0.001) were also significantly lower in the treatment group compared to those in the sepsis group. These data suggest that Ecballium elaterium contains some components that exert protective effects against SAE in part by attenuating accumulation of proinflammatory cytokines, which may be important contributors to its anti-inflammatory effects during sepsis. PMID:28859554

  9. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

    Science.gov (United States)

    Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    ); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of

  10. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

    Science.gov (United States)

    Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    -escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of

  11. Long-term survival and function after suspected gram-negative sepsis.

    Science.gov (United States)

    Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P

    1995-07-26

    To determine the long-term (> 3 months) survival of septic patients, to develop mathematical models that predict patients likely to survive long-term, and to measure the health and functional status of surviving patients. A large tertiary care university hospital and an associated Veterans Affairs Medical Center. From December 1986 to December 1990, a total of 103 patients with suspected gram-negative sepsis entered a double-blind, placebo-controlled efficacy trial of monoclonal antiendotoxin antibody. Of these, we followed up 100 patients for 7667 patient-months. Beginning in May 1992, we reviewed hospital records and contacted all known survivors. We measured the health status of all surviving patients. The determinants of long-term survival (up to 6 years) were identified through two Cox proportional hazard regression models: one that included patient characteristics identified at the time of sepsis (bedside model) and another that included bedside, infection-related, and treatment characteristics (overall model). Of the 60 patients in the cohort who died at a median interval of 30.5 days after sepsis, 32 died within the first month of the septic episode, seven died within 3 months, and four more died within 6 months. In the bedside multivariate model constructed to predict long-term survival, large hazard ratios (HRs) were associated with severity of underlying illness as classified by McCabe and Jackson criteria (for rapidly fatal disease, HR = 30.4, P respiratory distress syndrome (HR = 2.3; P = .02) predicted patients most likely to die. The Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P bedridden), suggesting that the patients' physical function

  12. Comparison of Intermittent and Bolus Enteral Feeding Methods on Enteral Feeding Intolerance of Patients with Sepsis: A Triple-blind Controlled Trial in Intensive Care Units.

    Science.gov (United States)

    Nasiri, Morteza; Farsi, Zahra; Ahangari, Mojtaba; Dadgari, Fahimeh

    2017-10-01

    BACKGROUND Recent trials have shown controversial results on which enteral feeding methods has a lower risk of enteral feeding intolerance. Therefore, we aimed to compare two methods of bolus and intermittent feeding on enteral feeding intolerance of patients with sepsis. METHODS This triple-blind randomized controlled trial was conducted on 60 patients with sepsis, who were fed through tubes for at least 3 days. The patients were randomly assigned into bolus feeding, intermittent feeding, and control groups. Enteral feeding intolerance of all patients was recorded in 3 consecutive days by a researcher-made checklist including the data on gastric residual volume, vomiting, diarrhea, constipation, and abdominal distension. RESULTS There were no significant differences between the three studied groups in none of the intervention days pertaining to constipation, diarrhea, vomiting, abdominal distention, and gastric residual volume ( p > 0.05). Also, no statistically significant difference was found between all variables in the three studied groups during the 3 days ( p > 0.05). CONCLUSION As enteral feeding intolerance of patients with sepsis was similar in both bolus and intermittent feeding methods, it can be concluded that bolus method can still be used as a standard method to decrease the risk of enteral feeding intolerance if it is used properly.

  13. Bacteriological profile of neonatal sepsis in a secondary care hospital in rural Tamil Nadu, Southern India.

    Science.gov (United States)

    Pavan Kumar, Doniparthi Venkata; Mohan, Jesinth; Rakesh, P S; Prasad, Jasmine; Joseph, Lenikumar

    2017-01-01

    Neonatal sepsis is a leading cause of neonatal mortality and morbidity in the world. The objective of the current study was to detect the common causative microorganisms of neonatal sepsis and their antimicrobial resistance patterns in a rural secondary hospital in Tamil Nadu, India. Neonates (0-28 days) admitted to this newborn care unit from October 2013 to September 2015, with a diagnosis of probable sepsis were studied. All the enrolled babies had blood cultures taken and were followed up till final outcome, which was discharge or death, irrespective of culture result. Univariate analysis was performed for factors associated with culture positivity, generating odds ratios, and confidence intervals. Among the 107 babies with a diagnosis of probable sepsis, 28 (26.2%) had shown bacteria in culture. The majority (94.4%) were of early-onset sepsis. The predominant organisms were Staphylococcus aureus (10/28) and Klebsiella (6/28). 100% of Gram-negative bacilli and 90% of Staphylococcus were resistant to Ampicillin. Gentamicin resistance among Gram-negative bacilli and Staphylococcus was 52.9% and 20%, respectively, while third-generation cephalosporin resistance was 31.2% and 20%, respectively. Among the neonates diagnosed as probable sepsis, idiopathic prematurity ( P = 0.007) was found to have a statistically significant association with culture-positive sepsis. The culture positivity rate among the neonates with probable sepsis in the current study was 26%. An alarmingly high degree of antibiotic resistance observed calls for robust infection control practices and an urgent evaluation and development of individual and national antibiotic policies for neonatal sepsis.

  14. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors

    NARCIS (Netherlands)

    Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico

    2017-01-01

    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all

  15. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

    Science.gov (United States)

    Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

    2014-01-01

    Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

  16. Injuria renal aguda en la sepsis grave Acute kidney injury in severe sepsis

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2009-06-01

    Full Text Available La sepsis afecta al 40% de los pacientes críticos, siendo su mortalidad de aproximadamente un 30% en el caso de la sepsis grave, y de 75% con injuria renal aguda, la cual sucede en el 20-51% de los casos. Se realizó un estudio prospectivo, observacional, longitudinal, en 80 pacientes sépticos graves en el lapso de 1 año para determinar el desarrollo de injuria renal aguda y su relación con la mortalidad; correlacionar antecedentes clínicos y variaciones del laboratorio con la mortalidad; determinar la tasa de mortalidad de la sepsis grave; relacionar óbito y foco séptico primario; evaluar la predictibilidad de mortalidad según niveles de creatinina de ingreso y sus variaciones finales. Se definieron dos grupos: Obito (n = 25 y No-óbito (n = 55. Analizados según la creatinina de ingreso, 39 tenían valores normales de creatinina (10 óbitos y 41 la presentaban elevada (15 óbitos; según la creatinina de egreso, 48 presentaron creatinina normal y fallecieron 7, mientras que 32 tenían daño renal agudo, de los cuales 18 fallecieron. De los 25 pacientes fallecidos, el 72% presentaron daño renal. De éstos, 7 pacientes vivos y 2 fallecidos requirieron hemodiálisis. El foco primario más frecuente fue el respiratorio (26.4%. El desarrollo de daño renal es un alto predictor de mortalidad en la sepsis, independientemente de los valores iniciales de creatinina. Edad más avanzada, hipertensión arterial, score APACHE más elevado, anemia más grave, hipoalbuminemia, hiperfosfatemia e hiperkalemia se asociaron a mayor mortalidad. La mortalidad global fue 31.3%. La imposibilidad de identificar el foco séptico primario se asoció a mayor mortalidad. El foco respiratorio se relacionó a mayor riesgo de requerir hemodiálisis.Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study

  17. Endothelial Activation: The Ang/Tie Axis in Sepsis

    Directory of Open Access Journals (Sweden)

    Aleksandra Leligdowicz

    2018-04-01

    Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

  18. Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

    Directory of Open Access Journals (Sweden)

    Weera Mahavanakul

    Full Text Available The Surviving Sepsis Campaign (SSC guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting.We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53% of who died within 28 days. One third of patients were treated in intensive care units (ICUs. Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis.It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

  19. Severe hyperglycaemia due to neonatal sepsis - A case report ...

    African Journals Online (AJOL)

    Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life. The clinical signs of neonatal sepsis are neither specific nor uniform. Neonatal sepsis may present with fever, hypotonia, respiratory distress, apnea and hyperglycaemia.

  20. [Pharmaconutrition with parenteral selenium in sepsis].

    Science.gov (United States)

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  1. Complement activation in emergency department patients with severe sepsis.

    Science.gov (United States)

    Younger, John G; Bracho, David O; Chung-Esaki, Hangyul M; Lee, Moonseok; Rana, Gurpreet K; Sen, Ananda; Jones, Alan E

    2010-04-01

    This study assessed the extent and mechanism of complement activation in community-acquired sepsis at presentation to the emergency department (ED) and following 24 hours of quantitative resuscitation. A prospective pilot study of patients with severe sepsis and healthy controls was conducted among individuals presenting to a tertiary care ED. Resuscitation, including antibiotics and therapies to normalize central venous and mean arterial pressure (MAP) and central venous oxygenation, was performed on all patients. Serum levels of Factor Bb (alternative pathway), C4d (classical and mannose-binding lectin [MBL] pathway), C3, C3a, and C5a were determined at presentation and 24 hours later among patients. Twenty patients and 10 healthy volunteer controls were enrolled. Compared to volunteers, all proteins measured were abnormally higher among septic patients (C4d 3.5-fold; Factor Bb 6.1-fold; C3 0.8-fold; C3a 11.6-fold; C5a 1.8-fold). Elevations in C5a were most strongly correlated with alternative pathway activation. Surprisingly, a slight but significant inverse relationship between illness severity (by sequential organ failure assessment [SOFA] score) and C5a levels at presentation was noted. Twenty-four hours of structured resuscitation did not, on average, affect any of the mediators studied. Patients with community-acquired sepsis have extensive complement activation, particularly of the alternative pathway, at the time of presentation that was not significantly reversed by 24 hours of aggressive resuscitation.

  2. Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

    Science.gov (United States)

    Pedrazza, Leonardo; Pereira, Talita Carneiro Brandão; Abujamra, Ana Lucia; Nunes, Fernanda Bordignon; Bogo, Maurício Reis; de Oliveira, Jarbas Rodrigues

    2017-07-01

    Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10 6 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

  3. Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells.

    Science.gov (United States)

    Yan, Jun; Mitra, Abhisek; Hu, Jiemiao; Cutrera, Jeffery J; Xia, Xueqing; Doetschman, Thomas; Gagea, Mihai; Mishra, Lopa; Li, Shulin

    2016-05-01

    Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death. Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice. Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise, deficiency in IL-10 or NKT cells abolished the protective role of IL-30 against sepsis. Furthermore, IL-30 induced IL-10 production in purified and LPS-stimulated NKT cells. Blocking IL-6R or gp130 inhibited IL-30 mediated IL-10 production. IL-30 is important in modulating production of NKT cytokines and subsequent NKT cell-mediated immune regulation of other cells. Therefore, IL-30 has a role in prevention and treatment of sepsis via modulation of cytokine production by NKT. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

    Science.gov (United States)

    Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

    2017-11-01

    The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

  5. Augmenting Plant Immune Responses and Biological Control by Microbial Determinants

    Directory of Open Access Journals (Sweden)

    Sang Moo Lee

    2015-09-01

    Full Text Available Plant have developed sophisticated defence mechanisms against microbial pathogens. The recent accumulated information allow us to understand the nature of plant immune responses followed by recognition of microbial factors/determinants through cutting-edge genomics and multi-omics techniques. However, the practical approaches to sustain plant health using enhancement of plant immunity is yet to be fully appreciated. Here, we overviewed the general concept and representative examples on the plant immunity. The fungal, bacterial, and viral determinants that was previously reported as the triggers of plant immune responses are introduced and described as the potential protocol of biological control. Specifically, the role of chitin, glucan, lipopolysaccharides/extracellular polysaccharides, microbe/pathogen-associated molecular pattern, antibiotics, mimic-phytohormones, N-acyl homoserine lactone, harpin, vitamins, and volatile organic compounds are considered. We hope that this review stimulates scientific community and farmers to broaden their knowledge on the microbial determinant-based biological control and to apply the technology on the integrated pest management program.

  6. Comportamiento del fallo renal agudo en niños con sepsis grave Behavior of acute renal failure in children presenting with severe sepsis

    Directory of Open Access Journals (Sweden)

    María del Carmen Saura Hernández

    2010-03-01

    Full Text Available INTRODUCCIÓN. El objetivo de esta investigación fue determinar los factores de riesgo asociados al fallo renal agudo (FRA en un grupo de niños con sepsis grave atendidos entre enero del 2004 y diciembre del 2008. MÉTODOS. Se realizó un estudio observacional y analítico con una muestra de 171 pacientes. Se constituyeron dos grupos: el de estudio, integrado por 38 pacientes con estado de choque séptico o disfunción múltiple de órganos (DMO y FRA, y un grupo control, conformado por 133 niños en igual estadio de sepsis pero con función renal normal. Se revisaron las historias clínicas y se tuvieron en cuenta variables epidemiológicas, factores de riesgo de FRA y evolución de los casos. RESULTADOS. La incidencia de FRA fue del 22,2 %, y aunque disminuyó considerablemente en los 3 últimos años del estudio, la mortalidad fue del 42,1 %, mayoritariamente en el DMO (89,5 %. Se encontró dependencia entre la insuficiencia renal y la respuesta diurética no adecuada a la fluidoterapia (51,2 %, la inestabilidad hemodinámica por más de 24 h (46,5 %, la disfunción miocárdica (43,3 % y el uso de medicamentos nefrotóxicos (42,8 %. CONCLUSIONES. La respuesta diurética no adecuada a la fluidoterapia, la inestabilidad hemodinámica por más de 24 h, la disfunción miocárdica y el uso de medicamentos nefrotóxicos incrementan el riesgo de FRA en la sepsis grave, la cual duplica la mortalidad en relación con los pacientes que conservan la función renal. No obstante, la prevención de las formas graves de sepsis y un tratamiento adecuado de ésta disminuyen la incidencia de FRA.INTRODUCTION: The aim of present research was to determine the risk factor associated with the acute renal failure (ARF in a group of children with severe sepsis seen between January, 2004 and December, 2008. METHODS: An analytical and observational study was conducted in a sample including 171 patients. There were two groups: the study-group with 138 patients with

  7. Critical control points for the management of microbial growth in HVAC systems

    NARCIS (Netherlands)

    Gommers, S; Franchimon, F.; Bronswijk, van J.E.M.H.; Strøm-Tejsen, P; Olesen, BW; Wargocki, P; Zukowska, D; Toftum, J

    2008-01-01

    Office buildings with HVAC systems consistently report Sick Building Symptoms that are derived from microbial growth. We used the HACCP methodology to find the main critical control points (CCPs) for microbial management of HVAC systems in temperate climates. Desk research revealed relative humidity

  8. Microbial profile and critical control points during processing of 'robo ...

    African Journals Online (AJOL)

    Microbial profile and critical control points during processing of 'robo' snack from ... the relevant critical control points especially in relation to raw materials and ... to the quality of the various raw ingredients used were the roasting using earthen

  9. Corticosteroids in sepsis: an updated systematic review and meta-analysis (protocol).

    Science.gov (United States)

    Rochwerg, Bram; Oczkowski, Simon; Siemieniuk, Reed Alexander; Menon, Kusum; Szczeklik, Wojciech; English, Shane; Agoritsas, Thomas; Belley-Cote, Emilie; D'Aragon, Frédérick; Alhazzani, Waleed; Duan, Erick; Gossack-Keenan, Kira; Sevransky, Jon; Vandvik, Per; Venkatesh, Bala; Guyatt, Gordon; Annane, Djillali

    2017-06-30

    Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature. A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel. The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids

  10. Management of severe sepsis: advances, challenges, and current status

    Directory of Open Access Journals (Sweden)

    Martin-Loeches I

    2015-04-01

    Full Text Available Ignacio Martin-Loeches,1 Mitchell M Levy,2 Antonio Artigas31Multidisciplinary Intensive Care Research Organization (MICRO, St James’s University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland; 2Brown University, Providence, RI, USA; 3Critical Care Center, CIBER Enfermedades Respiratorias, Sabadell Hospital, Corporació Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Barcelona, SpainAbstract: The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.Keywords: sepsis, septic shock, guidelines, critical care, biomarkers, surviving sepsis campaign

  11. Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

    Directory of Open Access Journals (Sweden)

    T. Barichello

    2007-06-01

    Full Text Available Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g were submitted to cecal ligation and puncture (CLP, and 44 were submitted to sham operation. Forty-four rats (40% survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory, 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05. In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05, suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.

  12. Impact of Prehospital Care on Outcomes in Sepsis: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Michael A Smyth

    2016-06-01

    Full Text Available Introduction: Sepsis is a common and potentially life-threatening response to an infection. International treatment guidelines for sepsis advocate that treatment be initiated at the earliest possible opportunity. It is not yet clear if very early intervention by ambulance clinicians prior to arrival at hospital leads to improved clinical outcomes among sepsis patients. Methoda: We systematically searched the electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed up to June 2015. In addition, subject experts were contacted. We adopted the GRADE (grading recommendations assessment, development and evaluation methodology to conduct the review and follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations to report findings. Results: Nine studies met the eligibility criteria – one study was a randomized controlled trial while the remaining studies were observational in nature. There was considerable variation in the methodological approaches adopted and outcome measures reported across the studies. Because of these differences, the studies did not answer a unique research question and meta-analysis was not appropriate. A narrative approach to data synthesis was adopted. Conclusion: There is little robust evidence addressing the impact of prehospital interventions on outcomes in sepsis. That which is available is of low quality and indicates that prehospital interventions have limited impact on outcomes in sepsis beyond improving process outcomes and expediting the patient’s passage through the emergency care pathway. Evidence indicating that prehospital antibiotic therapy and fluid resuscitation improve patient outcomes is currently lacking. [West J Emerg Med. 2017;17(4427-437.

  13. Role of C5 Activation Products in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward

    2010-01-01

    Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.

  14. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo

    2014-01-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

  15. Sepsis in HIV-infected patients; epidemiology and host response

    NARCIS (Netherlands)

    Huson, M.A.M.

    2016-01-01

    In this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive

  16. Culture proven newborn sepsis with a special emphasis on late onset sepsis caused by Enterobacteriaceae in a level III neonatal care unit in Astana, Kazakhstan.

    Science.gov (United States)

    Kangozhinova, Kalamkas; Abentayeva, Botakoz; Repa, Andreas; Baltabayeva, Assem; Erwa, Wolfgang; Stauffer, Friedrich

    2013-10-01

    Newborn sepsis is one of the major public health concerns worldwide. Also in our neonatal care unit, it is one of the major problems and especially infections with Enterobacteriaceae were noted to pose an increasing problem in the last years. Data collection was done retrospectively for 2011. Early onset sepsis was defined as having a positive blood culture within 72 h and late onset sepsis after 72 h of delivery. Out of 599 patients being admitted, 58 newborns were assessed having a neonatal sepsis. Of these 58 newborns with sepsis, 11 were diagnosed within 72 h post delivery (early onset) and 47 were diagnosed after 72 h post delivery (late onset). The percentage of Enterobacteriaceae causing late onset sepsis was 57.5 %. Among these, Klebsiella pneumoniae could be isolated in 29.8 %, Enterobacter cloacae in 12.8 %, Enterobacter aerogenes in 8.5 %, and Escherichia coli in 6.4 % of late onset sepsis. Majority of the strains showed a resistance to antibiotics used in empiric treatment. Antibiotic prophylaxis/treatment from birth until the onset of late onset sepsis could be analyzed in 20 out of 27 newborns with late onset sepsis caused by Enterobacteriaceae. A regimen of empirical antibiotic treatment containing aminopenicillin and/or gentamicin was administered in 16 newborns and that of cephalosporin in 14 out of 20 newborns for at least 5 days before onset of sepsis. The association of empiric long-term antibiotic treatment and the high number of late onset sepsis with often multiresistant Enterobacteriaceae might be causal and urges for a change in general antibiotic prophylaxis/treatment in newborns admitted to the neonatal care unit of our hospital.

  17. Bacteriological profile of neonatal sepsis in a secondary care hospital in rural Tamil Nadu, Southern India

    Directory of Open Access Journals (Sweden)

    Doniparthi Venkata Pavan Kumar

    2017-01-01

    Full Text Available Introduction: Neonatal sepsis is a leading cause of neonatal mortality and morbidity in the world. The objective of the current study was to detect the common causative microorganisms of neonatal sepsis and their antimicrobial resistance patterns in a rural secondary hospital in Tamil Nadu, India. Materials and Methods: Neonates (0–28 days admitted to this newborn care unit from October 2013 to September 2015, with a diagnosis of probable sepsis were studied. All the enrolled babies had blood cultures taken and were followed up till final outcome, which was discharge or death, irrespective of culture result. Univariate analysis was performed for factors associated with culture positivity, generating odds ratios, and confidence intervals. Results: Among the 107 babies with a diagnosis of probable sepsis, 28 (26.2% had shown bacteria in culture. The majority (94.4% were of early-onset sepsis. The predominant organisms were Staphylococcus aureus (10/28 and Klebsiella (6/28. 100% of Gram-negative bacilli and 90% of Staphylococcus were resistant to Ampicillin. Gentamicin resistance among Gram-negative bacilli and Staphylococcus was 52.9% and 20%, respectively, while third-generation cephalosporin resistance was 31.2% and 20%, respectively. Among the neonates diagnosed as probable sepsis, idiopathic prematurity (P = 0.007 was found to have a statistically significant association with culture-positive sepsis. Conclusion: The culture positivity rate among the neonates with probable sepsis in the current study was 26%. An alarmingly high degree of antibiotic resistance observed calls for robust infection control practices and an urgent evaluation and development of individual and national antibiotic policies for neonatal sepsis.

  18. The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study.

    Science.gov (United States)

    Davies, Gareth R; Lawrence, Matthew; Pillai, Suresh; Mills, Gavin M; Aubrey, Robert; Thomas, Dafydd; Williams, Rhodri; Morris, Keith; Evans, Phillip Adrian

    2018-04-01

    The study purpose was to define changes in coagulation across the sepsis spectrum using rotational thromboelastometry (ROTEM). Sepsis patients were recruited on admission to the Emergency Department and Intensive Care Units of a large teaching hospital in Wales. ROTEM markers of clot development and fibrinolysis were determined, as well as standard coagulation markers. A healthy control group matched for age and gender was also recruited (n=44). 100 patients were recruited (50 sepsis, 20 severe sepsis and 30 septic shock). Maximum clot firmness was significantly higher in the sepsis (p<0.001) and severe sepsis (p=0.012) groups than the healthy control (71.6±4.5 and 70.4±4.1 vs 64.4 respectively). In septic shock there was prolonged clot development; however, maximum clot firmness remained normal. Fibrinolytic function was significantly impaired in septic shock, which was also significantly associated with 28-day mortality (p<0.001). ROTEM indicated significantly enhanced clot structural development in sepsis and severe sepsis, which could be indicative of a hypercoagulable phase. In septic shock, despite there being a prolongation of clotting pathways and impaired fibrinolysis, clot mass was comparably normal, suggestive of the development of a clot with healthy characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

    International Nuclear Information System (INIS)

    Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

    1987-01-01

    Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

  20. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  1. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  2. Not All Abdomens Are the Same: A Comparison of Damage Control Surgery for Intra-abdominal Sepsis versus Trauma.

    Science.gov (United States)

    Smith, Jason W; Nash, Nick; Procter, Levi; Benns, Matthew; Franklin, Glen A; Miller, Keith; Harbrecht, Brian G; Bernard, Andrew C

    2016-05-01

    Damage control surgery (DCS) was developed to manage exsanguinating trauma patients, but is increasingly applied to the management of peritoneal sepsis and abdominal catastrophes. Few manuscripts compare the outcomes of these surgeries on disparate patient populations. A multi-institutional three group propensity score matched case cohort study comparing penetrating trauma (PT-DCS), blunt trauma (BT-DCS), and intraperitoneal sepsis (IPS-DCS) was performed comparing patients treated with DSC between 2008 and 2013. Propensity scoring was performed using demographic and presenting physiologic data. Four hundred and twelve patients were treated with DCS across two institutions. Propensity matching for age, gender, and initial Acute Physiology and Chronic Health Evaluation II score 80 identified 80 patients per group for comparison. Rate of primary fascial closure was lowest in the IPS-DCS group, and highest in the penetrating trauma DCS group. Intra-abdominal complication rates were highest in the IPS-DCS group. IPS-DCS had increased time to definitive closure compared with the other two groups (RR 1.8; 1.3-2.2; P eight days were more than twice the risk of death at 90 days across all groups. (RR 2.15; 1.2-3.5; P managed via DCS.

  3. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  4. Can Resistin be a New Indicator of Neonatal Sepsis?

    Directory of Open Access Journals (Sweden)

    Didem Aliefendioglu

    2014-02-01

    Conclusion: Resistin levels were higher in premature newborns with sepsis and correlated with IL-6 levels, which is an indicator of neonatal sepsis. This suggests that resistin may also be used in the diagnosis of neonatal sepsis. However, it has limited value when compared with the other inflammatory markers including C-reactive protein, procalcitonin, and IL-6.

  5. High-sensitivity C-reactive protein and risk of sepsis.

    Directory of Open Access Journals (Sweden)

    Henry E Wang

    Full Text Available Conventional C-reactive protein assays have been used to detect or guide the treatment of acute sepsis. The objective of this study was to determine the association between elevated baseline high-sensitivity C-reactive protein (hsCRP and the risk of future sepsis events.We studied data from 30,239 community dwelling, black and white individuals, age ≥45 years old enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS cohort. Baseline hsCRP and participant characteristics were determined at the start of the study. We identified sepsis events through review of hospital records. Elevated hsCRP was defined as values >3.0 mg/L. Using Cox regression, we determined the association between elevated hsCRP and first sepsis event, adjusting for sociodemographic factors (age, sex, race, region, education, income, health behaviors (tobacco and alcohol use, chronic medical conditions (coronary artery disease, diabetes, dyslipidemia, hypertension, chronic kidney disease, chronic lung disease and statin use.Over the mean observation time of 5.7 years (IQR 4.5-7.1, 974 individuals experienced a sepsis event, and 11,447 (37.9% had elevated baseline hsCRP (>3.0 mg/L. Elevated baseline hsCRP was independently associated with subsequent sepsis (adjusted HR 1.56; 95% CI 1.36-1.79, adjusted for sociodemographics, health behaviors, chronic medical conditions and statin use.Elevated baseline hsCRP was associated with increased risk of future sepsis events. hsCRP may help to identify individuals at increased risk for sepsis.

  6. The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Wadowsky, R M; DePudyt, L; Rowe, M I

    1991-04-01

    In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

  7. Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Morota, Saori; Persson, Johan Mikael

    2013-01-01

    to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content. RESULTS: In intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0......INTRODUCTION: In sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood.......001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective...

  8. Biomimicry of volatile-based microbial control for managing emerging fungal pathogens.

    Science.gov (United States)

    Gabriel, K T; Joseph Sexton, D; Cornelison, C T

    2018-05-01

    Volatile organic compounds (VOCs) are known to be produced by a wide range of micro-organisms and for a number of purposes. Volatile-based microbial inhibition in environments such as soil is well-founded, with numerous antimicrobial VOCs having been identified. Inhibitory VOCs are of interest as microbial control agents, as low concentrations of gaseous VOCs can elicit significant antimicrobial effects. Volatile organic compounds are organic chemicals typically characterized as having low molecular weight, low solubility in water, and high vapour pressure. Consequently, VOCs readily evaporate to the gaseous phase at standard temperature and pressure. This contact-independent antagonism presents unique advantages over traditional, contact-dependent microbial control methods, including increased surface exposure and reduced environmental persistence. This approach has been the focus of our recent research, with positive results suggesting it may be particularly promising for the management of emerging fungal pathogens, such as the causative agents of white-nose syndrome of bats and snake fungal disease, which are difficult or impossible to treat using traditional approaches. Here, we review the history of volatile-based microbial control, discuss recent progress in formulations that mimic naturally antagonistic VOCs, outline the development of a novel treatment device, and highlight areas where further work is needed to successfully deploy VOCs against existing and emerging fungal pathogens. © 2017 The Society for Applied Microbiology.

  9. Evaluation of the Adequacy of GMP to Control Microbial Hazards in Dairy Factories in Fars Province

    Directory of Open Access Journals (Sweden)

    Sajjad Abdi no

    2016-07-01

    Full Text Available Background and Objectives: Pre-requisite programs (PRPs are “primary conditions and requirements essential for HACCP operations, which are crucial in food safety programs”. The present study was conducted to evaluate the impact of implementation of PRPs on the microbial parameters of pasteurized milk (according to the National Standard of Iran. Effectiveness of HACCP operation requirements and efficiency of Good Laboratory Practice (GLP were also evaluated in control of the above-mentioned microbial parameters. Materials and Methods: According to the approved checklist of the Vice-chancellor in Food and Drug affairs, PRPs of 26 factories were evaluated from March 2014 to March 2015 in two-month intervals, and their total and component scores were obtained along with the microbial parameters of pasteurized milk. Generalized Estimating Equations (GEEs were used to determine the significance of total score and the impact of its components on controlling microbial hazards. Results: There was a reverse significant relation between the total scores of the PRPs and microbial hygiene indices (total and coliform count which approves the effectiveness of operating the programs in controlling the mentioned microorganisms. Efficiency of each pre-requisite program was different in controlling the microbial parameters. Good Laboratory Practice (GLP had a prominent effect on controlling of the index microorganisms of hygienic operations. Overall, the results showed a little probability of contamination with E. coli in the pasteurized milk samples of Fars Province for which the statistical analysis was ignored. Conclusions: The exact operation of PRPs resulted in reduction of microbial parameters in a way that increasing the total score of PRPs led to decrease in microbial parameters of total count (TC, coliforms, molds and yeasts. The findings further suggest the application of this checklist in evaluation and prediction of microbial parameters. Keywords

  10. Sepsis and ARDS: The Dark Side of Histones

    Science.gov (United States)

    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases. PMID:26609197

  11. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

  12. Procalcitonin: A Reliable Marker for the Diagnosis of Neonatal Sepsis

    Science.gov (United States)

    Adib, Minoo; Bakhshiani, Zahra; Navaei, Fakhri; Saheb Fosoul, Fereshteh; Fouladi, Salomeh; Kazemzadeh, Hamidreza

    2012-01-01

    Objective(s) In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis. Materials and Methods Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively. Results Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other. Conclusion We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis. PMID:23493845

  13. Importance of measuring lactate levels in children with sepsis.

    Science.gov (United States)

    Anil, Nisha

    2017-10-10

    Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  14. Implications of the new sepsis definition on research and practice.

    Science.gov (United States)

    Peach, Brian C

    2017-04-01

    The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and

  15. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  16. Nursing considerations to complement the Surviving Sepsis Campaign guidelines.

    Science.gov (United States)

    Aitken, Leanne M; Williams, Ged; Harvey, Maurene; Blot, Stijn; Kleinpell, Ruth; Labeau, Sonia; Marshall, Andrea; Ray-Barruel, Gillian; Moloney-Harmon, Patricia A; Robson, Wayne; Johnson, Alexander P; Lan, Pang Nguk; Ahrens, Tom

    2011-07-01

    To provide a series of recommendations based on the best available evidence to guide clinicians providing nursing care to patients with severe sepsis. Modified Delphi method involving international experts and key individuals in subgroup work and electronic-based discussion among the entire group to achieve consensus. We used the Surviving Sepsis Campaign guidelines as a framework to inform the structure and content of these guidelines. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to rate the quality of evidence from high (A) to very low (D) and to determine the strength of recommendations, with grade 1 indicating clear benefit in the septic population and grade 2 indicating less confidence in the benefits in the septic population. In areas without complete agreement between all authors, a process of electronic discussion of all evidence was undertaken until consensus was reached. This process was conducted independently of any funding. Sixty-three recommendations relating to the nursing care of severe sepsis patients are made. Prevention recommendations relate to education, accountability, surveillance of nosocomial infections, hand hygiene, and prevention of respiratory, central line-related, surgical site, and urinary tract infections, whereas infection management recommendations related to both control of the infection source and transmission-based precautions. Recommendations related to initial resuscitation include improved recognition of the deteriorating patient, diagnosis of severe sepsis, seeking further assistance, and initiating early resuscitation measures. Important elements of hemodynamic support relate to improving both tissue oxygenation and macrocirculation. Recommendations related to supportive nursing care incorporate aspects of nutrition, mouth and eye care, and pressure ulcer prevention and management. Pediatric recommendations relate to the use of antibiotics, steroids, vasopressors and

  17. Antipyretic therapy in critically ill patients with established sepsis: a trial sequential analysis.

    Directory of Open Access Journals (Sweden)

    Zhongheng Zhang

    Full Text Available antipyretic therapy for patients with sepsis has long been debated. The present study aimed to explore the beneficial effect of antipyretic therapy for ICU patients with sepsis.systematic review and trial sequential analysis of randomized controlled trials.Pubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014.Mortality was dichotomized as binary outcome variable and odds ratio (OR was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients.A total of 6 randomized controlled trials including 819 patients were included into final analysis. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1.02, 95% CI: 0.50-2.05. The required information size (IS was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O'Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power.our study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis.

  18. Immune disorders in sepsis and their treatment as a significant problem of modern intensive care

    Directory of Open Access Journals (Sweden)

    Lidia Łysenko

    2017-08-01

    Full Text Available Despite the great advances in the treatment of sepsis over the past 20 years, sepsis remains the main cause of death in intensive care units. In the context of new possibilities of treating sepsis, a comprehensive response of the immune system to the infection, immunosuppression, in particular, has in recent years gained considerable interest. There is vast evidence pointing to the correlation between comorbid immunosuppression and an increased risk of recurrent infections and death. Immune disorders may impact the clinical course of sepsis. This applies in particular to patients with deteriorated clinical response to infections. They usually suffer from comorbidities and conditions accompanied by immunosuppression. Sepsis disrupts innate and adaptive immunity. The key to diagnose the immune disorders in sepsis and undertake targeted immunomodulatory therapy is to define the right biomarkers and laboratory methods, which permit prompt “bedside” diagnosis. Flow cytometry is a laboratory tool that meets these criteria. Two therapeutic methods are currently being suggested to restore the immune homeostasis of sepsis patients. Excessive inflammatory response may be controlled through extracorporeal blood purification techniques, in large part derived from renal replacement therapy. These are such techniques as high-volume haemofiltration, cascade haemofiltration, plasma exchange, coupled plasma filtration and adsorption, high-absorption membranes, high cut-off membranes. The main task of theses techniques is the selective elimination of middle molecular weight molecules, such as cytokines. Pharmacotherapy with the use of such immunostimulants as interleukin 7, granulocyte-macrophage colony-stimulating factor, interferon gamma, PD-1, PD-L1 and CTLA-4 antagonists, intravenous immunoglobulins may help fight immunosuppressive immune disorders.

  19. Immune disorders in sepsis and their treatment as a significant problem of modern intensive care.

    Science.gov (United States)

    Łysenko, Lidia; Leśnik, Patrycja; Nelke, Kamil; Gerber, Hanna

    2017-08-22

    Despite the great advances in the treatment of sepsis over the past 20 years, sepsis remains the main cause of death in intensive care units. In the context of new possibilities of treating sepsis, a comprehensive response of the immune system to the infection, immunosuppression, in particular, has in recent years gained considerable interest. There is vast evidence pointing to the correlation between comorbid immunosuppression and an increased risk of recurrent infections and death. Immune disorders may impact the clinical course of sepsis. This applies in particular to patients with deteriorated clinical response to infections. They usually suffer from comorbidities and conditions accompanied by immunosuppression. Sepsis disrupts innate and adaptive immunity. The key to diagnose the immune disorders in sepsis and undertake targeted immunomodulatory therapy is to define the right biomarkers and laboratory methods, which permit prompt "bedside" diagnosis. Flow cytometry is a laboratory tool that meets these criteria. Two therapeutic methods are currently being suggested to restore the immune homeostasis of sepsis patients. Excessive inflammatory response may be controlled through extracorporeal blood purification techniques, in large part derived from renal replacement therapy. These are such techniques as high-volume haemofiltration, cascade haemofiltration, plasma exchange, coupled plasma filtration and adsorption, high-absorption membranes, high cut-off membranes. The main task of theses techniques is the selective elimination of middle molecular weight molecules, such as cytokines. Pharmacotherapy with the use of such immunostimulants as interleukin 7, granulocyte-macrophage colony-stimulating factor, interferon gamma, PD-1, PD-L1 and CTLA-4 antagonists, intravenous immunoglobulins may help fight immunosuppressive immune disorders.

  20. Ureteric stent dwelling time: a risk factor for post-ureteroscopy sepsis.

    Science.gov (United States)

    Nevo, Amihay; Mano, Roy; Baniel, Jack; Lifshitz, David A

    2017-07-01

    To evaluate the association between stent dwelling time and sepsis after ureteroscopy, and identify risk factors for sepsis in this setting. The prospectively collected database of a single institution was queried for all patients who underwent ureteroscopy for stone extraction between 2010 and 2016. Demographic, clinical, preoperative and operative data were collected. The primary study endpoint was sepsis within 48 h of ureteroscopy. Logistic regressions were performed to identify predictors of post-ureteroscopy sepsis in the ureteroscopy cohort and specifically in patients with prior stent insertion. Between October 2010 and April 2016, 1 256 patients underwent ureteroscopy for stone extraction. Risk factors for sepsis included prior stent placement, female gender and Charlson comorbidity index. A total of 601 patients had a ureteric stent inserted before the operation and were included in the study cohort, in which the median age was 56 years, 90 patients were women (30%), and 97 patients were treated for positive preoperative urine cultures (16.1%). Postoperative sepsis, Sepsis rates after stent dwelling times of 1, 2, 3 and >3 months were 1, 4.9, 5.5 and 9.2%, respectively. On multivariate analysis, stent dwelling time, stent insertion because of sepsis, and female gender were significantly associated with post-ureteroscopy sepsis in patients with prior stent placement. Patients who undergo ureteroscopy after ureteric stent insertion have a higher risk of postoperative sepsis. Prolonged stent dwelling time, sepsis as an indication for stent insertion, and female gender are independent risk factors. Stent placement should be considered cautiously, and if inserted, ureteroscopy should be performed within 1 month. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  1. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    Science.gov (United States)

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  2. Prevalence and factors associated with neonatal sepsis among ...

    African Journals Online (AJOL)

    TOSHIBA

    Relationship between outcome variable and exposure variable was done using Chi ... A recent study in Ethiopia indicates that neonatal sepsis in the major newborn ... Neonatal sepsis was defined as infection that had occurred during the.

  3. Sepsis: at-risk patients, clinical manifestations and management

    African Journals Online (AJOL)

    management of sepsis has resulted in a remarkable increase of new knowledge on the ... As sepsis progresses to septic shock, the risk of dying increases substantially. Where .... altered mental state, thrombocytopenia, raised serum lactate ...

  4. Implementatie van de Surviving Sepsis Campaign bundels : Monitoring van ervaringen

    NARCIS (Netherlands)

    Lilian Vloet; J. Schouten; N. Stevens; A. Rensen; A. Willems; F. Zeegers

    2011-01-01

    Sepsis komt vaak voor in ziekenhuizen. Ernstige sepsis is verantwoordelijk voor 10 - 20% van alle Intensive Care (IC) opnames en is de belangrijkste doodsoorzaak op niet-cardiale IC?s. De gemiddelde mortaliteit van volwassenen met ernstige sepsis op de IC is 33% en van volwassenen met septische

  5. Utilization and control of ecological interactions in polymicrobial infections and community-based microbial cell factories

    DEFF Research Database (Denmark)

    Wigneswaran, Vinoth; Amador Hierro, Cristina Isabel; Jelsbak, Lotte

    2016-01-01

    Microbial activities are most often shaped by interactions between co-existing microbes within mixed-species communities. Dissection of the molecular mechanisms of species interactions within communities is a central issue in microbial ecology, and our ability to engineer and control microbial co...

  6. Sepsis after renal transplantation: Clinical, immunological, and microbiological risk factors.

    Science.gov (United States)

    Schachtner, Thomas; Stein, Maik; Reinke, Petra

    2017-06-01

    As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease-free survival after renal transplantation. We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. In all, 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV-specific and alloreactive T cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations. Five-year patient survival was 70.3% with sepsis compared to 88.2% without (Psepsis (Psepsis (Psepsis was associated with decreased CD3+ and CD4+ T cells pre-transplantation (Psepsis (Psepsis (Psepsis show inferior patient survival and allograft function. Identified risk factors and differences in lymphocyte counts, CMV-specific immunity, and alloreactivity may prove useful to identify KTRs at increased risk. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Recombinant human interleukin-11 (IL-11) is a protective factor in severe sepsis with thrombocytopenia: A case-control study.

    Science.gov (United States)

    Wan, Bing; Zhang, Hao; Fu, Haiyan; Chen, Yikun; Yang, Liping; Yin, Jiangtao; Wan, Yin; Shi, Yongqing

    2015-12-01

    To examine the platelet recovering and anti-inflammatory effects of IL-11 in the treatment of sepsis, accompanied with thrombocytopenia and to investigate the associated mechanisms via a case-control study. 105 patients enrolled for the study were segregated into (1) IL-11 therapy group and (2) conventional therapy group. The IL-11 therapy group was given additional recombinant human IL-11 treatment. Laboratory examinations of IL-11, IL-6, TNF-α, PT, APTT, WBC, PLT counts in blood routine assays and PCT, CRP and APACHE II scores were performed and the results were recorded. The PLT counts in the IL-11 therapy group were higher than those in the conventional therapy group. No obvious difference in WBC counts or CRP levels was observed between the two groups. The highest levels of TNF-α were observed on day 3 in the conventional therapy group while it was observed on day 1 in the IL-11 therapy group, both of which subsequently declined gradually. The level of IL-6 was significantly lower in the IL-11 therapy group from 3 to 14 days, while there was a gradual elevation of IL-11. IL-11 therapy downregulated the expression of the sepsis indicator PCT and reduced the APACHE II score from 3 to 14 days. The conventional therapy group had a significantly higher mortality rate within 28 days. IL-11 has a protective role and can accelerate recovery of platelets, and remarkably lessen the extent of inflammatory responses, hence reducing the mortality in sepsis patients accompanied with thrombocytopenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Severe sepsis and septic shock [author's reply

    NARCIS (Netherlands)

    Angus, Derek C.; van der Poll, Tom

    2013-01-01

    To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.

  9. Sepsis in intensive care patients: challenges in diagnosis and prognostication

    NARCIS (Netherlands)

    Klein Klouwenberg, P.M.C.

    2015-01-01

    Sepsis is a syndrome that arises when the body’s response to a severe infection injures its own tissues. It is a major and increasing cause of in-hospital morbidity and mortality. Despite recent advances in the management of sepsis, the morbidity and mortality caused by sepsis remain unacceptably

  10. PROTEOMIC AND EPIGENOMIC MARKERS OF SEPSIS-INDUCED DELIRIUM (SID

    Directory of Open Access Journals (Sweden)

    Adonis eSfera

    2015-10-01

    Full Text Available In elderly population sepsis is one of the leading causes of intensive care unit (ICU admissions in the United States. Sepsis-induced delirium (SID is the most frequent cause of delirium in ICU (1. Together delirium and SID represent under recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143 to 152 billion dollars per year (2. The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (3-4. Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium.This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis?

  11. Experimental models of sepsis and septic shock: an overview

    Directory of Open Access Journals (Sweden)

    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  12. Microbial control of caged population of Zonocerus variegatus using ...

    African Journals Online (AJOL)

    Microbial control of caged populations of Zonocerus variegatus was carried out using indigenous fungal entomopathogens isolated from the grasshopper's cadaver. Bioassay response indicated a dose-dependent mortality coupled with drastic reduction in food consumption among spores infected grasshoppers. Lethal time ...

  13. Sepsis procedente de la comunidad en cuidados intensivos: Factores de riesgo

    Directory of Open Access Journals (Sweden)

    Pilar Legón Blasco

    2000-03-01

    Full Text Available Se realizó un estudio prospectivo y transversal en pacientes sépticos ingresados en la Unidad de Cuidados Intensivos del hospital "Dr. Ángel Arturo Aballí" con los criterios de sepsis procedente de la comunidad en un período de 18 meses, comprendido desde septiembre de 1996 hasta marzo de 1998, con el objetivo de analizar la frecuencia de factores de riesgo asociados con la infección. Se evaluaron 70 pacientes que cumplían los criterios antes mencionados. Se tomó en la comunidad un grupo control de niños sanos. En los resultados se encontró que los factores asociados con la sepsis fueron: el sexo masculino (p=0,002, RR=2,7, la no lactancia materna (p=0,01, RR=3,3, la malnutrición por defecto (p=0,04, RR=2,1, el hacinamiento (p=0,0008, RR=2,4, el hábito de fumar (p=0,02, RR=2,4 y la mala higiene (p=0,01, RR=1,5.A prospective and crossover study was carried out in patients admitted in Intensive Care Unit (ICU of "Dr. Angel Arturo Aballí" Hospital where criteria of sepsis came from community for a period of 18 months, September 1996 to March 1998, to analyze frequency of risk factors associated with infection. We assessed 70 patients who fulfiled criteria above mentioned. Healthy children were control group. By findings, we found that factors associated with sepsis included: male sex (p=0.002, RR=2.7, non-breast feeding (p=0.01, RR=3.3, malnutrition by defect (p=0.04, RR=2.1, crowding (p=0.0008, RR= 2.4, smoking (p=0.02, RR=2.4, and a poor hygiene (p=0.01, RR=1.5.

  14. Immunotherapy in the management of sepsis.

    Science.gov (United States)

    Sikora, Janusz Piotr

    2002-01-01

    This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

  15. Radiodiagnosis of lung syndrome in surgical sepsis

    International Nuclear Information System (INIS)

    Dvojnykh, V.P.; Palagin, E.K.

    1991-01-01

    The results of treatment of 23 patients with acute surgical sepsis were analysed. It was shown that the X-ray examination must be obligatory in surveillance of patients with purulent foci. Two roentgenological variants are possible in surgical sepsis: central and perepheric. X-ray examinations of chest organs should be conducted every 2-3 day

  16. [Effects of Na(+) /H(+) exchanger 1 inhibitor on intestinal injury of rats with burn sepsis and the mechanism].

    Science.gov (United States)

    Li, W P; Zhao, G Y; Yang, X K

    2017-06-20

    Objective: To observe the effects of Na(+) /H(+) exchanger 1 (NHE1) inhibitor on intestinal injury of rats with burn sepsis, and to explore the possible mechanism preliminarily. Methods: Ninety SD rats were divided into control group, pure sepsis group, and NHE1 inhibitor group according to the random number table, with 30 rats in each group. Full-thickness scald (hereinafter referred to as burn) model with 20% total body surface area were reproduced on the back of rats in pure sepsis and NHE1 inhibitor groups, and then 50 μL liquid of Pseudomonas aeruginosa ATCC 27853 (2×10(5) colony forming unit/mL) were injected into the center of wounds on the back. Rats in NHE1 inhibitor group were intraperitoneally injected with 0.1 mmol/L NHE1 inhibitor cariporide (0.4 mg/kg) rapidly after the successful establishment of burn sepsis model, while rats in pure sepsis group were injected with the same volume of normal saline. Except for not being made burn wounds nor receiving bacterination, rats in control group were treated the same as those in pure sepsis group. Rats with burn sepsis in each group were laparotomized and injected with 200 mL fluorescein isothiocyanate (FITC)-dextran in the concentration of 0.1 mol/L in terminal ileum at 12 hours post injury, and their left ventricular blood and terminal ileum were collected 30 minutes later. The serum content of FITC-dextran was detected with fluorescence spectrophotometer ( n =10); the morphology of intestinal tissue was observed with HE staining ( n =10); the content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in serum and intestinal tissue was determined with enzyme-linked immunosorbent assay ( n =20); the activity of myeloperoxidase (MPO) in serum and intestinal tissue was detected with colorimetric method ( n =20); the protein expression of nuclear factor-kappa B-p65 (NF-κB-p65) and phosphorylation levels of mitogen-activated protein kinase (MAPK) signal pathway related proteins p38MAPK

  17. Development of an e-learning package for sepsis care.

    Science.gov (United States)

    Davis, Anna; Henderson, James; Langmack, Gill

    Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.

  18. Microbial control on decomposition of radionuclides-containing oily waste in soil

    Science.gov (United States)

    Selivanovskaya, Svetlana; Galitskaya, Polina

    2014-05-01

    The oily wastes are formed annually during extraction, refinement, and transportation of the oil and may cause pollution of the environment. These wastes contain different concentrations of waste oil (40-60%), waste water (30-90%), and mineral particles (5-40%). Some oily wastes also contain naturally occurring radionuclides which were incorporated by water that was pumped up with the oil. For assessment of the hazard level of waste treated soil, not only measurements of contaminants content are needed, because bioavailability of oily components varies with hydrocarbon type, and soil properties. As far as namely microbial communities control the decomposition of organic contaminants, biological indicators have become increasingly important in hazard assessment and the efficiency of remediation process. In this study the decomposition of radionuclides-containing oily waste by soil microbial communities were estimated. Waste samples collected at the Tikchonovskii petroleum production yard (Tatarstan, Russia) were mixed with Haplic greyzem soil at ratio 1:4 and incubated for 120 days. During incubation period, the total hydrocarbon content of the soil mixed with the waste reduced from 156 ± 48 g kg-1 to 54 ± 8 g kg-1 of soil. The concentrations of 226Ra and 232Th were found to be 643 ± 127, 254 ± 56 Bq kg-1 and not changed significantly during incubation. Waste application led to a soil microbial biomass carbon decrease in comparison to control (1.9 times after 1 day and 1.3 times after 120 days of incubation). Microbial respiration increased in the first month of incubation (up to 120% and 160% of control after 1 and 30 days, correspondingly) and decreased to the end of incubation period (74% of control after 120 days). Structure of bacterial community in soil and soil/waste mixture was estimated after 120 days of incubation using SSCP method. The band number decreased in contaminated soil in comparison to untreated soil. Besides, several new dominant DNA

  19. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

  20. Early onset neonatal sepsis in preterm premature rupture of membranes

    International Nuclear Information System (INIS)

    Ashraf, M.N.

    2015-01-01

    To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis. (author)

  1. Neonatal Sepsis: past, present and future; a review article | Tripathi ...

    African Journals Online (AJOL)

    Sepsis is the most common cause of neonatal mortality. As per National Neonatal Perinatal Database (NNPD) 2002-2003, the incidence of neonatal sepsis in India was 30 per 1000 live birth. It is 3% among intramural babies and 39.7% among extramural admissions. The early manifestations of neonatal sepsis are vague ...

  2. Age, exercise, and the outcome of sepsis.

    Science.gov (United States)

    Banerjee, Debasree; Opal, Steven M

    2017-11-23

    We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

  3. Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis.

    Science.gov (United States)

    Septimus, Edward J; Coopersmith, Craig M; Whittle, Jessica; Hale, Caleb P; Fishman, Neil O; Kim, Thomas J

    2017-10-16

    The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    Science.gov (United States)

    Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

    2017-02-01

    Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

  5. An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU.

    Science.gov (United States)

    Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G

    2018-04-01

    Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Observational cohort study. Academic medical center from January 2013 to December 2015. Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. None. High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the

  6. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

    Science.gov (United States)

    Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

    2018-01-01

    Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

  7. Disseminated intravascular coagulation in meningococcal sepsis. Case 7

    NARCIS (Netherlands)

    Zeerleder, S.; Zürcher Zenklusen, R.; Hack, C. E.; Wuillemin, W. A.

    2003-01-01

    We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis.

  8. Barriers to implementing the Sepsis Six guidelines in an acute hospital setting.

    Science.gov (United States)

    Breen, Sarah-Jane; Rees, Sharon

    2018-05-10

    To identify the barriers to implementation of the Sepsis Six pathway. Research has suggested that compliance with the Sepsis Six pathway remains low. A convenience sample of doctors and nurses from one emergency department, two medical wards and two surgical wards were asked to complete a survey questionnaire. Data from 108 respondents were available for analysis. Doctors and nurses agreed that lack of sepsis recognition during observation rounds and failure to associate sepsis with deranged temperature and blood results acted as barriers to the identification of sepsis. Doctors and nurses agreed that nursing delays and knowledge deficits were the top barriers leading to delay in sepsis treatment. Knowledge deficits, lack of resources and practical issues were barriers identified in this survey. This will inform the educational and process needs of both doctors and nurses in order to improve sepsis care.

  9. Pilot study comparing sepsis management with and without electronic clinical practice guidelines in an academic emergency department.

    Science.gov (United States)

    Bond, Christopher M; Djogovic, Dennis; Villa-Roel, Cristina; Bullard, Michael J; Meurer, David P; Rowe, Brian H

    2013-03-01

    Sepsis is a potentially life-threatening condition that requires urgent management in an Emergency Department (ED). Evidence-based guidelines for managing sepsis have been developed; however, their integration into routine practice is often incomplete. Care maps may help clinicians meet guideline targets more often. To determine if electronic clinical practice guidelines (eCPGs) improve management of patients with severe sepsis and septic shock (SS/SS). The impact of an eCPG on the management of patients presenting with SS/SS over a 3-year period at a tertiary care ED was evaluated using retrospective case-control design and chart review methods. Cases and controls, matched by age and sex, were chosen from an electronic database using physician sepsis diagnoses. Data were compared using McNemar tests or paired t-tests, as appropriate. Overall, 51 cases and controls were evaluated; the average age was 62 years, and 60% were male. eCPG patients were more likely to have a central venous pressure and central venous oxygen saturation measured; however, lactate measurement, blood cultures, and other investigations were similarly ordered (all p > 0.05). The administration of antibiotics within 3 h (63% vs. 41%; p = 0.03) and vasopressors (45% vs. 20%; p = 0.02) was more common in the eCPG group; however, use of corticosteroids and other interventions did not differ between the groups. Overall, survival was high and similar between groups. A sepsis eCPG experienced variable use; however, physicians using the eCPG achieved more quality-of-care targets for SS/SS. Strategies to increase the utilization of eCPGs in Emergency Medicine seem warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Physiopathology, importance and usefulness of lactate in patients with sepsis Fisiopatología, importancia y utilidad del lactato en pacientes con sepsis*

    Directory of Open Access Journals (Sweden)

    Maycos Leandro Zapata Muñoz

    2010-08-01

    Full Text Available

    Worldwide, sepsis is acknowledged as a significant cause of hospital-associated mortality. There is an increasing interest in identifying the group of patients that can benefit more from an early and aggressive therapy. Lactate is an important cellular metabolite, traditionally interpreted as a marker of low oxygen delivery to tissues during sepsis. Given recent investigations about the physiology of lactate production, and with the understanding of sepsis as a systemic response, interpretation of a high lactate level may include various processes, not all of them harmful. In this review, the different cellular processes that may explain high lactate levels in sepsis are described. Its current clinical usefulness and proposals for future interpretation in the reanimation of patients with sepsis are analyzed.

    La sepsis como causante de alta mortalidad en instituciones hospitalarias es un evento reconocido mundialmente. Existe un interés creciente en identificar el grupo de pacientes que más se pueda beneficiar de una terapia temprana e intensiva. El lactato es un marcador importante de los procesos metabólicos celulares, y en sepsis se lo ha interpretado como un biomarcador que indica la deficiencia de aporte de oxígeno a los tejidos. Si se tienen en cuenta investigaciones recientes sobre la fisiología de la producción de lactato, y se entiende

  11. Can mean platelet volume and mean platelet volume/platelet count ratio be used as a diagnostic marker for sepsis and systemic inflammatory response syndrome?

    Science.gov (United States)

    Ates, Selma; Oksuz, Hafıze; Dogu, Bırsen; Bozkus, Fulsen; Ucmak, Hasan; Yanıt, Fadime

    2015-01-01

    Objectives: To determine whether the mean platelet volume (MPV) and MPV/platelet (PLT) values can be used in the study of sepsis and systemic inflammatory response syndrome (SIRS). Methods: In this retrospective case-controlled study, 69 sepsis, 69 SIRS patients, and 72 control group who were treated in the years 2012-2013 were reviewed, and both the MPV and MPV/PLT rates were evaluated in all groups at Kahramanmaras Sutcu Imam University Intensive Care Unit, Kahramanmaras, Turkey. Results: Statistically significant difference was found between sepsis, SIRS, and control groups when comparing the MPV and MPV/PLT ratio (p0.05). Mean platelet volume values for sepsis and control groups was 10.07/8.731 femtoliter (fL) (p=0.000), and 9.45/8.731 fL (p=0.000) for SIRS and control groups. In the group of sepsis patients, the MPV was found to be at cut-off 8.915, sensitivity 71%, and specificity 63.9%. In the group of patients with SIRS, MPV was found to be at cut-off 8.85, sensitivity 69.6%, and specificity 62.5%. For the MPV/PLT values, the specificity and sensitivity were found to be insignificant. Conclusion: This study shows that although there was no significant reduction in the PLT values between the sepsis and SIRS patients, the MPV and MPV/PLT ratio values were found to have significant differences. However, the specificity and sensitivity of the values were not reliable standard to be used as a test. PMID:26446329

  12. Farm management, not soil microbial diversity, controls nutrient loss from smallholder tropical agriculture

    Directory of Open Access Journals (Sweden)

    Stephen A Wood

    2015-03-01

    Full Text Available Tropical smallholder agriculture supports the livelihoods of over 900 million of the world’s poorest people. This form of agriculture is undergoing rapid transformation in nutrient cycling pathways as international development efforts strongly promote greater use of mineral fertilizers to increase crop yields. These changes in nutrient availability may alter the composition of microbial communities with consequences for rates of biogeochemical processes that control nutrient losses to the environment. Ecological theory suggests that altered microbial diversity will strongly influence processes performed by relatively few microbial taxa, such as denitrification and hence nitrogen losses as nitrous oxide, a powerful greenhouse gas. Whether this theory helps predict nutrient losses from agriculture depends on the relative effects of microbial community change and increased nutrient availability on ecosystem processes. We find that mineral and organic nutrient addition to smallholder farms in Kenya alters the taxonomic and functional diversity of soil microbes. However, we find that the direct effects of farm management on both denitrification and carbon mineralization are greater than indirect effects through changes in the taxonomic and functional diversity of microbial communities. Changes in functional diversity are strongly coupled to changes in specific functional genes involved in denitrification, suggesting that it is the expression, rather than abundance, of key functional genes that can serve as an indicator of ecosystem process rates. Our results thus suggest that widely used broad summary statistics of microbial diversity based on DNA may be inappropriate for linking microbial communities to ecosystem processes in certain applied settings. Our results also raise doubts about the relative control of microbial composition compared to direct effects of management on nutrient losses in applied settings such as tropical agriculture.

  13. Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat.

    Directory of Open Access Journals (Sweden)

    Mani Chopra

    Full Text Available We tested the hypothesis that 5-Hydroxydecanoic acid (5HD, a putative mitoK(ATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival.Male Sprague-Dawley rats (350-400 g were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1, Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles in the presence/absence of 5HD (100 µmoles. A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40% and at 6 hr post-sepsis (-20%. Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group. The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C.The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP channels in sepsis. We concluded that mitoK(ATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

  14. Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat.

    Science.gov (United States)

    Chopra, Mani; Golden, Honey B; Mullapudi, Srinivas; Dowhan, William; Dostal, David E; Sharma, Avadhesh C

    2011-01-01

    We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoK(ATP) channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40%) and at 6 hr post-sepsis (-20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP) channels in sepsis. We concluded that mitoK(ATP) channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

  15. Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

    Science.gov (United States)

    Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

    2017-11-01

    Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

  16. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Science.gov (United States)

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  17. Multi-analytical Approaches Informing the Risk of Sepsis

    Science.gov (United States)

    Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

    Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

  18. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  19. New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study.

    Science.gov (United States)

    Ranzani, Otavio T; Prina, Elena; Menéndez, Rosario; Ceccato, Adrian; Cilloniz, Catia; Méndez, Raul; Gabarrus, Albert; Barbeta, Enric; Bassi, Gianluigi Li; Ferrer, Miquel; Torres, Antoni

    2017-11-15

    The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.

  20. Predicting Sepsis Risk Using the "Sniffer" Algorithm in the Electronic Medical Record.

    Science.gov (United States)

    Olenick, Evelyn M; Zimbro, Kathie S; DʼLima, Gabrielle M; Ver Schneider, Patricia; Jones, Danielle

    The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities.

  1. Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room.

    Directory of Open Access Journals (Sweden)

    Anna M Kauppi

    Full Text Available A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99 and a specificity 0.84 (95% CI 0.58-0.94 with an AUC of 0.93 (95% CI 0.89-1.01. Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00 and specificity of 0.95 (95% CI 0.74-0.99, and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.

  2. Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

    Science.gov (United States)

    Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

    2012-01-01

    Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by

  3. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

    Directory of Open Access Journals (Sweden)

    Jessica A Dominguez

    Full Text Available The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption.Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and

  4. Cost and mortality impact of an algorithm-driven sepsis prediction system.

    Science.gov (United States)

    Calvert, Jacob; Hoffman, Jana; Barton, Christopher; Shimabukuro, David; Ries, Michael; Chettipally, Uli; Kerem, Yaniv; Jay, Melissa; Mataraso, Samson; Das, Ritankar

    2017-06-01

    To compute the financial and mortality impact of InSight, an algorithm-driven biomarker, which forecasts the onset of sepsis with minimal use of electronic health record data. This study compares InSight with existing sepsis screening tools and computes the differential life and cost savings associated with its use in the inpatient setting. To do so, mortality reduction is obtained from an increase in the number of sepsis cases correctly identified by InSight. Early sepsis detection by InSight is also associated with a reduction in length-of-stay, from which cost savings are directly computed. InSight identifies more true positive cases of severe sepsis, with fewer false alarms, than comparable methods. For an individual ICU with 50 beds, for example, it is determined that InSight annually saves 75 additional lives and reduces sepsis-related costs by $560,000. InSight performance results are derived from analysis of a single-center cohort. Mortality reduction results rely on a simplified use case, which fixes prediction times at 0, 1, and 2 h before sepsis onset, likely leading to under-estimates of lives saved. The corresponding cost reduction numbers are based on national averages for daily patient length-of-stay cost. InSight has the potential to reduce sepsis-related deaths and to lead to substantial cost savings for healthcare facilities.

  5. Spontaneous neutrophil migration patterns during sepsis after major burns.

    Science.gov (United States)

    Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

  6. A case study in intra-abdominal sepsis.

    Science.gov (United States)

    Paul, Jasmeet S; Ridolfi, Timothy J

    2012-12-01

    Intra-abdominal infections are a common problem for the general surgeon and major sources of morbidity and mortality in the intensive care unit. Some of these patients present with peritonitis that can rapidly progress to septic shock. The basic principles of care include prompt resuscitation, antibiotics, and source control. This article will use a detailed case study to outline the management of a patient with severe intra-abdominal infection from diverticulitis from initial resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as they pertain to surgical patients are discussed and updated, and the concept of damage control general surgery is applied. Copyright © 2012. Published by Elsevier Inc.

  7. Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

    International Nuclear Information System (INIS)

    Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.; James, J.H.; Li, S.; Rigel, D.F.; Fischer, J.E.

    1989-01-01

    Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle

  8. Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin.

    Science.gov (United States)

    Wang, Rui-lan; Kang, Fu-xin

    2010-06-01

    Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

  9. Nitrogenoxid og sepsis

    DEFF Research Database (Denmark)

    El-Haj, Lama; Bestle, Morten Heiberg

    2018-01-01

    The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological functions of nitric oxide in the human body, and how these functions can and have been used clinically. Nitric oxide plays an important ...

  10. Role of Cytokines as a Double-edged Sword in Sepsis

    Science.gov (United States)

    CHAUDHRY, HINA; ZHOU, JUHUA; ZHONG, YIN; ALI, MIR MUSTAFA; MCGUIRE, FRANKLIN; NAGARKATTI, PRAKASH S.; NAGARKATTI, MITZI

    2014-01-01

    Background Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. Materials and Methods Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. Results In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. Conclusion Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis. PMID:24292568

  11. Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

    Science.gov (United States)

    Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2017-08-01

    To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

  12. Biomarkers of Endothelial Cell Activation in Early Sepsis

    DEFF Research Database (Denmark)

    Skibsted, Simon; Jones, Alan E; Puskarich, Michael A

    2013-01-01

    and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one...

  13. [New Concept for Surviving Sepsis: from Phenomenon to Essence].

    Science.gov (United States)

    Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan

    2016-07-01

    Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

  14. IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

    Science.gov (United States)

    Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

    2018-01-01

    Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

  15. Loss of Sympathetic Nerves in Spleens from Patients with End Stage Sepsis

    Directory of Open Access Journals (Sweden)

    Donald B. Hoover

    2017-12-01

    Full Text Available The spleen is an important site for central regulation of immune function by noradrenergic sympathetic nerves, but little is known about this major region of neuroimmune communication in humans. Experimental studies using animal models have established that sympathetic innervation of the spleen is essential for cholinergic anti-inflammatory responses evoked by vagal nerve stimulation, and clinical studies are evaluating this approach for treating inflammatory diseases. Most data on sympathetic nerves in spleen derive from rodent studies, and this work has established that remodeling of sympathetic innervation can occur during inflammation. However, little is known about the effects of sepsis on spleen innervation. Our primary goals were to (i localize noradrenergic nerves in human spleen by immunohistochemistry for tyrosine hydroxylase (TH, a specific noradrenergic marker, (ii determine if nerves occur in close apposition to leukocytes, and (iii determine if splenic sympathetic innervation is altered in patients who died from end stage sepsis. Staining for vesicular acetylcholine transporter (VAChT was done to screen for cholinergic nerves. Archived paraffin tissue blocks were used. Control samples were obtained from trauma patients or patients who died after hemorrhagic stroke. TH + nerves were associated with arteries and arterioles in all control spleens, occurring in bundles or as nerve fibers. Individual TH + nerve fibers entered the perivascular region where some appeared in close apposition to leukocytes. In marked contrast, spleens from half of the septic patients lacked TH + nerves fibers and the average abundance of TH + nerves for the septic group was only 16% of that for the control group (control: 0.272 ± 0.060% area, n = 6; sepsis: 0.043 ± 0.026% area, n = 8; P < 0.005. All spleens lacked cholinergic innervation. Our results provide definitive evidence for the distribution of noradrenergic

  16. Role of presepsin for the evaluation of sepsis in the emergency department.

    Science.gov (United States)

    Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

    2014-10-01

    Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

  17. Is there NO treatment for severe sepsis? | Bredan | Libyan Journal of ...

    African Journals Online (AJOL)

    Sepsis is a systemic inflammatory response syndrome in the presence of suspected or proven infection, and it may progress to or encompass organ failure (severe sepsis) and hypotension (septic shock). Clinicians possess an arsenal of supportive measures to combat severe sepsis and septic shock, and some success, ...

  18. Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

    Science.gov (United States)

    Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

    2014-01-01

    To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

  19. Attenuation of sepsis-induced rat liver injury by epigallocatechin ...

    African Journals Online (AJOL)

    rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar ... capacity, resulting in excessive oxidants in cells. [6]. ... Care (NIH publication no. 85-23 ..... estimates of severe sepsis in United States emergency.

  20. Neonatal sepsis: Highlighting the principles of diagnosis and ...

    African Journals Online (AJOL)

    Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal ...

  1. Laboratory changes and levels of biomarkers in localized bacterial infections and sepsis in children

    Directory of Open Access Journals (Sweden)

    Larysa Pypa

    2017-08-01

    Full Text Available Background. The success of sepsis treatment depends on early diagnosis of the generalization of bacterial infection, but the nonspecificity of clinical manifestations often makes the diagnosis delayed. Therefore, the search for highly specific and sensitive biomarkers for early diagnosis of sepsis is relevant. The aim of our research is investigate the laboratory features and diagnostic value of a number of modern biomarkers for the diagnosis of sepsis in children. Materials and methods. of general laboratory studies and determination of CRP level were performed in 115 children with generalized and localized forms of bacterial infections. The main group (47 children - children with sepsis, a comparison group (68 children - with a localized bacterial infection of various localization. The age of children was from 1 month. up to 18 years. Grouping was performed according to the presence of signs and symptoms of SIRS and organ dysfunction. Determination of the level of procalcitonin and TNF-α was performed in 31 children of the main group, 45 children in the comparison group and 30 children in the control group (children without signs of inflammation. Prespepsin levels were determined in 16 main group children,14 in the comparison group and26 in the control group. Results. During the study, it was found that the level of leukocytosis was much higher and continued 2.6 times longer in the main group than in the children of the comparison group (p <0.01.Anemia was found in 76.6% of the children in the main group, while in the comparator group, the anemia syndrome was diagnosed 3.7 times less frequently. In the study of CRP in the main group, its level reached 44.7 mg / l and 28.3 mg / l in the comparison group, the specificity and sensitivity for diagnosis of sepsis was 46.8% and 51.5% respectively. The mean TNF-α level in children in the main group was 280.3 pg / ml CI 95% [243.9-316.7], which was 1.5 times higher than in children with a localized

  2. Sepsis in the intensive care unit: epidemiology, outcome and host response

    NARCIS (Netherlands)

    van Vught, L.A.

    2016-01-01

    Sepsis is a life-threatening syndrome that arises when a dysbalanced patient response to an infection causes damage to the body’s own organs and tissues. Sepsis is, to date, still a major cause of morbidity and mortality worldwide. A detailed understanding of the pathogenesis of sepsis is likely to

  3. Septris: a novel, mobile, online, simulation game that improves sepsis recognition and management.

    Science.gov (United States)

    Evans, Kambria H; Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa

    2015-02-01

    Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming.The authors sought to assess the game's dissemination and its impact on learners' sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P game scores with sepsis knowledge.

  4. Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study.

    Science.gov (United States)

    Yu, Ying; Li, Xia-Xi; Jiang, Ling-Xiao; Du, Meng; Liu, Zhan-Guo; Cen, Zhong-Ran; Wang, Hua; Guo, Zhen-Hui; Chang, Ping

    2016-01-01

    Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required. Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture. A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively. PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.

  5. An unusual case of sepsis and petechial rash.

    Science.gov (United States)

    Gardner, Christina

    2017-05-01

    This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.

  6. Exploitation of microbial antagonists for the control of postharvest diseases of fruits: a review.

    Science.gov (United States)

    Dukare, Ajinath Shridhar; Paul, Sangeeta; Nambi, V Eyarkai; Gupta, Ram Kishore; Singh, Rajbir; Sharma, Kalyani; Vishwakarma, Rajesh Kumar

    2018-01-16

    Fungal diseases result in significant losses of fruits and vegetables during handling, transportation and storage. At present, post-production fungal spoilage is predominantly controlled by using synthetic fungicides. Under the global climate change scenario and with the need for sustainable agriculture, biological control methods of fungal diseases, using antagonistic microorganisms, are emerging as ecofriendly alternatives to the use of fungicides. The potential of microbial antagonists, isolated from a diversity of natural habitats, for postharvest disease suppression has been investigated. Postharvest biocontrol systems involve tripartite interaction between microbial antagonists, the pathogen and the host, affected by environmental conditions. Several modes for fungistatic activities of microbial antagonists have been suggested, including competition for nutrients and space, mycoparasitism, secretion of antifungal antibiotics and volatile metabolites and induction of host resistance. Postharvest application of microbial antagonists is more successful for efficient disease control in comparison to pre-harvest application. Attempts have also been made to improve the overall efficacy of antagonists by combining them with different physical and chemical substances and methods. Globally, many microbe-based biocontrol products have been developed and registered for commercial use. The present review provides a brief overview on the use of microbial antagonists as postharvest biocontrol agents and summarises information on their isolation, mechanisms of action, application methods, efficacy enhancement, product formulation and commercialisation.

  7. Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

    Science.gov (United States)

    Despins, Laurel A

    Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

  8. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    Directory of Open Access Journals (Sweden)

    Sang Hoon Lee

    2015-01-01

    Full Text Available Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98] who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL, free fatty acid (FFA, and apolipoprotein (Apo A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043, p=0.020, p=0.005, and p=0.015, resp.. According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018 and p=0.008, resp.. Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.

  9. Sepsis progression and outcome: a dynamical model

    Directory of Open Access Journals (Sweden)

    Gessler Damian DG

    2006-02-01

    Full Text Available Abstract Background Sepsis (bloodstream infection is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. Results We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC, a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. Conclusion The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates.

  10. [Recognizing prevention and treatment of burn sepsis with the concept of holistic integrative medicine].

    Science.gov (United States)

    Huan, J N

    2017-04-20

    Sepsis remains a major cause of death in severe burns. The effect of sepsis management is influenced by its complicated pathophysiologic changes. In order to improve the outcome of burn sepsis, the predisposing factor of sepsis after burn analyzed by advanced technology, the early prevention, antibiotics therapy, and combined treatment in severe burns with sepsis are discussed using the concept of holistic integrative medicine.

  11. Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

    Science.gov (United States)

    Prescott, Hallie C; Cope, Tara M; Gesten, Foster C; Ledneva, Tatiana A; Friedrich, Marcus E; Iwashyna, Theodore J; Osborn, Tiffany M; Seymour, Christopher W; Levy, Mitchell M

    2018-05-01

    Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Observational cohort study. First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Sepsis regulations with mandated reporting. We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p New York State Department of Health Sepsis Clinical Database. Incomplete reporting appears to be driven more by underrecognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement.

  12. Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia

    Directory of Open Access Journals (Sweden)

    Dick Andrew

    2012-11-01

    Full Text Available Abstract Background Hospital associated infections are major problems, which are increasing in incidence and very costly. However, most research has focused only on measuring consequences associated with the initial hospitalization. We explored the long-term consequences of infections in elderly Medicare patients admitted to an intensive care unit (ICU and discharged alive, focusing on: sepsis, pneumonia, central-line-associated bloodstream infections (CLABSI, and ventilator-associated pneumonia (VAP; the relationships between the infections and long-term survival and resource utilization; and how resource utilization was related to impending death during the follow up period. Methods Clinical data and one year pre- and five years post-index hospitalization Medicare records were examined. Hazard ratios (HR and healthcare utilization incidence ratios (IR were estimated from state of the art econometric models. Patient demographics (i.e., age, gender, race and health status and Medicaid status (i.e., dual eligibility were controlled for in these models. Results In 17,537 patients, there were 1,062 sepsis, 1,802 pneumonia, 42 CLABSI and 52 VAP cases. These subjects accounted for 62,554 person-years post discharge. The sepsis and CLABSI cohorts were similar as were the pneumonia and VAP cohorts. Infection was associated with increased mortality (sepsis HR = 1.39, P  Conclusions The infections had significant and lasting adverse consequences among the elderly. Yet, many of these infections may be preventable. Investments in infection prevention interventions are needed in both community and hospitals settings.

  13. In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.

    Science.gov (United States)

    Okeke, Emeka B; Uzonna, Jude E

    2016-01-01

    In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.

  14. Increased Resistin Levels in Intra-abdominal Sepsis: Correlation with proinflammatory cytokines & Acute Physiology & Chronic Health Evaluation II scores

    Directory of Open Access Journals (Sweden)

    Tonguç U. Yilmaz

    2014-10-01

    Full Text Available Objectives: Resistin, a hormone secreted from adipocytes and considered to be a likely cause of insulin resistance, has recently been accepted as a proinflammatory cytokine. This study aimed to determine the correlation between resistin levels in patients with intra-abdominal sepsis and mortality. Methods: Of 45 patients with intraabdominal sepsis, a total of 35 adult patients were included in the study. This study was undertaken from December 2011 to December 2012 and included patients who had no history of diabetes mellitus and who were admitted to the general surgery intensive care units of Gazi University and Bülent Ecevit University School of Medicine, Turkey. Evaluations were performed on 12 patients with sepsis, 10 patients with severe sepsis, 13 patients with septic shock and 15 healthy controls. The patients’ plasma resistin, interleukin-6 (IL-6, tumour necrosis factor alpha (TNF-α, interleukin-1 beta (IL-1β, procalcitonin, lactate and glucose levels and Acute Physiology and Chronic Health Evaluation (APACHE II scores were studied daily for the first five days after admission. A correlation analysis of serum resistin levels with cytokine levels and APACHE II scores was performed. Results: Serum resistin levels in patients with sepsis were significantly higher than in the healthy controls (P <0.001. A significant correlation was found between serum resistin levels and APACHE II scores, serum IL-6, IL-1β, TNF-α, procalcitonin, lactate and glucose levels. Furthermore, a significant correlation was found between serum resistin levels and all-cause mortality (P = 0.02. Conclusion: The levels of resistin were significantly positively correlated with the severity of disease and were a possible mediator of a prolonged inflammatory state in patients with intra-abdominal sepsis.

  15. Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development.

    Science.gov (United States)

    Constantino, Larissa; Galant, Letícia Selinger; Vuolo, Francieli; Guarido, Karla Lorena; Kist, Luiza Wilges; de Oliveira, Giovanna Medeiros Tavares; Pasquali, Matheus Augusto de Bittencourt; de Souza, Cláudio Teodoro; da Silva-Santos, José Eduardo; Bogo, Maurício Reis; Moreira, José Cláudio Fonseca; Ritter, Cristiane; Dal-Pizzol, Felipe

    2017-12-01

    Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.

  16. The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

    Science.gov (United States)

    Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

    2017-11-01

    The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Degree of agreement among sepsis diagnosis criteria in adult emergency room patients with infection

    Science.gov (United States)

    Sinto, R.; Chandra, A. T.; Lie, K. C.; Suwarto, S.

    2018-03-01

    The study on the degree of agreement among three established sepsis diagnosis criteria become the necessity to investigate the best sepsis diagnosis criteria in Indonesia further. A cross-sectional study of adult Emergency Room patients hospitalized with a diagnosis of infection in CiptoMangunkusumo Hospital, Indonesia was conducted during March and April 2017. We recorded diagnosis, gender, age, comorbidities, infection source, and origin. Every subject was classified into sepsis and non-sepsis based on 1991, 2001 and sepsis-3 criteria. Raw % and Kappa agreement coefficients (κ) were calculated according to previously established formula to measure the degree of agreement among three diagnostic criteria. As many as 278 subjects were included in this study. The raw % agreement and κ between 1991 and 2001 criteria is 69.07% and 0.34 respectively. The raw % agreement and κ between 2001 and sepsis-3 criteria is 56.12% and 0.15 respectively. The raw % agreement and κ between 1991 and sepsis-3 criteria is 48.19% and -0.02. In conclusions, there is afair agreement between 1991 and 2001 criteria, poor agreement between 2001 and sepsis-3 criteria, and poor disagreement between 1991 and sepsis-3 criteria. This necessitates further Indonesian study of the best diagnosis criteria to diagnose an infected patient with sepsis.

  18. Pregnancy-Associated Severe Sepsis: Contemporary State and Future Challenges.

    Science.gov (United States)

    Oud, Lavi

    2014-12-01

    Pregnancy is associated with an increased risk of infection related to its associated mechanical and physiological changes. Sepsis remains among the top causes of maternal death worldwide and is associated with substantial maternal morbidity. However, there are sparse data on pregnancy-associated severe sepsis (PASS), related in part to infrequent reports, varying case definitions and methodological approach, small cohort size, and often limited focus on severe sepsis in selected phases of pregnancy outcomes. Available reports vary, but indicate that PASS is a rare but likely increasing complication, and it is more likely to develop with increased maternal age, among minority women, the poor, those lacking health insurance, those with chronic illness or pregnancy-associated complications, and following invasive procedures. Obstetric sites of infection are the most prevalent, but non-obstetric infections often underlie pregnancy-associated severe sepsis, though the source of infection is often not readily apparent during initial care. Women with PASS can have a rapidly fatal course and require heightened clinician vigilance for early diagnosis and timely effective intervention. Nevertheless, available reports raise concerns about prevalent substandard care of these patients, contributing to adverse outcomes. The case fatality of PASS appears lower than that in the general population with severe sepsis, while the long-term outcomes of survivors remain unknown.

  19. Designing and testing computer based screening engine for severe sepsis/septic shock.

    Science.gov (United States)

    Herasevich, V; Afessa, B; Chute, C G; Gajic, O

    2008-11-06

    This study addresses the role of a sepsis "sniffer", an automatic screening tool for the timely identification of patients with severe sepsis/septic shock, based electronic medical records. During the two months prospective implementation in a medical intensive care unit, 37 of 320 consecutive patients developed severe sepsis/septic shock. The sniffer demonstrated a sensitivity of 48% and specificity of 86%, and positive predictive value 32%. Further improvements are needed prior to the implementation of sepsis sniffer in clinical practice and research.

  20. Development of Immunopathobiogenesis on SIRS-Sepsis

    Directory of Open Access Journals (Sweden)

    A Guntur Hermawan

    2009-04-01

    Full Text Available Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS. In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT and C-reactive protein (CRP, despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO.The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome. KEYWORDS: sepsis, innate immunity, adaptive.

  1. Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation.

    Science.gov (United States)

    Ekaney, Michael Liembo; Otto, Gordon Philipp; Sossdorf, Maik; Sponholz, Christoph; Boehringer, Michael; Loesche, Wolfgang; Rittirsch, Daniel; Wilharm, Arne; Kurzai, Oliver; Bauer, Michael; Claus, Ralf Alexander

    2014-09-24

    Circulating histones have been identified as mediators of damage in animal models of sepsis and in patients with trauma-associated lung injury. Despite existing controversies on actual histone concentrations, clinical implications and mechanism of action in various disease conditions, histone levels in human sepsis, association with disease progression and mediated effects on endothelial and immune cells remain unreported. This study aimed to determine histone levels and its clinical implication in septic patients and to elucidate histone-mediated effects ex-vivo. Histone levels, endogenous activated protein C (APC) levels and clinical data from two independent cohorts of septic patients were obtained. Histone levels were compared with various control groups including healthy individuals, intensive care unit (ICU) patients without sepsis, ICU patients with multiple organ failure and patients with minor or multiple trauma, all without infection. Endothelial and monocytic cells were stimulated with histones. Cellular integrity and sepsis prototypical cytokines were evaluated. The mechanism of action of histones via Toll-like receptor 4 (TLR4) was evaluated using a function blocking antibody. Histone degradation in plasma was studied by immunoblotting. Histone H4 levels were significantly elevated in patients with sepsis (cohort I; n = 15 and cohort II; n = 19) versus ICU controls (n = 12), patients with multiple organ failure (n = 12) or minor trauma (n = 7), associated with need for renal replacement therapy and decrease in platelet count during disease progression, and remarkably were significantly associated with increased mortality rates in septic patients (ICU-, 28 day- and 90 day mortality rates). There was an inverse correlation between plasma histones and endogenous APC levels. Histone stimulation induced the release of sepsis prototypic cytokines and decreased cell integrity indicated by a significant increase of lactate dehydrogenase (LDH) and propidium

  2. Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates.

    Science.gov (United States)

    Hiensch, Robert; Poeran, Jashvant; Saunders-Hao, Patricia; Adams, Victoria; Powell, Charles A; Glasser, Allison; Mazumdar, Madhu; Patel, Gopi

    2017-10-01

    Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility-onset (HCFO) Clostridium difficile infection (CDI) rates. We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative. Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P antibiotic use were not those included in the sepsis order set. The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  3. The Rate of Sepsis in a National Pediatric Population, 2006 to 2012.

    Science.gov (United States)

    Schuller, Kristin A; Hsu, Benson S; Thompson, Allyson B

    2017-10-01

    The rate of pediatric severe sepsis is reported to be on the rise in the United States, increasing by approximately 6000 cases annually. The goal of this study was to determine the rate of pediatric sepsis per 100 000 inpatient discharges over time. The 2006, 2009, and 2012 Agency for Healthcare Research and Quality Healthcare Cost Utilization Project Kid's Inpatient Databases were used to analyze the rate of sepsis in children over time. The rate of pediatric sepsis has increased over time from 92.8 per 100 000 in 2006 to 158.7 per 100 000 in 2012. Children less than a year old with Medicaid coverage and 3 or more procedures during hospitalization have significantly higher rates than their counterparts. This study helps clarify the population demographics that are at greater risk for sepsis infections. Understanding the at-risk population aids policymakers and care providers in targeting these populations and make drastic changes to sepsis policies.

  4. Approach to neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Shankar Narayan

    2015-01-01

    The treatment includes supportive care along with administration of appropriate antibiotics. Adjuvant treatment includes IVIG, GCSF, exchange transfusion and pentoxifylline administration. This paper aims to present an algorithmic approach to neonatal sepsis to expedite the diagnosis along with providing appropriate and adequate treatment.

  5. Computer versus paper system for recognition and management of sepsis in surgical intensive care.

    Science.gov (United States)

    Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

    2014-02-01

    A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system

  6. Immature platelet fraction in bacterial sepsis severity assessment

    Science.gov (United States)

    Djuang, M. H.; Ginting, F.; Hariman, H.

    2018-03-01

    Sepsis is an infection-induced syndrome, mostly caused by bacteria, of organ dysfunctions that caused by host response dysregulations. One of the simplest sepsis-indicator is platelet and its indexes. A new platelet parameter called immature platelet count (IPF) became theinterest in this study. The study aims to see whether IPF could assess sepsis severity by procalcitonin (PCT).Sixty-four of seventy-one patients with increased PCT were included in this cross-sectional study and separated into three groups based on their PCT levels. IPF showed no significance among the three groups (p-value>0.05) while platelet count was significant (p-valuesepsis severity based on PCT showed larger platelet count, as the result of platelet destructions caused by pro-inflammatory cytokines and endotoxins.

  7. CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Balázs Csóka

    2009-07-01

    Full Text Available Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2 receptors on immune cells. Here we examined the role of CB(2 receptors in regulating the host's response to sepsis.The role of CB(2 receptors was studied by subjecting CB(2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+ and CD19(+ cells during CLP.Taken together, our results establish for the first time that CB(2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.

  8. The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

    Science.gov (United States)

    Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

    2017-10-01

    Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

  9. Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis.

    Science.gov (United States)

    Iwashyna, Theodore J; Odden, Andrew; Rohde, Jeffrey; Bonham, Catherine; Kuhn, Latoya; Malani, Preeti; Chen, Lena; Flanders, Scott

    2014-06-01

    Severe sepsis is a common and costly problem. Although consistently defined clinically by consensus conference since 1991, there have been several different implementations of the severe sepsis definition using ICD-9-CM codes for research. We conducted a single center, patient-level validation of 1 common implementation of the severe sepsis definition, the so-called "Angus" implementation. Administrative claims for all hospitalizations for patients initially admitted to general medical services from an academic medical center in 2009-2010 were reviewed. On the basis of ICD-9-CM codes, hospitalizations were sampled for review by 3 internal medicine-trained hospitalists. Chart reviews were conducted with a structured instrument, and the gold standard was the hospitalists' summary clinical judgment on whether the patient had severe sepsis. Three thousand one hundred forty-six (13.5%) hospitalizations met ICD-9-CM criteria for severe sepsis by the Angus implementation (Angus-positive) and 20,142 (86.5%) were Angus-negative. Chart reviews were performed for 92 randomly selected Angus-positive and 19 randomly-selected Angus-negative hospitalizations. Reviewers had a κ of 0.70. The Angus implementation's positive predictive value was 70.7% [95% confidence interval (CI): 51.2%, 90.5%]. The negative predictive value was 91.5% (95% CI: 79.0%, 100%). The sensitivity was 50.4% (95% CI: 14.8%, 85.7%). Specificity was 96.3% (95% CI: 92.4%, 100%). Two alternative ICD-9-CM implementations had high positive predictive values but sensitivities of Angus implementation of the international consensus conference definition of severe sepsis offers a reasonable but imperfect approach to identifying patients with severe sepsis when compared with a gold standard of structured review of the medical chart by trained hospitalists.

  10. Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

    Science.gov (United States)

    Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita

    2018-04-18

    Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.

  11. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    International Nuclear Information System (INIS)

    Ouzounian, T.J.; Thompson, L.; Grogan, T.J.; Webber, M.M.; Amstutz, H.C.

    1987-01-01

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement

  12. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

    Science.gov (United States)

    Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

    2014-07-01

    The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design

  13. Time for a neonatal-specific consensus definition for sepsis.

    Science.gov (United States)

    Wynn, James L; Wong, Hector R; Shanley, Thomas P; Bizzarro, Matthew J; Saiman, Lisa; Polin, Richard A

    2014-07-01

    To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

  14. Metabolomics in Sepsis and Its Impact on Public Health.

    Science.gov (United States)

    Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela

    2017-01-01

    Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.

  15. Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study.

    Science.gov (United States)

    Ulla, Marco; Pizzolato, Elisa; Lucchiari, Manuela; Loiacono, Maria; Soardo, Flavia; Forno, Daniela; Morello, Fulvio; Lupia, Enrico; Moiraghi, Corrado; Mengozzi, Giulio; Battista, Stefania

    2013-07-30

    Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. In our

  16. Situación de la sepsis intrahospitalaria: subregistro e incumplimiento de las normas higienicosanitarias establecidas Status of nosocomial sepsis: underreporting and non-observance of established health standards

    Directory of Open Access Journals (Sweden)

    Haidee Marrero Rodríguez

    2013-03-01

    Full Text Available Se realizó un estudio descriptivo, retrospectivo y transversal de los 315 pacientes con sepsis intrahospitalaria en el Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, de enero a septiembre del 2011, con vistas a determinar la situación de ese proceso morboso, a través de algunas variables de interés, tales como: número de afectados con sepsis según el servicio hospitalario, tasa que representaban, localización de la sepsis, mapa microbiológico, entre otras. Sobre la base de los resultados, pudo concluirse que existían un subregistro en la notificación de las infecciones intrahospitalarias y deficiencias en el cumplimiento de las normas higiénico-epidemiológicas. A fin de reducir o eliminar algunos elementos que pueden causar sepsis, se recomendó que debieran realizarse estrategias de intervención en dicha institución de salud.A descriptive, retrospective and cross sectional study was carried out in 315 patients with nosocomial sepsis in "Dr. Juan Bruno Zayas Alfonso" General Teaching Hospital of Santiago de Cuba, from January to September 2011, to determine the status of the morbid process through some variables of interest, such as number of people affected with sepsis according to the hospital service, rate that they represented, location of sepsis, microbiological map, among others. Based on the results, it could be concluded that there was an underreporting of nosocomial infections and deficiencies in the observance of epidemiological health standards. To reduce or eliminate some elements that can cause sepsis, intervention strategies were recommended in this health institution.

  17. A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available OBJECTIVE: Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD, was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis. DESIGN: Laboratory investigation. SETTING: University of Michigan Medical School. SUBJECTS: Pigs weighing 30-35 kg. INTERVENTIONS: To assess the effect of the SCD in septic shock, pigs were administered 30×10(10 bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD. MEASUREMENTS AND MAIN RESULTS: In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation. CONCLUSIONS: These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.

  18. The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

    Science.gov (United States)

    Bonet, Mercedes; Souza, Joao Paulo; Abalos, Edgardo; Fawole, Bukola; Knight, Marian; Kouanda, Seni; Lumbiganon, Pisake; Nabhan, Ashraf; Nadisauskiene, Ruta; Brizuela, Vanessa; Metin Gülmezoglu, A

    2018-01-30

    Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study

  19. A Randomized Case-Controlled Study of Recombinant Human Granulocyte Colony Stimulating Factor for the Treatment of Sepsis in Preterm Neutropenic Infants

    OpenAIRE

    Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

    2015-01-01

    To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Methods: Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were ...

  20. Irradiation of microbial controlling on package tofu

    International Nuclear Information System (INIS)

    Gao Meixu; Li Shurong; Wang Li; Wang Shuo; Wang Ning

    2009-01-01

    The effects of irradiation on microbiological controlling, nutrient and sensory qualities of packaged tofu (bean curd) stored at commercial condition. Results showed that D 10 values of Listeria innocua and Samonella enteritidis inoculated in packaged tofu were 0.225 and 0.240kGy, respectively. Irradiation dose lower than 2.0kGy had no significant effects on content of crude protein and amino acid (p>0.05). γ-irradiation could decrease microbial in packaged tofu and 2.0kGy should be applied to ensure the hygienic quality of the products. (authors)

  1. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom

    2014-01-01

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median

  2. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Science.gov (United States)

    Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  3. Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

    Science.gov (United States)

    Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

    2016-05-01

    Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants open heart surgery. © The Author(s) 2016.

  4. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis.

    Directory of Open Access Journals (Sweden)

    Li Qin

    2017-02-01

    Full Text Available Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally "unintended" interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.

  5. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

    Science.gov (United States)

    Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

    2017-09-15

    Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Relationship of plasma proadrenomedullin and cortisol levels with systemic inflammatory response and target organ damage in children with sepsis after burn

    Directory of Open Access Journals (Sweden)

    Xing Wei

    2017-08-01

    Full Text Available Objective: To study the relationship of plasma proadrenomedullin (pro-ADM and cortisol (Cor levels with systemic inflammatory response and target organ damage in children with sepsis after burn. Methods: A total of 30 children with sepsis after burn who were treated in the hospital between August 2014 and August 2016 were collected as observation group, and 30 normal children who received vaccination in the hospital during the same period were collected as normal control group. The pro-ADM and Cor levels in plasma as well as the levels of inflammatory factors, myocardial injury markers and intestinal barrier function indexes in serum of the two groups were determined. Pearson test was used to assess the correlation of plasma pro-ADM and Cor levels with systemic inflammatory response and target organ damage in patients with sepsis after burn. Results: Plasma pro-ADM and Cor levels in observation group were higher than those in normal control group. Serum inflammatory cytokines IL-1, IL-6, IL-10 and TNF-α levels in observation group were higher than those in normal control group; serum myocardial injury markers CK-MB, cTnⅠ and NT-proBNP levels were higher than those in normal control group; serum intestinal barrier function indexes ET, DAO and D-L levels were higher than those in normal control group. Conclusion: Plasma pro-ADM and Cor levels increase in patients with sepsis after burn, and are highly consistent with systemic inflammatory response and target organ injury.

  7. The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

    Science.gov (United States)

    Coopersmith, Craig M; Deutschman, Clifford S

    2017-03-01

    New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

  8. Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.

    Science.gov (United States)

    Lupia, E; Bosco, O; Mariano, F; Dondi, A E; Goffi, A; Spatola, T; Cuccurullo, A; Tizzani, P; Brondino, G; Stella, M; Montrucchio, G

    2009-06-01

    Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se, but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro. Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro, plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.

  9. Utilization and control of ecological interactions in polymicrobial infections and community-based microbial cell factories.

    Science.gov (United States)

    Wigneswaran, Vinoth; Amador, Cristina Isabel; Jelsbak, Lotte; Sternberg, Claus; Jelsbak, Lars

    2016-01-01

    Microbial activities are most often shaped by interactions between co-existing microbes within mixed-species communities. Dissection of the molecular mechanisms of species interactions within communities is a central issue in microbial ecology, and our ability to engineer and control microbial communities depends, to a large extent, on our knowledge of these interactions. This review highlights the recent advances regarding molecular characterization of microbe-microbe interactions that modulate community structure, activity, and stability, and aims to illustrate how these findings have helped us reach an engineering-level understanding of microbial communities in relation to both human health and industrial biotechnology.

  10. Unique transcriptomic response to sepsis is observed among patients of different age groups.

    Science.gov (United States)

    Raymond, Steven L; López, María Cecilia; Baker, Henry V; Larson, Shawn D; Efron, Philip A; Sweeney, Timothy E; Khatri, Purvesh; Moldawer, Lyle L; Wynn, James L

    2017-01-01

    Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with and without sepsis. Nine public whole-blood gene expression datasets (636 patients) were employed. Age impacted the transcriptomic host response to sepsis. Gene expression from septic neonates and adults was more dissimilar whereas infants and children were more similar. Neonates showed reductions in inflammatory recognition and signaling pathways compared to all other age groups. Likewise, adults demonstrated decreased pathogen sensing, inflammation, and myeloid cell function, as compared to children. This may help to explain the increased incidence of sepsis-related organ failure and death in adults. The number of dysregulated genes in septic patients was proportional to age and significantly differed among septic adults, children, infants, and neonates. Overall, children manifested a greater transcriptomic intensity to sepsis as compared to the other age groups. The transcriptomic magnitude for adults and neonates was dramatically reduced as compared to children and infants. These findings suggest that the transcriptomic response to sepsis is age-dependent, and diagnostic and therapeutic efforts to identify and treat sepsis will have to consider age as an important variable.

  11. Sepsis in general surgery: the 2005-2007 national surgical quality improvement program perspective.

    Science.gov (United States)

    Moore, Laura J; Moore, Frederick A; Todd, S Rob; Jones, Stephen L; Turner, Krista L; Bass, Barbara L

    2010-07-01

    To document the incidence, mortality rate, and risk factors for sepsis and septic shock compared with pulmonary embolism and myocardial infarction in the general-surgery population. Retrospective review. American College of Surgeons National Surgical Quality Improvement Program institutions. General-surgery patients in the 2005-2007 National Surgical Quality Improvement Program data set. Incidence, mortality rate, and risk factors for sepsis and septic shock. Of 363 897 general-surgery patients, sepsis occurred in 8350 (2.3%), septic shock in 5977 (1.6%), pulmonary embolism in 1078 (0.3%), and myocardial infarction in 615 (0.2%). Thirty-day mortality rates for each of the groups were as follows: 5.4% for sepsis, 33.7% for septic shock, 9.1% for pulmonary embolism, and 32.0% for myocardial infarction. The septic-shock group had a greater percentage of patients older than 60 years (no sepsis, 40.2%; sepsis, 51.7%; and septic shock, 70.3%; P surgery resulted in more cases of sepsis (4.5%) and septic shock (4.9%) than did elective surgery (sepsis, 2.0%; septic shock, 1.2%) (P surgery, and the presence of any comorbidity. This study emphasizes the need for early recognition of patients at risk via aggressive screening and the rapid implementation of evidence-based guidelines.

  12. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    Science.gov (United States)

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  13. [Sepsis with Staphylococcus aureus in immunocompromised patients].

    Science.gov (United States)

    Petrache, Simona Magdalena; Miftode, Egidia; Vâţă, A; Petrovici, Cristina Mirela; Dorneanu, Olivia; Luca, V

    2009-01-01

    The aim of our study was to analyze clinical and biological characteristics of immunocompromised patients with staphylococcal sepsis and to compare with the same data in non-immunocompromised patients. The diagnosis of sepsis was made based on Bone criteria. MiniAPI system ID 32 STAPH was used for identification and antibiotic susceptibility was assessed by ATB STAPH method and by E-test for oxacillin and vancomycin. Among the 147 patients with Staphylococcus aureus sepsis--66.67% had concomitant immunosuppressive conditions (diabetes mellitus, liver diseases, renal failure, corticotherapy, etc). We have found a significant correlation between the immunosuppressed status and MRSA (methicillin-resistant Staphylococcus aureus) involvement (p = 0.0018) and also, between this group of patients and treatment failure (p = 0.0012). Because of the high rate of MRSA involvement in systemic infections in the Eastern region of Romania first intention treatment of patients with staphylococcal infections and conditions of immunosuppression must include antibiotics effective against methicillin-resistant strains.

  14. Sepsis Definitions: The Search for Gold and What CMS Got Wrong.

    Science.gov (United States)

    Kalantari, Annahieta; Mallemat, Haney; Weingart, Scott D

    2017-08-01

    On October 1, 2015, the United States Centers for Medicare and Medicaid Services (CMS) issued a core measure addressing the care of septic patients. These core measures are controversial among healthcare providers. This article will address that there is no gold standard definition for sepsis, severe sepsis or septic shock and the CMS-assigned definitions for severe sepsis and septic shock are premature and inconsistent with evidence-based definitions.

  15. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

    Directory of Open Access Journals (Sweden)

    Koji Tanaka

    Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

  16. Long-term risk of seizures in adult survivors of sepsis.

    Science.gov (United States)

    Reznik, Michael E; Merkler, Alexander E; Mahta, Ali; Murthy, Santosh B; Claassen, Jan; Kamel, Hooman

    2017-10-03

    To examine the association between sepsis and the long-term risk of seizures. We conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries. We identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%-1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%-0.16%) in the general population (IRR 4.98; 95% CI 4.92-5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13-4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60-2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78-2.88). We found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae. © 2017 American Academy of Neurology.

  17. SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis.

    Science.gov (United States)

    Khader, Adam; Yang, Weng-Lang; Hansen, Laura W; Rajayer, Salil R; Prince, Jose M; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

    2017-11-01

    Sepsis affects 800,000 patients in the United States annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis. Male C57BL/6 mice (20-25 g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2-mL saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) and renal injury markers (blood urea nitrogen and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines interleukin (IL)-1β and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components (nucleotide oligomerization domain-like receptor protein 3, adapter apoptosis-associated speck-like protein containing caspase-recruitment domain, IL-1β, and IL-18) in the liver, compared with the vehicle group. SRT1720 treatment attenuates multiorgan injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

    Science.gov (United States)

    Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

    2001-01-01

    Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

  19. Towards a consensus definition of maternal sepsis: results of a systematic review and expert consultation.

    Science.gov (United States)

    Bonet, Mercedes; Nogueira Pileggi, Vicky; Rijken, Marcus J; Coomarasamy, Arri; Lissauer, David; Souza, João Paulo; Gülmezoglu, Ahmet Metin

    2017-05-30

    There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition "Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period". Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of

  20. Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

    Directory of Open Access Journals (Sweden)

    Zhi-Hong Ren

    2017-10-01

    Full Text Available Objective: To study the changes of serum pancreatic stone protein (PSP and cholinesterase (ChE contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group; serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group; liver function indexes TBIL, ALT and AST contents were higher than those of normal control group; kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.

  1. Microbial contamination control in fuels and fuel systems since 1980 - a review

    Energy Technology Data Exchange (ETDEWEB)

    Passman, Frederick J. [Biodeterioration Control Associates, Inc (United States)], email: fredp@biodeterioration-control.com

    2011-07-01

    This paper presents a review of microbial contamination control in fuel and fuel systems. Some examples of the biodeterioration of components of fuel systems are given. Root cause analysis (RCA) and modeling can help in condition monitoring of fuel systems. RCA is a systematic process that starts after symptoms become apparent and facilitates improvement. Modeling, by contrast, starts before the problem occurs and the objective is to improve understanding of the process. Some of the different areas creating risk due to the process are climate, microbiology, chemistry, maintenance, and engineering. Condition monitoring is explained in detail, using representative samples. Contamination control plays a very important role. Various aspects of microbial contamination control are design, inventory control, house keeping and remediation. These aspects are explained in detail, using various examples. Since the deterioration cost involved is very high, its is important to avoid this problem by reducing the quantity of water used and using better risk assessment models.

  2. Impact of Operative Delay on Sepsis and Mortality in Patients with Acute Diverticulitis

    Directory of Open Access Journals (Sweden)

    Robin F. Irons

    2017-03-01

    Full Text Available Background Ideal operative timing for non-emergent, acute diverticulitis (AD remains unclear. Medical management is initially attempted to convert a high risk urgent surgery to a less morbid elective surgery, or to avoid surgery altogether. A large proportion of patients will fail medical treatment and require colectomy. Objectives To evaluate the effect of operative delay on sepsis and mortality in patients with AD. Methods Patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP database who underwent colectomy with a primary diagnosis of diverticulitis between 2005 and 2014 were included. Multiple patient variables were analyzed to see their combined effect on death and sepsis. Patients undergoing surgical intervention on hospital day 0, emergent cases and those with preoperative sepsis were excluded. The impact of operative delay on mortality and sepsis was evaluated using day from admission as the predictor of the primary outcomes. Secondary outcomes included urinary tract infection (UTI, pneumonia (PNA, need for blood transfusion, septic shock, return to the operating room, length of stay (LOS, readmission, wound dehiscence, and surgical site infections (SSI. Frequency of patient variables was recorded and a multiple variable logistic regression analysis was performed to control for possible confounders. Odds ratios (OR with 95% confidence intervals (CI were calculated for primary and secondary outcomes. Results 32,399 patients underwent colectomy for AD on hospital day 1 - 20. Adjusted for other factors, days to operation was found to be a significant predictor for death (OR = 1.038, 95% CI 1.020 - 1.057; P < 0.0001 and sepsis (OR = 1.051, 95% CI, 1.035 - 1.067; P < 0.0001. Each day in which surgical intervention was delayed was associated with a 3.8% increased risk of mortality and 5.1% increased risk of sepsis. Delay of surgery was also associated with an increased risk of blood transfusion

  3. The role of heparin in sepsis: much more than just an anticoagulant.

    Science.gov (United States)

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  4. Initial management of pneumonia and sepsis: factors associated with improved outcome.

    Science.gov (United States)

    Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

    2012-01-01

    Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

  5. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Directory of Open Access Journals (Sweden)

    Lindsay M Margoles

    Full Text Available Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43 and effector molecules (IFN-γ, TNF as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  6. Central-peripheral Temperature Monitoring as a Marker for Diagnosing Late-onset Neonatal Sepsis.

    Science.gov (United States)

    Leante-Castellanos, José Luis; Martínez-Gimeno, Antonio; Cidrás-Pidré, Manuel; Martínez-Munar, Gerardo; García-González, Ana; Fuentes-Gutiérrez, Carmen

    2017-12-01

    The prognosis for late-onset sepsis depends largely on a timely diagnosis. We assess central-peripheral temperature difference monitoring as a marker for late-onset neonatal sepsis diagnosis. We performed a prospective, observational study focusing on a cohort of 129 very low-birth-weight infants. Thermal gradient alteration was defined as a difference of > 2°C maintained during 4 hours. We then determined its association with the late-onset sepsis variable through logistic regression. We enrolled 129 preterm babies in 52 months. Thermal gradient alterations showed an adjusted odds ratio for late-onset sepsis of 23.60 (95% confidence interval [CI], 6.80-81.88), with a sensitivity of 83% and negative predictive value of 94%. In 71% of cases, thermal gradient alteration was the first clinical sign of sepsis, while C-reactive protein was peripheral temperature differences are an early sign of evolving late-onset sepsis.

  7. Effect of dextran-70 on outcome in severe sepsis; a propensity-score matching study.

    Science.gov (United States)

    Bentzer, Peter; Broman, Marcus; Kander, Thomas

    2017-07-06

    Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. No

  8. Psychosocial stress as a risk factor for sepsis: a population-based cohort study.

    Science.gov (United States)

    Ojard, Connor; Donnelly, John P; Safford, Monika M; Griffin, Russell; Wang, Henry E

    2015-01-01

    To characterize the relationship between stress and future risk of sepsis. We also evaluated the role of depression in this relationship. We used population-based data on 30,183 participants in the Reasons for Geographic and Racial Differences in Stroke cohort, characterizing stress using the Perceived Stress Scale (PSS) and depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). We identified incident sepsis events as hospitalizations for a serious infection with the presence of at least two systemic inflammatory response syndrome criteria. We assessed associations between PSS and incidence of sepsis for 1 and 10 years of follow-up, adjusting for demographics and chronic medical conditions and assessing the role of health behaviors and CES-D in these relationships. In 2003 to 2012, 1500 participants experienced an episode of sepsis. Mean PSS and CES-D scores were 3.2 (2.9) and 1.2 (2.1). PSS was associated with increased 1-year adjusted incidence of sepsis (hazard ratio [HR] = 1.21 per PSS standard deviation, 95% confidence interval = 1.06-1.38); multivariable adjustment for health behaviors and CES-D did not change this association (1.20, 1.03-1.39). PSS was also associated with increased 10-year adjusted incidence of sepsis (HR = 1.07 per PSS standard deviation; 95% confidence interval = 1.02-1.13). Multivariable adjustment showed that health behaviors did not affect this long-term association, whereas the addition of CES-D reduced the association between PSS and sepsis during 10-year follow-up (HR = 1.04, 0.98-1.11). Increased stress was associated with higher 1-year adjusted incidence of sepsis, even after accounting for depressive symptoms. The association between stress and 10-year adjusted incidence of sepsis was also significant, but this association was reduced when adjusting for depressive symptoms. Reduction of stress may limit short-term sepsis risk.

  9. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    International Nuclear Information System (INIS)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-01-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and 75 selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES

  10. The recognition and management of sepsis and septic shock: a guide for non-intensivists.

    Science.gov (United States)

    Keeley, Alexander; Hine, Paul; Nsutebu, Emmanuel

    2017-10-01

    Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Accurate coding in sepsis: clinical significance and financial implications.

    Science.gov (United States)

    Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

    2016-09-01

    Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

  12. Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

    Science.gov (United States)

    Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

    2017-10-01

    Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

    Directory of Open Access Journals (Sweden)

    Yu Jiang

    2015-01-01

    Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

  14. The effect of ghrelin upon the early immune response in lean and obese mice during sepsis.

    Directory of Open Access Journals (Sweden)

    Daniel Siegl

    Full Text Available It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis.In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis.In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement.In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.

  15. Stem cells in sepsis and acute lung injury.

    Science.gov (United States)

    Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

    2010-12-01

    Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

  16. Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis

    Science.gov (United States)

    Wynn, James L; Guthrie, Scott O; Wong, Hector R; Lahni, Patrick; Ungaro, Ricardo; Lopez, M Cecilia; Baker, Henry V; Moldawer, Lyle L

    2015-01-01

    Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ≥3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age. PMID:26052715

  17. Impact of CT in patients with sepsis of unknown origin

    International Nuclear Information System (INIS)

    Barkhausen, J.; Stoeblen, F.; Mueller, R.D.

    1999-01-01

    Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)

  18. Impact of CT in patients with sepsis of unknown origin

    Energy Technology Data Exchange (ETDEWEB)

    Barkhausen, J.; Stoeblen, F.; Mueller, R.D. [University Hospital Essen (Germany). Dept. of Radiology; Dominguez-Fernandez, E. [University Hospital Essen (Germany). Dept. of General Surgery; Henseke, P. [Nycomed-Amersham Arzneimittel GmbH, Muenchen (Germany)

    1999-09-01

    Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)

  19. Indium 111 leucocyte scintigraphy in abdominal sepsis

    International Nuclear Information System (INIS)

    Baba, A.A.; McKillop, J.H.; Gray, H.W.; Cuthbert, G.F.; Neilson, W.; Anderson, J.R.

    1990-01-01

    We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based. (orig.)

  20. A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

    NARCIS (Netherlands)

    Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

    2013-01-01

    Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

  1. Renal blood flow in sepsis: a complex issue

    OpenAIRE

    Molitoris, Bruce A

    2005-01-01

    The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery of oxygen and substrates is of critical importance. Therefore, measuring total...

  2. Significance of blood pressure variability in patients with sepsis.

    Science.gov (United States)

    Pandey, Nishant Raj; Bian, Yu-Yao; Shou, Song-Tao

    2014-01-01

    This study was undertaken to observe the characteristics of blood pressure variability (BPV) and sepsis and to investigate changes in blood pressure and its value on the severity of illness in patients with sepsis. Blood parameters, APACHE II score, and 24-hour ambulatory BP were analyzed in 89 patients with sepsis. In patients with APACHE II score>19, the values of systolic blood pressure (SBPV), diasystolic blood pressure (DBPV), non-dipper percentage, cortisol (COR), lactate (LAC), platelet count (PLT) and glucose (GLU) were significantly higher than in those with APACHE II score ≤19 (Pblood cell (WBC), creatinine (Cr), PaO2, C-reactive protein (CRP), adrenocorticotropic hormone (ACTH) and tumor necrosis factor α (TNF-α) were not statistically significant (P>0.05). Correlation analysis showed that APACHE II scores correlated significantly with SBPV and DBPV (P0.05). Logistic regression analysis of SBPV, DBPV, APACHE II score, and LAC was used to predict prognosis in terms of survival and non-survival rates. Receiver operating characteristics curve (ROC) showed that DBPV was a better predictor of survival rate with an AUC value of 0.890. However, AUC of SBPV, APACHE II score, and LAC was 0.746, 0.831 and 0.915, respectively. The values of SBPV, DBPV and non-dipper percentage are higher in patients with sepsis. DBPV and SBPV can be used to predict the survival rate of patients with sepsis.

  3. Associated factors with Puerperal Sepsis among Reproductive Age Women in Nandi County, Kenya

    Directory of Open Access Journals (Sweden)

    Maritim Violet Chepchirchir

    2017-10-01

    integration of hygiene education and puerperal sepsis awareness into antenatal care services should be performed as a strategy to prevent and control the infection.

  4. Effect of Nisin's Controlled Release on Microbial Growth as Modeled for Micrococcus luteus.

    Science.gov (United States)

    Balasubramanian, Aishwarya; Lee, Dong Sun; Chikindas, Michael L; Yam, Kit L

    2011-06-01

    The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added ("formulated") nisin. While instant addition experiments achieved microbial inhibition only at the beginning, controlled release experiments achieved complete microbial inhibition for a longer time, even when as little as 15% of the amount of nisin was used as compared to instant addition.

  5. Dynamic changes in amino acid concentration profiles in patients with sepsis.

    Directory of Open Access Journals (Sweden)

    Longxiang Su

    Full Text Available The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases and severe sepsis (23 cases groups or survivor (20 cases and non-survivor (15 cases groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU admission, and the serum concentrations of 42 amino acids were measured.The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs, especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA (r=-0.319 and Acute Physiology and Chronic Health Evaluation (APACHE II (r=-0.325 scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.ClinicalTrial.gov identifier NCT01818830.

  6. The effect of hospital volume on mortality in patients admitted with severe sepsis.

    Directory of Open Access Journals (Sweden)

    Sajid Shahul

    Full Text Available IMPORTANCE: The association between hospital volume and inpatient mortality for severe sepsis is unclear. OBJECTIVE: To assess the effect of severe sepsis case volume and inpatient mortality. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. EXPOSURES: The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. MAIN OUTCOMES AND MEASURES: Inpatient mortality. RESULTS: Compared with the highest tertile of severe sepsis volume (>60 cases per year, the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year was 1.188 (95% CI: 1.074-1.315, while the odds ratio was 1.090 (95% CI: 1.031-1.152 for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64-38.03 for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51-32.64 for hospitals with the highest volume. CONCLUSIONS AND RELEVANCE: We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients.

  7. [CONTEMPORARY MOLECULAR-GENETIC METHODS USED FOR ETIOLOGIC DIAGNOSTICS OF SEPSIS].

    Science.gov (United States)

    Gavrilov, S N; Skachkova, T S; Shipulina, O Yu; Savochkina, Yu A; Shipulin, G A; Maleev, V V

    2016-01-01

    Etiologic diagnostics of sepsis is one of the most difficult problems of contemporary medicine due to a wide variety of sepsis causative agents, many of which are components of normal human microflora. Disadvantages of contemporary "golden standard" of microbiologic diagnostics of sepsis etiology by seeding of blood for sterility are duration of cultivation, limitation in detection of non-cultivable forms of microorganisms, significant effect of preliminary empiric antibiotics therapy on results of the analysis. Methods of molecular diagnostics that are being actively developed and integrated during the last decade are deprived of these disadvantages. Main contemporary methods of molecular-biological diagnostics are examined in the review, actualdata on their diagnostic characteristic are provided. Special attention is given to methods of PCR-diagnostics, including novel Russian developments. Methods of nucleic acid hybridization and proteomic analysis are examined in comparative aspect. Evaluation of application and perspectives of development of methods of molecular diagnostics of sepsis is given.

  8. Cerebral blood flow is reduced in patients with sepsis syndrome

    International Nuclear Information System (INIS)

    Bowton, D.L.; Bertels, N.H.; Prough, D.S.; Stump, D.A.

    1989-01-01

    The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO 2 in nine patients with sepsis syndrome using the 133 Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO 2 was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study

  9. Continuous multi-parameter heart rate variability analysis heralds onset of sepsis in adults.

    Directory of Open Access Journals (Sweden)

    Saif Ahmad

    Full Text Available BACKGROUND: Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We monitored heart rate continuously in adult bone marrow transplant (BMT patients (n = 21 beginning a day before their BMT and continuing until recovery or withdrawal (12+/-4 days. We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment. Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25% reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14, wavelet HRV demonstrated a 25% drop from

  10. Additional traditional Chinese medicine on gastrointestinal dysfunction in patients with sepsis: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Yajing; Zhao, Zhiqiang; Tang, E; Hu, Yucai; Mao, Jingyuan

    2016-03-01

    To evaluate the clinical effect and safety of western medicine plus Traditional Chinese medicine for sepsis with gastrointestinal dysfunction. We searched CNKI (January 1979 to June 2014), VIP (January 1989 to June 2014), CBM (1978 to 2014), Wan Fang DATA (January 1990 to June 2014), PubMed (1978 to June 2014), The Cochrane Library (Issue 5, 2014), Embase (1974 to June 2014), and other relevant databases and journals to identify randomized controlled trials (RCTs) on western medicine plus Traditional Chinese medicine versus western medicine only for sepsis with gastrointestinal dysfunction. The methodological quality was assessed and the data was extracted according to the Cochrane Reviewer's Handbook and related methods. Meta-analyses were performed by RevMan 5.1.0 software. Five eligible studies included 278 patients. The results of meta-analyses showed that western medicine plus Traditional Chinese medicine therapy can improve the APACHEII score, the peristaltic sound score and SIRS score, improve abdominal distension, decreased white blood cell count, reduce DAO in sepsis patients with gastrointestinal dysfunction. 3 studies reported adverse reactions, there was no significant difference between two groups. Western medicine plus Traditional Chinese medicine can improve gastrointestinal dysfunction in sepsis.

  11. Role of human recombinant activated protein C and low dose corticosteroid therapy in sepsis

    Directory of Open Access Journals (Sweden)

    Aparna Shukla

    2010-01-01

    Full Text Available Despite advances in modern medicine, sepsis remains a complex syndrome that has been associated with significant morbidity and mortality. Multiple organ failure associated with sepsis leads to high mortality and morbidity. About 28 - 50% deaths have been reported in patients with sepsis. The number of sepsis patients is increasing, with considerable burden on healthcare facilities. Various factors leading to a rise in the incidence of sepsis are (1 Improvement of diagnostic procedures (2 Increase in the number of immunocompromised patients taking treatment for various autoimmune disease, carcinomas, organ transplantation (3 Advances in intensive procedures (4 Nosocomial infections (5 Extensive use of antibiotics. With the better understanding of sepsis various modalities to modify pathophysiological response of septic patients have developed. Activated protein C and low-dose corticosteroid therapy have been tried in patients, with variable results.

  12. Serum procalcitonin as an early marker of neonatal sepsis | Ballot ...

    African Journals Online (AJOL)

    Background. It has recently been suggested that procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role of PCT as a single early marker of neonatal sepsis. Setting. Neonatal Unit, Johannesburg Hospital, and Microbiology Laboratory, National Health ...

  13. Trends in profiles of bacteria causing neonatal sepsis in Central ...

    African Journals Online (AJOL)

    Developing countries suffer from a huge burden of neonatal sepsis. Neonatal mortality and long term sequelae or morbidity portends huge costs for the poor Nigerian economy. We identified trends in bacterial agents implicated in neonatal sepsis and their antibiotic susceptibility profiles at the National Hospital Abuja over ...

  14. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    OpenAIRE

    Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan

    2014-01-01

    Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals w...

  15. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  16. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

    2017-06-01

    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  17. Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

    Science.gov (United States)

    Ishimaru, Naoto; Ohnishi, Hisashi; Nishiuma, Teruaki; Doukuni, Ryota; Umezawa, Kanoko; Oozone, Sachiko; Kuramoto, Emi; Yoshimura, Sho; Kinami, Saori

    2013-01-01

    Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

  18. Paramedic-Initiated CMS Sepsis Core Measure Bundle Prior to Hospital Arrival: A Stepwise Approach.

    Science.gov (United States)

    Walchok, Jason G; Pirrallo, Ronald G; Furmanek, Douglas; Lutz, Martin; Shope, Colt; Giles, Brandi; Gue, Greta; Dix, Aaron

    2017-01-01

    To improve patient outcomes, the Center for Medicare and Medicaid Services (CMS) implemented core measures that outline the initial treatment of the septic patient. These measures include initial blood culture collection prior to antibiotics, adequate intravenous fluid resuscitation, and early administration of broad spectrum antibiotics. We sought to determine if Paramedics can initiate the CMS sepsis core measure bundle in the prehospital field reliably. This is a retrospective, case series from a 3rd service EMS system model in Greenville, South Carolina between November 17, 2014 and February 20, 2016. An adult Prehospital Sepsis Assessment Tool was created using the 2012 Surviving Sepsis guidelines: 2 of 3 signs of systemic inflammatory response (heart rate, respiratory rate, oral temperature) and a known or suspected source of infection. A "Sepsis Alert" was called by paramedics and upon IV access a set of blood cultures and blood for lactate analysis was collected prior to field antibiotic administration. The Sepsis Alert was compared to serum lactate levels and ICD 9 or 10 admitting diagnosis of Sepsis, Severe Sepsis, or Septic Shock. Blood culture contamination, serum lactate, and antibiotic match were determined by in-hospital laboratory analysis. A total of 120 trained paramedics called 1,185 "Sepsis Alerts" on 56,643 patients (50.3% Male, mean age 70). Patients with missing discharge diagnosis were eliminated (n = 31). The admitting diagnosis of sepsis overall was 73.5% (848/1154): Sepsis 50% (578/1154), Severe Sepsis 14.6% (169/1154), Septic Shock 8.9% (101/1154). A total of 946 blood cultures were collected in the prehospital setting, with a 95.04% (899/946) no contamination rate. Contamination was found in 4.96% (47/946). A total of 179 (18.9%) of the uncontaminated blood cultures were found to have positive growth with 720 (76.1%) having no growth. EMS administered antibiotics matched blood culture positive growth in 72% of patients. The lactate

  19. Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Schneider, Uffe Vest; Scheel, Troels

    2006-01-01

    Sepsis is a common and often fatal disease. Because sepsis can be caused by many different organisms, biomarkers that can aid in diagnosing sepsis and monitoring treatment efficacy are highly warranted. New sepsis markers may provide additional information to complement the currently used markers....

  20. Sepsis risk factors in infants with congenital diaphragmatic hernia.

    Science.gov (United States)

    Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre

    2017-12-01

    Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.

  1. Aetiology of neonatal sepsis at QECH, Blantyre: 1996-2001 | Phiri ...

    African Journals Online (AJOL)

    Neonatal sepsis is common and often fatal in Malawi. The aim of this retrospective study was to report causes, antibiotic resistance and outcome of sepsis in Malawian neonates. We reviewed all blood and cerebrospinal fluid isolates collected between January, 1996, and December, 2001, from inpatients aged 0-30 days ...

  2. Neonatal sepsis is mediated by maternal fever in labour epidural analgesia.

    Science.gov (United States)

    Wassen, M M L H; Winkens, B; Dorssers, E M I; Marcus, M A; Moonen, R M J; Roumen, F J M E

    2014-11-01

    Women delivering with EA (EA group) were matched on parity with 453 women with deliveries without EA (non-EA group). Significantly more neonates born in the EA-group had fever ≥ 38.0°C (11.6% vs 1.8%, p neonatal sepsis, based on clinical symptoms and defined as proven (by a positive blood culture) or suspected (no positive blood culture), was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA turned out to be an independent risk factor for neonatal sepsis (adjusted OR 2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non-EA group, the incidence of neonatal sepsis was significantly higher in mothers with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we conclude, that the positive association between neonatal sepsis and labour EA is possibly mediated by maternal intrapartum fever.

  3. A Complex Systems View of Sepsis: Implications for Nursing

    Science.gov (United States)

    2013-02-01

    multi- faceted approach to the management of sepsis. Rapid pro- vision of broad-spectrum antibiotic coverage is coupled with aggressive organ support...setting of sepsis may include (1) exposure to infectious agents, (2) immunocompromise , (3) injury or illness, (4) genetic abnormalities, or (5) under- lying...assays 2. Obtain culture panel (blood, respiratory, urine, wound) 3. Prompt administration of broad-spectrum antibiotics 4. Manage organ dysfunction

  4. Bacterial pattern and role of laboratory parameters as marker for neonatal sepsis

    Science.gov (United States)

    Ruslie, R. H.; Tjipta, D. G.; Samosir, C. T.; Hasibuan, B. S.

    2018-03-01

    World Health Organization (WHO) recorded 5 million neonatal mortality each year due to sepsis, and 98% were in developing countries. Diagnosis of neonatal sepsis needs to be confirmed with a positive culture from normally sterile sites. On the other hand, postponing treatment will worsen the disease and increase mortality. This study conducted to evaluate the bacterial pattern of neonatal sepsis and to compare laboratory parameter differences between suspected and confirmed sepsis. It was a retrospective analytic study on 94 neonates in Perinatology Division, Adam Malik General Hospital Medan, from November 2016 until January 2017. Blood cultures were taken to confirm the diagnosis. Laboratory parameters collected from medical records. Variables with significant results analyzed for their accuracy. Pculture positives found in 55.3% neonates, with most common etiology was Klebsiella pneumonia (22.6%). There were significant neutrophil/lymphocyte ratio and procalcitonin differences between suspected and confirmed sepsis (p 0.025 and 0.008 respectively). With a diagnostic threshold of 9.4, sensitivity and specificity of neutrophil/lymphocyte ratio were 61.5% and 66.7%, respectively. Procalcitonin sensitivity and specificity were 84.6% and 71.4%, respectively, with 3.6mg/L diagnostic threshold. Neutrophil/lymphocyte ratio and procalcitonin were significantly higher in confirmed sepsis.

  5. The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan Sulfate in Murine and Human Sepsis.

    Directory of Open Access Journals (Sweden)

    Lukas Martin

    Full Text Available Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.

  6. A STUDY OF LABORATORY PROFILE OF NEONATAL SEPSIS AT NICU (SNCU, WARANGAL

    Directory of Open Access Journals (Sweden)

    Sudhakar

    2016-05-01

    Full Text Available BACKGROUND Of the 130 million babies born worldwide each year, 26 million are born in India alone. Four million babies die with in first 30 days of birth and another four million are stillborn. Newborn mortality represents 40% of all deaths of children less than five years of age. Of the four million deaths each year, nearly 98% occur in developing countries. Globally major causes of neonatal deaths are due to preterm births (28%, sepsis or pneumonia (26% and birth asphyxia (23%. Neonatal sepsis is one of the commonest causes of neonatal deaths in the developing world accounting to 30-50% of all neonatal deaths per year. The present study is intended to help the practising paediatrician to accurately diagnose the sepsis early using the specific laboratory tests and avert the progression of the disease. METHODS It is an observational cross-sectional study in NICU, Mahatma Gandhi Memorial Hospital. The study was conducted in the period November 2013 to October 2014. After admission, detailed history and thorough clinical examination was done. Required data was entered in a pre-set proforma and statistical analysis was done. Blood culture was sent. Bacterial culture and sensitivity was checked. RESULTS In proven sepsis, 50.25% were Gram-positive, 43.65% were Gram-negative and 6.09% were fungal sepsis Candida. Klebsiella (32.48% was the most common organism followed by Coagulase positive Staphylococcus (25.38% and CONS (20.81%. In this study, Gram-negative sepsis was more common in preterm and Gram-positive sepsis was more common in term neonates. Early onset sepsis was the common presentation of proven sepsis, Klebsiella was common organism causing EOS. Whereas CONS was commonest causing late onset sepsis. Among Gram-negative organisms, 58.1% and 27.9% were resistant to cefotaxime and ampicillin+sulbactam respectively. Among Gram-positive isolates, 35% and 22% were resistant to cefotaxime and ampicillin+sulbactam respectively. Klebsiella, most

  7. Combination therapy with milrinone and esmolol for heart protection in patients with severe sepsis: a prospective, randomized trial.

    Science.gov (United States)

    Wang, Zenggeng; Wu, Qinghua; Nie, Xiangbi; Guo, Jinghua; Yang, Chunli

    2015-11-01

    As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patients with severe sepsis. This prospective randomized study was conducted in patients with severe sepsis in the intensive care unit of the Jiangxi Provincial People's Hospital (Nanchang, Jiangsu, China) between June 2013 and June 2014. Patients were randomly divided into control (C), milrinone (M), and milrinone-esmolol (ME) groups. The primary outcome was the rate of controlling the heart rate (HR) to achieve target levels. Secondary outcomes included the 28-day survival rate and changes in hemodynamic variables, organ function variables, myocardial injury markers, and the serum levels of proinflammatory factors. A total of 90 patients with severe sepsis were included in this study (30 per group). The HR in the ME group was lower than in the M and C groups after 12 h. The rate of successful HR control during the first 96 h was significantly higher in the ME group (60.0 vs. 33.3 % in the M group, vs. 26.7 % in the C group). Also, patients in the ME group had higher 28-day overall survival compared with the M (Log rank statistic = 5.452; P = 0.020) and C groups (Log rank statistic = 10.206; P = 0.001). Additionally, several variables showed significant improvement in the ME group 96 h after treatment compared with the M and C groups (P milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.

  8. Associations of Hospital and Patient Characteristics with Fluid Resuscitation Volumes in Patients with Severe Sepsis

    DEFF Research Database (Denmark)

    Hjortrup, Peter Buhl; Haase, Nicolai; Wetterslev, Jørn

    2016-01-01

    PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient characte....... The data indicate variations in clinical practice not explained by patient characteristics emphasizing the need for RCTs assessing fluid resuscitation volumes fluid in patients with sepsis.......PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient...... characteristics and fluid resuscitation volumes in ICU patients with severe sepsis. METHODS: We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume...

  9. Strategies to diagnose and control microbial souring in natural gas storage reservoirs and produced water systems

    Energy Technology Data Exchange (ETDEWEB)

    Morris, E.A.; Derr, R.M.; Pope, D.H.

    1995-12-31

    Hydrogen sulfide production (souring) in natural gas storage reservoirs and produced water systems is a safety and environmental problem that can lead to operational shutdown when local hydrogen sulfide standards are exceeded. Systems affected by microbial souring have historically been treated using biocides that target the general microbial community. However, requirements for more environmentally friendly solutions have led to treatment strategies in which sulfide production can be controlled with minimal impact to the system and environment. Some of these strategies are based on microbial and/or nutritional augmentation of the sour environment. Through research sponsored by the Gas Research Institute (GRI) in Chicago, Illinois, methods have been developed for early detection of microbial souring in natural gas storage reservoirs, and a variety of mitigation strategies have been evaluated. The effectiveness of traditional biocide treatment in gas storage reservoirs was shown to depend heavily on the methods by which the chemical is applied. An innovative strategy using nitrate was tested and proved ideal for produced water and wastewater systems. Another strategy using elemental iodine was effective for sulfide control in evaporation ponds and is currently being tested in microbially sour natural gas storage wells.

  10. Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms.

    Science.gov (United States)

    David, Vlad Laurentiu; Ercisli, Muhammed Furkan; Rogobete, Alexandru Florin; Boia, Eugen S; Horhat, Razvan; Nitu, Razvan; Diaconu, Mircea M; Pirtea, Laurentiu; Ciuca, Ioana; Horhat, Delia; Horhat, Florin George; Licker, Monica; Popovici, Sonia Elena; Tanasescu, Sonia; Tataru, Calin

    2017-06-01

    Several diagnostic methods for the evaluation and monitoring were used to find out the pro-inflammatory status, as well as incidence of sepsis in critically ill patients. One such recent method is based on investigating the genetic polymorphisms and determining the molecular and genetic links between them, as well as other sepsis-associated pathophysiologies. Identification of genetic polymorphisms in critical patients with sepsis can become a revolutionary method for evaluating and monitoring these patients. Similarly, the complications, as well as the high costs associated with the management of patients with sepsis, can be significantly reduced by early initiation of intensive care.

  11. Intracranial Pressure during HighVolume Hemofiltration in Severe Sepsis

    Directory of Open Access Journals (Sweden)

    A. P. Berdnikov

    2014-01-01

    Full Text Available Objective: to define the prognostic value of intracranial pressure (ICP changes in highvolume hemofiltration (HVHF in patients with severe sepsis and normal preperfusion ICP.Subjects and methods. A retrospective study was conducted in 50 patients (a total of 134 sessions with severe sepsis and normal baseline ICP who received ther apy using HVHF for extrarenal indications. Based on ICP changes before and after HVHF, the investigators identified 2 groups: 1 no ICP changes (n=81; 2 elevated ICP (n=53.Conclusion. HVHF is ineffective when the normal preperfusion ICP is increased in patients with severe sepsis who have a concurrence of an arteriovenous carbon dioxide difference of more than 8 mm Hg and a Glasgow coma score of less than 10.

  12. Attrition of memory CD8 T cells during sepsis requires LFA-1.

    Science.gov (United States)

    Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W

    2016-11-01

    CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.

  13. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    Energy Technology Data Exchange (ETDEWEB)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-10-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.

  14. The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

    Science.gov (United States)

    Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

    2017-09-01

    The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

  15. Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

    Science.gov (United States)

    Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung

    2018-05-08

    Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.

  16. Effect of small-dose levosimendan on mortality rates and organ functions in Chinese elderly patients with sepsis

    Directory of Open Access Journals (Sweden)

    Wang X

    2017-05-01

    Full Text Available Xin Wang,1,* Shikui Li2,* 1Intensive Care Unit, 2Cardiothoracic Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Aim: As a primary cause of death not only in Western countries but also in the People’s Republic of China, sepsis is diagnosed as abnormal organ functions as a result of a disordered response to a severe infection. This study was designed to assess the effect of small-dose levosimendan without a loading dose on mortality rates and organ functions in Chinese elderly patients with sepsis.Methods: Following a prospective, randomized, and double-blinded design, 240 Chinese elderly patients with sepsis shock were admitted to the intensive care unit (ICU. All patients were randomly and evenly assigned into a levosimendan group (number of patients =120 and a control group (number of patients =120. The control group underwent standard care, and the levosimendan group was administered levosimendan in addition to standard care.Results: All participants, comprising 134 males (55.8% and 106 females (44.2%, were 70 (67–73 years old. Baseline characteristics, preexisting illnesses, initial infections, organ failures, and additional agents and therapies showed no significant difference between the two groups (P>0.05 for all. There were no significant differences in mortality rates at 28 days, at ICU discharge, and at hospital discharge between the two groups (P>0.05 for all. The number of days of ICU and hospital stay in the levosimendan group was significantly less than for those in the control group (P<0.05 for all. Mean daily total sequential organ failure assessment score and all organ scores except the cardiovascular scores showed no significant difference between the two groups (P>0.05 for all. Cardiovascular scores in the levosimendan group were significantly higher than those in the control group (P<0.05 for all.Conclusion: Small

  17. Heparin defends against the toxicity of circulating histones in sepsis.

    Science.gov (United States)

    Wang, Feifei; Zhang, Naipu; Li, Biru; Liu, Lanbo; Ding, Lei; Wang, Ying; Zhu, Yimin; Mo, Xi; Cao, Qing

    2015-06-01

    Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

  18. Recent advances in prevention of sepsis in the premature neonates in NICU.

    Science.gov (United States)

    Manzoni, P; Rizzollo, S; Decembrino, L; Ruffinazzi, G; Rossi Ricci, A; Gallo, E; Stolfi, I; Mostert, M; Stronati, M; Farina, D

    2011-03-01

    Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Graphite anode surface modification with controlled reduction of specific aryl diazonium salts for improved microbial fuel cells power output.

    Science.gov (United States)

    Picot, Matthieu; Lapinsonnière, Laure; Rothballer, Michael; Barrière, Frédéric

    2011-10-15

    Graphite electrodes were modified with reduction of aryl diazonium salts and implemented as anodes in microbial fuel cells. First, reduction of 4-aminophenyl diazonium is considered using increased coulombic charge density from 16.5 to 200 mC/cm(2). This procedure introduced aryl amine functionalities at the surface which are neutral at neutral pH. These electrodes were implemented as anodes in "H" type microbial fuel cells inoculated with waste water, acetate as the substrate and using ferricyanide reduction at the cathode and a 1000 Ω external resistance. When the microbial anode had developed, the performances of the microbial fuel cells were measured under acetate saturation conditions and compared with those of control microbial fuel cells having an unmodified graphite anode. We found that the maximum power density of microbial fuel cell first increased as a function of the extent of modification, reaching an optimum after which it decreased for higher degree of surface modification, becoming even less performing than the control microbial fuel cell. Then, the effect of the introduction of charged groups at the surface was investigated at a low degree of surface modification. It was found that negatively charged groups at the surface (carboxylate) decreased microbial fuel cell power output while the introduction of positively charged groups doubled the power output. Scanning electron microscopy revealed that the microbial anode modified with positively charged groups was covered by a dense and homogeneous biofilm. Fluorescence in situ hybridization analyses showed that this biofilm consisted to a large extent of bacteria from the known electroactive Geobacter genus. In summary, the extent of modification of the anode was found to be critical for the microbial fuel cell performance. The nature of the chemical group introduced at the electrode surface was also found to significantly affect the performance of the microbial fuel cells. The method used for

  20. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

  1. VIP as a potential therapeutic agent in gram negative sepsis.

    Science.gov (United States)

    Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2012-12-01

    Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

  2. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    Science.gov (United States)

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  3. Automatic control of load increases power and efficiency in a microbial fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Premier, Giuliano C.; Kim, Jung Rae; Michie, Iain [Sustainable Environment Research Centre (SERC), Faculty of Advanced Technology, University of Glamorgan, Pontypridd, Mid-Glamorgan CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [Sustainable Environment Research Centre (SERC), Faculty of Health, Sport and Science, University of Glamorgan, Pontypridd, Mid-Glamorgan CF37 1DL (United Kingdom)

    2011-02-15

    Increasing power production and coulombic efficiency (CE) of microbial fuel cells (MFCs) is a common research ambition as the viability of the technology depends to some extent on these measures of performance. As MFCs are typically time varying systems, comparative studies of controlled and un-controlled external load impedance are needed to show if control affects the biocatalyst development and hence MFC performance. The application of logic based control of external load resistance is shown to increase the power generated by the MFC, when compared to an equivalent system which has a static resistive load. The controlled MFC generated 1600 {+-} 400 C, compared to 300 {+-} 10 C with an otherwise replicate fixed load MFC system. The use of a parsimonious gradient based control was able to increase the CE to within the range of 15.1-22.7%, while the CE for a 200 {omega} statically loaded MFC lay in the range 3.3-3.7%. The controlled MFC improves the electrogenic anodic biofilm selection for power production, indicating that greater power and substrate conversion can be achieved by controlling load impedance. Load control ensured sustainable current demand, applied microbial selection pressures and provided near-optimal impedance for power transference, compared to the un-controlled system. (author)

  4. Innovative haematological parameters for early diagnosis of sepsis in adult patients admitted in intensive care unit.

    Science.gov (United States)

    Buoro, Sabrina; Manenti, Barbara; Seghezzi, Michela; Dominoni, Paola; Barbui, Tiziano; Ghirardi, Arianna; Carobbio, Alessandra; Marchesi, Gianmariano; Riva, Ivano; Nasi, Alessandra; Ottomano, Cosimo; Lippi, Giuseppe

    2018-04-01

    This study was aimed to investigate the role of erythrocyte, platelet and reticulocyte (RET) parameters, measured by new haematological analyser Sysmex XN and C reactive protein (CRP), for early diagnosis of sepsis during intensive care unit (ICU) stay. The study population consisted of 62 ICU patients, 21 of whom developed sepsis during ICU stay and 41 who did not. The performance for early diagnosing of sepsis was calculated as area under the curve (AUC) of receiver operating characteristics curves analysis. Compared with CRP (AUC 0.81), immature platelet fraction (IPF) (AUC 0.82) showed comparable efficiency for identifying the onset of sepsis. The association with the risk of developing sepsis during ICU stay was also assessed. One day before the onset of sepsis, a decreased of RET% was significantly associated with the risk of developing sepsis (OR=0.35, 95% CI 0.14 to 0.87), whereas an increased of IPF absolute value (IPF#) was significantly associated with the risk of developing sepsis (OR=1.13, 95% CI 1.03 to 1.24) 2 days before the onset of sepsis. The value of CRP was not predictive of sepsis at either time points. IPF# and RET% may provide valuable clinical information for predicting the risk of developing sepsis, thus allowing early management of patients before the onset of clinically evident systemic infections. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

    Science.gov (United States)

    Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

    2017-11-01

    The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Circulating Histones Are Major Mediators of Cardiac Injury in Patients With Sepsis.

    Science.gov (United States)

    Alhamdi, Yasir; Abrams, Simon T; Cheng, Zhenxing; Jing, Shengjie; Su, Dunhao; Liu, Zhiyong; Lane, Steven; Welters, Ingeborg; Wang, Guozheng; Toh, Cheng-Hock

    2015-10-01

    To investigate the impact of circulating histones on cardiac injury and dysfunction in a murine model and patients with sepsis. Prospective, observational clinical study with in vivo and ex vivo translational laboratory investigations. General ICU and university research laboratory. Sixty-five septic patients and 27 healthy volunteers. Twelve-week-old male C57BL/6N mice. Serial blood samples from 65 patients with sepsis were analyzed, and left ventricular function was assessed by echocardiography. Patients' sera were incubated with cultured cardiomyocytes in the presence or absence of antihistone antibody, and cellular viability was assessed. Murine sepsis was initiated by intraperitoneal Escherichia coli injection (10(8) colony-forming unit/mouse) in 12-week-old male C57BL/6N mice, and the effect of antihistone antibody (10 mg/kg) was studied. Murine blood samples were collected serially, and left ventricular function was assessed by intraventricular catheters and electrocardiography. Circulating histones and cardiac troponins in human and murine plasma were quantified. In 65 patients with sepsis, circulating histones were significantly elevated compared with healthy controls (n = 27) and linearly correlated with cardiac troponin T levels (rs = 0.650; p histone levels were significantly associated with new-onset left ventricular dysfunction (p = 0.001) and arrhythmias (p = 0.01). Left ventricular dysfunction only predicted adverse outcomes when combined with elevated histones or cardiac troponin levels. Furthermore, patients' sera directly induced histone-specific cardiomyocyte death ex vivo, which was abrogated by antihistone antibodies. In vivo studies on septic mice confirmed the cause-effect relationship between circulating histones and the development of cardiac injury, arrhythmias, and left ventricular dysfunction. Circulating histones are novel and important mediators of septic cardiomyopathy, which can potentially be utilized for prognostic and therapeutic

  7. Methods for reducing sepsis mortality in emergency departments and inpatient units.

    Science.gov (United States)

    Doerfler, Martin E; D'Angelo, John; Jacobsen, Diane; Jarrett, Mark P; Kabcenell, Andrea I; Masick, Kevin D; Parmentier, Darlene; Nelson, Karen L; Stier, Lori

    2015-05-01

    As part of a zero-tolerance approach to preventable deaths, North Shore-LIJ Health System (North Shore-LIJ) leadership prioritized a major patient safety initiative to reduce sepsis mortality in 2009 across 10 acute care hospitals (an 11th joined later). At baseline (2008), approximately 3,500 patients were discharged with a diagnosis of sepsis, which ranked as the top All Patient Refined Diagnosis-Related Group by number of deaths (N = 883). Initially, the focus was sepsis recognition and treatment in the emergency departments (EDs). North Shore-LIJ, the 14th largest health care system in the United States, cares for individuals at every stage of life at 19 acute care and specialty hospitals and more than 400 outpatient physician practice sites throughout New York City and the greater New York metropolitan area. The health system launched a strategic partnership with the Institute for Healthcare Improvement (IHI) in August 2011 to accelerate the pace of sepsis improvement. Throughout the course of the initiative, North Shore-LIJ collaborated with many local, state, national, and international organizations to test innovative ideas, share evidence-based best practices, and, more recently, to raise public awareness. North Shore-LIJ reduced overall sepsis mortality by approximately 50% in a six-year period (2008-2013; sustained through 2014) and increased compliance with sepsis resuscitation bundle elements in the EDs and inpatient units in the 11 acute care hospitals. Improvements were achieved by engaging leadership; fostering interprofessional collaboration, collaborating with other leading health care organizations; and developing meaningful, real-time metrics for all levels of staff.

  8. Screening for sepsis in general hospitalized patients: a systematic review.

    Science.gov (United States)

    Alberto, L; Marshall, A P; Walker, R; Aitken, L M

    2017-08-01

    Sepsis is a condition widely observed outside critical care areas. To examine the application of sepsis screening tools for early recognition of sepsis in general hospitalized patients to: (i) identify the accuracy of these tools; (ii) determine the outcomes associated with their implementation; and (iii) describe the implementation process. A systematic review method was used. PubMed, CINAHL, Cochrane, Scopus, Web of Science, and Embase databases were systematically searched for primary articles, published from January 1990 to June 2016, that investigated screening tools or alert mechanisms for early identification of sepsis in adult general hospitalized patients. The review protocol was registered with PROSPERO (CRD42016042261). More than 8000 citations were screened for eligibility after duplicates had been removed. Six articles met the inclusion criteria testing two types of sepsis screening tools. Electronic tools can capture, recognize abnormal variables, and activate an alert in real time. However, accuracy of these tools was inconsistent across studies with only one demonstrating high specificity and sensitivity. Paper-based, nurse-led screening tools appear to be more sensitive in the identification of septic patients but were only studied in small samples and particular populations. The process of care measures appears to be enhanced; however, demonstrating improved outcomes is more challenging. Implementation details are rarely reported. Heterogeneity of studies prevented meta-analysis. Clinicians, researchers and health decision-makers should consider these findings and limitations when implementing screening tools, research or policy on sepsis recognition in general hospitalized patients. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  9. Survival benefits of remote ischemic conditioning in sepsis.

    Science.gov (United States)

    Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2017-06-01

    Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an

  10. Role of extracellular histones in the cardiomyopathy of sepsis.

    Science.gov (United States)

    Kalbitz, Miriam; Grailer, Jamison J; Fattahi, Fatemeh; Jajou, Lawrence; Herron, Todd J; Campbell, Katherine F; Zetoune, Firas S; Bosmann, Markus; Sarma, J Vidya; Huber-Lang, Markus; Gebhard, Florian; Loaiza, Randall; Valdivia, Hector H; Jalife, José; Russell, Mark W; Ward, Peter A

    2015-05-01

    The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca(2+)]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht-, LRR-, and PYD-domains-containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca(2+)]i, as well as defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction. © FASEB.

  11. Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization.

    Science.gov (United States)

    Zaccone, Vincenzo; Tosoni, Alberto; Passaro, Giovanna; Vallone, Carla Vincenza; Impagnatiello, Michele; Li Puma, Domenica Donatella; De Cosmo, Salvatore; Landolfi, Raffaele; Mirijello, Antonio

    2017-11-01

    Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists' increased adherence to guidelines and "bundles". The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment. Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization.

  12. Symptoms of depression in survivors of severe sepsis: a prospective cohort study of older Americans.

    Science.gov (United States)

    Davydow, Dimitry S; Hough, Catherine L; Langa, Kenneth M; Iwashyna, Theodore J

    2013-09-01

    To examine if incident severe sepsis is associated with increased risk of subsequent depressive symptoms and to assess which patient characteristics are associated with increased risk of depressive symptoms. Prospective longitudinal cohort study. Population-based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998-2006). A total of 439 patients who survived 471 hospitalizations for severe sepsis and completed at least one follow-up interview. Depressive symptoms were assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. Severe sepsis was identified using a validated algorithm in Medicare claims. The point prevalence of substantial depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis (relative risk [RR]: 1.00; 95% confidence interval [CI]: 0.73, 1.34) nor severe sepsis-related clinical characteristics were significantly associated with subsequent depressive symptoms. These results were robust to potential threats from missing data or alternative outcome definitions. After adjustment, presepsis substantial depressive symptoms (RR: 2.20; 95% CI: 1.66, 2.90) and worse postsepsis functional impairment (RR: 1.08 per new limitation; 95% CI: 1.03, 1.13) were independently associated with substantial depressive symptoms after sepsis. The prevalence of substantial depressive symptoms in severe sepsis survivors is high but is not increased relative to their presepsis levels. Identifying this large subset of severe sepsis survivors at increased risk for major depression, and beginning interventions before hospital discharge, may improve outcomes. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    Science.gov (United States)

    Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan

    2014-01-01

    Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals were pretreated with Gallic acid at the dose rate of 20 mg/kg body weight for 2 days before induction of sepsis. Animals were sacrificed on 8th day and the tissue samples were obtained for further investigation on lipid peroxidation (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH). Gallic acid pretreatment significant (P Gallic acid pretreated mice showed significant improvement in SOD activity of kidney and spleen when compared to septic mice. Finally, the beneficial effects of Gallic acid pretreatment in sepsis are evident from the observations that Gallic acid partially restored SOD and catalase activity and completely reversed lipid peroxidation. Further studies are required to find out the possible mechanisms underlying the beneficial effects of Gallic acid on large population. PMID:25018890

  14. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  15. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

    Directory of Open Access Journals (Sweden)

    Kenneth Lyn-Kew

    2010-06-01

    Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

  16. Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

    Science.gov (United States)

    Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

    2012-11-01

    Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

  17. Spatial variation in microbial processes controlling carbon mineralization within soils and sediments

    Energy Technology Data Exchange (ETDEWEB)

    Fendorf, Scott [Stanford Univ., CA (United States); Kleber, Markus [Oregon State Univ., Corvallis, OR (United States); Nico, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-10-19

    Soils have a defining role in global carbon cycling, having one of the largest dynamic stocks of C on earth—3300 Pg of C are stored in soils, which is three-times the amount stored in the atmosphere and more than the terrestrial land plants. An important control on soil organic matter (SOM) quantities is the mineralization rate. It is well recognized that the rate and extent of SOM mineralization is affected by climatic factors and mineral-organic matter associations. What remained elusive is to what extent constraints on microbial metabolism induced by the respiratory pathway, and specifically the electron acceptor in respiration, control overall rates of carbon mineralization in soils. Therefore, physical factors limiting oxygen diffusion such as soil texture and aggregate size (soil structure) may therefore be central controls on C mineralization rates. The goal of our research was therefore to determine if variations in microbial metabolic rates induced by anaerobic microsites in soils are a major control on SOM mineralization rates and thus storage. We performed a combination of laboratory experiments and field investigations will be performed to fulfill our research objectives. We used laboratory studies to examine fundamental factors of respiratory constraints (i.e., electron acceptor) on organic matter mineralization rates. We ground our laboratory studies with both manipulation of field samples and in-field measurements. Selection of the field sites is guided by variation in soil texture and structure while having (other environmental/soil factors constant. Our laboratory studies defined redox gradients and variations in microbial metabolism operating at the aggregate-scale (cm-scale) within soils using a novel constructed diffusion reactor. We further examined micro-scale variation in terminal electron accepting processes and resulting C mineralization rates within re-packed soils. A major outcome of our research is the ability to quantitatively place

  18. Contemporary Trends of Reported Sepsis Among Maternal Decedents in Texas: A Population-Based Study.

    Science.gov (United States)

    Oud, Lavi

    2015-09-01

    Recent studies indicate that death certificate-based single-cause-of-death diagnoses can substantially underestimate the contribution of sepsis to mortality in the general population and among maternal decedents. There are no population-based data in the United States on the patterns of the contribution of sepsis to pregnancy-associated deaths. We studied the Texas Inpatient Public Use Data File to identify pregnancy-associated hospitalizations with reported hospital death during 2001-2010. We then examined the annual reporting of sepsis, and that of other reported most common causes of maternal death, including hemorrhage, embolism, preeclampsia/eclampsia, cardiovascular conditions, cardiomyopathy, cerebrovascular accidents, and anesthesia complications. The annual rate of sepsis among decedents, its trend over time, and changes of its annual rank among other examined potential causes of maternal death were assessed. There were 557 pregnancy-associated hospital deaths during study period. Sepsis was reported in 131 (23.5%) decedents. Sepsis has been increasingly reported among decedents, rising by 9.1%/year (P = 0.0025). The rank of sepsis, as compared to the other examined potential causes of maternal death rose from the 5th in 2001 to 1st since 2008. At the end of the last decade, sepsis has been reported in 28.1% of pregnancy-associated deaths. More than one potential cause of maternal death was reported in 39% of decedents. Sepsis has become the most commonly reported potential cause of death among maternal decedents in the present cohort, noted in over 1 in 4 fatal hospitalizations by the end of the last decade. Although causality cannot be inferred from administrative data, given its known contribution to maternal death, it is likely that sepsis plays an increasing role in fatal maternal hospital outcomes. The prevalent co-reporting of multiple potential causes of maternal death in the present cohort underscores the complexity of determining the sources of

  19. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

    International Nuclear Information System (INIS)

    Ognibene, F.P.; Parker, M.M.; Natanson, C.; Shelhamer, J.H.; Parrillo, J.E.

    1988-01-01

    Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock

  20. New strategy for sepsis: Targeting a key role of platelet-neutrophil interaction

    Directory of Open Access Journals (Sweden)

    Xu Wang

    2014-07-01

    Full Text Available Neutrophil and platelet are essential arms of the innate immune response. In sepsis, platelet abnormal activation as well as neutrophil paralysis are well recognized. For platelet, it is characterized by the contribution to disseminated intravascular coagulation (DIC and the enhanced inflammation response. In terms of neutrophil, its dysfunction is manifested by the impaired recruitment and migration to the infectious foci, abnormal sequestration in the remote organs, and the delayed clearance. More recently, it has been apparent that together platelet-neutrophil interaction can induce a faster and harder response during sepsis. This article focuses on the activation of platelet, dysfunction of neutrophil, and the interaction between them during sepsis and profiles some of the molecular mechanisms and outcomes in these cellular dialogues, providing a novel strategy for treatment of sepsis.

  1. The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

    Science.gov (United States)

    Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

    2011-04-01

    In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney

  2. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    Science.gov (United States)

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

  3. DMPD: Role of Toll-like receptor responses for sepsis pathogenesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18086373 Role of Toll-like receptor responses for sepsis pathogenesis. Weighardt H,... of Toll-like receptor responses for sepsis pathogenesis. PubmedID 18086373 Title Role of Toll-like receptor... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication

  4. Application of the new Sepsis-3 definition in a cohort of patients with severe sepsis and septic shock admitted to Intensive Care Unit from the Emergency Department.

    Science.gov (United States)

    García-Gigorro, Renata; Molina-Collado, Zaira; Sáez-de la Fuente, Ignacio; Sanchez-Izquierdo, José Ángel; Montejo González, Juan Carlos

    2018-04-18

    After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank definition could help improve the evaluation of risk of hospital death. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  5. Systemic inflammatory response syndrome criteria in defining severe sepsis.

    Science.gov (United States)

    Kaukonen, Kirsi-Maija; Bailey, Michael; Pilcher, David; Cooper, D Jamie; Bellomo, Rinaldo

    2015-04-23

    The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in

  6. MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

    Science.gov (United States)

    Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

    2017-07-18

    Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

  7. In vitro diagnosis of sepsis: a review

    Directory of Open Access Journals (Sweden)

    Guido M

    2016-03-01

    Full Text Available Marcello Guido,1 Maria Rosaria Tumolo,2 Antonella De Donno,1 Tiziano Verri,3 Francesca Serio,1 Francesco Bagordo,1 Antonella Zizza2 1Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, Italy; 2National Research Council, Institute of Clinical Physiology, 3Laboratory of Physiology, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, ItalyAbstract: Sepsis, severe sepsis and septic shock, systemic inflammatory response, and other related manifestations represent a relevant medical problem with high morbidity and mortality, despite the improvements in diagnosis, treatment, and preventive measures over the last few decades. The limited knowledge of the pathophysiology in association with the lack of in vitro diagnostic methods for the certain and quick determination of the causative microbiological agents and their antibiotic resistance means the condition is still critical and of high impact in health care. The current gold standard method to detect the sepsis-causing pathogens, which is based on blood culture, is still insufficiently sensitive and slow. The new culture-independent molecular biology-based techniques can lead to the identification of a broad range of microorganisms and resistance markers within a few hours and with high sensitivity and specificity; nevertheless, limitations of, for example, the polymerase chain reaction-based methods still hamper their application in the clinical routine. This review summarizes the in vitro diagnostic methods and their approach in the clinical diagnosis of the bloodstream infections, and explores their advantages and disadvantages at the current state of the art. A quick analysis of the future prospective in multiplex technologies for microbiological diagnosis of sepsis is also provided. Keywords: PCR, PCR/ESI-MS, microarray, MALDI-TOF, next

  8. Expression of NK cell and monocyte receptors in critically ill patients - potential biomarkers of sepsis

    DEFF Research Database (Denmark)

    Kjaergaard, A G; Nielsen, Jeppe Sylvest; Tønnesen, Else

    2015-01-01

    UNLABELLED: Sepsis is characterized by activation of both the innate and adaptive immune systems as a response to infection. During sepsis, the expression of surface receptors expressed on immune competent cells, such as NKG2D and NKp30 on NK cells and TLR4 and CD14 on monocytes, is partly...... regulated by pro- and anti-inflammatory mediators. In this observational study, we aimed to explore whether the expression of these receptors could be used as diagnostic and/or prognostic biomarkers in sepsis. Patients with severe sepsis or septic shock (n = 21) were compared with critically ill non...... were higher in the septic patients compared with the non-septic patients (P sepsis...

  9. Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis.

    Science.gov (United States)

    Wang, Meng-Meng; Hao, Li-Ying; Guo, Feng; Zhong, Bin; Zhong, Xiao-Mei; Yuan, Jing; Hao, Yi-Fei; Zhao, Shuang; Sun, Xue-Fei; Lei, Ming; Jiao, Guang-Yu

    2017-12-01

    Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca 2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca 2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca 2+ ] was measured by confocal microscopy and fluorescence spectrophotometry. Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca 2+ ] were significantly decreased in the rat sepsis model compared with controls. Decreased intracellular [Ca 2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017. © 2017 Wiley Periodicals, Inc.

  10. Procalcitonin levels in sepsis and its association with clinical outcome in southern India.

    Science.gov (United States)

    Rebello, Alex; Thabah, Molly Mary; Dutta, Tarun Kumar; Bobby, Zachariah; Harish, B N; Mehalingam, Vadivelan

    2017-10-01

    Procalcitonin has been found to be a good marker for the diagnosis of sepsis. However, data on procalcitonin levels to predict the clinical outcome in patients with sepsis are limited. The aim of our study was to estimate serum procalcitonin levels in patients with sepsis and to identify its relationship with the clinical outcome. This was a prospective observational study conducted on 112 patients with sepsis admitted to the medical wards and medical intensive care unit of a tertiary care teaching hospital. Serum procalcitonin was measured at baseline before antibiotic administration and on day 5. The clinical outcome studied was death or survival on day 28. Baseline mean serum procalcitonin was highest in patients with septic shock and lowest in patients having sepsis without organ dysfunction. Mean values of procalcitonin at baseline and on day 5 were significantly higher in non-survivors when compared with survivors. There was a significant difference in the change in procalcitonin levels from baseline to day 5 between survivors and non-survivors, with survivors having declining values on day 5 while non-survivors had increasing values from baseline. The baseline APACHE II and SOFA scores also showed a significant correlation with the baseline procalcitonin level. Declining values of procalcitonin therefore indicate a favourable clinical outcome in patients with sepsis.

  11. N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.

    Science.gov (United States)

    Chertoff, Jason

    2018-02-01

    To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.

  12. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.

    Science.gov (United States)

    Rayes, Julie; Lax, Siân; Wichaiyo, Surasak; Watson, Stephanie K; Di, Ying; Lombard, Stephanie; Grygielska, Beata; Smith, Stuart W; Skordilis, Kassiani; Watson, Steve P

    2017-12-21

    Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.

  13. Managing sepsis: Electronic recognition, rapid response teams, and standardized care save lives.

    Science.gov (United States)

    Guirgis, Faheem W; Jones, Lisa; Esma, Rhemar; Weiss, Alice; McCurdy, Kaitlin; Ferreira, Jason; Cannon, Christina; McLauchlin, Laura; Smotherman, Carmen; Kraemer, Dale F; Gerdik, Cynthia; Webb, Kendall; Ra, Jin; Moore, Frederick A; Gray-Eurom, Kelly

    2017-08-01

    Sepsis can lead to poor outcomes when treatment is delayed or inadequate. The purpose of this study was to evaluate outcomes after initiation of a hospital-wide sepsis alert program. Retrospective review of patients ≥18years treated for sepsis. There were 3917 sepsis admissions: 1929 admissions before, and 1988 in the after phase. Mean age (57.3 vs. 57.1, p=0.94) and Charlson Comorbidity Scores (2.52 vs. 2.47, p=0.35) were similar between groups. Multivariable analyses identified significant reductions in the after phase for odds of death (OR 0.62, 95% CI 0.39-0.99, p=0.046), mean intensive care unit LOS (2.12days before, 95%CI 1.97, 2.34; 1.95days after, 95%CI 1.75, 2.06; p<0.001), mean overall hospital LOS (11.7days before, 95% CI 10.9, 12.7days; 9.9days after, 95% CI 9.3, 10.6days, p<0.001), odds of mechanical ventilation use (OR 0.62, 95% CI 0.39, 0.99, p=0.007), and total charges with a savings of $7159 per sepsis admission (p=0.036). There was no reduction in vasopressor use (OR 0.89, 95% CI 0.75, 0.1.06, p=0.18). A hospital-wide program utilizing electronic recognition and RRT intervention resulted in improved outcomes in patients with sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

    DEFF Research Database (Denmark)

    Johansen, Maria E; Johansson, Pär I.; Ostrowski, Sisse R

    2015-01-01

    levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. organ failure and death in septic......Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively......), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels...

  15. The etiology of neonatal sepsis and patterns of antibiotic resistance

    International Nuclear Information System (INIS)

    Waheed, M.; Laeeq, A.; Maqbool, S.

    2003-01-01

    Objective: To study the patterns of causative bacteria and antibiotic resistance in neonatal sepsis. Results: Among 228 cases included in the study, the male to female ratio was 2.1 to 1. The gestational age was less than 36 weeks in 68 (30%) cases and low birth weight babies were 143 (62.6%). History of birth asphyxia was present in 103 (45%) cases. There were 142 (62.3%) cases of early onset ( 7 days). Out of 233 positive blood cultures Escherichia coli was found to be commonest (47.8%, n =111, p<0.05) both in early onset (47.8%, n=68, p <0.05) and late onset sepsis (47.3%,n=43, p<0.05). Staphylococcus aureus was the most common among gram positive organism. Resistance to cefotaxime, ceftazidime and amikacin was 34% to 80% and to ciprofloxacin 13% to 72%. A total of 64 cases (28%) died. Mortality was four times higher in early onset sespis. Conclusion: Gram negative bacteria are the commenst cause of neonatal sepsis. The resistance to the commonly used antibiotics is alarmingly high. Mortality is four times higher in early one set sepsis. (author)

  16. Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

    Directory of Open Access Journals (Sweden)

    M. Neri

    2016-01-01

    Full Text Available Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

  17. Platelets and Multi-Organ Failure in Sepsis

    Directory of Open Access Journals (Sweden)

    Elisabetta Greco

    2017-10-01

    Full Text Available Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  18. Platelets and Multi-Organ Failure in Sepsis.

    Science.gov (United States)

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-10-20

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  19. The Surviving Sepsis Campaign: Where have we been and where are we going?

    Science.gov (United States)

    Dellinger, R Phillip

    2015-04-01

    The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and performance-improvement practices aimed at reducing deaths from sepsis worldwide. The most recent guidelines, published in 2013, provide detailed management strategies for acute care, fluid resuscitation, and vasopressor use. In addition, the campaign has developed simple, short protocols for what to do within 3 and 6 hours of recognition of sepsis. These protocols are associated with reduced mortality rates. Copyright © 2015 Cleveland Clinic.

  20. Development and validation of a mortality risk model for pediatric sepsis

    Science.gov (United States)

    Chen, Mengshi; Lu, Xiulan; Hu, Li; Liu, Pingping; Zhao, Wenjiao; Yan, Haipeng; Tang, Liang; Zhu, Yimin; Xiao, Zhenghui; Chen, Lizhang; Tan, Hongzhuan

    2017-01-01

    Abstract Pediatric sepsis is a burdensome public health problem. Assessing the mortality risk of pediatric sepsis patients, offering effective treatment guidance, and improving prognosis to reduce mortality rates, are crucial. We extracted data derived from electronic medical records of pediatric sepsis patients that were collected during the first 24 hours after admission to the pediatric intensive care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014. A total of 788 children were randomly divided into a training (592, 75%) and validation group (196, 25%). The risk factors for mortality among these patients were identified by conducting multivariate logistic regression in the training group. Based on the established logistic regression equation, the logit probabilities for all patients (in both groups) were calculated to verify the model's internal and external validities. According to the training group, 6 variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate levels, and mechanical ventilation in 24 hours) were included in the final logistic regression model. The areas under the curves of the model were 0.854 (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups, respectively. The Mortality Risk Model for Pediatric Sepsis we established in this study showed acceptable accuracy to predict the mortality risk in pediatric sepsis patients. PMID:28514310

  1. Defining and measuring suspicion of sepsis: an analysis of routine data.

    Science.gov (United States)

    Inada-Kim, Matthew; Page, Bethan; Maqsood, Imran; Vincent, Charles

    2017-06-09

    To define the target population of patients who have suspicion of sepsis (SOS) and to provide a basis for assessing the burden of SOS, and the evaluation of sepsis guidelines and improvement programmes. Retrospective analysis of routinely collected hospital administrative data. Secondary care, eight National Health Service (NHS) Acute Trusts. Hospital Episode Statistics data for 2013-2014 was used to identify all admissions with a primary diagnosis listed in the 'suspicion of sepsis' (SOS) coding set. The SOS coding set consists of all bacterial infective diagnoses. We identified 47 475 admissions with SOS, equivalent to a rate of 17 admissions per 1000 adults in a given year. The mortality for this group was 7.2% during their acute hospital admission. Urinary tract infection was the most common diagnosis and lobar pneumonia was associated with the most deaths. A short list of 10 diagnoses can account for 85% of the deaths. Patients with SOS can be identified in routine administrative data. It is these patients who should be screened for sepsis and are the target of programmes to improve the detection and treatment of sepsis. The effectiveness of such programmes can be evaluated by examining the outcomes of patients with SOS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Importance of microbial pest control agents and their metabolites In relation to the natural microbiota on strawberry

    DEFF Research Database (Denmark)

    Jensen, Birgit; Knudsen, Inge M. B.; Jensen, Dan Funck

    control. A series of laboratory, growth chamber, semi-field and field experiments using strawberry as a model plant focusing on commercial microbial pest control products (MPCPs) or laboratory MPCAs expected to be on the market within 10 years served as our experimental platform. Initially the background...... level of indigenous microbial communities and their mycotoxins/metabolites on strawberries was examined in a field survey with 4 conventional and 4 organic growers with different production practise and geographic distribution. Culturable bacteria, yeasts and filamentous fungi were isolated...... and identified using both chemotaxonomy (fatty acids and metabolite profiling) and morphological characteristics. Microbial communities on strawberries were complex including potential plant pathogens, opportunistic human pathogens, plant disease biocontrol agents and mycotoxin producers. Bacteria were the most...

  3. Culture-positive sepsis in neonatal camelids: 21 cases.

    Science.gov (United States)

    Dolente, Brett A; Lindborg, Susan; Palmer, Jonathan E; Wilkins, Pamela A

    2007-01-01

    There is limited literature on neonatal bacterial sepsis in New World (NW) camelids. Bacterial culture-positive crias have clinical differences based on the specific bacterial genera isolated. Bacterial culture-positive NW camelid crias blood gas abnormalities, potentially complicating diagnosis. Affected crias may not have localizing signs at presentation and are not usually febrile, although hypothermia, tachypnea, and tachycardia are relatively common. Total protein concentration was not a substitute for immunoglobulin G measurement in septic crias in this study. Familiarity with the clinical presentation and common pathogens isolated should improve early recognition and treatment and ultimately outcome of crias with sepsis.

  4. Whey Peptide-Based Formulas With ω-3 Fatty Acids Are Protective in Lipopolysaccharide-Mediated Sepsis.

    Science.gov (United States)

    Tsutsumi, Rie; Horikawa, Yousuke T; Kume, Katsuyoshi; Tanaka, Katsuya; Kasai, Asuka; Kadota, Takako; Tsutsumi, Yasuo M

    2015-07-01

    Sepsis and septic shock syndrome are among the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon may translocate across a compromised epithelium, leading to oxidative stress, inflammation, sepsis, and eventually death. We examined the effects of a whey-based enteral formula high in cysteine (antioxidant precursor) and the addition of ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against a mouse model of LPS-induced sepsis. Mice were fed either a whey-based diet with EPA-DHA (PAF), a whey-based diet without EPA-DHA (PSTD), or a casein-based control diet (CONT). Mice fed PAF or PSTD were protected against LPS-induced weight loss. Whey-based diets suppressed inflammatory cytokine release and oxidative stress damage. Furthermore, PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles. These anti-inflammatory and antioxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microbiota within the intestines. These data suggest a clinical role for whey peptide-based diets in promoting healing and recovery in critically ill patients. © 2014 American Society for Parenteral and Enteral Nutrition.

  5. Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

    Science.gov (United States)

    Wang, Yumei; Yin, Xiaoling; Yang, Fang

    2018-02-01

    Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

  6. Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

    Science.gov (United States)

    Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

    2009-06-01

    Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

  7. Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

    DEFF Research Database (Denmark)

    Olsen, Helle G; Kjelgaard-Hansen, Mads; Tveden-Nyborg, Pernille

    2016-01-01

    A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged by the sev......A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged....... Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation. While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3......, according to humane endpoints. A usable balance between scientific purpose and animal welfare could not be achieved, and we therefore find it hard to justify further use of this conscious porcine sepsis model. In order to make a model of translational relevance for human sepsis, we suggest that future model...

  8. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

    Science.gov (United States)

    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  9. Association of Neighborhood Socioeconomic Status With Risk of Infection and Sepsis.

    Science.gov (United States)

    Donnelly, John P; Lakkur, Sindhu; Judd, Suzanne E; Levitan, Emily B; Griffin, Russell; Howard, George; Safford, Monika M; Wang, Henry E

    2018-02-12

    Prior studies suggest disparities in sepsis risk and outcomes based on place of residence. We sought to examine the association between neighborhood socioeconomic status (nSES) and hospitalization for infection and sepsis. We conducted a prospective cohort study using data from 30239 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. nSES was defined using a score derived from census data and classified into quartiles. Infection and sepsis hospitalizations were identified over the period 2003-2012. We fit Cox proportional hazards models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs) and examining mediation by participant characteristics. Over a median follow-up of 6.5 years, there were 3054 hospitalizations for serious infection. Infection incidence was lower for participants in the highest nSES quartile compared with the lowest quartile (11.7 vs 15.6 per 1000 person-years). After adjustment for demographics, comorbidities, and functional status, infection hazards were also lower for the highest quartile (HR, 0.84 [95% CI, .73-.97]), with a linear trend (P = .011). However, there was no association between nSES and sepsis at presentation among those hospitalized with infection. Physical weakness, income, and diabetes had modest mediating effects on the association of nSES with infection. Our study shows that differential infection risk may explain nSES disparities in sepsis incidence, as higher nSES is associated with lower infection hospitalization rates, but there is no association with sepsis among those hospitalized. Mediation analysis showed that nSES may influence infection hospitalization risk at least partially through physical weakness, individual income, and comorbid diabetes. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. Interval Changes in Myocardial Performance Index Predict Outcome in Severe Sepsis.

    Science.gov (United States)

    Nizamuddin, Junaid; Mahmood, Feroze; Tung, Avery; Mueller, Ariel; Brown, Samuel M; Shaefi, Shahzad; O'Connor, Michael; Talmor, Daniel; Shahul, Sajid

    2017-06-01

    Septic cardiomyopathy is a well-described consequence of septic shock and is associated with increased sepsis-related mortality. The myocardial performance index (MPI), a parameter derived from echocardiographic tissue Doppler measurements, allows for a more sensitive assessment of global cardiac function than do traditional metrics for cardiac function. The authors hypothesized that changes in left ventricular MPI in patients with severe sepsis would be associated with a higher 90-day mortality. Prospective, observational study. Intensive care units of a tertiary medical center. The study comprised 47 patients admitted with new diagnoses of severe sepsis or septic shock. All patients underwent transthoracic echocardiograms with assessment of MPI at enrollment and 24 hours later. Hemodynamic data and information on sepsis-related mortality were collected. In the primary analysis, the association between change in MPI from enrollment to 24 hours and sepsis-related 90-day mortality was assessed. Of the 47 patients enrolled, 30 demonstrated an improvement in MPI from 0 to 24 hours ("improved" group), and MPI worsened in the remaining 17 patients ("worsened" group). Despite no significant differences in ejection fraction or severity of illness, the median MPI at enrollment in the "improved" group was higher than baseline values in the "worsened" group (p = 0.005). A worsening MPI over the 24-hour study interval was associated with increased mortality at 90 days (p = 0.04), which remained significant (hazard ratio 3.72; 95% confidence interval 1.12-12.41; p = 0.03) after adjusting for severity of illness (Acute Physiology and Chronic Health Evaluation II score), intravenous fluids, and vasopressor use. In patients admitted to the intensive care unit with a diagnosis of severe sepsis or septic shock, a worsening MPI during the first 24 hours after intensive care unit admission was associated with higher 90-day mortality. Copyright © 2017 Elsevier Inc. All rights

  11. Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis.

    Science.gov (United States)

    Chen, Jin; Yan, Jing; Cai, Guo-Long; Xu, Qiang-Hong; Gong, Shi-Jin; Dai, Hai-Wen; Yu, Yi-Hua; Li, Li

    2013-06-01

    The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis, but there is controversial in choosing a parenteral nutrition formulation. This study was designed to compare the therapeutic effects of structured lipid emulsion, physically mixed medium, and long-chain fat emulsion in the treatment of severe sepsis in elderly patients. A total number of 64 elder patients with severe sepsis were enrolled in the study. After a week of enteral nutritional support, the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation). The alterations of plasma albumin, lipid metabolism, and blood glucose level were recorded after parenteral alimentation and were compared between the two groups. The plasma levels of albumin, prealbumin, cholesterol, and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t = 7.78, P = 0.000; t = 10.21, P = 0.000; t = 7.99, P = 0.000; and t = 10.99, P = 0.000). Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t = 3.316, P = 0.002; t = 3.200, P = 0.002), whilst had no effects on the blood glucose and triglyceride level (t = 7.78, P = 0.000; t = 4.228, P = 0.000). In addition, the two groups had a significantly different Apache II score, ventilator time, and hospital stay time (t = -2.213, P = 0.031; t = 2.317, P = 0.024; t = 2.514, P = 0.015). The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis. It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

  12. Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

    Science.gov (United States)

    Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M

    2010-03-01

    Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may

  13. The coagulopathy in sepsis: significance and implications for treatment

    Directory of Open Access Journals (Sweden)

    Berardino Pollio

    2011-09-01

    Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

  14. Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.

    Science.gov (United States)

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R; Merriman, Joseph A; Stach, Christopher S; Horswill, Alexander R; Peterson, Marnie L; Schlievert, Patrick M

    2013-08-20

    Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that

  15. Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.

    Science.gov (United States)

    Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M

    2013-10-01

    Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte

  16. Inhibition of IKKß in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality

    Science.gov (United States)

    Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.

    2013-01-01

    Objective NF-kB is a critical regulator of cell survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase (IKK)-ß. Design Prospective, randomized, controlled study. Setting Animal laboratories in university medical centers. Subjects and Interventions Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkßf/Δ) and wild type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture (CLP). Animals were sacrified at 24 hours or followed seven days for survival. Measurements and Main Results Septic WT mice had decreased villus length compared to sham mice while villus atrophy was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared to sham mice which was further exacerbated in Vil-Cre/Ikkßf/Δ mice. Sepsis induced intestinal hyperpermeability in WT mice compared to sham mice, which was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. This was associated with increased intestinal expression of claudin-2 in septic WT mice, which was further increased in septic Vil-Cre/Ikkßf/Δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following CLP, and IL-10 and MCP-1 levels were higher in septic Vil-Cre/Ikkßf/Δ mice than septic WT mice. All septic mice were bacteremic, but no differences in bacterial load were identified between WT and Vil-Cre/Ikkßf/Δ mice. To determine the functional significance of these results, animals were followed for survival. Septic WT mice had lower mortality than septic Vil-Cre/Ikkßf/Δ mice (47% vs. 80%, p<0.05). Anti-TNF administration decreased intestinal apoptosis, permeability and mortality in WT septic mice and a similar improvement in intestinal integrity and survival were seen when anti-TNF was given to Vil-Cre/Ikkßf/Δ mice. Conclusions Enterocyte-specific NF

  17. Role of presepsin compared to C-reactive protein in sepsis diagnosis and prognostication

    Directory of Open Access Journals (Sweden)

    Mohamed El-Saied El-Shafie

    2017-04-01

    Full Text Available Early identification of sepsis and its differentiation from non-infective SIRS are important for sepsis outcome. We intended to evaluate the use of presepsin in differentiating sepsis from noninfectious SIRS and its prognostic value compared to CRP. We included 31 patients (median age 60 year old, 16 males admitted with SIRS to El-Sahel Teaching Hospital, Egypt after excluding 21 patients with preadmission corticosteroids therapy, blood transfusion, immunosuppressive illness, and ICU length of stay (ICU-LOS less than 24-hours. Patients were classified into non-infective SIRS group (13 patients and sepsis group (18 patients. Presepsin, CRP and SOFA score were measured on admission and on days 2 and 4 of admission. The outcome parameters studied were ICU-LOS and in-hospital survival. Apart from temperature and AST which were significantly higher in sepsis group, the two groups were comparable. All the presepsin levels and CRP on days 2 and 4 were significantly higher in sepsis than in SIRS groups. The ICU-LOS was positively correlated with all the presepsin levels and with the CRP levels on days 2 and 4. All presepsin values were significantly higher in survivors while none of the CRP levels were significantly different in survivors and non-survivors. The decrease of presepsin over time was significantly associated with better survival. It was found to be 70% sensitive and 91% specific for predicting survival in SIRS patients. This relation was not found in CRP levels. We concluded that the presepsin can be used for early differentiation between sepsis and non-infectious SIRS and predict higher mortality.

  18. Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

    Science.gov (United States)

    Xie, Jianfeng; Robertson, Jennifer M; Chen, Ching-Wen; Zhang, Wenxiao; Coopersmith, Craig M; Ford, Mandy L

    2018-01-01

    The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy

  19. Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

    Directory of Open Access Journals (Sweden)

    Jianfeng Xie

    Full Text Available The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre

  20. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis

    DEFF Research Database (Denmark)

    Perner, Anders; Haase, Nicolai; Guttormsen, Anne B

    2012-01-01

    Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.......Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis....