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Article ; Online: Multisite validation of a host response signature for predicting likelihood of bacterial and viral infections in patients with suspected influenza.

Shojaei, Maryam / Chen, Uan-I / Midic, Uros / Thair, Simone / Teoh, Sally / McLean, Anthony / Sweeney, Timothy E / Thompson, Matthew / Liesenfeld, Oliver / Khatri, Purvesh / Tang, Benjamin

European journal of clinical investigation

2023 Volume 53, Issue 5, Page(s) e13957

Abstract: Background: Indiscriminate use of antimicrobials and antimicrobial resistance is a public health threat. IMX-BVN-1, a 29-host mRNA classifier, provides two separate scores that predict likelihoods of bacterial and viral infections in patients with ... ...

Abstract	Background: Indiscriminate use of antimicrobials and antimicrobial resistance is a public health threat. IMX-BVN-1, a 29-host mRNA classifier, provides two separate scores that predict likelihoods of bacterial and viral infections in patients with suspected acute infections. We validated the performance of IMX-BVN-1 in adults attending acute health care settings with suspected influenza. Method: We amplified 29-host response genes in RNA extracted from blood by NanoString nCounter. IMX-BVN-1 calculated two scores to predict probabilities of bacterial and viral infections. Results were compared against the infection status (no infection; highly probable/possible infection; confirmed infection) determined by clinical adjudication. Results: Amongst 602 adult patients (74.9% ED, 16.9% ICU, 8.1% outpatients), 7.6% showed in-hospital mortality and 15.5% immunosuppression. Median IMX-BVN-1 bacterial and viral scores were higher in patients with confirmed bacterial (0.27) and viral (0.62) infections than in those without bacterial (0.08) or viral (0.21) infection, respectively. The AUROC distinguishing bacterial from nonbacterial illness was 0.81 and 0.87 when distinguishing viral from nonviral illness. The bacterial top quartile's positive likelihood ratio (LR) was 4.38 with a rule-in specificity of 88%; the bacterial bottom quartile's negative LR was 0.13 with a rule-out sensitivity of 96%. Similarly, the viral top quartile showed an infinite LR with rule-in specificity of 100%; the viral bottom quartile had a LR of 0.22 and a rule-out sensitivity of 85%. Conclusion: IMX-BVN-1 showed high accuracy for differentiating bacterial and viral infections from noninfectious illness in patients with suspected influenza. Clinical utility of IMX-BVN will be validated following integration into a point of care system.
MeSH term(s)	Adult ; Humans ; Influenza, Human ; Virus Diseases ; Critical Care ; RNA, Messenger ; Probability ; Bacterial Infections/diagnosis ; Bacterial Infections/microbiology
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2023-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.13957
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Zs.A 677: Show issues

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Article ; Online: Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection.

Ram-Mohan, Nikhil / Thair, Simone A / Litzenburger, Ulrike M / Cogill, Steven / Andini, Nadya / Yang, Xi / Chang, Howard Y / Yang, Samuel

Life science alliance

2021 Volume 4, Issue 8

Abstract: Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid ...

Abstract	Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after
MeSH term(s)	Adult ; Chromatin Immunoprecipitation Sequencing/methods ; Epigenomics ; Escherichia coli/pathogenicity ; Escherichia coli Infections/genetics ; Female ; Gene Expression Regulation ; Humans ; Models, Biological ; Neutrophils/chemistry ; Neutrophils/microbiology ; Promoter Regions, Genetic ; Sepsis/genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Time Factors
Language	English
Publishing date	2021-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202000976
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Article: Noncanonical Nuclear Factor Kappa B (NF-κB) Signaling and Potential for Therapeutics in Sepsis.

Thair, Simone / Russell, James A

Current infectious disease reports

2013 Volume 15, Issue 5, Page(s) 364–371

Abstract: NF-κB signaling plays a central role in the pathophysiology of severe sepsis and septic shock. Despite tremendous and missed efforts, novel therapeutics for severe sepsis and septic shock are still needed. Many drugs have been designed to target the ... ...

Abstract	NF-κB signaling plays a central role in the pathophysiology of severe sepsis and septic shock. Despite tremendous and missed efforts, novel therapeutics for severe sepsis and septic shock are still needed. Many drugs have been designed to target the canonical NF-κB signaling pathway with limited success, potentially due to the nonspecificity of the drugs for other kinases and the interaction of canonical signaling with other pathways. Here, we review the canonical and noncanonical signaling pathways of NF-κB, the cross talk and negative regulation of the two pathways, and the potential for therapeutics arising from the noncanonical NF-κB pathway in relation to the pathophysiology of septic shock.
Language	English
Publishing date	2013-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2019948-X
ISSN	1534-3146 ; 1523-3847
ISSN (online)	1534-3146
ISSN	1523-3847
DOI	10.1007/s11908-013-0362-0
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Zs.A 5519: Show issues

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Article ; Online: Sepsis in transit: from clinical to molecular classification.

Thair, Simone A / Russell, James A

Critical care (London, England)

2012 Volume 16, Issue 6, Page(s) 173

Abstract: In the previous issue of Critical Care, Maslove and colleagues studied circulating neutrophil transcriptional expression to discover and validate a molecular subclassification of adult patients with sepsis. The authors divided patients into small ... ...

Abstract	In the previous issue of Critical Care, Maslove and colleagues studied circulating neutrophil transcriptional expression to discover and validate a molecular subclassification of adult patients with sepsis. The authors divided patients into small derivation (n = 55) and validation (n = 71) cohorts. Their complex methodology included partitioning around medoid and hierarchical clustering methods to define two transcriptionally distinct subtypes of sepsis. Pathway analysis found that chemokine and cytokine pathways as well as Toll-like receptor signaling were enhanced. Investigation of specific drug target genes relevant to sepsis found significantly different expression levels between the two molecular subtypes. Interestingly, most patient characteristics did not differ between groups, except for an increase in the proportion of severe sepsis in molecular subtype 1. Possible confounders of this study were the small sample size, population stratification, and lack of information regarding drug interventions, all of which support the need for more studies with larger cohorts that include transcriptional profiles. This thought-provoking hypothesis-generating study could lead to a new neutrophil expression-based molecular classification of adult sepsis.
MeSH term(s)	Critical Illness ; Female ; Gene Expression Profiling/methods ; Humans ; Male ; Sepsis/classification ; Sepsis/genetics
Language	English
Publishing date	2012-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/cc11813
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Zs.A 5517: Show issues

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Article ; Online: Gene Expression-Based Diagnosis of Infections in Critically Ill Patients-Prospective Validation of the SepsisMetaScore in a Longitudinal Severe Trauma Cohort.

Thair, Simone / Mewes, Caspar / Hinz, José / Bergmann, Ingo / Büttner, Benedikt / Sehmisch, Stephan / Meissner, Konrad / Quintel, Michael / Sweeney, Timothy E / Khatri, Purvesh / Mansur, Ashham

Critical care medicine

2021 Volume 49, Issue 8, Page(s) e751–e760

Abstract: Objectives: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the ... ...

Abstract	Objectives: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients. Design: Prospective observational cohort study. Setting: Surgical ICUs of the University Medical Center Goettingen, Germany. Patients: Critically ill patients with severe traumatic injuries. Interventions: None. Measurements and main results: Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014). Conclusions: We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.
MeSH term(s)	Adult ; Biomarkers/blood ; Cohort Studies ; Critical Illness/therapy ; Gene Expression ; Germany ; Humans ; Intensive Care Units/organization & administration ; Length of Stay/statistics & numerical data ; Male ; Middle Aged ; Systemic Inflammatory Response Syndrome/diagnosis ; Systemic Inflammatory Response Syndrome/genetics ; Systemic Inflammatory Response Syndrome/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-04-23
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000005027
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Zs.A 1261: Show issues

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Article ; Online: A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations.

Rao, Aditya M / Popper, Stephen J / Gupta, Sanjana / Davong, Viengmon / Vaidya, Krista / Chanthongthip, Anisone / Dittrich, Sabine / Robinson, Matthew T / Vongsouvath, Manivanh / Mayxay, Mayfong / Nawtaisong, Pruksa / Karmacharya, Biraj / Thair, Simone A / Bogoch, Isaac / Sweeney, Timothy E / Newton, Paul N / Andrews, Jason R / Relman, David A / Khatri, Purvesh

Cell reports. Medicine

2022 Volume 3, Issue 12, Page(s) 100842

Abstract: Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 ... ...

Abstract	Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) > 0.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity and 91% sensitivity). The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections.
MeSH term(s)	Humans ; Prospective Studies ; Bacterial Infections/diagnosis ; Sensitivity and Specificity ; Transcriptome ; Virus Diseases/diagnosis
Language	English
Publishing date	2022-12-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100842
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Article ; Online: The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock.

Nakada, Taka-Aki / Wacharasint, Petch / Russell, James A / Boyd, John H / Nakada, Emiri / Thair, Simone A / Shimada, Tadanaga / Walley, Keith R

Journal of innate immunity

2018 Volume 10, Issue 3, Page(s) 181–188

Abstract: Background: The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock.: ... ...

Abstract	Background: The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock. Methods: Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality. Results: Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10-4). Patients with the GG genotype had more organ dysfunction (p < 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032). Conclusions: The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.
MeSH term(s)	Aged ; Cell Line ; Cohort Studies ; Female ; Gene Expression ; Genetic Association Studies ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Intensive Care Units ; Interleukin-10/genetics ; Interleukins/genetics ; Length of Stay ; Male ; Middle Aged ; Organ Dysfunction Scores ; Polymorphism, Single Nucleotide ; Shock, Septic/genetics ; Shock, Septic/mortality ; Shock, Septic/surgery
Chemical Substances	Interleukins ; Interleukin-10 (130068-27-8) ; interleukin 20 (U91R7IMG8U)
Language	English
Publishing date	2018-01-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454158-8
ISSN	1662-8128 ; 1662-811X
ISSN (online)	1662-8128
ISSN	1662-811X
DOI	10.1159/000486104
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Zs.A 6727: Show issues

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Article ; Online: Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.

Novak, Tanya / Crawford, Jeremy Chase / Hahn, Georg / Hall, Mark W / Thair, Simone A / Newhams, Margaret M / Chou, Janet / Mourani, Peter M / Tarquinio, Keiko M / Markovitz, Barry / Loftis, Laura L / Weiss, Scott L / Higgerson, Renee / Schwarz, Adam J / Pinto, Neethi P / Thomas, Neal J / Gedeit, Rainer G / Sanders, Ronald C / Mahapatra, Sidharth /

Coates, Bria M / Cvijanovich, Natalie Z / Ackerman, Kate G / Tellez, David W / McQuillen, Patrick / Kurachek, Stephen C / Shein, Steven L / Lange, Christoph / Thomas, Paul G / Randolph, Adrienne G

Frontiers in immunology

2023 Volume 14, Page(s) 1220028

Abstract: Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.: Methods: We measured RNA ... ...

Abstract	Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation ( Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
MeSH term(s)	Humans ; Multiple Organ Failure/genetics ; Influenza, Human/genetics ; Influenza, Human/complications ; Transcriptome ; Phenotype ; Hospitalization ; Bacterial Infections/complications
Language	English
Publishing date	2023-07-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1220028
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Article ; Online: Identification of a nonsynonymous polymorphism in the SVEP1 gene associated with altered clinical outcomes in septic shock.

Nakada, Taka-aki / Russell, James A / Boyd, John H / Thair, Simone A / Walley, Keith R

Critical care medicine

2015 Volume 43, Issue 1, Page(s) 101–108

Abstract: Objectives: Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified nonsynonymous single-nucleotide polymorphisms in conserved genomic regions that ... ...

Abstract	Objectives: Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified nonsynonymous single-nucleotide polymorphisms in conserved genomic regions that are predicted to have significant effects on protein function. We then test the hypothesis that these nonsynonymous single-nucleotide polymorphisms across the genome alter clinical outcome of septic shock. Design: Genetic-association study plus in vitro experiment using primary cells plus in silico analysis using genomic DNA and protein database. Setting: Twenty-seven ICUs at academic teaching centers in Canada, Australia, and the United States. Patients: Patients with septic shock of European ancestry (n = 520). Interventions: Patients with septic shock were genotyped for 843 nonsynonymous single-nucleotide polymorphisms in conserved regions of the genome and are predicted to have damaging effects from the protein sequence. Measurements and main results: The primary outcome variable was 28-day mortality. Secondary outcome variables were organ dysfunction. Productions of adhesion molecules including interleukin-8, growth-regulated oncogene-α, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3 were measured in human umbilical vein endothelial cells after SVEP1 gene silencing by RNA interference. Patients with septic shock having the SVEP1 C allele of nonsynonymous single-nucleotide polymorphism, SVEP1 c.2080A>C (p. Gln581His, rs10817033), had a significant increase in the hazard of death over the 28 days (hazard ratio, 1.72; 95% CI, 1.31-2.26; p = 9.7 × 10-5) and increased organ dysfunction and needed more organ support (p < 0.05). Silencing SVEP1 significantly increased interleukin-8, growth-regulated oncogene-α, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 production in human umbilical vein endothelial cells under lipopolysaccharide stimulation (p < 0.01). Conclusions: C allele of SVEP1 c.2080A>C (p. Gln581His) single-nucleotide polymorphism, a non-synonymous single-nucleotide polymorphism in conserved regions and predicted to have damaging effects on protein structure, was associated with increased 28-day mortality and organ dysfunction of septic shock. SVEP1 appears to regulate molecules of the leukocyte adhesion pathway.
MeSH term(s)	Aged ; Cell Adhesion Molecules/genetics ; Chemokines/genetics ; Chemokines/physiology ; Conserved Sequence/genetics ; Female ; Genetic Association Studies ; Genome-Wide Association Study ; Humans ; Interleukin-8/blood ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Shock, Septic/blood ; Shock, Septic/genetics ; Shock, Septic/mortality
Chemical Substances	Cell Adhesion Molecules ; Chemokines ; Interleukin-8 ; SVEP1 protein, human
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000000604
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Article ; Online: Cytokines and signaling molecules predict clinical outcomes in sepsis.

Fjell, Christopher D / Thair, Simone / Hsu, Joseph L / Walley, Keith R / Russell, James A / Boyd, John

PloS one

2013 Volume 8, Issue 11, Page(s) e79207

Abstract: Introduction: Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST) compared the addition of ... ...

Abstract	Introduction: Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST) compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment) and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. Hypothesis: Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. Methods: Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. Results: Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. Conclusions: A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from small numbers of cytokines. Design of clinical trials and interventions may benefit from consideration of cytokine levels.
MeSH term(s)	Aged ; Disease-Free Survival ; Double-Blind Method ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/blood ; Hemostatics/administration & dosage ; Humans ; Interleukin-2/blood ; Male ; Middle Aged ; Norepinephrine/administration & dosage ; Predictive Value of Tests ; Risk Factors ; Sepsis/blood ; Sepsis/drug therapy ; Sepsis/mortality ; Survival Rate ; Time Factors ; Vasoconstrictor Agents/administration & dosage ; Vasopressins/administration & dosage
Chemical Substances	Hemostatics ; IL2 protein, human ; Interleukin-2 ; Vasoconstrictor Agents ; Vasopressins (11000-17-2) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2013-11-14
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0079207
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