Publications by authors named "Emanuel P Rivers"

76 Publications

Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study.

Chest 2021 Aug 6. Epub 2021 Aug 6.

Wayne State University, Detroit, MI; Department of Emergency Medicine and Surgery, Henry Ford Hospital, Detroit, MI.

Background: US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness.

Research Question: What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries?

Study Design And Methods: Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay.

Results: We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001).

Interpretation: Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths.
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http://dx.doi.org/10.1016/j.chest.2021.07.2167DOI Listing
August 2021

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.

Crit Care Med 2021 10;49(10):1651-1663

Durham Veterans Affairs Health Care System, Durham, NC.

Objectives: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test.

Design: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results.

Setting: Four U.S. emergency departments.

Patients: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis.

Interventions: Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes.

Measurements And Main Results: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance.

Conclusions: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.
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http://dx.doi.org/10.1097/CCM.0000000000005085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448917PMC
October 2021

Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls.

J Clin Med 2020 Sep 11;9(9). Epub 2020 Sep 11.

Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.

Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30-130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known about how early changes related to exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic profiles of plasma derived exosomes obtained from septic ED patients and healthy controls.

Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood.

Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using fusion mass spectroscopy and Proteome Discoverer. Principal component analysis (PCA) and differential expression analysis (DEA) for sepsis versus control was performed.

Results: PCA of 261 proteins demonstrated septic patients and healthy controls were distributed in two groups. DEA revealed that 62 (23.8%) proteins differed between the exosomes of septic patients and healthy controls, -value < 0.05. Adjustments using the False Discovery Rate (FDR) showed 23 proteins remained significantly different (FDR < 0.05) between sepsis and controls. Septic patients and controls were classified into two distinct groups by hierarchical clustering using the 62 nominally DE proteins. After adjustment multiple comparisons, three acute phase proteins remained significantly different between patients and controls: Serum amyloid A-1, C-reactive protein and Serum Amyloid A-2. Inflammatory response proteins immunoglobulin heavy constant Δ and Fc-fragment of IgG binding protein were increased.

Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation.
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http://dx.doi.org/10.3390/jcm9092930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564089PMC
September 2020

Performance of PCR/Electrospray Ionization-Mass Spectrometry on Whole Blood for Detection of Bloodstream Microorganisms in Patients with Suspected Sepsis.

J Clin Microbiol 2020 08 24;58(9). Epub 2020 Aug 24.

Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States ( = 13) and Europe ( = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and species, 83%. The specificities were >94% for all individual species. Patients who had received prior antimicrobial medications ( = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment-31% versus 22% ( < 0.0001)-with pronounced differences for Gram-negative bacteria and species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics to be used with whole blood for detection of bloodstream microorganisms in sepsis.
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http://dx.doi.org/10.1128/JCM.01860-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448645PMC
August 2020

A Physiologic Approach to Hemodynamic Monitoring and Optimizing Oxygen Delivery in Shock Resuscitation.

J Clin Med 2020 Jun 30;9(7). Epub 2020 Jun 30.

Division of Pulmonary, Critical Care, Hyperbaric, Allergy, and Sleep Medicine, Loma Linda University, Loma Linda, CA 92354, USA.

The approach to shock resuscitation focuses on all components of oxygen delivery, including preload, afterload, contractility, hemoglobin, and oxygen saturation. Resuscitation focused solely on preload and fluid responsiveness minimizes other key elements, resulting in suboptimal patient care. This review will provide a physiologic and practical approach for the optimization of oxygen delivery utilizing available hemodynamic monitoring technologies. Venous oxygen saturation (SvO) and lactate will be discussed as indicators of shock states and endpoints of resuscitation within the framework of resolving oxygen deficit and oxygen debt.
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http://dx.doi.org/10.3390/jcm9072052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408843PMC
June 2020

F-Actin is associated with a worsening qSOFA score and intensive care unit admission in emergency department patients at risk for sepsis.

Biomarkers 2020 Jul 1;25(5):391-396. Epub 2020 Jun 1.

Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.

We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls and may serve as biomarkers for the diagnosis of sepsis. The current study aims to determine if these proteins are associated with or predictive of illness severity in patients at risk for sepsis in the Emergency Department (ED). Prospective, biomarker study enrolling patients (>18 years) who met the Shock Precautions on Triage Sepsis rule placing them at-risk for sepsis. In this study of 203 ED patients, F-actin plasma levels had a linear trend of increase when the quick Sequential Organ Failure Assessment (qSOFA) score increased. F-actin was also increased in patients who were admitted to the Intensive Care Unit (ICU) from the ED, and in those with positive urine cultures. Thymosin Beta 4 was not associated with or predictive of any significant outcome measures. Increased levels of plasma F-actin measured in the ED were associated with incremental illness severity as measured by the qSOFA score and need for ICU admission. F-actin may have utility in risk stratification of undifferentiated patients in the ED presenting with signs and symptoms of sepsis.
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http://dx.doi.org/10.1080/1354750X.2020.1771419DOI Listing
July 2020

Centers for Medicare and Medicaid Services Measure Stewards' Assessment of the Infectious Diseases Society of America's Position Paper on SEP-1.

Clin Infect Dis 2021 02;72(4):553-555

Center for Clinical Standards and Quality, Centers for Medicare and Medicaid Services, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1093/cid/ciaa458DOI Listing
February 2021

Early High-Dose Vitamin D for Critically Ill, Vitamin D-Deficient Patients.

N Engl J Med 2019 12 11;381(26):2529-2540. Epub 2019 Dec 11.

The affiliations of the members of the writing committee are as follows: the Department of Emergency Medicine, University of Colorado School of Medicine, Aurora (A.A.G., L.F.); the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (R.G.B.); the Department of Emergency Medicine, Ohio State University, Columbus (J.M.C.); the Departments of Anesthesia, Critical Care, and Pain Medicine (V.M.B.-G., D.T.) and Emergency Medicine (N.I.S.), Beth Israel Deaconess Medical Center, and the Biostatistics Center (D.H.) and the Department of Medicine (N.R., B.T.T.), Massachusetts General Hospital - all in Boston; the Department of Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City (C.K.G.); the Department of Medicine, University of Washington, Seattle (C.L.H.); the Departments of Medicine (R.C.H.) and Surgery (P.K.P.), University of Michigan, Ann Arbor; the Department of Emergency Medicine and Surgery, Henry Ford Hospital, Detroit (E.P.R.); the Department of Medicine, Oregon Health and Science University, Portland (A.K.); the Department of Medicine, Stanford University, Palo Alto, CA (J.E.L.); the Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville (W.H.S.); and the Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh (D.M.Y.).

Background: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D or matched placebo. The primary end point was 90-day all-cause, all-location mortality.

Results: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.

Conclusions: Early administration of high-dose enteral vitamin D did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).
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http://dx.doi.org/10.1056/NEJMoa1911124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306117PMC
December 2019

Validation of a host response test to distinguish bacterial and viral respiratory infection.

EBioMedicine 2019 Oct 17;48:453-461. Epub 2019 Oct 17.

Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA. Electronic address:

Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases.

Methods: Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin.

Findings: 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02).

Interpretation: The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.
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http://dx.doi.org/10.1016/j.ebiom.2019.09.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838360PMC
October 2019

Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis.

J Intensive Care 2018 13;6:72. Epub 2018 Nov 13.

1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA.

Background: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes.

Methods: The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated.

Results: Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74.

Conclusions: To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool.
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http://dx.doi.org/10.1186/s40560-018-0341-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234551PMC
November 2018

Thymosin beta 4 regulation of actin in sepsis.

Expert Opin Biol Ther 2018 07 6;18(sup1):193-197. Epub 2018 Mar 6.

f Department of Emergency Medicine , Henry Ford Hospital , Detroit , MI , USA.

Introduction: Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. Thymosin Beta 4 decreases inflammatory mediators, lowers reactive oxygen species, up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis.

Areas Covered: The authors summarize the current knowledge of actin and Thymosin Beta 4 as it relates to sepsis via a comprehensive literature search.

Expert Opinion: Sepsis results in measurable levels of F-actin in the circulation as well as a decreased concentration of Thymosin Beta 4. It is speculated that F-actinemia contributes to microcirculatory perturbations present in patients with sepsis by disturbing laminar flow. Given that Thymosin Beta 4 inhibits the polymerization of F-actin, it is possible that Thymosin Beta 4 decreases mortality in sepsis via the regulation of actin as well as its other anti-inflammatory properties and should be further pursued as a clinical trial in humans with sepsis.
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http://dx.doi.org/10.1080/14712598.2018.1448381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556887PMC
July 2018

Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease.

Ann Emerg Med 2018 06 6;71(6):737-742. Epub 2017 Nov 6.

Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI; Department of Surgery, Henry Ford Hospital, Wayne State University, Detroit, MI.

Study Objective: Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels.

Methods: This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions.

Results: The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L.

Conclusion: The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED.
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http://dx.doi.org/10.1016/j.annemergmed.2017.09.022DOI Listing
June 2018

Early Liberal Fluid Therapy for Sepsis Patients Is Not Harmful: Hydrophobia Is Unwarranted but Drink Responsibly.

Crit Care Med 2016 12;44(12):2263-2269

1Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI.2Department of Surgery, Henry Ford Hospital, Detroit, MI.

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http://dx.doi.org/10.1097/CCM.0000000000002145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113226PMC
December 2016

Protocolized care for early shock resuscitation.

Curr Opin Crit Care 2016 10;22(5):416-23

aDepartment of SurgerybDepartment of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, Michigan, USA.

Purpose Of Review: Protocolized care for early shock resuscitation (PCESR) has been intensely examined over the last decade. The purpose is to review the pathophysiologic basis, historical origin, clinical applications, components and outcome implications of PCESR.

Recent Findings: PCESR is a multifaceted systems-based approach that includes early detection of high-risk patients and interventions to rapidly reverse hemodynamic perturbations that result in global or regional tissue hypoxia. It has been applied to perioperative surgery, trauma, cardiology (heart failure and acute myocardial infarction), pulmonary embolus, cardiac arrest, undifferentiated shock, postoperative cardiac surgery and pediatric septic shock. When this approach is used for adult septic shock, in particular, it is associated with a mortality reduction from 46.5 to less than 30% over the last 2 decades. Challenges to these findings are seen when repeated trials contain enrollment, diagnostic and therapeutic methodological differences.

Summary: PCESR is more than a hemodynamic optimization procedure. It also provides an educational framework for the less experienced and objective recognition of clinical improvement or deterioration. It further minimizes practices' variation and provides objective measures that can be audited, evaluated and amendable to continuous quality improvement. As a result, morbidity and mortality are improved.
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http://dx.doi.org/10.1097/MCC.0000000000000346DOI Listing
October 2016

Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

Crit Care 2016 Jul 1;20(1):160. Epub 2016 Jul 1.

Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.
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http://dx.doi.org/10.1186/s13054-016-1288-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929762PMC
July 2016

Relationship between Central and Peripheral Venous Oxygen Saturation and Lactate Levels: A Prospective Study.

J Emerg Med 2016 Jun 19;50(6):809-17. Epub 2016 May 19.

Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan; Department of Surgery, Henry Ford Health System, Detroit, Michigan.

Background: Optimization of tissue oxygen delivery to meet consumption demands is important in the resuscitation of critically ill patients. Central venous oxygen saturation (ScvO2) and lactate levels are often used to guide resuscitation; however, invasive monitoring is required for the former. Clinicians searching for less invasive alternatives may consider using peripheral venous oxygen saturation (SpvO2) and lactate levels as a substitute.

Objectives: To determine the relationship between SpvO2 and ScvO2 and peripheral and central lactate levels.

Methods: All patients with a central venous catheter in an academic emergency department and intensive care unit were eligible for the study. Blood was obtained simultaneously from a central and peripheral vein and measured for oxygen saturation and lactate levels. Results were analyzed using intraclass correlation coefficient (ICC), Bland-Altman plots, and receiver operating characteristic curves.

Results: Seventy-nine paired blood samples were analyzed. SpvO2 and ScvO2 have moderate agreement: ICC = 0.53 (95% confidence interval [CI] 0.35-0.67). A Bland-Altman plot revealed substantial bias (-4.47; limits of agreement -38.6, 29.6). SpvO2 ≥ 85% was 90% specific for ScvO2 ≥ 70%, and SpvO2 of ≤ 55% had a 94% sensitivity for ScvO2 < 70%. Central and peripheral venous lactate levels showed almost perfect agreement: ICC = 0.92 (95% CI 0.87-0.95), bias of 0.46 (limits of agreement -1.78-2.70).

Conclusion: SpvO2 and ScvO2 have moderate agreement. There was excellent agreement between peripheral and central lactate levels, making them interchangeable. The clinical implications of these substitutions in real-time patient management require further study.
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http://dx.doi.org/10.1016/j.jemermed.2016.03.021DOI Listing
June 2016

The association between blood glucose levels and matrix-metalloproteinase-9 in early severe sepsis and septic shock.

J Inflamm (Lond) 2016 22;13:13. Epub 2016 Apr 22.

Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202 USA.

Background: Hyperglycemia is a frequent and important metabolic derangement that accompanies severe sepsis and septic shock. Matrix-Metalloproteinase 9 (MMP-9) has been shown to be elevated in acute stress hyperglycemia, chronic hyperglycemia, and in patient with sepsis. The objective of this study was to examine the clinical and pathogenic link between MMP-9 and blood glucose (BG) levels in patients with early severe sepsis and septic shock.

Methods: We prospectively examined 230 patients with severe sepsis and septic shock immediately upon hospital presentation and before any treatment including insulin administration. Clinical and laboratory data were obtained along with blood samples for the purpose of this study. Univariate tests for mean and median distribution using Spearman correlation and analysis of variance (ANOVA) were performed. A p value ≤ 0.05 was considered statistically significant.

Results: Patients were grouped based on their presenting BG level (mg/dL): BG <80 (n = 32), 80-120 (n = 53), 121-150 (n = 38), 151-200 (n = 23), and > 201 (n = 84). Rising MMP-9 levels were significantly associated with rising BG levels (p = 0.043). A corresponding increase in the prevalence of diabetes for each glucose grouping from 6.3 to 54.1 % (p = 0.0001) was also found. As MMP-9 levels increased a significantly (p < 0.001) decreases in IL-8 (pg/mL) and ICAM-1 (ng/mL) were noted.

Conclusion: This is the first study in humans demonstrating a significant and early association between MMP-9 and BG levels in in patients with severe sepsis and septic shock. Neutrophil affecting biomarkers such as IL-8 and ICAM-1 are noted to decrease as MMP-9 levels increase. Clinical risk stratification using MMP-9 levels could potentially help determine which patients would benefit from intensive versus conventional insulin therapy. In addition, antagonizing the up-regulation of MMP-9 could serve as a potential treatment option in severe sepsis or septic shock patients.
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http://dx.doi.org/10.1186/s12950-016-0122-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840979PMC
April 2016

Host gene expression classifiers diagnose acute respiratory illness etiology.

Sci Transl Med 2016 Jan;8(322):322ra11

Center for Applied Genomics & Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708.

Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.
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http://dx.doi.org/10.1126/scitranslmed.aad6873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905578PMC
January 2016

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

Biomarkers 2016 12;21(2):180-5. Epub 2016 Jan 12.

b Department of Emergency Medicine , Henry Ford Hospital , Detroit , MI , USA .

Objective: To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls.

Results: F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml).

Conclusions: F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.
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http://dx.doi.org/10.3109/1354750X.2015.1126646DOI Listing
December 2016

Oxygen extraction and perfusion markers in severe sepsis and septic shock: diagnostic, therapeutic and outcome implications.

Curr Opin Crit Care 2015 Oct;21(5):381-7

aDepartment of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, Michigan bDepartment of Internal Medicine, Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, Kentucky, USA.

Purpose Of Review: The purpose of this study is to review the recent literature examining the clinical utility of markers of systemic oxygen extraction and perfusion in the diagnosis, treatment and prognosis of severe sepsis and septic shock.

Recent Findings: When sepsis is accompanied by conditions in which systemic oxygen delivery does not meet tissue oxygen demands, tissue hypoperfusion begins. Tissue hypoperfusion leads to oxygen debt, cellular injury, organ dysfunction and death. Tissue hypoperfusion can be characterized using markers of tissue perfusion (central venous oxygen saturation and lactate), which reflect the interaction between systemic oxygen delivery and demands. For the last two decades, studies and quality initiatives incorporating the early detection and interruption of tissue hypoperfusion have been shown to improve mortality and altered sepsis care. Three recent trials, while confirming an all-time improvement in sepsis mortality, challenged the concept that rapid normalization of markers of perfusion confers outcome benefit. By defining and comparing haemodynamic phenotypes using markers of tissue perfusion, we may better understand which patients are more likely to benefit from early goal-directed haemodynamic optimization.

Summary: The phenotypic haemodynamic characterization of patients using perfusion markers has diagnostic, therapeutic and outcome implications in severe sepsis and septic shock. However, irrespective of haemodynamic phenotype, the outcome reflects the quality of care provided at the point of presentation. Utilizing these principles may allow more objective interpretation of resuscitation trials and translate these findings into current practice.
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http://dx.doi.org/10.1097/MCC.0000000000000241DOI Listing
October 2015

Renal systems biology of patients with systemic inflammatory response syndrome.

Kidney Int 2015 Oct 20;88(4):804-14. Epub 2015 May 20.

National Center for Genome Resources, Santa Fe, New Mexico, USA.

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.
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http://dx.doi.org/10.1038/ki.2015.150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591107PMC
October 2015

An integrated transcriptome and expressed variant analysis of sepsis survival and death.

Genome Med 2014 26;6(11):111. Epub 2014 Nov 26.

National Center for Genome Resources, Santa Fe, NM 87505 USA ; Department of Pediatrics, Center for Translational Sciences, University of New Mexico, Albuquerque, NM 87131 USA.

Background: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality.

Methods: The Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (SIRS due to infection), including 78 sepsis survivors and 28 sepsis non-survivors who had previously undergone plasma proteomic and metabolomic profiling. Gene expression differences were identified between sepsis survivors, sepsis non-survivors, and SIRS followed by gene enrichment pathway analysis. Expressed sequence variants were identified followed by testing for association with sepsis outcomes.

Results: The expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflecting immune activation in sepsis. Expression of 1,238 genes differed with sepsis outcome: non-survivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease-rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors. The presence of variants was associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology.

Conclusions: The activation of immune response-related genes seen in sepsis survivors was muted in sepsis non-survivors. The association of sepsis survival with a robust immune response and the presence of missense variants in VPS9D1 warrants replication and further functional studies.

Trial Registration: ClinicalTrials.gov NCT00258869. Registered on 23 November 2005.
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http://dx.doi.org/10.1186/s13073-014-0111-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274761PMC
December 2014

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

Am J Respir Crit Care Med 2014 Aug;190(4):445-55

1 Respiratory Immunology Program.

Rationale: Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis.

Objectives: To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis.

Methods: Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers.

Measurements And Main Results: The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82).

Conclusions: A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.
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http://dx.doi.org/10.1164/rccm.201404-0624OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214130PMC
August 2014

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

Shock 2014 Aug;42(2):99-107

*Department of Emergency Medicine, University of Colorado School of Medicine; and †Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado; ‡Department of Emergency Medicine, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, New Jersey; §Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ∥New York Methodist Hospital, Brooklyn; and Weill Cornell Medical Center, New York, New York; ¶Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan; **Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; ††Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; ‡‡Departments of Emergency Medicine and Medicine, Loma Linda University Medical Center, Loma Linda, California; §§Departments of Anesthesiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan; ∥∥Departments of Emergency Medicine, and ¶¶Internal Medicine, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, District of Columbia; ***Department of Emergency Medicine, University of North Carolina, Chapel Hill, North Carolina; †††Department of Emergency Medicine, Wayne State University, Detroit, Michigan; and ‡‡‡Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.
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http://dx.doi.org/10.1097/SHK.0000000000000182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101036PMC
August 2014

A cost-effective analysis of postoperative goal-directed therapy for high-risk surgical patients: improved outcomes are not enough … you have to "show me the money".

Crit Care Med 2014 May;42(5):1311-2

Department of Surgery and Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI Department of Anesthesiology, Henry Ford Hospital, Wayne State University, Detroit, MI Department of Anesthesiology, Cleveland Clinic, Cleveland, OH.

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http://dx.doi.org/10.1097/CCM.0000000000000272DOI Listing
May 2014

Metabolomic derangements are associated with mortality in critically ill adult patients.

PLoS One 2014 30;9(1):e87538. Epub 2014 Jan 30.

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America.

Objective: To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults.

Rationale: Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.

Methods: We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study.

Results: We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations).

Conclusion: Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087538PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907548PMC
September 2014

The incidence and significance of bacteremia in out of hospital cardiac arrest.

Resuscitation 2014 Feb 12;85(2):196-202. Epub 2013 Oct 12.

Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, United States; Department of Surgery, Henry Ford Hospital, Detroit, MI, United States.

Background: The most common etiology of cardiac arrest is presumed of myocardial origin. Recent retrospective studies indicate that preexisting pneumonia, a form of sepsis, is frequent in patients who decompensate with abrupt cardiac arrest without preceding signs of septic shock, respiratory failure or severe metabolic disorders shortly after hospitalization. The contribution of pre-existing infection on pre and post cardiac arrest events remains unknown and has not been studied in a prospective fashion. We sought to examine the incidence of pre-existing infection in out-of hospital cardiac arrest (OHCA) and assess characteristics associated with bacteremia, the goal standard for presence of infection.

Methods And Results: We prospectively observed 250 OHCA adult patients who presented to the Emergency Department (ED) between 2007 and 2009 to an urban academic teaching institution. Bacteremia was defined as one positive blood culture with non-skin flora bacteria or two positive blood cultures with skin flora bacteria. 77 met pre-defined exclusion criteria. Of the 173 OHCA adults, 65 (38%) were found to be bacteremic with asystole and PEA as the most common presenting rhythms. Mortality in the ED was significantly higher in bacteremic OHCA (75.4%) compared to non-bacteremic OHCA (60.2%, p<0.05). After adjustment for potential confounders, predictive factors associated with bacteremic OHCA were lower initial arterial pH, higher lactate, WBC, BUN and creatinine.

Conclusions: Over one-third of OHCA adults were bacteremic upon presentation. These patients have greater hemodynamic instability and significantly increased short-term mortality. Further studies are warranted to address the epidemiology of infection as possible cause of cardiac arrest.
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http://dx.doi.org/10.1016/j.resuscitation.2013.09.022DOI Listing
February 2014

"I Can't Walk!" Acute Thrombosis of Descending Aorta Causing Paraplegia.

West J Emerg Med 2013 Sep;14(5):424-7

Henry Ford Hospital, Department of Emergency Medicine, Detroit, Michigan.

A 50-year-old man presented to the emergency department (ED) with acute, bilateral lower extremity weakness and loss of sensation, as well as absent pulses bilaterally. Computed tomography angiography showed complete occlusion of the aorta below the inferior mesenteric artery, extending to the iliac bifurcations. Echocardiographic findings showed severe systolic dysfunction (ejection fraction of 15%) and cryptic cardiogenic shock in spite of stable vital signs. Prior to early operative intervention, an early goal-oriented hemodynamic strategy of shock management resulted in the resolution of motor and sensory deficits.After definitive surgical intervention, the patient was discharged neurologically intact. Acute aortic occlusion is frequently accompanied by myocardial dysfunction, which can be from mild to severe. The most severe form can even occur with normal vital signs or occult cardiogenic shock. Early detection and goal-directed preoperative hemodynamic optimization, along with surgical intervention in the ED, is required to optimize outcomes.
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http://dx.doi.org/10.5811/westjem.2013.2.15836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789898PMC
September 2013

A host-based RT-PCR gene expression signature to identify acute respiratory viral infection.

Sci Transl Med 2013 Sep;5(203):203ra126

Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC 27710, USA.

Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.
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http://dx.doi.org/10.1126/scitranslmed.3006280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286889PMC
September 2013
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