DOCSLIB.ORG

Biomarkers and Disease Severity in Children with Community-Acquired Pneumonia Todd A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biomarkers and Disease Severity in Children with Community-Acquired Pneumonia Todd A Biomarkers and Disease Severity in Children With Community-Acquired Pneumonia Todd A. Florin, MD, MSCE,a Lilliam Ambroggio, PhD, MPH,b Cole Brokamp, PhD,c,d Yin Zhang, MS,c,d Mantosh Rattan, MD,e,f Eric Crotty, MD,e,f Michael A. Belsky, MS,g Sara Krueger, BA,f Thomas N. Epperson, IV, BA,h Andrea Kachelmeyer, BS,d,i Richard Ruddy, MD,d,i Samir S. Shah, MD, MSCEd,j BACKGROUND: Host biomarkers predict disease severity in adults with community-acquired abstract pneumonia (CAP). We evaluated the association of the white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), and procalcitonin with the development of severe outcomes in children with CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years of age with CAP in the emergency department. The primary outcome was disease severity: mild (discharged from the hospital), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with receipt of intravenous fluids, supplemental oxygen, complicated pneumonia), and severe (eg, intensive care, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of 477 children, there were no statistical differences in the median WBC count, ANC, CRP, or procalcitonin across severity categories. No biomarker had adequate discriminatory ability between severe and nonsevere disease (area under the curve [AUC]: 0.53–0.6 for suspected CAP and 0.59–0.64 for radiographic CAP). In analyses adjusted for age, antibiotic use, fever duration, and viral pathogen detection, CRP was associated with moderate-severe disease (odds ratio 1.12; 95% confidence interval, 1.0–1.25). CRP and procalcitonin revealed good discrimination of children with empyema requiring chest drainage (AUC: 0.83) and sepsis with vasoactive infusions (CRP AUC: 0.74; procalcitonin AUC: 0.78), although prevalence of these outcomes was low. CONCLUSIONS: WBC count, ANC, CRP, and procalcitonin are generally not useful to discriminate nonsevere from severe disease in children with CAP, although CRP and procalcitonin may have some utility in predicting the most severe outcomes. WHAT’S KNOWN ON THIS SUBJECT: Prognostic tools are limited for children aDepartment of Pediatrics, Feinberg School of Medicine, Northwestern University and Division of Emergency with community-acquired pneumonia (CAP). Host biomarkers, including Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; bDepartment of Pediatrics, C-reactive protein (CRP) and procalcitonin, have been shown to be ’ University of Colorado and Sections of Emergency Medicine and Hospital Medicine, Childrens Hospital Colorado, associated with severe clinical outcomes in adults with CAP. Data in children c i j Aurora, Colorado; Divisions of Biostatistics and Epidemiology, Emergency Medicine, and Hospital Medicine and are limited. Infectious Diseases and eDepartment of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; dDepartment of Pediatrics, fCollege of Medicine, University of Cincinnati, Cincinnati, Ohio; gSchool of Medicine, WHAT THIS STUDY ADDS: White blood cell count, CRP, and procalcitonin are University of Pittsburgh, Pittsburgh, Pennsylvania; and hSchool of Medicine, University of Louisville, Louisville, generally not useful to discriminate overall disease severity in children with Kentucky CAP. CRP and procalcitonin may have utility in predicting the most severe outcomes, but research is necessary to validate these findings. Dr Florin conceptualized and designed the study, supervised participant enrollment and data acquisition, performed the statistical analysis and interpreted the data, and drafted the initial To cite: Florin TA, Ambroggio L, Brokamp C, et al. manuscript; Dr Ambroggio conceptualized and designed the study, supervised participant Biomarkers and Disease Severity in Children With enrollment and data acquisition, and participated in data interpretation; (Continued) Community-Acquired Pneumonia. Pediatrics. 2020;145(6): e20193728 Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 145, number 6, June 2020:e20193728 ARTICLE Community-acquired pneumonia (CARPE DIEM) study was parent by using a structured (CAP) is one of the most common a prospective cohort study of children questionnaire. Clinicians completed serious infections in children, resulting aged 3 months to 18 years who a case report form assessing clinical in a substantial number of emergency presented to the ED with signs and signs and severity impressions. Blood, department (ED) visits and symptoms of lower respiratory tract urine, and/or nasopharyngeal swabs hospitalizations.1 Accurate assessment infection (LRTI) and received a chest were collected at enrollment from of disease severity is essential to radiograph (CXR) for clinical those who consented to collection of clinical decision-making. Although the suspicion of CAP. The study was each specimen type. Complete blood site-of-care decision is one of the most approved by the Cincinnati Children’s cell count, CRP and procalcitonin important in the management of CAP, Hospital Medical Center (CCHMC) assays were performed within 1 hour there are no validated prognostic tools Institutional Review Board. Written after blood collection. Clinicians to assist with this determination. informed consent was obtained from caring for enrolled patients were Biomarkers reflecting the host’s all legal guardians, and assent was blinded to all study laboratory test $ response to an infection offer an obtained from children 11 years results, with the exception of values objective measure of disease severity of age. from the complete blood cell count that warranted immediate action (eg, that may improve prognostication of For this analysis, we included low hemoglobin level). Clinicians did children with CAP. The white blood children aged 3 months to 18 years not have access to CRP or cell (WBC) count and absolute with signs and symptoms of LRTI procalcitonin test results in all cases. neutrophil count (ANC) are often who presented to the CCHMC ED Clinical data, including vital signs, evaluated in children with CAP; from July 2013 to December 2017, medications, and interventions, were however, WBC count was not had focal findings on a CXR indicating extracted from the electronic medical associated with disease severity in 1 suspected CAP (defined as CXRs with record. Patients received a follow-up study of children who were focal opacities documented by the 2,3 phone call ∼7 to 15 days after they hospitalized. C-reactive protein (CRP) radiologist during the ED visit), and were discharged from the ED or is an acute-phase reactant produced in had blood drawn. LRTI was defined hospital to assess disease course. response to interleukin-6, an as $1 of the following: new or 4 inflammatory cytokine. Procalcitonin, different cough or sputum Given the variation in CXR a116–amino acid precursor of production, chest pain, dyspnea, interpretation, a subset of the cohort calcitonin, is barely detectable in the tachypnea, or abnormal auscultatory with suspected CAP was defined as blood of healthy individuals but findings.16 We excluded children having radiographic CAP, which was increases in response to severe hospitalized for #14 days before the defined on the basis of the bacterial infection, sepsis, and multiple- index ED visit, those with a history of evaluations of 2 independent study 5 organ dysfunction. Both CRP and aspiration or aspiration pneumonia, radiologists blinded to clinical procalcitonin have been studied as and those with information after the study visit. a means of differentiating viral from immunocompromising or chronic Radiographs were classified as bacterial etiology; less work has been medical conditions that predispose to normal, definite/probable atelectasis, done to understand their prognostic severe or recurrent pneumonia (eg, atelectasis versus pneumonia, or abilities. Studies in adults with CAP immunodeficiency, chronic definite/probable pneumonia. have revealed that these markers are corticosteroid use, chronic lung Radiographic CAP was defined as 6–10 associated with disease severity but disease, malignancy, sickle cell both radiologists classifying CXR 11–15 data in children remain limited. disease, congenital heart disease, findings as atelectasis versus Our objective for this study was to patients dependent on tracheostomy, pneumonia or definite/probable 17 evaluate the association of these host and neuromuscular disorders pneumonia. In cases of biomarkers with the development of impacting respiration). Patients disagreement, the attending severe outcomes in a prospective enrolled within 30 days before the ED radiologist’s reading from the ED visit cohort of children with CAP. visit were excluded to ensure was used as a tiebreaker. If there was a distinct infection episode. persistent disagreement, consensus was reached during an in-person METHODS Study Procedures meeting with the study radiologists. Study Design, Setting, and Potential participants were identified Participants by trained research coordinators. Outcome Measurements The Catalyzing Ambulatory Research After informed consent, demographic The primary outcome, assessed after in Pneumonia Etiology and Diagnostic and historical information were the ED visit, was disease severity. Innovations in Emergency Medicine obtained from the patient and/or Mild disease was defined
Load more

Recommended publications
  • Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma
    International Journal of Molecular Sciences Article Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma Chang-Kyu Heo 1, Hai-Min Hwang 1, Won-Hee Lim 1,2, Hye-Jung Lee 3, Jong-Shin Yoo 4, Kook-Jin Lim 3 and Eun-Wie Cho 1,2,* 1 Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea; [email protected] (C.-K.H.); [email protected] (H.-M.H.); [email protected] (W.-H.L.) 2 Department of Functional Genomics, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea 3 ProteomeTech Inc. 401, Yangcheon-ro, Gangseo-gu, Seoul 07528, Korea; [email protected] (H.-J.L.); [email protected] (K.-J.L.) 4 Biomedical Omics Group, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongju, Chungbuk 28119, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-42-860-4155 Received: 12 November 2020; Accepted: 16 December 2020; Published: 19 December 2020 Abstract: Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC.
    [Show full text]
  • Positron Emission Tomography (PET) and Neuroimaging in the Personalized Approach to Neurodegenerative Causes of Dementia
    International Journal of Molecular Sciences Review Positron Emission Tomography (PET) and Neuroimaging in the Personalized Approach to Neurodegenerative Causes of Dementia Maria Ricci 1,* , Andrea Cimini 1 , Agostino Chiaravalloti 1,2, Luca Filippi 3 and Orazio Schillaci 1,2 1 Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; [email protected] (A.C.); [email protected] (A.C.); [email protected] (O.S.) 2 Nuclear Medicine Section, IRCCS Neuromed, 86077 Pozzilli, Italy 3 Nuclear Medicine Section, “Santa Maria Goretti” Hospital, 04100 Latina, Italy; lucfi[email protected] * Correspondence: [email protected] Received: 17 September 2020; Accepted: 8 October 2020; Published: 11 October 2020 Abstract: Generally, dementia should be considered an acquired syndrome, with multiple possible causes, rather than a specific disease in itself. The leading causes of dementia are neurodegenerative and non-neurodegenerative alterations. Nevertheless, the neurodegenerative group of diseases that lead to cognitive impairment and dementia includes multiple possibilities or mixed pathologies with personalized treatment management for each cause, even if Alzheimer’s disease is the most common pathology. Therefore, an accurate differential diagnosis is mandatory in order to select the most appropriate therapy approach. The role of personalized assessment in the treatment of dementia is rapidly growing. Neuroimaging is an essential tool for differential diagnosis of multiple causes of dementia and allows a personalized diagnostic and therapeutic protocol based on risk factors that may improve treatment management, especially in early diagnosis during the prodromal stage. The utility of structural and functional imaging could be increased by standardization of acquisition and analysis methods and by the development of algorithms for automated assessment.
    [Show full text]
  • Biomarker Discovery: an Array of Potential
    Sponsored By: Custom Publishing From: BIOMARKER DISCOVERY: AN ARRAY OF POTENTIAL Page 3 Page 4 Page 5 Page 6 Candidate Screening: Journey of a A Multiplexed Overcoming Low Abundance with Biomarker Candidate Approach Bottlenecks in High Sensitivity Cancer Treatment BROADEN YOUR PERSPECTIVE See up to 2000 proteins at a glance. The RayBio® L2000 Array Our largest antibody array to date: includes 2000 human proteins on your choice of glass slide or membrane support. Explore an extensive panel of metabolic enzymes, structural proteins, epigenetic markers, hormones, and neuroregulatory factors – in addition to our popular list of cytokines, growth factors, receptors, adipokines, proteases, and signaling proteins. Ideal for biomarker discovery studies and exploratory screens. Available as an easy-to-use kit or a full service. Get more out of your sample. RayBiotech Learn more R Empowering your proteomics 1.888.494.8555 / RAYBIOTECH.COM / ISO 13485:2016 BIOMARKER DISCOVERY: AN ARRAY OF POTENTIAL Candidate Screening: Low Abundance with High Sensitivity hen processes regulating life – such as growth, of mass spectrometry instruments. Large-panel arrays allow reproduction, and movement – go awry, disease researchers with modest budgets to screen for hundreds Wcan result. Chemical moieties become imbalanced of potential biomarkers, including cytokines, chemokines, in these disease states, often resulting in measurable levels of and other secreted molecules that could be missed through certain signature molecules, termed biomarkers. Biomarker traditional proteomics approaches. discovery has traditionally been performed through A Streamlined Workflow: From Discovery to proteomic approaches. However, these techniques have been limited in their ability to detect low abundance molecules. Validation Moreover, they are generally unable to scan for chemokines, Once thought of as being too narrow in scope for the biomarker cytokines, growth factors, and other secreted molecules.
    [Show full text]
  • Imaging As a Personalized Biomarker for Prostate Cancer Risk Stratification
    diagnostics Review Imaging as a Personalized Biomarker for Prostate Cancer Risk Stratification Kyle H. Gennaro 1, Kristin K. Porter 2 , Jennifer B. Gordetsky 1,3, Samuel J. Galgano 2 and Soroush Rais-Bahrami 1,2,* 1 Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] (K.H.G.); [email protected] (J.B.G.) 2 Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] (K.K.P.); [email protected] (S.J.G.) 3 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA * Correspondence: [email protected] Received: 12 September 2018; Accepted: 15 November 2018; Published: 30 November 2018 Abstract: Biomarkers provide objective data to guide clinicians in disease management. Prostate-specific antigen serves as a biomarker for screening of prostate cancer but has come under scrutiny for detection of clinically indolent disease. Multiple imaging techniques demonstrate promising results for diagnosing, staging, and determining definitive management of prostate cancer. One such modality, multiparametric magnetic resonance imaging (mpMRI), detects more clinically significant disease while missing lower volume and clinically insignificant disease. It also provides valuable information regarding tumor characteristics such as location and extraprostatic extension to guide surgical planning. Information from mpMRI may also help patients avoid unnecessary biopsies in the future. It can also be incorporated into targeted biopsies as well as following patients on active surveillance. Other novel techniques have also been developed to detect metastatic disease with advantages over traditional computer tomography and magnetic resonance imaging, which primarily rely on defined size criteria.
    [Show full text]
  • Biomarker Terminology: Speaking the Same Language
    BIOMARKER QUALIFICATION PROGRAM EDUCATIONAL MODULE SERIES—MODULE 1 BIOMARKER TERMINOLOGY: SPEAKING THE SAME LANGUAGE Shashi Amur, Ph.D. Scientific Lead, Biomarker Qualification Program, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA www.fda.gov BEST Resource: Harmonizing Terminology • Created by the NIH-FDA Biomarker Working Group • A glossary of terminology and uses of biomarkers and endpoints in basic biomedical research, medical product development, and clinical care Available at: http://www.ncbi.nlm.nih.gov/books/NBK326791/ www.fda.gov BIOMARKER TERMINOLOGY • Definition of a Biomarker • Types of Biomarkers • Categories of Biomarkers • Biomarker Validation • Biomarker Qualification • Context of Use www.fda.gov WHAT IS A BIOMARKER? A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Types: Molecular, histologic, radiographic, and physiologic characteristics are types of biomarkers. Examples: • Blood glucose (molecular) • Tumor size (radiographic) • Blood pressure (physiologic) www.fda.gov DIFFERENT CATEGORIES OF BIOMARKERS www.fda.gov PROGNOSTIC BIOMARKERS Can be used to select patients with greater likelihood of having a disease-related endpoint event or a substantial worsening in condition in clinical trials. For example: Total kidney volume, to select patients with autosomal dominant polycystic kidney disease at high risk for progressive decline in renal function
    [Show full text]
  • Multibiomarker Disease Activity Blood Test for Rheumatoid Arthritis
    FEP 2.04.119 Multibiomarker Disease Activity Blood Test for Rheumatoid Arthritis FEP Medical Policy Manual FEP 2.04.119 Multibiomarker Disease Activity Blood Test for Rheumatoid Arthritis Related Policies: Effective Policy Date: October 2020 None Original Policy Date: September 2014 Multibiomarker Disease Activity Blood Test for Rheumatoid Arthritis Description Description Assessment of disease activity in rheumatoid arthritis is an important component of management with a goal of treatment to maintain low disease activity or achieve remission. There are a variety of instruments for measuring rheumatoid arthritis disease activity. The instruments use combinations of physical exam findings, radiologic results, and serum biomarkers to construct a disease activity score. A multibiomarker disease activity instrument is a disease activity measure that is comprised entirely of serum biomarkers. The Vectra test is a commercially available multibiomarker disease activity blood test that measures 12 biomarkers to construct a disease activity score. Concentrations of these 12 biomarkers are entered into a proprietary formula which, after adjustment by age, gender and adiposity (i.e., leptin) levels, generates a disease activity score ("adjusted MBDA score") that ranges from 1 (low disease activity) to 100 (high disease activity). OBJECTIVE The objective of this evidence review is to determine whether the use of a multibiomarker disease activity (eg, Vectra) blood test as an adjunct or as a replacement of other disease activity measures improves the net health outcome in individuals with rheumatoid arthritis. The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are not intended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member.
    [Show full text]
  • The Variability of Functional MRI Brain Signal Increases in Alzheimer's
    www.nature.com/scientificreports OPEN The variability of functional MRI brain signal increases in Alzheimer’s disease at cardiorespiratory frequencies Timo Tuovinen1,2*, Janne Kananen1,2, Zalan Rajna1,3, Johannes Lieslehto4, Vesa Korhonen1,2, Riikka Rytty1,5, Heli Mattila1,2, Niko Huotari1,2, Lauri Raitamaa1,2, Heta Helakari1,2, Ahmed Abou Elseoud6, Johanna Krüger2,7, Pierre LeVan8,9,10,11, Osmo Tervonen1,2, Juergen Hennig8, Anne M. Remes2,7, Maiken Nedergaard12 & Vesa Kiviniemi1,2* Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer’s disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly diferentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fuid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans. Te presence of aggregates of amyloid-beta (Aβ) protein and tau-protein in brain tissue are canonical pathologies of established Alzheimer’s disease (AD)1,2. Te mechanism ultimately resulting in deposition of these aggregates remains unclear3, and the causal relationship between Aβ and tau deposition is debated 4. Te clinical diagnosis of AD is based on a battery of examinations, including neurological and neuropsychological tests, supplemented in recent years by structural MRI of the brain and metabolic imaging with FDG-PET5,6.
    [Show full text]
  • Venous Blood Based Biomarker Data from CHARLS
    Venous Blood Based Biomarker Data from the China Health and Retirement Longitudinal Study (CHARLS) Perry Hu, John Strauss, Yaohui Zhao, Eileen Crimmins Collaborators • Capital Medical University – Tao Ge • Beijing University – Yisong Hu, Yafeng Wang • China Center for Disease Control and Prevention – Xiangjun Yin • Peking Union Medical University – Gonghuan Yang • University of Southern California – Jung Ki Kim Rationales for Objectively Measured Biomarkers • Validate and supplement self-reported health information • Capture aspects of health unknown to survey participants • Allow richer modeling of pathways of influence between socioeconomic factors and health Sampling of CHARLS Biomarkers Study • CHARLS national baseline survey – 17,708 individuals in 10.257 households – Households from 28 provinces, 150 counties/districts, 450 villages/urban communities – Representative of people aged 45 and over, living in households in China – Collected blood samples from 11,847 individuals (an overall response rate of 67%) – Higher response rate in women (69%) than in men (65%) – Younger men were less likely to have blood drawn – Higher response rate in rural (71%) than in urban (6%) – No significant effect from education levels Blood Sample Collection, Processing, Transportation, Storage • Collaboration with the China Center for Disease Control and Prevention • 92% respondents reported fasting overnight • 3 tubes of venous blood were collected by medically-trained staff – 2 mL blood for complete blood count (CBC) test • Transported at 4oC to local
    [Show full text]
  • Personalized Medicine: Challenges in Biomarker-Related Clinical Trial Design
    Clinical Trial Methodology He Personalized medicine: challenges in bio- marker-related clinical trial design 5 Clinical Trial Methodology Personalized medicine: challenges in biomarker-related clinical trial design Clin. Invest. (Lond.) Personalized medicine becomes an area of great interest following the recent Pei He development in human genetics, proteomics and metabolomics. There is an increasing Amgen, Inc. 1120 Veterans Boulevard, need to embed the scientific discoveries from basic medical research into real life clinical South San Francisco, CA 94080, USA [email protected] practices, such that a patient’s biological traits can be used to facilitate treatment. Those individualized biological traits, termed as biomarkers, are actively involved in developing personalized medicine and therefore bring out challenges to clinical trial designs. The necessity of biomarker validation and patient subgroup selection make the trial design more complex. This paper will first introduce different types of biomarkers and then review the challenges of clinical trial design with biomarkers from the clinical, statistical and regulatory perspectives. Keywords: biomarkers • clinical trial design • personalized medicine • predictive • prognostic • targeted cancer therapy Personalized medicine is an increasingly recently added more complexity to clinical promising field of interest that connects trial design and data analysis. biological research with clinical practices. All biomarkers of different types require Recent developments in human genetics and clinical trials to confirm their properties and 10.4155/CLI.14.123 sequencing techniques make it possible to to inform and influence daily clinical prac- identify disease-related genes that affect the tices. Regulatory agencies, such as FDA in onset risk of a certain disease and influence the U.S.
    [Show full text]
  • Biomarkers, New and Old, in the Diagnosis of Acute Myocardial Infarction
    Biomarkers, new and old, in the diagnosis of acute myocardial infarction Joseph S. Alpert, MD Professor of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA; Editor-in-Chief, American Journal of Medicine The WHO Definition from the 1970’s • Based on epidemiological principles • Non-specific • Did not use biomarkers early on; later biomarker use was not standardized • Not clinician friendly The Diagnostic Triad for AMI Pain ECG Serum Markers The Criteria The Criteria for the diagnosis of acute MI as established by WHO, included 2 of the following 3: •History: Chest discomfort or equivalent • Diagnostic changes on ECG • Elevated cardiac enzymes (or markers) WHO MI Definition: Serum Enzymes “Appropriate enzyme tests will be used whenever possible.” WHO Criteria - 1971 Primordial Biomarkers: Prior to 1980 • White blood cell count • Body temperature • Blood sedimentation rate • Lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT) • Non-fractionated creatine kinase (CK) Biomarkers after the 1980’s • MB fraction of creatine kinase (CK-MB) – various assays with variable sensitivity and specificity from assay to assay; • Troponin T and I – recently, high sensitivity troponin assays have become widely available. The troponin revolution Definition of MI from 2000, 2007, and 2012: Circulation, Eur Heart Journal, and Journal of the Amer College of Cardiology • Based on measurement of highly sensitive and specific troponin in association with: --Clinical evidence of myocardial ischemia from history, ECG, or following a coronary intervention; --Non-invasive imaging can assist with the diagnosis; Definition of Myocardial Infarction Pathology Acute myocardial infarction is defined as myocardial cell death due to prolonged myocardial ischemia. Biomarkers for Detection of Myocardial Infarction Preferably Detection of rise and/or fall of Troponin (I or T) with at least one value above the 99th percentile of the upper reference limit measured with a coefficient of variation 10%.
    [Show full text]
  • Antibody Biomarker Discovery Through in Vitro Directed Evolution of Consensus Recognition Epitopes
    Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes John T. Ballewa,b, Joseph A. Murrayc, Pekka Collind, Markku Mäkie,f, Martin F. Kagnoffg,h, Katri Kaukinend,e,i, and Patrick S. Daughertya,b,1 aDepartment of Chemical Engineering and bCenter for Bioengineering, Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106; cDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905; dDepartment of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, FIN-33520, Tampere, Finland; eSchool of Medicine, University of Tampere, FIN-33520, Tampere, Finland; fTampere Center for Child Health Research, University of Tampere and Tampere University Hospital, FIN-33520, Tampere, Finland; gLaboratory of Mucosal Immunology, Department of Medicine and hDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093; and iDepartment of Medicine, Seinäjoki Central Hospital, FIN-60220, Seinäjoki, Finland Edited by K. Christopher Garcia, Stanford University, Stanford, CA, and approved October 17, 2013 (received for review August 5, 2013) To enable discovery of serum antibodies indicative of disease and their clinical development (11–13). Although approved antibody- simultaneously develop reagents suitable for diagnosis, in vitro based diagnostic assays often exhibit sensitivity and/or specificity directed evolution was applied to identify consensus peptides rec- values in excess of 95% (14, 15), library isolated peptides
    [Show full text]
  • The COVID-19 Lab Score Is Performed, Ranging from 0 to 30 Points
    www.nature.com/scientificreports OPEN The COVID‑19 lab score: an accurate dynamic tool to predict in‑hospital outcomes in COVID‑19 patients Pablo Jose Antunez Muiños1,3, Diego López Otero1,3*, Ignacio J. Amat‑Santos2, Javier López País1,3, Alvaro Aparisi2, Carla E. Cacho Antonio1,3, Pablo Catalá2, Teba González Ferrero1,3, Gonzalo Cabezón2, Oscar Otero García1,3, José Francisco Gil2, Marta Pérez Poza1,3, Jordi Candela2, Gino Rojas2, Víctor Jiménez Ramos1,3, Carlos Veras2, J. Alberto San Román2 & José R. González‑Juanatey1,3 Deterioration is sometimes unexpected in SARS‑CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID‑19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid‑19 disease were included. Laboratory biomarkers that contributed with signifcant predictive value for predicting mortality to the clinical model were included. Cut‑of points were established, and fnally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid‑19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C‑reactive protein, interleukin‑6, procalcitonin, lactate dehydrogenase (LDH), and D‑dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points.
    [Show full text]