Biomarkers in Trauma, Injury and Critical Care

Series Preface
Preface
Contents
About the Editors
Contributors
Part I: General Overviews: Circulating and Body Fluid Biomarkers in Organ Injury and Trauma
1 A Synopsis of Routine Blood Biomarkers in Trauma, Injury Critical Care and Recovery: General Overview
Introduction
Characteristics of Biomarkers in Trauma, Injury Critical Care, and Recovery
Various Definitions of Biomarkers
Significance of Medical Biomarkers in Trauma, Injury Critical Care, and Recovery
Biomarkers in Critical Care
Established Blood Biomarkers in Orthopedic Trauma
Biomarkers for Mild Traumatic Brain Injury: Unresolved Issues
Established Blood Biomarkers in Acute Cardiac Disease
Established Blood Biomarkers in Acute Lung Injury
Established Blood Biomarkers in Acute Kidney Injury
Established Blood Biomarkers in Acute Medical Condition of Gastrointestinal Track and/or Liver
Conclusion
Mini-Dictionary of Terms
Key Facts of Biomarkers in Trauma, Injury Critical Care, and Recovery
Summary Points
References
2 A Synopsis of Emerging Blood Biomarkers in Trauma, Injury Critical Care, and Recovery: General Overview
Introduction
Different Types of Emerging Biomarkers in Trauma, Injury Critical Care, and Recovery
Classification of Emerging Biomarkers According to Their Main Clinical Application in Trauma, Injury Critical Care, and Recove...
Role of Biomedicine and Emerging Biomarkers in Modern Medicine´s Trauma, Injury Critical Care, and Recovery
Modern Medical Diagnostics in Trauma, Injury Critical Care, and Recovery
An Overview on Emerging Biomarkers in Cardiovascular Events in Trauma, Injury Critical Care, and Recovery
Emerging Biomarkers in COVID-19 Critical Care and Recovery
Emerging Biomarkers of Infection in the Critical Care
Clinical Outcomes and Emerging Biomarkers: Overlaps and Differences
Conclusion
Limitations of Biomarkers
Mini-Dictionary of Terms
Key Facts on Emerging Blood Biomarkers in Trauma, Injury Critical Care, and Recovery
Summary Points
References
3 Biomarkers in Neurological Injury: Fibrinogen, Fibrinogen/Fibrin Degradation Products (FDPs), and D-dimer
Introduction
Fibrinogen
The Fibrinogen and Coagulation Cascade (Fig. 1)
Fibrinogen and Inflammation
Fibrinogen and the CNS
FDP and D-dimer
FDP, D-dimer and Fibrinolysis Cascades (Fig. 2)
FDP, D-dimer, and the CNS
Fibrinolytic Biomarker and Treatment
Applications to Prognosis, Other Diseases, and Conditions
Key Facts About Fibrinogen
Key Facts About D-dimer
Mini-Dictionary of Terms
Summary Points
Cross-References
References
4 Nerve Injury and Biomarkers
Introduction
Psychological and Cognitive and Behavioral Testing
Peripheral Neurography of Nerve Fiber Integrity
Central Markers of Nerve Fiber Integrity
Use of Molecular Genetics to Understand Nerve Injury
Artificial Intelligence
Remaining Questions
Conclusions
References
5 Blunt Abdomen Trauma and Biomarkers
Introduction
Biomarkers for Liver Injury
Biomarkers for Kidney Injury
Unsolved Mysteries
Summary
References
6 Therapeutic Strategies in Patients with Postoperative Elevation of Cardiac Biomarkers
Introduction
Association Between Postoperative Elevation of Biomarkers and Outcome
Pathophysiologic Background of Myocardial Injury and Infarction
Evidence-Based Therapeutic Strategies in Nonoperative Myocardial Injury and Infarction
Derivation of Therapeutic Strategies in Perioperative Myocardial Injury and Infarction
Proposed Algorithm for Therapeutic Strategies of Perioperative Myocardial Injury and Infarction (Fig. 1)
Basic and Advanced Risk Stratifications and Strategies to Prevent Postoperative Myocardial Injury and Infarction
Perioperative Optimization Strategies
Advanced Strategies for Biomarker-Based Perioperative Risk Stratification
Other Biomarkers Under Investigation
Conclusion and Perspectives
Applications to Perioperative Myocardial Infarction/Injury
Mini-Dictionary of Terms
Key Facts of Perioperative Myocardial Injury/Infarction
Summary Points
Cross-References
References
7 Prognostic Biomarkers to Predict Outcomes in Trauma
Introduction
Prognostic Markers in Traumatic Brain Injury
Putative Biomarker Molecules in Trauma
IL-6
CRP
MCP-1
Correlative Cytokines
Single Nucleotide Polymorphisms
Transcriptomics
Syndecan-1
Syndecan-1 and Thrombomodulin in Relation to Acute Kidney Injury Following Trauma
Angiopoietin-2
High-Mobility Group Box 1 (HMGB1)
Mitochondrial DNA (mtDNA)
Heat Shock Protein 70 (HSP70)
Histones
Multi-Omics: Emerging Technologies with Predictive Capability
Conclusions
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Summary Points
References
Part II: Biomarkers in Critical Care and Illness
8 The Role of C-Reactive Protein and Implications to the Neonatal Intensive Care Unit
Introduction
Neonatal Sepsis
Rational Antibiotic Use
Blood Cultures
CRP Kinetics and Clinical Utility
Factors Affecting CRP Measurement
Clinical Applications of C-Reactive Protein in Sepsis
Disease Severity and Outcome Prediction
CRP Response to Guide Antibiotic Therapy
CRP Combined with Other Biomarkers
Conclusion
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Acute Phase Reactant
Antimicrobial Stewardship
Biomarker
Immunoassay
Immunoturbidimetry
Microbiome
Nephelometry
Negative Predictive Value
Point-of-Care Test
Positive Predictive Value
Sensitivity
Specificity
Vertical Transmission
Hospital-Acquired Infection
Key Facts of Neonatal Sepsis
Summary Points
References
9 Cell Cycle Arrest Biomarkers in the Intensive Care Unit
Introduction
Cell Cycle and Cell Cycle Arrest
Cell Cycle
Cell Cycle Arrest
Cell Cycle Arrest in AKI
AKI in ICU
Application of Cell Cycle Arrest Biomarkers in Predicting AKI
[TIMP-2] x [IGFBP7] Findings
[TIMP-2] x [IGFBP7] to Predict Different Types of AKI
Applications to Prognosis
[TIMP-2] x [IGFBP7] Disadvantage in Predicting AKI
Conclusion
Mini-Dictionary of Terms
Key Facts of AKI
Key Facts of Cell Cycle Arrest
Summary Points
References
10 Plasma Markers of Cholestasis in Critical Illness
Introduction
Etiology and Pathophysiological Mechanisms
Normal Hepatobiliary Transport
Hepatobiliary Transport During Critical Illness
Diagnosis of Critical Illness-Induced Cholestasis
Plasma Markers of Cholestasis
Bilirubin and Bile Acids
Alkaline Phosphatase and Gamma-Glutamyl Transpeptidase
Other Diagnostic Tools
Indocyanine Green Clearance
Abdominal Sonography
Other Laboratory Markers
Epidemiology of Cholestasis in Critical Illness
Pathologies Affecting Liver Function
Interventions Affecting Liver Function
Association of Critical Illness-Induced Cholestasis with Outcome
Management of Critical Illness-Induced Cholestasis
Current Management Strategies
Future Research
Mini-Dictionary of Terms
Key Facts of Plasma Markers of Cholestasis in Critical Illness
Summary Points
Cross-References
References
11 Biomarkers of Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy
Introduction
Oxidative Stress
Neonatal Hypoxic-Ischemic Encephalopathy: A Clinical Overview
The Role of Oxidative Stress in Neonatal HIE
Biomarkers of Oxidative Stress in Neonatal HIE
Lipid Peroxidation Markers
Malondialdehyde
4-Hydroxynonenal (HNE)
Prostaglandin-like Peroxidation Products (PPPs)
Protein Oxidation Markers
DNA Peroxidation Markers
Antioxidant Enzymes
Uric Acid
Nonprotein-Bound Iron
Nitric Oxide
Bilirubin
Galectin-3 and Quinolinic Acid
Diagnostic and Prognostic Applications of Oxidative Biomarkers in Neonatal HIE
Mini-Dictionary of Terms
Key Facts of Oxidative Biomarkers in Neonatal HIE
Summary Points
References
12 Measures of Classical and Alternative Complement Function in Serum as Markers in Critical Care
Introduction
Review of Classical, Lectin, and Alternative Pathways of Complement Activation
Key Principles of Complement Pathway Regulation
Evaluation of Complement Pathway Function
Complement Pathway Biomarkers During Critical Illness
Sepsis and Other Infections
Acute Respiratory Failure
Trauma
Applications to Prognosis
Conclusion
Mini-Dictionary of Terms
Key Facts of ``Measures of Classical and Alternative Complement Function in Serum as Markers in Critical Care´´
Summary Points
References
13 Serum Aromatic Microbial Metabolites as Biological Markers in Intensive Care
Summary Points
Introduction
In Search for Promising Metabolites
Metabolites of Aromatic Amino Acids
The Origin of Aromatic Metabolites in Human Blood
Bacteria Producing AMM
Why AMMs Are Biomarkers in Intensive Care?
Association of AMM with Mortality
AMM and Septic Shock
Applications to Prognosis
Application to Meningitis
Short About Methods
Conclusion
References
Part III: Biomarkers in Trauma
14 Viscoelastic Hemostatic Tests and Fibrinogen Concentrations in Trauma
Introduction
Viscoelastic Hemostatic Tests
Fibrinogen
Principles of TEG and ROTEM FF Tests
Comparison of TEG and ROTEM FF Tests
New Viscoelastic Hemostatic Testing Systems
Applications to Diagnosis of TIC and Hypofibrinogenemia
Assessment of the FF Level and Hemostatic Effect of Fibrinogen Replacement
TEG/ROTEM-Guided Fibrinogen Replacement
Mini-Dictionary of Terms
Key Facts of Trauma
Summary Points
References
15 Radiotracers, Positron Emission Tomography Imaging and Traumatic Brain Injury
Introduction
Defining Traumatic Brain Injury
Epidemiology of Traumatic Brain Injury
Acute Consequences of mTBI: Primary and Secondary Injury
Acute Consequences of mTBI: Neuroinflammatory Responses
Repeat mTBI
Repeat mTBI: Neurodegenerative Disorders
Chronic Traumatic Encephalopathy
Chronic Traumatic Encephalopathy: Theories
Positron Emission Tomography Imaging
Inflammatory Neuroimaging
Metabolic Imaging
Tau Imaging
Amyloid Imaging
Conclusions
Mini-Dictionary of Terms
Key Facts of Traumatic Brain Injury
Summary Points
References
16 Circulating Polyunsaturated Fatty Acids (PUFAs) as Biological Indicators in Trauma
Introduction
PUFA Biosynthesis and Metabolism
The Role of PUFAs in Trauma-Induced Inflammation and Coagulation
Specialized Pro-Resolving Lipid Mediators (SPMs)
Effects of Dietary Supplementation with PUFAs in Trauma Populations
Traumatic Brain Injury (TBI) and Concussions
Acute Respiratory Distress Syndrome (ARDS)
Orthopedic Trauma and Arthritis
Genetic and Epigenetic Determinants of PUFA Biosynthesis and Metabolism
Future Directions
Applications to Prognosis, Other Diseases, and Conditions
Glossary: Mini-Dictionary
Key Facts of PUFAs
Summary Points
References
Part IV: Biomarkers in Specific Conditions
17 Blood Count Profiles as Biomarkers in Burns: Red Cells, Platelets, and Beyond
Usefulness of CBC-Derived Biomarkers in Different Clinical Situations
Sepsis and Septic Shock
ARDS
Cancer
COVID-19
COPD
Cardiovascular Diseases
Inflammation and Biomarkers in Burn Injury
Procalcitonin (PCT)
C-Reactive Protein (CRP)
Cytokines
IL-6
IL-8
Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Acute Kidney Injury (AKI)
Blood Count Profiles in Burns
Red Blood Cells
Platelets
White Blood Cells
Complete Blood Count-Derived Parameters
Summary Points
References
18 The Opportunity of Surfactant Protein D as a Potential Biomarker for Detecting Acute Lung Injury
Definitions of Words and Terms
Key Facts
Key Facts for Acute Lung Injury
Key Facts for Surfactant Protein D
Introduction
Biomarker Combination
What Is Surfactant Protein D?
Respiratory Epithelium Markers
The Advantage and Disadvantage of Using Circulating SP-D
The Rationalization of Using Circulating SP-D as Biomarker Diagnostic for Acute Lung Injury Based on Literature Study
Summary
References
19 Troponin as a Biomarker: Use in Non-cardiac Surgery
Introduction
Myocardial Infarction or Injury?
Cardiac Troponin Assays
Pathophysiology
Prognosis and Predictors
Future Perspectives
Applications to Prognosis in General Population and Other Diseases
Mini-dictionary of Terms
Key Facts of Troponin as a Biomarker in Non-cardiac Surgery
Summary Points
References
20 Glucose Variability Measures in Critical Care
Introduction
Blood Glucose Variability Measures
Blood Glucose Variability in the Surgical Intensive Care Unit
Post-Surgical and Trauma ICU
Cardiac and Vascular Surgery
Blood Glucose Variability in the Medical Intensive Care Unit
Sepsis
Post-Cardiac Arrest
Blood Glucose in Neurocritical Care Unit
Traumatic Brain Injury
Stroke
Subarachnoid Hemorrhage (SAH)
Applications to Prognosis, Other Diseases, or Conditions
Conclusion
Mini-Dictionary of Terms
Key Facts of Glucose Variability Measures in Critical Care
References
21 Fluid Biomarkers in Sports-Related Mild Traumatic Brain Injuries: Current Status and Novel Trends
Introduction
Mild TBI: Prevalence and Risk Factors
Acute Pathophysiology of mTBI and Associated Symptoms
Excitotoxicity
Axonal Injury
Neuroinflammation
Connection to Clinical Symptoms
Transition from Acute to Chronic Pathophysiology
Challenges with Diagnosis of mTBI
Blood Biomarkers for mTBI
Neuronal Damage Biomarkers
Glial Activation Markers
Inflammatory Markers
Extracellular Vesicle Biomarkers
Exosomal Biomarkers in mTBI
Conclusion and Future Directions
Applications to Prognosis, Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of mTBI
Summary Points
References
22 Biomarkers in Hypoxic Brain Injury: Methods, Discoveries, and Applications
Introduction
Discovery
Pathophysiology
Methodology
Other Biomarkers in Hypoxic Brain Injury
Method
Application to Other Diseases
Key Facts
Summary
References
23 D-Dimer Levels, Stroke, and Critical Care
Introduction
Ideal Criteria of Biomarkers for brain disorders
Use of a Panel of Serum Protein Markers
Serum Biomarkers for Stroke Diagnosis
Biomarkers for the Diagnosis of Ischemic Stroke
Biomarkers of Ischemic Stroke Etiology
Biomarkers of Final Infarct Volume and Outcome
Biomarkers of Hemorrhagic Transformation
Biomarkers of Arterial Recanalization
D-Dimer and Ischemic Stroke
D-Dimer Formation
Coagulation
Fibrinolysis
D-Dimer Test Collection and Panels
Medical Conditions Affecting D-Dimer (DD) Levels
The Clinical Implications of D-Dimer Measurement
Relation Between D-Dimer and Different Phases and Subtypes of IS
D-Dimers in Critically Ill COVID-19 Patients
Importance of D-Dimer in Different Diseases
D-Dimer and Venous Thromboembolism
Pulmonary Embolism and D-Dimer (PE)
D-Dimer Significance in Critically Ill Patients
Stroke Biomarkers´ Limitations
Terms in Mini-Dictionary
Key Facts of D-Dimers
Summary of D-Dimer
References
24 Intraoperative Management and Its Influence on Postoperative Biomarker Release
Introduction
The Importance of Perioperative Organ Injury Following Noncardiac Surgery
Organ Injury Versus Biomarker Release
Perioperative Organ Injury Is Common
Perioperative Organ Injury Is Clinically Relevant
The Link Between Intraoperative Management and Perioperative Organ Injury Following Noncardiac Surgery
Physiologic Primer
Oxygen Supply/Demand Mismatch as an Initiator of Organ Injury
The Importance of Pressure and Flow
Myocardial Oxygen Demand in the Perioperative Setting
Risk Factors for Postoperative Organ Injury
Major Bleeding
Hemodynamic Derangements
Arterial Hypotension as the Common Denominator of Intraoperative Circulatory Insufficiency
Prognostic Importance of Intraoperative Hypotension.
Myocardial Injury: Other Relevant Hemodynamic Disturbances.
Severe Hypoxemia
Perioperative Strategies to Avoid Postoperative Organ Injury Following Noncardiac Surgery
Risk Stratification
Major Bleeding
Intraoperative Hemodynamic Derangements
Blood Pressure Goals
Etiologies of Intraoperative Hemodynamic Derangements
Treatment of Intraoperative Hemodynamic Derangements
Fluid Therapy
Vasopressors
Inotropes
Avoidance of Venous Congestion
Future Directions
Research Priorities in Perioperative Medicine
Understanding Perioperative Organ Injury: Moving from Populations to Individuals
Biomarkers Poised to Transform Perioperative Medicine
Preventing Perioperative Organ Injury: Leveraging Not Fearing Heterogeneity Through Individualization
Conclusion
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts of Perioperative Organ Injury
Summary Points
References
25 Biomarkers in Neonatal Brain Injury: Interpreting Research into Clinical Practice
Introduction
S100B
S100B in Neonatal Brain Injury
S100B in CSF
S100B in Cord Blood
S100B in Serum
S100B in Urine
S100B in Saliva
S100B in Amniotic Fluid
Applications to Prognosis
NSE
NSE in Cord Blood
NSE in Serum
NSE in CSF
Applications to Prognosis
Conclusion
Mini-Dictionary of Terms
Key Facts of Neonatal Brain Injury
Summary Points
Cross-References
References
26 Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) in Emergency Medicine and the Intensive Care Unit:...
Introduction
Blood Biomarkers
C-Reactive Peptide
Fibrinogen
Procalcitonin
B-Natriuretic Peptide (BNP)
Neopterin
SP-d
sRAGE (Serum Levels of Soluble Receptor for Advanced Glycation End Products)
Biomarker Panels
Exhaled Biomarkers
Fractional Excretion of Nitric Oxide (Fe No)
Exhaled Carbon Monoxide
Exhaled Breath Condensate (EBC)
Sputum Biomarkers
Biomarkers in BAL and Bronchial Biopsies
Imaging Biomarkers
MRI
CT Scan
Conclusion
Mini-Dictionary of Terms (5-15 Terms)
Key Facts of Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) in Intensive care unit and Emergency med...
Key Facts of COPD
Key Facts of Ideal Biomarkers
Summary Points
References
Part V: Specific Components
27 Procalcitonin As a Biomarker and Mediator of Sepsis: Implications for Critical Care
Introduction
Pathophysiology of PCT Secretion
Diagnostic Accuracy
Procalcitonin-Guided Antibiotic Stewardship
COVID-19 and PCT
Experimental Data on a Potential Mediator Role of PCT
PCT Mediates Cytokine Release and Immune Cell Migration
Neutralization of PCT Is Associated with Reduced Mortality and Morbidity in Experimental Sepsis
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Procalcitonin As a Biomarker and Mediator of Sepsis: Implications for Critical Care
Key Facts of PCT As Prognostic Marker of Sepsis
Key Facts of PCT in COVID-19
Key Facts of PCT in Experimental Sepsis
Summary Points (5-15)
References
28 Serum Interleukin-6 Levels as a Biomarker in Trauma
The Effect of Trauma on the Organism
SIRS Caused by Trauma
Pathophysiology
Interleukin-6
The Other Biomarkers of the SIRS
Conclusion
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Serum IL-6 Levels
Summary Points
References
29 The Role of Vitamin D As a Biomarker in Trauma
Introduction
Production and Absorption
Immune Function
Traumatic Brain Injury
Burns
Musculoskeletal Injury
Lung Injury and Acute Respiratory Distress Syndrome
Critical Illness
Acute Kidney Injury
Anemia of Critical Illness
Mortality
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts About Vitamin D
Summary Points
References
30 Selenium Concentrations and Multiple Trauma/Trace Elements in Trauma: A Focus on Selenium
Introduction
Physiological Changes in Patients after Trauma
Physiological Function of Trace Elements
Selenium Deficiency and Supplementation in Critically ill Patients
Selenium in Trauma Patients
Selenium Supplementation in Trauma Patients
Applications to Prognosis, Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Selenium in Trauma
Summary Points
References
31 Presepsin: Methods of Measure, Features and Biomarker Potential in Sepsis and Critical Care
Introduction
Presepsin: A Biomarker of Early Immune Response
Presepsin in Sepsis Diagnosis and Prognosis
Presepsin and Renal Function
Pediatric Sepsis
Diagnosis of Sepsis in Emergency Department
Application in Perioperative Medicine
Presepsin in Orthopedic Surgery
Application in Viral Infections
Methods of Measure
Mini-Dictionary of Terms
Key Facts of ``Presepsin: Methods of Measure, Features and Biomarker Potential in Sepsis and Critical Care.´´
Key Facts of Sepsis
Key Facts of Severe COVID-19
Key Facts of Perioperative Medicine
Summary Points
References
32 Review of our Current Understanding of ADAMTS13 and Von Willebrand Factor in Sepsis and Other Critical Illnesses
VWF and ADAMTS13 in Hemostasis
Known Associations Between VWF and ADAMTS13 in Disease
ADAMTS13 and VWF in Critically Ill Patients with Sepsis
Mechanistic Insights on the Dysfunction of ADAMTS13 and VWF in Sepsis
Role of ADAMTS13 and VWF in Driving ICU Mortality
Potential Therapies
Conclusions
Dictionary of Terms
Key Facts of Review of our Current Understanding of ADAMTS13 and Von Willebrand Factor in Sepsis and Other Critical Illnesses
Summary
References
33 Circulating TGF-β1 Levels: Linking Muscle and Trauma
Introduction
Disease States with Altered Circulating TGF-β Levels
Cardiovascular Diseases
Fibrosis and Wound Healing
Infection and Cancer
Trauma
Effects of TGF-β1 on Different Cell Types During Muscle Regeneration
Inflammatory Cells
Myogenic Cells
Connective Tissue Cells
Circulating TGF-β1 Levels: Linking Muscle and Trauma
Source of Circulating TGF-β1
Factors Affecting Circulating TGF-β1 Levels Following Trauma
Circulating Versus Muscle TGF-β1
Function of Circulating TGF-β1 in Muscle
Conclusion and Future Direction
Applications to Prognosis, Other Diseases or Conditions.
Mini-Dictionary of Terms
Key Facts of TGF-β1
Summary Points
References
34 Neurofilament Light Chain in the Blood As Biochemical Markers in the Critically Ill
Introduction
Biochemical and Biological Characteristics of Neurofilament Light Chain
Potential Confounders and Interferences with Serum Neurofilament Light Chain Concentrations
Volume of Distribution
Increasing Age
Neurological Comorbidities
Renal Insufficiency
Non-Neurological Comorbidities
Treatment-Related Influences on Serum Neurofilament Levels
Advantage of Neurofilament Light Chains in Contrast to Neuron-Specific Enolase with Hemolysis
Temporal Profile
CSF/Serum Correlation and Blood-Brain Barrier
Evidence Regarding Neurofilament Light Chain in Specific Critical Illnesses
Cerebrovascular Accidents
Nontraumatic Subarachnoid Hemorrhage (SAH)
Traumatic Brain Injury (TBI)
Hypoxic-Ischemic Brain Injury After Cardiac Arrest (CA)
Epilepsy
Neuroinflammatory Conditions of the CNS
Guillain-Barré Syndrome (GBS)
Delirium, Anesthesia, and Surgery
Infectious Disease and Sepsis
Coronavirus Infectious Disease (COVID)-19
Applications to Prognosis
Conclusions
Mini-Dictionary of Terms
Key Facts of Serum Neurofilament Light Chain Levels
Summary Points
References
35 S100B As a Biomarker in Traumatic Brain Injury
Introduction
Biomarkers
S100B
Predicting Positive CT Findings in Mild TBI
Predicting Outcome
Predict Secondary Injury Development and Treatment Efficacy
Other Biomarkers
Conclusion
Applications to Prognosis, Other Diseases, or Conditions
Key Facts
Mini Dictionary of Terms
Summary Points
References
36 Biomarkers of Sepsis and a Focus on PCSK9
Introduction
Biomarkers in Sepsis: An Overview
PCSK9: What About This Molecule? Could PCSK9 Be a Useful New Sepsis Biomarker?
PCSK9 Inhibitors
PCSK9 Inhibitors and COVID-19
Future Perspectives
Applications to Prognosis, Other Disease or Conditions
Mini-Dictionary of Term (5-15)
Key Fact of Sepsis
Summary Points
References
37 Urinary Potassium Excretion as a Biomarker in Critically Ill for the Identification of AKI: A Review
Introduction
Physiology of Potassium Homeostasis
Renal Handling of Potassium
Potassium Handling in Pediatric Age Group
Potassium Handling during Pregnancy
High Dietary Intake
Enteric Sensors of K
Potassium Physiology During Exercise
Circadian Rhythm of K Secretion
Potassium Handling During Pathological States
Effect of Plasma Tonicity and Acid-Base Disorders
Effect of Volume Status
Hypertension
Chronic Kidney Disease (CKD)
Acute Kidney Injury
Urine Output
Serum Creatinine
Urinary Biochemistry as Biomarkers in the Assessment of AKI
Urinary Microscopy
Fractional Excretion of Urea (FeUr)
Fractional Excretion of Sodium (FeNa)
Spot Urine Na and Urine Na/ Urine K Ratio
Fractional Excretion of Potassium (FeK)
Conclusion
References
38 Blood Cortisol as a Biomarker in Intensive Care Unit
Introduction: Blood Cortisol as a Biomarker in Intensive Care Unit
Blood Cortisol and Delirium
Blood Cortisol and Trauma
Blood Cortisol and Sepsis-Septic Shock
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Blood Cortisol as a Biomarker in Intensive Care Unit
Summary Points
References
39 Citrullinated Histone H3 as a Biomarker in Sepsis and Critical Care
Introduction
Sepsis and Cit-H3
Comparison of Cit-H3 and Other Sepsis Biomarkers
Cit-H3 in Urosepsis
Cit-H3 in Critical Care Patients
Cit-H3 in ARDS
Cit-H3 in Pediatric Sepsis
Cit-H3 and Liver Dysfunction
Cit-H3 and Cardiopulmonary Resuscitation
Cit-H3 and Patient Follow-Up
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Cit-H3 in Sepsis and Critical Care
Summary Points
References
40 Tumor Necrosis Factor-Alpha (TNF-Alpha) as a Biomarker in Trauma and Critical Care
Introduction
TNF-α
History of TNF
The Structure of TNF-α
The Role of TNF-α in Trauma
The Role of TNF-α in Sepsis
The Role of TNF-α in Traumatic Brain Injury (TBI)
The Role of TNF-α in Lung Injury/ARDS
Applications to Prognosis, Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of TNF-Alpha
Summary Points
References
41 ADAM10 as a Biological Marker in Traumatic Brain Injury
Introduction
Pathophysiology of TBI
Recent Advances in Imaging Diagnostics
Need for TBI Biomarkers
A Disintegrin and Metalloproteinase 10 (ADAM10)
ADAM10 and Traumatic Brain Injury
Mini-Dictionary of Terms
References
Part VI: Biomarkers in COVID-19
42 Laboratory Markers of COVID-19 in the Emergency Room
Introduction
Disease Progression and Laboratory Markers in Emergency Room
Disease Progression
Viral Entry and Replication
Immune Response and Inflammation
The Coagulative Cascade and Growing Inflammation
Laboratory Markers in Emergency Room
Blood Gas-Analyses (BGA): Partial Pressure of Oxygen and Oxygen Saturation
Hematological Biomarkers
Hemoglobin Quantification
WBC-Related Numbers: Absolute Lymphocyte Count (Cells/μL) and Neutrophil to Lymphocyte Ratio
Platelet Count (Cells/μL)
Inflammatory Biomarkers
C-Reactive Protein (CRP)
Procalcitonin (PCT)
Creatine Kinase (CK)
Comprehensive Metabolic Panel Biomarkers
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)
Creatinine
High-Sensitivity Troponin (hs-Tn) and Natriuretic Peptides Type B (BNP)
Other Biomarkers
D-Dimer
Lactate Dehydrogenase (LDH)
Biomarkers: From Bench to Patient
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts of COVID-19 Biomarkers
Summary Points
References
43 Serum Angiotensin II as a Biomarker in COVID-19
Introduction
Renin-Angiotensin System (RAS)
Angiotensin II
The Role of Angiotensin II in the Classical Renin-Angiotensin System (First Axis)
The Role of Angiotensin II in the Non-classical Renin-Angiotensin System (Second Axis)
The Role of Angiotensin II in the Tissue Renin-Angiotensin System
The Effects of Angiotensin II
The Role of Angiotensin II in COVID-19
Serum Angiotensin II Levels in COVID-19
Applications to Prognosis, Other Diseases, or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Angiotensin II
Summary Points
References
44 Polyunsaturated Fatty Acid-Derived Lipid Mediators as Biomarkers in Critical Care
Introduction
Discovery of Resolution as the Flip Side of Inflammation
Inflammation Contains the Seeds of Resolution
The Role of Dysregulated Inflammation in the Pathogenesis of COVID-19
Pathologic Implications of Dysregulated Inflammation
Sepsis
Acute Respiratory Distress Syndrome
Influenza
Pro-inflammatory Cascade and Inflammation Resolution in COVID-19
Pathogenesis of Severe COVID-19
PUFAs in COVID-19
Beyond PUFAs: Lipidomics and SPMs in COVID-19
Therapeutic Targets and Future Directions for Specialized Pro-resolving Mediators
Applications to Prognosis, Other Diseases, or Conditions
Conclusions
Mini-Dictionary of Terms
Specialized Pro-resolving Mediator
Key Facts
Key Facts of Inflammation Resolution
Key Facts of Sepsis
Key Facts of Acute Respiratory Distress Syndrome
Key Facts of N-3/N-6 PUFA Ratio
Summary Points
References
Part VII: Physical Platforms and Physiology
45 Optic Nerve Sheath Diameter as a Biological Marker and Its Radiological Evaluation in Brain Injury
Introduction
Intracranial Pressure in Traumatic Brain Injury
Pathophysiology
Clinical Findings
ICP Monitoring
Invasive Methods
Non-invasive Methods
Optical Nerve Sheath Diameter
ONSD Measurement Methods
Ultrasonography
Computed Tomography
Magnetic Resonance Imaging
Applications to Prognosis
Conclusion
Mini-Dictionary of Terms
Key Facts of ONSD
Summary Points
References
46 Neural Activity and Oscillations as Biological Markers in Traumatic Brain Injury
Introduction
Signs, Symptoms, and Sequelae of mTBI
The Biomechanical Forces and Neurochemical Consequence Serving mTBI
Invisible Fingerprinting of the Brain: Magnetoencephalography
Revealing the ``Spectral Fingerprints´´ of mTBI with MEG
Resting-State Studies
Task-Based Studies
Differentiating ``Invisible Injuries´´: Disentangling mTBI from PTSD
Future Directions and Applications
Conclusion
Applications to Prognosis and Conditions
Mini-Dictionary of Terms
Mild Traumatic Brain Injury/Concussion
Neural Oscillations/Brain Waves/Brain Rhythms
Magnetoencephalography
Key Facts of Neural Activity and Oscillations as Biological Markers in Traumatic Brain Injury
Mild Traumatic Brain Injury
Summary Points
References
47 Viscoelastic Hemostatic Assays in the Management of the Trauma Patient
Introduction
Trauma-Induced Coagulopathy
Impaired Clot Formation, Dysregulated Fibrinolysis, and Platelet Dysfunction
Acidosis, Hypothermia, and Hypocalcemia
How Viscoelastic Monitoring Assays Work
Understanding VMA Results as They Reflect the Clotting Process
VEM-Guided Trauma Resuscitation
Limitations
Predicting Hypercoagulability
Future Directions
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Trauma-Induced Coagulopathy (TIC)
Key Facts of Viscoelastic Hemostatic Assays
Summary Points
References
48 Biomarkers of Cardiac Stretch in Critical Illness: A Narrative Review
Introduction
Biomarkers of Cardiac Stretch
Natriuretic Peptides in Diagnosis and Prognosis of Heart Failure
Natriuretic Peptides in Multisystem Critical Illness
Sepsis
Major Trauma
Natriuretic Peptides in Cardiac Critical Illness
Cardiac Surgery
Cardiac Arrest and Cardiogenic Shock
Natriuretic Peptides in Respiratory Critical Illness
SARI, ARDS, and Mechanical Ventilation
Pulmonary Vascular Disease
Airways Disease
Natriuretic Peptides in Non-cardiorespiratory Illness
Mini Dictionary of Terms
Key Facts of Natriuretic Peptides
Summary Points
References
49 Cerebrospinal Fluid as a Platform for Biomarker Identification in Traumatic Brain Injury
Introduction
Current State of Proteomic Biomarker Research Following Traumatic Brain Injury
Biological and Methodological Aspects of Cerebrospinal Fluid
Cerebrospinal Fluid Physiology
Specific Methodological Considerations in Cerebrospinal Fluid Proteomics
Proteomic Methods for Biomarker Discovery in CSF
Cerebrospinal Fluid Protein Biomarkers Show Promise Across Traumatic Brain Injury Studies
Discussion and Conclusions
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts
Summary Points
Cross-References
References
Part VIII: Scoring Systems, Models, and Indirect Measures
50 The APACHE II Scoring Systems and the ICU
Introduction
Characteristics of an Ideal Scoring System
Why Do We Need Scoring Systems in ICU?
Evolution of the APACHE Scores
Pitfalls While Calculating APACHE II Score
Uses of APACHE II Score in the ICU
APACHE III and APACHE IV
Other Scoring Systems Used in ICU
Evaluating a Scoring System
Conclusion
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of APACHE II Score Calculation
Summary Points
References
51 The Score for Trauma Triage in Geriatric and Middle-Age (STTGMA): Utilizing Macroscopic Clinical Biomarkers to Guide Patien...
Introduction
Origin of STTGMA
How STTGMA Was Created
Evolution of STTGMA
Frailty Factor
COVID-19 Factor
ASA Score
STTGMA Has Wide Applicability
STTGMA Application for Various Fracture Patterns
Fracture Locations
STTGMA Application for Inpatient Admission
Delays to Surgery
Effective Timing of Blood Transfusions in Hip Fracture Patients
STTGMA Application after Discharge
Discharge Location
Post-Discharge Fall Risk
Loss of Ambulatory Level and ADLs at 1 Year
Conclusion
Additional Applications
Applications to a Healthcare Landscape Increasing in Cost
Applications to Other Diseases or Conditions
Application to Orthopedic Biomarkers
Mini-Dictionary of Terms
Key Facts of Hip Fractures
Key Facts of Osteoporosis
Key Facts of Abbreviated Injury Scale and Charlson Comorbidity Scale
Summary Points
References
52 Body Mass as a Biomarker and Femoral Fracture
Introduction
Body Mass and Its Components
Five Level Model
Change in Body Composition Through Aging
Body Mass as a Risk Factor of Hip Fracture
Body Mass and Mortality
Body Mass and Functional Status
Body Mass and Complication and Secondary Fracture
Conclusion
Mini-Dictionary of Terms
ADL
AWGS
BI
BIA
DXA
FIM
HHS
Mini Mental State Examination
Mini Nutritional Assessment-Short Form
Muscle Fiber
PMS
Sarcopenia
SMI
TUG Test
YAM
Applications to Other Diseases or Conditions
Key Facts of Body Mass as a Biomarker and Femoral Fracture
Summary Points
References
53 Scoring for Hemorrhage Severity in Traumatic Injury
Introduction
Severity Scores As Biomarkers
Patient Stratification
ML for Patient Stratification in Trauma
Artificial Intelligence (AI) for Predictive Analytics in Trauma
Challenges and Opportunities
Mini-Dictionary of Terms
Key Facts of Scoring for Hemorrhage Severity in Traumatic Injury
Summary Points
Cross-References
References
54 Modeling Orthopedic Injury and Its Impact: Biological Measures of Hypercoagulability and their Applications
Introduction
Hypercoagulability, Fibrinolysis, and Viscoelastic Testing in Trauma
The Impact of Orthopedic Injury on Coagulation
Current Orthopedic Trauma Animal Models Including Coagulation Assays
Benefits of Using Animal Models
Overview
Nonhuman Primates
Swine
Sheep
Rabbits
Rats
Mice
Summary of Coagulation Profiles in Animal Model Species
Large Animals
Small Animals
Considerations and Limitations of Specific Models for Future Studies
Conclusion
References
Part IX: Resources
55 Recommended Resources for Biomarkers in Disease: Trauma, Injury, and Critical Care
Introduction
Resources
Other Resources
Summary Points
References
Index