Biomarkers in Trauma, Injury and Critical Care (Biomarkers in Disease: Methods, Discoveries and Applications)

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