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Predictive and Prognostic Markers in Critically Ill Patients

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 20337

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Special Issue Editor

Dr. Silvia De Rosa

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Guest Editor

1. Centre for Medical Sciences—CISMed, University of Trento, Via S. Maria, Maddalena 1, 38122 Trento, Italy
2. Anesthesia and Intensive Care, Santa, Chiara Regional Hospital, APSS, Trento, Italy
Interests: acute brain injury; acute kidney injury; blood purification in sepsis; airway management; infectious disease; extracorporeal organ support; nutrition and metabolism in critical care
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Special Issue Information

Dear Colleagues,

We are delighted to present a Special Issue in the Section Pathology and Molecular Diagnostics: “Predictive and Prognostic Markers in Critically Ill Patients”.

Today, with the exponential growth in biomarker research, there is enthusiasm that our expanding knowledge will translate into improved decision making and outcomes. Continuous evaluation of our practice and incorporation of these new ideas and studies has the potential to improve patient care. Prognostic biomarkers may predict the course or trajectory of disease, allowing for early determination of disposition and goals of care. The future development and adoption of guidelines and protocols using biomarkers has the potential to minimize variability and maximize benefit. Through thoughtful study design and collaboration, the biomarker era will surely transform and shape the future of medicine.

Therefore, Diagnostics is proud to offer this platform to promote and to highlight evaluable research on predictive and prognostic markers in the specific field of critical care medicine.

Dr. Silvia De Rosa
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

acute brain injury
acute kidney injury
acute mesenteric ischemia
acute pancreatitis
acute respiratory failure
heart failure
infectious disease

Published Papers (11 papers)

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Research

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11 pages, 517 KiB

Open AccessArticle

Impact of Serum Lactate as an Early Serum Biomarker for Cardiopulmonary Parameters within the First 24 Hours of Intensive Care Unit Treatment in Patients with Isolated Traumatic Brain Injury

by Michael Bender, Michaela Friedrich, Hans Voigtmann, Kristin Haferkorn, Eberhard Uhl and Marco Stein

Diagnostics 2023, 13(10), 1777; https://doi.org/10.3390/diagnostics13101777 - 17 May 2023

Viewed by 1136

Abstract

Objective: Cardiopulmonary (CP) complications are well-known phenomena in patients with isolated traumatic brain injury (iTBI) that can lead to tissue hypoperfusion and hypoxia. Serum lactate level is a well-known biomarker, indicating these systemic dysregulations in various diseases, but this has not been investigated in iTBI patients so far. The current study evaluates the association between serum lactate levels upon admission and CP parameters within the first 24 h of intensive care unit (ICU) treatment in iTBI patients. Patients and Methods: 182 patients with iTBI who were admitted to our neurosurgical ICU between December 2014 and December 2016 were retrospectively evaluated. Serum lactate levels on admission, demographic, medical, and radiological data upon admission, as well as several CP parameters within the first 24 h of ICU treatment, were analyzed, as well as the functional outcome at discharge. The total study population was dichotomized into patients with an elevated serum lactate level (lactate-positive) and patients with a low serum lactate level (lactate-negative) upon admission. Results: 69 patients (37.9%) had an elevated serum lactate level upon admission, which was significantly associated with a lower Glasgow Coma Scale score (p = 0.04), a higher head AIS score (p = 0.03), and a higher Acute Physiology and Chronic Health Evaluation II score (p = 0.01) upon admission, as well as a higher modified Rankin Scale score (p = 0.002) and a lower Glasgow Outcome Scale score (p < 0.0001) at discharge. Furthermore, the lactate-positive group required a significantly higher norepinephrine application rate (NAR; p = 0.04) and a higher fraction of inspired oxygen (FiO2; p = 0.04) to maintain the defined CP parameters within the first 24 h. Conclusion: ICU-admitted iTBI patients with elevated serum lactate levels upon admission required higher CP support within the first 24 h of ICU treatment after iTBI. Serum lactate may be a helpful biomarker for improving ICU treatment in the early stages. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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10 pages, 996 KiB

Open AccessArticle

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock

by Pasquale Innelli, Teresa Lopizzo, Giovanni Paternò, Noemi Bruno, Rosa Paola Radice, Pietro Bertini, Alberto Marabotti, Giampaolo Luzi, Eugenio Stabile, Aldo Di Fazio, Giuseppe Pittella and Gianluca Paternoster

Diagnostics 2023, 13(7), 1350; https://doi.org/10.3390/diagnostics13071350 - 04 Apr 2023

Cited by 1 | Viewed by 1378

Abstract

Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase that is released into circulation upon cell death. DPP3 is involved in the degradation of angiotensins, enkephalines, and endomorphines. It has been shown that circulating DPP3 (cDPP3) plasma concentration increases in cardiogenic shock (CS) patients and correlates with high mortality risk. Cardiogenic shock is a life-threatening syndrome associated with organ hypoperfusion. One of the common causes of CS is acute myocardial infarction (AMI). This study aimed to investigate if cDPP3 levels are associated with CS severity and the need for ventilation in patients suffering from CS. Fifteen patients with CS were included in this study. Six patients were invasively ventilated. The values of cDPP3 were higher in ventilated patients than in non-ventilated patients at admission, 3 h, and 24 h after admission in the intensive care unit. Patients with pulmonary hypertension at admission also showed high cDPP3 values at all time points. Furthermore, high cDPP3 levels were associated with reduced stroke volume. Our results suggest that cDPP3 could predict CS progression and guide therapy escalation. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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13 pages, 1759 KiB

Open AccessArticle

Undernutrition Scored Using the CONUT Score with Hypoglycemic Status in ICU-Admitted Elderly Patients with Sepsis Shows Increased ICU Mortality

by Junko Yamaguchi, Kosaku Kinoshita, Katsuhiro Nakagawa and Minori Mizuochi

Diagnostics 2023, 13(4), 762; https://doi.org/10.3390/diagnostics13040762 - 17 Feb 2023

Cited by 1 | Viewed by 1158

Abstract

This study aimed to clarify whether the influence of undernutrition status and the degree of glycemic disorders affected the prognosis of patients with sepsis. A total of 307 adult patients with sepsis were retrospectively enrolled and analyzed. Characteristics, including nutrition status, calculated according to the Controlling Nutritional Status (CONUT) score of survivors and non-survivors, were examined. The independent prognostic factors of these patients with sepsis were extracted using multivariable logistic regression analysis. The CONUT scores in three glycemic categories were compared. Most patients with sepsis (94.8%) in the study had an undernutrition status according to their CONUT scores. High CONUT scores (odds ratio, 1.214; p = 0.002), indicating a poor nutritional status, were associated with high mortality. The CONUT scores in the hypoglycemic group were significantly higher than those in other groups with an undernutrition status (vs. hyperglycemic, p < 0.001; vs. intermediate glycemic, p = 0.006). The undernutrition statuses of patients with sepsis in the study scored using the CONUT were independent predictors of prognostic factors. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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10 pages, 1724 KiB

Open AccessArticle

Kinetics of the Cell Cycle Arrest Biomarkers (TIMP2 and IGFBP7) for the Diagnosis of Acute Kidney Injury in Critically Ill COVID-19 Patients

by Massimiliano Greco, Silvia De Rosa, Fabian Boehm, Sofia Spano, Romina Aceto, Antonio Voza, Francesco Reggiani, Marta Calatroni, Gianluca Castellani, Elena Costantini, Gianluca Villa and Maurizio Cecconi

Diagnostics 2023, 13(2), 317; https://doi.org/10.3390/diagnostics13020317 - 15 Jan 2023

Cited by 1 | Viewed by 1866

Abstract

Background: Acute kidney injury (AKI) is highly prevalent in critical COVID-19 patients. The diagnosis and staging of AKI are based on serum creatinine (sCr) and urinary output criteria, with limitations in the functional markers. New cell-cycle arrest biomarkers [TIMP2]*[IGFBP7] have been proposed for early detection of AKI, but their role in critically ill COVID-19 patients is poorly understood. Methods: We conducted an observational study to assess the performance of [TIMP2]*[IGFBP7] for the detection of AKI in critical COVID-19 patients admitted to our intensive care unit (ICU). We sampled urinary [TIMP2]*[IGFBP7] levels at ICU admission, 12 h, 24 h, and 48 h, and compared the results to the development of AKI, as well as baseline and laboratory data. Results: Forty-one patients were enrolled. The median age was 66 years [57–72] and most were males (85%). Thirteen patients (31.7%) developed no/mild stage AKI, 19 patients (46.3%) moderate AKI, and nine patients (22.0%) severe AKI. The ICU mortality was 29.3%. sCr levels in the Emergency Department or at ICU admission were not significantly different according to AKI stage. [TIMP-2]*[IGFBP-7] urinary levels were elevated in severe AKI at 12 h after ICU admission, but not at ICU admission or 24 h or 48 h after ICU admission. Conclusion: Urinary biomarkers [TIMP-2]*[IGFBP-7] were generally increased in this population with a high prevalence of AKI, and were higher in patients with severe AKI measured at 12 h from ICU admission. Further studies are needed to evaluate the best timing of these biomarkers in this population. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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11 pages, 299 KiB

Open AccessArticle

Sex and Age Influence on Association of CYP450 Polymorphism with Midazolam Levels in Critically Ill Children

by Carmen Flores-Pérez, Janett Flores-Pérez, Manuel de Jesús Castillejos López, Juan Luis Chávez-Pacheco, Karla Miroslava Tejada-Gutiérrez, Arnoldo Aquino-Gálvez and Luz María Torres-Espíndola

Diagnostics 2022, 12(11), 2797; https://doi.org/10.3390/diagnostics12112797 - 15 Nov 2022

Cited by 2 | Viewed by 1120

Abstract

Midazolam is a drug that is metabolized by cytochrome P450 (CYP450) enzymes, particularly CYP3A4 and CYP3A5. The present study aimed to determine the sex and age influence on association of CYP450 polymorphism with midazolam levels in critically ill children. Seventy-two DNA samples were genotyped by real-time PCR. Children ≤ five years of age who carry the rs776746 (T) allele in CYP3A5 gene were associated with lower plasma midazolam levels. The concentration median in patients was 0.0 ng/mL, while in patients with the normal (C) allele, it was 438.17 ng/mL (Q₂₅ 135.75–Q₇₅ 580.24), p = 0.005. The midazolam plasmatic concentration in female patients with the minor (T) allele was 0.0 ng/mL (Q₂₅0.00–Q₇₅204.3), while in patients with the normal (C) allele median it was 459.0 ng/mL (Q₂₅296.9–Q₇₅789.7), p = 0.002. Analysis of the dominant model for the rs2740574 variant in CYP3A4 revealed a median of 0.38 L/kg (Q₂₅0.02–Q₇₅1.5) for the volume of distribution parameter in female patients with the normal T allele, while female patients with the minor C allele showed a median of 18.1 L/kg (Q₂₅7.5–Q₇₅28.7) p = 0.02. Our results suggest an altered midazolam metabolism due to the presence the allelic rs2740574 variants of CYP3A4 and rs776746 of CYP3A5, and also the strong influence of age and sex. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

14 pages, 1869 KiB

Open AccessArticle

Incidence of Acute Kidney Injury in Polytrauma Patients and Predictive Performance of TIMP2 × IGFBP7 Biomarkers for Early Identification of Acute Kidney Injury

by Gianlorenzo Golino, Massimiliano Greco, Alessandro Rigobello, Vinicio Danzi, Massimo De Cal, Nicola Malchiorna, Monica Zannella, Paolo Navalesi, Rahul Costa-Pinto, Claudio Ronco and Silvia De Rosa

Diagnostics 2022, 12(10), 2481; https://doi.org/10.3390/diagnostics12102481 - 13 Oct 2022

Cited by 3 | Viewed by 2329

Abstract

Background: Acute kidney injury (AKI) is a common cause of organ failure in trauma patients who survive their initial injuries. It is independently associated with increased morbidity and mortality and prolongs the length of hospital stays. The objectives of this study were to describe the incidence of early AKI and influence of risk factors in polytrauma patients and evaluate the predictive potential of TIMP2 × IGFBP7 biomarkers in this patient cohort. Methods: We conducted a retrospective cohort study of severely injured adult patients who were consecutively admitted to a multidisciplinary ICU from May 2017 to May 2019. Detailed patient data was retrieved from ICU medical records. Fluid balance, urinary output, and sCr values up to 72 h were collected. Urine samples for measuring TIMP2 × IGFBP7 concentrations were obtained and analyzed from ICU admission to 72 h. Results: Among the 153 patients eligible for analysis, 45 were included in the AKI, and 108 in the no AKI cohorts. The incidence of AKI within 72 h, based on KDIGO criteria, was 28.8%. There were no differences in ISS, type and mechanism of injury, heart rate, and systolic BP at admission between groups. Patients with early AKI were older (68 vs. 49 years, p < 0.001), obese (BMI 26.2 vs. 24.7, p < 0.048), and more likely to have previous cardiac disease (27% vs. 5.6%, p < 0.001). TIMP2 × IGFBP7 values on ICU admission were associated with subsequent AKI in patients without evidence of AKI at the time of ICU admission. They were also higher in the AKI cohort and significantly correlated with renal replacement therapy (RRT) and episodes of hypotension. Multivariable analysis confirmed age, previous cardiac disease, and NephroCheck as the variables mostly associated with AKI, with AUC 0.792. Conclusions: TIMP2 × IGFBP7 may help identify trauma patients with tubular damage that may evolve into a clinically manifested syndrome. Prospective studies of TIMP2 × IGFBP7, as a trigger for early AKI bundle care, are warranted. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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13 pages, 1477 KiB

Open AccessArticle

Serum Lactate as Serum Biomarker for Cardiopulmonary Parameters within the First 24 Hours after a Spontaneous Intracerebral Hemorrhage

by Michael Bender, Kristin Haferkorn, Jasmin Nagl, Eberhard Uhl and Marco Stein

Diagnostics 2022, 12(10), 2414; https://doi.org/10.3390/diagnostics12102414 - 05 Oct 2022

Cited by 4 | Viewed by 1383

Abstract

Objective: Cardiopulmonary (CP) complications are well known in patients with an intracerebral hemorrhage (ICH) and could be associated with a higher serum lactate level. The present study aimed to assess the associations between the initial serum lactate level and the CP parameters within the first 24 h of intensive care unit (ICU) treatment in neurosurgical ICH patients. Patients and Methods: A total of 354 patients admitted to the ICU between 01/2009 and 12/2017 with a diagnosis of an ICH were retrospectively analyzed. Blood samples were taken upon admission, and each patient’s demographic, medical, and radiological data upon admission, as well as several CP parameters, were recorded within the first 24 h of ICU treatment. Results: A higher serum lactate level was associated with a lower GCS score (p < 0.0001), as well as a higher Acute Physiology and Chronic Health Evaluation II score (p = 0.002) upon admission. Additionally, patients with initially higher serum lactate levels had a significantly higher need for a norepinephrine application (p = 0.004) and inspiratory oxygen fraction (p = 0.03) within the first 24 h. Conclusion: Neurosurgical ICH patients with higher serum lactate levels upon admission require more CP support within the first 24 h of ICU treatment. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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18 pages, 12474 KiB

Open AccessArticle

Lipoprofiling Assessed by NMR Spectroscopy in Patients with Acute Coronary Syndromes: Is There a Need for Fasting Prior to Sampling?

by Laura-Adina Stănciulescu, Alexandru Scafa, Cătălin Duduianu, Raluca Stan, Alina Nicolescu, Calin Deleanu and Maria Dorobanțu

Diagnostics 2022, 12(7), 1675; https://doi.org/10.3390/diagnostics12071675 - 10 Jul 2022

Cited by 4 | Viewed by 2171

Abstract

Most patients presenting in an emergency unit with acute coronary syndromes (ACS) (which include non-ST-elevation myocardial infarction (NSTEMI), ST-elevation MI (STEMI), and unstable angina) usually meet at least two cardiovascular risk factors, such as dyslipidemia, arterial hypertension, diabetes mellitus type 2, obesity, history of or current smoking, etc. Most ACS patients suffer from a type of dyslipidemia, and in addition to this there are ACS patients rushed into the emergency units for which the feeding status is unknown. Thus, we set out to evaluate the effect of fasting on 16 blood metabolite concentrations and 114 lipoprotein parameters on one control group and a group of statin-treated ACS patients hospitalized in a cardiovascular emergency unit, using Nuclear Magnetic Resonance (NMR) spectroscopy. The results indicated trends (in terms of number of cases, but not necessarily in terms of the magnitude of the effect) for as many as four metabolites and 48 lipoproteins. The effect was defined as a trend for results showing over 70% of the cases from either one or both groups that experienced parameter changes in the same direction (i.e., either increased or decreased). In terms of magnitude, the effect is rather low, leading to the overall conclusion that in cardiovascular (CV) emergency units, the blood samples analyzed in any feeding status would provide close results and very valuable information regarding prognosis and for fast decisions on patient’s proper management. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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Graphical abstract

11 pages, 1325 KiB

Open AccessArticle

Carboxyhemoglobin (CO-Hb) Correlates with Hemolysis and Hospital Mortality in Extracorporeal Membrane Oxygenation: A Retrospective Registry

by Xavier Bemtgen, Jonathan Rilinger, Manuel Holst, Felix Rottmann, Corinna N. Lang, Markus Jäckel, Viviane Zotzmann, Christoph Benk, Tobias Wengenmayer, Alexander Supady and Dawid L. Staudacher

Diagnostics 2022, 12(7), 1642; https://doi.org/10.3390/diagnostics12071642 - 05 Jul 2022

Cited by 6 | Viewed by 1723

Abstract

Background: Patients supported with extracorporeal membrane oxygenation (ECMO) may develop elevated carboxyhemoglobin (CO-Hb), a finding described in the context of hemolysis. Clinical relevance of elevated CO-Hb in ECMO is unclear. We therefore investigated the prognostic relevance of CO-Hb during ECMO support. Methods: Data derives from a retrospective single-center registry study. All ECMO patients in a medical ICU from October 2010 through December 2019 were considered. Peak arterial CO-Hb value during ECMO support and median CO-Hb values determined by point-of-care testing for distinct time intervals were determined. Groups were divided by CO-Hb (<2% or ≥2%). The primary endpoint was hospital survival. Results: A total of 729 patients with 59,694 CO-Hb values met the inclusion criteria. Median age (IQR) was 59 (48–68) years, 221/729 (30.3%) were female, and 278/729 (38.1%) survived until hospital discharge. Initial ECMO configuration was veno-arterial in 431/729 (59.1%) patients and veno-venous in 298/729 (40.9%) patients. Markers for hemolysis (lactate dehydrogenase, bilirubin, hemolysis index, and haptoglobin) all correlated significantly with higher CO-Hb (p < 0.001, respectively). Hospital survival was significantly higher in patients with CO-Hb < 2% compared to CO-Hb ≥ 2%, evaluating time periods 24–48 h (48.6% vs. 35.2%, p = 0.003), 48–72 h (51.5% vs. 36.8%, p = 0.003), or >72 h (56.9% vs. 31.1%, p < 0.001) after ECMO cannulation. Peak CO-Hb was independently associated with lower hospital survival after adjustment for confounders. Conclusions: In ECMO, CO-Hb correlates with hemolysis and hospital survival. If high CO-Hb measured should trigger a therapeutic intervention in order to reduce hemolysis has to be investigated in prospective trials. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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8 pages, 4620 KiB

Open AccessCommunication

Comparison of the Mortality Prediction Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in COVID-19 and Sepsis

by Alice G. Vassiliou, Alexandros Zacharis, Charikleia S. Vrettou, Chrysi Keskinidou, Edison Jahaj, Zafeiria Mastora, Stylianos E. Orfanos, Ioanna Dimopoulou and Anastasia Kotanidou

Diagnostics 2022, 12(5), 1261; https://doi.org/10.3390/diagnostics12051261 - 18 May 2022

Cited by 2 | Viewed by 1384

Abstract

In the last years, biomarkers of infection, such as the soluble urokinase plasminogen activator receptor (suPAR), have been extensively studied as potential diagnostic and prognostic biomarkers in the intensive care unit (ICU). In this study, we investigated whether this biomarker can be used in COVID-19 and non-COVID-19 septic patients for mortality prediction. Serum suPAR levels were measured in 79 non-COVID-19 critically ill patients upon sepsis (within 6 h), and on admission in 95 COVID-19 patients (66 critical and 29 moderate/severe). The non-COVID-19 septic patients were matched for age, sex, and disease severity, while the site of infection was the respiratory system. On admission, COVID-19 patients presented with higher suPAR levels, compared to non-COVID-19 septic patients (p < 0.01). More importantly, suPAR measured upon sepsis could not differentiate survivors from non-survivors (p > 0.05), as opposed to suPAR measured on admission in COVID-19 survivors and non-survivors (p < 0.0001). By the generated ROC curve, the prognostic value of suPAR in COVID-19 was 0.81, at a cut-off value of 6.3 ng/mL (p < 0.0001). suPAR measured early (within 24 h) after hospital admission seems like a specific and sensitive mortality risk predictor in COVID-19 patients. On the contrary, suPAR measured at sepsis diagnosis in non-COVID-19 critically ill patients, does not seem to be a prognostic factor of mortality. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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Review

Jump to: Research

17 pages, 1119 KiB

Open AccessReview

Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

by Grazia Maria Virzì, Maria Mattiotti, Massimo de Cal, Claudio Ronco, Monica Zanella and Silvia De Rosa

Diagnostics 2023, 13(1), 79; https://doi.org/10.3390/diagnostics13010079 - 27 Dec 2022

Cited by 13 | Viewed by 3309

Abstract

Lipopolysaccharide (LPS) or endotoxin, the major cell wall component of Gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. A large amount of LPS induces inappropriate activation of the immune system, triggering an exaggerated inflammatory response and consequent extensive organ injury, providing the basis of sepsis damage. In this review, we will briefly describe endotoxin’s molecular structure and its main pathogenetic action during sepsis. In addition, we will summarize the main different available methods for endotoxin detection with a special focus on the wider spectrum offered by omics technologies (genomics, transcriptomics, proteomics, and metabolomics) and promising applications of these in the identification of specific biomarkers for sepsis. Full article

(This article belongs to the Special Issue Predictive and Prognostic Markers in Critically Ill Patients)

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