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Article ; Online: Biomarkers to guide immunomodulatory treatment: where do we stand?

Kyriazopoulou, Evdoxia / Giamarellos-Bourboulis, Evangelos J / Akinosoglou, Karolina

2023 Volume 23, Issue 11, Page(s) 945–958

Abstract: Introduction: This review summarizes current progress in the development of biomarkers to guide immunotherapy in oncology, rheumatology, and critical illness.: Areas covered: An extensive literature search was performed about biomarkers classifying ... ...

Abstract	Introduction: This review summarizes current progress in the development of biomarkers to guide immunotherapy in oncology, rheumatology, and critical illness. Areas covered: An extensive literature search was performed about biomarkers classifying patients' immune responses to guide immunotherapy in oncology, rheumatology, and critical illness. Surface markers, such as programmed death-ligand 1 (PD-L1), genetic biomarkers, such as tumor mutation load, and circulating tumor DNA are biomarkers associated with the effectiveness of immunotherapy in oncology. Genomics, metabolomics, and proteomics play a crucial role in selecting the most suitable therapeutic options for rheumatologic patients. Phenotypes and endotypes are a promising approach to detect critically ill patients with hyper- or hypo-inflammation. Sepsis trials using biomarkers such as ferritin, lymphopenia, HLA-DR expression on monocytes and PD-L1 to guide immunotherapy have been already conducted or are currently ongoing. Immunotherapy in COVID-19 pneumonia, guided by C-reactive protein and soluble urokinase plasminogen activator receptor (suPAR) has improved patient outcomes globally. More research is needed into immunotherapy in other critical conditions. Expert opinion: Targeted immunotherapy has improved outcomes in oncology and rheumatology, paving the way for precision medicine in the critically ill. Transcriptomics will play a crucial role in detecting the most suitable candidates for immunomodulation.
Language	English
Publishing date	2023-09-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1080/14737159.2023.2258063
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Article: Antimicrobial Stewardship Using Biomarkers: Accumulating Evidence for the Critically Ill.

Kyriazopoulou, Evdoxia / Giamarellos-Bourboulis, Evangelos J

Antibiotics (Basel, Switzerland)

2022 Volume 11, Issue 3

Abstract: This review aims to summarize current progress in the management of critically ill, using biomarkers as guidance for antimicrobial treatment with a focus on antimicrobial stewardship. Accumulated evidence from randomized clinical trials (RCTs) and ... ...

Abstract	This review aims to summarize current progress in the management of critically ill, using biomarkers as guidance for antimicrobial treatment with a focus on antimicrobial stewardship. Accumulated evidence from randomized clinical trials (RCTs) and observational studies in adults for the biomarker-guided antimicrobial treatment of critically ill (mainly sepsis and COVID-19 patients) has been extensively searched and is provided. Procalcitonin (PCT) is the best studied biomarker; in the majority of randomized clinical trials an algorithm of discontinuation of antibiotics with decreasing PCT over serial measurements has been proven safe and effective to reduce length of antimicrobial treatment, antibiotic-associated adverse events and long-term infectious complications like infections by multidrug-resistant organisms and
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics11030367
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Article ; Online: Immunogenicity and safety of vaccines in multiple sclerosis: A systematic review and meta-analysis.

Marantos, Theodoros / Kyriazopoulou, Evdoxia / Lekakis, Vasileios / Voumvourakis, Konstantinos I / Tsiodras, Sotirios

Journal of the neurological sciences

2023 Volume 456, Page(s) 122852

Abstract: Background: Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis.!# ...

Abstract	Background: Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis. Methods: MEDLINE(PubMed) and Cochrane databases were searched based on a pre-specified protocol (PROSPERO: CRD42020202018). Studies reporting on patients with MS, diagnosed with McDonald criteria getting vaccinated with any type of vaccine were included in the analysis. The primary endpoint was the incidence of patients being seropositive and experience adverse events after vaccination. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Two reviewers independently screened and reviewed existing literature and assessed study quality with the Methodological index for non-randomized studies. Results: Of 295 articles, 45 studies were analyzed. Seroconversion after COVID-19 vaccines was 76% (95% CI, 70-80; I Conclusion: The majority of MS patients vaccinated for COVID-19 or seasonal influenza mount an adequate immune response without safety concerns. Data on other vaccines are limited.
MeSH term(s)	Humans ; Multiple Sclerosis/drug therapy ; COVID-19 Vaccines ; Influenza, Human ; Influenza Vaccines/adverse effects ; Sphingosine 1 Phosphate Receptor Modulators ; COVID-19 ; Recurrence
Chemical Substances	COVID-19 Vaccines ; Influenza Vaccines ; Sphingosine 1 Phosphate Receptor Modulators
Language	English
Publishing date	2023-12-20
Publishing country	Netherlands
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2023.122852
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Article ; Online: Biomarkers in sepsis: can they help improve patient outcome?

Kyriazopoulou, Evdoxia / Poulakou, Garyfallia / Giamarellos-Bourboulis, Evangelos J

Current opinion in infectious diseases

2021 Volume 34, Issue 2, Page(s) 126–134

Abstract: Purpose of review: Biomarkers, mainly procalcitonin, are commonly used in sepsis diagnosis, prognosis and treatment follow-up. This review summarizes the potential benefit of their use for the critically ill.: Recent findings: Increased clinical ... ...

Abstract	Purpose of review: Biomarkers, mainly procalcitonin, are commonly used in sepsis diagnosis, prognosis and treatment follow-up. This review summarizes the potential benefit of their use for the critically ill. Recent findings: Increased clinical evidence from randomized clinical trials of biomarker-guided treatment suggests a trend for appropriate but short antimicrobial treatment for the critically ill. Procalcitonin (PCT) is the most studied biomarker; in the majority of randomized clinical trials, the use of a stopping rule of antibiotics on the day when PCT is below 80% from baseline or less than 0.5 ng/ml was proven effective to reduce length of antimicrobial treatment, antibiotic-associated adverse events and infectious complications like infections by multidrug-resistant organisms and Clostridium difficile. Survival benefit was also noted. Summary: Biomarkers, mainly PCT, may help improve sepsis outcome by restriction of injudicious antimicrobial use.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Biomarkers/blood ; Critical Illness/therapy ; Humans ; Procalcitonin/blood ; Sepsis/blood ; Sepsis/diagnosis ; Sepsis/drug therapy ; Sepsis/microbiology
Chemical Substances	Anti-Bacterial Agents ; Biomarkers ; Procalcitonin
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000707
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Article ; Online: Monitoring immunomodulation in patients with sepsis.

Kyriazopoulou, Evdoxia / Giamarellos-Bourboulis, Evangelos J

Expert review of molecular diagnostics

2020 Volume 21, Issue 1, Page(s) 17–29

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Animals ; Biomarkers ; Endophenotypes ; Ferritins ; HLA-DR Antigens ; Humans ; Immunomodulation/drug effects ; Macrophages/immunology ; Sepsis/diagnosis ; Sepsis/immunology ; Sepsis/therapy
Chemical Substances	Biomarkers ; HLA-DR Antigens ; Ferritins (9007-73-2)
Language	English
Publishing date	2020-12-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1080/14737159.2020.1851199
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Article ; Online: BIOMARKERS: CAN THEY REALLY GUIDE OUR DAILY PRACTICE?

Tsangaris, Iraklis / Antonakos, Nikolaos / Fantoni, Massimo / Kaplanski, Gilles / Kyriazopoulou, Evdoxia / Veas, Francisco / Clemens, Mark

Shock (Augusta, Ga.)

2022 Volume 59, Issue 3S Suppl 1, Page(s) 16–20

Abstract: Abstract: Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of ... ...

Abstract	Abstract: Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on "Biomarkers: can they really use guide our daily practice?" presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.
MeSH term(s)	Humans ; Biomarkers ; C-Reactive Protein ; Bacteremia ; Ferritins ; Procalcitonin
Chemical Substances	Biomarkers ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2) ; Procalcitonin
Language	English
Publishing date	2022-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0000000000001957
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Article ; Online: Pharmacological management of sepsis in adults with a focus on the current gold standard treatments and promising adjunctive strategies: evidence from the last five years.

Kyriazopoulou, Evdoxia / Giamarellos-Bourboulis, Evangelos J

Expert opinion on pharmacotherapy

2019 Volume 20, Issue 8, Page(s) 991–1007

Abstract: Introduction: The last five years, there have been considerable changes in our perception on the pathogenesis of sepsis. This review aims to summarize the current progress of the last five years in the management and research fields of sepsis in a ... ...

Abstract	Introduction: The last five years, there have been considerable changes in our perception on the pathogenesis of sepsis. This review aims to summarize the current progress of the last five years in the management and research fields of sepsis in a holistic approach. To achieve this, accumulated evidence over the last five years coming from randomized clinical trials (RCTs) and observational studies in adults for the management of sepsis is provided. Areas covered: In this review, the authors discuss available strategies in sepsis, divided into standard-of-care and adjunctive therapies. Standard-of-care approaches comprise antimicrobials, fluids, vasoactive agents, steroids. Antimicrobials remain the mainstay of treatment. However, key-point of management is early recognition of the patient that guides early start of antimicrobials. Patients with suspected infection and any two of: an altered mental state, more than 22 breaths per minute and systolic blood pressure below 100 mmHg should receive early intervention with broad-spectrum antimicrobials and fluids. Expert opinion: Low dose hydrocortisone replacement and fludrocortisone seem promising for the patient at septic shock. Adjunctive macrolide treatment of severe CAP is also associated with survival benefit. Future studies will help to provide additional insight into the field.
MeSH term(s)	Adult ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents/therapeutic use ; Humans ; Macrolides/therapeutic use ; Randomized Controlled Trials as Topic ; Sepsis/drug therapy ; Shock, Septic/drug therapy ; Steroids/therapeutic use
Chemical Substances	Anti-Bacterial Agents ; Anti-Infective Agents ; Macrolides ; Steroids
Language	English
Publishing date	2019-03-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2019.1589451
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Article ; Online: HEPARIN-BINDING PROTEIN LEVELS PREDICT UNFAVORABLE OUTCOME IN COVID-19 PNEUMONIA: A POST HOC ANALYSIS OF THE SAVE TRIAL.

Kyriazopoulou, Evdoxia / Dalekos, George N / Metallidis, Symeon / Poulakou, Garyphalia / Papanikolaou, Ilias C / Tzavara, Vasiliki / Argyraki, Katerina / Alexiou, Zoi / Panagopoulos, Periklis / Samarkos, Michael / Chrysos, George / Tseliou, Aikaterini / Milionis, Haralampos / Sympardi, Styliani / Vasishta, Anil / Giamarellos-Bourboulis, Evangelos J

Shock (Augusta, Ga.)

2024 Volume 61, Issue 3, Page(s) 395–399

Abstract: Abstract: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble ... ...

Abstract	Abstract: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.
MeSH term(s)	Humans ; Antimicrobial Cationic Peptides ; Biomarkers ; Blood Proteins ; COVID-19 ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; Prognosis ; Respiratory Insufficiency
Chemical Substances	Antimicrobial Cationic Peptides ; AZU1 protein, human ; Biomarkers ; Blood Proteins ; Interleukin 1 Receptor Antagonist Protein
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Clinical Study ; Journal Article
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0000000000002315
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Article ; Online: Soluble fms-like tyrosine kinase 1, placental growth factor and procalcitonin as biomarkers of gram-negative sepsis: Analysis through a derivation and a validation cohort.

Vittoros, Vasileios / Kyriazopoulou, Evdoxia / Lada, Malvina / Tsangaris, Iraklis / Koutelidakis, Ioannis M / Giamarellos-Bourboulis, Evangelos J

Medicine

2021 Volume 100, Issue 44, Page(s) e27662

Abstract: Abstract: Further improvement of the diagnostic and prognostic performance of biomarkers for the critically ill is needed. Procalcitonin (PCT), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 raise interest for sepsis diagnosis and ...

Abstract	Abstract: Further improvement of the diagnostic and prognostic performance of biomarkers for the critically ill is needed. Procalcitonin (PCT), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 raise interest for sepsis diagnosis and prognosis.Serum samples from 2 cohorts of 172 patients (derivation cohort) and of 164 patients (validation cohort) comprising only patients with microbiologically confirmed gram-negative infections were analyzed. PlGF, s-Flt-1 and procalcitonin (PCT) were measured in serum within 24 hours from sepsis onset and repeated on days 3 and 7.PCT and s-Flt-1 baseline levels were higher in sepsis and septic shock compared to non-sepsis; this was not the case for PlGF. s-Flt-1 at concentrations greater than 60 pg/ml diagnosed sepsis with sensitivity 72.3% and specificity 54.9% whereas at concentrations greater than 70 pg/ml predicted unfavorable outcome with specificity 73.0% and sensitivity 63.7%. At least 80% decrease of PCT and/or PCT less than 0.5 ng/ml on day 7 was protective from sepsis-associated death.Both s-Flt-1 and PCT should be measured in the critically ill since they provide additive information for sepsis diagnosis and prognosis.ClinicalTrials.gov numbers NCT01223690 and NCT00297674.
MeSH term(s)	Aged ; Aged, 80 and over ; Bacteremia ; Biomarkers/blood ; Critical Illness ; Female ; Humans ; Middle Aged ; Placenta Growth Factor/blood ; Procalcitonin/blood ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis/blood ; Sepsis/diagnosis ; Sepsis/microbiology ; Shock, Septic/blood ; Shock, Septic/diagnosis ; Shock, Septic/microbiology ; Vascular Endothelial Growth Factor Receptor-1/blood
Chemical Substances	Biomarkers ; PGF protein, human ; Procalcitonin ; Placenta Growth Factor (144589-93-5) ; FLT1 protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1)
Language	English
Publishing date	2021-12-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000027662
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Article ; Online: Presepsin as a diagnostic and prognostic biomarker of severe bacterial infections and COVID-19.

Kyriazopoulou, Evdoxia / Leventogiannis, Konstantinos / Tavoulareas, Georgios / Mainas, Efstratios / Toutouzas, Konstantinos / Mathas, Christos / Prekates, Athanassios / Sakka, Vissaria / Panagopoulos, Periklis / Syrigos, Konstantinos / Giamarellos-Bourboulis, Evangelos J

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3814

Abstract: We aimed to develop presepsin as a marker of diagnosis of severe infections of either bacterial and viral origin. The derivation cohort was recruited from 173 hospitalized patients with acute pancreatitis or post-operative fever or infection suspicion ... ...

Abstract	We aimed to develop presepsin as a marker of diagnosis of severe infections of either bacterial and viral origin. The derivation cohort was recruited from 173 hospitalized patients with acute pancreatitis or post-operative fever or infection suspicion aggravated by at least one sign of the quick sequential organ failure assessment (qSOFA). The first validation cohort was recruited from 57 admissions at the emergency department with at least one qSOFA sign and the second validation cohort from 115 patients with COVID-19 pneumonia. Presepsin was measured in plasma by the PATHFAST assay. Concentrations more than 350 pg/ml had sensitivity 80.2% for sepsis diagnosis in the derivation cohort (adjusted odds ratio 4.47; p < 0.0001). In the derivation cohort, sensitivity for 28-day mortality prognosis was 91.5% (adjusted odds ratio 6.82; p: 0.001). Concentrations above 350 pg/ml had sensitivity 93.3% for the diagnosis of sepsis in the first validation cohort; this was 78.3% in the second validation cohort of COVID-19 aiming at the early diagnosis of acute respiratory distress syndrome necessitating mechanical ventilation. The respective sensitivity for 28-day mortality was 85.7% and 92.3%. Presepsin may be a universal biomarker for the diagnosis of severe infections of bacterial origin and prediction of unfavorable outcome.
MeSH term(s)	Humans ; Acute Disease ; Prognosis ; COVID-19/diagnosis ; Pancreatitis ; Bacterial Infections ; Sepsis/diagnosis ; COVID-19 Testing ; Peptide Fragments ; Lipopolysaccharide Receptors
Chemical Substances	presepsin protein, human ; Peptide Fragments ; Lipopolysaccharide Receptors
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30807-5
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