|
1
|
Uchiumi T, Nishibori M, Morimatsu H, Inoue Y, Nishi H, Ota N. Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis. J Immunol Methods 2025; 541:113868. [PMID: 40324742 DOI: 10.1016/j.jim.2025.113868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 04/29/2025] [Accepted: 05/01/2025] [Indexed: 05/07/2025]
Abstract
The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204. The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future.
Collapse
Affiliation(s)
| | - Masahiro Nishibori
- Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroshi Morimatsu
- Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoko Inoue
- Diagnostic Drug Office, Shionogi & Co., Ltd., Osaka, Japan
| | - Hiroshi Nishi
- Diagnostic Drug Office, Shionogi & Co., Ltd., Osaka, Japan
| | - Norio Ota
- Diagnostic Drug Office, Shionogi & Co., Ltd., Osaka, Japan
| |
Collapse
|
|
2
|
Roccaforte V, Sabbatini G, Panella R, Daves M, Formenti P, Gotti M, Galimberti A, Spreafico M, Piccin A, Lippi G, Pezzi A, Pastori S. The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit. Clin Chem Lab Med 2025; 63:1031-1042. [PMID: 39851139 DOI: 10.1515/cclm-2024-1202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/11/2024] [Indexed: 01/26/2025]
Abstract
OBJECTIVES The aim of the study was to evaluate the predictive value of cell population data (CPD) parameters in comparison with procalcitonin (PCT) and C-reactive protein (CRP) for an early diagnosis of sepsis in intensive care unit (ICU). The effect of renal function on CPD, PCT and CRP, in septic and non-septic patients was also investigated. METHODS This is a retrospective, observational and single-center study, performed with data collected from patients consecutively admitted to the ICU of the Edoardo Bassini Hospital in Milan. Patients were divided in septic and non-septic according to Sepsis-III criteria. The control group was formed by critically ill patients without sepsis. Patients with sepsis were further divided in patients with sepsis and patients with septic shock. RESULTS A significant difference between septic and non-septic patients was found for neutrophils complexity (NE-SSC), neutrophils fluorescence intensity (NE-SFL), width of dispersion of neutrophils fluorescence (NE-WY), monocytes complexity (MO-X), monocytes fluorescence intensity (MO-Y), PCT and CRP parameters. PCT, neutrophils sixe (NE-FSC), NE-WY, width of dispersion of neutrophils size (NE-WZ) and MO-X discriminated sepsis and septic-shock patients. CPD parameters were not influenced by renal function. CPD, PCT and CRP had a heterogeneous diagnostic performance efficiency in the prediction of sepsis. Overall, NE-SSC, NE-SFL, width of dispersion of neutrophils complexity (NE-WX), MO-X, MO-Y, PCT and CRP displayed the best diagnostic performance for sepsis. CONCLUSIONS This study suggested that some CPD parameters (i.e., NE-SFL and MO-X) might provide useful information for diagnosis and management of sepsis.
Collapse
Affiliation(s)
- Vincenzo Roccaforte
- S.C. Analisi Chimico Cliniche e Microbiologiche, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Giovanni Sabbatini
- S.C. Anestesia, Rianimazione e Terapia Intensiva, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Rossella Panella
- S.C. Analisi Chimico Cliniche e Microbiologiche, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Massimo Daves
- Laboratory of Clinical Biochemistry (SABES-ASDAA), Hospital of Bolzano, Bolzano, Italy
| | - Paolo Formenti
- S.C. Anestesia, Rianimazione e Terapia Intensiva, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Miriam Gotti
- S.C. Anestesia, Rianimazione e Terapia Intensiva, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Andrea Galimberti
- S.C. Anestesia, Rianimazione e Terapia Intensiva, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Marta Spreafico
- Department of Transfusion Medicine and Hematology, ASST-Lecco, Lecco, Italy
| | - Andrea Piccin
- Northern Ireland Blood Transfusion Service, Belfast, UK
- University of Medicine Innsbruck, Innsbruck, Austria
- Department of Industrial Engineering, University of Trento, Trento, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Angelo Pezzi
- S.C. Anestesia, Rianimazione e Terapia Intensiva, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| | - Stefano Pastori
- S.C. Analisi Chimico Cliniche e Microbiologiche, 159114 ASST Nord Milano , Ospedale Bassini, Cinisello Balsamo, Italy
| |
Collapse
|
|
3
|
Piccioni A, Baroni S, Rozzi G, Belvederi F, Leggeri S, Spagnuolo F, Novelli M, Pignataro G, Candelli M, Covino M, Gasbarrini A, Franceschi F. Evaluation of Presepsin for Early Diagnosis of Sepsis in the Emergency Department. J Clin Med 2025; 14:2480. [PMID: 40217929 PMCID: PMC11989492 DOI: 10.3390/jcm14072480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Background: to date, there are no specific markers available for diagnosing sepsis. Diagnosis is, indeed, mainly determined by clinical suspicion and the evaluation of the patient's overall condition. This evaluation involves assessing various inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), along with markers of tissue hypoxia, such as serum lactate. Additionally, it includes scores that account for complete blood count (CBC), organ function markers, and the patient's vital parameters, including SOFA, qSOFA, SIRS, and NEWS. Over the years, various potential biomarkers have been studied; among these presepsin appears to offer some significant advantages. Objective: Presepsin, which is the N-terminal fragment of the soluble component of CD14, is primarily elevated in infectious conditions. Its levels rise much earlier in the context of infection compared to currently used biomarkers. As a result, Presepsin shows promise for the early identification of septic patients and could aid in prognostic assessment, allowing clinicians to prioritize care for critically ill individuals. Methods: this study aims to evaluate the role of serum presepsin in the early diagnosis of sepsis in patients who present to the emergency room with a clinical suspicion of sepsis. The secondary objectives include comparing the diagnostic performance of presepsin with traditional biomarkers currently used for sepsis diagnosis and assessing its utility as a prognostic biomarker for mortality risk stratification, in comparison with validated severity prediction scores. Result: Presepsin had valuable diagnostic utility for sepsis (AUC 0.946, p < 0.001) comparable to PCT (AUC 0.905, p < 0.001). Conclusions: the combination of Presepsin, PCT, and EWS yielded the highest diagnostic accuracy for sepsis.
Collapse
Affiliation(s)
- Andrea Piccioni
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.P.); (M.C.); (M.C.); (F.F.)
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Silvia Baroni
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
- Unit of Chemistry, Biochemistry and Clinical Molecular Biology, Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.B.); (S.L.)
| | - Gloria Rozzi
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Fabio Belvederi
- Unit of Chemistry, Biochemistry and Clinical Molecular Biology, Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.B.); (S.L.)
| | - Simone Leggeri
- Unit of Chemistry, Biochemistry and Clinical Molecular Biology, Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.B.); (S.L.)
| | - Fabio Spagnuolo
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Michela Novelli
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Giulia Pignataro
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.P.); (M.C.); (M.C.); (F.F.)
| | - Marcello Candelli
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.P.); (M.C.); (M.C.); (F.F.)
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Marcello Covino
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.P.); (M.C.); (M.C.); (F.F.)
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| | - Antonio Gasbarrini
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesco Franceschi
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.P.); (M.C.); (M.C.); (F.F.)
- Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (S.B.); (G.R.); (F.S.); (M.N.); (A.G.)
| |
Collapse
|
|
4
|
Mišura Jakobac K, Milunović V, Kušec V, Hrabač P, Martinović M, Radić-Krišto D, Ostojić Kolonić S, Pavliša G. Biomarkers Affecting Treatment Outcomes of Febrile Neutropenia in Hematological Patients with Lymphomas: Is Presepsin the New Promising Diagnostic and Prognostic Biomarker? J Clin Med 2025; 14:2238. [PMID: 40217689 PMCID: PMC11989253 DOI: 10.3390/jcm14072238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: In hematological patients receiving treatment for lymphomas, febrile neutropenia (FN) is a serious complication associated with significant morbidity and mortality. This prospective study aimed to evaluate the diagnostic and prognostic value of the novel biomarker presepsin (PSP) in episodes of FN in this specific cohort of patients. Methods: The study enrolled 37 patients with FN and 18 patients with neutropenia without fever as a control group. Patients with FN were divided into two groups: those with confirmed infections and those without them. Various clinical and laboratory parameters were analyzed, including inflammatory and biochemical markers, focusing on implications of PSP. Results: Among patients with FN, 65% had proven infections with significantly higher PSP levels compared to those without infections and control group (p < 0.001). Positive blood cultures were found in 13.5% of all FN episodes. PSP showed greater sensitivity than traditional biomarkers like procalcitonin and C-reactive protein for differentiating septic from non-septic complications. Increased PSP levels at admission suggested a poorer survival prognosis. Each 1 ng/mL increase in PSP correlated with a 5% increase in mortality risk (HR 1.05; p < 0.001), with a one-year mortality rate of 56.7%, underscoring the necessity for better predictive markers. Other markers, including CRP, PCT, IgG, and albumin, were not significantly associated with mortality; however, platelets and qSOFA exhibited borderline significance. Conclusions: PSP is a valuable biomarker for identifying high-risk FN in lymphoma patients and predicting mortality, correlating with infection severity. Larger multi-center studies are needed to validate these findings and optimize PSP's clinical application to improve outcomes.
Collapse
Affiliation(s)
- Karla Mišura Jakobac
- Division of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Vibor Milunović
- Division of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, Croatia
| | - Vesna Kušec
- Department of Innovative Diagnostics, Children’s Hospital Srebrnjak, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Pero Hrabač
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Marko Martinović
- Division of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, Croatia
- School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia
| | - Delfa Radić-Krišto
- Division of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Slobodanka Ostojić Kolonić
- Division of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Gordana Pavliša
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
| |
Collapse
|
|
5
|
de Moura ELB, Pereira RW. Crossing Age Boundaries: The Unifying Potential of Presepsin in Sepsis Diagnosis Across Diverse Age Groups. J Clin Med 2024; 13:7038. [PMID: 39685497 DOI: 10.3390/jcm13237038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 12/18/2024] Open
Abstract
Sepsis is a pervasive condition that affects individuals of all ages, with significant social and economic consequences. The early diagnosis of sepsis is fundamental for establishing appropriate treatment and is based on warning scores and clinical characteristics, with positive microbiological cultures being the gold standard. Research has yet to identify a single biomarker to meet this diagnostic demand. Presepsin is a molecule that has the potential as a biomarker for diagnosing sepsis. In this paper, we present a narrative review of the diagnostic and prognostic performance of presepsin in different age groups. Given its particularities, it is identified that presepsin is a potential biomarker for sepsis at all stages of life.
Collapse
Affiliation(s)
- Edmilson Leal Bastos de Moura
- Health Sciences Doctoral Program, University of Brasília (UnB), Brasilia 70910-900, Distrito Federal, Brazil
- School of Health Sciences, Distrito Federal University (UnDF), Brasilia 70710-907, Distrito Federal, Brazil
| | - Rinaldo Wellerson Pereira
- Health Sciences Doctoral Program, University of Brasília (UnB), Brasilia 70910-900, Distrito Federal, Brazil
- Genomic Sciences and Biotechnology Graduate Program, Catholic University of Brasilia, Brasilia 71966-700, Distrito Federal, Brazil
| |
Collapse
|
|
6
|
Zhou Y, Feng Y, Liang X, Gui S, Ren D, Liu Y, She J, Zhang X, Song F, Yu L, Zhang Y, Wang J, Zou Z, Mei J, Wen S, Yang M, Li X, Tan X, Li Y. Elevations in presepsin, PCT, hs-CRP, and IL-6 levels predict mortality among septic patients in the ICU. J Leukoc Biol 2024; 116:890-900. [PMID: 38776408 DOI: 10.1093/jleuko/qiae121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 04/06/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024] Open
Abstract
This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and third days (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP_3 - PSEP_0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17-6.22), ΔPCT (= PCT_3 - PCT_0) > -0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68-19.80), ΔhsCRP (= hsCRP_3 - hsCRP_0) > -19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61-29.40), and ΔIL-6 (= IL-6_3 - IL-6_0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance.
Collapse
Affiliation(s)
- Yan Zhou
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Yongwen Feng
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Xiaomin Liang
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Shuiqing Gui
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Di Ren
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Yuanzhi Liu
- Laboratory Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Jijia She
- Laboratory Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Xiaomei Zhang
- Department of IVD Clinical Research & Medical Affairs, Shenzhen Mindray Biomedical Electronics Co., Ltd. Mindray Building, Keji 12th Road South, High-tech Industrial Park, Nanshan, Shenzhen, Guangdong 518057, China
| | - Fei Song
- Department of IVD Clinical Research & Medical Affairs, Shenzhen Mindray Biomedical Electronics Co., Ltd. Mindray Building, Keji 12th Road South, High-tech Industrial Park, Nanshan, Shenzhen, Guangdong 518057, China
| | - Lina Yu
- Department of IVD Clinical Research & Medical Affairs, Shenzhen Mindray Biomedical Electronics Co., Ltd. Mindray Building, Keji 12th Road South, High-tech Industrial Park, Nanshan, Shenzhen, Guangdong 518057, China
| | - Yiwen Zhang
- Department of IVD Clinical Research & Medical Affairs, Shenzhen Mindray Biomedical Electronics Co., Ltd. Mindray Building, Keji 12th Road South, High-tech Industrial Park, Nanshan, Shenzhen, Guangdong 518057, China
| | - Jinping Wang
- Department of Pharmacy, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Zhiye Zou
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Jiang Mei
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Sha Wen
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Mei Yang
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Xinsi Li
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| | - Xuerui Tan
- Cardiovascular medicine, First Affiliated Hospital of Shantou University Medical College, No. 22 Xinling Road, Jinping District, Shantou, Guangdong 515041, China
| | - Ying Li
- Department of Critical Care Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong 518035, China
| |
Collapse
|
|
7
|
Taha AM, Najah Q, Omar MM, Abouelmagd K, Ali M, Hasan MT, Allam SA, Hamam YA, Arian R, Abd-ElGawad M. Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis. Medicine (Baltimore) 2024; 103:e38525. [PMID: 38905400 PMCID: PMC11191987 DOI: 10.1097/md.0000000000038525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 05/17/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients. METHODS We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value. RESULTS In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%. CONCLUSION Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.
Collapse
Affiliation(s)
| | - Qasi Najah
- Faculty of Medicine, University of EL-Mergib, Al Khums, Libya
| | | | - Khaled Abouelmagd
- Cardiology Department, Faculty of Medicine, Al-Azhar University, Egypt
| | - Mohammed Ali
- Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | | | | | - Yasser A. Hamam
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine
| | - Roua Arian
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
| | | |
Collapse
|
|
8
|
Srivastava A, Nalroad Sundararaj S, Bhatia J, Singh Arya D. Understanding long COVID myocarditis: A comprehensive review. Cytokine 2024; 178:156584. [PMID: 38508059 DOI: 10.1016/j.cyto.2024.156584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/21/2024] [Accepted: 03/15/2024] [Indexed: 03/22/2024]
Abstract
Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.
Collapse
Affiliation(s)
- Arti Srivastava
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India
| | | | - Jagriti Bhatia
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Dharamvir Singh Arya
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
| |
Collapse
|
|
9
|
Efremova I, Maslennikov R, Poluektova E, Medvedev O, Kudryavtseva A, Krasnov G, Fedorova M, Romanikhin F, Zharkova M, Zolnikova O, Bagieva G, Ivashkin V. Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis. World J Hepatol 2024; 16:822-831. [PMID: 38818295 PMCID: PMC11135270 DOI: 10.4254/wjh.v16.i5.822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/12/2024] [Accepted: 04/12/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate. AIM To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection. METHODS This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months. RESULTS Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis. CONCLUSION The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.
Collapse
Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia.
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia
| | - Oleg Medvedev
- Department of Pharmacology, Lomonosov Moscow State University, Moscow 119192, Russia
| | - Anna Kudryavtseva
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - George Krasnov
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Maria Fedorova
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Filipp Romanikhin
- Department of Pharmacology, Lomonosov Moscow State University, Moscow 119192, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Gyunay Bagieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia
| |
Collapse
|
|
10
|
Lee B, Park JE, Yoon SJ, Park CM, Lee NY, Shin TG, Kang ES. No Significant Differences in Presepsin Levels According to the Causative Microorganism of Bloodstream Infection. Infect Chemother 2024; 56:47-56. [PMID: 38178709 PMCID: PMC10990877 DOI: 10.3947/ic.2023.0066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 09/06/2023] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND CD14 recognizes lipopolysaccharide (LPS), and presepsin is a fragment of soluble CD14. Still, it remains uncertain whether Gram-negative bacteria induce higher presepsin levels than other microorganisms. To address this question, this study aimed to analyze presepsin levels based on microorganisms isolated in blood cultures. MATERIALS AND METHODS This study was a single-center study comprising suspected sepsis patients enrolled from July 2020 to September 2020. A total of 95 patients with a single isolate confirmed in blood culture were analyzed to evaluate if there are any differences in presepsin levels according to microbial isolates. Plasma presepsin level was measured using PATHFAST assay kit and analyzer (LSI Medience Corporation, Tokyo, Japan). RESULTS There were 26 Gram-positive bacteremia, 65 Gram-negative bacteremia, and 3 fungemia patients with median presepsin levels of 869, 1,439, and 11,951 pg/mL, respectively. Besides, one case of algaemia demonstrated a presepsin level of 1,231 pg/mL. Our results showed no statistically significant difference in presepsin levels among patients with Gram-positive bacteremia, Gram-negative bacteremia, and fungemia. Furthermore, presepsin levels did not differ significantly among bloodstream infections caused by bacteria that were isolated from at least three different patients. In particular, Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis were able to induce presepsin levels comparable to those induced by Gram-negative bacteria. CONCLUSION We demonstrated that there were no significant differences in plasma presepsin levels according to microbial isolates in blood culture. The major cause of the variability in presepsin levels during bloodstream infection might be the immunogenicity of each microorganism rather than the presence of LPS in the microorganism.
Collapse
Affiliation(s)
- Beomki Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Eun Park
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Emergency Medicine, College of Medicine, Kangwon National University, Chuncheon, Korea
| | - Sun Joo Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Chi-Min Park
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nam Yong Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Gun Shin
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun-Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| |
Collapse
|
|
11
|
Marin MJ, van Wijk XMR, Chambliss AB. Advances in sepsis biomarkers. Adv Clin Chem 2024; 119:117-166. [PMID: 38514209 DOI: 10.1016/bs.acc.2024.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
Sepsis, a dysregulated host immune response to an infectious agent, significantly increases morbidity and mortality for hospitalized patients worldwide. This chapter reviews (1) the basic principles of infectious diseases, pathophysiology and current definition of sepsis, (2) established sepsis biomarkers such lactate, procalcitonin and C-reactive protein, (3) novel, newly regulatory-cleared/approved biomarkers, such as assays that evaluate white blood cell properties and immune response molecules, and (4) emerging biomarkers and biomarker panels to highlight future directions and opportunities in the diagnosis and management of sepsis.
Collapse
Affiliation(s)
- Maximo J Marin
- Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, Florida, USA
| | | | - Allison B Chambliss
- Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA
| |
Collapse
|
|
12
|
Efremova I, Maslennikov R, Poluektova E, Medvedev O, Kudryavtseva A, Krasnov G, Fedorova M, Romanikhin F, Bakhitov V, Aliev S, Sedova N, Kuropatkina T, Ivanova A, Zharkova M, Pervushova E, Ivashkin V. Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis. Int J Mol Sci 2024; 25:1988. [PMID: 38396668 PMCID: PMC10888218 DOI: 10.3390/ijms25041988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/30/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.
Collapse
Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
- Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Pogodinskaya Str. 1-1, 119435 Moscow, Russia
- Consultative and Diagnostic Center 2 of the Moscow Health Department, Millionnaya Str. 6, 107564 Moscow, Russia (N.S.)
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
- Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Pogodinskaya Str. 1-1, 119435 Moscow, Russia
| | - Oleg Medvedev
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, 119991 Moscow, Russia; (O.M.)
| | - Anna Kudryavtseva
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, 119991 Moscow, Russia
| | - George Krasnov
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, 119991 Moscow, Russia
| | - Maria Fedorova
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, 119991 Moscow, Russia
| | - Filipp Romanikhin
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, 119991 Moscow, Russia; (O.M.)
| | - Vyacheslav Bakhitov
- Consultative and Diagnostic Center 2 of the Moscow Health Department, Millionnaya Str. 6, 107564 Moscow, Russia (N.S.)
| | - Salekh Aliev
- Consultative and Diagnostic Center 2 of the Moscow Health Department, Millionnaya Str. 6, 107564 Moscow, Russia (N.S.)
- First Hospital Surgery Department, Pirogov Russian National Research Medical University, Ostrovityanova Str. 1-7, 117997 Moscow, Russia
| | - Natalia Sedova
- Consultative and Diagnostic Center 2 of the Moscow Health Department, Millionnaya Str. 6, 107564 Moscow, Russia (N.S.)
- Department of Clinical Laboratory Diagnostics, FGBOU DPO “Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation”, Barricadnaya Str. 2/1-2, 125993 Moscow, Russia
| | - Tatiana Kuropatkina
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, 119991 Moscow, Russia; (O.M.)
| | - Anastasia Ivanova
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, 119991 Moscow, Russia; (O.M.)
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
| | - Ekaterina Pervushova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str. 1-1, 119435 Moscow, Russia; (I.E.); (E.P.)
- Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Pogodinskaya Str. 1-1, 119435 Moscow, Russia
| |
Collapse
|
|
13
|
Ahuja N, Mishra A, Gupta R, Ray S. Biomarkers in sepsis-looking for the Holy Grail or chasing a mirage! World J Crit Care Med 2023; 12:188-203. [PMID: 37745257 PMCID: PMC10515097 DOI: 10.5492/wjccm.v12.i4.188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/12/2023] [Accepted: 06/12/2023] [Indexed: 09/05/2023] Open
Abstract
Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection. It is a complex syndrome and is characterized by physiologic, pathologic and biochemical abnormalities in response to an infection. Diagnosis of sepsis is based on history, physical examination and other investigations (including biomarkers) which may help to increase the certainty of diagnosis. Biomarkers have been evaluated in the past for many diseases and have been evaluated for sepsis as well. Biomarkers may find a possible role in diagnosis, prognostication, therapeutic monitoring and anti-microbial stewardship in sepsis. Since the pathophysiology of sepsis is quite complex and is incompletely understood, a single biomarker that may be robust enough to provide all information has not been found as of yet. However, many biomarkers have been studied and some of them have applications at the bedside and guide clinical decision-making. We evaluated the PubMed database to search for sepsis biomarkers for diagnosis, prognosis and possible role in antibiotic escalation and de-escalation. Clinical trials, meta-analyses, systematic reviews and randomized controlled trials were included. Commonly studied biomarkers such as procalcitonin, Soluble urokinase-type plasminogen activator (Supar), presepsin, soluble triggering receptor expressed on myeloid cells 1, interleukin 6, C-reactive protein, etc., have been described for their possible applications as biomarkers in septic patients. The sepsis biomarkers are still an area of active research with newer evidence adding to the knowledge base continuously. For patients presenting with sepsis, early diagnosis and prompt resuscitation and early administration of anti-microbials (preferably within 1 h) and source control are desired goals. Biomarkers may help us in the diagnosis, prognosis and therapeutic monitoring of septic patients. The marker redefining our view on sepsis is yet a mirage that clinicians and researchers continue to chase.
Collapse
Affiliation(s)
- Neelmani Ahuja
- Department of Critical Care Medicine, Holy Family Hospital, Delhi 110025, India
| | - Anjali Mishra
- Department of Critical Care Medicine, Holy Family Hospital, Delhi 110025, India
| | - Ruchi Gupta
- Department of Critical Care Medicine, Holy Family Hospital, Delhi 110025, India
| | - Sumit Ray
- Department of Critical Care Medicine, Holy Family Hospital, Delhi 110025, India
| |
Collapse
|
|
14
|
Lee GH, Park M, Hur M, Kim H, Lee S, Moon HW, Yun YM. Utility of Presepsin and Interferon-λ3 for Predicting Disease Severity and Clinical Outcomes in COVID-19 Patients. Diagnostics (Basel) 2023; 13:2372. [PMID: 37510116 PMCID: PMC10377783 DOI: 10.3390/diagnostics13142372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
We explored the utility of novel biomarkers, presepsin and interferon-λ3 (IFN-λ3), for predicting disease severity and clinical outcomes in hospitalized Coronavirus (COVID-19) patients. In a total of 55 patients (non-critical, n = 16; critical, n = 39), presepsin and IFN-λ3 were compared with sequential organ failure assessment (SOFA) scores and age. Disease severity and clinical outcomes (in-hospital mortality, intensive care unit admission, ventilator use, and kidney replacement therapy) were analyzed using receiver operating characteristic (ROC) curves. In-hospital mortality was also analyzed using the Kaplan-Meier method with hazard ratios (HR). SOFA scores, age, presepsin, and IFN-λ3 predicted disease severity comparably (area under the curve [AUC], 0.67-0.73). SOFA score and IFN-λ3 predicted clinical outcomes comparably (AUC, 0.68-0.88 and 0.66-0.74, respectively). Presepsin predicted in-hospital mortality (AUC = 0.74). The combination of presepsin and IFN-λ3 showed a higher mortality risk than SOFA score or age (HR [95% confidence interval, CI], 6.7 [1.8-24.1]; 3.6 [1.1-12.1]; 2.8 [0.8-9.6], respectively) and mortality rate further increased when presepsin and IFN-λ3 were added to SOFA scores or age (8.5 [6.8-24.6], 4.2 [0.9-20.6], respectively). In the elderly (≥65 years), in-hospital mortality rate was significantly higher when both presepsin and IFN-λ3 levels increased than when either one or no biomarker level increased (88.9% vs. 14.3%, p < 0.001). Presepsin and IFN-λ3 predicted disease severity and clinical outcomes in hospitalized COVID-19 patients. Both biomarkers, whether alone or added to the clinical assessment, could be useful for managing COVID-19 patients, especially the elderly.
Collapse
Affiliation(s)
- Gun-Hyuk Lee
- Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Republic of Korea
| | - Mikyoung Park
- Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Republic of Korea
| | - Mina Hur
- Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Republic of Korea
| | - Hanah Kim
- Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Republic of Korea
| | - Seungho Lee
- Department of Preventive Medicine, College of Medicine, Dong-A University, Busan 49201, Republic of Korea
| | - Hee-Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Republic of Korea
| | - Yeo-Min Yun
- Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Republic of Korea
| |
Collapse
|
|
15
|
Liang J, Cai Y, Shao Y. Comparison of presepsin and Mid-regional pro-adrenomedullin in the diagnosis of sepsis or septic shock: a systematic review and meta-analysis. BMC Infect Dis 2023; 23:288. [PMID: 37147598 PMCID: PMC10160726 DOI: 10.1186/s12879-023-08262-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 04/17/2023] [Indexed: 05/07/2023] Open
Abstract
BACKGROUND The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin (MR-proADM) are promising biomarkers in the diagnosis of sepsis. This study was conducted to evaluate and compare the diagnostic value of MR-proADM and presepsin in sepsis patients. METHODS We searched Web of Science, PubMed, Embase, China national knowledge infrastructure, and Wanfang up to 22th July, 2022, for studies evaluating the diagnosis performance of presepsin and MR-proADM in adult sepsis patients. Risk of bias was assessed using quadas-2. Pooled sensitivity and specificity were calculated using bivariate meta-analysis. Meta-regression and subgroup analysis were used to find source of heterogeneity. RESULTS A total of 40 studies were eventually selected for inclusion in this meta-analysis, including 33 for presepsin and seven for MR-proADM. Presepsin had a sensitivity of 0.86 (0.82-0.90), a specificity of 0.79 (0.71-0.85), and an AUC of 0.90 (0.87-0.92). The sensitivity of MR-proADM was 0.84 (0.78-0.88), specificity was 0.86 (0.79-0.91), and AUC was 0.91 (0.88-0.93). The profile of control group, population, and standard reference may be potential sources of heterogeneity. CONCLUSIONS This meta-analysis demonstrated that presepsin and MR-proADM exhibited high accuracy (AUC ≥ 0.90) in the diagnosis of sepsis in adults, with MR-proADM showing significantly higher accuracy than presepsin.
Collapse
Affiliation(s)
- Jun Liang
- Department of Emergency, the First People's Hospital of Zhaoqing, Zhaoqing City, China
| | - Yingli Cai
- Department of Emergency, the First People's Hospital of Zhaoqing, Zhaoqing City, China
| | - Yiming Shao
- Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, China.
| |
Collapse
|
|
16
|
Aliu-Bejta A, Kurshumliu M, Namani S, Dreshaj S, Baršić B. Ability of presepsin concentrations to predict mortality in adult patients with sepsis. J Clin Transl Sci 2023; 7:e121. [PMID: 37313382 PMCID: PMC10260338 DOI: 10.1017/cts.2023.538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/19/2023] [Accepted: 04/21/2023] [Indexed: 06/15/2023] Open
Abstract
Background Early diagnosis of sepsis is essential for a favorable disease outcome. The aim of this study was to evaluate the association of initial and subsequent presepsin concentrations with sepsis outcomes. Methods One hundred sepsis patients were enrolled in the study from two different university centers. Four times during study, concentrations of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) were measured, and Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score were calculated. Patients were grouped into survivors and nonsurvivors. A sandwich ELISA kit was used to measure presepsin concentrations. To test the changes in biomarkers concentrations and SOFA score and APACHE II score during the disease course and to estimate the differences between outcome groups, generalized linear mixed effects model was used. Receiver operating characteristic curve analysis was performed to determine the prognostic value of presepsin concentrations. Results Initial values of presepsin, SOFA score, and APACHE II score were significantly higher in nonsurvivors compared to survivors. Concentrations of PCT and CRP did not differ significantly between outcome groups. ROC curve analyses show a greater predictive ability of initial presepsin concentrations for predicting mortality compared to subsequent measurements of presepsin concentrations. Conclusions Presepsin has a good ability to predict mortality. Initial presepsin concentrations better reflects poor disease outcome compared to presepsin concentrations 24 and 72 hours after admission.
Collapse
Affiliation(s)
- Ajete Aliu-Bejta
- University Clinic of Infectious Diseases, Alexander Fleming, Pristina, 10000, Kosovo
- University of Pristina “Hasan Prishtina”, Faculty of Medicine, Lagja e spitalit, p.n, Pristina, 10000, Kosovo
| | - Mentor Kurshumliu
- “PROLAB” Biochemical Laboratory, Mark Dizdari, Pristina, 10000, Kosovo
| | - Sadie Namani
- University Clinic of Infectious Diseases, Alexander Fleming, Pristina, 10000, Kosovo
- University of Pristina “Hasan Prishtina”, Faculty of Medicine, Lagja e spitalit, p.n, Pristina, 10000, Kosovo
| | - Shemsedin Dreshaj
- University Clinic of Infectious Diseases, Alexander Fleming, Pristina, 10000, Kosovo
- University of Pristina “Hasan Prishtina”, Faculty of Medicine, Lagja e spitalit, p.n, Pristina, 10000, Kosovo
| | - Bruno Baršić
- University of Zagreb, School of Medicine, Šalata 4, Zagreb, 10000, Croatia
- University Hospital for Infectious Diseases “Dr. Fran Mihaljević,”Zagreb, 10000, Croatia
| |
Collapse
|
|
17
|
The Value of Peripheral Blood Leukocyte Parameters in the Early Diagnosis and Clinical Prognosis of Sepsis. Int J Anal Chem 2023; 2023:6052085. [PMID: 36691469 PMCID: PMC9867575 DOI: 10.1155/2023/6052085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/06/2022] [Accepted: 12/28/2022] [Indexed: 01/15/2023] Open
Abstract
Background Early diagnosis of sepsis is the key to timely, targeted treatment. Cell population data (CPD) has been widely used in many diseases, but its predictive value for early diagnosis and the clinical outcome of sepsis remains unclear. Therefore, this paper discusses whether peripheral blood leukocyte parameters can be used as predictive indicators for early diagnosis and the clinical outcome of sepsis. Methods A retrospective study of 45 patients with sepsis, 53 patients with nonseptic infections, and 86 healthy check-ups admitted to Gansu Provincial Hospital from January 2021 to June 2022 was done using a hematology analyzer. Results The results of LYMPH#, HFLC#, IG#, NE-WX, LY-WX, LY-WY, and MO-WX showed better diagnostic efficiency in the sepsis group and nonseptic infection group. When the seven differential leukocyte parameters were used to establish diagnostic models, the sensitivity and specificity were 82.20% and 77.40%, respectively. Correlation analysis showed that LYMPH# and HFLC# were positively correlated with PCT (P < 0.05). The clinical outcome of sepsis showed that the leukocyte parameters of discharged WBC and LY-X had better predictive efficacy. When the two differential leukocyte parameters were used to establish diagnostic models, the sensitivity and specificity were 90.90% and 100.00%. Cox regression analysis showed that leukocyte parameters of discharged WBC and LY-X were independent predictors of clinical outcomes (P < 0.05). Conclusion Leucocyte parameters HFLC#, IG#, NE-WX, LY-WX, LY-WY, and MO-WX had a certain auxiliary effect on the early diagnosis of sepsis leukocyte parameters of discharged WBC and LY-X were independent predictors of clinical outcomes in patients with sepsis. Therefore, peripheral blood leukocyte parameters may have predictive value for early diagnosis and the clinical outcome of sepsis, but large-scale retrospective studies are still needed to prove our preliminary results.
Collapse
|
|
18
|
Weferling M, Fischer-Rasokat U, Vietheer J, Renker M, Rolf A, Keller T, Choi YH, Arsalan M, Hamm CW, Kim WK, Liebetrau C. Presepsin predicts 1-year all-cause mortality better than N-terminal pro-B-type natriuretic peptide in patients undergoing transcatheter aortic valve implantation. Biomark Med 2022; 16:1209-1218. [PMID: 36861450 DOI: 10.2217/bmm-2022-0533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023] Open
Abstract
Aim: Presepsin is a sensitive biomarker for the diagnosis and estimation of prognosis in septic patients. The prognostic role of presepsin in patients undergoing transcatheter aortic valve implantation (TAVI) has never been investigated. Patients, materials & methods: In 343 patients, presepsin and N-terminal pro-B-type natriuretic peptide were measured before TAVI. One-year all-cause mortality was used as outcome measure. Results: Patients with high presepsin levels were more likely to succumb than patients with low presepsin values (16.9% vs 12.3%; p = 0.015). Elevated presepsin remained a significant predictor of 1-year all-cause mortality (odds ratio: 2.2 [95% CI: 1.12-4.29]; p = 0.022) after adjustment. N-terminal pro-B-type natriuretic peptide did not predict 1-year all-cause mortality. Conclusion: Elevated baseline presepsin levels are an independent predictor of 1-year mortality in TAVI patients.
Collapse
Affiliation(s)
- Maren Weferling
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
| | | | - Julia Vietheer
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
| | - Matthias Renker
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Cardiac Surgery, Kerckhoff Heart & Thorax Center, Bad Nauheim, Germany
| | - Andreas Rolf
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
| | - Till Keller
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Internal Medicine I, Cardiology, Justus Liebig University Giessen, Giessen, Germany
| | - Yeong-Hoon Choi
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Cardiac Surgery, Kerckhoff Heart & Thorax Center, Bad Nauheim, Germany
| | - Mani Arsalan
- Department of Internal Medicine I, Cardiology, Justus Liebig University Giessen, Giessen, Germany
| | - Christian W Hamm
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Internal Medicine I, Cardiology, Justus Liebig University Giessen, Giessen, Germany
| | - Won-Keun Kim
- Kerckhoff Heart & Thorax Center, Department of Cardiology, Bad Nauheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Cardiac Surgery, Kerckhoff Heart & Thorax Center, Bad Nauheim, Germany
- Department of Internal Medicine I, Cardiology, Justus Liebig University Giessen, Giessen, Germany
| | - Christoph Liebetrau
- German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Bad Nauheim, Germany
- Department of Cardiology, Cardioangiological Center Bethanien (CCB), Agaplesion Bethanien Hospital, Frankfurt, Germany
| |
Collapse
|
|
19
|
Kim CJ. Current Status of Antibiotic Stewardship and the Role of Biomarkers in Antibiotic Stewardship Programs. Infect Chemother 2022; 54:674-698. [PMID: 36596680 PMCID: PMC9840952 DOI: 10.3947/ic.2022.0172] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 12/19/2022] [Indexed: 12/27/2022] Open
Abstract
The importance of antibiotic stewardship is increasingly emphasized in accordance with the increasing incidences of multidrug-resistant organisms and accompanying increases in disease burden. This review describes the obstacles in operating an antibiotic stewardship program (ASP), and whether the use of biomarkers within currently available resources can help. Surveys conducted around the world have shown that major obstacles to ASPs are shortages of time and personnel, lack of appropriate compensation for ASP operation, and lack of guidelines or appropriate manuals. Sufficient investment, such as the provision of full-time equivalent ASP practitioners, and adoption of computerized clinical decision systems are useful measures to improve ASP within an institution. However, these methods are not easy in terms of both time commitments and cost. Some biomarkers, such as C-reactive protein, procalcitonin, and presepsin are promising tools in ASP due to their utility in diagnosis and forecasting the prognosis of sepsis. Recent studies have demonstrated the usefulness of algorithmic approaches based on procalcitonin level to determine the initiation or discontinuation of antibiotics, which would be helpful in decreasing antibiotics use, resulting in more appropriate antibiotics use.
Collapse
Affiliation(s)
- Chung-Jong Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| |
Collapse
|
|
20
|
Khera D, Toteja N, Singh S, Didel S, Singh K, Chugh A, Singh S. The Role of Presepsin as a Biomarker of Sepsis in Children: A Systemic Review and Meta-Analysis. J Pediatr Intensive Care 2022. [DOI: 10.1055/s-0042-1758479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Abstract
Objectives Biomarkers in sepsis are an arena of avid research as they can facilitate timely diagnosis and help reduce mortality. Presepsin is a promising candidate with good diagnostic performance reported in adult and neonatal studies. However, there is no clear consensus about its utility in the pediatric age group. This study aimed to synthesize scientific evidence regarding the diagnostic and prognostic performance of presepsin in pediatric sepsis.
Data Sources A systematic literature search was conducted in MEDLINE/PubMed, Cochrane Central Register of Clinical Trials, Google Scholar, and Scopus to identify relevant studies reporting the diagnostic and prognostic accuracy of presepsin.
Study Selection Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we retrieved all controlled trials and observational studies on presepsin as a biomarker in children aged <19 years with sepsis.
Data Extraction Two authors independently performed study screening, data extraction, and quality assessment of the included studies.
Data Synthesis Among the 267 citations identified, a total of nine relevant studies were included in the final analysis. The pooled diagnostic sensitivity and specificity of presepsin were 0.99 (95% confidence interval [CI]; 0.97–1.00) and 0.88 (95% CI; 0.83–0.92), respectively, with a diagnostic odds ratio (DOR) of 28.15 (95% CI; 0.74–1065.67) and area under the curve (AUC) in summary receiver operating curve of 0.89. Prognostic accuracy for presepsin had a sensitivity of 0.64 (95% CI; 0.35–1.0), specificity of 0.62 (95% CI; 0.44–0.87), and DOR of 3.3 (95% CI; 0.20–53.43). For procalcitonin, the pooled sensitivity for diagnostic accuracy was 0.97 (95% CI; 0.94–1.00), specificity was 0.76 (95% CI; 0.69–0.82), DOR was 10.53 (95% CI; 5.31–20.88), and AUC was 0.81.
Conclusion Presepsin has good diagnostic accuracy with high sensitivity and specificity. Its prognostic accuracy in predicting mortality is low.
Collapse
Affiliation(s)
- Daisy Khera
- Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Nisha Toteja
- Department of Paediatrics, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Simranjeet Singh
- Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Siyaram Didel
- Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Kuldeep Singh
- Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Ankita Chugh
- Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Surjit Singh
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| |
Collapse
|
|
21
|
Cai S, Wang Q, Chen C, Guo C, Zheng L, Yuan M. Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality of patients with sepsis in intensive care: A retrospective analysis of the fourth-generation Medical Information Mart for Intensive Care database. Front Nutr 2022; 9:967332. [PMID: 36407534 PMCID: PMC9672517 DOI: 10.3389/fnut.2022.967332] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND This study aimed to investigate the relationship between the blood urea nitrogen to serum albumin ratio (BAR) and in-hospital mortality in patients with sepsis. MATERIALS AND METHODS This is a retrospective cohort study. All septic patient data for the study were obtained from the intensive care unit of Beth Israel Deaconess Medical Center. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariable Cox regression analyses. Survival curves were plotted and subgroup analyses were stratified by relevant covariates. RESULTS Among 23,901 patients, 13,464 with sepsis were included. The overall in-hospital mortality rate was 18.9% (2550/13464). After adjustment for confounding factors, patients in the highest BAR quartile had an increased risk of sepsis death than those in the lowest BAR quartile (HR: 1.42, 95% CI: 1.3-1.55), using BAR as a categorical variable. When BAR was presented as a continuous variable, the prevalence of in-hospital sepsis-related death increased by 8% (adjusted HR: 1.08, 95% CI: 1.07-1.1, P < 0.001) for each 5-unit increase in BAR, irrespective of confounders. Stratified analyses indicated age interactions (P < 0.001), and the correlation between BAR and the probability of dying due to sepsis was stable. CONCLUSION BAR was significantly associated with in-hospital mortality in intensive care patients with sepsis. A higher BAR in patients with sepsis is associated with a worse prognosis in the ICU in the USA. However, further research is required to confirm this finding.
Collapse
Affiliation(s)
- Shaoyan Cai
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Qinjia Wang
- Department of Gastroenterology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Chao Chen
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Chunming Guo
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Liangjie Zheng
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Min Yuan
- Department of Neurology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| |
Collapse
|
|
22
|
Narendra S, Wyawahare M, Adole PS. Presepsin vs Procalcitonin as Predictors of Sepsis Outcome. THE JOURNAL OF THE ASSOCIATION OF PHYSICIANS OF INDIA 2022; 70:11-12. [PMID: 37355942 DOI: 10.5005/japi-11001-0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/26/2023]
Abstract
BACKGROUND Sepsis diagnosis and management is aided by the use of newer biomarkers like procalcitonin and presepsin. For prognostication, presepsin may be better than procalcitonin. METHODOLOGY Ninety-two participants, suspected to be suffering from sepsis of varied etiologies were included in this study at the time of their presentation to the emergency health services. Presepsin and procalcitonin were estimated and the patient followed up till discharge or death. Receiver operating curve (ROC) curves, sensitivity, specificity, and positive and negative likelihood ratios were calculated. Association between these markers and mortality was estimated. RESULTS Out of 92 participants enrolled on day 1, 73 survived till day 3. Patients who had thrombocytopenia, high neutrophil counts, and elevated levels of bilirubin, urea, presepsin, and procalcitonin were associated with poor outcomes. Presepsin and procalcitonin levels increased significantly from day 0 to day 3 in the nonsurvivor group as compared to the survivor group. On comparing the ROC curve of presepsin and procalcitonin, the area under the curve (AUC) of presepsin was more than procalcitonin, signifying that it was a better biomarker of mortality due to sepsis. At a cutoff value of 1.47 ng/dL, presepsin was a predictor of mortality in sepsis [odds ratio (OR) = 14]. It had similar sensitivity but better specificity than procalcitonin in predicting mortality.
Collapse
Affiliation(s)
| | | | - Prashant S Adole
- Additional Professor, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| |
Collapse
|
|
23
|
Muthyala A, Sasidharan S, John KJ, Lal A, Mishra AK. Utility of cardiac bioenzymes in predicting cardiovascular outcomes in SARS-CoV-2. World J Virol 2022; 11:375-390. [PMID: 36188743 PMCID: PMC9523328 DOI: 10.5501/wjv.v11.i5.375] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/12/2022] [Accepted: 08/10/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cardiovascular complications have been increasingly recognized in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19). Cardiac biomarkers are released because of this ongoing cardiovascular injury and can act as surrogate markers to assess the disease severity. AIM To review the variation and utility of these biomarkers in COVID-19 to ascertain their role in diagnosis, prognosis and clinical outcomes of the disease. METHODS We performed a literature search in PubMed, Medline and the Reference Citation Analysis (RCA), using the search terms "COVID-19" and "cardiac bioenzymes" or "cardiac biomarkers". Additionally, we also used the latest reference citation analysis tool to identify more articles. RESULTS Cardiac troponin has been consistently elevated in patients with COVID-19 associated myocarditis, and strongly correlated with adverse prognosis. Natri-uretic peptides including brain natriuretic peptide (BNP) and pro-BNP is elevated in patients with COVID-19 associated cardiac injury, irrespective of their prior heart failure status, and independently correlated with worst outcomes. Alongside these traditional biomarkers, novel cardiac bioenzymes including presepsin, soluble ST2 and copeptin, are also increasingly recognized as markers of cardiovascular injury in COVID-19 and can be associated with poor outcomes. CONCLUSION Assessment of cardiac bioenzymes at admission and their serial monitoring can help assess the severity of disease and predict mortality in patients with SARS-CoV-2 infection. Future studies are needed to elude the critical importance of novel biomarkers.
Collapse
Affiliation(s)
- Anjani Muthyala
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
| | - Sandeep Sasidharan
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
| | - Kevin John John
- Department of Critical Care, Belivers Church Medical College Hospital, Thiruvalla 689103, Kerela, India
| | - Amos Lal
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Ajay K Mishra
- Department of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
| |
Collapse
|
|
24
|
Igna R, Gîrleanu I, Cojocariu C, Huiban L, Muzîca C, Sîngeap AM, Sfarti C, Chiriac S, Petrea OC, Zenovia S, Nastasa R, Cuciureanu T, Stafie R, Stratina E, Rotaru A, Stanciu C, Blaj M, Trifan A. The Role of Presepsin and Procalcitonin in Early Diagnosis of Bacterial Infections in Cirrhotic Patients with Acute-on-Chronic Liver Failure. J Clin Med 2022; 11:5410. [PMID: 36143057 PMCID: PMC9501308 DOI: 10.3390/jcm11185410] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/04/2022] [Accepted: 09/12/2022] [Indexed: 11/27/2022] Open
Abstract
Background and Objectives: Bacterial infections represent one of the most frequent precipitating events of acute-on-chronic liver failure (ACLF) in a patient with liver cirrhosis (LC). Early diagnosis and treatment could influence the ACLF reversal rate and decrease the mortality rate in these patients. The study aimed to evaluate the role of presepsin, C-reactive protein (CRP), and procalcitonin (PCT) in the early diagnosis of bacterial infections in patients with LC and ACLF, defined according to the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. Material and Methods: We performed a prospective observational study including all consecutive cirrhotic patients with ACLF admitted to our tertiary university center. The patients were follow-up until discharge. All patients were screened for infection at admission, and we included patients with community-acquired or healthcare-associated bacterial infections. Results: In this study, we included 153 patients with a median age of 60 years, of whom 65.4% were male. Infections were diagnosed in 71 patients (46.4%). The presepsin, CRP, and PCT levels were higher in patients with infections than in those without infections (p < 0.001, p = 0.023, and p < 0.001, respectively). The ROC analysis results demonstrated that the best cut-offs values for infections diagnosis were for presepsin 2300 pg/mL (sensitivity of 81.7%, specificity of 92.7%, AUROC 0.959, p < 0.001), CRP 5.3 mg/dL (sensitivity of 54.9%, specificity of 69.6%, AUROC 0.648, p = 0.023), and PCT 0.9 ng/mL (sensitivity of 80.3%, specificity of 86.6%, AUROC 0.909, p < 0.001). Presepsin (OR 3.65, 95%CI 1.394−9.588, p = 0.008), PCT (OR 9.79, 95%CI 6.168−25.736, p < 0.001), and MELD score (OR 7.37, 95%CI 1.416−18.430, p = 0.018) were associated with bacterial infections in patients with ACLF. Conclusion: Presepsin level ≥2300 pg/mL and PCT level ≥0.9 ng/mL may be adequate non-invasive tools for the early diagnosis of infections in cirrhotics with ACLF.
Collapse
Affiliation(s)
- Razvan Igna
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Intensive Care Unit, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Irina Gîrleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cristina Muzîca
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ana-Maria Sîngeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cătălin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Oana Cristina Petrea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Mihaela Blaj
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Intensive Care Unit, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| |
Collapse
|
|
25
|
Nam M, Hur M, Kim H, Lee GH, Park M, Kwon HS, Hwang HS, Sohn IS. Distribution of Presepsin, Krebs von den Lungen 6, and Surfactant Protein A in Umbilical Cord Blood. Diagnostics (Basel) 2022; 12:diagnostics12092213. [PMID: 36140614 PMCID: PMC9498084 DOI: 10.3390/diagnostics12092213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 12/04/2022] Open
Abstract
Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9–428.3 pg/mL, 43.0–172.0 U/mL, and 2.1–36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.
Collapse
Affiliation(s)
- Minjeong Nam
- Department of Laboratory Medicine, Korea University Anam Hospital, Seoul 02841, Korea
| | - Mina Hur
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul 05030, Korea
- Correspondence: ; Tel.: +82-2-2030-5581
| | - Hanah Kim
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul 05030, Korea
| | - Gun-Hyuk Lee
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul 05030, Korea
| | - Mikyoung Park
- Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, Seoul 03312, Korea
| | - Han-Sung Kwon
- Department of Obstetrics & Gynecology, Konkuk University School of Medicine, Seoul 05030, Korea
| | - Han-Sung Hwang
- Department of Obstetrics & Gynecology, Konkuk University School of Medicine, Seoul 05030, Korea
| | - In-Sook Sohn
- Department of Obstetrics & Gynecology, Konkuk University School of Medicine, Seoul 05030, Korea
| |
Collapse
|
|
26
|
Igna R, Gîrleanu I, Cojocariu C, Muzîca C, Huiban L, Sfarti C, Cuciureanu T, Chiriac S, Sîngeap AM, Petrea OC, Stafie R, Zenovia S, Năstasă R, Stratina E, Rotaru A, Stanciu C, Trifan A, Blaj M. The Role of Presepsin in Diagnosing Infections in Patients with Liver Cirrhosis and Overt Hepatic Encephalopathy. Diagnostics (Basel) 2022; 12:2077. [PMID: 36140479 PMCID: PMC9497501 DOI: 10.3390/diagnostics12092077] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/19/2022] Open
Abstract
Infections and sepsis represent severe liver cirrhosis (LC) complications and the precipitating factors of hepatic encephalopathy (HE). The early diagnosis and treatment of infections in patients with LC and HE can significantly increase their survival. Presepsin is a serum biomarker evaluated for the early diagnosis of infections and sepsis in the general and cirrhotic populations. This study aimed to evaluate the role of presepsin in the early diagnosis of infections in patients with LC and HE. This prospective observational study included all consecutive cirrhotic patients admitted to our tertiary university center with overt HE. The patients were follow-up until discharge. In this study, we included 365 patients with a median age of 59 years, of whom 61.9% were male. Infections were diagnosed in 134 patients (36.7%). The presepsin level was higher in patients with infections than those without infections (3167 vs. 500, p < 0.001). The ROC analysis results demonstrated that the best cut-off value for presepsin in infections detection was 980 pg/mL with a sensitivity of 80.17%, specificity of 82.5% (AUROC 0.869, CI 95%: 0.819−0.909, p < 0.001, Youden index J of 0.622), a positive predictive value of 40.63%, and a negative predictive value of 96.53%. In conclusion, in patients with LC and overt HE, presepsin levels >980 pg/mL could enhance the suspicion of bacterial infections. Presepsin may be an adequate non-invasive tool for the early diagnosis of infections in patients with LC and overt HE.
Collapse
Affiliation(s)
- Razvan Igna
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Intensive Care Unit, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Irina Gîrleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cristina Muzîca
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ana-Maria Sîngeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Oana Cristina Petrea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Robert Năstasă
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Mihaela Blaj
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania
- Intensive Care Unit, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| |
Collapse
|
|
27
|
Kim SW, Lee H, Lee SH, Jo SJ, Lee J, Lim J. Usefulness of monocyte distribution width and presepsin for early assessment of disease severity in COVID-19 patients. Medicine (Baltimore) 2022; 101:e29592. [PMID: 35801752 PMCID: PMC9258971 DOI: 10.1097/md.0000000000029592] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Early predictors of severe coronavirus disease 2019 (COVID-19) would identify patients requiring intensive care. Recently, the monocyte distribution width (MDW) and presepsin level have been used for the early diagnosis of sepsis. Here, we assessed the utility of MDW and presepsin for the early assessment of COVID-19 severity. Eighty-seven inpatients with confirmed COVID-19 were enrolled and divided into 3 groups by the type of respiratory support: (1) mechanical ventilation or high-flow nasal cannula oxygen therapy (MVHF-OT), (2) conventional oxygen therapy, and (3) no oxygen therapy. We measured the complete blood count; MDW; erythrocyte sedimentation rate; and the levels of presepsin, C-reactive protein, procalcitonin, lactate dehydrogenase, ferritin, Krebs von den Lungen-6 (KL-6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody. Thirteen (14.9%) patients on MVHF-OT exhibited a significantly higher mortality and a longer hospital stay than did the others. The MDW and presepsin levels were significantly elevated on admission, and correlated with COVID-19 severity (both P < .001). Notably, only the MDW correlated significantly with symptoms in the no oxygen therapy group (P < .012). In the first week after admission, the MDW fell and no longer differed among the groups. The KL-6 level did not differ by disease severity at any time. Neutralizing antibodies were detected in 74 patients (91.4%) and the level of neutralization correlated significantly with COVID-19 severity (P < .001). The MDW and presepsin are useful indicators for early assessment of disease severity in COVID-19 patients.
Collapse
Affiliation(s)
- Sei Won Kim
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Heayon Lee
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Haak Lee
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Jin Jo
- Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jehoon Lee
- Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jihyang Lim
- Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- * Correspondence: Jihyang Lim, MD, PhD, Department of Laboratory Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-ro, Eunpyeong-gu, Seoul 03312, Korea (e-mail: )
| |
Collapse
|
|
28
|
Park M, Hur M, Kim H, Lee CH, Lee JH, Kim HW, Nam M. Prognostic Utility of Procalcitonin, Presepsin, and the VACO Index for Predicting 30-day Mortality in Hospitalized COVID-19 Patients. Ann Lab Med 2022; 42:406-414. [PMID: 35177561 PMCID: PMC8859553 DOI: 10.3343/alm.2022.42.4.406] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 11/19/2022] Open
Abstract
Background Biomarkers and clinical indices have been investigated for predicting mortality in patients with coronavirus disease (COVID-19). We explored the prognostic utility of procalcitonin (PCT), presepsin, and the Veterans Health Administration COVID-19 (VACO) index for predicting 30-day-mortality in COVID-19 patients. Methods In total, 54 hospitalized COVID-19 patients were enrolled. PCT and presepsin levels were measured using the Elecsys BRAHMS PCT assay (Roche Diagnostics GmbH, Mannheim, Germany) and HISCL Presepsin assay (Sysmex, Kobe, Japan), respectively. The VACO index was calculated based on age, sex, and comorbidities. PCT and presepsin levels and the VACO index were compared using ROC curve, Kaplan-Meier method, and reclassification analysis for the 30-day mortality. Results ROC curve analysis was used to measure PCT and presepsin levels and the VACO index to predict 30-day mortality; the optimal cut-off values were 0.138 ng/mL for PCT, 717 pg/mL for presepsin, and 12.1% for the VACO index. On Kaplan-Meier survival analysis, hazard ratios (95% confidence interval) were 15.9 (4.1-61.3) for PCT, 26.3 (6.4-108.0) for presepsin, and 6.0 (1.7-21.1) for the VACO index. On reclassification analysis, PCT and presepsin in addition to the VACO index significantly improved the prognostic value of the index. Conclusions This study demonstrated the prognostic utility of measuring PCT and presepsin levels and the VACO index in COVID-19 patients. The biomarkers in addition to the clinical index were more useful than the index alone for predicting clinical outcomes in COVID-19 patients.
Collapse
Affiliation(s)
- Mikyoung Park
- Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mina Hur
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hanah Kim
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Chae Hoon Lee
- Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Jong Ho Lee
- Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyung Woo Kim
- Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Minjeong Nam
- Department of Laboratory Medicine, Korea University Anam Hospital, Seoul, Korea
| |
Collapse
|
|
29
|
Priolo F, Fattore S, Tedesco M, De Rose DU, Chioma R, Perri A, Costa S, Rubortone SA, Patti ML, Sbordone A, Maggio L, Vento G. Presepsin levels in neonatal cord blood are not influenced by maternal SARS-CoV-2 infection. Clin Chem Lab Med 2022; 60:1486-1491. [PMID: 35748906 DOI: 10.1515/cclm-2022-0238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/10/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72 h. RESULTS The median presepsin value in umbilical cord blood samples collected after birth was 455 pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5 days had a significantly higher presepsin level at birth rather than those discharged up to 4 days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48 h. CONCLUSIONS This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.
Collapse
Affiliation(s)
- Francesca Priolo
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | | | | | - Domenico Umberto De Rose
- Neonatal Intensive Care Unit, Medical and Surgical Department of the Fetus - Newborn-Infant, "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy
| | | | - Alessandro Perri
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Simonetta Costa
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Serena Antonia Rubortone
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Maria Letizia Patti
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Annamaria Sbordone
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy
| | - Luca Maggio
- Università Cattolica del Sacro Cuore, Rome, Italy.,Neonatal Intensive Care Unit, Maternal-Fetal Department, "S. Camillo-Forlanini" Hospital, Rome, Italy
| | - Giovanni Vento
- Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.,Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
30
|
Samprathi A, Samprathi M, Reddy M. Presepsin: Hope in the Quest for the Holy Grail. Indian J Crit Care Med 2022; 26:664-666. [PMID: 35836630 PMCID: PMC9237159 DOI: 10.5005/jp-journals-10071-24251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
How to cite this article: Samprathi A, Samprathi M, Reddy M. Presepsin: Hope in the Quest for the Holy Grail. Indian J Crit Care Med 2022;26(6):664-666.
Collapse
Affiliation(s)
- Abhishek Samprathi
- Department of Critical Care Medicine, Fortis Hospitals, Bengaluru, Karnataka, India
| | - Madhusudan Samprathi
- Department of Pediatrics, All India Institute of Medical Sciences, Hyderabad, Telangana, India
| | - Mounika Reddy
- Department of Pediatrics, All India Institute of Medical Sciences, Hyderabad, Telangana, India
| |
Collapse
|
|
31
|
Jeong YK, Kim EY. Predictive Role of Changes in Presepsin and Early Sepsis in ICU Patients After Abdominal Surgery. J Surg Res 2022; 278:207-215. [PMID: 35623266 DOI: 10.1016/j.jss.2022.04.072] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/23/2022] [Accepted: 04/08/2022] [Indexed: 11/15/2022]
Abstract
INTRODUCTION It is difficult to identify early sepsis after surgery due to postoperative inflammatory reactions. Presepsin, a glycoprotein expressed on the surface of innate immune cells, is produced during bacterial phagocytosis, and its level increases in the bloodstream of sepsis patients. We aimed to measure the differences between the diagnostic ability of presepsin and other biomarkers to identify postoperative sepsis and septic shock in acute period after major abdominal surgery. METHODS From March 2020 to March 2021, patients who underwent surgery due to intra-abdominal infection were enrolled. Level of presepsin and procalcitonin, and white blood cell counts were prospectively measured every morning for 3 d from intensive care unit admission after surgery (from T0 to T3). Diagnostic values of inflammatory markers were compared to predict early development of sepsis or septic shock within 7 d after surgery. Cut-off value of significant risk factor associated with postoperative sepsis or septic shock were evaluated. RESULTS Among 298 patients, postoperative sepsis and septic shock occurred in 91 and 38 patients, respectively. For prediction of early postoperative sepsis or septic shock, presepsin and procalcitonin had comparable diagnostic abilities. In multivariate analysis, presepsin > 406.5 pg/mL at T0 (Odds Ratio [OR]:4.055, P = 0.047), presepsin > 1216 pg/mL at T2 (OR:40.030, P = 0.005) and procalcitonin > 1.685 ng/mL at T2 (OR: 5.229, P = 0.008) were significant factors for predicting the occurrence of early postoperative septic shock. CONCLUSIONS Diagnostic accuracy of presepsin for sepsis or septic shock was feasible in acute postoperative period. It would be useful to monitor newly developed sepsis from normal inflammatory response, especially in patients who underwent surgical operation for the elimination of intra-abdominal infection.
Collapse
Affiliation(s)
- Yong Ki Jeong
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Young Kim
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| |
Collapse
|
|
32
|
Dholariya S, Parchwani DN, Singh R, Radadiya M, Katoch CDS. Utility of P-SEP, sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection. Indian J Clin Biochem 2022; 37:131-138. [PMID: 34642555 PMCID: PMC8494168 DOI: 10.1007/s12291-021-01008-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 09/18/2021] [Indexed: 12/22/2022]
Abstract
The coronavirus disease 2019 is a highly contagious viral infection caused by SARS-CoV-2 virus, member of coronaviridae family. It causes life threatening complications due to complexity and rapid onset course of the disease. Early identification of high-risk patients who require close monitoring and aggressive treatment remains challengeable till date. Novel biomarkers which help to identify high risk patients at the early stage is high priority. Objective of this review to find utility of P-SEP, sTREM-1 and suPAR for diagnosis, risk stratification and prognosis of SARS-CoV-2 infected cases. Soluble receptors like, P-SEP, sTREM-1 and suPAR have been involved in immune regulation in SARS-CoV-2 infection and elevate more in severe cases. A comprehensive research of databases like PubMed, EMBASE, CNKI and Web of Science was performed for relevant studies. A total of nine out of fifteen research literature in initial screening were included for this review. Interestingly all studies have reported high levels of P-SEP, sTREM-1 and suPAR in SARS-CoV-2 infected cases and the biomarkers positively correlated with severity of infection. This implies that P-SEP, sTREM-1 and suPAR can be implemented as surrogate marker in blood profile for early diagnosis, risk stratification and prognosis in SARS-CoV-2 for better management in Indian population at the current situation.
Collapse
Affiliation(s)
- Sagar Dholariya
- All India Institute of Medical Sciences, Rajkot, Gujarat India
| | | | - Ragini Singh
- All India Institute of Medical Sciences, Rajkot, Gujarat India
| | | | - C. D. S. Katoch
- All India Institute of Medical Sciences, Rajkot, Gujarat India
| |
Collapse
|
|
33
|
Masetto T, Eidizadeh A, Peter C, Grimmler M. National External Quality Assessment and direct method comparison reflect crucial deviations of Procalcitonin measurements in Germany. Clin Chim Acta 2022; 529:67-75. [DOI: 10.1016/j.cca.2022.02.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/01/2022] [Accepted: 02/10/2022] [Indexed: 12/20/2022]
|
|
34
|
Lazzaro A, De Girolamo G, Filippi V, Innocenti GP, Santinelli L, Ceccarelli G, Trecarichi EM, Torti C, Mastroianni CM, d’Ettorre G, Russo A. The Interplay between Host Defense, Infection, and Clinical Status in Septic Patients: A Narrative Review. Int J Mol Sci 2022; 23:ijms23020803. [PMID: 35054993 PMCID: PMC8776148 DOI: 10.3390/ijms23020803] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/05/2022] [Accepted: 01/09/2022] [Indexed: 01/08/2023] Open
Abstract
Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.
Collapse
Affiliation(s)
- Alessandro Lazzaro
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella De Girolamo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Valeria Filippi
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giuseppe Pietro Innocenti
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Letizia Santinelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Enrico Maria Trecarichi
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Carlo Torti
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella d’Ettorre
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Alessandro Russo
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
- Correspondence:
| |
Collapse
|
|
35
|
Lee S, Song J, Park DW, Seok H, Ahn S, Kim J, Park J, Cho HJ, Moon S. Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions. BMC Infect Dis 2022; 22:8. [PMID: 34983420 PMCID: PMC8725484 DOI: 10.1186/s12879-021-07012-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/23/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). METHODS This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan-Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. RESULTS Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001-1.005; p = 0.042). CONCLUSIONS Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.
Collapse
Affiliation(s)
- Sukyo Lee
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Juhyun Song
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
| | - Dae Won Park
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Hyeri Seok
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Sejoong Ahn
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Jooyeong Kim
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Jonghak Park
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Han-Jin Cho
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Sungwoo Moon
- Department of Emergency Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea
| |
Collapse
|
|
36
|
Ozger H, Senol E. Use of infection biomarkers in the emergency department. Turk J Emerg Med 2022; 22:169-176. [PMID: 36353385 PMCID: PMC9639740 DOI: 10.4103/2452-2473.357347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/02/2022] [Accepted: 06/03/2022] [Indexed: 11/13/2022] Open
Abstract
The use of infection biomarkers in the emergency department is discussed in terms of their possible contributions to diagnostic-prognostic uncertainties, appropriate antibiotic treatments, and triage and follow-up planning. Procalcitonin (PCT), C-reactive protein (CRP), proadrenomedullin (proADM), and presepsin are among the most discussed infection biomarkers for use in the emergency department. Due to the variable sensitivity results and cutoff values, there are insufficient data to recommend the widespread use of CRP and procalcitonin (PCT) for the diagnosis and prognosis of infection in the emergency department. However, these biomarkers can be used for appropriate antibiotic use in selected infection groups, such as community-acquired pneumonia, especially to reduce unnecessary antibiotic prescribing. With its prognostic superiority over other biomarkers and its contribution to prognostic score systems in community-acquired pneumonia (CAP), proADM can be used to predict hospitalization, preferably within the scope of clinical studies. Although presepsin has been shown to have some advantages over other biomarkers to rule out sepsis, there are insufficient data for its clinical use in the emergency department.
Collapse
|
|
37
|
Byler S, Baker A, Freiman E, Herigon JC, Eisenberg MA. Utility of specific laboratory biomarkers to predict severe sepsis in pediatric patients with SIRS. Am J Emerg Med 2021; 50:778-783. [PMID: 34879502 DOI: 10.1016/j.ajem.2021.09.081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/27/2021] [Accepted: 09/30/2021] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE To identify the association between readily available laboratory biomarkers and the development of severe sepsis in children presenting to the emergency department (ED) with systemic inflammatory response syndrome (SIRS). METHODS In this retrospective cohort study, ED patient encounters from June 2018 to June 2019 that triggered an automated sepsis alert based on SIRS criteria were analyzed. Encounters were included if the patient had any of the following laboratory tests sent within 6 h of ED arrival: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactic acid, and procalcitonin. For each of the biomarkers, a receiver operating characteristic (ROC) curve was created for our primary outcome, severe sepsis within 24 h of ED disposition, and our secondary outcome, severe sepsis with a positive bacterial culture. For each ROC curve, we calculated the area under the curve (AUC) with 95% confidence intervals (95% CI) and created cutoff points to achieve 90% sensitivity and 90% sensitivity for the primary and secondary outcomes. RESULTS During the study period, 4349/61,195 (7.1%) encounters triggered an automated sepsis alert. Of those, 1207/4349 (27.8%) had one of the candidate biomarkers sent within 6 h of ED arrival and were included in the study. A total of 100/1207 (8.3%) met criteria for severe sepsis within 24 h of arrival, and 41/100 severe sepsis cases (41%) were deemed culture-positive. Procalcitonin had the highest AUC for identifying severe sepsis [0.62 (95% CI 0.52-0.73)] while ESR and CRP had the highest AUC for culture-positive sepsis [0.68 (95% CI 0.47-0.89) and 0.67 (95% CI 0.53-0.81), respectively]. At 90% sensitivity for detecting severe sepsis, all of the biomarker threshold values fell within that laboratory test's normal range. At 90% specificity for severe sepsis, threshold values were as follows: procalcitonin 2.72 ng/mL, CRP 16.79 mg/dL, ESR 79.5 mm/h and lactic acid 3.6 mmol/L. CONCLUSION Our data indicate that CRP, ESR, lactic acid, and procalcitonin elevations were all specific, but not sensitive, in identifying children in the ED with SIRS who go on to develop severe sepsis.
Collapse
Affiliation(s)
- Shannon Byler
- Boston Combined Residency Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States of America.
| | - Alexandra Baker
- Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States of America; Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America
| | - Eli Freiman
- Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States of America; Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America
| | - Joshua C Herigon
- Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America; Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States of America
| | - Matthew A Eisenberg
- Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States of America; Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America
| |
Collapse
|
|
38
|
Maddaloni C, De Rose DU, Santisi A, Martini L, Caoci S, Bersani I, Ronchetti MP, Auriti C. The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. Int J Mol Sci 2021; 22:ijms222212154. [PMID: 34830040 PMCID: PMC8620326 DOI: 10.3390/ijms222212154] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/11/2022] Open
Abstract
Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8-14 days and 52% among infants aged 15-28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.
Collapse
Affiliation(s)
- Chiara Maddaloni
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Domenico Umberto De Rose
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Alessandra Santisi
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Ludovica Martini
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Stefano Caoci
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Iliana Bersani
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
| | - Maria Paola Ronchetti
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
- Neonatal Intensive Care (NICU) and Neonatal Pathology, San Vincenzo Hospital, 98039 Taormina, Italy
| | - Cinzia Auriti
- Neonatal Intensive Care Unit (NICU), Medical and Surgical Department of the Fetus—Newborn-Infant, “Bambino Gesù” Children’s Hospital IRCCS, 00165 Rome, Italy; (C.M.); (D.U.D.R.); (A.S.); (L.M.); (S.C.); (I.B.); (M.P.R.)
- Correspondence: ; Tel.: +39-06-6859-2427; Fax: +39-06-6859-3916
| |
Collapse
|
|
39
|
Dell'Aquila P, Raimondo P, Orso D, De Luca P, Pozzessere P, Parisi CV, Bove T, Vetrugno L, Grasso S, Procacci V. A simple prognostic score based on troponin and presepsin for COVID-19 patients admitted to the emergency department: a single-center pilot study. ACTA BIO-MEDICA : ATENEI PARMENSIS 2021; 92:e2021233. [PMID: 34487072 PMCID: PMC8477102 DOI: 10.23750/abm.v92i4.11479] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 04/22/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND The need to determine prognostic factors that can predict a particularly severe or, conversely, the benign course of COVID-19 is particularly perceived in the Emergency Department (ED), considering the scarcity of resources for a conspicuous mass of patients. The aim of our study was to identify some predictors for 30-day mortality among some clinical, laboratory, and ultrasound variables in a COVID-19 patients population. METHODS Prospective single-center pilot study conducted in an ED of a University Hospital. A consecutive sample of confirmed COVID-19 patients with acute respiratory failure was enrolled from March 8th to April 15th, 2020. RESULTS 143 patients were enrolled. Deceased patients (n = 65) were older (81 vs. 61 years, p <0.001), and they had more frequently a history of heart disease, neurological disease, or chronic obstructive pulmonary disease (p-values = 0.026, 0.025, and 0.034, respectively) than survived patients. Troponin I and presepsin had a significant correlation with a worse outcome. Troponin achieved a sensitivity of 77% and a specificity of 82% for a cut-off value of 27.6 ng/L. The presepsin achieved a sensitivity of 54% and a specificity of 92% for a cut-off value of 871 pg/mL. CONCLUSION In a population of COVID-19 patients with acute respiratory failure in an ED, presepsin and troponin I are accurate predictors of 30-day mortality. Presepsin is highly specific and could permit the early identification of patients who could benefit from more intensive care as soon as they enter the ED. Further validation studies are needed to confirm this result.
Collapse
Affiliation(s)
- Paola Dell'Aquila
- Department of Emergency Medicine, University Hospital of Bari, Bari, Italy..
| | - Pasquale Raimondo
- Department of Emergency and Organ Transplant, University of Bari Aldo Moro, Bari, Italy.
| | - Daniele Orso
- Department of Medicine, University of Udine, Udine, Italy; Department of Anesthesia and Intensive Care, ASUFC Santa Maria della Misericordia University Hospital of Udine, Udine, Italy.
| | - Paola De Luca
- Department of Emergency Medicine, University Hospital of Bari, Bari, Italy..
| | - Pietro Pozzessere
- Department of Emergency Medicine, University Hospital of Bari, Bari, Italy..
| | - Carmen Vita Parisi
- Department of Emergency Medicine, University Hospital of Bari, Bari, Italy..
| | - Tiziana Bove
- Department of Medicine, University of Udine, Udine, Italy; Department of Anesthesia and Intensive Care, ASUFC Santa Maria della Misericordia University Hospital of Udine, Udine, Italy.
| | - Luigi Vetrugno
- Department of Medicine, University of Udine, Udine, Italy; Department of Anesthesia and Intensive Care Medicine, ASUFC Hospital of Udine, Udine, Italy.
| | - Salvatore Grasso
- Department of Emergency and Organ Transplant, University of Bari Aldo Moro, Bari, Italy.
| | - Vito Procacci
- Department of Emergency Medicine, University Hospital of Bari, Bari, Italy..
| |
Collapse
|
|
40
|
Complementary Use of Presepsin with the Sepsis-3 Criteria Improved Identification of High-Risk Patients with Suspected Sepsis. Biomedicines 2021; 9:biomedicines9091076. [PMID: 34572261 PMCID: PMC8469631 DOI: 10.3390/biomedicines9091076] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/20/2021] [Accepted: 08/21/2021] [Indexed: 12/29/2022] Open
Abstract
Presepsin has been proposed as an early indicator for diagnosis and prognosis in sepsis. We aimed to evaluate the prognostic accuracy of presepsin levels and additional value for identifying high-risk patients when taken together with the current sepsis criteria. This was a single-center, prospective, observational study of patients with suspected sepsis. The primary outcome was 28-day mortality. The prognostic performance of presepsin was evaluated by the area under the receiver operating characteristic curve (AUC), according to the sepsis definition using the Sequential Organ Failure Assessment (SOFA) score change (delta SOFA ≥ 2) and lactate level ≥ 2 mmol/L. A total of 755 patients were included. The AUC of presepsin for predicting 28-day mortality was 0.747. Presepsin showed adequate prognostic accuracy regardless of the delta SOFA score or lactate level. High presepsin levels (>755 pg/mL) showed an independent association with 28-day mortality (adjusted odds ratio: 5.17), and significant differences in mortality were observed, even in patients with non-sepsis low lactate level. Compared with a single criterion of the delta SOFA score or lactate, the addition of the high presepsin criterion significantly increased discrimination. Presepsin showed fair prognostic performance regardless of the clinical sepsis criteria. Complementary use of presepsin with the Sepsis-3 criteria may identify more high-risk septic patients and provide useful prognostic information.
Collapse
|
|
41
|
Piccioni A, Santoro MC, de Cunzo T, Tullo G, Cicchinelli S, Saviano A, Valletta F, Pascale MM, Candelli M, Covino M, Franceschi F. Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:770. [PMID: 34440976 PMCID: PMC8398764 DOI: 10.3390/medicina57080770] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/21/2021] [Accepted: 07/24/2021] [Indexed: 02/05/2023]
Abstract
The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.
Collapse
Affiliation(s)
- Andrea Piccioni
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
| | - Michele Cosimo Santoro
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
| | - Tommaso de Cunzo
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| | - Gianluca Tullo
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| | - Sara Cicchinelli
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
| | - Angela Saviano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| | - Federico Valletta
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| | - Marco Maria Pascale
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
| | - Marcello Candelli
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
| | - Marcello Covino
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| | - Francesco Franceschi
- Emergency Medicine Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (A.P.); (S.C.); (M.M.P.); (M.C.); (M.C.); (F.F.)
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (T.d.C.); (G.T.); (A.S.); (F.V.)
| |
Collapse
|
|
42
|
Koh JS, Kim YJ, Kang DH, Lee JE, Lee SI. Usefulness of presepsin in predicting the prognosis of patients with sepsis or septic shock: a retrospective cohort study. Yeungnam Univ J Med 2021; 38:318-325. [PMID: 34126701 PMCID: PMC8688790 DOI: 10.12701/yujm.2021.01018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 05/12/2021] [Indexed: 11/22/2022] Open
Abstract
Background The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. Methods Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (32 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. Results Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p<0.001) were higher in the non-survivor group. Receiver operating characteristic curve analysis revealed poor performances of presepsin and lactate in predicting the prognosis of sepsis (presepsin: area under the curve [AUC]=0.656, p=0.001; lactate: AUC=0.646, p=0.003). The SOFA score showed the best performance, with the highest AUC value (AUC=0.751, p<0.001). The prognostic cutoff point for presepsin was 1,176 pg/mL. Presepsin levels higher than 1,176 pg/mL (odds ratio [OR], 3.352; p<0.001), higher lactate levels (OR, 1.203; p=0.003), and higher SOFA score (OR, 1.249; p<0.001) were risk factors for in-hospital mortality. Conclusion Presepsin levels were higher in non-survivors than in survivors. Thus, presepsin may be a valuable biomarker in predicting the prognosis of sepsis.
Collapse
Affiliation(s)
- Jeong Suk Koh
- Department of Pulmonary and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Yoon Joo Kim
- Department of Pulmonary and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Da Hyun Kang
- Department of Pulmonary and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jeong Eun Lee
- Department of Pulmonary and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Song-I Lee
- Department of Pulmonary and Critical Care Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| |
Collapse
|
|
43
|
Kocyigit A, Sogut O, Durmus E, Kanimdan E, Guler EM, Kaplan O, Yenigun VB, Eren C, Ozman Z, Yasar O. Circulating furin, IL-6, and presepsin levels and disease severity in SARS-CoV-2-infected patients. Sci Prog 2021; 104:368504211026119. [PMID: 34187224 PMCID: PMC10305811 DOI: 10.1177/00368504211026119] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls (p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity (r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.
Collapse
Affiliation(s)
- Abdurrahim Kocyigit
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Ozgur Sogut
- Department of Emergency Medicine,
Health Science University, Haseki Training and Research Hospital, Istanbul,
Turkey
| | - Ezgi Durmus
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Ebru Kanimdan
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Eray Metin Guler
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Onur Kaplan
- Department of Emergency Medicine,
Health Science University, Haseki Training and Research Hospital, Istanbul,
Turkey
| | - Vildan Betul Yenigun
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Canan Eren
- Marmara University Pendik Training and
Research Hospital, Medical Microbiology and Blood Centre, Pendik, Istanbul
| | - Zeynep Ozman
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| | - Oznur Yasar
- Department of Medical Biochemistry,
Bezmialem Vakif University, Istanbul, Turkey
| |
Collapse
|
|
44
|
Abstract
INTRODUCTION Rapid diagnosis accompanied by appropriate treatment is essential in the therapy of sepsis. However, there is no blood marker available, which reliably predicts sepsis and associated mortality. Therefore, the aim of the present study was to evaluate presepsin and endotoxin in comparison with established blood markers in patients undergoing emergency visceral surgery for abdominal infection. PATIENTS AND METHODS This prospective study included 31 patients with abdominal infection undergoing emergency surgery between March and August 2014. The Sepsis-2 and Sepsis-3 definitions of sepsis were used. Blood markers (presepsin, endotoxin, C-reactive protein, procalcitonin (PCT), interleukin 6 (IL-6), white blood count) were analyzed preoperatively and correlated with the clinical course and mortality. Additionally, a combination of the three markers, which performed best, was tested. RESULTS Twenty patients (64.5%) in the analyzed cohort developed sepsis from an abdominal focus according to the latest sepsis definition. Out of the analyzed blood markers, presepsin exhibited the highest area under the curve, sensitivity, and specificity for the prediction of the development of sepsis. Moreover, presepsin had the highest predictive value for mortality as opposed to both endotoxin and previously established blood markers (i.e., PCT, IL-6). The multimarker approach, which included PCT, IL-6, and presepsin, showed no additional predictive value over presepsin alone. CONCLUSION The present study suggests that presepsin is a novel predictor of sepsis and mortality from sepsis in patients undergoing surgery for intra-abdominal infections. The findings of the present study should be validated in a larger cohort.
Collapse
|
|
45
|
Velissaris D, Zareifopoulos N, Karamouzos V, Karanikolas E, Pierrakos C, Koniari I, Karanikolas M. Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis. Cureus 2021; 13:e15019. [PMID: 34150378 PMCID: PMC8202808 DOI: 10.7759/cureus.15019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Sepsis is a condition characterized by high morbidity and mortality which is commonly encountered in an emergency and critical care setting. Despite a substantial body of research, the ideal biomarker for the diagnosis and prognostic stratification of septic patients remains unknown. This review aimed to summarize the publications referring to the validity of the biomarker presepsin when used for the detection, monitoring and prognosis in patients suffering with sepsis. This work is a narrative review based on a PubMed/Medline search conducted in order to identify all relevant publications referring to the use of presepsin in sepsis. Search was not limited by year of publication so all articles archived in the database would be retrieved. No article from before 2010 was identified. A total of 57 publications of the last decade were included, all of which support the use of presepsin as a biomarker for the assessment of septic patients. It has been used alone or in combination with commonly used biomarkers in the evaluation of patients with sepsis in settings such as the emergency department and the intensive care unit. It is useful in the initial workup of patients with suspected sepsis in the emergency setting and may be a predictive factor of mortality and the most severe complication of sepsis. Presepsin seems to be a valuable tool for the laboratory workup of sepsis, especially when used in conjunction with other biomarkers and clinical rating scores with an established role in this population. Further research is needed to evaluate the clinical implications of utilizing presepsin measurements in the workup of sepsis.
Collapse
Affiliation(s)
- Dimitrios Velissaris
- Department of Internal Medicine, General University Hospital of Patras, Patras, GRC
| | - Nicholas Zareifopoulos
- Department of Psychiatry, General Hospital of Nikaia, Piraeus "Agios Panteleimon", Athens, GRC.,Department of Internal Medicine, University of Patras School of Health Sciences, Patras, GRC
| | | | | | - Charalampos Pierrakos
- Intensive Care Unit, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, BEL
| | - Ioanna Koniari
- Department of Electrophysiology and Device, University Hospital of South Manchester NHS Foundation Trust, Manchester, GBR
| | - Menelaos Karanikolas
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA
| |
Collapse
|
|
46
|
Histidine-rich glycoprotein as a prognostic biomarker for sepsis. Sci Rep 2021; 11:10223. [PMID: 33986340 PMCID: PMC8119687 DOI: 10.1038/s41598-021-89555-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/26/2021] [Indexed: 12/26/2022] Open
Abstract
Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7–16.6] vs. 30.6 [22.1–39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.
Collapse
|
|
47
|
Ferrarese A, Frigo AC, Mion MM, Plebani M, Russo FP, Germani G, Gambato M, Cillo U, Cattelan A, Burra P, Senzolo M. Diagnostic and prognostic role of presepsin in patients with cirrhosis and bacterial infection. Clin Chem Lab Med 2021; 59:775-782. [PMID: 33095752 DOI: 10.1515/cclm-2020-1212] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 10/14/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Serum biomarkers have suboptimal accuracy for the early diagnosis of bacterial infection (BI) in cirrhosis. The aim of the study was to evaluate the diagnostic and prognostic accuracy of presepsin (PSP) in a cohort of hospitalized patients with cirrhosis. METHODS All adult cirrhotics admitted between 03.2016 and 06.2019 were consecutively evaluated. PSP was measured using chemiluminescent enzyme immunoassay, and its accuracy was compared with that of common biomarkers. RESULTS A total of 278 cirrhotic patients for a total of 448 hospitalizations were prospectively collected. Prevalence of BI at admission was 28.3%. Median (range) Log10PSP in the whole cohort was 2.83 (2.48-3.19) ng/L, significantly higher in patients with BI than in patients without (p<0.001). For a cutoff value of 2.87 ng/L, Log10PSP showed sensitivity, specificity and AUC-ROC of 0.66 (95% CI 0.57-0.74), 0.63 (95% CI 0.57-0.68) and 0.69 (95% CI 0.63-0.73), lower than that of C-reactive protein (p=0.002), but similar to procalcitonin (p=0.18) Patients with BI at hospitalization had higher probability of 28-day mortality (sub-hazard ratio [sHR] 2.65;95% CI 1.49-4.70; p=0.001). At multivariate Cox's regression analysis, Log10PSP (sHR 2.4; 95% CI 1.22-4.82; p=0.01) together with age and severity of liver disease, was an independent predictor of short-term mortality. CONCLUSIONS PSP shows low diagnostic accuracy for BI in cirrhosis, but it is an independent predictor of short-term mortality. PSP may be a biomarker of systemic inflammation, commonly seen in end-stage liver disease.
Collapse
Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| | - Anna Chiara Frigo
- Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padova University Hospital, Padova, Italy
| | - Monica Maria Mion
- Department of Laboratory Medicine, Padova University Hospital, Padova, Italy
| | - Mario Plebani
- Department of Laboratory Medicine, Padova University Hospital, Padova, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Center, Padova University Hospital, Padova, Italy
| | - Annamaria Cattelan
- Tropical and Infectious Disease Unit, Padova University Hospital, Padova, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy
| |
Collapse
|
|
48
|
Abdelshafey EE, Nasa P, Elgohary AE, Khalil MF, Rashwan MA, Ghezala HB, Tayar AA. Role of Presepsin for the Diagnosis of Sepsis and ICU Mortality: A Prospective Controlled Study. Indian J Crit Care Med 2021. [PMID: 33707892 DOI: 10.5005/jp-journals-10071-23715.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background This study aimed at evaluating the role of presepsin in early identification of sepsis and prediction of mortality in intensive care unit (ICU) patients in comparison to systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) score. Materials and methods Forty patients were selected randomly after admission to adult ICU. Data from emergency room (ER) triaging, and initial laboratory results were gathered to calculate qSOFA score, SIRS criteria, and SOFA score. Presepsin measurement was performed within 6 hours from ER triaging.The patients were categorized into sepsis and nonsepsis groups depending on the clinical and microbiological criteria and SOFA score changes. Results Twenty-six patients were diagnosed as septic with an average age of 68.04 ± 18.60 years, while 14 patients were nonseptic with an average age of 51.71 ± 24.88 years.Presepsin with a cutoff value >640 pg/mL (area under the curve [AUC] of 0.848 (p < 0.001}) had a significant diagnostic accuracy of identifying septic cases with sensitivity of 73.08% and specificity of 92.86% as compared to the nonsignificant SIRS (AUC, 0.670; sensitivity, 69.23%; and specificity, 57.14%) or qSOFA (AUC, 0.652; sensitivity, 38.46%; and specificity, 78.57%) criteria.Prespsin with a cutoff value >640 pg/mL also significantly (AUC of 0.920 [p < 0.001]) predicted mortality with sensitivity of 100.0% and specificity of 66.67% compared to the nonsignificant SIRS (AUC, 0.540; sensitivity, 70.0%; and specificity, 43.33%) or qSOFA (AUC, 0.670; sensitivity, 60%; and specificity, 76.67%) criteria. Conclusion Early presepsin measurement in ICU patients is more accurate in the diagnosis of sepsis and prediction of mortality as compared to SIRS or qSOFA score. How to cite this article Abdelshafey EE, Nasa P, Elgohary AE, Khalil MF, Rashwan MA, Ghezala HB, et al. Role of Presepsin for the Diagnosis of Sepsis and ICU Mortality: A Prospective Controlled Study. Indian J Crit Care Med 2021;25(2):153-157.
Collapse
Affiliation(s)
- Eslam E Abdelshafey
- Department of Critical Care Medicine, Alexandria, Egypt.,Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Prashant Nasa
- Department of Critical Care Medicine, NMC Specialty Hospital, Dubai, United Arab Emirates
| | - Ahmed E Elgohary
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Mohammad F Khalil
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Mohammad A Rashwan
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Hassen B Ghezala
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Ashraf A Tayar
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| |
Collapse
|
|
49
|
Abdelshafey EE, Nasa P, Elgohary AE, Khalil MF, Rashwan MA, Ghezala HB, Tayar AA. Role of Presepsin for the Diagnosis of Sepsis and ICU Mortality: A Prospective Controlled Study. Indian J Crit Care Med 2021; 25:153-157. [PMID: 33707892 PMCID: PMC7922455 DOI: 10.5005/jp-journals-10071-23715] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This study aimed at evaluating the role of presepsin in early identification of sepsis and prediction of mortality in intensive care unit (ICU) patients in comparison to systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) score. MATERIALS AND METHODS Forty patients were selected randomly after admission to adult ICU. Data from emergency room (ER) triaging, and initial laboratory results were gathered to calculate qSOFA score, SIRS criteria, and SOFA score. Presepsin measurement was performed within 6 hours from ER triaging.The patients were categorized into sepsis and nonsepsis groups depending on the clinical and microbiological criteria and SOFA score changes. RESULTS Twenty-six patients were diagnosed as septic with an average age of 68.04 ± 18.60 years, while 14 patients were nonseptic with an average age of 51.71 ± 24.88 years.Presepsin with a cutoff value >640 pg/mL (area under the curve [AUC] of 0.848 (p < 0.001}) had a significant diagnostic accuracy of identifying septic cases with sensitivity of 73.08% and specificity of 92.86% as compared to the nonsignificant SIRS (AUC, 0.670; sensitivity, 69.23%; and specificity, 57.14%) or qSOFA (AUC, 0.652; sensitivity, 38.46%; and specificity, 78.57%) criteria.Prespsin with a cutoff value >640 pg/mL also significantly (AUC of 0.920 [p < 0.001]) predicted mortality with sensitivity of 100.0% and specificity of 66.67% compared to the nonsignificant SIRS (AUC, 0.540; sensitivity, 70.0%; and specificity, 43.33%) or qSOFA (AUC, 0.670; sensitivity, 60%; and specificity, 76.67%) criteria. CONCLUSION Early presepsin measurement in ICU patients is more accurate in the diagnosis of sepsis and prediction of mortality as compared to SIRS or qSOFA score. HOW TO CITE THIS ARTICLE Abdelshafey EE, Nasa P, Elgohary AE, Khalil MF, Rashwan MA, Ghezala HB, et al. Role of Presepsin for the Diagnosis of Sepsis and ICU Mortality: A Prospective Controlled Study. Indian J Crit Care Med 2021;25(2):153-157.
Collapse
Affiliation(s)
- Eslam E Abdelshafey
- Department of Critical Care Medicine, Alexandria, Egypt
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Prashant Nasa
- Department of Critical Care Medicine, NMC Specialty Hospital, Dubai, United Arab Emirates
| | - Ahmed E Elgohary
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Mohammad F Khalil
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Mohammad A Rashwan
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Hassen B Ghezala
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| | - Ashraf A Tayar
- Department of Intensive Care Unit, Security Forces Hospital, Dammam, Saudi Arabia
| |
Collapse
|
|
50
|
Biban P, Teggi M, Gaffuri M, Santuz P, Onorato D, Carpenè G, Gregori D, Lippi G. Cell Population Data (CPD) for Early Recognition of Sepsis and Septic Shock in Children: A Pilot Study. Front Pediatr 2021; 9:642377. [PMID: 33777867 PMCID: PMC7989813 DOI: 10.3389/fped.2021.642377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/11/2021] [Indexed: 01/30/2023] Open
Abstract
Objectives: Innovative Cell Population Data (CPD) have been used as early biomarkers for diagnosing sepsis in adults. We assessed the usefulness of CPD in pediatric patients with sepsis/septic shock, in terms of early recognition and outcome prediction. We revised 54 patients (0-15 y) admitted to our Pediatric Intensive Care Unit (PICU) for sepsis/septic shock during a 4-year period. Twenty-eight patients were excluded, 26 septic patients were enrolled (G1). Forty children admitted for elective surgery served as controls (G2). Data on five selected CPD parameters, namely neutrophils fluorescence intensity (NE-SFL), monocytes cells complexity (MO-X), monocytes fluorescence intensity (MO-Y), monocytes complexity and width of dispersion of events measured (MO-WX), and monocytes cells size and width dispersion (MO-WZ), were obtained at time of PICU admission (t0) by a hematological analyzer (Sysmex XN 9000®). As the primary outcome we evaluated the relevance of CPD for diagnosing sepsis/septic shock on PICU admission. Furthermore, we investigated if CPD at t0 were correlated with C-reactive protein (CRP), patient survival, or complicated sepsis course. Results: On PICU admission (t0), NE-SFL, MO-WX, and MO-Y were higher in sepsis/septic shock patients compared to controls. NE-SFL values were correlated with CRP values in G1 patients (r = 0.83). None of the five CPD parameters was correlated with survival or complicated sepsis course. Conclusion: We found higher values of NE-SFL, MO-WX, and MO-Y in children with sepsis/septic shock upon PICU admission. These parameters may be a promising adjunct for early sepsis diagnosis in pediatric populations. Larger, prospective studies are needed to confirm our preliminary observations.
Collapse
Affiliation(s)
- Paolo Biban
- Pediatric Intensive Care Unit, Division of Pediatric Critical and Emergency Care, Verona University Hospital, Verona, Italy
| | - Martina Teggi
- Pediatric Intensive Care Unit, Division of Pediatric Critical and Emergency Care, Verona University Hospital, Verona, Italy
| | - Marcella Gaffuri
- Pediatric Intensive Care Unit, Division of Pediatric Critical and Emergency Care, Verona University Hospital, Verona, Italy
| | - Pierantonio Santuz
- Pediatric Intensive Care Unit, Division of Pediatric Critical and Emergency Care, Verona University Hospital, Verona, Italy
| | - Diletta Onorato
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Giovanni Carpenè
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University Hospital of Padua, Padova, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| |
Collapse
|