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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.
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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.)
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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.
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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
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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.
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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
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Gamarra-Morales Y, Molina-López J, Santiago-Ruiz FC, Herrera-Quintana L, Vázquez-Lorente H, Gascón-Luna F, Planells E. Efficiency of IL-6 in Early Prognosis and Follow-Up in Critically Ill Patients with Septic Shock. Diseases 2024; 12:298. [PMID: 39589972 PMCID: PMC11592789 DOI: 10.3390/diseases12110298] [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: 10/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: The aim of this study was to investigate the response of interleukin-6 (IL-6) during the first few hours of a patient's stay in the Intensive Care Unit (ICU) in a sample of critically ill patients with septic shock, compared to healthy subjects as controls. Additionally, the study examined the association of IL-6 with morbidity and mortality in these patients, as well as its relationship with biomarkers such as lactic acid, C-reactive protein (CRP) and procalcitonin (PCT). Methods: This was a prospective analytical study involving 28 critically ill patients with septic shock, monitored from ICU admission through to their first three days of stay. Demographic data, comorbidities and clinical information, including IL-6 and severity scores, were recorded. Results: IL-6 levels were significantly higher in patients with septic shock compared to healthy subjects (p < 0.001) upon admission. IL-6 levels decreased by the third day of ICU stay (p < 0.005). An association between IL-6 and mortality was observed (areas under the curve 0.826, confidence interval (CI) 95% 0.659-0.994, p < 0.008). Significant correlations between IL-6 and lactic acid (p < 0.009 and p < 0.018) and partial thromboplastin time (p < 0.004 and p < 0.007) were found on the first and third days, respectively. IL-6 was also the correlated with an anion gap at admission to the ICU (p < 0.009). Conclusions: In conclusion, this study suggests that IL-6 could be a valuable marker for early sepsis follow-up in ICU patients, particularly during the first 72 h of hospitalization, providing important prognostic information in patients with septic shock.
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Affiliation(s)
| | - Jorge Molina-López
- Faculty of Education, Psychology and Sports Sciences, University of Huelva, 21007 Huelva, Spain
| | | | - Lourdes Herrera-Quintana
- Department of Physiology, School of Pharmacy, Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (E.P.)
| | - Héctor Vázquez-Lorente
- Department of Physiology, School of Pharmacy, Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (E.P.)
| | - Félix Gascón-Luna
- Clinical Analysis Unit, Valle de los Pedroches Hospital, 14400 Córdoba, Spain;
| | - Elena Planells
- Department of Physiology, School of Pharmacy, Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.); (E.P.)
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Babel J, Košuta I, Vujaklija Brajković A, Lončar Vrančić A, Premužić V, Rogić D, Duraković N. Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools? J Clin Med 2024; 13:5991. [PMID: 39408051 PMCID: PMC11478026 DOI: 10.3390/jcm13195991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/02/2024] [Accepted: 10/07/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.
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Affiliation(s)
- Jakša Babel
- Division of Intensive Care Medicine, Department of Internal Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia; (I.K.); (A.V.B.)
| | - Iva Košuta
- Division of Intensive Care Medicine, Department of Internal Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia; (I.K.); (A.V.B.)
| | - Ana Vujaklija Brajković
- Division of Intensive Care Medicine, Department of Internal Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia; (I.K.); (A.V.B.)
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Ana Lončar Vrančić
- Department of Laboratory Diagnostics, University Hospital Center Zagreb, 10000 Zagreb, Croatia; (A.L.V.); (D.R.)
| | - Vedran Premužić
- Division of Nephrology, Hypertension, Dialysis and Transplantation, Department of Internal Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia;
| | - Dunja Rogić
- Department of Laboratory Diagnostics, University Hospital Center Zagreb, 10000 Zagreb, Croatia; (A.L.V.); (D.R.)
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
| | - Nadira Duraković
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia
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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.
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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
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Wang G, Lian H, Guo Q, Zhang H, Wang X. A Prospective Study of the Association of IL6 with the Critical Unit and Their Effect on in-Hospital Mortality in Critically Ill Patients. Int J Gen Med 2024; 17:3257-3268. [PMID: 39070225 PMCID: PMC11283831 DOI: 10.2147/ijgm.s474250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 07/16/2024] [Indexed: 07/30/2024] Open
Abstract
Purpose We previously proposed a new concept, the "critical unit", which covers the structural integrity and function of mitochondria and endothelium. Injury of the critical unit plays a key role in the development of critical illnesses. High levels of inflammation may lead to abnormalities of the critical unit, which is an important mechanism for critical illnesses, and both inflammation and critical unit dysfunction may affect patient prognosis. Here we evaluated the correlation between interleukin-6 (IL6) and the critical unit biomarkers in critically ill patients and the impact of both on prognosis. Patients and Methods This study included adult patients admitted to the intensive care unit for various reasons from January 1st to May 31st, 2023. Baseline characteristics, intensive care unit parameters, and laboratory test and outcome data were obtained from the electronic medical records system. Critical unit parameters were measured using polymerase chain reaction and enzyme-linked immunosorbent assay methods. Correlations were examined between IL6, critical unit parameters, and various outcomes. Results In critically ill patients, IL6 was closely associated with all the critical unit biomarkers (activated partial thromboplastin time, sphingosine 1-phosphate, mitochondrial DNA, mitochondrial fission 1, and Parkin) and the prognoses of patients. A nomogram was constructed using the critical unit biomarkers to predict the in-hospital mortality of critically ill patients. The area under the curve for the mortality prediction model was 0.708. In sensitivity analyses, the predictive effect was better in the non-surgery and tumor groups compared with the surgery and non-tumor groups, with area under the curve values of 0.885 and 0.891, respectively. Conclusion Our study innovatively integrated mitochondrial and endothelial markers in the critical unit to comprehensively evaluate patient prognosis, which may be a trend in the future assessment of critically ill patients. There are few such studies, and ours may promote the progress of related research.
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Affiliation(s)
- Guangjian Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Qirui Guo
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Hongmin Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xiaoting Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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Igna R, Muzica C, Zenovia S, Minea H, Girleanu I, Huiban L, Trifan A. The value of presepsin and procalcitonin as prognostic factors for mortality in patients with alcoholic liver cirrhosis and acute on chronic liver failure. Arch Clin Cases 2024; 11:61-68. [PMID: 39015298 PMCID: PMC11250657 DOI: 10.22551/2024.43.1102.10290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024] Open
Abstract
Background: Acute on chronic liver failure (ACLF) is typically characterized by a rapid progression of liver failure in patients with liver cirrhosis and it is triggered by a precipitant factor, usually a bacterial infection (BI). Considering the low accuracy of the inflammation biomarkers in liver cirrhosis, presepsin and procalcitonin have demonstrated a good diagnostic performance for BI. Understanding the key prognostic factors that influence patient outcomes can significantly impact clinical decision-making and improve patient care in ACLF which can lead to lower mortality rates. Aim: To evaluate the prognostic factors associated with 30-day mortality in patients with alcohol-related liver cirrhosis and ACLF. Methods: This retrospective study on 227 patients diagnosed with ACLF and alcohol-related liver cirrhosis analyzed the prognostic role of presepsin and procalcitonin serum levels. Results: The survival analysis according to the grade of ACLF showed that more than 80% of patients with ACLF grade 1 survived after 30 days, with a mean estimated time of death of 29 ±0.44 days (95 % CI: 28.17-29.92) compared to ACLF grade 2 (24.9±1.064 days; 95 % CI: 22.82-26.99) and ACLF grade 3 (21.05±1.17 days; 95 % CI: 18.75-23.34), with a mean overall survival on entire cohort of 25.69±0.52 days (95 % CI: 24.65-26.73). Presepsin (OR: 4.008, CI 95:3.130-6.456, p=0.001) and procalcitonin (OR: 3.666, CI 95:2.312-5.813, p=0.001) were the most significant factors associated with 30-day mortality. In ACLF grade 2, presepsin provides a better prediction of mortality at the cutoff value of 1050 pg/mL (Sensitivity 72%, Specificity 69%) than procalcitonin (AUC=0.727 95% CI 0.594-0.860, p<0.002) whereas in ACLF grade 3, a cutoff of 1450 pg/mL (Sensitivity 89%, Specificity 91%) presepsin had a more significant accuracy of mortality prediction (AUC=0.93 95% CI 0.81-0.99, p<0.001) than procalcitonin (AUC=0.731 95% CI 0.655-0.807, p<0.001). Conclusion: ACLF is associated with a high mortality rate and the risk of death increases with the grade of ACLF. Presepsin and procalcitonin serum levels are good prognostic factors for 30-day mortality and should be used in clinical practice to stratify the risk and provide and early and efficient treatment in patients with ACLF.
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Affiliation(s)
- Răzvan Igna
- Intensive Care Unit, “Sf. Spiridon” University Hospital, Iasi, Romania
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
| | - Horia Minea
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” University Hospital, Iasi, Romania
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Reddy PRV, Cherukuri M, Eshwara VK, Kudru CU, Prabhu RVK. Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study. Indian J Crit Care Med 2024; 28:637-644. [PMID: 38994269 PMCID: PMC11234134 DOI: 10.5005/jp-journals-10071-24754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 06/06/2024] [Indexed: 07/13/2024] Open
Abstract
Background This study aimed to assess the potential of serum interleukin-6 (IL-6) as a diagnostic marker in predicting bacteremia and to determine its association with severity and outcome among sepsis patients. Materials and methods A prospective observational study was conducted, comprising a cohort of 118 patients admitted to the ICU with suspected sepsis from January 2019 to April 2020. Results Among the 108 patients analyzed, 60 (55.6%) were bacteremic and 48 (44.4%) were nonbacteremic. Of 60 patients with bacteremia, 13 (21.6%) had sepsis and 47 (78.3%) had septic shock. In predicting bacteremia, the area under the curve (AUC) for IL-6 was 0.512 [95% CI, 0.400-0.623]. The AUC for IL-6 in differentiating sepsis from septic shock was 0.724 [95% CI, 0.625-0.823]. The sensitivity and specificity for predicting bacteremia for IL-6 were 66% and 67%, respectively (p < 0.001). Multivariate analysis revealed that C-reactive protein (CRP) (p = 0.04) and APACHE II score (p = 0.025) were significant predictors of bacteremia, whereas lactate (p = 0.04), and APACHE II score (p < 0.001) were significant predictors of sepsis severity. Patients with elevated levels of procalcitonin PCT (p = 0.024), APACHE II (p = 0.003), and SOFA (p = 0.002) scores had significantly higher mortality rates. Conclusion C-reactive protein and APACHE II score, lactate and APACHE II score, and PCT, SOFA, and APACHE II scores performed better in predicting bacteremia, sepsis severity, and clinical outcome, respectively compared with IL-6. How to cite this article Reddy PRV, Cherukuri M, Eshwara VK, Kudru CU, Prabhu RVK. Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study. Indian J Crit Care Med 2024;28(7):637-644.
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Affiliation(s)
- Penna RV Reddy
- Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Mounika Cherukuri
- Faculty of General Medicine, Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Vandana K Eshwara
- Faculty of Microbiology, Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Chandrashekar Udyavara Kudru
- Faculty of General Medicine, Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - RV Krishnananda Prabhu
- Faculty of Biochemistry, Department of Biochemistry, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
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10
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Wu Z, Geng N, Liu Z, Pan W, Zhu Y, Shan J, Shi H, Han Y, Ma Y, Liu B. Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction. Virol J 2024; 21:96. [PMID: 38671532 PMCID: PMC11046891 DOI: 10.1186/s12985-024-02367-1] [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: 12/12/2023] [Accepted: 04/15/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.
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Affiliation(s)
- Zhipeng Wu
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmenwai Street, Fengtai District, Beijing City, 100069, People's Republic of China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, People's Republic of China
| | - Nan Geng
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China
| | - Zhao Liu
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China
| | - Wen Pan
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China
| | - Yueke Zhu
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China
| | - Jing Shan
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China
| | - Hongbo Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Ying Han
- Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Yingmin Ma
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmenwai Street, Fengtai District, Beijing City, 100069, People's Republic of China.
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, People's Republic of China.
| | - Bo Liu
- Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing City, 100069, People's Republic of China.
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11
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Wei S, Shen Z, Yin Y, Cong Z, Zeng Z, Zhu X. Advances of presepsin in sepsis-associated ARDS. Postgrad Med J 2024; 100:209-218. [PMID: 38147883 DOI: 10.1093/postmj/qgad132] [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: 08/04/2023] [Revised: 10/30/2023] [Accepted: 12/02/2023] [Indexed: 12/28/2023]
Abstract
This article reviews the correlation between presepsin and sepsis and the resulting acute respiratory distress syndrome (ARDS). ARDS is a severe complication of sepsis. Despite the successful application of protective mechanical ventilation, restrictive fluid therapy, and neuromuscular blockade, which have effectively reduced the morbidity and mortality associated with ARDS, the mortality rate among patients with sepsis-associated ARDS remains notably high. The challenge lies in the prediction of ARDS onset and the timely implementation of intervention strategies. Recent studies have demonstrated significant variations in presepsin (PSEP) levels between patients with sepsis and those without, particularly in the context of ARDS. Moreover, these studies have revealed substantially elevated PSEP levels in patients with sepsis-associated ARDS compared to those with nonsepsis-associated ARDS. Consequently, PSEP emerges as a valuable biomarker for identifying patients with an increased risk of sepsis-associated ARDS and to predict in-hospital mortality.
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Affiliation(s)
- Senhao Wei
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
- Graduate School of Peking University Health Science Center, Peking University Health Science Center, Beijing 100191, China
| | - Ziyuan Shen
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
- Graduate School of Peking University Health Science Center, Peking University Health Science Center, Beijing 100191, China
| | - Yiyuan Yin
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Zhukai Cong
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Zhaojin Zeng
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
- Graduate School of Peking University Health Science Center, Peking University Health Science Center, Beijing 100191, China
| | - Xi Zhu
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
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12
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Palalıoğlu B, Erdoğan S, Atay G, Tugrul HC, Özer ÖF. Diagnostic and Prognostic Value of Pentraxin 3, Interleukin-6, CRP, and Procalcitonin Levels in Patients with Sepsis and Septic Shock. Niger J Clin Pract 2024; 27:317-324. [PMID: 38528351 DOI: 10.4103/njcp.njcp_615_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 12/16/2023] [Indexed: 03/27/2024]
Abstract
INTRODUCTION AND PURPOSE In this prospective study, we aim to evaluate the effects of antibiotherapy on pentraxin-3 (PTX3), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in patients with sepsis and septic shock. MATERIALS AND METHODS In our study, CRP, procalcitonin, IL-6, and PTX3 levels at initial and 48 hours of the antibiotherapy of patients who were admitted to the pediatric intensive care unit (PICU) with the diagnosis of sepsis and septic shock between June 2020 and March 2021 were compared. Patients were compared with the age-appropriate case-control group formed from the patients who received pre-operative routines to investigate the diagnostic value. RESULTS CRP, IL-6, and PTX3 levels of the patients were significantly higher compared to controls (P < 0.05). After the 48th hour of treatment compared to initial CRP, lactate and PCT levels were significantly lower (P < 0.05). The IL-6 and PCT levels were significantly higher in patients with mortality than in surviving patients. Surviving patients showed a significant decrease in CRP level at the 48th hour. IL-6 levels of patients with septic shock were significantly higher than those with sepsis (P = 0.010; P < 0.05). In the diagnosis of septic shock, the area under curve was 0.785 for IL-6 and the standard deviation was 0.09 (P = 0.002, cut-off value, >32 pg/mL, 88.9% sensitivity, 65.6% specifity). CONCLUSION The results of this study indicated that IL-6 level is an appropriate biomarker with high specificity in the diagnosis of sepsis and septic shock and in evaluating the response to treatment and determining the prognosis.
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Affiliation(s)
- B Palalıoğlu
- Department of Pediatrics, University of Health Sciences Zeynep Kamil Training and Research Hospital, Uskudar Opr. Dr. Burhanettin Ustunel Cad. No:10, Istanbul, Turkey
| | - S Erdoğan
- Department of Pediatric Intensive Care, University of Health Sciences Umraniye Training and Research Hospital, Elmalıkent, Adem Yavuz Cd., Istanbul, Turkey
| | - G Atay
- Department of Pediatric Intensive Care, University of Health Sciences Umraniye Training and Research Hospital, Elmalıkent, Adem Yavuz Cd., Istanbul, Turkey
| | - H C Tugrul
- Department of Pediatric Intensive Care, University of Health Sciences Umraniye Training and Research Hospital, Elmalıkent, Adem Yavuz Cd., Istanbul, Turkey
| | - Ö F Özer
- Bezmialem Vakif University, Department of Biochemistry Adnan Menderes Bulvarı (Vatan Cad.) P.K. 34093 Fatih/Istanbul, Turkey
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13
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Shimoyama Y, Kadono N, Umegaki O. Presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients than for young sepsis patients in ICUs: a pilot study. BMC Res Notes 2024; 17:53. [PMID: 38378647 PMCID: PMC10877906 DOI: 10.1186/s13104-024-06719-6] [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: 08/19/2023] [Accepted: 02/14/2024] [Indexed: 02/22/2024] Open
Abstract
OBJECTIVE Sepsis is a syndrome of life-threatening organ dysfunction. This study aimed to determine whether presepsin is a useful predictor of septic acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and shock in very-old sepsis patients aged 75 years in intensive care units (ICUs). RESULTS A total of 83 adult patients diagnosed with sepsis were prospectively examined and divided into two groups: those aged 75 years and older (over 75 group) and those aged younger than 75 years (under 75 group). Presepsin values were measured after ICU admission. Inflammation-based prognostic scores were also examined. For category classification, total scores ("inflammation-presepsin scores [iPS]") were calculated. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with septic AKI, ARDS, DIC, or shock and those without these disorders in the over 75 and under 75 groups. Areas under the curve of presepsin for predicting septic AKI and ARDS in the over 75 group were both > 0.7, which were significantly higher than those in the under 75 group. In conclusion, presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients (over 75 years) than for younger sepsis patients (under 75 years).
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Affiliation(s)
- Yuichiro Shimoyama
- Department of Anesthesiology, Intensive Care Unit, Osaka Medical and Pharmaceutical University, Osaka Medical and Pharmaceutical University Hospital, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan.
| | - Noriko Kadono
- Department of Anesthesiology, Intensive Care Unit, Osaka Medical and Pharmaceutical University, Osaka Medical and Pharmaceutical University Hospital, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan
| | - Osamu Umegaki
- Department of Anesthesiology, Intensive Care Unit, Osaka Medical and Pharmaceutical University, Osaka Medical and Pharmaceutical University Hospital, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan
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14
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Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Dudda J, Brück LM, Hoffmann U, Bertsch T, Akin I, Behnes M. C-reactive protein and procalcitonin during course of sepsis and septic shock. Ir J Med Sci 2024; 193:457-468. [PMID: 37204560 PMCID: PMC10196281 DOI: 10.1007/s11845-023-03385-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 04/20/2023] [Indexed: 05/20/2023]
Abstract
OBJECTIVE The study investigates the diagnostic and prognostic value of C-reactive protein (CRP) and procalcitonin (PCT) in patients with sepsis and septic shock. BACKGROUND Limited data regarding the prognostic value of CRP and PCT during the course of sepsis or septic shock is available. METHODS Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), day 2, 3, 5, 7, and 10. Firstly, the diagnostic value of CRP and PCT for the diagnosis of a septic shock, as well as for the discrimination of positive blood cultures, was tested. Secondly, the prognostic value of the CRP and PCT was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, and Kaplan-Meier analyses. RESULTS A total of 349 patients were included, of which 56% had a sepsis and 44% a septic shock on day 1. The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.861 on day 7 and 0.833 on day 10, the PCT revealed a superior AUC than the CRP (AUC 0.440-0.652) with regard to the discrimination between patients with sepsis and septic shock. In contrast, the prognostic AUCs for 30-day all-cause mortality were poor. Both higher CRP (HR = 0.999; 95% CI 0.998-1.001; p = 0.203) and PCT levels (HR = 0.998; 95% CI 0.993-1.003; p = 0.500) were not associated with the risk of 30-day all-cause mortality. During the first 10 days of ICU treatment, both CRP and PCT declined irrespective of clinical improvement or impairment. CONCLUSION PCT was a reliable diagnostic tool for the diagnosis of septic shock compared to CRP. Both CRP and PCT were shown to have poor predictive value with regard to 30-day all-cause mortality and were not associated with the risk of all-cause mortality in patients admitted with sepsis or septic shock.
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Affiliation(s)
- Tobias Schupp
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Kathrin Weidner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Rusnak
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Schanas Jawhar
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jan Forner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Floriana Dulatahu
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Dudda
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Lea Marie Brück
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Ursula Hoffmann
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
| | - Ibrahim Akin
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Michael Behnes
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany.
- European Center for AngioScience (ECAS), German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany.
- First Department of Medicine, University Medical Center Mannheim (UMM), Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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de Nooijer AH, Pickkers P, Netea MG, Kox M. Inflammatory biomarkers to predict the prognosis of acute bacterial and viral infections. J Crit Care 2023; 78:154360. [PMID: 37343422 DOI: 10.1016/j.jcrc.2023.154360] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/07/2023] [Indexed: 06/23/2023]
Abstract
Mortality in acute infections is mostly associated with sepsis, defined as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. It remains challenging to identify the patients with increased mortality risk due to the high heterogeneity in the dysregulated host immune response and disease progression. Biomarkers reflecting different pathways involved in the inflammatory response might improve prediction of mortality risk (prognostic enrichment) among patients with acute infections by reducing heterogeneity of the host response, as well as suggest novel strategies for patient stratification and treatment (predictive enrichment) through precision medicine approaches. The predictive value of inflammatory biomarkers has been extensively investigated in bacterial infections and the recent COVID-19 pandemic caused an increased interest in inflammatory biomarkers in this viral infection. However, limited research investigated whether the prognostic potential of these biomarkers differs between bacterial and viral infections. In this narrative review, we provide an overview of the value of various inflammatory biomarkers for the prediction of mortality in bacterial and viral infections.
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Affiliation(s)
- Aline H de Nooijer
- Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands
| | - Mihai G Netea
- Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany
| | - Matthijs Kox
- Department of Intensive Care Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud University Medical Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
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Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Kittel M, Bertsch T, Akin I, Behnes M. Diagnostic and prognostic role of platelets in patients with sepsis and septic shock. Platelets 2023; 34:2131753. [PMID: 36484263 DOI: 10.1080/09537104.2022.2131753] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 106/ml. The presence of thrombocytopenia (i.e. <150 × 106/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057-1.878; p = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045-2.109; p = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567-2.026; p = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock.
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Affiliation(s)
- Tobias Schupp
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Kathrin Weidner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Rusnak
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Schanas Jawhar
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Jan Forner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Floriana Dulatahu
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Lea Marie Brück
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Ursula Hoffmann
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Maximilian Kittel
- Institute for Clinical Chemistry, Faculty of Medicine Mannheim, Heidelberg University, Mannheim, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
| | - Ibrahim Akin
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Michael Behnes
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
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17
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Songjang W, Paiyabhroma N, Jumroon N, Jiraviriyakul A, Nernpermpisooth N, Seenak P, Kumphune S, Thaisakun S, Phaonakrop N, Roytrakul S, Pankhong P. Proteomic Profiling of Early Secreted Proteins in Response to Lipopolysaccharide-Induced Vascular Endothelial Cell EA.hy926 Injury. Biomedicines 2023; 11:3065. [PMID: 38002065 PMCID: PMC10669054 DOI: 10.3390/biomedicines11113065] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Sepsis is a crucial public health problem with a high mortality rate caused by a dysregulated host immune response to infection. Vascular endothelial cell injury is an important hallmark of sepsis, which leads to multiple organ failure and death. Early biomarkers to diagnose sepsis may provide early intervention and reduce risk of death. Damage-associated molecular patterns (DAMPs) are host nuclear or cytoplasmic molecules released from cells following tissue damage. We postulated that DAMPs could potentially be a novel sepsis biomarker. We used an in vitro model to determine suitable protein-DAMPs biomarkers for early sepsis diagnosis. Low and high lipopolysaccharide (LPS) doses were used to stimulate the human umbilical vein endothelial cell line EA.hy926 for 24, 48, and 72 h. Results showed that cell viability was reduced in both dose-dependent and time-dependent manners. Cell injury was corroborated by a significant increase in lactate dehydrogenase (LDH) activity within 24 h in cell-conditioned medium. Secreted protein-DAMPs in the supernatant, collected at different time points within 24 h, were characterized using shotgun proteomics LC-MS/MS analysis. Results showed that there were 2233 proteins. Among these, 181 proteins from the LPS-stimulated EA.hy926 at 1, 12, and 24 h were significantly different from those of the control. Twelve proteins were up-regulated at all three time points. Furthermore, a potential interaction analysis of predominant DAMPs-related proteins using STITCH 5.0 revealed the following associations with pathways: response to stress; bacterium; and LPS (GO:0080134; 0009617; 0032496). Markedly, alpha-2-HS-glycoprotein (AHSG or fetuin-A) and lactotransferrin (LTF) potentially presented since the first hour of LPS stimulation, and were highly up-regulated at 24 h. Taken together, we reported proteomic profiling of vascular endothelial cell-specific DAMPs in response to early an in vitro LPS stimulation, suggesting that these early damage-response protein candidates could be novel early biomarkers associated with sepsis.
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Affiliation(s)
- Worawat Songjang
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Nitchawat Paiyabhroma
- Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Noppadon Jumroon
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Arunya Jiraviriyakul
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Nitirut Nernpermpisooth
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Porrnthanate Seenak
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
| | - Sarawut Kumphune
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Biomedical Engineering and Innovation Research Center, Chiang Mai University, Mueang Chiang Mai District, Chiang Mai 50200, Thailand
- Biomedical Engineering Institute (BMEI), Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siriwan Thaisakun
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
| | - Narumon Phaonakrop
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
| | - Sittiruk Roytrakul
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand
| | - Panyupa Pankhong
- Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand; (W.S.)
- Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
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18
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Paraskevas T, Chourpiliadi C, Demiri S, Micahilides C, Karanikolas E, Lagadinou M, Velissaris D. Presepsin in the diagnosis of sepsis. Clin Chim Acta 2023; 550:117588. [PMID: 37813329 DOI: 10.1016/j.cca.2023.117588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/05/2023] [Accepted: 10/06/2023] [Indexed: 10/11/2023]
Abstract
OBJECTIVES Sepsis is a life-threatening condition characterized by organ dysfunction. It occurs due to the host's dysregulated response to an infection. Clinicians use inflammatory biomarkers to evaluate patients at risk of sepsis in various settings. METHODS We included studies focusing on the diagnostic accuracy of presepsin in patients under suspicion of sepsis. The bivariate model of Reitsma was used for the quantitative synthesis, and summary estimates were calculated. The Zhou-Dendukuri approach was followed to assess heterogeneity. Subgroup analyses were performed based on settings and diagnostic criteria. RESULTS The summary sensitivity for diagnosing sepsis was 0.805 (95 % CI: 0.759-0.844), while the false positive rate (FPR) was 0.174 (95 % CI: 0.124-0.239). The area under the curve (AUC) for the summary receiver operating characteristic (SROC) curve was 0.875, with a slightly lower partial AUC of 0.833. The analysis using the Zhou-Dendukuri approach revealed low heterogeneity (I2 = 15.9 %). Subgroup analyses showed no significant differences in SROC curves and summary estimates between the ED and ICU settings, although the ED subgroup exhibited higher heterogeneity (I2 = 52.7 % vs. 20.2 %). The comparison between the diagnostic criteria, Sepsis 1 and Sepsis 3, demonstrated similar summary estimates and SROC curves. The examination of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool revealed a high risk of bias regarding the participants and their applicability. Also, there was an increased risk of bias in all the studies concerning the index test. CONCLUSION Based on our research, presepsin is a promising biomarker for triage and early diagnosis of sepsis.
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Affiliation(s)
| | | | - Silvia Demiri
- Department of Internal Medicine, University Hospital of Patras, Patras, Greece.
| | | | - Evangelos Karanikolas
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA.
| | - Maria Lagadinou
- Department of Internal Medicine, University Hospital of Patras, Patras, Greece.
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19
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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.
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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
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20
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Bizzoca D, Piazzolla A, Moretti L, Vicenti G, Moretti B, Solarino G. Physiologic postoperative presepsin kinetics following primary cementless total hip arthroplasty: A prospective observational study. World J Orthop 2023; 14:547-553. [PMID: 37485426 PMCID: PMC10359746 DOI: 10.5312/wjo.v14.i7.547] [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: 12/23/2022] [Revised: 03/09/2023] [Accepted: 06/12/2023] [Indexed: 07/17/2023] Open
Abstract
BACKGROUND Presepsin is an emerging biomarker in the diagnosis of sepsis. In the field of orthopaedics, it could be useful in diagnosing and managing periprosthetic joint infections. AIM To define the normal postoperative presepsin plasmatic curve, in patients undergoing primary cementless total hip arthroplasty (THA). METHODS Patients undergoing primary cementless THA at our Institute were recruited. Inclusion criteria were: Primary osteoarthritis of the hip; urinary catheter time of permanence < 24 h; peripheral venous cannulation time of permanence < 24 h; no postoperative homologous blood transfusion administration and hospital stay ≤ 8 d. Exclusion criteria were: The presence of other articular prosthetic replacement or bone fixation devices; chronic inflammatory diseases; chronic kidney diseases; history of recurrent infections or malignant neoplasms; previous surgery in the preceding 12 mo; diabetes mellitus; immunosuppressive drug or corticosteroid assumption. All the patients received the same antibiotic prophylaxis. All the THA were performed by the same surgical and anaesthesia team; total operative time was defined as the time taken from skin incision to completion of skin closure. At enrollment, anthropometric data, smocking status, osteoarthritis stage according to Kellgren and Lawrence, Harris Hip Score, drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS) and C-reactive protein 24 h before arthroplasty and at 24, 48, 72 and 96 h postoperatively and at 3, 6 and 12-mo follow-up. RESULTS A total of 96 patients (51 female; 45 male; mean age = 65.74 ± 5.58) were recruited. The mean PS values were: 137.54 pg/mL at baseline, 192.08 pg/mL at 24 h post-op; 254.85 pg/mL at 48 h post-op; 259 pg/mL at 72 h post-op; 248.6 pg/mL at 96-h post-op; 140.52 pg/mL at 3-mo follow-up; 135.55 pg/mL at 6-mo follow-up and 130.11 pg/mL at 12-mo follow-up. In two patients (2.08%) a soft-tissue infection was observed; in these patients, higher levels (> 350 pg/mL) were recorded at 3-mo follow-up. CONCLUSION The dosage of plasmatic PS concentration is highly recommended in patients undergoing THA before surgery to exclude the presence of an unknown infection. The PS plasmatic concentration should be also assessed at 72 h post-operatively, evaluate the maximum postoperative PS value, and at 96 h post-operatively when a decrease of presepsin should be found. The lack of a presepsin decrease at 96 h post-operatively could be a predictive factor of infection.
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Affiliation(s)
- Davide Bizzoca
- DAI Neuroscienze, Organi di Senso e Apparato Locomotore, AOU Consorziale Policlinico di Bari, Bari 70124, Italy
| | - Andrea Piazzolla
- DAI Neuroscienze, Organi di Senso e Apparato Locomotore, AOU Consorziale Policlinico di Bari, Bari 70124, Italy
| | - Lorenzo Moretti
- DAI Neuroscienze, Organi di Senso e Apparato Locomotore, AOU Consorziale Policlinico di Bari, Bari 70124, Italy
| | | | - Biagio Moretti
- Di BraiN, University of Bari "Aldo Moro", Bari 70124, Italy
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21
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Lin SP, Xu XJ, Liao C, Zhao N, Chen YY, Song H, Xu WQ, Liang J, Shen DY, Zhang JY, Shen HP, Zhao FY, Tang YM. The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock. Pediatr Hematol Oncol 2023; 41:1-14. [PMID: 37452625 DOI: 10.1080/08880018.2023.2233567] [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: 01/09/2023] [Revised: 06/15/2023] [Accepted: 06/24/2023] [Indexed: 07/18/2023]
Abstract
Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.
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Affiliation(s)
- Shu-Peng Lin
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Xiao-Jun Xu
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Chan Liao
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Ning Zhao
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Yuan-Yuan Chen
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Hua Song
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Wei-Qun Xu
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Juan Liang
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Di-Ying Shen
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Jing-Ying Zhang
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - He-Ping Shen
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Fen-Ying Zhao
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
| | - Yong-Min Tang
- Division/Center of Pediatric Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Research Center of Pediatric Leukemia Diagnostic and Therapeutic Technology of Zhejiang Province, National Medical Research Center for Child Health, Hangzhou, China
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22
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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.
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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.
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23
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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.
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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
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Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Bertsch T, Weiß C, Akin I, Behnes M. Diagnostic and prognostic value of the AST/ALT ratio in patients with sepsis and septic shock. Scand J Gastroenterol 2023; 58:392-402. [PMID: 36259154 DOI: 10.1080/00365521.2022.2131331] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The study investigates the diagnostic and prognostic value of the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in patients with sepsis and septic shock. Limited data regarding the prognostic value of the AST/ALT ratio in patients suffering from sepsis or septic shock is available. METHODS Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from day of disease onset (day 1), day 2, 3, 5 and 7. First, the diagnostic value of the AST/ALT ratio was tested for septic shock compared to sepsis. Second, the prognostic value of the AST/ALT ratio was tested for 30-d all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. RESULTS A total of 289 patients were included, of which 55% had sepsis and 45% septic shock. The overall rate of all-cause mortality at 30 d was 53%. With an area under the curve (AUC) of 0.651 on day 1 and 0.794 on day 7, the AST/ALT ratio revealed moderate but better diagnostic discrimination of septic shock compared to bilirubin. Furthermore, the AST/ALT ratio was able to discriminate 30-d all-cause mortality (AUC = 0.624; 95% CI 0.559 - 0.689; p = 0.001). Patients with an AST/ALT ratio above the median (>1.8) had higher rates of 30-d all-cause mortality compared to lower values (mortality rate 63 vs. 43%; log-rank p = 0.001), even after multivariable adjustment (HR = 1.703; 95% CI 1.182 - 2.453; p = 0.004) and propensity score matching. CONCLUSIONS The AST/ALT was a reliable diagnostic tool for the diagnosis of septic shock as well as a reliable tool to predict 30-d all-cause mortality in patients suffering from sepsis and septic shock.
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Affiliation(s)
- Tobias Schupp
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Kathrin Weidner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Rusnak
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Schanas Jawhar
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jan Forner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Floriana Dulatahu
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Lea Marie Brück
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Ursula Hoffmann
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
| | - Christel Weiß
- Department of Statistical Analysis, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
| | - Ibrahim Akin
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Michael Behnes
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
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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.
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Affiliation(s)
- Chung-Jong Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
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26
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Xiao HL, Wang GX, Wang Y, Tan ZM, Zhou J, Yu H, Xie MR, Li CS. Dynamic blood presepsin levels are associated with severity and outcome of acute pancreatitis: A prospective cohort study. World J Gastroenterol 2022; 28:5203-5216. [PMID: 36188715 PMCID: PMC9516673 DOI: 10.3748/wjg.v28.i35.5203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/10/2022] [Accepted: 09/01/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.
AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.
METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.
RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve (AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.
CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.
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Affiliation(s)
- Hong-Li Xiao
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Guo-Xing Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Yan Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhi-Min Tan
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jie Zhou
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Han Yu
- Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Miao-Rong Xie
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Chun-Sheng Li
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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Qin J, Wang H, Lyu Z, Liao Y, Zeng N, Wang K, Zhou Y, Zeng Z, Liao Z, Cao Y, He J, Wang T, Wen F. Elevated soluble death receptor 5 can predict poor prognosis in patients with acute respiratory distress syndrome. Expert Rev Respir Med 2022; 16:823-832. [PMID: 35822538 DOI: 10.1080/17476348.2022.2100351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND : The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5), participate in pulmonary cell apoptosis. This study aimed to investigate the clinical value of soluble DR5 and TRAIL for prognosis assessment in acute respiratory distress syndrome (ARDS). RESEARCH DESIGN AND METHODS : Serum and bronchoalveolar lavage fluid (BALF) samples were collected from ARDS patients and controls. Patients were followed-up until death or discharge. Soluble DR5, TRAIL, TNF-α, soluble receptor for advanced glycation end-products (sRAGE), and albumin levels were measured using the Magnetic Luminex or enzyme-linked immunosorbent assays. Data were analyzed according to their distribution and statistical purpose. RESULTS : Serum and BALF DR5 levels were elevated in patients with ARDS; TRAIL elevation and reduction was observed in BALF and serum, respectively. Serum DR5 was higher in non-survivors compared to survivors. Serum DR5 was positively correlated with serum TNF-α and critical illness scores and negatively correlated with serum TRAIL. Serum and BALF DR5 was positively correlated with the alveolar epithelial cell damage (sRAGE) and lung fluid leakage indicators. Serum DR5 exhibited potential for predicting mortality in patients with ARDS. CONCLUSIONS : Serum soluble DR5 elevation, a valuable prognosis predictor in ARDS, may be associated with alveolar epithelial cell apoptosis.
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Affiliation(s)
- Jiangyue Qin
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Hao Wang
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Zhuoyao Lyu
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Yue Liao
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Ni Zeng
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Ke Wang
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Yongfang Zhou
- Department of Critical Care Medicine, West China Hospital of Sichuan University, China
| | - Zijian Zeng
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Zenglin Liao
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Yufang Cao
- Department of Critical Care Medicine, Haikou Municipal People's Hospital and Central South University Xiangya School of Medicine Affiliated Haikou Hospital, China
| | - Junyun He
- Department of Respiratory Medicine, Hospital of Chengdu Office of People's Government of Tibetan autonomous Region, China
| | - Tao Wang
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
| | - Fuqiang Wen
- Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University. Guoxuexiang 37, Chengdu, Sichuan 610041, China
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de Hond TAP, Hamelink WJ, de Groot MCH, Hoefer IE, Oosterheert JJ, Haitjema S, Kaasjager KAH. Axial light loss of monocytes as a readily available prognostic biomarker in patients with suspected infection at the emergency department. PLoS One 2022; 17:e0270858. [PMID: 35816504 PMCID: PMC9273078 DOI: 10.1371/journal.pone.0270858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 06/19/2022] [Indexed: 11/26/2022] Open
Abstract
Objectives To evaluate the prognostic value of the coefficient of variance of axial light loss of monocytes (cv-ALL of monocytes) for adverse clinical outcomes in patients suspected of infection in the emergency department (ED). Methods We performed an observational, retrospective monocenter study including all medical patients ≥18 years admitted to the ED between September 2016 and June 2019 with suspected infection. Adverse clinical outcomes included 30-day mortality and ICU/MCU admission <3 days after presentation. We determined the additional value of monocyte cv-ALL and compared to frequently used clinical prediction scores (SIRS, qSOFA, MEWS). Next, we developed a clinical model with routinely available parameters at the ED, including cv-ALL of monocytes. Results A total of 3526 of patients were included. The OR for cv-ALL of monocytes alone was 2.21 (1.98–2.47) for 30-day mortality and 2.07 (1.86–2.29) for ICU/MCU admission <3 days after ED presentation. When cv-ALL of monocytes was combined with a clinical score, the prognostic accuracy increased significantly for all tested scores (SIRS, qSOFA, MEWS). The maximum AUC for a model with routinely available parameters at the ED was 0.81 to predict 30-day mortality and 0.81 for ICU/MCU admission. Conclusions Cv-ALL of monocytes is a readily available biomarker that is useful as prognostic marker to predict 30-day mortality. Furthermore, it can be used to improve routine prediction of adverse clinical outcomes at the ED. Clinical trial registration Registered in the Dutch Trial Register (NTR) und number 6916.
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Affiliation(s)
- Titus A. P. de Hond
- Department of Internal Medicine and Acute Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
- * E-mail:
| | - Wout J. Hamelink
- Department of Internal Medicine and Acute Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Mark C. H. de Groot
- Central Diagnostic Laboratory, Division Laboratory, Pharmacy and Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Imo E. Hoefer
- Central Diagnostic Laboratory, Division Laboratory, Pharmacy and Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jan Jelrik Oosterheert
- Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Saskia Haitjema
- Central Diagnostic Laboratory, Division Laboratory, Pharmacy and Biomedical Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Karin A. H. Kaasjager
- Department of Internal Medicine and Acute Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
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Biomarkers of sepsis in pigs, horses and cattle: from acute phase proteins to procalcitonin. Anim Health Res Rev 2022; 23:82-99. [PMID: 35795920 DOI: 10.1017/s1466252322000019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Sepsis is a complex clinical syndrome triggered by an inflammatory host response to an infection. It is usually complicated to detect and diagnose, and has severe consequences in human and veterinary health, especially when treatment is not started early. Therefore, efforts to detect sepsis accurately are needed. In addition, its proper diagnosis could reduce the misuse of antibiotics, which is essential fighting against antimicrobial resistance. This case is a particular issue in farm animals, as antibiotics have been traditionally given massively, but now they are becoming increasingly restricted. When sepsis is suspected in animals, the most frequently used biomarkers are acute phase proteins such as C-reactive protein, serum amyloid A and haptoglobin, but their concentrations can increase in other inflammatory conditions. In human patients, the most promising biomarkers to detect sepsis are currently procalcitonin and presepsin, and there is a wide range of other biomarkers under study. However, there is little information on the application of these biomarkers in veterinary species. This review aims to describe the general concepts of sepsis and the current knowledge about the biomarkers of sepsis in pigs, horses, and cattle and to discuss possible advances in the field.
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SCD14-ST and New Generation Inflammatory Biomarkers in the Prediction of COVID-19 Outcome. Biomolecules 2022; 12:biom12060826. [PMID: 35740951 PMCID: PMC9220996 DOI: 10.3390/biom12060826] [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] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/09/2022] [Accepted: 06/11/2022] [Indexed: 12/18/2022] Open
Abstract
Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients.
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Abstract
INTRODUCTION The immunobiology defining the clinically apparent differences in response to sepsis remains unclear. We hypothesize that in murine models of sepsis we can identify phenotypes of sepsis using non-invasive physiologic parameters (NIPP) early after infection to distinguish between different inflammatory states. METHODS Two murine models of sepsis were used: gram-negative pneumonia (PNA) and cecal ligation and puncture (CLP). All mice were treated with broad spectrum antibiotics and fluid resuscitation. High-risk sepsis responders (pDie) were defined as those predicted to die within 72 h following infection. Low-risk responders (pLive) were expected to survive the initial 72 h of sepsis. Statistical modeling in R was used for statistical analysis and machine learning. RESULTS NIPP obtained at 6 and 24 h after infection of 291 mice (85 PNA and 206 CLP) were used to define the sepsis phenotypes. Lasso regression for variable selection with 10-fold cross-validation was used to define the optimal shrinkage parameters. The variables selected to discriminate between phenotypes included 6-h temperature and 24-h pulse distention, heart rate (HR), and temperature. Applying the model to fit test data (n = 55), area under the curve (AUC) for the receiver operating characteristics (ROC) curve was 0.93. Subgroup analysis of 120 CLP mice revealed a HR of <620 bpm at 24 h as a univariate predictor of pDie. (AUC of ROC curve = 0.90). Subgroup analysis of PNA exposed mice (n = 121) did not reveal a single predictive variable highlighting the complex physiological alterations in response to sepsis. CONCLUSION In murine models with various etiologies of sepsis, non-invasive vitals assessed just 6 and 24 h after infection can identify different sepsis phenotypes. Stratification by sepsis phenotypes can transform future studies investigating novel therapies for sepsis.
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Combined Use of Presepsin and (1,3)-β-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients. J Fungi (Basel) 2022; 8:jof8030308. [PMID: 35330311 PMCID: PMC8954802 DOI: 10.3390/jof8030308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/07/2022] [Accepted: 03/14/2022] [Indexed: 11/17/2022] Open
Abstract
New biomarker panel was developed and validated on 165 critically ill adult patients to enable a more accurate invasive candidiasis (IC) diagnosis. Serum levels of the panfungal biomarker (1,3)-β-D-glucan (BDG) and the inflammatory biomarkers C-reactive protein, presepsin (PSEP), and procalcitonin (PCT) were correlated with culture-confirmed candidemia or bacteremia in 58 and 107 patients, respectively. The diagnostic utility was evaluated in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). BDG was the best marker for IC, achieving 96.6% sensitivity, 97.2% specificity, 94.9% PPV, and 98.1% NPV at a cut-off of 200 pg/mL (p ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL but had a lower PPV (36.5%) and low specificity (5.6%). Combined use of PSEP and BDG, thus, seems to be the most powerful laboratory approach for diagnosing IC. Furthermore, PSEP was more accurate for 28-day mortality prediction the area under the receiver operating characteristic curve (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off = 0.5 ng/mL). Finally, serum PSEP levels decreased significantly after only 14 days of echinocandin therapy (p = 0.0012). The probability of IC is almost 100% in critically ill adults with serum BDG and PSEP concentrations > 200 pg/mL and >700 pg/mL, respectively, defining a borderline between non-invasive superficial Candida colonization and IC.
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Rahn S, Becker-Pauly C. Meprin and ADAM proteases as triggers of systemic inflammation in sepsis. FEBS Lett 2022; 596:534-556. [PMID: 34762736 DOI: 10.1002/1873-3468.14225] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/19/2021] [Accepted: 10/28/2021] [Indexed: 12/24/2022]
Abstract
Systemic inflammatory disorders (SIDs) comprise a broad range of diseases characterized by dysregulated excessive innate immune responses. Severe forms of SIDs can lead to organ failure and death, and their increasing incidence represents a major issue for the healthcare system. Protease-mediated ectodomain shedding of cytokines and their receptors represents a central mechanism in the regulation of inflammatory responses. The metalloprotease A disintegrin and metalloproteinase (ADAM) 17 is the best-characterized ectodomain sheddase capable of releasing TNF-α and soluble IL-6 receptor, which are decisive factors of systemic inflammation. Recently, meprin metalloproteases were also identified as IL-6 receptor sheddases and activators of the pro-inflammatory cytokines IL-1β and IL-18. In different mouse models of SID, particularly those mimicking a sepsis-like phenotype, ADAM17 and meprins have been found to promote disease progression. In this review, we summarize the role of ADAM10, ADAM17, and meprins in the onset and progression of sepsis and discuss their potential as therapeutic targets.
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Affiliation(s)
- Sascha Rahn
- Biochemical Institute, Christian-Albrechts-University Kiel, Germany
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Güleç RD, Arslan FD, Çalışkan T, Şenol N, Yılmaz N, Atalay S, Pirim İ. Could presepsin be an alternative marker in the early diagnosis of sepsis in COVID-19? Scandinavian Journal of Clinical and Laboratory Investigation 2022; 82:108-114. [DOI: 10.1080/00365513.2022.2031278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Rasime Derya Güleç
- Department of Tissue Typing Laboratory, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Fatma Demet Arslan
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Taner Çalışkan
- Department of Anesthesia and Reanimation, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Nimet Şenol
- Department of Anesthesia and Reanimation, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Nisel Yılmaz
- Department of Medical Microbiology, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Sabri Atalay
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - İbrahim Pirim
- Department of Medical Biology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey
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Golovnya EG, Kharitidi TY, Sotnikov AV, Somonova OV, Kushlinskii NE. Diagnostic levels of sepsis biomarkers in children with oncological diseases. Klin Lab Diagn 2022; 67:13-18. [PMID: 35077064 DOI: 10.51620/0869-2084-2022-67-1-13-18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The data on the diagnostic levels of sepsis markers in blood plasma in 117 patients with oncological diseases at the age from 1 to 18 years are presented. The patients were divided into 4 groups depending on the outcome of the clinical course of the inflammatory process or infectious complications: group 1 - patients with no complications of anticancer treatment (n = 13/11.1%), group 2 - the presence of a systemic inflammatory response in patients (n = 64/54.7%), group 3 - patients with sepsis (n = 27/23.1%), group 4 - patients with septic shock (n = 13/11.1%). The threshold level of presepsin between groups 1 and 2 was 202 pg/ml, 371 pg/ml between groups 1 and 3, 604 pg/ml between groups 2 and 3 and 1500 pg/ml between groups 3 and 4. For procalcitonin, the threshold level between groups 1and 2 was 0.23 ng/ml, 0.48 ng/ml between groups 1 and 3, 0.51 ng/ml between groups 2 and 3 and 3.9 ng/ml between groups 3 and 4. The threshold value of C-reactive protein in patients with solid tumors was 12.6 g/l between groups 1 and 2. In patients with oncohematological diseases, the threshold level of C-reactive protein was 43.4 g / L between groups 2 and 3, 77.1 g / L between groups 2 and 4. According to the ROC analysis, presepsin was superior to procalcitonin and C-reactive protein in the diagnosis of septic complications.
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Affiliation(s)
- E G Golovnya
- N.N. Blokhin National Medical Research Center of Oncology
| | - T Yu Kharitidi
- N.N. Blokhin National Medical Research Center of Oncology
| | - A V Sotnikov
- N.N. Blokhin National Medical Research Center of Oncology
| | - O V Somonova
- N.N. Blokhin National Medical Research Center of Oncology
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Wu D, Wang L, Hong D, Zheng C, Zeng Y, Ma H, Lin J, Chen J, Zheng R. Interleukin 35 contributes to immunosuppression by regulating inflammatory cytokines and T cell populations in the acute phase of sepsis. Clin Immunol 2022; 235:108915. [PMID: 34995813 DOI: 10.1016/j.clim.2021.108915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 02/17/2021] [Accepted: 12/22/2021] [Indexed: 12/30/2022]
Abstract
Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focused on the associations of a cytokine network with IL-35 in sepsis. First, the retrospective study included 42 patients with sepsis and 23 healthy controls. Blood samples were collected from patients on days 1, 2, 4. Levels of IL-35, IL-1β, IL-4, IL-6, IL-10, IL-17A, TNF-α and IFN-γ were measured. They all increased to various extend on days 1, 2, 4, and strongly associated with markers of disease severity. Network analysis revealed a network formed by IL-35, with IL-6, IL-10, IL-17A, TNF-α and IFN-γ throughout the acute phase of sepsis(days 1, 2 and4). Then, the CLP-induced septic rats were used. The recombinant human IL-35(rIL-35) upregulated the levels of IL-10, but downregulated IL-4, IL-6, IL-17A, TNF-α and IFN-γ, while it had no significant effect on IL-1β, and upregulated the percentages of CD4+CD25+Tregs, and iTR35, but downregulated Teff cells in the peripheral blood. The rIL-35 reduced inflammation damage and improved prognosis of the septic rats. IL-35 forms a network with other cytokines and plays a major role in the immunopathogenesis of sepsis.
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Affiliation(s)
- Dansen Wu
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China.
| | - Liming Wang
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Donghuang Hong
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Caifa Zheng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Yongping Zeng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Huolan Ma
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Jing Lin
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Jialong Chen
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Ronghui Zheng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
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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.
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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
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38
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Xiao H, Wang G, Wang Y, Tan Z, Sun X, Zhou J, Duan M, Zhi D, Tang Z, Hang C, Zhang G, Li Y, Wu C, Li F, Zhang H, Wang J, Zhang Y, Zhang X, Guo W, Qi W, Xie M, Li C. Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial. Shock 2022; 57:63-71. [PMID: 34618727 DOI: 10.1097/shk.0000000000001870] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
INTRODUCTION Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.
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Affiliation(s)
- Hongli Xiao
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guoxing Wang
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yan Wang
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhimin Tan
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xuelian Sun
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jie Zhou
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Meili Duan
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Deyuan Zhi
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ziren Tang
- EICU of Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Chenchen Hang
- EICU of Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Guoqiang Zhang
- EICU of Department of Emergency Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Yan Li
- EICU of Department of Emergency Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Caijun Wu
- EICU of Department of Emergency Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Fengjie Li
- EICU of Department of Emergency Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Haiyan Zhang
- EICU of Department of Emergency Medicine, The Hospital of Shunyi District Beijing, China Medical University, Beijing, China
| | - Jing Wang
- EICU of Department of Emergency Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yun Zhang
- EICU of Department of Emergency Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xinchao Zhang
- EICU of Department of Emergency Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Guo
- EICU of Department of Emergency Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wenjie Qi
- Department of Infectious Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Miaorong Xie
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chunsheng Li
- EICU of Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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39
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Yildiz C, Çaglar FT, Korkusuz R, Yasar K, Isiksacan N. Serum presepsin levels among patients with COVID-19. INDIAN JOURNAL OF MEDICAL SPECIALITIES 2022. [DOI: 10.4103/injms.injms_77_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Bertsch T, Müller J, Weiß C, Akin I, Behnes M. Diagnostic and Prognostic Significance of the Prothrombin Time/International Normalized Ratio in Sepsis and Septic Shock. Clin Appl Thromb Hemost 2022; 28:10760296221137893. [PMID: 36503298 DOI: 10.1177/10760296221137893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The study investigates the diagnostic and prognostic significance of the prothrombin time/international normalized ratio (PT/INR) in patients with sepsis and septic shock. BACKGROUND Sepsis may be complicated by disseminated intravascular coagulation (DIC). While the status of coagulopathy of septic patients is represented within the sepsis-3 definition by assessing the platelet count, less data regarding the prognostic impact of the PT/INR in patients admitted with sepsis and septic shock is available. METHODS Consecutive patients with sepsis and septic shock from 2019 to 2021 were included. Blood samples were retrieved from day of disease onset (ie, day 0), as well as on day 1, 2, 4, 6 and 9 thereafter. Firstly, the diagnostic value of the PT/INR in comparison to the activated partial thromboplastin time (aPTT) was tested for septic shock compared to sepsis without shock. Secondly, the prognostic value of the PT/INR for 30-day all-cause mortality was tested. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, Kaplan-Meier analyses and Cox proportional regression analyses. RESULTS 338 patients were included (56% sepsis without shock, 44% septic shock). The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.682 (p= .001) on day 0, the PT/INR revealed moderate discrimination of septic shock and sepsis without shock. Furthermore, PT/ INR was able to discriminate non-survivors and survivors at 30 days (AUC = 0.612; p = .001). Patients with a PT/INR >1.5 had higher rates of 30-day all-cause mortality than patients with lower values (mortality rate 73% vs 48%; log rank p = .001; HR = 2.129; 95% CI 1.494-3.033; p = .001), even after multivariable adjustment (HR = 1.793; 95% CI 1.343-2.392; p = .001). Increased risk of 30-day all-cause mortality was observed irrespective of concomitant thrombocytopenia. CONCLUSION The PT/INR revealed moderate diagnostic accuracy for septic shock but was associated with reliable prognostic accuracy with regard to 30-day all-cause mortality in patients admitted with sepsis and septic shock.
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Affiliation(s)
- Tobias Schupp
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Kathrin Weidner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Rusnak
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Schanas Jawhar
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Jan Forner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Floriana Dulatahu
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Lea Marie Brück
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Ursula Hoffmann
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
| | - Julian Müller
- Clinic for Interventional Electrophysiology, Heart Centre Bad Neustadt, Bad Neustadt a. d. Saale, Germany.,Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany
| | - Christel Weiß
- Department of Statistical Analysis, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
| | - Ibrahim Akin
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Michael Behnes
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, 36642University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany
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41
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Affiliation(s)
- Chang-Eun Park
- Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University, Cheonan, Korea
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42
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Kluge S, Strauß R, Kochanek M, Weigand MA, Rohde H, Lahmer T. Aspergillosis: Emerging risk groups in critically ill patients. Med Mycol 2021; 60:6408468. [PMID: 34677613 DOI: 10.1093/mmy/myab064] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/23/2021] [Accepted: 10/19/2021] [Indexed: 02/06/2023] Open
Abstract
Information on invasive aspergillosis (IA) and other invasive filamentous fungal infections is limited in non-neutropenic patients admitted to the intensive care unit (ICU) and presenting with no classic IA risk factors. This review is based on the critical appraisal of relevant literature, on the authors' own experience and on discussions that took place at a consensus conference. It aims to review risk factors favoring aspergillosis in ICU patients, with a special emphasis on often overlooked or neglected conditions. In the ICU patients, corticosteroid use to treat underlying conditions such as chronic obstructive pulmonary disease (COPD), sepsis, or severe COVID-19, represents a cardinal risk factor for IA. Important additional host risk factors are COPD, decompensated cirrhosis, liver failure, and severe viral pneumonia (influenza, COVID-19). Clinical observations indicate that patients admitted to the ICU because of sepsis or acute respiratory distress syndrome are more likely to develop probable or proven IA, suggesting that sepsis could also be a possible direct risk factor for IA, as could small molecule inhibitors used in oncology. There are no recommendations for prophylaxis in ICU patients; posaconazole mold-active primary prophylaxis is used in some centers according to guidelines for other patient populations and IA treatment in critically ill patients is basically the same as in other patient populations. A combined evaluation of clinical signs and imaging, classical biomarkers such as the GM assay, and fungal cultures examination, remain the best option to assess response to treatment. LAY SUMMARY The use of corticosteroids and the presence of co-morbidities such as chronic obstructive pulmonary disease, acute or chronic advanced liver disease, or severe viral pneumonia caused by influenza or Covid-19, may increase the risk of invasive aspergillosis in intensive care unit patients.
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Affiliation(s)
- Stefan Kluge
- Department of Intensive Care Medicine, University Medical Center Hamburg - Eppendorf, Hamburg, D-20246, Germany
| | - Richard Strauß
- Department of Medicine 1, Medizinische Klinik 1, University Hospital Erlangen, Erlangen, D-91054, Germany
| | - Matthias Kochanek
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, D-50937, Germany
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, D-69120, Germany
| | - Holger Rohde
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, D-20246, Germany
| | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität Munich, Munich, D-81675, Germany
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43
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Abstract
BACKGROUND "Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. METHODS A literature review was conducted to identify cytokine levels released during 11 assorted clinical conditions or diseases. Weighted averages for various cytokines were calculated by multiplying the number of patients in the paper by the average concentration of each cytokine. Correlation between cytokine levels for individual conditions or diseases were assessed using Pearson correlation coefficient. RESULTS The literature was reviewed to determine blood levels of cytokines in a wide variety of clinical conditions. These conditions ranged from exercise and autoimmune disease to septic shock and therapy with chimeric antigen receptor T cells. The most frequently measured cytokine was IL-6 which ranged from 24,123 pg/mL in septic shock to 11 pg/mL after exercise. In patients with severe SARS CoV-2 infections, blood levels of IL-6 were only 43 pg/mL, nearly three magnitudes lower than IL-6 levels in patients with septic shock. The clinical presentations of these different diseases do not correlate with blood levels of cytokines. Additionally, there is poor correlation between the concentrations of different cytokines among the different diseases. Specifically, blood levels of IL-6 did not correlate with levels of IL-8, IL-10, or TNF. Septic shock had the highest concentrations of cytokines, yet multiple cytokine inhibitors have failed to demonstrate improved outcomes in multiple clinical trials. Patients with autoimmune diseases have very low blood levels of cytokines (rheumatoid arthritis, IL-6 = 34 pg/mL; Crohn's disease, IL-6 = 5 pg/mL), yet respond dramatically to cytokine inhibitors. CONCLUSION The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.
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Affiliation(s)
- Allan E Stolarski
- Department of Surgery, Boston Medical Center, Boston University, Boston, Massachusetts
- Department of Pathology and Laboratory Medicine, Boston University, Boston, Massachusetts
| | - Jiyoun Kim
- Department of Pathology and Laboratory Medicine, Boston University, Boston, Massachusetts
| | - Qiuyang Zhang
- Department of Pathology and Laboratory Medicine, Boston University, Boston, Massachusetts
| | - Daniel G Remick
- Department of Pathology and Laboratory Medicine, Boston University, Boston, Massachusetts
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Abstract
PURPOSE The proteome during lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice is unclear. MATERIALS AND METHODS In this study, eight-week-old male C57BL/6 mice were intraperitoneally injected with LPS and sacrificed 18 hours after LPS administration to identify protein expression levels in lung tissue using tandem mass tag (TMT) analysis for relative quantification. Hematoxylin-eosin (HE) staining was used to evaluate lung injury in mice. Immunohistochemical staining was used to calculate the production of myeloperoxidase (MPO) and TUNEL staining was performed to detect apoptosis. GO functional clustering and KEGG pathway enrichment analyses were performed to determine functions of differentially expressed proteins (DEPs) and transduction pathways. Domain annotation and subcellular localization analysis of the DEPs were also performed. Furthermore, parallel reaction monitoring (PRM) analysis was used to verify the top 30 DEPs. RESULTS A total of 5188 proteins were found to be expressed in lung tissues from LPS- and saline-treated mice. Among these proteins, 293 were differentially expressed between the two groups; 255 proteins were upregulated in the LPS-treated ALI mice, while 38 were downregulated. GO analysis showed that the DEPs are mainly extracellular, and KEGG analysis suggested that the DEPs are mainly enriched in the NOD-like receptor signaling pathway, complement and coagulation cascades and natural killer cell-mediated cytotoxicity. Enrichment of the DEPs is mainly peptidase S1A, serine proteases, peptidase S1, and the serpin domain. 26.6% of the DEPs are in the nucleus, 24.6% are in the cytosol, 19.1% are in the extracellular space, and 18.8% are in the plasma membrane. PRM validation showed that the trend of 30 DEPs was same with TMT analysis. Among these, Cytochrome b-245 heavy chain (Cybb), Monocyte differentiation antigen CD14 (Cd14) and Neutrophil gelatinase-associated lipocalin (NGAL) were the most obvious change. CONCLUSIONS Our results may help to identify markers and therapeutic targets for LPS-induced ALI.
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Affiliation(s)
- Shengsong Chen
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China
| | - Yi Zhang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China
| | - Qingyuan Zhan
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing , P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, P. R. China.,Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, P. R. China
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Yamaguchi T, Ohira M, Kawagoe N, Nakamura S, Tanaka S, Oka R, Watanabe Y, Sato Y, Nagayama D, Saiki A, Matsuzawa Y, Bujo H, Terai K, Hiruta N, Tatsuno I, Nakaseko C, Kikuchi H, Matsuoka K, Yokota H, Shimizu N. High presepsin concentrations in bile and its marked elevation in biliary tract diseases: A retrospective analysis. Clin Chim Acta 2021; 521:278-284. [PMID: 34331951 DOI: 10.1016/j.cca.2021.07.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/15/2021] [Accepted: 07/24/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels. METHOD We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver. RESULTS Spearman's rank correlation analysis with loge change revealed that presepsin levels were closely associated with loge-transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that loge-transformed SOFA score (β-coefficient = 0.316), ALP level (β-coefficient = 0.380), and creatinine level (β-coefficient = 0.290) independently and significantly affected loge presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining. CONCLUSION Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells.
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Affiliation(s)
- Takashi Yamaguchi
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Masahiro Ohira
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Naoyuki Kawagoe
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Shoko Nakamura
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Sho Tanaka
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Rena Oka
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Yasuhiro Watanabe
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Yuta Sato
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Daiji Nagayama
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Atsuhito Saiki
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Yasuo Matsuzawa
- Department of Internal Medicine, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Hideaki Bujo
- Department of Clinical Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Kensuke Terai
- Department of Surgical Pathology, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Nobuyuki Hiruta
- Department of Surgical Pathology, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Ichiro Tatsuno
- Center for Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Chiaki Nakaseko
- Department of Hematology, International University of Health and Welfare School of Medicine, 2860852 Chiba, Japan
| | - Hidemasa Kikuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, 2858741 Chiba, Japan
| | - Hiromitsu Yokota
- Clinical Laboratory Program, Education Development Center, Faculty of Science Toho University, 2748510 Chiba, Japan
| | - Naomi Shimizu
- Department of Hematology, Toho University Sakura Medical Center, 2858741 Chiba, Japan.
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Reinhart K. [Methodological weaknesses and errors in the data extraction lead to a substantial underestimation of the mortality of sepsis and septic shock in Germany]. Anaesthesist 2021; 70:683-685. [PMID: 34282480 DOI: 10.1007/s00101-021-00988-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Konrad Reinhart
- Klinik für Anästhesiologie m. S. operative Intensivmedizin, Charité Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Pl. 1, 13353, Berlin, Deutschland.
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Shimoyama Y, Umegaki O, Kadono N, Minami T. Presepsin values and prognostic nutritional index predict mortality in intensive care unit patients with sepsis: a pilot study. BMC Res Notes 2021; 14:245. [PMID: 34193271 PMCID: PMC8243529 DOI: 10.1186/s13104-021-05659-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 06/17/2021] [Indexed: 12/12/2022] Open
Abstract
Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320). Supplementary Information The online version contains supplementary material available at 10.1186/s13104-021-05659-9.
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Affiliation(s)
- Yuichiro Shimoyama
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
| | - Osamu Umegaki
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Noriko Kadono
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Toshiaki Minami
- Department of Anesthesiology, Osaka Medical College, Osaka Medical College Hospital, Takatsuki, Osaka, 569-8686, Japan
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Bauer M, Groesdonk HV, Preissing F, Dickmann P, Vogelmann T, Gerlach H. [Sepsis in German intensive care units-Last position worldwide?… Not so fast]. Anaesthesist 2021; 70:686-688. [PMID: 34152445 PMCID: PMC8346455 DOI: 10.1007/s00101-021-00986-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Michael Bauer
- Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland.
| | - Heinrich Volker Groesdonk
- Klinik für Interdisziplinäre Intensivmedizin und Intermediate Care, Helios Klinikum Erfurt, Nordhäuser Straße 74, 99089, Erfurt, Deutschland
| | | | - Petra Dickmann
- Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | | | - Herwig Gerlach
- Klinik für Anästhesie, operative Intensivmedizin und Schmerztherapie, Vivantes Klinikum Neukölln, Rudower Straße 48, 12351, Berlin, Deutschland
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Shimoyama Y, Umegaki O, Kadono N, Minami T. Presepsin and prognostic nutritional index are predictors of septic acute kidney injury, renal replacement therapy initiation in sepsis patients, and prognosis in septic acute kidney injury patients: a pilot study. BMC Nephrol 2021; 22:219. [PMID: 34118899 PMCID: PMC8199821 DOI: 10.1186/s12882-021-02422-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 06/03/2021] [Indexed: 12/30/2022] Open
Abstract
Background Sepsis is the most common cause of acute kidney injury (AKI) among critically ill patients. This study aimed to determine whether presepsin is a predictor of septic acute kidney injury, renal replacement therapy initiation (RRTi) in sepsis patients, and prognosis in septic AKI patients. Methods Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, Prognostic Index, and Prognostic Nutritional Index (PNI) were measured at baseline, and total scores (“inflammation-presepsin scores [iPS]”) were calculated for category classification. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with and without septic AKI or RRTi and between survivors and non-survivors. Results Receiver operating characteristic curve analyses identified the following variables as predictors of septic AKI and RRTi in sepsis patients: presepsin on Day 1 (AUC: 0.73) and Day 2 (AUC: 0.71) for septic AKI, and presepsin on Day 1 (AUC: 0.71), Day 2 (AUC: 0.9), and Day 5 (AUC: 0.96), Δpresepsin (Day 2 – Day 1) (AUC: 0.84), Δpresepsin (Day 5 – Day 1) (AUC: 0.93), and PNI (AUC: 0.72) for RRTi. Multivariate logistic regression analyses identified presepsin on Day 2 as a predictor of prognosis in septic AKI patients. Conclusions Presepsin and PNI were found to be predictors of septic AKI, RRTi in sepsis patients, and prognosis in septic AKI patients.
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Affiliation(s)
- Yuichiro Shimoyama
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
| | - Osamu Umegaki
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Noriko Kadono
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Toshiaki Minami
- Department of Anesthesiology, Osaka Medical College, Osaka Medical College Hospital, Takatsuki, Japan
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Lee MJ, Han WH, Chun JY, Kim SY, Kim JH. Presepsin in the Rapid Response System for Cancer Patients: A Retrospective Analysis. J Clin Med 2021; 10:jcm10102153. [PMID: 34065685 PMCID: PMC8155948 DOI: 10.3390/jcm10102153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/06/2021] [Accepted: 05/14/2021] [Indexed: 12/29/2022] Open
Abstract
Introduction: Early diagnosis of sepsis is paramount to effective management. The present study aimed to compare the prognostic accuracy of presepsin levels and other biomarkers in the assessment of septic shock and mortality risk in cancer patients. Materials and methods: A total of 74 cancer patients were evaluated for presepsin, lactic acid, C-reactive protein (CRP) levels, and white blood cell count (WBC). Specificity and sensitivity values for septic shock and death were compared between four biomarkers in all patients and those with and without acute kidney injury (AKI). Results: A total of 27 and 29 patients experienced septic shock and died, respectively. The area under the curve (AUC) and sensitivity and specificity estimated for presepsin levels for septic shock were 60%, 74%, and 51%, respectively. The corresponding values for mortality were 62%, 72%, and 49%, respectively. In patients without AKI, AUC of presepsin levels for septic shock and death were 62% and 65%, respectively; in those with AKI, these values were 44% and 58%, respectively. Presepsin levels showed higher sensitivity and specificity values than WBC and higher specificity than CRP but were similar to those of lactic acid levels. Conclusions: Presepsin levels are similar to lactic acid levels in the assessment of septic shock and mortality risk in cancer patients. In patients with AKI, presepsin levels should be considered carefully.
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Affiliation(s)
- Min-Jung Lee
- National Cancer Center, Department of Surgery, Goyang 410-769, Korea
| | - Won-Ho Han
- National Cancer Center, Department of Surgery, Goyang 410-769, Korea
| | - June-Young Chun
- National Cancer Center, Department of Internal Medicine, Goyang 410-769, Korea
| | - Sun-Young Kim
- National Cancer Center, Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, Goyang 410-769, Korea
| | - Jee-Hee Kim
- National Cancer Center, Department of Anesthesiology, Goyang 410-769, Korea
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