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Iglesias-Ussel MD, O’Grady N, Anderson J, Mitsis PG, Burke TW, Henao R, Scavetta J, Camilleri C, Naderi S, Carittini A, Perelman M, Myers RA, Ginsburg GS, Ko ER, McClain MT, van Westrienen J, Tsalik EL, Tillekeratne LG, Woods CW. A Rapid Host Response Blood Test for Bacterial/Viral Infection Discrimination Using a Portable Molecular Diagnostic Platform. Open Forum Infect Dis 2025; 12:ofae729. [PMID: 39758742 PMCID: PMC11697109 DOI: 10.1093/ofid/ofae729] [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: 09/18/2024] [Accepted: 12/10/2024] [Indexed: 01/07/2025] Open
Abstract
Background Difficulty discriminating bacterial versus viral etiologies of infection drives unwarranted antibacterial prescriptions and, therefore, antibacterial resistance. Methods Utilizing a rapid portable test that measures peripheral blood host gene expression to discriminate bacterial and viral etiologies of infection (the HR-B/V assay on Biomeme's polymerase chain reaction-based Franklin platform), we tested 3 cohorts of subjects with suspected infection: the HR-B/V training cohort, the HR-B/V technical correlation cohort, and a coronavirus disease 2019 cohort. Results The Biomeme HR-B/V test showed very good performance at discriminating bacterial and viral infections, with a bacterial model accuracy of 84.5% (95% confidence interval [CI], 80.8%-87.5%), positive percent agreement (PPA) of 88.5% (95% CI, 81.3%-93.2%), negative percent agreement (NPA) of 83.1% (95% CI, 78.7%-86.7%), positive predictive value of 64.1% (95% CI, 56.3%-71.2%), and negative predictive value of 95.5% (95% CI, 92.4%-97.3%). The test showed excellent agreement with a previously developed BioFire HR-B/V test, with 100% (95% CI, 85.7%-100.0%) PPA and 94.9% (95% CI, 86.1%-98.3%) NPA for bacterial infection, and 100% (95% CI, 93.9%-100.0%) PPA and 100% (95% CI, 85.7%-100.0%) NPA for viral infection. Among subjects with acute severe acute respiratory syndrome coronavirus 2 infection of ≤7 days, accuracy was 93.3% (95% CI, 78.7%-98.2%) for 30 outpatients and 75.9% (95% CI, 57.9%-87.8%) for 29 inpatients. Conclusions The Biomeme HR-B/V test is a rapid, portable test with high performance at identifying patients unlikely to have bacterial infection, offering a promising antibiotic stewardship strategy that could be deployed as a portable, laboratory-based test.
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Affiliation(s)
| | - Nicholas O’Grady
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Jack Anderson
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | | | - Thomas W Burke
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Ricardo Henao
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Department of Biostatistics and Informatics, Duke University, Durham, North Carolina, USA
| | | | | | | | | | | | - Rachel A Myers
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Geoffrey S Ginsburg
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- All of Us Research Program, National Institutes of Health, Bethesda, Maryland, USA
| | - Emily R Ko
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Hospital Medicine, Division of General Internal Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Micah T McClain
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | | | - Ephraim L Tsalik
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
- Danaher Corporation, Washington, District of Columbia, USA
| | - L Gayani Tillekeratne
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
- Duke Global Health Institute, Duke University, Durham, North Carolina, USA
| | - Christopher W Woods
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Biomeme, Inc, Philadelphia, Pennsylvania, USA
- Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
- Duke Global Health Institute, Duke University, Durham, North Carolina, USA
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2
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Huang G, Li X, Zhang C, Li H, Jian M, Huang C, Zhang Y, Xian L, Zeng H, Xia Y, Jiang W. Evaluation of CD4 + T Lymphocyte Counts to Predict Survival of ICU Patients with Sepsis Using Sepsis-3 Criteria: A Prospective Cohort Study. Emerg Med Int 2024; 2024:4293700. [PMID: 39290582 PMCID: PMC11407885 DOI: 10.1155/2024/4293700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/14/2024] [Accepted: 07/22/2024] [Indexed: 09/19/2024] Open
Abstract
Background Sepsis remains a major health condition with a high mortality rate that may be related to immunosuppression. T lymphocyte subsets may reflect the immune function of sepsis patients. The purpose of this study was to investigate the predictive value of CD4+ T lymphocyte counts of ICU patients for their short-term prognosis. Methods We conducted a prospective, observational cohort study in a general ICU and enrolled patients with sepsis using the Sepsis-3 criteria. Peripheral blood samples were collected within 24 hours of enrollment or measurement of blood cell analysis and biomarkers of CD4+ T lymphocytes and CD8+ T lymphocytes. Severity was classified by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores. The primary outcome was 28-day mortality. Results A total of 100 patients with sepsis were enrolled and analyzed. CD4+ T lymphocyte counts gradually decreased based on 28-day mortality (p < 0.001). Similarly, multivariate logistic regression analysis showed that only CD4+ T lymphocyte counts were an independent predictor of 28-day mortality in sepsis patients. The area under the receiver operating characteristic curve of the combination of CD4+ T lymphocyte counts and the SOFA score was 0.78. Conclusion Our study demonstrated that CD4+ T lymphocyte counts are associated with 28-day mortality. A combination of CD4+ T lymphocyte counts with the SOFA score increased the predictive accuracy for 28-day mortality.
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Affiliation(s)
- Guoge Huang
- Guangdong Cardiovascular Institute Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Xusheng Li
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Chunmei Zhang
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Haizhong Li
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
- Department of Emergency Boai Hospital of Zhongshan, No. 6 Chenggui Road, Zhongshan 528403, Guangdong, China
| | - Mengling Jian
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Chunyang Huang
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Yingqin Zhang
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
- School of Medicine South China University of Technology Guangzhou University City, Guangzhou 510006, Guangdong, China
| | - Luhua Xian
- Department of Laboratory Medicine Guangdong Provincial People's Hospital Academy of Medical Sciences, Guangzhou, China
| | - Hongke Zeng
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
| | - Yuanyuan Xia
- Medical Oncology Department The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University, Guangzhou 510700, China
| | - Wenqiang Jiang
- Guangdong Cardiovascular Institute Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
- Emergency Intensive Care Unit Department of Emergency Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China
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He RR, Yue GL, Dong ML, Wang JQ, Cheng C. Sepsis Biomarkers: Advancements and Clinical Applications-A Narrative Review. Int J Mol Sci 2024; 25:9010. [PMID: 39201697 PMCID: PMC11354379 DOI: 10.3390/ijms25169010] [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: 07/22/2024] [Revised: 08/14/2024] [Accepted: 08/18/2024] [Indexed: 09/03/2024] Open
Abstract
Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment.
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Affiliation(s)
- Rong-Rong He
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (R.-R.H.); (G.-L.Y.)
| | - Guo-Li Yue
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (R.-R.H.); (G.-L.Y.)
| | - Mei-Ling Dong
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China;
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
| | - Jia-Qi Wang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
| | - Chen Cheng
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China;
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
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Wang B, Zhou Q, Qian W, He Z, Yang Z, Chen C, Zheng L, Shi H. The predictive value of laboratory tests in oro-maxillofacial infection of different severity. Oral Dis 2024; 30:1695-1701. [PMID: 37094078 DOI: 10.1111/odi.14590] [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: 05/07/2022] [Revised: 03/19/2023] [Accepted: 04/03/2023] [Indexed: 04/26/2023]
Abstract
OBJECTIVE We aimed to investigate the value of individual laboratory tests and combinations of tests for predicting disease severity. METHODS We retrospectively reviewed 62 patients with space infections in the oral and maxillofacial head and neck regions. Patients were divided into three groups according to severity. Laboratory tests associated with disease severity were identified. RESULTS As the severity of infection increased, leukocytes, neutrophils, C-reactive protein (CRP), procalcitonin (PCT), soluble interleukin receptor (sILR) 2, IL6, and creatinine (CR) increased. In the ROC analysis of group 1 (moderate infection) versus group 2 (severe infection), the area under the curve (AUC) values for leukocytes (AUC = 0.724), neutrophils (AUC = 0.714), PCT (AUC = 0.762) and a combination of the 3 tests (AUC = 0.768) suggested a strong predictive value. Furthermore, in the ROC analysis of group 2 (severe infection) versus group 3 (extremely severe infection), the AUC values for CRP (AUC = 0.84), PCT (AUC = 0.799), sIL2R (AUC = 0.937), IL6 (AUC = 0.863) and a combination of the four tests (AUC = 0.943) suggested a strong predictive value. CONCLUSIONS Leukocytes, neutrophils, and PCT were associated with multispace infection and high severity. CRP, PCT, sIL2R, and/or IL6 were associated with extremely severe infections occurring in the oral and maxillofacial head and neck regions.
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Affiliation(s)
- Baoli Wang
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Qin Zhou
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Wentao Qian
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Zhiyuan He
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Zuoyi Yang
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Changyu Chen
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Lingyan Zheng
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Huan Shi
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
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Zaki HA, Bensliman S, Bashir K, Iftikhar H, Fayed MH, Salem W, Elmoheen A, Yigit Y. Accuracy of procalcitonin for diagnosing sepsis in adult patients admitted to the emergency department: a systematic review and meta-analysis. Syst Rev 2024; 13:37. [PMID: 38254218 PMCID: PMC10802075 DOI: 10.1186/s13643-023-02432-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 12/11/2023] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS) is challenging. Biomarkers like procalcitonin (PCT) aid early risk assessment and guide antibiotic use. This study aims to ascertain PCT's accuracy as a sepsis biomarker among adult emergency department admissions. METHOD The PRISMA guidelines were followed to search for relevant articles in five electronic databases between April 14th and August 4th, 2023: PubMed, Cochrane Library, ProQuest, EMBASEs, and ScienceDirect. Studies had to be published in English to avoid directly translating scientific terms. Besides, the inclusion criteria were based on the diagnosis of sepsis in adult patients admitted to an emergency department. QUADAS-2 tool provided by the Review Manager version 5.4.1 was utilized to assess the risk of bias in included studies. STATA (v. 16) software was used to perform the meta-analysis. RESULTS Ten of 2457 studies were included. We sampled 2980 adult sepsis patients for the under-investigated role of PCT in ED sepsis diagnosis. PCT emerged as the primary early diagnostic biomarker with high levels (29.3 ± 85.3 ng/mL) in sepsis patients. Heterogeneity in outcomes, possibly due to bias in cohort and observational studies, was observed. CONCLUSION PCT tests offer moderate accuracy in diagnosing sepsis and stand out for rapidly and precisely distinguishing between viral and bacterial inflammations.
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Affiliation(s)
- Hany A Zaki
- Hamad Medical Corporation Doha, Ar-Rayyan, Qatar
| | | | - Khalid Bashir
- Hamad Medical Corporation Doha, Ar-Rayyan, Qatar
- Medicine, Qatar University, Doha, Qatar
| | | | | | - Waleed Salem
- Hamad Medical Corporation Doha, Ar-Rayyan, Qatar
| | - Amr Elmoheen
- Hamad Medical Corporation Doha, Ar-Rayyan, Qatar
- Medicine, Qatar University, Doha, Qatar
| | - Yavuz Yigit
- Hamad Medical Corporation Doha, Ar-Rayyan, Qatar.
- Blizard Institute, Queen Mary University, London, UK.
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Ansari MA, Das S, Rai G, Singh PK, Lahan S, Tyagi A, Alamer E, Dar SA. Low monocytic HLA-DR expression in critically ill patients of sepsis: An indicator for antimicrobial and/or immunomodulatory intervention. Transpl Immunol 2023; 81:101942. [PMID: 37866671 DOI: 10.1016/j.trim.2023.101942] [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: 08/26/2023] [Revised: 10/10/2023] [Accepted: 10/19/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Sepsis is a result of suppressed host immune response which leads to fatal multi-organ dysfunctionality. Low frequency of active monocytes or reduced expression of human leukocyte antigen (HLA)-DR on monocytes shows the suppressed immune response in sepsis patients. One of the well-studied markers in patients with sepsis is procalcitonin (PCT). The role of monocytic (m) HLA-DR expression has been monitored in sepsis and is being considered a marker of the severity of interim immuno-depression in these patients. The study describes the impact of HLA-DR expression on monocytes quantitatively using flow cytometry. METHODS In this prospective study, we quantified monocytes and their HLA-DR expression in 20 patients of sepsis admitted to the Intensive Care Unit (ICU). Serum levels of PCT and interleukin (IL)-6 production were also measured in these patients, and the results were compared with those in healthy controls. RESULTS Monocyte frequency calculated was higher in sepsis patients as compared to healthy controls, however, HLA-DR expressing monocytes were significantly reduced as was the mean fluorescence intensity (MFI) of HLA-DR. Contrastingly, IL-6 and PCT levels were significantly high in sepsis than controls. The results suggest that low HLA-DR expression, combined with PCT, is a better prognostic parameter in the early phase of sepsis. CONCLUSION Poor recovery of mHLA-DR may serve as an early guide for clinicians to assess the prognosis of sepsis patients and consider immunomodulatory therapy in its management.
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Affiliation(s)
- Mohammad Ahmad Ansari
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Shukla Das
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India.
| | - Gargi Rai
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Praveen Kumar Singh
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Shubham Lahan
- University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Asha Tyagi
- Department of Anesthesiology and Critical Care, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Edrous Alamer
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Sajad Ahmad Dar
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India; Research and Scientific Studies Unit, College of Nursing, Jazan University, Jazan 45142, Saudi Arabia.
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Wang X, Li R, Qian S, Yu D. Multilevel omics for the discovery of biomarkers in pediatric sepsis. Pediatr Investig 2023; 7:277-289. [PMID: 38050541 PMCID: PMC10693667 DOI: 10.1002/ped4.12405] [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: 05/31/2023] [Accepted: 09/27/2023] [Indexed: 12/06/2023] Open
Abstract
Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi-omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi-levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.
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Affiliation(s)
- Xinyu Wang
- Laboratory of DermatologyBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityKey Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's HealthBeijingChina
| | - Rubo Li
- Department of Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Suyun Qian
- Department of Pediatric Intensive Care UnitBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina
| | - Dan Yu
- Laboratory of DermatologyBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityKey Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's HealthBeijingChina
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Lawandi A, Oshiro M, Warner S, Diao G, Strich JR, Babiker A, Rhee C, Klompas M, Danner RL, Kadri SS. Reliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008-2017. Crit Care Med 2023; 51:1527-1537. [PMID: 37395622 DOI: 10.1097/ccm.0000000000005968] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
OBJECTIVES Serum procalcitonin is often ordered at admission for patients with suspected sepsis and bloodstream infections (BSIs), although its performance characteristics in this setting remain contested. This study aimed to evaluate use patterns and performance characteristics of procalcitonin-on-admission in patients with suspected BSI, with or without sepsis. DESIGN Retrospective cohort study. SETTING Cerner HealthFacts Database (2008-2017). PATIENTS Adult inpatients (≥ 18 yr) who had blood cultures and procalcitonin drawn within 24 hours of admission. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Testing frequency of procalcitonin was determined. Sensitivity of procalcitonin-on-admission for detecting BSI due to different pathogens was calculated. Area under the receiver operating characteristic curve (AUC) was calculated to assess discrimination by procalcitonin-on-admission for BSI in patients with and without fever/hypothermia, ICU admission and sepsis defined by Centers for Disease Control and Prevention Adult Sepsis Event criteria. AUCs were compared using Wald test and p values were adjusted for multiple comparisons. At 65 procalcitonin-reporting hospitals, 74,958 of 739,130 patients (10.1%) who had admission blood cultures also had admission procalcitonin testing. Most patients (83%) who had admission day procalcitonin testing did not have a repeat procalcitonin test. Median procalcitonin varied considerably by pathogen, BSI source, and acute illness severity. At a greater than or equal to 0.5 ng/mL cutoff, sensitivity for BSI detection was 68.2% overall, ranging between 58.0% for enterococcal BSI without sepsis and 96.4% for pneumococcal sepsis. Procalcitonin-on-admission displayed moderate discrimination at best for overall BSI (AUC, 0.73; 95% CI, 0.72-0.73) and showed no additional utility in key subgroups. Empiric antibiotic use proportions were not different between blood culture sampled patients with a positive procalcitonin (39.7%) and negative procalcitonin (38.4%) at admission. CONCLUSIONS At 65 study hospitals, procalcitonin-on-admission demonstrated poor sensitivity in ruling out BSI, moderate-to-poor discrimination for both bacteremic sepsis and occult BSI and did not appear to meaningfully alter empiric antibiotic usage. Diagnostic stewardship of procalcitonin-on-admission and risk assessment of admission procalcitonin-guided clinical decisions is warranted.
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Affiliation(s)
- Alexander Lawandi
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
| | - Marissa Oshiro
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
- Division of Internal Medicine, Department of Medicine, Medstar Georgetown University Hospital, Washington, DC
- School of Medicine, Georgetown University, Washington, DC
| | - Sarah Warner
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
| | - Guoqing Diao
- Department of Biostatistics and Bioinformatics, George Washington University, Washington, DC
| | - Jeffrey R Strich
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
| | - Ahmed Babiker
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Chanu Rhee
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA
| | - Michael Klompas
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA
| | - Robert L Danner
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
| | - Sameer S Kadri
- Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD
- Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD
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Turan YB. The role of proadrenomedullin, interleukin 6 and CD64 in the diagnosis and prognosis of septic shock. BMC Anesthesiol 2023; 23:278. [PMID: 37592204 PMCID: PMC10433549 DOI: 10.1186/s12871-023-02237-3] [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: 06/01/2023] [Accepted: 08/07/2023] [Indexed: 08/19/2023] Open
Abstract
INTRODUCTION Sepsis and septic shock are disorders of tissue perfusion and microcirculation associated with increased mortality. The role of biomarkers such as proadrenomedullin (PRO-ADM), interleukin 6 (IL-6) and neutrophil CD64 (CD64) in the diagnosis and prognosis of septic shock has been studied. METHODS GCS, SOFA score, APACHE 2 score, lactate, CRP, procalcitonin, PRO-ADM, IL-6, CD64 level and 28-day mortality were evaluated in patients with septic shock followed-up in the intensive care unit of Marmara University Hospital between July 2021 and December 2021. The study was planned as prospective, non-drug clinical research Committee. RESULTS There were no statistically significant differences between patient groups in gender, BMI, and presence of comorbidities (p > 0.05). The alive patient group had significantly higher GCS values and lower SOFA, APACHE 2, lactate and CD64 values than the dead patient group (p < 0.01). The cut-off values of laboratory parameters were determined using ROC analysis to predict mortality, SOFA and CD64 had high AUC. This is also a good indicator for mortality.The multivariate logistic regression model was estimated using the backward selection method. The mortality of ICU patients was predicted by a SOFA-value ≥ 12 (OR (95%CI) = 56.13 (5.44-578.64)), CD64 value ≥ 28.54 (OR (95% CI) = 23.78 (2.61-216.85)), and ADM-value ≥ 86.79 (OR (95% CI) = 15.86 (1.02-246.49)) (p < 0.05) . CONCLUSION In conclusion, serum CD64 level, PRO-ADM level, and SOFA score proved to be effective parameters for predicting prognosis and mortality in septic shock. However, IL-6 proved to be a weak biomarker and failed to predict mortality. CD64, which is easier and more practical to use, can be used instead of the SOFA score.
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Affiliation(s)
- Yasemin Bozkurt Turan
- Department of Critical Care, Faculty of Medicine, Marmara University, Istanbul, 34899, Turkey.
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10
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Ho SF, Tan SJ, Mazlan MZ, Iberahim S, Lee YX, Hassan R. Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units. Diagnostics (Basel) 2023; 13:2445. [PMID: 37510189 PMCID: PMC10378205 DOI: 10.3390/diagnostics13142445] [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: 05/18/2023] [Revised: 07/08/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.
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Affiliation(s)
- Sook Fong Ho
- Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Swee Jin Tan
- Sysmex Asia Pacific Pte Ltd., Singapore 528735, Singapore
| | - Mohd Zulfakar Mazlan
- Department of Anaesthesiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Salfarina Iberahim
- Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Ying Xian Lee
- Sysmex Asia Pacific Pte Ltd., Singapore 528735, Singapore
| | - Rosline Hassan
- Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
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11
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Turgman O, Schinkel M, Wiersinga WJ. Host Response Biomarkers for Sepsis in the Emergency Room. Crit Care 2023; 27:97. [PMID: 36941681 PMCID: PMC10027585 DOI: 10.1186/s13054-023-04367-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023] Open
Abstract
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
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Affiliation(s)
- Oren Turgman
- Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Michiel Schinkel
- Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Division of Infectious Diseases, Department of Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Willem Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Division of Infectious Diseases, Department of Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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12
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Fan D, Hou J, Yang J, Zhao Z, Fang Q, Wu X. Predictive value of serum interleukin-6 to determine surgical drainage of deep neck space infection in adults. Eur Arch Otorhinolaryngol 2023; 280:1403-1410. [PMID: 36208332 DOI: 10.1007/s00405-022-07683-2] [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: 08/09/2022] [Accepted: 09/28/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this study was to determine whether interleukin-6 (IL-6) could be used as a predictor for surgical drainage in deep neck space infection (DNSI). METHODS A retrospective study was conducted to analyze 69 adult patients newly diagnosed as DNSI from January 2017 to December 2021 at a single center. The patients were treated with either surgical drainage or not. The following clinical data including age, gender, maximum diameter of abscess (MDA), laboratory data, therapeutic modalities, comorbidities, duration of hospitalization and complications were collected and evaluated. RESULTS Patients in drained group had significantly elevated MDA, IL-6, procalcitonin, C-reactive protein and neutrophil to lymphocyte ratio compared to patients in non-drained group (all P < 0.01). Significant predictors for surgical drainage were IL-6 and MDA as independent factors, with the optimum cutoff values of 52.5 pg/mL and 14.4 mm, respectively. Moreover, the IL-6 had a wider area under the curve than MDA for prediction of surgical drainage in DNSI. CONCLUSIONS IL-6 as a promising predictor of the need for surgical drainage can be effectively used for routine assessment in the early stage of DNSI to determine the optimal treatments.
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Affiliation(s)
- Dachuan Fan
- Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, China.
| | - Jinxiao Hou
- Department of Hematology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China
| | - Jianming Yang
- Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, China
| | - Zhentao Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, China
| | - Qi Fang
- Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, China
| | - Xiaoman Wu
- Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Hefei, 230601, Anhui, China
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Intrinsic values of procalcitonin in bacterial bloodstream infections in people aged 75 years and over: a retrospective study. Diagn Microbiol Infect Dis 2023; 105:115887. [PMID: 36640698 DOI: 10.1016/j.diagmicrobio.2022.115887] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 12/08/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate PCT measurement in the diagnosis of bloodstream infection (BSI) in hospitalized patients aged 75+. METHOD Descriptive, retrospective, monocentric study conducted in France, in patients with at least one blood culture and PCT and CRP measurements within the 24 hours before or after blood culture. RESULTS The mean PCT and CRP values for the 118 (15.2%) positive blood cultures were 18.90 ng/ml [95%CI: 0.007-334.7] and 153.93 mg/l [1-557], respectively. With a threshold of 0.3 ng/ml, PCT measurement had a sensitivity of 84%, a specificity of 53%, a PPV of 24%, and an NPV of 95%, making it possible to rule out BSI in 350 (45.1%) patients (α-risk=5%). CONCLUSION PCT measurement may eliminate BSI diagnosis more quickly than does blood culture reducing the inadequate and detrimental use of antibiotic therapy. A prospective study is required to validate its usefulness and confirm the cut-off value in geriatric populations.
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14
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Gandhi P, Shrivastava P. Adult sepsis as an emerging hospital-acquired infection: Challenges and solutions. ANTIBIOTICS - THERAPEUTIC SPECTRUM AND LIMITATIONS 2023:575-593. [DOI: 10.1016/b978-0-323-95388-7.00025-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Jerome E, McPhail MJ, Menon K. Diagnostic accuracy of procalcitonin and interleukin-6 for postoperative infection in major gastrointestinal surgery: a systematic review and meta-analysis. Ann R Coll Surg Engl 2022; 104:561-570. [PMID: 36044921 PMCID: PMC9433179 DOI: 10.1308/rcsann.2022.0053] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2022] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND We aim to assess the diagnostic accuracy of procalcitonin (PCT) and interleukin-6 (IL-6) as diagnostic biomarkers for postoperative infection/sepsis following major abdominal surgery. Postoperative infection is an important cause for morbidity and mortality in major surgery. Early diagnosis and antimicrobial treatment improves outcomes, and high-performing biomarkers could guide clinical decision making. METHODS A systematic database search was conducted for studies reporting diagnostic performance of biomarkers (including PCT and IL-6) for infection/sepsis following major abdominal surgery. Studies were assessed for reporting of diagnostic accuracy, relevance and quality. Data were extracted for meta-analysis. RESULTS Ten studies with 1,611 participants reported the diagnostic accuracy of PCT, with pooled sensitivity, specificity and summary receiver operator curve of 72% (95% CI 66-78), 62% (95% CI 59-64) and 0.766, respectively. Four studies with 175 participants reported the diagnostic accuracy of IL-6, with pooled sensitivity, specificity and summary receiver operator curve of 84% (95% CI 72-92), 76% (95% CI 68-84) and 0.878, respectively There was variability in the timing of sampling and cut-off values and significant heterogeneity and inconsistency between studies (I2 diagnostic odds ratio (DOR)= 43.2% for PCT, I2 DOR=0% for IL-6). CONCLUSIONS PCT performs only moderately well as a diagnostic test for postoperative infection/sepsis in major abdominal surgery, demonstrating limited sensitivity and specificity. Heterogeneity between studies is a limitation of the meta-analysis. There is an ongoing need for a rapid, accurate biomarker for postoperative infection or sepsis.
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C-Reactive Protein Velocity (CRPv) as a New Biomarker for the Early Detection of Acute Infection/Inflammation. Int J Mol Sci 2022; 23:ijms23158100. [PMID: 35897672 PMCID: PMC9330915 DOI: 10.3390/ijms23158100] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 01/08/2023] Open
Abstract
C-reactive protein (CRP) is considered a biomarker of infection/inflammation. It is a commonly used tool for early detection of infection in the emergency room or as a point-of-care test and especially for differentiating between bacterial and viral infections, affecting decisions of admission and initiation of antibiotic treatments. As C-reactive protein is part of a dynamic and continuous inflammatory process, a single CRP measurement, especially at low concentrations, may erroneously lead to a wrong classification of an infection as viral over bacterial and delay appropriate antibiotic treatment. In the present review, we introduce the concept of C-reactive protein dynamics, measuring the velocity of C-reactive protein elevation, as a tool to increase this biomarker’s diagnostic ability. We review the studies that helped define new metrics such as estimated C-reactive protein velocity (velocity of C-reactive protein elevation from symptoms’ onset to first C-reactive protein measurement) and the measured C-reactive protein velocity (velocity between sequential C-reactive protein measurements) and the use of these metrics in different clinical scenarios. We also discuss future research directions for this novel metric.
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17
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Serum Cytokine Profile in Patients with Candidemia versus Bacteremia. Pathogens 2021; 10:pathogens10101349. [PMID: 34684298 PMCID: PMC8537900 DOI: 10.3390/pathogens10101349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/13/2021] [Accepted: 10/13/2021] [Indexed: 11/17/2022] Open
Abstract
Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1β, IL-6, IL-17A, IL-10, IFN-γ, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections.
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18
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van der Feltz-Cornelis CM, Bakker M, Kaul A, Kuijpers TW, von Känel R, van Eck van der Sluijs JF. IL-6 and hsCRP in Somatic Symptom Disorders and related disorders. Brain Behav Immun Health 2021; 9:100176. [PMID: 34589907 PMCID: PMC8474154 DOI: 10.1016/j.bbih.2020.100176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/16/2020] [Accepted: 10/28/2020] [Indexed: 12/26/2022] Open
Abstract
Interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are biomarkers of systemic low-grade inflammation (SLI) in depression and anxiety. The question if SLI in those conditions is related to comorbid chronic medical conditions has not been resolved. DSM-5 Somatic symptom disorders and related disorders (SSRD) are conditions with serious distress related to physical symptoms as main criterion. They can occur in patients with medically unexplained symptoms (MUS) and in patients with known comorbid chronic medical conditions. Often, comorbid depression and anxiety are present. SSRDs offer the opportunity to explore the role of SLI in relation to mental distress, including trauma, MUS, chronic medical conditions and comorbid mental disorder. AIM We hypothesized that increased IL-6 and hsCRP may be directly linked to SLI in SSRD, and that comorbid chronic medical conditions, childhood trauma, current stress and comorbid depression and anxiety may be risk factors that account for some of the variance of SLI in SSRD. METHODS We explored these relationships in a large sample of 241 consecutive outpatients with SSRD. RESULTS Mean hsCRP level was 3.66 mg/l, and mean IL-6 level was 3.58 pg/ml. IL-6 and hsCRP levels were associated with each other: τ = 0.249, p < .001; a medium size correlation. Comorbid chronic medical conditions, adverse childhood events other than sexual trauma, and current stress levels were not associated with IL-6 or hsCRP levels. CONCLUSION IL-6 and hsCRP are elevated in SSRD, indicating SLI in SSRD independently of comorbid chronic medical conditions. In clinical research, elevated IL-6 and hsCRP can be used as biomarkers of SLI and can indicate risk for childhood sexual abuse in SSRD. Elevated hsCRP may be a biomarker indicating risk for comorbid depression or high pain levels in SSRD as well.
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Affiliation(s)
- Christina M. van der Feltz-Cornelis
- Department of Health Sciences, Hull York Medical School, University of York, York, UK
- Corresponding author. Department of Health Sciences, MHARG, HYMS, YBRI, University of York, ARRC Building, T204, Heslington, York, YO10 5DN, UK.
| | - Marjan Bakker
- Department of Methodology and Statistics, Tilburg University, Tilburg, the Netherlands
| | - Arvind Kaul
- St. George’s University Hospitals NHS Foundation Trust, London, UK
| | - Taco W. Kuijpers
- Emma Children’s Hospital, Dept. of Pediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam University Medical Center (Amsterdam UMC), Amsterdam, the Netherlands
| | - Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jonna F. van Eck van der Sluijs
- Clinical Centre of Excellence for Body, Mind and Health, GGz Breburg, Tilburg, the Netherlands
- Altrecht Psychosomatic Medicine, Zeist, the Netherlands
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Tsalik EL, Henao R, Montgomery JL, Nawrocki JW, Aydin M, Lydon EC, Ko ER, Petzold E, Nicholson BP, Cairns CB, Glickman SW, Quackenbush E, Kingsmore SF, Jaehne AK, Rivers EP, Langley RJ, Fowler VG, McClain MT, Crisp RJ, Ginsburg GS, Burke TW, Hemmert AC, Woods CW. Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test. Crit Care Med 2021; 49:1651-1663. [PMID: 33938716 PMCID: PMC8448917 DOI: 10.1097/ccm.0000000000005085] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING Four U.S. emergency departments. PATIENTS Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes. MEASUREMENTS AND MAIN RESULTS Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.
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Affiliation(s)
- Ephraim L. Tsalik
- Durham Veterans Affairs Health Care System, Durham, NC, USA
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Ricardo Henao
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
- Department of Biostatistics and Informatics, Duke University, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | | | | | - Mert Aydin
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Emily C. Lydon
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Emily R. Ko
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Regional Hospital, Durham, NC, USA
| | - Elizabeth Petzold
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
| | | | - Charles B. Cairns
- University of North Carolina Medical Center, Chapel Hill, NC, USA
- Drexel University, Philadelphia, PA, USA
| | - Seth W. Glickman
- University of North Carolina Medical Center, Chapel Hill, NC, USA
| | | | | | | | | | | | - Vance G. Fowler
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Micah T. McClain
- Durham Veterans Affairs Health Care System, Durham, NC, USA
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | | | - Geoffrey S. Ginsburg
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Thomas W. Burke
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
| | | | - Christopher W. Woods
- Durham Veterans Affairs Health Care System, Durham, NC, USA
- Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
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Belcaro G, Cornelli U, Cesarone MR, Scipione C, Scipione V, Hu S, Feragalli B, Corsi M, Cox D, Cotellese R, Hosoi M, Burki C. Preventive effects of Pycnogenol® on cardiovascular risk factors (including endothelial function) and microcirculation in subjects recovering from coronavirus disease 2019 (COVID-19). Minerva Med 2021; 113:300-308. [PMID: 34060731 DOI: 10.23736/s0026-4806.21.07650-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The aim of this open supplement study was to evaluate the effects of Pycnogenol® in comparison with controls on symptoms of post-COVID-19 syndrome and in improving endothelial function, microcirculation, inflammatory markers and oxidative stress over 3 months in symptomatic subjects recovering from COVID-19. METHODS Sixty subjects recovering from symptomatic COVID-19 were included. One group of 30 followed a standard recovery management while 30 comparable subjects received a supplement of 150 mg Pycnogenol® daily (in 3 doses of 50 mg) in addition to standard management. RESULTS Two groups of selected subjects were comparable at baseline. The groups progressively improved both with the SM (standard management) and with the SM in combination with the supplement. Patients, supplemented with Pycnogenol® showed significantly better improvement compared to the control group patients. No side effects from the supplementation were observed; tolerability was optimal. The progressive evolution over time was visible in all target measurements. Physiological tests. Endothelial function, low in all subjects at inclusion was assessed by flow mediated dilation (FMD) and finger reactive hyperemia in the microcirculation (laser Doppler measurements) after the release of an occluding suprasystolic cuff). It was significantly improved in the Pycnogenol® group after one month and after 3 months (p<0.05 vs controls). The rate of ankle swelling (RAS) by strain gauge decreased significantly in the supplemented group (p<0.05) in comparison with controls showing an improvement of the capillary filtration rate. At inclusion, the kidney cortical flow velocity indicated a decrease in perfusion (lower systolic and diastolic flow velocity) in all patients. Kidney cortical flow velocity increased significantly with the supplement (p<0.05) in comparison with controls with improvement in systolic velocity and in diastolic component. High sensitivity CRP (hs-CRP) and Il-6 plasma levels decreased progressively over 3 months with a significant more pronounced decrease in the supplement group (p<0.05). The number of patients with normal plasma IL-6 levels at the end of the study was higher (p<0,05) with the supplement. ESR followed the same pattern with a progressive and a more significant decrease in the supplemented subjects (p<0.02). Oxidative stress decreased significantly in the supplemented group (p<0.05) compared with the control group. Blood pressure and heart rate were normalized in all subjects in the supplement group; systolic pressure was significantly lower in the supplemented group (p<0,05) at the end of the study. Finally, the scores of Quality-of-life, mood and fatigue questionnaire and the Karnofsky scale performance index significantly improved in the supplement group (p<0.05) compared to controls after 1 and 3 months. All other blood parameters (including platelets and clotting factors) were within normal values at the end of the study. CONCLUSIONS In conclusion, Pycnogenol® may offer a significant option for managing some of the signs and symptoms associated with post-COVID-19 syndrome. This pilot evaluation offers some potential rationale for the use of Pycnogenol® in this condition that will have significant importance in the coming years.
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Affiliation(s)
| | - Umberto Cornelli
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | - Maria Rosaria Cesarone
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | | | | | - Shu Hu
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | - Beatrice Feragalli
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | - Marcello Corsi
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | - David Cox
- Irvine3 Labs, OOLEX Project for Covid, Chieti, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
| | - Morio Hosoi
- Department of Medical, Oral and Biotechnological Sciences, D'Annunzio University, Pescara, Italy
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21
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Cong S, Ma T, Di X, Tian C, Zhao M, Wang K. Diagnostic value of neutrophil CD64, procalcitonin, and interleukin-6 in sepsis: a meta-analysis. BMC Infect Dis 2021; 21:384. [PMID: 33902476 PMCID: PMC8072745 DOI: 10.1186/s12879-021-06064-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 04/09/2021] [Indexed: 12/12/2022] Open
Abstract
Background The aim of the study was to conduct a meta-analysis to evaluate the accuracy of neutrophil CD64, procalcitonin (PCT), and interleukin-6 (IL-6) as markers for the diagnosis of sepsis in adult patients. Methods Various databases were searched to collect published studies on the diagnosis of sepsis in adult patients using neutrophil CD64, PCT, and IL-6 levels. Utilizing the Stata SE 15.0 software, forest plots and the area under the summary receiver operating characteristic curves were drawn. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. Results Fifty-four articles were included in the study. The pooled sensitivity, specificity, and AUC of neutrophil CD64 for the diagnosis of sepsis were 0.88 (95% confidence interval [CI], 0.81–0.92), 0.88 (95% CI, 0.83–0.91), and 0.94 (95% CI, 0.91–0.96), respectively. The pooled sensitivity, specificity, and AUC of PCT for the diagnosis of sepsis were 0.82 (95% CI, 0.78–0.85), 0.78 (95% CI, 0.74–0.82), and 0.87 (95% CI, 0.83–0.89), respectively. Subgroup analysis showed that the AUC for PCT diagnosis of intensive care unit (ICU) sepsis was 0.86 (95% CI, 0.83–0.89) and the AUC for PCT diagnosis of non-ICU sepsis was 0.82 (95% CI, 0.78–0.85). The pooled sensitivity, specificity, and AUC of IL-6 for the diagnosis of sepsis were 0.72 (95% CI, 0.65–0.78), 0.70 (95% CI, 0.62–0.76), and 0.77 (95% CI, 0.73–0.80), respectively. Conclusions Of the three biomarkers studied, neutrophil CD64 showed the highest diagnostic value for sepsis, followed by PCT, and IL-6. On the other hand, PCT showed a better diagnostic potential for the diagnosis of sepsis in patients with severe conditions compared with that in patients with non-severe conditions.
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Affiliation(s)
- Shan Cong
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China
| | - Tiangang Ma
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China
| | - Xin Di
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China
| | - Chang Tian
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China
| | - Min Zhao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China
| | - Ke Wang
- Department of Respiratory Medicine, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, 130041, Jilin Province, China.
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22
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Xu X, Li X, Miao J, Liu L, Huang X, Wei Q, Cao W. A dual-mode label-free electrochemical immunosensor for ultrasensitive detection of procalcitonin based on g-C 3N 4-NiCo 2S 4-CNTs-Ag NPs. Analyst 2021; 146:3169-3176. [PMID: 33999069 DOI: 10.1039/d1an00372k] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Herein, a label-free electrochemical immunosensor based on differential pulse voltammetry (DPV) and amperometric i-t curve (i-t) dual-mode analysis is proposed for early quantitative detection of procalcitonin (PCT). Due to the advantages of high chemical stability and biocompatibility, graphite carbon nitride (g-C3N4) was adopted as a high-capacity sensing interface to carry signal indicators. As an effective indicator of chronoamperometry, nickel cobalt sulfide (NiCo2S4) was uniformly dispersed on the surface of g-C3N4 through in-situ hydrothermal synthesis, which not only promotes the activation of bimetallic activity, but also effectively prevents the aggregation of NiCo2S4. At the same time, in order to establish a dual-mode analysis platform to improve accuracy and sensitivity, highly conductive carbon nanotubes (CNTs) were hybridized with composite materials to load Ag nanoparticles (Ag NPs), which have excellent oxidizing properties and are used as indicators of DPV. On account of this advanced sensing strategy, a wide linear response (DPV: 0.05 ng mL-1-50 ng mL-1 and i-t: 1.00 pg mL-1-10.00 ng mL-1) and a low detection limit (DPV: 16.70 pg mL-1 and i-t: 0.33 pg mL-1) are demonstrated. The immunosensor synthesized by this method has good stability and sensitivity, which could be applied in clinical diagnosis and treatment.
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Affiliation(s)
- Xiaoting Xu
- Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, PR China.
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23
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Schneidewind L. [Reducing mortality in adults with sepsis, severe sepsis, or septic shock: effectiveness and safety of procalcitonin]. Urologe A 2021; 60:624-627. [PMID: 33779788 DOI: 10.1007/s00120-021-01506-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/04/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Laila Schneidewind
- Urologische Klinik Und Poliklinik, Universitätsmedizin Rostock, Ernst-Heydemann-Str. 6, 18055, Rostock, Deutschland. .,UroEvidence@DGU, Berlin, Deutschland.
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24
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Saito K, Sugawara H, Ichihara K, Watanabe T, Ishii A, Fukuchi T. Prediction of 72-hour mortality in patients with extremely high serum C-reactive protein levels using a novel weighted average of risk scores. PLoS One 2021; 16:e0246259. [PMID: 33606735 PMCID: PMC7894915 DOI: 10.1371/journal.pone.0246259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 01/18/2021] [Indexed: 01/10/2023] Open
Abstract
The risk factors associated with mortality in patients with extremely high serum C-reactive protein (CRP) levels are controversial. In this retrospective single-center cross-sectional study, the clinical and laboratory data of patients with CRP levels ≥40 mg/dL treated in Saitama Medical Center, Japan from 2004 to 2017 were retrieved from medical records. The primary outcome was defined as 72-hour mortality after the final CRP test. Forty-four mortal cases were identified from the 275 enrolled cases. Multivariate logistic regression analysis (MLRA) was performed to explore the parameters relevant for predicting mortality. As an alternative method of prediction, we devised a novel risk predictor, “weighted average of risk scores” (WARS). WARS features the following: (1) selection of candidate risk variables for 72-hour mortality by univariate analyses, (2) determination of C-statistics and cutoff value for each variable in predicting mortality, (3) 0–1 scoring of each risk variable at the cutoff value, and (4) calculation of WARS by weighted addition of the scores with weights assigned according to the C-statistic of each variable. MLRA revealed four risk variables associated with 72-hour mortality—age, albumin, inorganic phosphate, and cardiovascular disease—with a predictability of 0.829 in C-statistics. However, validation by repeated resampling of the 275 records showed that a set of predictive variables selected by MLRA fluctuated occasionally because of the presence of closely associated risk variables and missing data regarding some variables. WARS attained a comparable level of predictability (0.837) by combining the scores for 10 risk variables, including age, albumin, electrolytes, urea, lactate dehydrogenase, and fibrinogen. Several mutually related risk variables are relevant in predicting 72-hour mortality in patients with extremely high CRP levels. Compared to conventional MLRA, WARS exhibited a favorable performance with flexible coverage of many risk variables while allowing for missing data.
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Affiliation(s)
- Kai Saito
- Nara Medical University, Kashihara, Nara, Japan
| | - Hitoshi Sugawara
- Division of General Medicine, Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama, Japan
- * E-mail:
| | - Kiyoshi Ichihara
- Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Tamami Watanabe
- Division of General Medicine, Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Akira Ishii
- Division of General Medicine, Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Takahiko Fukuchi
- Division of General Medicine, Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama, Japan
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25
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Didembourg M, Douxfils J, Mullier F, Hardy M, Favresse J, Morimont L. Influence of C-reactive protein on thrombin generation assay. Clin Chem Lab Med 2021; 59:e301-e305. [PMID: 33561909 DOI: 10.1515/cclm-2020-1686] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/29/2021] [Indexed: 11/15/2022]
Affiliation(s)
- Marie Didembourg
- Faculty of Medicine, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium
| | - Jonathan Douxfils
- Faculty of Medicine, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium.,QUALIblood SA, Namur, Belgium
| | - François Mullier
- Laboratory Hematology, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
| | - Michael Hardy
- Department of Anesthesiology, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
| | - Julien Favresse
- Faculty of Medicine, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium.,Clinique Saint-Luc Bouge A.S.B.L. "Santé & Prévoyance", Namur, Belgium
| | - Laure Morimont
- Faculty of Medicine, Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium.,QUALIblood SA, Namur, Belgium
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26
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Torres MJM, Peterson JM, Wolf SE. Detection of Infection and Sepsis in Burns. Surg Infect (Larchmt) 2020; 22:20-27. [PMID: 33021433 DOI: 10.1089/sur.2020.348] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Infection is the most frequent complication after severe burns and has a propensity to progress into sepsis then septic shock and multiple organ dysfunction syndrome (MODS). Improving outcomes in acute burn care depends on early detection of infection to allow prompt interventions. Diagnosis of sepsis in severe burns is uniquely challenging because otherwise-typical clinical signs are masked by the hypermetabolic state and systemic inflammation induced by the burn itself. For this reason, burns have historically been excluded from high-impact studies on the diagnosis and treatment of sepsis. Methods: This article provides a comprehensive three-fold review of current findings and guidelines pertinent to the early detection of infection and sepsis in severe burns. Results: First, evidence-based detection of the most common infections encountered in the burn intensive care unit is reviewed. Second, we analyze the evolution of the diagnostic criteria for sepsis and the evidence regarding their utility in severe burns. Last, we examine the development of biomarkers, from procalcitonin to molecular genomics, for the detection of sepsis. Conclusions: Although gold standard methods of early detection of sepsis in burn patients have yet to be identified, improved understanding and appropriate application of the available diagnostic criteria and assays are paramount to providing effective care of patients with severe burns.
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Affiliation(s)
- Mark Jason M Torres
- School of Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| | - Joshua M Peterson
- Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA
| | - Steven E Wolf
- Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA.,Shriners Hospitals for Children, Galveston, Texas, USA
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27
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Levinson T, Tamir N, Shenhar-Tsarfaty S, Paran Y, Zeltzer D, Shapira I, Halpern P, Meilik A, Raykhshtat E, Goldiner I, Adler A, Berliner S, Rogowski O, Wasserman A. The potential benefit of a second C-reactive protein measurement in patients with gram-negative bacteraemia presenting to the emergency medicine department. Biomarkers 2020; 25:533-538. [PMID: 32715769 DOI: 10.1080/1354750x.2020.1797878] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Low C-reactive protein in acute bacterial infections could convey the erroneous impression of a mild infection. We focussed on gram-negative bacteraemia, a phenomenon frequently seen at the emergency room. METHODS Of 2200 patients with gram-negative bacteraemia, 460 patients with first C-reactive protein <30 mg/L and 460 patients with C-reactive protein >187 mg/L were reviewed. Following exclusions, we finally investigated 229 and 289 patients with low and high C-reactive protein concentrations, respectively. RESULTS The cohort was divided into low and high C-reactive protein groups. Median first C-reactive protein was 13.6 and 219.9 mg/L, respectively (interquartile range 6.4-21.6 and 195-270.1). Compared to patients with first high C-reactive protein, patients with first low C-reactive protein concentrations had a significant five-fold higher C-reactive protein level with their second test. CONCLUSIONS Patients with gram-negative bacteraemia can present with C-reactive protein within the range of apparently healthy individuals. A second C-reactive protein might help to avoid an erroneous decision regarding the severity of the infection.
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Affiliation(s)
- Tal Levinson
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Natalie Tamir
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shani Shenhar-Tsarfaty
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Paran
- Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - David Zeltzer
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Itzhak Shapira
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Pinchas Halpern
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Emergency Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Ahuva Meilik
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Data Science and Quality Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Eli Raykhshtat
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Data Science and Quality Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Ilana Goldiner
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Clinical Laboratory Services, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Amos Adler
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Clinical Microbiology Laboratory, The Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Shlomo Berliner
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ori Rogowski
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Asaf Wasserman
- Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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28
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Shilpakar R, Paudel BD, Neupane P, Shah A, Acharya B, Dulal S, Wood LA, Shahi R, Khanal U, Poudyal BS. Procalcitonin and C-Reactive Protein As Markers of Bacteremia in Patients With Febrile Neutropenia Who Receive Chemotherapy for Acute Leukemia: A Prospective Study From Nepal. J Glob Oncol 2020; 5:1-6. [PMID: 31526283 PMCID: PMC6872183 DOI: 10.1200/jgo.19.00147] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
PURPOSE The purpose of this study was to evaluate the clinical significance of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP) in patients with febrile neutropenia (FN) undergoing chemotherapy for acute leukemia. METHODS We conducted a prospective, observational study in patients who developed FN while undergoing chemotherapy for acute leukemia. PCT and CRP were obtained in patients who presented with FN. Blood cultures also were obtained. The primary goals were to evaluate the ability of PCT and CRP to predict bacteremia in patients with FN. The secondary goals were to assess the prognostic role of PCT and CRP and to assess the microbiologic profile and culture sensitivity patterns in the study population. RESULTS A total of 124 episodes of FN that involved 67 patients with acute leukemia occurred in the study. PCT was superior to CRP in the prediction of bacteremia. The median PCT level in the bacteremia group was 3.25 ng/mL compared with 0.51 ng/mL in the group without bacteremia (P < .01). The median values of CRP in the bacteremia and without-bacteremia groups were 119.3 mg/L and 94.5 mg/L, respectively (P = .07). There were no differences in median PCT and CRP in patients who died and those who improved. Of the 42 positive cultures, Gram-negative bacteremia was common (86%), and Escherichia coli was the most frequent organism isolated. Carbapenem resistance was seen in 39% of positive cultures. CONCLUSION PCT is an effective biomarker to predict bacteremia in patients with FN undergoing chemotherapy for acute leukemia.
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Affiliation(s)
- Ramila Shilpakar
- National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
| | | | | | - Aarati Shah
- National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
| | - Bibek Acharya
- National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
| | - Soniya Dulal
- National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
| | - Lori Anne Wood
- Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
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29
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Kortz TB, Nyirenda J, Tembo D, Elfving K, Baltzell K, Bandawe G, Rosenthal PJ, Macfarlane SB, Mandala W, Nyirenda TS. Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis. Am J Trop Med Hyg 2020; 101:1424-1433. [PMID: 31595873 DOI: 10.4269/ajtmh.18-0635] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.
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Affiliation(s)
- Teresa B Kortz
- Department of Pediatrics, University of California, San Francisco, California.,Institute of Global Health Sciences, University of California, San Francisco, California
| | - James Nyirenda
- Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.,Department of Pathology, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Dumizulu Tembo
- Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Kristina Elfving
- Department of Infectious Diseases, Institution for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Kimberly Baltzell
- Department of Family Health Care Nursing, University of California, San Francisco, California.,Institute of Global Health Sciences, University of California, San Francisco, California
| | - Gama Bandawe
- Department of Biological Sciences, Malawi University of Science and Technology, Thyolo, Malawi
| | - Philip J Rosenthal
- Department of Medicine, University of California, San Francisco, California
| | - Sarah B Macfarlane
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California
| | - Wilson Mandala
- Department of Biological Sciences, Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi.,Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Tonney S Nyirenda
- Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.,Department of Pathology, College of Medicine, University of Malawi, Blantyre, Malawi
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30
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Colón-Emeric C, Pieper CF, Schmader KE, Sloane R, Bloom A, McClain M, Magaziner J, Huffman KM, Orwig D, Crabtree DM, Whitson HE. Two Approaches to Classifying and Quantifying Physical Resilience in Longitudinal Data. J Gerontol A Biol Sci Med Sci 2020; 75:731-738. [PMID: 30993327 PMCID: PMC7328208 DOI: 10.1093/gerona/glz097] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Approaches for quantifying physical resilience in older adults have not been described. METHODS We apply two conceptual approaches to defining physical resilience to existing longitudinal data sets in which outcomes are measured after an acute physical stressor. A "recovery phenotype" approach uses statistical methods to describe how quickly and completely a patient recovers. Statistical methods using a recovery phenotype approach can consider multiple outcomes simultaneously in a composite score (eg, factor analysis and principal components analysis) or identify groups of patients with similar recovery trajectories across multiple outcomes (eg, latent class profile analysis). An "expected recovery differential" approach quantifies how patients' actual outcomes are compared to their predicted outcome based on a population-derived model and their individual clinical characteristics at the time of the stressor. RESULTS Application of the approaches identified different participants as being the most or least physically resilient. In the viral respiratory cohort (n = 186) weighted kappa for agreement across resilience quartiles was 0.37 (0.27-0.47). The expected recovery differential approach identified a group with more comorbidities and lower baseline function as highly resilient. In the hip fracture cohort (n = 541), comparison of the expected recovery differentials across 10 outcome measures within individuals provided preliminary support for the hypothesis that there is a latent resilience trait at the whole-person level. CONCLUSIONS We posit that recovery phenotypes may be useful in clinical applications such as prediction models because they summarize the observed outcomes across multiple measures. Expected recovery differentials offer insight into mechanisms behind physical resilience not captured by age and other comorbidities.
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Affiliation(s)
- Cathleen Colón-Emeric
- Division of Geriatrics, Duke University, Durham, North Carolina
- Geriatric Research Education Clinical Center, Durham Veteran Affairs Medical Center, North Carolina
- Duke Claude D. Pepper Older American Independence Center, Duke University, Durham, North Carolina
| | - Carl F Pieper
- Geriatric Research Education Clinical Center, Durham Veteran Affairs Medical Center, North Carolina
- Duke Claude D. Pepper Older American Independence Center, Duke University, Durham, North Carolina
| | - Kenneth E Schmader
- Division of Geriatrics, Duke University, Durham, North Carolina
- Geriatric Research Education Clinical Center, Durham Veteran Affairs Medical Center, North Carolina
- Duke Claude D. Pepper Older American Independence Center, Duke University, Durham, North Carolina
| | - Richard Sloane
- Geriatric Research Education Clinical Center, Durham Veteran Affairs Medical Center, North Carolina
- Duke Claude D. Pepper Older American Independence Center, Duke University, Durham, North Carolina
| | - Allison Bloom
- Center for Applied Genomics and Precision Medicine, Duke University Medical Centre, Durham, North Carolina
| | - Micah McClain
- Center for Applied Genomics and Precision Medicine, Duke University Medical Centre, Durham, North Carolina
| | - Jay Magaziner
- Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore
| | - Kim M Huffman
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina
| | - Denise Orwig
- Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore
| | - Donna M Crabtree
- Duke Office of Clinical Research, School of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Heather E Whitson
- Division of Geriatrics, Duke University, Durham, North Carolina
- Geriatric Research Education Clinical Center, Durham Veteran Affairs Medical Center, North Carolina
- Duke Claude D. Pepper Older American Independence Center, Duke University, Durham, North Carolina
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31
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Molano Franco D, Gómez Duque M, Beltrán E, Villabón González M, Robayo Valbuena IF, Franco LF, Cárdenas Colmenares JA, Estupiñán Monsalve Á, Sánchez Vanegas G, Arévalo Rodriguez I, Zamora Romero J. Medicina de precisión en sepsis: utilidad de los biomarcadores en pacientes biomarcadores en pacientes críticamente enfermos. REPERTORIO DE MEDICINA Y CIRUGÍA 2020. [DOI: 10.31260/repertmedcir.01217273.973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Durante años la evolución del cuidado intensivo ha intentado ofrecer una atención basada en protocolos y paquetes de manejo agrupados por patologías y cuadro sindromáticos. Aunque se logró disminuir la mortalidad en diferentes patologías (sepsis y síndromes coronario agudo y de distrés respiratorio agudo), no se han resuelto por completo los problemas clínicos, en especial el diagnóstico y el manejo. Una nueva opción ha surgido en el horizonte denominada “medicina de precisión”, entendida como estrategia de prevención y tratamiento que tiene en cuenta la variabilidad individual. La sepsis es un síndrome con múltiples aristas en cuanto al fenotipo y genotipo, cuyo diagnóstico temprano es relevante para los desenlaces clínicos. Hasta el momento el enfoque principal ha sido la identificación de un germen etiológico para diferenciarla del síndrome de respuesta inflamatoria sistémica (SIRS). En los últimos años el paradigma en enfermedades infecciosas ha cambiado debido a estudios que demuestran como la respuesta inmunitaria del paciente séptico tiene un papel clave en el desarrollo de la enfermedad, con implicaciones en el diagnóstico, pronóstico y tratamiento, que podrían ayudar a cambiar el abordaje en los próximos años gracias a una estrategia basada en medicina de precisión. Hoy los aislamientos microbiológicos y los cultivos siguen siendo el estándar de referencia con varias desventajas como el tiempo para obtener resultados, sobre todo en infecciones por gérmenes resistentes u hongos, que pueden retrasar el inicio de la terapia antimicrobiana. Como alternativa se ha planteado el uso de biomarcadores en sepsis que siendo productos de la respuesta inflamatoria del individuo ante la infección, son útiles para el diagnóstico y pronóstico primordialmente en los críticamente enfermos. Decidimos realizar esta revisión narrativa acerca de la utilidad de los biomarcadores en pacientes con sepsis críticamente enfermos, para enfocarlos en un modelo de medicina personalizada.
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Early-Stage Staphylococcus aureus Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors. mSystems 2020; 5:5/1/e00632-19. [PMID: 31964768 PMCID: PMC6977072 DOI: 10.1128/msystems.00632-19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
S. aureus sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with S. aureus bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic S. aureus infection patients had low preexisting anti-S. aureus antibody levels. This strengthens the notion that a robust immune memory for S. aureus protects against infections with the pathogen. Systemic and quantitative investigations of human plasma proteins (proteomics) and Staphylococcus aureus-specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in Staphylococcus aureus bloodstream infection (SABSI). Usually, data-dependent acquisition (DDA) is used for proteome analysis of serum or plasma, but data-independent acquisition (DIA) is more comprehensive and reproducible. In this prospective cohort study, we aimed to identify biomarkers associated with the early stages of SABSI using a serum DIA proteomic and immunoproteomic approach. Sera from 49 SABSI patients and 43 noninfected controls were analyzed. In total, 608 human serum proteins were identified with DIA. A total of 386 proteins could be quantified, of which 9 proteins, mainly belonging to acute-phase proteins, were significantly increased, while 7 high-density lipoproteins were lower in SABSI. In SABSI, total anti-S. aureus serum IgG was reduced compared with controls as shown by immunoproteomic quantification of IgG binding to 143 S. aureus antigens. IgG binding to 48 of these anti-S. aureus proteins was significantly lower in SABSI, while anti-Ecb IgG was the only one increased in SABSI. Serum IgG binding to autoinducing peptide MsrB, FadB, EsxA, Pbp2, FadB, SspB, or SodA was very low in SABSI. This marker panel discriminated early SABSI from controls with 95% sensitivity and 100% specificity according to random forest prediction. This holds promise for patient stratification according to their risk of S. aureus infection, underlines the protective function of the adaptive immune system, and encourages further efforts in the development of a vaccine against S. aureus. IMPORTANCES. aureus sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with S. aureus bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic S. aureus infection patients had low preexisting anti-S. aureus antibody levels. This strengthens the notion that a robust immune memory for S. aureus protects against infections with the pathogen.
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Sharma A, Ray S, Mamidipalli R, Kakar A, Chugh P, Jain R, Ghalaut MS, Choudhury S. A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome. Indian J Crit Care Med 2020; 24:245-251. [PMID: 32565634 PMCID: PMC7297249 DOI: 10.5005/jp-journals-10071-23385] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introduction Differentiation between sepsis and systemic inflammation response syndrome (SIRS) remains a diagnostic challenge for clinicians as both may have similar clinical presentation. A quick and accurate diagnostic tool that can discriminate between these two conditions would aid in appropriate therapeutic decision-making. This prospective study was conducted to evaluate the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) and procalcitonin (PCT) in sepsis and SIRS patients. Materials and methods Eighty-eight patients were enrolled, of which 29 were SIRS and 59 were sepsis patients. The levels of suPAR and PCT were measured on the day of admission (day 1), day 3, and day 7. Results The levels of suPAR and PCT were significantly higher (p = 0.05 and p < 0.001, respectively) in sepsis group as compared to the SIRS group. The soluble urokinase-type plasminogen activator receptor was a better diagnostic tool in predicting sepsis over PCT [area under curve (AUC) 0.89 vs 0.82] on day 1. The best cutoff for suPAR was 5.58 pg/mL [96% sensitivity and 90% negative predictive value (NPV)] and the best cut-off for PCT was 1.96 ng/mL (93.1% sensitivity and 80% NPV). However, PCT had better prognostic trends (p = 0.006) to identify nonsurvivors in sepsis group. Conclusion Our findings suggest that both suPAR and PCT can be used as potential test tools to differentiate between SIRS and sepsis. Procalcitonin showed significant prognostic trends to identify nonsurvivors. The soluble urokinase-type plasminogen activator receptor showed better diagnostic potential than PCT on day 1. Clinical significance Both suPAR and PCT can be used as surrogate biomarkers to distinguish sepsis from SIRS. Procalcitonin showing a significant prognostic trend to identify nonsurvivors can help the clinicians to take relevant clinical decisions. Also, the use of biomarkers like PCT and suPAR could reduce the inappropriate use of antibiotics in noninfective SIRS. How to cite this article Sharma A, Ray S, Mamidipalli R, Kakar A, Chugh P, Jain R, et al. A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome. Indian J Crit Care Med 2020;24(4):245–251.
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Affiliation(s)
- Ankita Sharma
- Department of Research, Sir Ganga Ram Hospital, New Delhi, India
| | - Sumit Ray
- Department of Critical Care Medicine, Artemis Hospital, Gurugram, Haryana, India
| | | | - Atul Kakar
- Department of Medicine, Sir Ganga Ram Hospital, New Delhi, India
| | - Parul Chugh
- Department of Research, Sir Ganga Ram Hospital, New Delhi, India
| | - Ridhima Jain
- Department of Research, Sir Ganga Ram Hospital, New Delhi, India
| | - Manvender S Ghalaut
- Department of Biotechnology, University Institute of Engineering and Technology, Maharshi Dayanand University, Rohtak, Haryana, India
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Tsalik EL, Khine A, Talebpour A, Samiei A, Parmar V, Burke TW, Mcclain MT, Ginsburg GS, Woods CW, Henao R, Alavie T. Rapid, Sample-to-Answer Host Gene Expression Test to Diagnose Viral Infection. Open Forum Infect Dis 2019; 6:ofz466. [PMID: 34150923 DOI: 10.1093/ofid/ofz466] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 10/23/2019] [Indexed: 12/14/2022] Open
Abstract
Objective Distinguishing bacterial, viral, or other etiologies of acute illness is diagnostically challenging with significant implications for appropriate antimicrobial use. Host gene expression offers a promising approach, although no clinically useful test has been developed yet to accomplish this. Here, Qvella's FAST HR (Richmond Hill, Ontario, Canada) process was developed to quantify previously identified host gene expression signatures in whole blood in <45 minutes. Method Whole blood was collected from 128 human subjects (mean age 47, range 18-88) with clinically adjudicated, microbiologically confirmed viral infection, bacterial infection, noninfectious illness, or healthy controls. Stabilized mRNA was released from cleaned and stabilized RNA-surfactant complexes using e-lysis, an electrical process providing a quantitative real-time reverse transcription polymerase chain reaction-ready sample. Threshold cycle values (CT) for 10 host response targets were normalized to hypoxanthine phosphoribosyltransferase 1 expression, a control mRNA. The transcripts in the signature were specifically chosen to discriminate viral from nonviral infection (bacterial, noninfectious illness, or healthy). Classification accuracy was determined using cross-validated sparse logistic regression. Results Reproducibility of mRNA quantification was within 1 cycle as compared to the difference seen between subjects with viral versus nonviral infection (up to 5.0 normalized CT difference). Classification of 128 subjects into viral or nonviral etiologies demonstrated 90.6% overall accuracy compared to 82.0% for procalcitonin (P = .06). FAST HR achieved rapid and accurate measurement of the host response to viral infection in less than 45 minutes. Conclusions These results demonstrate the ability to translate host gene expression signatures to clinical platforms for use in patients with suspected infection. Clinical Trials Registration NCT00258869.
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Affiliation(s)
- Ephraim L Tsalik
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.,Emergency Medicine Service, Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | - Ayeaye Khine
- Qvella Corporation, Richmond Hill, Ontario, Canada
| | | | | | - Vilcy Parmar
- Qvella Corporation, Richmond Hill, Ontario, Canada
| | - Thomas W Burke
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Micah T Mcclain
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.,Medicine Service, Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | - Geoffrey S Ginsburg
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Christopher W Woods
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.,Medicine Service, Durham Veterans Affairs Health Care System, Durham, North Carolina, USA
| | - Ricardo Henao
- Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.,Pratt School of Engineering, Duke University, Durham, North Carolina, USA
| | - Tino Alavie
- Qvella Corporation, Richmond Hill, Ontario, Canada
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Lydon EC, Henao R, Burke TW, Aydin M, Nicholson BP, Glickman SW, Fowler VG, Quackenbush EB, Cairns CB, Kingsmore SF, Jaehne AK, Rivers EP, Langley RJ, Petzold E, Ko ER, McClain MT, Ginsburg GS, Woods CW, Tsalik EL. Validation of a host response test to distinguish bacterial and viral respiratory infection. EBioMedicine 2019; 48:453-461. [PMID: 31631046 PMCID: PMC6838360 DOI: 10.1016/j.ebiom.2019.09.040] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 09/19/2019] [Accepted: 09/20/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases. METHODS Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin. FINDINGS 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02). INTERPRETATION The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.
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Affiliation(s)
- Emily C Lydon
- Duke University School of Medicine, Durham, NC, USA; Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| | - Ricardo Henao
- Duke University Department of Biostatistics and Informatics, Durham, NC, USA
| | - Thomas W Burke
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| | - Mert Aydin
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| | - Bradly P Nicholson
- Institute of Medical Research, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Seth W Glickman
- University of North Carolina Medical Center, Chapel Hill, NC, USA
| | - Vance G Fowler
- Duke University Department of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA
| | | | - Charles B Cairns
- University of North Carolina Medical Center, Chapel Hill, NC, USA; United Arab Emirates University, Al Ain, UAE
| | | | | | | | - Raymond J Langley
- University of South Alabama Health University Hospital, Mobile, AL, USA
| | - Elizabeth Petzold
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| | - Emily R Ko
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Department of Hospital Medicine, Duke Regional Hospital, Durham, NC 27705, USA
| | - Micah T McClain
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA
| | - Geoffrey S Ginsburg
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| | - Christopher W Woods
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA.
| | - Ephraim L Tsalik
- Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA.
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Sharma S, Duggal N. Role of procalcitonin, Il-6 and C- reactive protein in suspected cases of sepsis. INDIAN J PATHOL MICR 2019; 62:578-581. [PMID: 31611443 DOI: 10.4103/ijpm.ijpm_762_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES To study the role of serum procalcitonin as a diagnostic biomarker in sepsis and to compare it with other sepsis markers (IL-6, CRP) in patients of suspected sepsis. MATERIALS AND METHODS A total of 80 patients were included in this study from ICU and each patient was investigated for serum Procalcitonin, Interleukin-6 and C-reactive protein levels by ELISA along with blood cultures by BacT/Alert system. RESULT Procalcitonin along with CRP is a better diagnostic tool for sepsis.
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Affiliation(s)
- Shiwangi Sharma
- Department of Microbiology, PGIMER, Dr. RML Hospital, New Delhi, India
| | - Nandini Duggal
- Department of Microbiology, PGIMER, Dr. RML Hospital, New Delhi, India
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Mou L, Dong R, Hu B, Li Z, Zhang J, Jiang X. Hierarchically structured microchip for point-of-care immunoassays with dynamic detection ranges. LAB ON A CHIP 2019; 19:2750-2757. [PMID: 31338499 DOI: 10.1039/c9lc00517j] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Point-of-care (POC) medical assays provide critical information to guide clinical therapy for a broad range of medical scenarios, such as resource-poor settings and specialty departments in hospitals. Even though many types of POC assays can be done in automated devices, these POC assays typically cannot well accommodate the multiplexed detection of biomarkers where a large dynamic range is needed. Here, we report a POC assay, which is both automated and suitable for detecting multiple biomarkers with dynamic detection ranges. We call it a dynamic multiplexed immunoassay (DMI). We control the concentrations of capture antibodies and the intensity of the readout signal to dynamically modulate the detection range of immunoassays (pg mL-1 to μg mL-1), leading to the multiplexed detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin 6 (IL-6) simultaneously in undiluted human serum samples. The POC assay allows the rapid and accurate detection of infection in patients.
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Affiliation(s)
- Lei Mou
- Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China and University of Chinese Academy of Sciences, No. 19 A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China
| | - Ruihua Dong
- Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China
| | - Binfeng Hu
- Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China and University of Chinese Academy of Sciences, No. 19 A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China
| | - Zulan Li
- Reproduction Center of the 306th Hospital of People's Liberation Army, No. 9, Anxiang Beili, Chaoyang District, Beijing 100101, P. R. China
| | - Jiangjiang Zhang
- Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China and University of Chinese Academy of Sciences, No. 19 A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China
| | - Xingyu Jiang
- Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China and Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Rd, Nanshan District, Shenzhen, Guangdong 518055, P. R. China. and University of Chinese Academy of Sciences, No. 19 A Yuquan Road, Shijingshan District, Beijing 100049, P. R. China
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Bloom AS, Suchindran S, Steinbrink J, McClain MT. Utility of predictive tools for risk stratification of elderly individuals with all-cause acute respiratory infection. Infection 2019; 47:617-627. [PMID: 30929142 DOI: 10.1007/s15010-019-01299-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 03/18/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE A number of scoring tools have been developed to predict illness severity and patient outcome for proven pneumonia, however, less is known about the utility of clinical prediction scores for all-cause acute respiratory infection (ARI), especially in elderly subjects who are at increased risk of poor outcomes. METHODS We retrospectively analyzed risk factors and outcomes of individuals ≥ 60 years of age presenting to the emergency department with a clinical diagnosis of ARI. RESULTS Of 276 individuals in the study, 40 had proven viral infection and 52 proven bacterial infection, but 184 patients with clinically adjudicated ARI (67%) remained without a proven microbial etiology despite extensive clinical (and expanded research) workup. Patients who were older, had multiple comorbidities, or who had proven bacterial infection were more likely to require hospital and ICU admission. We identified a novel model based on 11 demographic and clinical variables that were significant risk factors for ICU admission or mortality in elderly subjects with all-cause ARI. As comparators, a modified PORT score was found to correlate more closely with all-cause ARI severity than a modified CURB-65 score (r, 0.54, 0.39). Interestingly, modified Jackson symptom scores were found to inversely correlate with severity (r, - 0.34) but show potential for differentiating viral and bacterial etiologies. CONCLUSIONS Modified PORT, CURB-65, Jackson symptom scores, and a novel ARI scoring tool presented herein all offer predictive ability for all-cause ARI in elderly subjects. Such broadly applicable scoring metrics have the potential to assist in treatment and triage decisions at the point of care.
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Affiliation(s)
| | - Sunil Suchindran
- Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC, USA
| | - Julie Steinbrink
- Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
| | - Micah T McClain
- Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC, USA.
- Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
- Durham Veteran's Affairs Medical Center, Durham, NC, USA.
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Schmidt de Oliveira-Netto AC, Morello LG, Dalla-Costa LM, Petterle RR, Fontana RM, Conte D, Pereira LA, Raboni SM. Procalcitonin, C-Reactive Protein, Albumin, and Blood Cultures as Early Markers of Sepsis Diagnosis or Predictors of Outcome: A Prospective Analysis. CLINICAL PATHOLOGY 2019; 12:2632010X19847673. [PMID: 31245791 PMCID: PMC6582287 DOI: 10.1177/2632010x19847673] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 04/09/2019] [Indexed: 11/23/2022]
Abstract
Purpose: Sepsis is a condition with high mortality rates and its diagnosis remains a challenge. We assessed epidemiological, clinical data, multiple biomarker profiles, and blood culture with respect to sepsis diagnosis and predictors of outcome. Methods: In total, 183 patients who were suspected of having sepsis and underwent blood culture collection were followed up for 7 days. Sepsis-related Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated daily; biomarkers and blood culture test results were evaluated. Results: In total, 78 (43%) had sepsis, 50 (27%) had septic shock, and 55 (30%) had no sepsis. Blood culture was positive in 28% and 42% of the sepsis and septic shock groups, respectively (P < .001). Regarding clinical profiles and biomarker values, there were no differences between the sepsis and non-sepsis groups, but significant differences were observed in the septic shock group. Multivariate logistic regression models revealed that age, serum albumin level, APACHE II, and SOFA 1st day scores were the independent variables for death. Conclusions: The challenge in the diagnosis of sepsis continues as clinical and laboratory differences found between the groups were due to septic shock. Older aged patients with lower albumin levels and higher APACHE II and SOFA 1st day scores have a greater probability of mortality.
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Affiliation(s)
| | - Luis G Morello
- Instituto de Biologia Molecular do Paraná, Curitiba, Brazil.,Laboratory of Applied Science and Technology in Health (LASTH), Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, Brazil
| | - Libera M Dalla-Costa
- Laboratory of Bacteriology, Universidade Federal do Paraná, Curitiba, Brazil.,Faculdades e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil
| | - Ricardo R Petterle
- Statistic, Setor de Ciências da Saúde, Universidade Federal do Paraná, Curitiba, Brazil
| | - Rafael M Fontana
- Infectious Disease Division, Universidade Federal do Paraná, Curitiba, Brazil
| | - Danieli Conte
- Laboratory of Applied Science and Technology in Health (LASTH), Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, Brazil
| | - Luciane A Pereira
- Laboratory of Applied Science and Technology in Health (LASTH), Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, Brazil
| | - Sonia M Raboni
- Postgraduate Program in Internal Medicine and Health Science, Universidade Federal do Paraná, Curitiba, Brazil.,Infectious Disease Division, Universidade Federal do Paraná, Curitiba, Brazil
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Lavoignet CE, Le Borgne P, Chabrier S, Bidoire J, Slimani H, Chevrolet-Lavoignet J, Lefebvre F, Jebri R, Sengler L, Bilbault P. White blood cell count and eosinopenia as valuable tools for the diagnosis of bacterial infections in the ED. Eur J Clin Microbiol Infect Dis 2019; 38:1523-1532. [PMID: 31119578 DOI: 10.1007/s10096-019-03583-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 05/06/2019] [Indexed: 12/29/2022]
Abstract
Identifying an infection may be difficult in the ED. Neutrophilic leukocytosis is often used in the diagnosis of infection despite its lack of specificity in situations of stress. Our objective was to study the value of each parameter of the WBC count, in particular eosinopenia, to diagnose bacterial infections in the ED. We conducted a retrospective and observational study over a period of 6 months. All patients with one of the following diagnoses were eligible: pneumonia (9.9%), pyelonephritis (26.2%), prostatitis (8.4%), appendicitis (26.2%), cholecystitis (8.4%), and diverticular sigmoiditis (5%). A total of 466 infected patients were included for statistical analysis, and a control group of 466 uninfected patients was randomly selected in the same period of time. All leukocyte count parameters were significantly modified (p < 0.001) in the infected group compared with the control group. Neutrophils and total leukocytes remain the two most suitable parameters for the diagnosis of infections in the ED. Eosinopenia represented the most efficient parameter of the WBC count for the diagnosis of urinary and biliary tract infections. Deep eosinopenia presented a specificity of 94% for the diagnosis of infection. Any modification of the WBC count associated with an elevation of CRP (> 40 mg/L) or fever (> 38.5 °C) showed a high specificity for the diagnosis of infection. A careful analysis of the WBC count remains a valuable tool for the diagnosis of infection in the ED.
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Affiliation(s)
- Charles-Eric Lavoignet
- Emergency Department, Nord Franche-Comté Hospital, Trevenans, France
- Emergency Department, Hautepierre Hospital, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France
- CREMS: Clinical Research in Emergency Medicine and Sepsis Network, Wolfisheim, France
| | - Pierrick Le Borgne
- Emergency Department, Hautepierre Hospital, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France.
- CREMS: Clinical Research in Emergency Medicine and Sepsis Network, Wolfisheim, France.
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative NanoMedicine (RNM), Fédération de Médecine Translationnelle (FMTS), University of Strasbourg, Strasbourg, France.
| | - Sylvie Chabrier
- Emergency Department, Hautepierre Hospital, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France
| | - Joffrey Bidoire
- Emergency Department, Nord Franche-Comté Hospital, Trevenans, France
| | - Hakim Slimani
- Emergency Department, Nord Franche-Comté Hospital, Trevenans, France
| | | | - François Lefebvre
- Department of Public Health, University Hospital of Strasbourg, Strasbourg, France
| | - Rania Jebri
- Emergency Department, Erasme Hospital, Anderlecht, Belgium
| | - Luc Sengler
- Emergency Department, Nord Franche-Comté Hospital, Trevenans, France
| | - Pascal Bilbault
- Emergency Department, Hautepierre Hospital, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France
- CREMS: Clinical Research in Emergency Medicine and Sepsis Network, Wolfisheim, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative NanoMedicine (RNM), Fédération de Médecine Translationnelle (FMTS), University of Strasbourg, Strasbourg, France
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Larian N, Ensor M, Thatcher SE, English V, Morris AJ, Stromberg A, Cassis LA. Pseudomonas aeruginosa-derived pyocyanin reduces adipocyte differentiation, body weight, and fat mass as mechanisms contributing to septic cachexia. Food Chem Toxicol 2019; 130:219-230. [PMID: 31078726 DOI: 10.1016/j.fct.2019.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/07/2019] [Accepted: 05/08/2019] [Indexed: 12/29/2022]
Abstract
Pseudomonas aeruginosa, a leading cause of sepsis, produces pyocyanin, a blue-pigmented virulence factor. Sepsis is associated with cachexia, but mechanisms are unknown and conventional nutrition approaches are not effective treatments. Pyocyanin has affinity for the aryl hydrocarbon receptor (AhR), which is expressed on adipocytes and regulates adipocyte differentiation. The purpose of this study was to define in vitro and in vivo effects of pyocyanin on adipocyte differentiation and body weight regulation as relates to septic cachexia. In 3T3-L1 preadipocytes, pyocyanin activated AhR and its downstream marker CYP1a1, and reduced differentiation. Administration of pyocyanin to male C57BL/6J mice acutely reduced body temperature with altered locomotion, but caused sustained weight loss. Chronic pyocyanin administration to male and female C57BL/6J mice resulted in sustained reductions in body weight and fat mass, with adipose-specific AhR activation. Pyocyanin-treated male mice had decreased energy expenditure and physical activity, and increased adipose explant lipolysis. In females, pyocyanin caused robust reductions in body weight, adipose-specific AhR activation, and increased expression of inflammatory cytokines in differentiated adipocytes. These results demonstrate that pyocyanin reduces adipocyte differentiation and decreases body weight and fat mass in male and female mice, suggesting that pyocyanin may play a role in septic cachexia.
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Affiliation(s)
- Nika Larian
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA
| | - Mark Ensor
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA
| | - Sean E Thatcher
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA
| | - Victoria English
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA
| | - Andrew J Morris
- Department of Internal Medicine,University of Kentucky, Lexington, KY, USA
| | - Arnold Stromberg
- Department of Statistics, University of Kentucky, Lexington, KY, USA
| | - Lisa A Cassis
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
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Molano Franco D, Arevalo‐Rodriguez I, Roqué i Figuls M, Montero Oleas NG, Nuvials X, Zamora J. Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults. Cochrane Database Syst Rev 2019; 4:CD011811. [PMID: 31038735 PMCID: PMC6490303 DOI: 10.1002/14651858.cd011811.pub2] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The definition of sepsis has evolved over time, along with the clinical and scientific knowledge behind it. For years, sepsis was defined as a systemic inflammatory response syndrome (SIRS) in the presence of a documented or suspected infection. At present, sepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Even though sepsis is one of the leading causes of mortality in critically ill patients, and the World Health Organization (WHO) recognizes it as a healthcare priority, it still lacks an accurate diagnostic test. Determining the accuracy of interleukin-6 (IL-6) concentrations in plasma, which is proposed as a new biomarker for the diagnosis of sepsis, might be helpful to provide adequate and timely management of critically ill patients, and thus reduce the morbidity and mortality associated with this condition. OBJECTIVES To determine the diagnostic accuracy of plasma interleukin-6 (IL-6) concentration for the diagnosis of bacterial sepsis in critically ill adults. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 25 January 2019. We screened references in the included studies to identify additional studies. We did not apply any language restriction to the electronic searches. SELECTION CRITERIA We included diagnostic accuracy studies enrolling critically ill adults aged 18 years or older under suspicion of sepsis during their hospitalization, where IL-6 concentrations were evaluated by serological measurement. DATA COLLECTION AND ANALYSIS Two review authors independently screened the references to identify relevant studies and extracted data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity using the HSROC model parameters. We conducted all analyses in the SAS statistical software package and R software. MAIN RESULTS We included 23 studies (n = 4192) assessing the accuracy of IL-6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS-2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL-6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above. AUTHORS' CONCLUSIONS Our evidence assessment of plasma interleukin-6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin-6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included.
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Affiliation(s)
- Daniel Molano Franco
- Fundacion Universitaria de Ciencias de la Salud, Hospital de San JoséDepartment of Critical CareCarrera 19 # 8‐32BogotaBogotaColombia11001
| | - Ingrid Arevalo‐Rodriguez
- Hospital Universitario Ramón y Cajal (IRYCIS). CIBER Epidemiology and Public Health (CIBERESP)Clinical Biostatistics UnitCtra. Colmenar Km. 9,100MadridSpain28034
- Cochrane Associate Centre of MadridMadridSpain
- Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTECentro Asociado Cochrane de EcuadorQuitoEcuador
| | - Marta Roqué i Figuls
- CIBER Epidemiología y Salud Pública (CIBERESP)Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau)Sant Antoni Maria Claret 171Edifici Casa de ConvalescènciaBarcelonaCatalunyaSpain08041
| | - Nadia G Montero Oleas
- Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTECentro Asociado Cochrane de EcuadorQuitoEcuador
| | - Xavier Nuvials
- Hospital Vall d’HebronDepartment of Critical Care MedicinePasseig Vall d’Hebron 119‐129BarcelonaSpain08035
- Vall d'Hebron Institut de Recerca (VHIR)SODIR research groupBarcelonaSpain
| | - Javier Zamora
- Cochrane Associate Centre of MadridMadridSpain
- Women’s Health Research Unit, Centre for Primary Care and Public Health, Queen Mary University of LondonLondonUK
- Hospital Universitario Ramon y Cajal (IRYCIS). CIBER Epidemiology and Public Health (CIBERESP)Clinical Biostatistics UnitMadridSpain
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Manrique Abril F, Mendez Fandiño Y, Herrera-Amaya G, Rodriguez J, Manrique-Abril R. Uso de procalcitonina como diagnóstico de sepsis o shock séptico: revisión sistemática y metaanálisis. INFECTIO 2019. [DOI: 10.22354/in.v23i2.769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Introducción: La procalcitonina (PCT) es una prohormona de la calcitonina, producida por las células C de la glándula tiroides y convertida intracelularmente por enzimas proteolíticas en la hormona activa. La producción de PCT durante procesos inflamatorios, está ligada a endotoxinas bacterianas y a citoquinas inflamatorias. La mortalidad por sepsis, depende en gran medida de la detección precoz y del inicio de una terapia adecuada, incluyendo la administración de antibióticos apropiados, sin embargo, no está claro si el rendimiento diagnóstico de la PCT en el contexto de la nueva definición de sepsis en el tercer consenso es igual que con la definición previa.Métodos: Se incluyeron estudios que describieran el uso de PCT dentro de las primeras 24 horas de admisión, como prueba diagnóstica de sepsis. Se realizó la búsqueda en las bases de datos de Medline (Pubmed) y Embase. La calidad metodológica se evaluó según la Colaboración Cochrane en el desarrollo de Revisiones Sistemáticas sobre Test de Análisis para la herramienta QUADAS-II. El sesgo de publicación fue estudiado con el Test de Asimetría de Deeks. Se usó el módulo de MIDAS de STATA 14 para el análisis univariado y la construcción de la Curva de ROC.Resultados: Se obtuvieron 2076 registros (783 de Medline y 1293 de Embase). De los 12 estudios seleccionados, se incluyeron un total de 1353 pacientes, con una prevalencia en los estudios revisados entre el 9% y 88%, con un promedio del 47%. La Sensibilidad agrupada fue 0,83% (IC95% (0,74-0,89)) y la Especificidad fue 0,84% (IC95%(0,76-0,89)). El área bajo la Curva fue 0,90 (IC95%(0,87-0,92)). La heterogeneidad entre los estudios es importante I2 88% (IC95%(77-100)). Existe un sesgo de publicación según el test de Deek, con resultado P=0,04. En el análisis sobre la Probabilidad Post test según el nomograma de Fagan, es del 56%, teniendo en cuenta una probabilidad pretest del 20% según el LR positivo 5.Conclusión: La PCT es una prueba diagnóstica con buen rendimiento para sepsis o shock séptico, en pacientes adultos, no gestantes. Aunque hay sesgo de publicación y una gran heterogeneidad en los resultados, la prueba se considera adecuada para el escenario de sepsis según las nuevas definiciones.
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Zhu X, Meyers A, Long D, Ingram B, Liu T, Yoza BK, Vachharajani V, McCall CE. Frontline Science: Monocytes sequentially rewire metabolism and bioenergetics during an acute inflammatory response. J Leukoc Biol 2019; 105:215-228. [PMID: 30633362 DOI: 10.1002/jlb.3hi0918-373r] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/26/2018] [Accepted: 12/12/2018] [Indexed: 12/13/2022] Open
Abstract
Metabolism directs the severe acute inflammatory reaction of monocytes to guard homeostasis. This occurs by sequentially activating anabolic immune effector mechanisms, switching to immune deactivation mechanisms and then restoring immunometabolic homeostasis. Nuclear sirtuin 1 and mitochondrial pyruvate dehydrogenase kinase metabolically drive this dynamic and are druggable targets that promote immunometabolic resolution in septic mice and increase survival. We used unbiased metabolomics and a validated monocyte culture model of activation, deactivation, and partial resolution of acute inflammation to sequentially track metabolic rewiring. Increases in glycogenolysis, hexosamine, glycolysis, and pentose phosphate pathways were aligned with anabolic activation. Activation transitioned to combined lipid, protein, amino acid, and nucleotide catabolism during deactivation, and partially subsided during early resolution. Lipid metabolic rewiring signatures aligned with deactivation included elevated n-3 and n-6 polyunsaturated fatty acids and increased levels of fatty acid acylcarnitines. Increased methionine to homocysteine cycling increased levels of s-adenosylmethionine rate-limiting transmethylation mediator, and homocysteine and cysteine transsulfuration preceded increases in glutathione. Increased tryptophan catabolism led to elevated kynurenine and de novo biosynthesis of nicotinamide adenine dinucleotide from quinolinic acid. Increased branched-chain amino acid catabolism paralleled increases in succinyl-CoA. A rise in the Krebs cycle cis-aconitate-derived itaconate and succinate with decreased fumarate and acetyl-CoA levels occurred concomitant with deactivation and subsided during early resolution. The data suggest that rewiring of metabolic and mitochondrial bioenergetics by monocytes sequentially activates, deactivates, and resolves acute inflammation.
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Affiliation(s)
- Xuewei Zhu
- Department of Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.,Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Allison Meyers
- Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - David Long
- Department of Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Brian Ingram
- Metabolon, Inc., Morrisville, North Carolina, USA
| | - Tiefu Liu
- Department of Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Barbara K Yoza
- Department of Surgery/General Surgery and Trauma, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Vidula Vachharajani
- Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Charles E McCall
- Department of Internal Medicine/Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.,Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
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45
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Duplessis C, Gregory M, Frey K, Bell M, Truong L, Schully K, Lawler J, Langley RJ, Kingsmore SF, Woods CW, Rivers EP, Jaehne AK, Quackenbush EB, Fowler VG, Tsalik EL, Clark D. Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis. J Intensive Care 2018; 6:72. [PMID: 30459950 PMCID: PMC6234551 DOI: 10.1186/s40560-018-0341-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 10/10/2018] [Indexed: 11/10/2022] Open
Abstract
Background Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. Methods The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. Results Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. Conclusions To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool.
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Affiliation(s)
- Christopher Duplessis
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Michael Gregory
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Kenneth Frey
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Matthew Bell
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Luu Truong
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Kevin Schully
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - James Lawler
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
| | - Raymond J Langley
- 2Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, USA
| | - Stephen F Kingsmore
- 3Rady Pediatric Genomic and Systems Medicine Institute, Rady Children's Hospital, Encinitas, USA
| | - Christopher W Woods
- 4Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, USA.,5Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, USA.,6Section on Infectious Diseases, Durham Veteran's Affairs Medical Center, Durham, USA
| | - Emanuel P Rivers
- 7Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, USA
| | - Anja K Jaehne
- 7Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, USA
| | - Eugenia B Quackenbush
- 8Department of Emergency Medicine, University of North Carolina Health Care, Chapel Hill, USA
| | - Vance G Fowler
- 4Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, USA
| | - Ephraim L Tsalik
- 4Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, USA.,5Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, USA.,9Emergency Medicine Service, Durham Veteran's Affairs Medical Center, Durham, USA
| | - Danielle Clark
- 1Biological Defense Research Directorate, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910 USA
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Langley RJ, Wong HR. Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward? Mol Diagn Ther 2018. [PMID: 28624903 DOI: 10.1007/s40291-017-0282-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Sepsis remains one of the leading causes of death in the USA and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug-resistant organisms. There is a dire need for the development of new antibiotics, improved antibiotic stewardship, and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic, and proteomic platforms have allowed for a broad-spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic datasets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis.
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Affiliation(s)
- Raymond J Langley
- Department of Pharmacology, University of South Alabama, Mobile, AL, USA
| | - Hector R Wong
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. .,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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47
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Tsalik EL, Bonomo RA, Fowler VG. New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance. Annu Rev Med 2018; 69:379-394. [PMID: 29414265 PMCID: PMC6214178 DOI: 10.1146/annurev-med-052716-030320] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. Host-focused diagnostics have recently emerged and are based on detecting the activation of biological pathways that are highly specific to the type of infecting pathogen (e.g., viral, bacterial, protozoan, fungal). Although this progress is encouraging, it is unlikely that any single diagnostic platform will fully address the clinician's need for actionable data with short turnaround times in all settings.
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Affiliation(s)
- Ephraim L Tsalik
- Division of Infectious Diseases & International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710
- Emergency Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina 27705
| | - Robert A Bonomo
- Medical and Research Services, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106
- Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
| | - Vance G Fowler
- Division of Infectious Diseases & International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710
- Duke Clinical Research Institute, Durham, North Carolina 27705;
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48
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Procalcitonin May Not Discriminate Between Sepsis and Non-Infective Systemic Inflammatory Response Syndrome (SIRS) in Heterogonous Critically Ill Patients. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2018. [DOI: 10.5812/archcid.55618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Wilson J, Baskerville J, Zarabi S. BET 2: Can procalcitonin accurately diagnose serious bacterial infection in emergency department patients with SIRS? Emerg Med J 2017; 34:622-624. [PMID: 28827294 DOI: 10.1136/emermed-2017-207038.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
A shortcut review was carried out to establish whether serum procalcitonin levels can be used to identify serious bacterial infection in ED patients with undifferentiated SIRS. 14 papers presented the best evidence to answer the clinical question. The review concludes that raised procalcitonin levels are associated with bacteraemia; however, there are no clinical management studies addressing this question in ED patients with SIRS.
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Affiliation(s)
- Joel Wilson
- Christus Spohn Memorial Hospital, Corpus Christi, Texas, USA
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50
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Bhattacharya S, Rosenberg AF, Peterson DR, Grzesik K, Baran AM, Ashton JM, Gill SR, Corbett AM, Holden-Wiltse J, Topham DJ, Walsh EE, Mariani TJ, Falsey AR. Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness. Sci Rep 2017; 7:6548. [PMID: 28747714 PMCID: PMC5529430 DOI: 10.1038/s41598-017-06738-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 06/16/2017] [Indexed: 02/02/2023] Open
Abstract
Lower respiratory tract infection (LRTI) commonly causes hospitalization in adults. Because bacterial diagnostic tests are not accurate, antibiotics are frequently prescribed. Peripheral blood gene expression to identify subjects with bacterial infection is a promising strategy. We evaluated whole blood profiling using RNASeq to discriminate infectious agents in adults with microbiologically defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical data and blood was collected, and comprehensive microbiologic testing performed. Gene expression was measured using RNASeq and qPCR. Genes discriminatory for bacterial infection were identified using the Bonferroni-corrected Wilcoxon test. Constrained logistic models to predict bacterial infection were fit using screened LASSO. We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.
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Affiliation(s)
- Soumyaroop Bhattacharya
- Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, Department of Pediatrics, University of Rochester School Medicine, Rochester, NY, USA
| | - Alex F Rosenberg
- Division of Allergy Immunology & Rheumatology, Department of Medicine, University of Rochester School Medicine, Rochester, NY, USA
| | - Derick R Peterson
- Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA
| | - Katherine Grzesik
- Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA
| | - Andrea M Baran
- Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA
| | - John M Ashton
- Genomics Research Center, University of Rochester School Medicine, Rochester, NY, USA
| | - Steven R Gill
- Genomics Research Center, University of Rochester School Medicine, Rochester, NY, USA
| | - Anthony M Corbett
- Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA
| | - Jeanne Holden-Wiltse
- Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA
| | - David J Topham
- David H. Smith Center for Vaccine Biology and Immunology, University of Rochester School Medicine, Rochester, NY, USA.,Department of Microbiology and Immunology, University of Rochester School Medicine, Rochester, NY, USA
| | - Edward E Walsh
- Division of Infectious Diseases, Department of Medicine, University of Rochester School Medicine and Rochester General Hospital, Rochester, NY, USA
| | - Thomas J Mariani
- Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, Department of Pediatrics, University of Rochester School Medicine, Rochester, NY, USA
| | - Ann R Falsey
- Division of Infectious Diseases, Department of Medicine, University of Rochester School Medicine and Rochester General Hospital, Rochester, NY, USA.
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