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      Diagnostic and therapeutic value of biomarkers in urosepsis

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          Abstract

          Urosepsis is sepsis caused by urogenital tract infection and is one of the most common critical illnesses in urology. If urosepsis is not diagnosed early, it can rapidly progress and worsen, leading to increased mortality. In recent years, with the increase of urinary tract surgery, the incidence of urosepsis continues to rise, posing a serious threat to patients. Early diagnosis of urosepsis, timely and effective treatment can greatly reduce the mortality of patients. Biomarkers such as WBC, NLR, PCT, IL-6, CRP, lactate, and LncRNA all play specific roles in the early diagnosis or prognosis of urosepsis. In addition to the abnormal increase of WBC, we should be more alert to the rapid decline of WBC. NLR values were superior to WBC counts alone in predicting infection severity. Compared with several other biomarkers, PCT values can differentiate between bacterial and non-bacterial sepsis. IL-6 always has high sensitivity and specificity for the diagnosis of sepsis, and CRP also has high sensitivity and specificity for the diagnosis of urosepsis. Lactic acid is closely related to the prognosis of patients with urosepsis. LncRNAs may be potential biomarkers of urosepsis. This article summarizes the main biomarkers, hoping to provide a reference for the timely diagnosis and evaluation of urosepsis.

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          Most cited references95

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            IL-6 in inflammation, immunity, and disease.

            Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
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              Role of C-Reactive Protein at Sites of Inflammation and Infection

              C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation. CRP is produced as a homopentameric protein, termed native CRP (nCRP), which can irreversibly dissociate at sites of inflammation and infection into five separate monomers, termed monomeric CRP (mCRP). CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes. Evidence suggests that estrogen in the form of hormone replacement therapy influences CRP levels in the elderly. Having been traditionally utilized as a marker of infection and cardiovascular events, there is now growing evidence that CRP plays important roles in inflammatory processes and host responses to infection including the complement pathway, apoptosis, phagocytosis, nitric oxide (NO) release, and the production of cytokines, particularly interleukin-6 and tumor necrosis factor-α. Unlike more recent publications, the findings of early work on CRP can seem somewhat unclear and at times conflicting since it was often not specified which particular CRP isoform was measured or utilized in experiments and whether responses attributed to nCRP were in fact possibly due to dissociation into mCRP or lipopolysaccharide contamination. In addition, since antibodies for mCRP are not commercially available, few laboratories are able to conduct studies investigating the mCRP isoform. Despite these issues and the fact that most CRP research to date has focused on vascular disorders, there is mounting evidence that CRP isoforms have distinct biological properties, with nCRP often exhibiting more anti-inflammatory activities compared to mCRP. The nCRP isoform activates the classical complement pathway, induces phagocytosis, and promotes apoptosis. On the other hand, mCRP promotes the chemotaxis and recruitment of circulating leukocytes to areas of inflammation and can delay apoptosis. The nCRP and mCRP isoforms work in opposing directions to inhibit and induce NO production, respectively. In terms of pro-inflammatory cytokine production, mCRP increases interleukin-8 and monocyte chemoattractant protein-1 production, whereas nCRP has no detectable effect on their levels. Further studies are needed to expand on these emerging findings and to fully characterize the differential roles that each CRP isoform plays at sites of local inflammation and infection.
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                Author and article information

                Contributors
                Role: Writing - original draft
                Role: InvestigationRole: MethodologyRole: Writing - original draft
                Role: Writing - original draft
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Resources
                Role: Formal analysisRole: MethodologyRole: Resources
                Role: Writing - review & editing
                Role: Writing - review & editing
                Role: SupervisionRole: Writing - review & editing
                Journal
                Ther Adv Urol
                Ther Adv Urol
                TAU
                sptau
                Therapeutic Advances in Urology
                SAGE Publications (Sage UK: London, England )
                1756-2872
                1756-2880
                31 January 2023
                Jan-Dec 2023
                : 15
                : 17562872231151852
                Affiliations
                [1-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [2-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [3-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [4-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [5-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [6-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
                [7-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dian-Mian Avenue, Kunming 650101, Yunnan, P.R. China
                [8-17562872231151852]The Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dian-Mian Avenue, Kunming 650101, Yunnan, P.R. China
                Author notes
                [*]

                Yuyun Wu and Guang Wang to contribute equally to this article.

                Author information
                https://orcid.org/0000-0002-6358-9559
                Article
                10.1177_17562872231151852
                10.1177/17562872231151852
                9893402
                36744043
                319fa425-6bc4-4575-b388-a68c1a242f8a
                © The Author(s), 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 10 August 2022
                : 3 January 2023
                Funding
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 82160150
                Funded by: Yunnan Provincial Science and Technology Department, FundRef https://doi.org/10.13039/501100008871;
                Award ID: 2019FE001(-149)
                Funded by: Yunnan Provincial Science and Technology Department, FundRef https://doi.org/10.13039/501100008871;
                Award ID: 202001AY070001-062
                Funded by: Yunnan Provincial Science and Technology Department, FundRef https://doi.org/10.13039/501100008871;
                Award ID: 202105AF150063
                Funded by: Yunnan Provincial Science and Technology Department, FundRef https://doi.org/10.13039/501100008871;
                Award ID: H-2017045
                Categories
                Review
                Custom metadata
                January-December 2023
                ts1

                biomarkers,diagnosis,sepsis,urinary tract infection,urosepsis

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