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      Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

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          Highlights

          • This review highlights pathogenesis and clinical challenges of sepsis.

          • Advantages of different types of nanoplatforms are presented, and the rationality of nanoplatforms in sepsis management is analyzed.

          • Advances of nanoplatforms in diagnosis and therapy of sepsis are systematically summarized, and ongoing challenges and future perspectives are discussed.

          Abstract

          Sepsis, a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection, is a leading contributor to mortality in intensive care units. Sepsis-related deaths have been reported to account for 19.7% of all global deaths. However, no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis. Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis. Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry, targeting infection and/or imbalanced immune responses, have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment. Nanoplatforms can overcome the barriers faced by clinical strategies, including delayed diagnosis, drug resistance and incapacity to manage immune disorders. Here, we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts, summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies. Based on these state-of-the-art studies, this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.

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          Most cited references266

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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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            Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study

            Summary Background Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. Methods We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. Findings In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Interpretation Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. Funding The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
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              Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

              To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".
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                Author and article information

                Contributors
                shuqiang@zju.edu.cn
                xmfang@zju.edu.cn
                Journal
                Nanomicro Lett
                Nanomicro Lett
                Nano-Micro Letters
                Springer Singapore (Singapore )
                2311-6706
                2150-5551
                8 March 2021
                8 March 2021
                December 2021
                : 13
                : 88
                Affiliations
                [1 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, School of Medicine, , Zhejiang University, ; Hangzhou, 310003 People’s Republic of China
                [2 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, National Clinical Research Center for Child Health, Children’s Hospital, School of Medicine, , Zhejiang University, ; Hangzhou, 310052 People’s Republic of China
                Article
                598
                10.1007/s40820-021-00598-3
                7938387
                33717630
                ad973cdf-0ad2-431d-af1f-05ae79e3370a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 October 2020
                : 14 December 2020
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                sepsis,nanoplatform,detection,immune homeostasis
                sepsis, nanoplatform, detection, immune homeostasis

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