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      Novel Diagnostics and Therapeutics in Sepsis

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          Abstract

          Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation. Currently employed diagnostic tools are ill-equipped to rapidly diagnose sepsis and isolate the offending pathogen, which limits the ability to offer targeted and lowest-toxicity treatment. Cutting edge diagnostics and therapeutics in development may improve time to diagnosis and address two broad management principles: (1) source control by removing the molecular infectious stimulus of sepsis, and (2) attenuation of the pathological immune response allowing the body to heal. This review addresses novel diagnostics and therapeutics and their role in the management of sepsis.

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          Most cited references157

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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
                Role: Academic Editor
                Journal
                Biomedicines
                Biomedicines
                biomedicines
                Biomedicines
                MDPI
                2227-9059
                18 March 2021
                March 2021
                : 9
                : 3
                : 311
                Affiliations
                [1 ]Division of Pulmonary & Critical Care, University of Maryland School of Medicine, Baltimore, MD 21201, USA; kleong@ 123456som.umaryland.edu
                [2 ]Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest University Hospital, Winston-Salem, NC 27157, USA; bgaglani@ 123456wakehealth.edu (B.G.); ashish@ 123456or.org (A.K.K.)
                [3 ]Department of Outcomes Research, Outcomes Research Consortium, Cleveland, OH 44195, USA
                Author notes
                [* ]Correspondence: drmccurdy@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-5620-9888
                Article
                biomedicines-09-00311
                10.3390/biomedicines9030311
                8003067
                33803628
                73a10b4a-aaef-4b70-aeb5-e366d313a073
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 February 2021
                : 16 March 2021
                Categories
                Review

                sepsis,novel,diagnosis,diagnostics,therapy,therapeutic,treatment,management,biomarkers,innovation

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