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      Management of Sepsis and Septic Shock: What Have We Learned in the Last Two Decades?

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      Microorganisms
      MDPI AG

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          Abstract

          Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in developing and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management’s most important yet controversial components and summarize the available evidence from the last two decades.

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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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              Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America

              Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
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                Author and article information

                Contributors
                Journal
                MICRKN
                Microorganisms
                Microorganisms
                MDPI AG
                2076-2607
                September 2023
                September 04 2023
                : 11
                : 9
                : 2231
                Article
                10.3390/microorganisms11092231
                37764075
                c2843384-0b3b-4a3a-a5de-39696d70690d
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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