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      Acute organ injury and long-term sequelae of severe pneumococcal infections

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          Abstract

          Streptococcus pneumoniae ( Spn) is a major public health problem, as it is a main cause of otitis media, community-acquired pneumonia, bacteremia, sepsis, and meningitis. Acute episodes of pneumococcal disease have been demonstrated to cause organ damage with lingering negative consequences. Cytotoxic products released by the bacterium, biomechanical and physiological stress resulting from infection, and the corresponding inflammatory response together contribute to organ damage accrued during infection. The collective result of this damage can be acutely life-threatening, but among survivors, it also contributes to the long-lasting sequelae of pneumococcal disease. These include the development of new morbidities or exacerbation of pre-existing conditions such as COPD, heart disease, and neurological impairments. Currently, pneumonia is ranked as the 9 th leading cause of death, but this estimate only considers short-term mortality and likely underestimates the true long-term impact of disease. Herein, we review the data that indicates damage incurred during acute pneumococcal infection can result in long-term sequelae which reduces quality of life and life expectancy among pneumococcal disease survivors.

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          Most cited references363

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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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            The NLRP3 inflammasome: molecular activation and regulation to therapeutics

            NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
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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
                corihuel@uab.edu
                Journal
                Pneumonia (Nathan)
                Pneumonia (Nathan)
                Pneumonia
                BioMed Central (London )
                2200-6133
                5 March 2023
                5 March 2023
                2023
                : 15
                : 5
                Affiliations
                [1 ]GRID grid.265892.2, ISNI 0000000106344187, Department of Microbiology, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [2 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, McMaster Immunology Research Centre and the Firestone Institute for Respiratory Health, , McMaster University, ; Hamilton, Canada
                Article
                110
                10.1186/s41479-023-00110-y
                9985869
                36870980
                a5e80cf8-e0f6-4b74-b34f-7fe1a8cc0486
                © The Author(s) 2023

                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
                : 3 September 2022
                : 31 January 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01AI114800-08
                Award ID: R01AI114800-08
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2023

                streptococcus pneumoniae,pneumonia,invasive pneumococcal disease (ipd),organ injury,inflammation,pneumolysin,sequelae,adverse cardiac events,acute kidney injury,mortality

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