1. Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.
- Author
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Cajander S, Kox M, Scicluna BP, Weigand MA, Mora RA, Flohé SB, Martin-Loeches I, Lachmann G, Girardis M, Garcia-Salido A, Brunkhorst FM, Bauer M, Torres A, Cossarizza A, Monneret G, Cavaillon JM, Shankar-Hari M, Giamarellos-Bourboulis EJ, Winkler MS, Skirecki T, Osuchowski M, Rubio I, Bermejo-Martin JF, Schefold JC, and Venet F
- Subjects
- Humans, Artificial Intelligence, Goals, Algorithms, Precision Medicine methods, Sepsis diagnosis, Sepsis therapy
- Abstract
Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes., Competing Interests: Declaration of interests SC reports personal fees from Pfizer, AstraZeneca, Swedish Orphan Biovitrum (SOBI), GSK, and Merck Sharp & Dohme (MSD). MK reports personal fees from ARTCLINE, Atriva, AOP pharma, Inflammatix, and 4TEEN4; and discloses institutional funding from MediSieve, 4TEEN4, Adrenomed, Spinghotec, Cytosorbents, and Inflammatix. MAW reports personal fees from MSD, Gilead, Pfizer, Shionogi, Eumedica, Coulter, Biotest, Sedana, SOBI, and Böhringer; and patent EPA17198330 “Delta-Like Ligand 1 for diagnosing severe infections”. IM-L reports personal fees from MSD, Pfizer, and Gilead. GL reports personal fees from SOBI. EJG-B discloses institutional funding from Abbott, bioMérieux, InflaRx, Johnson & Johnson, MSD, SOBI, XBiotech, Horizon 2020 Marie Skłodowska-Curie International Training Network “the European Sepsis Academy”, Horizon 2020 European Grants ImmunoSep and RISCinCOVID, and Horizon Health European Grants EPIC-CROWN-2. MSW has received unrestricted funding from Sartorius and reports personal fees from GRIFOLS, Gilead, and Amomed. MO is president of the European Shock Society and Deputy Editor of Intensive Care Medicine Experimental. JFB-M reports personal fees from GSK, PROFARMA programme, Ministry of Industry Spain, GSK-MODUS programme, and Inflammatix; and patents on the following biomarkers related to management of severe infections: PCT/EP2018/064363 “MMP-8 as a marker for identifying infectious disease”, PCT/EP2018/052499 “Pro-ADM as marker indicating an adverse event”, WO2020030745 “Pro-ADM for prognosing the risk of a medical condition requiring hospitalisation in patients with symptoms of infectious disease”, and EP20383140.9 “In vitro method for predicting mortality in COVID-19 patients” (based on detecting N-antigenaemia of SARS-CoV-2 in plasma). JCS discloses institutional funding from Orion Pharma, Abbott Nutrition International, B Braun Medical, CSEM, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, Omnicare Clinical Research, Nestle, Pierre Fabre Pharma, Pfizer, Bard Medica, Abbott, Anandic Medical Systems, Pan Gas Healthcare, Bracco, Hamilton Medical, Fresenius Kabi, Getinge Group Maquet, Dräger, Teleflex Medical, GSK, MSD, Eli Lilly and Company, Baxter, Astellas, AstraZeneca, CSL Behring, Novartis, Covidien, Philips Medical, Prolong Pharmaceuticals and Nycomed, Phagenesis, and Cytel, outside of the submitted work. JCS is Chair of the Clinical Advisory Board of Hemotune. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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