The immunology of sepsis

Immunity, Journal Year: 2021, Volume and Issue: 54(11), P. 2450 - 2464

Published: Nov. 1, 2021

Language: Английский

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Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: Oct. 9, 2022

Sepsis is a common complication of combat injuries and trauma, defined as life-threatening organ dysfunction caused by dysregulated host response to infection. It also one the significant causes death increased health care costs in modern intensive units. The use antibiotics, fluid resuscitation, support therapy have limited prognostic impact patients with sepsis. Although its pathophysiology remains elusive, immunosuppression now recognized major septic death. Sepsis-induced resulted from disruption immune homeostasis. characterized release anti-inflammatory cytokines, abnormal effector cells, hyperproliferation suppressor expression checkpoints. By targeting immunosuppression, especially checkpoint inhibitors, preclinical studies demonstrated reversal immunocyte dysfunctions established resistance. Here, we comprehensively discuss recent findings on mechanisms, regulation biomarkers sepsis-induced highlight their implications for developing effective strategies treat shock.

Language: Английский

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Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 165, P. 54 - 66

Published: Jan. 18, 2021

Language: Английский

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Advancing precision medicine for acute respiratory distress syndrome

The Lancet Respiratory Medicine, Journal Year: 2021, Volume and Issue: 10(1), P. 107 - 120

Published: July 23, 2021

Language: Английский

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Predicting sepsis severity at first clinical presentation: The role of endotypes and mechanistic signatures

EBioMedicine, Journal Year: 2022, Volume and Issue: 75, P. 103776 - 103776

Published: Jan. 1, 2022

BackgroundInter-individual variability during sepsis limits appropriate triage of patients. Identifying, at first clinical presentation, gene expression signatures that predict subsequent severity will allow clinicians to identify the most at-risk groups patients and enable antibiotic use.MethodsBlood RNA-Seq data were collected from 348 in four emergency rooms (ER) one intensive-care-unit (ICU), 44 healthy controls. Gene profiles analyzed using machine learning mining clinically relevant reflecting disease severity, organ dysfunction, mortality, specific endotypes/mechanisms.FindingsGene obtained predicted severity/organ dysfunction mortality both ER ICU with accuracy/AUC 77–80%. Network analysis revealed these formed a coherent biological program, but overlapping mechanisms/pathways. Given heterogeneity sepsis, we asked if could be assorted into discrete distinct mechanisms (endotypes) varying severity. Patients early stratified five novel mechanistic endotypes, named Neutrophilic-Suppressive/NPS, Inflammatory/INF, Innate-Host-Defense/IHD, Interferon/IFN, Adaptive/ADA, each based on ∼200 unique differences, pathways/mechanisms (e.g., IL6/STAT3 NPS). Endotypes had overall two severe (NPS/INF) relatively benign (ADA) groupings, consistent reanalysis previous endotype studies. A 40 gene-classification tool (accuracy=96%) several gene-pairs (accuracy=89–97%) accurately status validation cohorts.InterpretationThe indicate immune precede onset lethality, providing method

Language: Английский

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Immunopathophysiology of human sepsis

EBioMedicine, Journal Year: 2022, Volume and Issue: 86, P. 104363 - 104363

Published: Dec. 1, 2022

Language: Английский

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Sepsis Subclasses: A Framework for Development and Interpretation*

Critical Care Medicine, Journal Year: 2021, Volume and Issue: 49(5), P. 748 - 759

Published: Feb. 15, 2021

Sepsis is defined as a dysregulated host response to infection that leads life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because heterogeneous syndrome, characterized by vast set of clinical biologic features. Combinations these features, however, identify previously unrecognized groups, or “subclasses” with different risks outcome given treatment. As efforts subclasses become more common, many unanswered questions challenges arise. These include: 1) semantic underpinning subclasses, 2) conceptual goal 3) considerations about study design, data sources, statistical methods, 4) role emerging types, 5) how determine whether represent “truth.” We discuss present framework broader subclasses. intended aid in understanding interpretation provide mechanism explaining generated methodologic approaches, guide clinicians consider bedside care.

Language: Английский

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The pathophysiology of sepsis and precision-medicine-based immunotherapy

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(1), P. 19 - 28

Published: Jan. 1, 2024

Language: Английский

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Development and validation of novel sepsis subphenotypes using trajectories of vital signs

Intensive Care Medicine, Journal Year: 2022, Volume and Issue: 48(11), P. 1582 - 1592

Published: Sept. 24, 2022

Language: Английский

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Sepsis biomarkers and diagnostic tools with a focus on machine learning

EBioMedicine, Journal Year: 2022, Volume and Issue: 86, P. 104394 - 104394

Published: Dec. 1, 2022

Language: Английский

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