Sepsis: the evolution of molecular pathogenesis concepts and clinical management

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 23, 2025

Abstract The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% the total global mortality. Since Lewis Thomas proposed in 1972 that “it our response makes disease (sepsis)” rather than invading microorganisms, numerous drugs have been developed to suppress “overwhelming” inflammatory response, but none them has achieved desired effect. Continued failure led investigators question whether deaths septic patients are indeed caused by uncontrolled inflammation. Here, we review history clinical trials based on evolving concepts pathogenesis over past half century, summarize factors these historical and prerequisites success future drugs, propose basic principles preclinical research ensure successful translation. strategy targeting like attempting eliminate invaders suppressing host's armed forces, which logically untenable. Sepsis may not be complex; rather, result a fight microbes when force an pathogen overwhelms defenses. Thus, strengthening body's defense forces instead correct overcome sepsis.

Language: Английский

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Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2028 - 2028

Published: Feb. 26, 2025

The human immune system is closely linked to microbiota such as a complex symbiotic relationship during the coevolution of vertebrates and microorganisms. transfer microorganisms from mother's newborn begins before birth gestation considered initial phase intestinal (IM). gut an important site where can establish colonies. IM contains polymicrobial communities, which show interactions with diet host immunity. tendency towards dysbiosis influenced by local but also extra-intestinal factors inflammatory processes, infections, or septic state that aggravate it. Pathogens could trigger response, proinflammatory responses. In addition, changes in influence community structure additional translocation pathogenic non-pathogenic bacteria. Finally, inflammation has been found be factor growth microorganisms, particularly its role sepsis. aim this article able detect current knowledge mechanisms lead cause bacterial risk infection vice versa.

Language: Английский

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Subphenotypes and the De Ritis ratio for mortality risk stratification in sepsis-associated acute liver injury: a retrospective cohort study

EClinicalMedicine, Journal Year: 2025, Volume and Issue: 82, P. 103173 - 103173

Published: March 29, 2025

Language: Английский

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Melatonin-Mediated Protection against Sepsis-Induced Organ Dysfunction

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Sepsis-induced organ dysfunction represents a critical challenge in intensive care medicine, characterized by complex pathophysiological mechanisms that can lead to multiple failure and death. This review examines the fundamental underlying sepsis-induced explores therapeutic potential of melatonin, multifaceted molecule with potent antioxidant anti-inflammatory properties. We analyzed pathways involved damage during sepsis, including inflammatory cascades, oxidative stress, mitochondrial dysfunction, endothelial injury. Special attention is given melatonin’s protective effects on various systems, cardiac, pulmonary, renal, hepatic, central nervous system function sepsis. Recent evidence suggests ability modulate these pathways, combined its excellent safety profile, makes it promising agent sepsis management. Understanding applications may provide new strategies for improving outcomes septic patients.

Language: Английский

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Organ crosstalk and dysfunction in Sepsis: harnessing emerging biotechnologies for future breakthroughs

Annals of Intensive Care, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 23, 2024

Language: Английский

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Development and validation of clinical criteria for critical illness-associated immune dysfunction: based on the MIMIC-IV database

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 11, 2024

Background Critical illness-associated immune dysfunction (CIID) is prevalent in the ICU and frequently resulted uncontrollably responses. immunological understood to be important, although there are currently no clinically accepted diagnostic criteria for it. Given this, we examined literature developed an initial criterion that validated using MIMIC-IV database. Methods We searched related last 32 years. Patients admitted first time were selected by screening Different used categorize patients into groups (ID) non-immune (NID). Within ID group, subdivided three subgroups: hyperinflammatory (HI), immunosuppression (IS), a subgroup combining hyperinflammation (HI+IS). The APACHE II was measure patients’ severity. association between mortality after 30 or 180 days evaluated through KM curves COX regression analysis. Results By summarizing relevant literature, proposed criteria. analysis included 43,965 patients, with approximately 77% meeting CIID. observed possessed higher scores differences peak among subgroups. When comparing 30-day model, it evident IS had lowest risk HI greatest accounting all covariates. In contrast, highest of death, those when long-term mortality. summary, propose validate Subgroup analyses carried out, which also revealed variations groups. Conclusion confirmed database, demonstrating scientifically valid reliable.

Language: Английский

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Gut Microbiota and Liver Dysfunction in Sepsis: The Role of Inflammatory Mediators and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13415 - 13415

Published: Dec. 14, 2024

Sepsis is a life-threatening complication caused by an uncontrolled immune response to infection that can lead multi-organ dysfunction, including liver injury. Recent research has shown the critical role of gut microbiota in sepsis pathogenesis, with gut–liver axis playing crucial disease progression. Mechanisms such as disruption barrier and injury pathways mediated cytokines, chemokines, adhesion molecules, hydrogen sulfide (H2S). substance P (SP) have been focus recent studies. Some potential biomarkers microbiota-targeted therapies promise emerging tools for predicting managing sepsis. This review describes biomarker-driven interventions improve outcomes.

Language: Английский

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