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Advances in Experimental Medicine and... 2020Multiple organ dysfunction syndrome (MODS), also referred to as external challenge-induced multiple organ injury, is characterized by dysfunction of two or more organs... (Review)
Review
Multiple organ dysfunction syndrome (MODS), also referred to as external challenge-induced multiple organ injury, is characterized by dysfunction of two or more organs during infection or following shock or trauma. The pathogenesis of MODS is multifactorial and involves systemic inflammation and cell stress responses including cell death; sepsis is defined as an infection with MODS. Gut microbiota contributes significantly to organ dysfunction and to the pathobiology of sepsis. However, the relationship between the development of sepsis and the composition of gut microbiota is equivocal and is only now starting to be elucidated. Recent studies by our group and others reveal that enteric microbial composition and function are disrupted during sepsis, and that microbial products can either promote or alleviate the progression of sepsis. Here, we summarize the current research on the functional link between gut microbiota and sepsis, and argue the point that gut microbiota is a potential therapeutic target in the management of sepsis.
Topics: Gastrointestinal Microbiome; Humans; Inflammation; Multiple Organ Failure; Sepsis
PubMed: 32323186
DOI: 10.1007/978-981-15-2385-4_11 -
Shock (Augusta, Ga.) Jul 2021Sepsis is a severe systemic response to infection; its ensuing organ failure commonly portends an unfavorable prognosis. Despite the fact that sepsis has been studied... (Review)
Review
Sepsis is a severe systemic response to infection; its ensuing organ failure commonly portends an unfavorable prognosis. Despite the fact that sepsis has been studied for decades, the molecular mechanisms underlying sepsis-induced organ dysfunction remain elusive and more complex than previously thought, and effective therapies are extremely limited. Calpain is a type of calcium-dependent cysteine protease that includes dozens of isoforms. Calpain, as well as its endogenous-specific inhibitor calpastatin, have been implicated in the pathogenesis of sepsis-induced organ dysfunction. Further, there is an accumulating body of evidence supporting the beneficial effect of calpain inhibition or regulation on multiple organ failure in sepsis. Better understanding of the underlying molecular mechanisms is helpful in the development of calpain/calpastatin-targeted therapeutic strategies to protect against sepsis-induced organ injury. The aim of this review is to summarize the recent literature and evidence surrounding the role of the calpain/calpastatin system in the process of organ dysfunction caused by sepsis-including regulation of cell death, modulation of inflammatory response, and disruption of critical proteins-to provide guidance for future research and therapy development.
Topics: Calpain; Humans; Multiple Organ Failure; Sepsis
PubMed: 33038189
DOI: 10.1097/SHK.0000000000001679 -
Acta Physiologica (Oxford, England) Feb 2020Acute kidney injury (AKI) is a common complication in critically ill patients and it is associated with increased morbidity and mortality. Epidemiological and clinical... (Review)
Review
Acute kidney injury (AKI) is a common complication in critically ill patients and it is associated with increased morbidity and mortality. Epidemiological and clinical data show that AKI is linked to a wide range of distant organ injuries, with the lungs, heart, liver, and intestines representing the most clinically relevant affected organs. This distant organ injury during AKI predisposes patients to progression to multiple organ dysfunction syndrome and ultimately, death. The strongest direct evidence of distant organ injury occurring in AKI has been obtained from animal models. The identified mechanisms include systemic inflammatory changes, oxidative stress, increases in leucocyte trafficking and the activation of proapoptotic pathways. Understanding the pathways driving AKI-induced distal organ injury are critical for the development and refinement of therapies for the prevention and attenuation of AKI-related morbidity and mortality. The purpose of this review is to summarize both clinical and preclinical studies of AKI and its role in distant organ injury.
Topics: Acute Kidney Injury; Animals; Humans; Multiple Organ Failure; Oxidative Stress
PubMed: 31379123
DOI: 10.1111/apha.13357 -
Medizinische Klinik, Intensivmedizin... May 2020Multiorgan failure is among the most frequent reasons of death in critically ill patients. Based on extensive and long-term use of renal replacement therapy,... (Review)
Review
Multiorgan failure is among the most frequent reasons of death in critically ill patients. Based on extensive and long-term use of renal replacement therapy, extracorporeal organ support became available for other organ failures. Initially, most of these techniques (e.g. extracorporeal membrane oxygenation, extracorporeal CO removal [ECCO2R] and extracorporeal liver support) were used as stand-alone single organ support systems. Considering multiple interactions between native organs ("crosstalk"), combined or integrated extracorporeal organ support (ECOS) devices are intriguing. The concept of multiple organ support therapy (MOST) providing simultaneous and combined support for different failing organs was described more than 15 years ago by Ronco and Bellomo. This concept also implicates overcoming the "compartmentalized" approach provided by different single organ specialized professionals by a multidisciplinary and multiprofessional strategy. The idea of MOST is supported by the failure of several recent studies on single organ support including liver and lung support. Improvement of outcome by ECOS necessarily depends on optimized patient selection, integrated organ support and limitation of its side effects. This implicates challenges for engineers, industry and healthcare professionals. From a technical viewpoint, modular combination of pre-existing technologies such as renal replacement, albumin-dialysis, ECCO2R and potentially cytokine elimination can be considered as a first step. While this allows for stepwise and individual combination of standard organ support facilities, it carries the disadvantage of large extracorporeal blood volume and surfaces as well as additive costs. The more intriguing next step is an integrated platform providing the capacity of multiple organ support within one device. (This article is freely available.).
Topics: Critical Illness; Extracorporeal Membrane Oxygenation; Humans; Multiple Organ Failure; Renal Dialysis; Renal Replacement Therapy
PubMed: 32095838
DOI: 10.1007/s00063-020-00658-3 -
European Journal of Medical Research Jul 2023Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin... (Review)
Review
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C.
Topics: Humans; Ascorbic Acid; Multiple Organ Failure; Sepsis; Oxidative Stress; Heart; Randomized Controlled Trials as Topic
PubMed: 37408078
DOI: 10.1186/s40001-023-01183-7 -
Biomolecules Dec 2022Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of... (Review)
Review
Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil's disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.
Topics: Humans; Weil Disease; Gastrointestinal Microbiome; Multiple Organ Failure; Leptospirosis; Liver
PubMed: 36551258
DOI: 10.3390/biom12121830 -
Pediatrics Jan 2022Since its introduction into the medical literature in the 1970s, the term multiple organ dysfunction syndrome (or some variant) has been applied broadly to any patient...
Since its introduction into the medical literature in the 1970s, the term multiple organ dysfunction syndrome (or some variant) has been applied broadly to any patient with >1 concurrent organ dysfunction. However, the epidemiology, mechanisms, time course, and outcomes among children with multiple organ dysfunction vary substantially. We posit that the term pediatric multiple organ dysfunction syndrome (or MODS) should be reserved for patients with a systemic pathologic state resulting from a common mechanism (or mechanisms) that affects numerous organ systems simultaneously. In contrast, children in whom organ injuries are attributable to distinct mechanisms should be considered to have additive organ system dysfunctions but not the syndrome of MODS. Although such differentiation may not always be possible with current scientific knowledge, we make the case for how attempts to differentiate multiple organ dysfunction from other states of additive organ dysfunctions can help to evolve clinical and research priorities in diagnosis, monitoring, and therapy from largely organ-specific to more holistic strategies.
Topics: Child; Critical Care; Critical Illness; Diagnosis, Differential; History, 20th Century; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970671
DOI: 10.1542/peds.2021-052888C -
The Journal of Trauma and Acute Care... May 2023Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time.
METHODS
Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable.
RESULTS
The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1-17.2%) in Denver score >3, 12.7% (95% CI, 9.3-16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12-45.1%) in Denver score >8, 25.6% (95% CI, 10.4-40.7%) in Goris score >4, 29.9% (95% CI, 14.9-45%) in Marshall score >5, 20.3% (95% CI, 9.4-31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33-44.3%) in SOFA score >3, 55.1% (95% CI, 49.7-60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7-40.8%) in SOFA score >5.
CONCLUSION
The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered.
LEVEL OF EVIDENCE
Systematic Review and Meta-analysis; Level III.
Topics: Humans; Adult; Multiple Organ Failure; Incidence; Multiple Trauma; Organ Dysfunction Scores; Wounds, Nonpenetrating
PubMed: 36809374
DOI: 10.1097/TA.0000000000003923 -
Injury Jul 2024
Topics: Humans; Multiple Organ Failure; Syndrome
PubMed: 38876542
DOI: 10.1016/j.injury.2024.111599 -
Critical Care (London, England) Dec 2022Acute kidney injury (AKI) is a common complication in sepsis. However, the trajectories of sepsis-induced AKI and their transcriptional profiles are not well...
BACKGROUND
Acute kidney injury (AKI) is a common complication in sepsis. However, the trajectories of sepsis-induced AKI and their transcriptional profiles are not well characterized.
METHODS
Sepsis patients admitted to centres participating in Chinese Multi-omics Advances In Sepsis (CMAISE) from November 2020 to December 2021 were enrolled, and gene expression in peripheral blood mononuclear cells was measured on Day 1. The renal function trajectory was measured by the renal component of the SOFA score (SOFA) on Days 1 and 3. Transcriptional profiles on Day 1 were compared between these renal function trajectories, and a support vector machine (SVM) was developed to distinguish transient from persistent AKI.
RESULTS
A total of 172 sepsis patients were enrolled during the study period. The renal function trajectory was classified into four types: non-AKI (SOFA = 0 on Days 1 and 3, n = 50), persistent AKI (SOFA > 0 on Days 1 and 3, n = 62), transient AKI (SOFA > 0 on Day 1 and SOFA = 0 on Day 3, n = 50) and worsening AKI (SOFA = 0 on Days 1 and SOFA > 0 on Day 3, n = 10). The persistent AKI group showed severe organ dysfunction and prolonged requirements for organ support. The worsening AKI group showed the least organ dysfunction on day 1 but had higher serum lactate and prolonged use of vasopressors than the non-AKI and transient AKI groups. There were 2091 upregulated and 1,902 downregulated genes (adjusted p < 0.05) between the persistent and transient AKI groups, with enrichment in the plasma membrane complex, receptor complex, and T-cell receptor complex. A 43-gene SVM model was developed using the genetic algorithm, which showed significantly greater performance predicting persistent AKI than the model based on clinical variables in a holdout subset (AUC: 0.948 [0.912, 0.984] vs. 0.739 [0.648, 0.830]; p < 0.01 for Delong's test).
CONCLUSIONS
Our study identified four subtypes of sepsis-induced AKI based on kidney injury trajectories. The landscape of host response aberrations across these subtypes was characterized. An SVM model based on a gene signature was developed to predict renal function trajectories, and showed better performance than the clinical variable-based model. Future studies are warranted to validate the gene model in distinguishing persistent from transient AKI.
Topics: Humans; Prognosis; Leukocytes, Mononuclear; Multiple Organ Failure; Acute Kidney Injury; Sepsis
PubMed: 36544199
DOI: 10.1186/s13054-022-04234-3