Contemporary Patterns of Multiple Organ Dysfunction in Trauma.
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ABSTRACT:
SUBMITTER: Shepherd JM
PROVIDER: S-EPMC5398901 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Contemporary Patterns of Multiple Organ Dysfunction in Trauma.
Shepherd Joanna M JM Cole Elaine E Brohi Karim K
Shock (Augusta, Ga.) 20170401 4
<h4>Background</h4>Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients.<h4>Methods</h4>Adult major trauma patients recruited to a p ...[more]
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Project description:BackgroundThe nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level.MethodsAdult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes.ResultsSome 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003).ConclusionContemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.
| S-EPMC7078999 | biostudies-literature
Project description:BackgroundUnderstanding temporal patterns of organ dysfunction (OD) may aid early recognition of complications after trauma and assist timing and modality of treatment strategies. Our aim was to analyse and characterise temporal patterns of OD in intensive care unit-admitted trauma patients.MethodsWe used group-based trajectory modelling to identify temporal trajectories of OD after trauma. Modelling was based on the joint development of all six subdomains comprising the sequential organ failure assessment score measured daily during the first two weeks post trauma. Further, the time for trajectories to stabilise and transition to final group assignments were evaluated.ResultsSix-hundred and sixty patients were included in the final model. Median age was 40 years, and median ISS was 26 (IQR 17-38). We identified five distinct trajectories of OD. Group 1, mild OD (n = 300), median ISS of 20 (IQR 14-27), had an early resolution of OD and a low mortality. Group 2, moderate OD (n = 135), and group 3, severe OD (n = 87), were fairly similar in admission characteristics and initial OD but differed in subsequent OD trajectories, the latter experiencing an extended course and higher mortality. In group 3, 56% of the patients developed sepsis as compared with 19% in group 2. Group 4, extreme OD (n = 40), received most blood transfusions, had the highest proportion of shock at admission and a median ISS of 41 (IQR 29-50). They experienced significant and sustained OD affecting all organ systems and a 28-day mortality of 30%. Group 5, traumatic brain injury with OD (n = 98), had the highest mortality of 35% and the shortest time to death for non-survivors, median 3.5 (IQR 2.4-4.8) days. Groups 1 and 5 reached their final group assignment early, > 80% of the patients within 48 h. In contrast, groups 2 and 3 had a prolonged time to final group assignment.ConclusionsWe identified five distinct trajectories of OD after severe trauma during the first two weeks post-trauma. Our findings underline the heterogeneous course after trauma and describe some potentially important clinical insights that are suggested by the groupings and temporal trajectories.
| S-EPMC8101241 | biostudies-literature
Project description:The objective was to explore the characteristics and outcomes of multiple organ dysfunction syndrome (MODS) in older trauma patients.BackgroundSeverely injured older people present an increasing challenge for trauma systems. Recovery for those who require critical care may be complicated by MODS. In older trauma patients, MODS may not be predictable based on chronological age alone and factors associated with its development and resolution are unclear.MethodsConsecutive adult patients (aged ≥16 years) admitted to 4 level 1 major trauma center critical care units were enrolled and reviewed daily until discharge or death. MODS was defined by a daily total sequential organ failure assessment score of >5.ResultsOne thousand three hundred sixteen patients were enrolled over 18 months and one-third (434) were aged ≥65 years. Incidence of MODS was high for both age groups (<65 years: 64%, ≥65 years: 70%). There were few differences in severity, patterns, and duration of MODS between cohorts, except for older traumatic brain injury (TBI) patients who experienced a prolonged course of MODS recovery (TBI: 9 days vs no TBI: 5 days, P < 0.01). Frailty rather than chronological age had a strong association with MODS development (odds ratio [OR], 6.9; 95% confidence intervals [CI], 3.0-12.4; P < 0.001) and MODS mortality (OR, 2.1; 95% CI, 1.31-3.38; P = 0.02). Critical care resource utilization was not increased in older patients, but MODS had a substantial impact on mortality (<65 years: 17%; ≥65 years: 28%). The majority of older patients who did not develop MODS survived and had favorable discharge outcomes (home discharge ≥65 years NoMODS: 50% vs MODS: 15%; P < 0.01).ConclusionsFrailty rather than chronological age appears to drive MODS development, recovery, and outcome in older cohorts. Early identification of frailty after trauma may help to predict MODS and plan care in older trauma.
| S-EPMC10013163 | biostudies-literature
Project description:Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr), at a clinically relevant time point in vivo would reduce the severity of organ injury in this model.ConclusionsWe have shown that the release of mtDNA is sufficient for the development of multiple organ injury. MtDNA concentrations likely peak at different points in the early postinjury phase dependent on the degree of isolated trauma vs combined trauma and hemorrhagic shock. HDMBr scavenging of circulating mtDNA (and nuclear DNA, nDNA) is associated with rescue from severe multiple organ injury in the animal model. This suggests that HDMBr could have utility in rescue from human trauma-induced MODS.
| S-EPMC5951958 | biostudies-literature
Project description:We performed whole blood transcriptome analysis on a total of 70 critically injured patients (Injury Severity Score [ISS] >25) in the hyperacute time period within 2 hours of injury, at 24h and again at 72h. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS < 4). Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours post injury.
2017-07-06 | E-MTAB-5882 | biostudies-arrayexpress
Project description:ContextMultiple scores exist to characterize organ dysfunction in children.ObjectiveTo review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children.Data sourcesElectronic searches of PubMed and Embase were conducted from January 1992 to January 2020.Study selectionStudies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes.Data extractionData were abstracted into a standard data extraction form by a task force member.ResultsOf 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially.LimitationsWhile scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely.ConclusionsThe multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children.
| S-EPMC9703039 | biostudies-literature
Project description:Background: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS.Methods and findings: We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ? 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ? 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts.Conclusions: In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.
| S-EPMC5513400 | biostudies-literature
Project description:Purpose: We sought to identify a MODS score parameter that highly correlates with adverse outcomes and then use this parameter to test the hypothesis that multiple severity-based MODS clusters could be identified after blunt trauma. Methods: MOD score across days (D) 2-5 was subjected to Fuzzy C-means Clustering Analysis (FCM) followed by eight Clustering Validity Indices (CVI) to derive organ dysfunction patterns among 376 blunt trauma patients admitted to the intensive care unit (ICU) who survived to discharge. Thirty-one inflammation biomarkers were assayed (Luminex™) in serial blood samples (3 samples within the first 24 h and then daily up to D 5) and were analyzed using Two-Way ANOVA and Dynamic Network analysis (DyNA). Results: The FCM followed by CVI suggested four distinct clusters based on MOD score magnitude between D2 and D5. Distinct patterns of organ dysfunction emerged in each of the four clusters and exhibited statistically significant differences with regards to in-hospital outcomes. Interleukin (IL)-6, MCP-1, IL-10, IL-8, IP-10, sST2, and MIG were elevated differentially over time across the four clusters. DyNA identified remarkable differences in inflammatory network interconnectivity. Conclusion: These results suggest the existence of four distinct organ failure patterns based on MOD score magnitude in blunt trauma patients admitted to the ICU who survive to discharge.
| S-EPMC7053419 | biostudies-literature
Project description:BackgroundMultiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24 h of traumatic injury. We then compared its performance to baseline injury severity scores and detection of infections.MethodsBuffy coat transcriptome and linked clinical datasets from blunt trauma patients from the Inflammation and the Host Response to Injury Study ("Glue Grant") multi-center cohort were used. According to the inclusion/exclusion criteria, 141 adult (age ≥ 16 years old) blunt trauma patients (excluding penetrating) with early buffy coat (≤ 24 h since trauma injury) samples were analyzed, with 58 MOF-cases and 83 non-cases. We applied the Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) algorithms to select features and develop models for MOF early outcome prediction.ResultsThe LASSO model included 18 transcripts (AUROC [95% CI]: 0.938 [0.890-0.987] (training) and 0.833 [0.699-0.967] (test)), and the XGBoost model included 41 transcripts (0.999 [0.997-1.000] (training) and 0.907 [0.816-0.998] (test)). There were 16 overlapping transcripts comparing the two panels (0.935 [0.884-0.985] (training) and 0.836 [0.703-0.968] (test)). The biomarker models notably outperformed models based on injury severity scores and sex, which we found to be significantly associated with MOF (APACHEII + sex-0.649 [0.537-0.762] (training) and 0.493 [0.301-0.685] (test); ISS + sex-0.630 [0.516-0.744] (training) and 0.482 [0.293-0.670] (test); NISS + sex-0.651 [0.540-0.763] (training) and 0.525 [0.335-0.714] (test)).ConclusionsThe accurate assessment of MOF from blood samples immediately after trauma is expected to aid in improving clinical decision-making and may contribute to reduced morbidity, mortality and healthcare costs. Moreover, understanding the molecular mechanisms involving the transcripts identified as important for MOF prediction may eventually aid in developing novel interventions.
| S-EPMC11358370 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pmed.1002352.].
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