A genomic storm in critically injured humans.
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ABSTRACT:
SUBMITTER: Xiao W
PROVIDER: S-EPMC3244029 | biostudies-literature | 2011 Dec
REPOSITORIES: biostudies-literature
Publications
A genomic storm in critically injured humans.
Xiao Wenzhong W Mindrinos Michael N MN Seok Junhee J Cuschieri Joseph J Cuenca Alex G AG Gao Hong H Hayden Douglas L DL Hennessy Laura L Moore Ernest E EE Minei Joseph P JP Bankey Paul E PE Johnson Jeffrey L JL Sperry Jason J Nathens Avery B AB Billiar Timothy R TR West Michael A MA Brownstein Bernard H BH Mason Philip H PH Baker Henry V HV Finnerty Celeste C CC Jeschke Marc G MG López M Cecilia MC Klein Matthew B MB Gamelli Richard L RL Gibran Nicole S NS Arnoldo Brett B Xu Weihong W Zhang Yuping Y Calvano Steven E SE McDonald-Smith Grace P GP Schoenfeld David A DA Storey John D JD Cobb J Perren JP Warren H Shaw HS Moldawer Lyle L LL Herndon David N DN Lowry Stephen F SF Maier Ronald V RV Davis Ronald W RW Tompkins Ronald G RG
The Journal of experimental medicine 20111121 13
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously ...[more]
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Project description:Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. Blood was sampled from 167 severe blunt trauma patients under the age of 55 yr who consented to blood sampling. The first blood sample was taken within 12 h of the injury and 1, 4, 7, 14, 21, and 28 d after injury. Study subjects were treated under the guidance of standard operating procedures developed, implemented, and audited across all participating centers to minimize treatment variation. In addition, 37 healthy control subjects were sampled. Total blood leukocytes were isolated according to protocols published previously. Total cellular RNA was extracted and hybridized onto an HU133 Plus 2.0 GeneChip (Affymetrix) according to the manufacturer’s recommendations.
2012-03-26 | E-GEOD-36809 | biostudies-arrayexpress
Project description:Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization.
2012-03-27 | GSE36809 | GEO
Project description:To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers.Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries.We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care.Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 ± 18.3 for adults and 57.8 ± 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant.This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions.
| S-EPMC4283803 | biostudies-literature
Project description:BackgroundPulmonary complications following injury significantly contribute to subsequent mortality. Obese patients have preexisting risk factors for pulmonary complications, and are at risk for these complications following elective surgery. Whether or not obesity contributes to pulmonary complications after critical injury is poorly understood.MethodsA secondary analysis of a prospective cohort study of critically injured adults requiring at least 48 h of intensive care was performed. Patients were classified into the following body mass index groups: < or = 18.5 kg/m2 (underweight); 18.5 to 24.9 kg/m2 (normal); 25 to 29.9 kg/m2 (overweight); 30.0 to 39.9 kg/m2 (obese); and > or = 40.0 kg/m2 (severely obese). Outcomes included the rates of ARDS and pneumonia, the placement of a tracheostomy tube, and in-hospital mortality rate.ResultsA total of 1,291 patients were available for analysis, and 30% of these patients were classified as either obese or severely obese. The age-, gender-, and severity-adjusted rate of ARDS was lower in severely obese patients (odds ratio, 0.36; 95% confidence interval [CI], 0.13 to 0.99) compared to normal weight patients. The rates of pneumonia (37%), tracheostomy (10%), and in-hospital mortality (11%) did not differ among the groups. Despite no difference in pulmonary complications, the severely obese group had an ICU length of stay that was 4.8 days (95% CI, 1.8 to 7.7 days) longer than the normal weight group.ConclusionObesity does not appear to be an independent risk factor for increased pulmonary complications after critical injury, but severely obese patients are likely to require longer ICU stays.
| S-EPMC2654260 | biostudies-literature
Project description:There is significant interest in the secondary transport of the critically ill and injured. High profile cases entailing the long distance transfer of patients have highlighted the lack of availability of critical care beds and appropriate systems for transferring this patient group. These and other issues have culminated in the release of Comprehensive Critical Care by the Department of Health in 2000. It has been shown that a large number of critical care transfers originate in the emergency department. The transportation of patients has not traditionally been part of the core curriculum of emergency medicine specialists in the UK. It is imperative that clinicians have an understanding of the issues surrounding transportation of the critically ill and injured. This should include appreciation of the local and regional organisational frameworks implemented for this patient group. This review describes the core issues relevant to emergency medicine relating to the transportation of the critically ill and injured.
| S-EPMC1726322 | biostudies-literature
Project description:BACKGROUND:Trauma is the leading cause of mortality under the age of 40 years. Recent observations on metabolic reprogramming during hypoxia and ischemia indicate that hypoxic mitochondrial uncoupling promotes the generation of succinate, which in turn mediates reperfusion injury and inflammatory sequelae upon reoxygenation. Plasma levels of succinate significantly increase in response to trauma and hemorrhage in experimental models and clinical samples, suggesting that succinate may represent a candidate marker of systemic perfusion in trauma. METHODS:Quantitative mass spectrometry-based metabolomics was used to quantify succinate and lactate in 595 plasma samples from severely injured patients enrolled at the Denver Health Medical Center, a Level I trauma center in Denver, Colorado. RESULTS:A total of 95 severely injured patients were sampled for up to 10 time points (595 total samples), from field blood to 7 days postinjury. Results indicate that plasma levels of succinate increased up to 25.9-fold in deceased patients versus the median of the surviving patients (p = 2.75e-100; receiver operating characteristic area under the curve, 0.911). On the other hand, only 2.4-fold changes increases in lactate were observed (p = 5.8e-21; area under the curve, 0.874). CONCLUSION:Succinate represents a uniquely sensitive biomarker of postshock metabolic derangement and may be an important mediator of sequelae. LEVEL OF EVIDENCE:Prognostic study, level III.
| S-EPMC5573618 | biostudies-literature
Project description:ObjectivesHyperoxia is common among critically ill patients and may increase morbidity and mortality. However, limited evidence exists for critically injured patients. The objective of this study was to determine the association between hyperoxia and in-hospital mortality in adult trauma patients requiring ICU admission.Design setting and participantsThis multicenter, retrospective cohort study was conducted at two level I trauma centers and one level II trauma center in CO between October 2015 and June 2018. All adult trauma patients requiring ICU admission within 24 hours of emergency department arrival were eligible. The primary exposure was oxygenation during the first 7 days of hospitalization.InterventionsNone.Measurements and main resultsPrimary outcome was in-hospital mortality. Secondary outcomes were hospital-free days and ventilator-free days. We included 3,464 critically injured patients with a mean age of 52.6 years. Sixty-five percent were male, and 66% had blunt trauma mechanism of injury. The primary outcome of in-hospital mortality occurred in 264 patients (7.6%). Of 226,057 patient-hours, 46% were spent in hyperoxia (oxygen saturation > 96%) and 52% in normoxia (oxygen saturation 90-96%). During periods of hyperoxia, the adjusted risk for mortality was higher with greater oxygen administration. At oxygen saturation of 100%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 6.4 (3.5-11.8), 5.4 (3.4-8.6), 2.7 (1.7-4.1), and 1.5 (1.1-2.2), respectively. At oxygen saturation of 98%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 7.7 (4.3-13.5), 6.3 (4.1-9.7), 3.2 (2.2-4.8), and 1.9 (1.4-2.7), respectively.ConclusionsDuring hyperoxia, higher oxygen administration was independently associated with a greater risk of mortality among critically injured patients. Level of evidence: Cohort study, level III.
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Project description:Critical illness following head injury is associated with a hypermetabolic state but there are insufficient epidemiological data describing acute nutrition delivery to this group of patients. Furthermore, there is little information describing relationships between nutrition and clinical outcomes in this population.We undertook an analysis of observational data, collected prospectively as part of International Nutrition Surveys 2007-2013, and extracted data obtained from critically ill patients with head trauma. Our objective was to describe global nutrition support practices in the first 12 days of hospital admission after head trauma, and to explore relationships between energy and protein intake and clinical outcomes. Data are presented as mean (SD), median (IQR), or percentages.Data for 1045 patients from 341 ICUs were analyzed. The age of patients was 44.5 (19.7) years, 78% were male, and median ICU length of stay was 13.1 (IQR 7.9-21.6) days. Most patients (94%) were enterally fed but received only 58% of estimated energy and 53% of estimated protein requirements. Patients from an ICU with a feeding protocol had greater energy and protein intakes (p <0.001, 0.002 respectively) and were more likely to survive (OR 0.65; 95% CI 0.42-0.99; p = 0.043) than those without. Energy or protein intakes were not associated with mortality. However, a greater energy and protein deficit was associated with longer times until discharge alive from both ICU and hospital (all p <0.001).Nutritional deficits are commonplace in critically ill head-injured patients and these deficits are associated with a delay to discharge alive.
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Project description:OBJECTIVES:To evaluate morbidity and mortality among critically injured children with acute respiratory distress syndrome. DESIGN:Retrospective cohort study. SETTING:Four-hundred sixty Level I/II adult or pediatric trauma centers contributing to the National Trauma Data Bank. PATIENTS:One hundred forty-six thousand fifty-eight patients less than 18 years old admitted to an ICU with traumatic injury from 2007 to 2016. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We assessed in-hospital mortality and need for postdischarge care among patients with and without acute respiratory distress syndrome and hospital resource utilization and discharge disposition among survivors. Analyses were adjusted for underlying mortality risk (age, Injury Severity Score, serious brain or chest injury, and admission heart rate and hypotension) and year, transfer status, and facility trauma level designation. Acute respiratory distress syndrome occurred in 2,590 patients (1.8%). Mortality was 20.0% among acute respiratory distress syndrome patients versus 4.3% among nonacute respiratory distress syndrome patients, with an adjusted relative risk of 1.76 (95% CI, 1.52-2.04). Postdischarge care was required in an additional 44.8% of acute respiratory distress syndrome patients versus 16.0% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.59; 2.87-4.49), with only 35.1% of acute respiratory distress syndrome patients discharging to home versus 79.8% of patients without acute respiratory distress syndrome. Acute respiratory distress syndrome mortality did not change over the 10-year study period (adjusted relative risk, 1.01/yr; 0.96-1.06) nor did the proportion of acute respiratory distress syndrome patients requiring postdischarge care (adjusted relative risk, 1.04/yr; 0.97-1.11). Duration of ventilation, ICU stay, and hospital stay were all significantly longer among acute respiratory distress syndrome survivors. Tracheostomy placement occurred in 18.4% of acute respiratory distress syndrome survivors versus 2.1% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.10; 2.59-3.70). CONCLUSIONS:Acute respiratory distress syndrome development following traumatic injury in children is associated with significantly increased risk of morbidity and mortality, even after adjustment for injury severity and hemodynamic abnormalities. Outcomes have not improved over the past decade, emphasizing the need for new therapeutic interventions, and prevention strategies for acute respiratory distress syndrome among severely injured children.
| S-EPMC6336518 | biostudies-literature
Project description:A mortality review of death caused by injury requires a determination of injury survivability prior to a determination of death preventability. If injuries are nonsurvivable, only non-medical primary prevention strategies have potential to prevent the death. Therefore, objective measures are needed to empirically inform injury survivability from complex anatomic patterns of injury. As a component of injury mortality reviews, network structures show promise to objectively elucidate survivability from complex anatomic patterns of injury resulting from explosive and firearm mechanisms. In this network analysis of 5,703 critically injured combat casualties, patterns of injury among fatalities from explosive mechanisms were associated with both a higher number and severity of anatomic injuries to regions such as the extremities, abdomen, and thorax. Patterns of injuries from a firearm were more isolated to individual body regions with fatal patterns involving more severe injuries to the head and thorax. Each injury generates a specific level of risk as part of an overall anatomic pattern to inform injury survivability not always captured by traditional trauma scoring systems. Network models have potential to further elucidate differences between potentially survivable and nonsurvivable anatomic patterns of injury as part of the mortality review process relevant to improving both the military and civilian trauma care systems.
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