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Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

Vanzant EL, Hilton RE, Lopez CM, Zhang J, Ungaro RF, Gentile LF, Szpila BE, Maier RV, Cuschieri J, Bihorac A, Leeuwenburgh C, Moore FA, Baker HV, Moldawer LL, Brakenridge SC, Efron PA, Inflammation and Host Response to Injury Investigato - Crit Care (2015)

Bottom Line: We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts.Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities.As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. erin.vanzant@surgery.ufl.edu.

ABSTRACT

Introduction: We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.

Methods: We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.

Results: We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. However, aged patients had more comorbidities. Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities. Additionally, advanced age was an independent predictor of a complicated recovery and 28-day mortality. Acutely after trauma, blood neutrophil genome-wide expression analysis revealed an attenuated transcriptomic response as compared to the young; this attenuated response was supported by the patients' plasma cytokine and chemokine concentrations. Later, these patients demonstrated gene expression changes consistent with simultaneous, persistent pro-inflammatory and immunosuppressive states.

Conclusions: We concluded that advanced age is one of the strongest non-injury related risk factors for poor outcomes after severe trauma with hemorrhagic shock and is associated with an altered and unique peripheral leukocyte genomic response. As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.

No MeSH data available.


Related in: MedlinePlus

Selected gene ontology pathway heat maps in complicated aged and young patients on days 0.5, 1.0 and 4.0 after severe traumatic injury. Dark blue represents upregulation, whereas light blue represents down regulation. In complicated young patients, gene ontology pathway analysis demonstrated that several pathways involved in innate immunity and neutrophil function (that is, antigen processing and presentation and neutrophil chemotaxis pathways) were significantly more aberrant from controls in the acute periods (days 0.5 and 1) than was seen in the aged. In the sub-acute period (day 4) after injury, these patterns switched. The young trended back toward baseline expression values while the aged continued to demonstrate significantly more aberrant expression patterns in pathways involved in innate immunity and neutrophil function (that is, neutrophil activation pathway) (Holm-Sidak, *P <0.05).
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Fig3: Selected gene ontology pathway heat maps in complicated aged and young patients on days 0.5, 1.0 and 4.0 after severe traumatic injury. Dark blue represents upregulation, whereas light blue represents down regulation. In complicated young patients, gene ontology pathway analysis demonstrated that several pathways involved in innate immunity and neutrophil function (that is, antigen processing and presentation and neutrophil chemotaxis pathways) were significantly more aberrant from controls in the acute periods (days 0.5 and 1) than was seen in the aged. In the sub-acute period (day 4) after injury, these patterns switched. The young trended back toward baseline expression values while the aged continued to demonstrate significantly more aberrant expression patterns in pathways involved in innate immunity and neutrophil function (that is, neutrophil activation pathway) (Holm-Sidak, *P <0.05).

Mentions: Gene ontology and Biocarta DFR pathway analysis demonstrated that complicated young trauma patients had significantly more aberrant expression patterns (fold change versus control baseline expression) for PMN pathways involved in innate immunity and neutrophil function in the acute period after trauma than those in the aged. By day 4, these patterns once again switched and the aged displayed significantly more aberrant expression patterns compared to controls than the young cohort (Figure 3). Additional IPA® analysis of functional pathways revealed that on day 1 after injury, the aged had significant further downregulation of PMN pathways important to immunity, as compared to the young cohort (Figure 4).Figure 3


Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock.

Vanzant EL, Hilton RE, Lopez CM, Zhang J, Ungaro RF, Gentile LF, Szpila BE, Maier RV, Cuschieri J, Bihorac A, Leeuwenburgh C, Moore FA, Baker HV, Moldawer LL, Brakenridge SC, Efron PA, Inflammation and Host Response to Injury Investigato - Crit Care (2015)

Selected gene ontology pathway heat maps in complicated aged and young patients on days 0.5, 1.0 and 4.0 after severe traumatic injury. Dark blue represents upregulation, whereas light blue represents down regulation. In complicated young patients, gene ontology pathway analysis demonstrated that several pathways involved in innate immunity and neutrophil function (that is, antigen processing and presentation and neutrophil chemotaxis pathways) were significantly more aberrant from controls in the acute periods (days 0.5 and 1) than was seen in the aged. In the sub-acute period (day 4) after injury, these patterns switched. The young trended back toward baseline expression values while the aged continued to demonstrate significantly more aberrant expression patterns in pathways involved in innate immunity and neutrophil function (that is, neutrophil activation pathway) (Holm-Sidak, *P <0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4404112&req=5

Fig3: Selected gene ontology pathway heat maps in complicated aged and young patients on days 0.5, 1.0 and 4.0 after severe traumatic injury. Dark blue represents upregulation, whereas light blue represents down regulation. In complicated young patients, gene ontology pathway analysis demonstrated that several pathways involved in innate immunity and neutrophil function (that is, antigen processing and presentation and neutrophil chemotaxis pathways) were significantly more aberrant from controls in the acute periods (days 0.5 and 1) than was seen in the aged. In the sub-acute period (day 4) after injury, these patterns switched. The young trended back toward baseline expression values while the aged continued to demonstrate significantly more aberrant expression patterns in pathways involved in innate immunity and neutrophil function (that is, neutrophil activation pathway) (Holm-Sidak, *P <0.05).
Mentions: Gene ontology and Biocarta DFR pathway analysis demonstrated that complicated young trauma patients had significantly more aberrant expression patterns (fold change versus control baseline expression) for PMN pathways involved in innate immunity and neutrophil function in the acute period after trauma than those in the aged. By day 4, these patterns once again switched and the aged displayed significantly more aberrant expression patterns compared to controls than the young cohort (Figure 3). Additional IPA® analysis of functional pathways revealed that on day 1 after injury, the aged had significant further downregulation of PMN pathways important to immunity, as compared to the young cohort (Figure 4).Figure 3

Bottom Line: We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts.Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities.As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Molecular Genetics and Microbiology, University of Florida, PO Box 100245, Gainesville, FL, 32610-0245, USA. erin.vanzant@surgery.ufl.edu.

ABSTRACT

Introduction: We wished to characterize the relationship of advanced age to clinical outcomes and to transcriptomic responses after severe blunt traumatic injury with hemorrhagic shock.

Methods: We performed epidemiological, cytokine, and transcriptomic analyses on a prospective, multi-center cohort of 1,928 severely injured patients.

Results: We found that there was no difference in injury severity between the aged (age ≥55, n = 533) and young (age <55, n = 1395) cohorts. However, aged patients had more comorbidities. Advanced age was associated with more severe organ failure, infectious complications, ventilator days, and intensive care unit length of stay, as well as, an increased likelihood of being discharged to skilled nursing or long-term care facilities. Additionally, advanced age was an independent predictor of a complicated recovery and 28-day mortality. Acutely after trauma, blood neutrophil genome-wide expression analysis revealed an attenuated transcriptomic response as compared to the young; this attenuated response was supported by the patients' plasma cytokine and chemokine concentrations. Later, these patients demonstrated gene expression changes consistent with simultaneous, persistent pro-inflammatory and immunosuppressive states.

Conclusions: We concluded that advanced age is one of the strongest non-injury related risk factors for poor outcomes after severe trauma with hemorrhagic shock and is associated with an altered and unique peripheral leukocyte genomic response. As the general population's age increases, it will be important to individualize prediction models and therapeutic targets to this high risk cohort.

No MeSH data available.


Related in: MedlinePlus