Objective
Our objective was to execute a prospective cohort study to determine relationships between plasma mtDNA DAMP levels and the occurrence of systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and mortality.
Background
Mitochondrial DNA damage-associated molecular patterns (DAMPs) accumulate in the circulation after severe injury. Observations in animal models demonstrate that mtDNA DAMPs contribute to organ dys-function; however, the link between plasma mtDNA DAMPs and outcome in severely injured human subjects has not been established.
Methods
DNA was isolated from plasma samples taken from severely injured patients at hospital days 0, 1, and 2. Real-time PCR was used to quantify selected ≈200 base pair sequences of mtDNA within the COX1, ND1, and ND6 genes, as well as from the D-Loop transcriptional regulatory region. MODS was defined as a Denver Multiple Organ Failure score of 4 or greater.
Results
MtDNA DAMPs were quantified as PCR threshold cycle number. Lower threshold cycles indicate increased mtDNA DAMP content. Patients with SIRS had significantly increased mtDNA DAMP levels in all 4 sequences examined (32.14 ± 0.90 vs 29.00 ± 1.15 for COX1, 31.90 ± 0.47 vs 30.16 ± 1.42 for ND1, 32.40 ± 0.61 vs 28.94 ± 1.13 for ND6, and 33.12 ± 0.83 vs 28.30 ± 1.14 for D-Loop). Patients who developed MODS also had elevated mtDNA DAMP levels compared with those who did not (32.57 ± 0.74 vs 27.12 ± 0.66 for COX1, 32.45 ± 0.65 vs 28.20 ± 0.73 for ND1, 32.52 ± 0.56 vs 27.60 ± 0.79 for ND6, and 32.85 ± 0.75 vs 27.86 ± 1.27 for D-Loop). Patients with above-median mtDNA DAMP levels had a significantly elevated relative risk for mortality. Four patients died secondary to severe MODS.
Conclusions
These findings comprise the first observational evidence that plasma mtDNA DAMPs is associated with the evolution of SIRS, MODS, and mortality in severely injured human subjects.
Telemedicine significantly improved rural LCH evaluation and management of trauma patients. More severely injured trauma patients were identified and more rapidly transferred to the TC. Total TC hospital costs were significantly decreased without significant changes in TC mortality. Introduction of telemedicine consultation to rural LCH emergency departments expanded LCH trauma capabilities and conserved TC resources, which were directed to more severely injured patients.
Introduction of proximal SAE in NOM of HDS splenic trauma patients with active extravasation did not alter mortality rates at a Level 1 Trauma Center. Increased incidence of ARDS and association of failure of NOM with higher splenic organ injury score identify areas for cautionary application of proximal SAE in the more severely injured trauma patient population. Better patient selection guidelines for proximal SAE are needed. Without these guidelines, outcomes from SAE will still lack transparency.
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