A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

Inhibition of neutrophil apoptosis after severe trauma is NFkappabeta dependent

BACKGROUND: Systemic inflammation may inhibit neutrophil (PMN) apoptosis and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma causes dysregulation of PMN apoptosis. METHODS: Neutrophils were isolated from trauma patients (24-72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated +/- the nuclear factor kappa beta (NFkappabeta) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFkappabeta activation was determined by Western blot for phosphorylated I kappabeta. RESULTS: Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosis correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis and induced phosphorylation of I kappabeta in control cells. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate. CONCLUSION: NFkappabeta-dependent inhibition of neutrophil apoptosis occurs after trauma. Early inhibition of PMN apoptosis is dependent on the magnitude of injury

Expanding the scope of quality measurement in surgery to include nonoperative care

Patients managed non-operatively have been excluded from risk-adjusted benchmarking programs, including the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP). Consequently, optimal performance evaluation is not possible for specialties like emergency general surgery (EGS) where non-operative management is common. We developed a multi-institutional EGS clinical data registry within ACS NSQIP that includes patients managed non-operatively to evaluate variability in non-operative care across hospitals and identify gaps in performance assessment that occur when only operative cases are considered.Using ACS NSQIP infrastructure and methodology, surgical consultations for acute appendicitis, acute cholecystitis, and small bowel obstruction (SBO) were sampled at 13 hospitals that volunteered to participate in the EGS clinical data registry. Standard NSQIP variables and 16 EGS-specific variables were abstracted with 30-day follow-up. To determine the influence of complications in non-operative patients, rates of adverse outcomes were identified and hospitals were ranked by performance with and then without including non-operative cases.2,091 patients with EGS diagnoses were included, 46.6% with appendicitis, 24.3% with cholecystitis, and 29.1% with SBO. The overall rate of non-operative management was 27.4%, 6.6% for appendicitis, 16.5% for cholecystitis, and 69.9% for SBO. Despite comprising only 27.4% of patients in the EGS Pilot, non-operative management accounted for 67.7% of deaths, 34.3% of serious morbidities, and 41.8% of hospital readmissions. After adjusting for patient characteristics and hospital diagnosis mix, addition of non-operative management to hospital performance assessment resulted in 12 of 13 hospitals changing performance rank, with 4 hospitals changing by 3 or more positions.This study identifies a gap in performance evaluation when non-operative patients are excluded from surgical quality assessment and demonstrates the feasibility of incorporating non-operative care into existing surgical quality initiatives. Broadening the scope of hospital performance assessment to include non-operative management creates an opportunity to improve the care of all surgical patients, not just those who have an operation.III, Prognostic and Epidemiological

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases

Prospective Study of Blunt Aortic Injury: Multicenter Trial of the American Association for the Surgery of Trauma

Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. METHODS: This study was a prospectively conducted multi-center trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. RESULTS: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of \u3e or = 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. CONCLUSIONS: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach