The COST of liver disease: The Cirrhosis Outcomes Score in Trauma Study.

BACKGROUND: Cirrhosis in trauma patients is an indicator of poor prognosis, but current trauma injury grading systems do not take into account liver dysfunction as a risk factor. Our objective was to construct a simple clinical mortality prediction model in cirrhotic trauma patients: Cirrhosis Outcomes Score in Trauma (COST). METHODS: Trauma patients with pre-existing cirrhosis or liver dysfunction who were admitted to our ACS Level I trauma center between 2013 and 2021 were reviewed. Patients with significant acute liver trauma (AAST Grade ≥ 3) or those that developed acute liver dysfunction while admitted were excluded. Demographics as well as ISS, MELD, complications, and mortality were evaluated. COST was defined as the sum of age, ISS, and MELD. Univariate and multivariable analysis was used to determine independent predictors of mortality. The area under the receiver operating curve (AUROC) was calculated to assess the ability of COST to predict mortality. RESULTS: A total of 318 patients were analyzed of which the majority were males 214 (67.3%) who suffered blunt trauma 305 (95.9%). Mortality at 30-days, 60-days, and 90-days was 20.4%, 23.6%, and 25.5%, respectively. COST was associated with inpatient, 30-day, and 90-day mortality on regression analyses and the AUROC for COST predicting mortality at these respective time points was 0.810, 0.801, and 0.813. CONCLUSION: Current trauma injury grading systems do not take into account liver dysfunction as a risk factor. COST is highly predictive of mortality in cirrhotic trauma patients. The simplicity of the score makes it useful in guiding clinical care and in optimizing goals of care discussions. Future studies to validate this prediction model are required prior to clinical use.

Duration of Antibiotic Therapy in Necrotizing Soft Tissue Infections: Shorter is Safe.

Background: Early debridement improves outcome in necrotizing soft tissue infection (NSTI), but there is no consensus on duration of antimicrobial therapy. We recently changed practice to discontinue antibiotic agents early with a goal of 48 hours after adequate source control. We hypothesized that discontinuing antibiotic agents after a short course is safe in the treatment of NSTI. Patients and Methods: This was a prospective study of patients with NSTI comparing short duration of antibiotic agents to a control population after a change in practice. In 2018 we began discontinuing antibiotic agents within 48 hours of source control (absence of cellulitis and no evidence of active infection). Previously, antibiotic duration was at the discretion of the attending surgeon (generally 7-10 days). Patients were excluded from analysis if they were initially debrided at a referring facility, immune compromised, or died prior to source control. Patient characteristics and outcomes were evaluated. The primary outcome was treatment failure requiring antibiotic agents to be restarted with or without further debridement of infected tissue. Secondary outcomes included the duration of antibiotic therapy after source control. Results: We evaluated 151 patients; 119 admitted between January 1, 2011 and January 31, 2018 (PRE) and 32 admitted after January 31, 2018 (POST). Patients were not statistically different regarding characteristics, admission physiologic variables, and comorbidities. The median duration of antibiotic agents after source control in the PRE group was 180.3 hours (interquartile range [IQR], 100.7-318.8) versus 48 hours (IQR, 32.3-100.8) in the POST group (p < 0.01). Patients in each group were treated as described above, and treatment failure occurred in seven (5.9%) PRE patients and two (6.3%) POST (99.3% post hoc power at non-inferiority limit 20%, significance p < 0.05). Thirty-day all-cause mortality was not different between groups (6.7% vs. 6.3%; p = 0.94). Conclusions: Short-duration (48 hours) antibiotic agents after NSTI source control is as safe and effective as a longer course.

Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes.

OBJECTIVE: To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death. SUMMARY BACKGROUND DATA: Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential. METHODS: This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30 days. RESULTS: Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome. CONCLUSIONS: Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.

SIRT1 Mediates Septic Cardiomyopathy in a Murine Model of Polymicrobial Sepsis.

BACKGROUND: Cardiac dysfunction, a common complication from severe sepsis, is associated with increased morbidity and mortality. However, the molecular mechanisms of septic cardiac dysfunction are poorly understood. SIRT1, a member of the sirtuin family of NAD+-dependent protein deacetylases, is an important immunometabolic regulator of sepsis, and sustained SIRT1 elevation is associated with worse outcomes and organ dysfunction in severe sepsis. Herein, we explore the role of SIRT1 in septic cardiac dysfunction using a murine model of sepsis. METHODS: An in vitro model of inflammation in isolated H9c2 cardiomyocytes was used to confirm SIRT1 response to stimulation with lipopolysaccharide (LPS), followed by a murine model of cecal ligation and puncture (CLP) to investigate the molecular and echocardiographic response to sepsis. A selective SIRT1 inhibitor, EX-527, was employed to test for SIRT1 participation in septic cardiac dysfunction. RESULTS: SIRT1 mRNA and protein levels in cultured H9c2 cardiomyocytes were significantly elevated at later time points after stimulation with LPS. Similarly, cardiac tissue harvested from C57BL/6 mice 36 h after CLP demonstrated increased expression of SIRT1 mRNA and protein compared with sham controls. Administration of EX-527 18 h after CLP reduced SIRT1 protein expression in cardiac tissue at 36 h. Moreover, treatment with EX-527 improved cardiac performance with increased global longitudinal strain and longitudinal strain rate. CONCLUSIONS: Our findings reveal that SIRT1 expression increases in isolated cardiomyocytes and cardiac tissue after sepsis inflammation. Moreover, rebalancing SIRT1 excess in late sepsis improves cardiac performance, suggesting that SIRT1 may serve as a therapeutic target for septic cardiomyopathy.

Antioxidant treatment after injury suppresses second hit immune priming.

BACKGROUND: Pulmonary contusion (PC) is a common injury that often results in priming for exaggerated inflammatory responses to a second hit. Previous studies used a mouse model of pulmonary contusion and showed an early and sustained reduction of SIRT1 protein and activity in the lung and bronchoalveolar lavage (BAL) cells of injured mice. Sustained decrease in SIRT1 was associated with a primed phenotype in injured mice challenged with an inflammatory stimulus. This study tests the hypothesis that pulmonary contusion induces oxidant production that modifies and decreases SIRT1 and primes the lung for the second-hit response. METHODS: A mouse model of pulmonary contusion was used to investigate injury-induced oxidant changes in SIRT1. Second-hit responses were evaluated by infection (Streptococcus pneumoniae) and inflammatory challenge using bacterial lipopolysaccharide. BAL, lung tissue, and blood were collected and used to evaluate inflammatory responses and SIRT1 levels, oxidant modification, and activity. Levels of NO in the BAL from mice and patients with PC were also assessed. RESULTS: We found that oxidants produced as a result of pulmonary contusion resulted in modification of SIRT1. S-Nitrosylation was observed and correlated with increased inducible nitric oxide synthase expression after injury. Anti-oxidant treatment of injured mice preserved SIRT1 activity, decreased second hit responses and improved lung function. Elevated NO levels in the BAL of PC patients was associated with acute respiratory distress syndrome or diagnosis of pneumonia. CONCLUSIONS: We conclude that oxidative stress in the lung after injury induces redox modification of SIRT1 and contributes to priming of the lung for a second-hit response. Antioxidant treatment suggests that SIRT1 activity after injury may be beneficial in suppressing second-hit responses.

Predicting Mortality and Independence at Discharge in the Aging Traumatic Brain Injury Population Using Data Available at Admission.

BACKGROUND: Aging worsens outcome in traumatic brain injury (TBI), but available studies may not provide accurate outcomes predictions due to confounding associated injuries. Our goal was to develop a predictive tool using variables available at admission to predict outcomes related to severity of brain injury in aging patients. STUDY DESIGN: Characteristics and outcomes of blunt trauma patients, aged 50 or older, with isolated TBI, in the National Trauma Data Bank (NTDB), were evaluated. Equations predicting survival and independence at discharge (IDC) were developed and validated using patients from our trauma registry, comparing predicted with actual outcomes. RESULTS: Logistic regression for survival and IDC was performed in 57,588 patients using age, sex, Glasgow Coma Scale score (GCS), and Revised Trauma Score (RTS). All variables were independent predictors of outcome. Two models were developed using these data. The first included age, sex, and GCS. The second substituted RTS for GCS. C statistics from the models for survival and IDC were 0.90 and 0.82 in the GCS model. In the RTS model, C statistics were 0.80 and 0.67. The use of GCS provided better discrimination and was chosen for further examination. Using a predictive equation derived from the logistic regression model, outcome probabilities were calculated for 894 similar patients from our trauma registry (January 2012 to March 2016). The survival and IDC models both showed excellent discrimination (p < 0.0001). Survival and IDC generally decreased by decade: age 50 to 59 (80% IDC, 6.5% mortality), 60 to 69 (82% IDC, 7.0% mortality), 70 to 79 (76% IDC, 8.9% mortality), and 80 to 89 (67% IDC, 13.4% mortality). CONCLUSIONS: These models can assist in predicting the probability of survival and IDC for aging patients with TBI. This provides important data for loved ones of these patients when addressing goals of care.

Subcapsular hematoma in blunt splenic injury: A significant predictor of failure of nonoperative management.

BACKGROUND: In patients with blunt splenic injury (BSI), patient selection, angiography, and embolization have contributed to low nonoperative management (NOM) failure rates. Despite these advances, some patients will fail NOM. We noted that a significant proportion of NOM failures had subcapsular hematomas (SCHs) identified on imaging. We sought to determine if there is a correlation between SCH and higher risk of NOM failure after BSI. METHODS: Our institutional trauma registry was queried for all patients with BSI during a 2-year period. Charts were reviewed to determine grade, presence of SCH, and outcome of NOM. Under current institutional protocol, all stable patients with BSI Grades III to V and those with contrast blush on computed tomography are referred for angiography and embolization. Failure of NOM was declared if splenectomy was required for bleeding after an initial plan of nonoperation. RESULTS: From May 2012 to May 2014, 312 patients with BSI were identified. A total of 253 patients (81%) underwent NOM. Overall, 15 (5.9%) failed NOM. Of those undergoing NOM, 34 had SCH and 12 failed (35.3% vs. 1.5% without SCH, p = 0.0001). Failure rates in Grades 1 to 4 were 2.3%, 3.8%, 8.8%, and 19.2%, respectively. NOM failure rates in the subset with SCH for Grades I to IV were 20%, 25%, 30.8%, and 80%, respectively. These are significantly higher than patients without SCH in Grades II to IV (0%, p = 0.003; 2.3%, p = 0.008; and 4.8%, p = 0.016) and approach significance in Grade I (1.2%, p = 0.11). There were no SCHs and no failures of NOM in Grade V injuries. CONCLUSION: The NOM failure rate of BSI patients with SCH is significantly higher than those without SCH. Patients with BSI Grades I to III slated for NOM must be observed as the failure rate approaches 30%. Splenectomy should be considered in patients with Grade IV BSI with SCH, as NOM failure rate is 80%. LEVEL OF EVIDENCE: Therapeutic study, level IV.

SIRT1 mediates a primed response to immune challenge after traumatic lung injury.

BACKGROUND: Pulmonary contusion (PC) is a common, potentially lethal injury that results in priming for exaggerated inflammatory responses to subsequent immune challenge like infection (second hit). The molecular mechanism of priming and the second hit phenomenon after PC remain obscure. With the use of a mouse model of PC, this study explores the role of sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, in priming for a second hit after injury. METHODS: With the use of a mouse model of PC, injury-primed second-hit host responses were tested at 24 hours after PC by (1) in vivo infectious challenge of injured mice or (2) ex vivo inflammatory challenge of isolated immune cells from injured mice. SIRT activators or repressors were used to test for SIRT1 participation in these second-hit responses. RESULTS: PC-injured mice given an in vivo infectious challenge by cecal ligation and puncture (CLP) had significantly increased mortality compared with injury or infectious challenge alone. Isolated bronchoalveolar lavage (BAL) cells from injured mice given an ex vivo inflammatory challenge with bacterial lipopolysaccharide (LPS) had increased levels of tumor necrosis factor α messenger RNA compared with uninjured mice. We found that PC reduced SIRT1 protein, messenger RNA, and SIRT1 enzymatic activity in injured lung tissue. We also found decreased SIRT1 protein levels in BAL cells from injured mice. We further found that injured mice treated with a SIRT1 activator, resveratrol, showed significantly decreased polymorphonuclear leukocytes (PMN) in the BAL in response to intratracheal LPS and increased survival from CLP. CONCLUSION: These results showed that PC decreased SIRT1 levels in the lung correlated with enhanced responses to infectious or inflammatory stimuli in injured mice. Treatment of injured mice with a SIRT1 activator, resveratrol, decreased LPS inflammatory response and increased survival after CLP. Our results suggest that SIRT1 participates in the second-hit response after injury.

Predicting risk of postoperative lung injury in high-risk surgical patients: a multicenter cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients. METHODS: This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test were used to assess model performance. RESULTS: Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and ≥30 breaths/min), FIO2 greater than 35%, and SpO2 less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS: In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS.

Prospective trial of angiography and embolization for all grade III to V blunt splenic injuries: nonoperative management success rate is significantly improved.

BACKGROUND: Nonoperative management (NOM) of blunt splenic injury is well accepted. Substantial failure rates in higher injury grades remain common, with one large study reporting rates of 19.6%, 33.3%, and 75% for grades III, IV, and V, respectively. Retrospective data show angiography and embolization can increase salvage rates in these severe injuries. We developed a protocol requiring referral of all blunt splenic injuries, grades III to V, without indication for immediate operation for angiography and embolization. We hypothesized that angiography and embolization of high-grade blunt splenic injury would reduce NOM failure rates in this population. STUDY DESIGN: This was a prospective study at our Level I trauma center as part of a performance-improvement project. Demographics, injury characteristics, and outcomes were compared with historic controls. The protocol required all stable patients with grade III to V splenic injuries be referred for angiography and embolization. In historic controls, referral was based on surgeon preference. RESULTS: From January 1, 2010 to December 31, 2012, there were 168 patients with grades III to V spleen injuries admitted; NOM was undertaken in 113 (67%) patients. The protocol was followed in 97 patients, with a failure rate of 5%. Failure rate in the 16 protocol deviations was 25% (p = 0.02). Historic controls from January 1, 2007 to December 31, 2009 were compared with the protocol group. One hundred and fifty-three patients with grade III to V injuries were admitted during this period, 80 (52%) patients underwent attempted NOM. Failure rate was significantly higher than for the protocol group (15%, p = 0.04). CONCLUSIONS: Use of a protocol requiring angiography and embolization for all high-grade spleen injuries slated for NOM leads to a significantly decreased failure rate. We recommend angiography and embolization as an adjunct to NOM for all grade III to V splenic injuries.

Complement mediates a primed inflammatory response after traumatic lung injury.

BACKGROUND: Pulmonary contusion (PC) is a common, potentially lethal injury that results in the priming for exaggerated responses to subsequent immune challenge such as an infection (second hit). We hypothesize a PC-induced complement (C) activation participates in the priming effect for a second hit. METHODS: Male, 8 weeks to 9 weeks, C57BL/6 mice (wild-type, C5) underwent blunt chest trauma resulting in PC. At 3 hours/24 hours after injury, the inflammatory response was measured in tissue, serum, and bronchoalveolar lavage (BAL). The thrombin inhibitor, hirudin, was used to determine if injury-induced thrombin participated in the activation of C. Injury-primed responses were tested by challenging injured mice with bacterial endotoxin (lipopolysaccharide, LPS) as a second hit. Inflammatory responses were assessed at 4 hours after LPS challenge. Data were analyzed using one-way analysis of variance with Bonferroni multiple comparison posttest (significance, p ≤ 0.05). Protocols were approved by the Institutional Animal Care and Use Committee. RESULTS: We found significantly increased levels of C5a in the BAL of injured animals as early as 24 hours, persisting for up to 72 hours after injury. Hirudin-treated injured mice had significantly decreased levels of thrombin in the BAL that correlated with reduced C5a levels. Injured mice challenged with intratracheal (IT) LPS had increased C5a and inflammatory response. Conversely, inhibition of C5a or its receptor, C5aR, before LPS challenge correlated with decreased inflammatory responses; C5a-deficient mice showed a similar loss of primed response to LPS challenge. CONCLUSION: Complement C5a levels in the BAL are increased over several days after PC. Premorbid inhibition of thrombin markedly decreases C5a levels after PC, suggesting that thrombin-induced C activation is the major pathway of activation after PC. Similarly, inhibition of C5a after PC will decrease injury-primed responses to LPS stimulation. Our findings suggest cross-talk between the coagulation and complement systems that induce immune priming after PC.

Investigation of pulmonary contusion extent and its correlation to crash, occupant, and injury characteristics in motor vehicle crashes.

BACKGROUND: Pulmonary contusion (PC) is a leading injury in blunt chest trauma and is most commonly caused by motor vehicle crashes (MVC). To improve understanding of the relationship between insult and outcome, this study relates PC severity to crash, occupant, and injury parameters in MVCs. METHODS: Twenty-nine subjects with PC were selected from the Crash Injury Research and Engineering Network (CIREN) database, which contains detailed crash and medical information on MVC occupants. Computed tomography scans of these subjects were segmented using a semi-automated protocol to quantify the volumetric percentage of injured tissue in each lung. Techniques were used to quantify the geometry and location of PC, as well as the location of rib fractures. Injury extent including percent PC volume and the number of rib fractures was analyzed and its relation to crash and occupant characteristics was explored. RESULTS: Frontal and near-side crashes composed 72% of the dataset and the near-side door was the component most often associated with PC causation. The number of rib fractures increased with age and fracture patterns varied with crash type. In near-side crashes, occupant weight and BMI were positively correlated with percent PC volume and the number of rib fractures, and the impact severity was positively correlated with percent PC volume in the lung nearest the impact. CONCLUSIONS: This study quantified PC morphology in 29 MVC occupants and examined the relationship between injury severity and crash and occupant parameters to better characterize the mechanism of injury. The results of this study may contribute to the prevention, mitigation, and treatment of PC.

Locally derived versus guideline-based approach to treatment of hospital-acquired pneumonia in the trauma intensive care unit.

BACKGROUND: Appropriate initial antibiotic therapy for presumed pneumonia in critically ill patients decreases the mortality rate. To achieve this goal, treatment guidelines developed by groups such as the American Thoracic Society (ATS) have been stressed. However, often overlooked is the importance of incorporating local microbiologic data into an empiric algorithm. Our hypothesis was that an empiric algorithm supported by our locally-driven analysis would predict more accurate coverage than one defined strictly by an unmodified guideline-driven approach. METHODS: Retrospective review of all first hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) pathogens in consecutive trauma intensive care unit (TICU) patients over 18 months. Microbiologic data were analyzed to update our TICU-specific empiric algorithm. The ATS guidelines define patients at risk for multidrug-resistant (MDR) organisms on the basis of standardized criteria and time since admission (early <5 days; late ≥5 days). RESULTS: A total of 164 pathogens caused 117 pneumonias. For early coverage, ATS guidelines stress identification of MDR risks; these criteria failed to identify 8 of 13 (62%) early MDR pneumonias. For early HAP/VAP with no MDR risks, the ATS guidelines recommend monotherapy; susceptibility differed (49% to ciprofloxacin, 68% to ampicillin-sulbactam, 83% to ceftriaxone). A total of 15% of early pathogens were MDR gram-positive, so addition of vancomycin resulted in adequate predicted coverage of 100%, 79%, and 95% for ciprofloxacin, ampicillin-sulbactam, and ceftriaxone, respectively. For late HAP/VAP, ATS recommends regimens based on broad-spectrum drugs. Vancomycin with ciprofloxacin, cefepime, or piperacillin-tazobactam had predicted coverage of 95%, 94%, and 93%, respectively. CONCLUSIONS: The empiric algorithm derived from analysis of local microbiologic data predicted significantly better coverage than one defined by an unmodified guideline-driven approach for early HAP/VAP. Our locally-derived TICU algorithm of ceftriaxone+vancomycin for early pneumonia and piperacillin-tazobactam+vancomycin for late pneumonia optimizes the adequacy of initial therapy. Understanding local patterns of pneumonia ensures the creation and maintenance of empiric algorithms that achieve the best clinical outcomes.

Does Acute Physiology and Chronic Health Evaluation II provide a valid metric to directly compare disease severity in trauma versus surgical intensive care unit patients?

The Acute Physiology and Chronic Health Evaluation II (APACHE II) score has never been validated to risk-adjust between critically ill trauma (TICU) and general surgical (SICU) intensive care unit patients, yet it is commonly used for such a purpose. To study this, we evaluated risk of death in TICU and SICU patients with pneumonia. We hypothesized that mortality for a given APACHE II would be significantly different and that using APACHE II to directly compare TICU and SICU patients would not be appropriate. We conducted a retrospective review of patients admitted to the TICU or SICU at a tertiary medical center over an 18-month period with pneumonia. Admission APACHE II scores, in-hospital mortality, demographics, and illness characteristics were recorded. One hundred eighty patients met inclusion criteria, 116 in the TICU and 64 in the SICU. Average APACHE II scores were not significantly different in the TICU versus SICU (25 vs 24; P = 0.4607), indicating similar disease severity; overall mortality rates, however, were significantly different (24 vs 50%; P = 0.0004). Components of APACHE II, which contributed to this mortality differential, were Glasgow Coma Score, age, presence of chronic health problems, and operative intervention. APACHE II fails to provide a valid metric to directly compare the severity of disease between TICU and SICU patients with pneumonia. These groups represent distinct populations and should be separated when benchmarking outcomes or creating performance metrics in ICU patients. Improved severity scoring systems are needed to conduct clinically relevant and methodologically valid comparisons between these unique groups.

An innovative approach to predict the development of adult respiratory distress syndrome in patients with blunt trauma.

BACKGROUND: Pulmonary contusion (PC) is a common injury associated with blunt chest trauma. Complications such as pneumonia and adult respiratory distress syndrome (ARDS) occur in up to 50% of patients with PC. The ability to predict which PC patients are at increased risk of developing complications would be of tremendous clinical utility. In this study, we test the hypothesis that a novel method that objectively measures percent PC can be used to identify patients at risk to develop ARDS after injury. METHODS: Patients with unilateral or bilateral PC with an admission chest computed tomographic angiogram were identified from the trauma registry. Demographic, infectious, and outcome data were collected. Percent PC was determined on admission chest computed tomography using our novel semiautomated, attenuation-defined computer-based algorithm, in which the lung was segmented with minimal manual editing. Factors contributing to the development of ARDS were identified by both univariate and multivariable logistic regression analyses. ARDS was defined as PaO2/FiO2 ratio of less than 200 with diffuse bilateral infiltrates on chest radiograph with no evidence of congestive heart failure. RESULTS: Quantifying percent PC from our objective computer-based approach proved successful. We found that a contusion size of 24% of total lung volume or greater was most significant at predicting ARDS, which occurred in 78% of these patients. Such patients also had a significantly higher incidence of pneumonia when compared with those with contusions less than 24%. The specificity of contusion size of 24% or greater was 94%, although sensitivity was 37%; positive predictive value was 78%, and negative predictive value was 72%. CONCLUSION: We developed and describe a software-based methodology to accurately measure the size of lung contusion in patients of blunt trauma. In our analyses, contusions of 24% or greater most significantly predict the development of ARDS. Such an objective approach can identify patients with PC who are at increased risk for developing respiratory complications before they happen. Further research is needed to use this novel methodology as a means to prevent posttraumatic lung injury in patients with blunt trauma. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; diagnostic study, level IV.

Systemic inflammation worsens outcomes in emergency surgical patients.

BACKGROUND: Acute care surgeons are uniquely aware of the importance of systemic inflammatory response and its influence on postoperative outcomes; concepts like damage control have evolved from this experience. For surgeons whose practice is mostly elective, the significance of such systemic inflammation may be underappreciated. This study sought to determine the influence of preoperative systemic inflammation on postoperative outcome in patients requiring emergent colon surgery. METHODS: Emergent colorectal operations were identified in the American College of Surgeons National Surgical Quality Improvement Program 2008 dataset. Four groups were defined by the presence and magnitude of the inflammatory response before operation: no inflammation, systemic inflammatory response syndrome (SIRS), sepsis, or severe sepsis/septic shock. Thirty-day survival was analyzed by Kaplan-Meier method. RESULTS: A total of 3,305 patients were identified. Thirty-day survival was significantly different (p < 0.0001) among the four groups; increasing magnitudes of preoperative inflammation had increasing probability of mortality (p < 0.0001). Hazard ratios indicated that, compared with patients without preoperative systemic inflammation, the relative risk of death from SIRS was 1.9 (p < 0.0001), from sepsis was 2.5 (p < 0.0001), and from severe sepsis/septic shock was 6.7 (p < 0.0001). Operative time of <150 minutes was associated with decreased risk of morbidity (odds ratio = 0.64; p < 0.0001). CONCLUSIONS: Upregulation of the systemic inflammatory response is the primary contributor to death in emergency surgical patients. In SIRS or sepsis patients, operations <2.5 hours are associated with fewer postoperative complications. These results further reinforce the concept of timely surgical intervention and suggest a potential role for damage control operations in emergency general surgery. LEVEL OF EVIDENCE: II, prognostic study.

Innate immune response to pulmonary contusion: identification of cell type-specific inflammatory responses.

Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.