Prehospital factors associated with mortality in injured air medical patients.

BACKGROUND: Air medical transport provides rapid transport to definitive care. Overtriage and the expense and risk of transport may offset survival benefits. OBJECTIVE: We assessed the ability of prehospital factors to predict resource need for helicopter-transported patients. METHODS: We performed a prospective, observational cohort analysis of injured scene patients taken to one of two level I trauma centers from October 2009 to September 2010. Variables analyzed included patient demographics, diagnoses, and clinical outcomes (in-hospital mortality, emergent surgery within 24 hours, blood transfusion within 24 hours, and intensive care unit [ICU] admission ≥24 hours, as well as a combined outcome of all clinical outcomes). Prehospital variables were prospectively obtained from air medical providers at the time of transport and included past medical history, mechanism of injury, and clinical factors. We compared those variables with and without the outcomes of interest via χ(2) analysis and the Kruskal-Wallis test, where appropriate. Multivariate logistic regression identified factors associated with outcomes of interest with the intent of developing a clinical prediction tool. RESULTS: Five hundred fifty-seven patients were transported during the study period. The majority of the patients were male (67%) and white (95%) and had an injury that occurred in a rural location (58%). Most injuries were blunt (97%), and patients had a median Injury Severity Score (ISS) of 9. The overall mortality was 4%; 48% of the patients had one of the four outcomes. The most common reasons for requesting air transport were motor vehicle collision (MVC) with high-risk mechanism (18%), MVC at a speed greater than 20 mph (18%), Glasgow Coma Scale score (GCS) less than 14 (15%), and loss of consciousness (LOC) greater than 5 minutes (15%). Factors associated with mortality were age greater than 44 years, GCS less than 14, systolic blood pressure (SBP) less than 90 mmHg, and flail chest. This model had 100% sensitivity and 50% specificity and missed no deaths. The combined endpoint of all four outcomes (death, receipt of blood, surgery, ICU admission) included intubation by emergency medical services, two or more fractures of the humerus/femur, presence of a neurovascular injury, a crush injury to the head, failure to localize to pain on examination, GCS less than 14, or the presence of a penetrating head injury. This model had a sensitivity of 57% (53%-61%) and a specificity of 78% (75%-87%). CONCLUSIONS: Very few prehospital criteria were associated with clinically important outcomes in helicopter-transported patients. Evidence-based guidelines for the most appropriate utilization of air medical transport need to be further evaluated and developed for injured patients.

Implementation and early outcomes of a peer-led traffic safety initiative for high school students.

Compared with other age groups, teenagers have the lowest rate of safety belt use. We sought to determine whether an ongoing, student-led initiative would be effective in increasing safety belt use among high school students compared with another school in which the intervention did not take place. At the intervention school, there was a statistically significant increase of 15% in observed safety belt use and evidence of increased knowledge regarding proper safety belt use. High schools can be effective in changing the traffic safety behaviors of its students.

Thrombospondin-1-deficient mice are not protected from bleomycin-induced pulmonary fibrosis.

Thrombospondin-1 (TSP-1) is an extracellular protein critical to normal lung homeostasis, and is reported to activate latent transforming growth factor-ß (TGF-ß). Because active TGF-ß is causally involved in lung fibrosis after bleomycin challenge, alterations in TSP-1 may be relevant to pulmonary fibrosis. We sought to determine the effects of TSP-1 deficiency on the susceptibility to bleomycin-induced pulmonary fibrosis in a murine model. Age-matched and sex-matched C57BL/6 wild-type (WT) and TSP-1-deficient mice were treated twice weekly for 4 weeks with intraperitoneal bleomycin (0.035 U/g) or PBS, and were allowed to rest 1 week before being killed. Their lungs were inflated with PBS, fixed in formalin, paraffin-embedded, and sectioned. A certified veterinary pathologist blindly scored each slide for inflammation and fibrosis. Lungs were homogenized to obtain RNA and protein for the real-time RT-PCR analysis of connective tissue growth factor (CTGF) and collagen I, and for Western blotting to detect phospho-Smad2, or total Smad2/3, respectively. In response to bleomycin treatment, measures of fibrosis and inflammation, along with CTGF and collagen I mRNA concentrations, were increased in TSP-1-deficient mice compared with WT mice. Notably, Smad 2/3 signaling was of equal strength in WT and TSP-1 knockout mice treated with bleomycin, suggesting that TSP-1 is not required for the activation of TGF-ß. These results demonstrate that TSP-1 deficiency does not protect mice from systemic bleomycin challenge, and that TSP-1 deficiency is associated with increased expression of lung collagen and CTGF.

Incidental findings in the cervical spine at CT for trauma evaluation.

OBJECTIVE: CT is the standard of care for assessment of traumatic injuries. Because of the detail depicted with this technique, findings incidental to the injury are easily detected. We sought to determine the frequency and types of incidental findings in the cervical spines of trauma patients undergoing CT. MATERIALS AND METHODS: The trauma registry was accessed to identify the cases of patients evaluated with cervical spine CT at a level 1 trauma center from January to July 2007. Trauma registry data, including age, sex, injury severity score, mechanism of injury, length of stay, and diagnosis were recorded, and all CT scans of the cervical spine were reviewed for incidental findings. Clinically significant incidental findings were classified according to bodily location, and the association between various patient characteristics and the likelihood of an incidental finding was assessed. RESULTS: We identified incidental CT findings in 230 of 1,256 patients (18.3%) who underwent CT of the cervical spine during an initial trauma evaluation. We stratified the incidental findings as trauma-related and not trauma-related. The likelihood of non-trauma-related incidental findings was associated with age (p < 0.0001). The likelihood of trauma-related incidental findings was associated with injury severity score (p < 0.0001). CONCLUSION: Incidental findings in the cervical spine were associated with age, injury severity score, and mechanism of injury. Awareness of the prevalence of incidental findings is important to assuring that both traumatic and nontraumatic pathologic findings are detected and appropriately managed.

Speaking the same language: underestimating financial impact when using diagnosis-related group versus ICD-9-based definitions for trauma inclusion criteria.

BACKGROUND: Hospital accounting methods use diagnosis-related group (DRG) data to identify patients and derive financial analyses and reports. The National Trauma Data Bank and trauma programs identify patients with trauma by International Classification of Diseases, Ninth Edition (ICD-9)-based definitions for inclusion criteria. These differing methods of identifying patients result in economic reports that vary significantly and fail to accurately identify the financial impact of trauma services. METHODS: Routine financial data were collected for patients admitted to our Trauma Service from July 1, 2005 to June 30, 2006 using two methods of identifying the cases; by trauma DRGs and by trauma registry database inclusion criteria. The resulting data were compared and stratified to define the financial impact on hospital charges, reimbursement, costs, contribution to margin, downstream revenue, and estimated profit or loss. The results also defined the impact on supporting services, market share and total revenue from trauma admissions, return visits, discharged trauma alerts, and consultations. RESULTS: A total of 3,070 patients were identified by the trauma registry as meeting ICD-9 inclusion criteria. Trauma-associated DRGs accounted for 871 of the 3,070 admissions. The DRG-driven data set demonstrated an estimated profit of $800,000 dollars; the ICD-9 data set revealed an estimated 4.8 million dollar profit, increased our market share, and showed substantial revenue generated for other hospital service lines. CONCLUSIONS: Trauma DRGs fail to account for most trauma admissions. Financial data derived from DRG definitions significantly underestimate the trauma service line's financial contribution to hospital economics. Accurately identifying patients with trauma based on trauma database inclusion criteria better defines the business of trauma.

Computed tomographic angiography versus conventional angiography for the diagnosis of blunt cerebrovascular injury in trauma patients.

BACKGROUND: Blunt cerebrovascular injuries (BCVI) in trauma patients are rare but potentially devastating injuries, particularly if the diagnosis is delayed. Conventional angiography (CA) has been the screening and diagnostic modality of choice for identifying BCVI. With the advent of high-resolution computed tomography (CT), CT angiography has become a common modality for the screening of BCVI. A liberalized screening approach has suggested that cerebrovascular injuries are missed in many patients; however, no standard BCVI screening protocol exists. Early diagnosis of the BCVI can prevent long-term sequelae. METHODS: In this prospective study, all patients received a CT angiogram (16-slice or 64-slice) at the time of injury assessment and followed 24 hours to 48 hours later with CA of the cerebrovasculature. RESULTS: A total of 158 patients were enrolled in the study. CA identified 32 injuries to the cerebrovasculature in 27 patients; CT detected only 13 true injuries (40.6%) in 12 patients. Of the 32 injuries, 11 were carotid artery injuries and 21 were of the vertebral artery. Seventy-four patients were screened with the 16-slice CT scanner with an overall sensitivity of 29%, and 84 patients were screened with the 64-slice CT scanner with an overall sensitivity of 54%. The combined specificity and sensitivity of 16- and 64-slice CT in detecting BCVI were 0.97 (95% confidence interval: 0.92-0.99) and 0.41 (95% confidence interval: 0.22-0.61), respectively. CONCLUSION: Neither 16- nor 64-slice CT angiography is as accurate as CA as a screening tool for BCVI.

A multidisciplinary motorcycle safety initiative.

Motorcycle registrations are on the rise in the United States, especially among riders over 40 years of age. While motorcycle popularity has been increasing, so have injuries and fatalities. Unfortunately, motorcycle crashes have been increasing at a disproportionately high rate. In 2007, motorcycle fatalities reached the highest level since the Department of Transportation began collecting data in 1975. Because of the increasing number of motorcycle crashes in Ohio and Central Ohio, a multidisciplinary team consisting of the Grant Medical Center's trauma program, Franklin County Safe Communities (a Columbus Public Health program), the American Motorcyclist Association, and Columbusbiker.com applied for and received a $5,000 motorcycle safety mini-grant from the American Public Health Association, Public Health Traffic Safety Institute. The mini-grant provided funding from October 2008 to September 2009. The 3 goals of the mini-grant were to promote "sharing the road" with motorcycles, inform the reentry riding community on the necessity of proper rider training, and train the Ohio injury prevention workforce on motorcycle safety and the motorcycling culture. However, the ultimate goal is to prevent death and reduce injury due to motorcycle crashes.

Wheelchair falls: 5 years of data from a level I trauma center.

Falling from a wheelchair can result in a serious injury. Our report details injuries sustained by 30 individuals who fell from a wheelchair and presented to our level I trauma center over 5 years. Most fall victims (60%) were older than 65 years. The most common injuries were traumatic brain injury, femur fractures, and concussion. The most serious injuries were traumatic brain injuries and a vertebral fracture with resultant spinal cord injury. In the trauma setting, practitioners discharging patients using wheelchairs should be aware of this mechanism of injury and should provide education to ensure proper fit and use of the device.

Temporal artery scanning falls short as a secondary, noninvasive thermometry method for trauma patients.

Oral and mandibular trauma pose barriers to oral thermometry. We sought to determine whether temporal artery (TA) scanning thermometry could be an accurate, noninvasive back up method of thermometry in patients with these types of traumatic injury. We compared 3 techniques of TA scanning, axillary thermometry, and oral thermometry in critical care patients. Our results indicate that TA scanning methods were, at best, comparable with axillary measurements. In addition, the performance of the TA scanners varied with body mass index, whereas axillary readings did not.

Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis.

RATIONALE: An increase in the number of mononuclear phagocytes in lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) worsens prognosis. Chemokines that recruit mononuclear phagocytes, such as CC chemokine ligand 2 (CCL2), are elevated in bronchoalveolar lavage (BAL) fluid (BALF) from patients with IPF. However, little attention is given to the role of the mononuclear phagocyte survival and recruitment factor, macrophage colony-stimulating factor (M-CSF), in pulmonary fibrosis. OBJECTIVES: To investigate the role of mononuclear phagocytes and M-CSF in pulmonary fibrosis. METHODS: Wild-type, M-CSF-/-, or CCL2-/- mice received intraperitoneal bleomycin. Lung inflammation and fibrosis were measured by immunohistochemistry, ELISA, collagen assay, BAL differentials, real-time polymerase chain reaction, and Western blot analysis. Human and mouse macrophages were stimulated with M-CSF for CCL2 expression. BALF from patients with IPF was examined for M-CSF and CCL2. MEASUREMENTS AND MAIN RESULTS: M-CSF-/- and CCL2-/- mice had less lung fibrosis, mononuclear phagocyte recruitment, collagen deposition, and connective tissue growth factor (CTGF) expression after bleomycin administration than wild-type littermates. Human and mouse macrophages stimulated with M-CSF had increased CCL2 production, and intratracheal administration of M-CSF in mice induced CCL2 production in BALF. Finally, BALF from patients with IPF contained significantly more M-CSF and CCL2 than BALF from normal volunteers. Elevated levels of M-CSF were associated with elevated CCL2 in BALF and the diagnosis of IPF. CONCLUSIONS: These data suggest that M-CSF contributes to the pathogenesis of pulmonary fibrosis in mice and in patients with IPF through the involvement of mononuclear phagocytes and CCL2 production.

Plating of acute humeral diaphyseal fractures through an anterior approach in multiple trauma patients.

OBJECTIVE: We evaluated the clinical and long-term functional outcomes of humeral diaphyseal fractures treated with acute anterior plating in a trauma population. DESIGN: Single-center, retrospective cohort analysis with long-term prospective follow-up. SETTING: Urban, Level I trauma center. PATIENTS: Ninety-six patients with high-energy fractures of the humeral shaft were treated over a 10-year period. INTERVENTION: All patients were treated by a standard surgical protocol of open reduction through an anterior approach with small or large fragment fixation in the supine position. MAIN OUTCOME MEASUREMENTS: Mechanism of injury, time to union, complications, and range of motion during clinical follow-up were obtained. We also prospectively assessed long-term strength, range of motion, and perceptions of disability using the Disabilities of the Arm, Shoulder and Hand questionnaire. RESULTS: Mean time to surgery was 5 days (standard deviation, 11 days); 97.5% of patients achieved union in an average of 16.9 weeks (range, 6-56 weeks). Complications included two postoperative infections, two nonunions, and three implant failures. Long-term follow-up (n = 34) averaged 4.75 years (range, 1.4-10.8 years). On average, no significant differences between the injured and uninjured extremities were seen in range of motion at the shoulder and elbow with the exception of shoulder flexion. A modest loss of upper extremity strength in the injured arm was appreciated. The mean Disabilities of the Arm, Shoulder and Hand score was 25.9 (range, 0-79). CONCLUSIONS: A standard anterior surgical approach with small fragment fixation is a safe and effective treatment for humeral shaft fractures in multiple trauma patients. We show a high union rate and few complications, although a modest loss of function and some perceived disability exists in the long-term.

Alveolar macrophages lack CCR2 expression and do not migrate to CCL2.

BACKGROUND: The recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression during in vitro monocyte to macrophage differentiation. To date, no study examined the in vivo differences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages. METHODS: We examined the expression of these receptors in human peripheral blood monocytes and alveolar macrophages using microarray analysis, reverse-transcriptase PCR, flow cytometry and migration analyses. RESULTS: In contrast to peripheral blood monocytes, alveolar macrophages did not express the CCL2 receptor, CCR2, and did not migrate toward CCL2. In contrast, monocytes and freshly isolated resident alveolar macrophages both migrated towards CCL3. However, up to 6-fold more monocytes migrated toward equivalent concentrations of CCL3 than did alveolar macrophages from the same donor. While peripheral blood monocytes expressed the CCL3 receptor, CCR1, alveolar macrophages expressed the alternate CCL3 receptor, CCR5. The addition of anti-CCR5 blocking antibodies completely abrogated CCL3-induced migration in alveolar macrophages, but did not affect the migration of peripheral blood monocytes. CONCLUSION: These data support the specificity of CCL2 to selectively drive monocyte, but not alveolar macrophage recruitment to the lung and CCR5 as the primary macrophage receptor for CCL3.

Proteome comparison of alveolar macrophages with monocytes reveals distinct protein characteristics.

Alveolar macrophages (AMs) are a subset of tissue macrophages situated in the alveolar milieu. Compared with their precursor blood monocytes, AMs exhibit distinct physiologic functions unique to their anatomic location. However, the molecular details that control monocyte differentiation into AMs remain unknown. This study employed a proteomic approach to define protein characteristics that distinguish AMs from monocytes. AMs and monocytes were obtained from six nonsmoking, healthy donors. Whole cell lysates from each donor's AMs and monocytes were analyzed by two-dimensional (2D) gel electrophoreses. The protein density for each protein spot in a 2D gel was compared between these two cell types. Proteins that demonstrated consistent level changes of greater than 2.5-fold in all six donors were subjected to tandem mass spectrometry for protein identity. Using this process, we revealed proteome changes in AMs that relate to their physiologic roles in proteolysis, actin reorganization, and cellular adaptation in the unique alveolar milieu. By comparison, blood monocytes displayed higher levels of the proteins involved in transcription, metabolism, inflammation, and in the control of proteolysis. These results provide new insights into the biology of mononuclear phagocytes and set a basis for future causality studies.

TGF-beta 1 suppresses [correction of supresses] myeloid Fc gamma receptor function by regulating the expression and function of the common gamma-subunit.

We have previously reported that FcgammaR-mediated function in myeloid cells is a tightly regulated event that is influenced by the cytokines present in the milieu. TGF-beta1 is an immunosuppressive cytokine with pleiotropic effects on immune responses; however, the molecular mechanism by which TGF-beta suppresses immune responses is poorly understood. In this study, we have analyzed the effect of TGF-beta on FcgammaR-mediated activation of myeloid cells. We report that TGF-beta1-treated THP-1 human myeloid cells displayed reduced ability to phagocytose IgG-coated particles. Because FcgammaR expression is modulated by cytokines, we analyzed expression levels of FcgammaRI, FcgammaRIIa, FcgammaRIIb, and FcgammaRIIIa in cells cultured with or without TGF-beta1 and found while total protein levels of the FcgammaR were not reduced, surface expression of FcgammaRI and FcgammaRIII was lower in cells cultured with TGF-beta1. Concomitantly, there was a dose-dependent reduction in the expression of the FcgammaR-associated gamma-subunit. This suppressive effect of TGF-beta was likewise observed in bone marrow-derived murine myeloid cells and human monocytes. Importantly, TGF-beta1 also significantly reduced the production of monocyte chemoattractant protein-1 induced by immobilized IgG, which would further reduce monocyte recruitment to the site of inflammation. In contrast, human alveolar macrophages were refractory to this effect, expressing low levels of TGF-beta type II receptors compared with peripheral blood monocytes from the same donor. These data provide insight into the regulation of immune responses by TGF-beta1 and demonstrate the selectivity of these effects.

Presentation of nitric oxide regulates monocyte survival through effects on caspase-9 and caspase-3 activation.

In the absence of survival factors, blood monocytes undergo spontaneous apoptosis, which involves the activation of caspase-3. Although nitric oxide can block caspase-3 activation and promote cell survival, it can also induce apoptosis. We hypothesized that nitrosothiols that promote protein S-nitrosylation would reduce caspase-3 activation and cell survival, whereas nitric oxide donors (such as 1-propamine 3-(2-hydroxy-2-nitroso-1-propylhydrazine (PAPA) NONOate and diethylamine (DEA) NONOate) that do not target thiol residues would not. Using human monocytes as a model, we observed that nitrosothiol donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine suppressed caspase-9 and caspase-3 activity and DNA fragmentation. In contrast, PAPA or DEA NONOate did not promote monocyte survival events and appeared to inhibit monocyte survival induced by macrophage colony-stimulating factor. The caspase-3-selective inhibitor DEVD-fluoromethyl ketone reversed DNA fragmentation events, and the caspase-9 inhibitor LEHD-fluoromethyl ketone reversed caspase-3 activity in monocytes treated with PAPA or DEA NONOate in the presence of macrophage colony-stimulating factor. These results were not caused by differences in glutathione levels or the kinetics of nitric oxide release. Moreover, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine directly blocked the activity of recombinant caspase-3, which was reversed by the reducing agent dithiothreitol, whereas PAPA or DEA NONOate did not block the enzymatic activity of caspase-3. These data support the hypothesis that nitrosylation of protein thiol residues by nitric oxide is critical for promoting the survival of human monocytes.