Nonsteroidal anti-inflammatory drugs' impact on nonunion and infection rates in long-bone fractures.

BACKGROUND: There is a dearth of clinical data regarding the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on long-bone fracture (LBF) healing in the acute trauma setting. The orthopedic community believes that the use of NSAIDs in the postoperative period will result in poor healing and increased infectious complications. We hypothesized that, first, NSAID use would not increase nonunion/malunion and infection rates after LBF. Second, we hypothesized that tobacco use would cause higher rates of these complications. METHODS: A retrospective study of all patients with femur, tibia, and/or humerus fractures between October 2009 and September 2011 at a Level 1 academic trauma center was performed . In addition to nonunion/malunion and infection rates, patient records were reviewed for demographic data, mechanism of fracture, type of fracture, tobacco use, Injury Severity Score (ISS), comorbidities, and medications given. RESULTS: During the 24-month period, 1,901 patients experienced LBF; 231 (12.1%) received NSAIDs; and 351 (18.4%) were smokers. The overall complication rate including nonunion/malunion and infection was 3.2% (60 patients). Logistic regression analysis with adjusted odds ratios were calculated on the risk of complications given NSAID use and/or smoking, and we found that a patient is significantly more likely to have a complication if he or she received an NSAID (odds ratio, 2.17; 95% confidence interval, 1.15-4.10; p < 0.016) in the inpatient postoperative setting. Likewise, smokers are significantly more likely to have complications (odds ratio, 3.19; 95% confidence interval, 1.84-5.53; p < 0.001). CONCLUSION: LBF patients who received NSAIDs in the postoperative period were twice as likely and smokers more than three times likely to suffer complications such as nonunion/malunion or infection. We recommend avoiding NSAID in traumatic LBF. LEVEL OF EVIDENCE: Epidemiologic & therapeutic study; level II.

A model to increase trauma reimbursement in the private practice environment.

BACKGROUND: Trauma physician reimbursement at many trauma centers is based on an academic or employed model. However, private practice is also used, especially at community-based trauma centers. Commercial insurance companies acknowledge that trauma care should be reimbursed at a higher rate than elective practice, but they often lack the ability to separate these lines of business. Federal law also prevents groups that are not integrated from shared negotiation. The objective of this study was to develop a model for private practice billing that provides increased reimbursement for trauma line of business. METHODS: The hospital created a trauma contracting organization. This organization contracted with the hospital and insurance companies to deliver trauma care. It obtained fee schedules for trauma care that were greater than for elective surgical care. It then contracted with trauma physicians to deliver trauma care using those fee schedules and its provider number. Data from 2009 were evaluated to determine the impact. RESULTS: Reimbursement rates were evaluated for multiple carriers and compared between the trauma contracting organization and the standard practice. Rate of reimbursement for self-pay patients and government carriers (Medicare, Medicaid, and Champus) were the same for both: 7% of charges for self-pay and 25% of charges for government carriers. Commercial carriers provided increased reimbursement for the trauma line of business, averaging 7% to 10% more return on charges. The annualized impact was over $300,000 more reimbursement on over $5,000,000 in charges. CONCLUSION: This model can provide a means to increase reimbursement for trauma care in a private practice environment.

Blockade of the Renin-Angiotensin system improves insulin receptor signaling and insulin-stimulated skeletal muscle glucose transport in burn injury.

Burn injury is associated with a decline in glucose utilization and insulin sensitivity due to alterations in postreceptor insulin signaling pathways. We have reported that blockade of the renin-angiotensin system with losartan, an angiotensin II type 1 (AT1) receptor blocker, improves whole body insulin sensitivity and glucose metabolism after burn injury. This study examines whether losartan improves insulin signaling pathways and insulin-stimulated glucose transport in skeletal muscle in burn-injured rats. Rats were injured by a 30% full-skin-thickness scalding burn and treated with losartan or placebo for 3 days after burn. Insulin signaling pathways were investigated in rectus abdominus muscle taken before and 90 s after intraportal insulin injection (10 U·kg). Insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3-kinase and plasma membrane-associated GLUT4 transporter were substantially increased with losartan treatment in burn-injured animals (59% above sham). Serine phosphorylated AKT/PKB was decreased with burn injury, and this decrease was attenuated with losartan treatment. In a separate group of rats, the effect of insulin on 2-deoxyglucose transport was significantly impaired in burned as compared with sham soleus muscles, in vitro; however, treatment of burned rats with losartan completely abolished the reduction of insulin-stimulated 2-deoxyglucose transport. These findings demonstrate a cross talk between the AT1 and insulin receptor that negatively modulates insulin receptor signaling and suggest a potential role of renin-angiotensin system blockade as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis in burn injury.

Evolution of a Level I Trauma System: changes in injury mechanism and its impact in the delivery of care.

BACKGROUND: Mechanisms of injury in trauma populations evolve over time as a result of system changes, prevention and safety activities, and shifts in population composition. Such changes have implications for reimbursement and resource utilization within all trauma centers. This study examines the evolution of trauma mechanisms at a regional Level I trauma center over 10 years to document the impact of these changes. METHODS: After IRB approval, the trauma registry was queried for total trauma admissions over 10 years. Data points of mechanism of injury, ISS, age, mortality, financial information, and discharge disposition were obtained. Statistical significance was determined by Chi square analysis. RESULTS: Total admissions increased steadily over the course of the 10 years studied. The percentage of motor vehicle crashes (MVC) decreased, while falls increased. Fall patients were older, with lower ISS and with longer length of stay. Mortality rates were higher, but statistically similar to those of the population as a whole. Fall patients were more frequently discharged to skilled nursing facilities. Federally supported Medicare programs increased steadily as a portion of payer mix. CONCLUSIONS: Mechanism of injury within our regional Level I trauma center changed over time with MVC as a percentage of blunt trauma mechanisms decreasing as falls increased. Falls are now a leading mechanism for traumatic injury, even at tertiary referral systems, and will continue to rise in incidence as the population of America ages. This change has direct implications for reimbursement and resource utilization. Current scoring systems employed by trauma centers do not predict this trend well.

Early evaluation of acute traumatic coagulopathy by thrombelastography.

Posttraumatic coagulopathy is a major cause of morbidity. This prospective study evaluated the thrombelastography (TEG) system and PlateletMapping (Haemoscope Corporation, Niles, Ill) values posttrauma, and it correlated those values with transfusions and fatalities. After institutional review board approval, assays were performed on 161 trauma patients. One citrated blood sample was collected onsite (OS), and 1 citrate and 1 heparinized sample were collected within 1 h of arrival to the emergency department (ED). Paired and unpaired t-testing was performed for nominal data with chi square testing for categorical values. Except for a slight increase in clot strength (maximal amplitude (MA)), there were no significant changes from OS to the ED. None of the TEG parameters were significantly different for the 22 patients who required transfusion. PlateletMapping showed lower platelet adenosine diphosphate (ADP) responsiveness in patients who needed transfusions (MA = 22.7 +/- 17.1 vs MA = 35.7 +/- 19.3, P = 0.004) and a correlation of fibrinogen <100 mg/dL with fatalities (P = 0.013). For the 14 fatalities, TEG reaction (R) time was 3703 +/- 11,618 versus 270 +/- 393 s (P = < 0.001), and MA was 46.4 +/- 22.4 versus 64.7 +/- 9.8 mm (P < 0.001). Hyperfibrinolysis (percent fibrinolysis after 60 min (LY60) >15%) was observed in 3 patients in the ED with a 67% fatality rate (P = < 0.001 by chi-square testing). PlateletMapping assays correlated with the need for blood transfusion. The abnormal TEG System parameters correlated with fatality. These coagulopathies were already evident OS. The TEG assays can assess coagulopathy, platelet dysfunction, and hyperfibrinolysis at an early stage posttrauma and suggest more effective interventions.

The role of laparoscopy in trauma: a ten-year review of diagnosis and therapeutics.

Minimally invasive surgery has found many applications in general surgery. The role of laparoscopy in trauma has been debated as a diagnostic, as well as therapeutic, tool in hemodynamically stable patients. This study evaluated laparoscopy in the trauma population. A retrospective review of all laparoscopies performed in hemodynamically stable trauma patients from 1996 until 2006 was conducted. Mechanisms of injury, perioperative data, and demographic variables were analyzed using descriptive statistics and Student's t test. Exploratory diagnostic laparoscopy was performed on 102 patients. Laparoscopy was negative for 65 per cent of patients; 12 per cent of these were converted to laparotomy due to adhesions, hemoperitoneum, or surgeon preference. None of the conversions revealed intra-abdominal injury at laparotomy. An injury was diagnosed at laparoscopy in the remaining 35 per cent, with 55 per cent conversion rate to repair the injury. Therapeutic laparoscopy included serosal repair, hemorrhage control, diaphragmatic repair, and other standard laparoscopic treatments. No patient required re-exploration, there were no missed injuries or other complications, and no patient died in this study. Laparoscopy has an important diagnostic and therapeutic role in selected hemodynamically stable trauma patients. Using a minimally invasive approach can reduce the potential morbidity of negative laparotomy.

Prospective comparison of microscopic and gross hematuria as predictors of bladder injury in blunt trauma.

OBJECTIVES: The evaluation of the genitourinary system in patients with blunt trauma remains controversial. Historically, patients with more than 50 red blood cells on urinalysis underwent additional genitourinary imaging. Retrospective studies have demonstrated that bladder injury is almost always associated with gross hematuria. We have prospectively demonstrated that bladder imaging is required for gross hematuria and unnecessary for microscopic hematuria. METHODS: Patients sustaining blunt trauma with hematuria were prospectively evaluated during a 3-year period. During the first 18 months of the study (first treatment arm), patients with microscopic hematuria (more than 50 red blood cells on urinalysis) underwent bladder imaging. During the second 18 months, patients underwent bladder imaging only for gross hematuria. RESULTS: A total of 8026 patients were evaluated. In the first arm, 214 patients underwent cystography for microscopic hematuria, and no bladder injuries were identified; 78 patients underwent cystography for gross hematuria, and 21 bladder injuries were identified. Chi-square analysis revealed no difference in the presence of microscopic hematuria to predict for bladder injury. In the second arm, 308 patients presented with microscopic hematuria, none of whom underwent cystography, and 91 patients underwent cystography for gross hematuria, with 15 bladder injuries identified. The presence of gross hematuria demonstrated 100% sensitivity and 98.5% specificity as a screening test for bladder injury. No bladder injuries were missed. CONCLUSIONS: The results of our study have shown that the presence of gross hematuria warrants evaluation of the bladder. The presence of gross hematuria demonstrated improved sensitivity, specificity, positive predictive value, negative predictive value, and accuracy over the presence of microscopic hematuria in the detection of bladder injury. Using gross hematuria as an indication for bladder imaging will eliminate unnecessary imaging without compromising the quality of patient care.

The consequences of high-risk behaviors: trauma during pregnancy.

BACKGROUND: Trauma during pregnancy places two lives at risk. Knowledge of risk factors for trauma during pregnancy may improve outcomes. METHODS: We reviewed the charts of 188 such patients admitted to a Level I trauma center from 1996 to 2004. A comparison was made of injury severity and outcome from a cohort of nonpregnant female trauma patients selected with a similar temporal occurrence and age range. RESULTS: Motor vehicle collisions comprised 160 cases, 67 using a restraint device. Of 84 patients tested, 45 tested positive for intoxicants, 16 positive for 2 or more intoxicants. A significant trend toward less testing through the study period was observed (p = 0.0002). Injury severity was assessed by Revised Trauma Score (RTS). RTS <11 or admission to operating room or intensive care units (OR/ICU) classified patients as severely injured. The six maternal fatalities had an RTS <11 or OR/ICU disposition. Fetal outcomes included 155 live in utero, 18 live births, and 15 fatalities correlating with injury severity by either criteria (p < 0.0001). Of the fetal fatalities, 7 occurred with RTS = 12, but only 3 fatalities occurred in the 147 cases not admitted to OR/ICU. Gestational age correlated (p < 0.0001) with fetal outcomes. The 18 live births had mean gestational ages of 35 +/- 4 weeks as compared with fetal fatalities at 20 +/- 9 weeks, and fetuses alive in utero at 22 +/- 9 weeks gestation. Coagulation tests prothrombin time (PT), international normalized ratio (INR) (both p < 0.008), and partial thromboplastin time (PTT) (p < 0.0001) correlated with maternal outcome. A matched cohort of nonpregnancy trauma cases during the same time frame indicated that, despite a significantly higher percentage of severely injured patients, fewer fatalities occurred. This might reflect a greater risk for the pregnant trauma patient. CONCLUSIONS: This study of trauma in pregnancy cases revealed a high percentage with risk behaviors. There was a significant trend toward less intoxicant testing in recent years. Coagulation tests were the most predictive of outcomes. Lower gestational age correlated with fetal demise.

Regulation of apoptosis in eicosapentaenoic acid-treated HL-60 cells.

BACKGROUND: Neutrophil apoptosis is an important physiological process in the resolution of pulmonary inflammation. Previous studies have shown that eicosapentaenoic acid (EPA; 20:5n-3) increases the rate of apoptosis in a concentration- and time-dependent manner in HL-60 cells. However, it is not known if the EPA-induced apoptosis involves the lipoxygenase (LO) and cyclooxygenase (COX) enzymes or the downstream metabolic products of these enzymes. Thus, the objective of this study was to determine the effects of inhibitors LO and COX enzymes on apoptosis, viability, and necrosis in EPA-treated HL-60 cells. MATERIALS AND METHODS: Cells were incubated with 50 mum EPA in the presence of an enzyme inhibitor (1-10 microm) for 12 h. Compounds were used to inhibit COX 1 and 2 (ibuprofen), 5-, 12-, 15-LO (NDGA), 12-LO (baicalein), 5-LO (AA-861), and 5-LO activating protein (MK-886). Eicosanoid (0.001-1.0 mum) add-back experiments were also conducted; LTB(4) and 5-HETE with 5-LO inhibition and 12-HETE with 12-LO inhibition. Flow cytometry was used to assess apoptosis. RESULTS: Inhibition of COX 1 and 2 had no effect on apoptosis. Inhibition of 5-LO and 12-LO significantly increased apoptosis in EPA-treated HL-60 cells. Addition of LTB(4) reduced apoptosis to levels significantly lower than in HL-60 cells treated with EPA alone; 5-HETE and 12-HETE also lowered apoptosis to control levels. CONCLUSIONS: These data indicate that inhibition of LO, particularly 5-LO, increased apoptosis in EPA-treated HL-60 cells. Furthermore, this study demonstrated that the products of the LO enzymes, particularly LTB(4), are critical in the regulation of apoptosis in EPA-treated HL-60 cells.

Blockade of the renin-angiotensin system improves insulin sensitivity in thermal injury.

Insulin resistance after burn is associated with alterations in postreceptor insulin signaling and abnormal glucose homeostasis. The renin-angiotensin system (RAS) exerts a largely inhibitory role on insulin action and is activated after burn injury. We hypothesized that upregulation of RAS is involved in the development of insulin resistance in burned rats. We examined the possibility that an angiotensin II type 1 (AT1) receptor blocker, losartan, enhances insulin sensitivity and thereby increases glucose tolerance in thermally injured rats. A 30% body surface area burn was induced by immersion of the dorsum into water with a temperature level of 95 degrees C for 15 s. Sham-burned rats were immersed in water with a temperature level of 23 degrees C. Losartan (30 mg/kg per day) or placebo (water) was given by gavage immediately after the burn injury and daily for 3 days postburn injury, resulting in sham-burned, burn placebo, and burn losartan groups. Plasma angiotensin II levels between burn placebo and sham-burned groups were not different 3 days after burn injury. However, losartan significantly increased plasma angiotensin II levels (P < 0.05), suggesting blockade of the AT1 receptor. An oral glucose tolerance test was performed 3 days postburn injury. There was an increase in the area under the curve for insulin and the glucose insulin index in burn placebo group as compared with sham-burned group, indicating insulin resistance. Losartan treatment abolished the insulin resistance in burn as evidenced by an area under the curve for insulin and glucose insulin index lower than that in the burn placebo group and similar to that in the sham-burned group. This suggests that insulin resistance and glucose intolerance associated with burn injury is, in part, caused by RAS.

Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid-treated HL-60 cells.

BACKGROUND: Enteral nutrition containing eicosapentaenoic (20:5 omega-3) and gamma-linolenic acid (18:3 omega-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/gamma-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. METHODS: Cells were incubated with 50 microM eicosapentaenoic/20 microM gamma-linolenic acid in the presence of an enzyme inhibitor (1-10 microM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. RESULTS: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. CONCLUSIONS: These data suggest that the processing of eicosapentaenoic and gamma-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival.

Role of downstream metabolic processing of proinflammatory fatty acids by 5-lipoxygenase in HL-60 cell apoptosis.

BACKGROUND: Proinflammatory eicosanoids formed from arachidonic acid (AA) by lipoxygenase (LO) and cyclooxygenase (COX) pathways have been shown to inhibit apoptosis in certain cell types. This study determined whether inhibition of LO and COX increased apoptosis in AA-treated HL-60 cells in vitro. METHODS: HL-60 cells were incubated with 50 micromol/L AA and an enzyme inhibitor (1-10 micromol/L) for COX, LO, 12-LO, and 5-LO for 12 hours. Flow cytometry was used to assess viability, apoptosis, and necrosis. Apoptosis was further assessed using terminal dUTP nick end-labeling and DNA fragmentation. RESULTS: The highest concentration of LO inhibitors, but not COX inhibitors, decreased viability and increased apoptosis and necrosis in the presence of exogenous AA. CONCLUSION: These results suggest that disruption of the metabolism of AA by LO, in particular 5-LO, decreases cell survival and increases apoptosis. Thus, downstream metabolic processing of AA by LO but not COX plays a critical role in the regulation of HL-60 cell apoptosis.

Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells.

Tamoxifen is an antiestrogen used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. It functions by competitively inhibiting the estrogen receptor and inducing apoptosis and G1 cell cycle arrest. Genistein is a soy phytoestrogen that inhibits breast cancer cell growth in vitro at doses of 10 microM or above. At lower doses genistein may stimulate cell growth and entry into the cell cycle. We hypothesized that treatment with low-dose genistein would reverse the inhibitory effects of tamoxifen in estrogen-receptor-positive breast cancer cells. Cell cycle kinetics and cell proliferation in T47-D human breast cancer cells were examined after exposure to genistein and tamoxifen in a low-estrogen environment designed to mimic a post-menopausal state. Cell proliferation was assessed by a colorimetric assay. Cell cycle kinetics were determined by flow cytometry. Tamoxifen caused G1 arrest and a decrease in proliferation. Genistein reversed the inhibitory effects of tamoxifen on both proliferation and G1 arrest. Thus low-dose genistein was able to inhibit the therapeutic effects of tamoxifen in this postmenopausal model of breast cancer.