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The data regarding rates of deep venous thrombosis and pulmonary embolism after foot and ankle trauma remain sparse. In this study of the National Trauma Data Bank Data set (2007-2009 and 2010-2016), these rates were reexamined and risk factors associated with these complications were assessed. Data quality is improved in the later data set; the incidence of deep venous thrombosis and pulmonary embolism was 0.28% and 0.21%, respectively, in the 2010-2016 data. Prophylaxis, male gender, treatment in a university hospital, open reduction, chronic obstructive pulmonary disease, and hypertension were notable significant risk factors for pulmonary embolism. For deep venous thrombosis, male gender, bleeding disorder, angina, and prophylaxis were risk factors. Careful, individualized assessment of the risk factors associated with deep venous thrombosis and pulmonary embolism is important, and the merits of routine prophylaxis remain in question.

Traumatic injuries account for millions of emergency room visits and hospital admissions annually. Motor vehicle crashes (MVCs) remain a leading cause of mortality between the ages of 1 and 44 years. With the popularity of smart devices, drivers are ever more distracted on the road. Programs that educate drivers on safe actions and to raise awareness of the perils of drunk and distracted driving exist, but there are few data that demonstrate a reduction in motor vehicle injury rates. We sought to determine if the implementation of such a program in our community would impact the rates of MVCs. Assessing the effectiveness of the Save A Life Tour, a risk reduction program, this intervention was instituted at a single area high school. The numbers of adolescent drivers aged 16 to 21 years involved in MVCs treated at the regional Level I trauma center were compared over two time intervals and between two adjoining counties. The time intervals consisted of preintervention and postintervention surveillance, each over a period of 3 years. Using our trauma registry, we compared the incidence of MVC between the two counties and between the two age groups. The data were also compared with the incidence among these populations nationally. In the preintervention period, the number of adolescent MVCs treated from the catchment area was 166, and the number in the postintervention period was 105. This represented a risk reduction of 37% (p < 0.05). During the same intervals, the incidence in the nonintervention control catchment area increased by 12%. There was no significant change in the population aged 16 to 21 years over the time intervals in either area. These results suggest that ongoing educational intervention programs aimed at adolescent drunk and distracted driving can have an impact on these life-threatening behaviors and on the incidence of MVCs. LEVEL OF EVIDENCE Therapy, level IV.

BACKGROUND Recent management of acute cholecystitis favors same admission (SA) or emergent cholecystectomy based on overall shorter hospital stay and therefore cost savings. We adopted the practice of SA cholecystectomy for the treatment of acute cholecystitis at our tertiary care center and wanted to evaluate the economic benefit of this practice. We hypothesized that the existence of complications, particularly among patients with a higher degree of disease severity, during SA cholecystectomy could negate the cost savings. AIM To compare complication rates and hospital costs between SA vs delayed cholecystectomy among patients admitted emergently for acute cholecystitis. METHODS Under an IRB-approved protocol, complications and charges for were obtained for SA, later after conservative management (Delayed), or elective cholecystectomies over an 8.5-year period. Patients were identified using the acute care surgery registry and billing database. Data was retrieved via EMR, operative logs, and Revenue Cycle Operations. The severity of acute cholecystitis was graded according to the Tokyo Guidelines. TG18 categorizes acute cholecystitis by Grades 1, 2, and 3 representing mild, moderate, and severe, respectively. Comparisons were analyzed with χ2, Fisher's exact test, ANOVA, t-tests, and logistic regression; significance was set at P < 0.05. RESULTS Four hundred eighty-six (87.7%) underwent a SA while 68 patients (12.3%) received Delayed cholecystectomy. Complication rates were increased after SA compared to Delayed cholecystectomy (18.5% vs 4.4%, P = 0.004). The complication rates of patients undergoing delayed cholecystectomy was similar to the rate for elective cholecystectomy (7.4%, P = 0.35). Mortality rates were 0.6% vs 0% for SA vs Delayed. Patients with moderate disease (Tokyo 2) suffered more complications among SA while none who were delayed experienced a complication (16.1% vs 0.0%, P < 0.001). Total hospital charges for SA cholecystectomy were increased compared to a Delayed approach ($44500 ± $59000 vs $35300 ± $16700, P = 0.019). The relative risk of developing a complication was 4.2x [95% confidence interval (CI): 1.4-12.9] in the SA vs Delayed groups. Among eight patients (95%CI: 5.0-12.3) with acute cholecystitis undergoing SA cholecystectomy, one patient will suffer a complication. CONCLUSION Patients with Tokyo Grade 2 acute cholecystitis had more complications and increased hospital charges when undergoing SA cholecystectomy. This data supports a selective approach to SA cholecystectomy for acute cholecystitis.

Department of Anesthesiology Botucatu Medical School University of Sao Paulo State, Distrito de Rubiao Junior, s/n, Botucatu, Sao Paulo

Evidence-based guidelines recommend cholecystectomy during initial hospitalization for complicated gallstone disease. Previous studies and quality initiative data from our institution demonstrated that only 40% to 75% of patients underwent cholecystectomy on index admission.In January 2009, we implemented a critical pathway to improve cholecystectomy rates for all patients emergently admitted for acute cholecystitis, mild gallstone pancreatitis, or common bile duct stones. We compared cholecystectomy rates during initial hospitalization, time to cholecystectomy, length of initial stay, and readmission rates in prepathway (January 2005 to February 2008) and postpathway patients (January 2009 to May 2010).Demographic and clinical characteristics were similar between prepathway (n = 455) and postpathway patients (n = 112). Cholecystectomy rates during initial hospitalization increased from 48% to 78% after pathway implementation (p0.0001). There were no differences in operative mortality or operative complications between the 2 groups. For patients undergoing cholecystectomy on initial hospitalization, the mean length of stay decreased after pathway implementation (7.1 days to 4.5 days; p0.0001), primarily due to a decrease in the time from admission to cholecystectomy (4.1 days to 2.1 days; p0.0001). Thirty-three percent of prepathway and 10% of postpathway patients required readmission for gallstone-related problems or operative complications (p0.0001), and each readmission generated an average of $19,000 in additional charges.Implementation of a multidisciplinary critical pathway improved cholecystectomy rates on initial hospitalization and lowered costs by shortening length of stay and markedly decreasing readmission rates for gallstone-related problems. Broader implementation of similar pathways offers the potential to translate evidence-based guidelines into clinical practice and minimize the cost of medical care.

Background: Postburn insulin dysfunction is a significant contributor to morbidity and mortality. A satisfactory mechanism for explaining this phenomenon remains elusive; however, resistin has been postulated to be involved. Initially discovered as an insulin antagonist secreted from adipose tissue in murine models, resistin’s function in humans has been more obscure. Resistin is not expressed significantly in human adipocytes although it has been detected in monocytes. We postulate that mononuclear activation at the site of burn injury affects the release of resistin and contributes to insulin dysfunction. Methods: Plasma from burned and healthy control individuals was characterized for glucose, insulin, and resistin protein levels. Adipose tissue from both groups was analyzed for resistin transcript; levels were found to be somewhat higher in the burned group though not significantly so. Circulating monocyte expression of resistin transcript was assayed in similar fashion. Results: In addition to finding that insulin and glucose were elevated postburn, a finding in agreement with past studies, we demonstrate that circulating resistin levels are significantly elevated as well. Insulin resistance was found to increase at a similar rate to resistin expression in the burn population, suggesting a correlation in these events. Adipose tissue from both groups was analyzed for resistin transcript; levels were found to be somewhat higher in the burned group though not significantly so. Circulating monocyte expression of resistin transcript was assayed and found to be profoundly elevated in the burn population. Conclusions: This data suggests that resistin is produced by activated monocytes in the adipose tissue around the periphery of burn wound. We suggest that postburn insulin function is adversely affected by resistin produced as a result of this monocyte activation.

Introduction: Motorcycles have become an increasingly popular mode of transportation despite their association with a greater risk for injury compared with automobiles. Whereas the recent incidence of annual passenger vehicle fatalities in the United States of America (USA) has progressively declined, motorcycle fatalities have steadily increased in the past 11 years. Although motorcycle injuries (MIs) have been studied, to the author’s knowledge there are no published reports on MIs in the USA during this 11-year period. Methods: Study data were derived from a prospectively collected Level I trauma center database. Data sampling included motorcycle crash injury evaluations for the 10-year period ending on 31 August 2008. This retrospective analysis included patient demographic and medical data, helmet use, Glasgow coma scale (GCS) score, injury severity score (ISS), length of hospital stay (LOS), specific injury diagnosis, and death. Data statistics were analyzed using the Spearman correlation coefficient, Kruskal-Wallis tests, and logistic regression. Results: The study identified 1252 motorcycle crash injuries. Helmets were worn by 40.7% of patients for which helmet data were available. The rates of the most common orthopedic injuries were tibia/fibula (19.01%), spine (16.21%), and forearm (10.14%) fractures. The most common non-orthopedic motorcycle crash injuries were concussions (21.09%), skull fractures (8.23%), face fractures (13.66%), and hemo- and pneumothorax (8.79%). There was a significant correlation between greater age and higher ISS (r=0.21, P

The purpose of this study was to show the relation between McBurney's point and the appendix in patients undergoing 3D MDCT and to investigate the effect of this information on a surgeon's choice of appendectomy incision.Among 142 adults undergoing consecutive MDCT studies, 100 patients (35 women, 65 men; mean age, 52.1 years) with an identifiable appendix on abdominopelvic MDCT examinations were selected for the study group. The presence of intraabdominal mass or a history of abdominal surgery were the exclusion criteria. Three-dimensional reconstruction of the CT data was performed with a surface shaded display algorithm. The locations of the base of the appendix and McBurney's point were marked on a single 3D image that allowed display of the skin surface markings for each patient. The superoinferior and mediolateral distances from the level of the appendix to the level of McBurney's point were measured, and the radial distance was calculated from these measurements. A surgeon experienced in emergency abdominal surgery reviewed 3D CT images and one axial image showing the appendix, and his choice of incision for each patient based on the CT information was recorded. The influence of the superoinferior and mediolateral distances of the appendix from McBurney's point on the surgeon's decision was analyzed with a multivariate logistic regression model.The appendix was exactly at McBurney's point in only 4% of the patients. In 36% of the cases, the appendix was within 3 cm, in 28% of cases it was 3-5 cm, and in 36% of the cases it was more than 5 cm away from McBurney's point. Mean +/- SD superoinferior, mediolateral, and radial distances between the appendix and McBurney's point were 33.0 +/- 24.1, 20.8 +/- 19.3, and 42.1 +/- 26.7 mm, respectively. After reviewing the images, the surgeon would have altered his incision site in 35% of the cases. The surgeon preferred a higher incision in 28% and a lower incision in 7% of the cases. Both positive and negative superoinferior displacement away from McBurney's point were significant factors regarding the surgeon's decision to alter the incision (p = 0.005), and the superoinferior distance was more than 3 cm in 94% of the cases in which the surgeon would have altered the incision.The location of the appendix varies widely among individuals, and McBurney's point has limitations as an anatomic landmark. Three-dimensional MDCT findings can be useful to surgeons customizing appendectomy incisions. Additional information about the location of the appendix in the CT report (if possible, together with a 3D image showing the location of the appendix) may be beneficial for surgeons performing appendectomy.

The purpose of this study was to determine the sensitivity and specificity of computed tomography (CT) without administration of oral contrast in confirming suspected acute appendicitis. One hundred seventy-three patient studies were retrieved by a computer-generated search for the word "appendicitis" in radiology reports. Patients presenting to the emergency department over an 8-month period were examined for acute abdominal pain or suspected acute appendicitis. IV-contrast-enhanced CT scans of the abdomen and pelvis were obtained without oral or rectal contrast. Criteria for diagnosis of acute appendicitis included a dilated appendix (>6 mm), periappendiceal inflammation, or abscess. Final diagnoses were established with surgical/clinical follow-up, histopathological analysis or both. The standard time (1 h) for the administration of oral contrast prior to the CT scan was eliminated. Fifty-nine CT diagnoses were made of acute appendicitis, 56 of which were histologically verified and three of which resulted in another diagnosis. One hundred fourteen CT diagnoses were negative for appendicitis. This corresponds to a sensitivity of 100% and specificity of 97%, a positive predictive value of 95%, and a negative predictive value of 100%. CT with IV contrast is sensitive and specific for the confirmation or exclusion of acute appendicitis. By eliminating the time required to administer oral contrast, the diagnosis might be made more rapidly.

Purpose: The surgical resident experience with trauma has changed. Many residents are exposed to predominantly nonoperative patient care experiences while on trauma rotations. Data from a large multicenter study were analyzed to estimate surgical resident exposure to trauma laparotomy, diagnostic peritoneal lavage (DPL), and focused abdominal sonography for trauma (U/S). Methods: Centers completed a self-report questionnaire on their institutional demographics, admissions, and procedure for a 2-year period (1998-1999). Results: A total of 82 trauma centers that provide resident teaching were included. The included centers represent over 247,000 trauma admissions. The majority of trauma centers (65.9%) had > 80% blunt injury. Although all centers performed laparotomies, other results were more variable. For U/S, 24.2% performed none at all and 47.0% performed fewer than two U/S examinations per month. For DPLs, 3.8% performed none and 66.7% performed fewer than two per month. Assuming 1 night of 4 on call, the average surgical resident training at a trauma center performing > 80% blunt trauma has the potential to participate in only 15 trauma laparotomies, 6 diagnostic peritoneal lavages, and 45 ultrasound examinations per year. In addition, the resident will care for an average of 500 blunt trauma patients before performing a splenectomy or liver repair. Conclusion: Surgical resident experience on most trauma services is heavily weighted to nonoperative management, with a relatively low number of procedures, little experience with DPL, and highly variable experience with ultrasound. These data have serious implications for resident training and recruitment into the specialty.

Burns are surrounded by an inflammatory zone of stasis that can progress to ischemia and extension of burn size. Synthetic fibronectin peptides have reduced tissue destruction in several models of inflammation. In this study, we postulate that administration of the peptide Trp-9-Tyr will alter the progression of tissue destruction following thermal injury. Baseline cutaneous blood flow was measured on New Zealand White rabbits with a laser doppler blood-flow meter. While the rabbits were under general anesthesia, 6 full-thickness burns were produced on the rabbits' backs. Blood flow in the zones of stasis was followed daily, and the number of zones that progressed to necrosis was determined at 72 hours. There were 3 experimental groups. Ten control animals received saline. Ten were treated with Trp-9-Tyr for 24 hours postburn. Ten received Trp-9-Tyr for 48 hours. Animals treated with Trp-9-Tyr had higher blood flow and less necrosis in the zones of stasis than did control animals, which was evident at 24 hours but more significant at 48 hours.

The most common cause of intraperitoneal adhesions is previous abdominal surgery. Postoperative adhesion formation results from a fibroproliferative inflammatory reaction that begins with an influx of polymorphonuclear leukocytes (PMNs) into the peritoneal cavity. Adherence of the PMNs to the endothelial cells (EC) is necessary for PMN migration into the tissue in response to a stimulus. Several receptor-counterreceptor pairs of ligands such as CD11/CD18 on the PMN and ICAM-1 (CD54) on EC have been identified. Monoclonal antibody against CD11/CD18 (R15.7) inhibits PMN adherence and migration and consequently protects against PMN-induced tissue injuries. We therefore studied the effect of preventing PMN-EC adherence, using anti-CD18 monoclonal antibody, on postoperative adhesion formation in rabbits. Group 1 was a control receiving physiologic saline, and group 2 received anti-CD18 antibody (R15.7, 2 mg/kg). The treatment was administered iv at the end of surgery and repeated on the first and second postoperative days. Peritoneal adhesions were induced at laparotomy by repairing two peritoneal defects, by oversewing the defect (model 1), and by resuturing the removed parietal peritoneum in its place as an ischemic graft (model 2). Adhesions were evaluated blindly at 10 days after operation by measuring the percentage of the suture line covered with adhesions (model 1) or by a scoring system (model 2). All control animals developed intraperitoneal adhesions and the percentage of the suture line covered with adhesions was 25 +/- 5.9% (mean +/- SEM) and the mean score in model 2 was 0.9 +/- 0.2. Anti-CD18 antibody, R15.7, increased the degree of postoperative adhesion formation in both models, but the results were significant only in model 2. Also, anti-CD18 antibody significantly decreased peritoneal neutrophils from 11.1 x 10(7) +/- 1.8 x 10(7) to 2.2 x 10(7) +/- 0.4 x 10(7) (P0.001) on the first postoperative day. It is concluded that inhibition of PMN-EC adherence does influence the postoperative adhesion formation. These results might suggest that PMNs have a role in modulating postoperative adhesion formation.

Evaluation of burn wound depth in pediatric patients is often difficult. A Laser Doppler Flowmeter with a temperature-controlled multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. The average perfusion levels for wounds that healed spontaneously in fewer than 21 days was significantly higher than the average perfusion levels for wounds that required excision and grafting or were not healed by day 21 after burn injury. Laser Doppler Flowmetry showed high positive predictive values for "nonhealing" wounds on postburn days 1, 2, and 3. These results suggest that Laser Doppler Flowmetry is a useful tool for burn wound assessment in pediatric patients.

The purpose of this study was to determine if hemorrhagic shock alters the alveolar macrophage (M phi) tumor necrosis factor (TNF) response to lipopolysaccharide (LPS) stimulation. New Zealand White rabbits underwent hemorrhage and resuscitation. At 1, 2, 3, 5, and 7 days post-shock, both M phis and peripheral whole blood monocytes were incubated in vitro with saline or Escherichia coli LPS. The supernatants were assayed for TNF activity using the L929 bioassay. Alveolar M phis from hemorrhaged animals showed reduced TNF activity during the first 5 days post-hemorrhage. Maximal depression of TNF activity was observed on days 3 and 5 post-hemorrhage (p < .05). In comparison, peripheral whole blood monocytes showed an increased TNF response on post-shock days 2 and 3. These results suggest that hemorrhagic shock and resuscitation differentially affect TNF response in alveolar and peripheral blood M phi populations.

Postoperative adhesion formation results from a fibroproliferative inflammatory reaction. Macrophages are critical in the final resolution of the inflammatory process and tissue repair, including modulation of proliferation and differentiation of fibroblasts and secretion of neutral proteases like plasminogen activator. We, therefore, studied the influence of peritoneal macrophage enhancement on postoperative adhesion formation in five groups of rabbits. Group 1 was a control with normal peritoneum. Animals in group 2 had increased macrophage population in their peritoneum by intraperitoneal injection of protease peptone 3 days before adhesion induction. In group 3, animals were treated by protease peptone as in group 2 and then depleted of the increased macrophage population by peritoneal lavage before adhesion induction. In group 4 macrophages were transplanted from animals enriched as in group 2 into a nonenriched peritoneum at the time of adhesion induction. Group 5 had a normal peritoneum with peritoneal lavage before adhesion induction. Peritoneal adhesions were induced at laparotomy by repairing a peritoneal defect in two different models. It was found that enhancement of peritoneal macrophages by protease peptone reduced markedly the degree of postoperative adhesion formation. After depletion of the enhanced peritoneal macrophages by peritoneal lavage the degree of adhesion formation was equivalent to that of controls. Finally, macrophage transplantation into a nonenhanced macrophage peritoneum also reduced the degree of postoperative adhesion formation. It is concluded that enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation.

Early trauma care is dependent on subjective assessments and sporadic vital sign assessments. We hypothesized that near-infrared spectroscopy-measured cerebral oxygenation (regional oxygen saturation [rSO₂]) would provide a tool to detect cardiovascular compromise during active hemorrhage. We compared rSO₂ with invasively measured mixed venous oxygen saturation (SvO₂), mean arterial pressure (MAP), cardiac output, heart rate, and calculated pulse pressure.Six propofol-anesthetized instrumented swine were subjected to a fixed-rate hemorrhage until cardiovascular collapse. rSO₂ was monitored with noninvasively measured cerebral oximetry; SvO₂ was measured with a fiber optic pulmonary arterial catheter. As an assessment of the time responsiveness of each variable, we recorded minutes from start of the hemorrhage for each variable achieving a 5%, 10%, 15%, and 20% change compared with baseline.Mean time to cardiovascular collapse was 35 minutes ± 11 minutes (54 ± 17% total blood volume). Cerebral rSO₂ began a steady decline at an average MAP of 78 mm Hg ± 17 mm Hg, well above the expected autoregulatory threshold of cerebral blood flow. The 5%, 10%, and 15% decreases in rSO₂ during hemorrhage occurred at a similar times to SvO₂, but rSO₂ lagged 6 minutes behind the equivalent percentage decreases in MAP. There was a higher correlation between rSO₂ versus MAP (R² =0.72) than SvO₂ versus MAP (R² =0.55).Near-infrared spectroscopy-measured rSO₂ provided reproducible decreases during hemorrhage that were similar in time course to invasively measured cardiac output and SvO₂ but delayed 5 to 9 minutes compared with MAP and pulse pressure. rSO₂ may provide an earlier warning of worsening hemorrhagic shock for prompt interventions in patients with trauma when continuous arterial BP measurements are unavailable.

Despite considerable experience the reported frequency of misdiagnosis in patients undergoing appendectomy continues in the range of 20% to 40% in some populations.We developed a clinical guideline that recommended abdominal computed tomography (CT) for all nonpregnant adults in whom the diagnosis of appendicitis was suspected unless the diagnosis could be ruled out clinically. The records of adult patients that underwent appendectomy from July 1998 through October 2001 were reviewed. The clinical guideline was developed in July 2000.There were 194 appendectomies performed, 114 prior to the guideline and 80 after the development of the guideline. The rate of misdiagnosis decreased from 25% to 6% (P0.05), the rate of CT use increased from 32% to 84% (P0.05), and the perforation rate remained unchanged.These results support the effectiveness of a clinical guideline that encourage the use of abdominal CT in decreasing the frequency of misdiagnosis in cases of suspected appendicitis.

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.

Leukocytes and the process of leukocyte adherence have been implicated in the pathogenesis of organ dysfunction after ischemic injury and inflammation. We asked the question: Will inhibition of leukocyte adherence by administration of a monoclonal antibody to intercellular adhesion molecule alter the systemic response to major thermal injury? New Zealand white rabbits instrumented to measure mean arterial pressure, cardiac output, urine output, and arterial oxygenation were deeply anesthetized, and 30% total body surface area full-thickness burn was created by applying brass probes heated to 100 degrees C to the animals' backs for 15 seconds. The animals were continuously monitored, resuscitated, and given analgesic for 24 hours. There were three experimental groups: I-controls (n = 7), anesthetized and monitored; II-30% burn (n = 7) given 30% total body surface area + vehicle (saline solution 1.0 ml/kg every 8 hours); III-30% burn + R6.5 (n = 6) animals given a monoclonal antibody (R6.5, 2.0 mg/kg every 8 hours) directed against the intercellular adhesion molecule beginning 30 minutes after burn. This model of a 30% total body surface area burn injury resulted in hypotension and hypoxemia in the burn group. The animals given the antibody R6.5 maintained higher mean arterial pressure and arterial oxygenation at several points. These results suggest that leukocytes and leukocyte adherence may be involved in the pathogenesis of the systemic sequellae of major thermal injury.

Leukocyte (WBC) adherence to endothelial cells (EC) has been implicated in the pathogenesis of microvascular injury. WBC-EC adherence is largely dependent on interaction between the WBC-CD18 complex and the endothelial ligand, intercellular adhesion molecule-1 (ICAM-1). Administration of monoclonal antibodies directed against CD18 and/or ICAM-1 inhibit WBC-EC adherence and have been reported to modulate ischemia-reperfusion and inflammatory injury. We asked the question, does inhibition of WBC-EC adherence by administration of monoclonal antibody directed against either CD18 (R15.7) or against ICAM-1 (R6.5) increase susceptibility to infection. New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Staphylococcus aureus (ATCC No. 25923) at two sites each with 10(9), 10(8), 10(7), and 10(6) colony-forming units (CFUs). A second set of rabbits were injected subcutaneously with Pseudomonas aeruginosa (ATCC No. 27853) at two sites each of 10(8) and 10(7) CFUs. Animals were monitored for 1 week with daily determination of weight, temperature, WBC counts, hematocrit, and gross evidence of abscess formation. There were three blinded experimental groups; animals given R15.7 (2.0 mg/kg), animals given R6.5 (2.0 mg/kg), and controls given saline (2.0 ml/kg). Administration of the anti-CD18 antibody, R15.7, resulted in significantly increased rates of abscess formation following innoculation with S. aureus and with P. aeruginosa, compared to controls and to the animals given the antibody to ICAM-1, R6.5. The administration of R6.5 did not increase the incidence or severity of abscess formation.

The immunoinflammatory response following trauma and hemorrhage may predispose to the development of sepsis and multiple-organ failure syndrome. Cardiac output (CO), arterial pressure, arterial PO2, and pulmonary permeability index were measured. We examined the sensitivity of rabbits to infusions of lipopolysaccharide (LPS) after hemorrhagic shock. Shock was produced by reducing CO to 40% of baseline for 90 min, followed by resuscitation with shed blood and then with lactated Ringer solution to maintain CO near baseline. Animals were assigned to three groups: 1) hemorrhagic shock only, 2) LPS only, and 3) hemorrhagic shock + LPS. Groups 1 and 3 were subjected to hemorrhagic shock on day 1. Escherichia coli LPS was infused (1.0 microgram/kg i.v.) into groups 2 and 3 on day 2. Fluid resuscitation with lactated Ringer solution was continued in an effort to maintain CO at baseline. Five hours after LPS infusion, 125I-albumin was injected intravenously, and rabbits were killed 1 h later for measurement of pulmonary permeability index. LPS infusion after shock (group 3) caused significant decreases in CO, arterial pressure, and PO2 and an increase in pulmonary permeability. These changes were not seen in the groups 1 and 2. We conclude that hemorrhagic shock and resuscitation result in a proinflammatory state, leading to increased sensitivity to subsequent exposure to LPS.

Progressive microvascular damage in the tissue adjacent to a cutaneous burn injury results in extension of burn size. The role of neutrophils (PMNs) in the pathogenesis of microvascular injury was investigated by inhibition of PMN adherence to the microvascular endothelium using monoclonal antibodies directed to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using New Zealand White rabbits. Under general anesthesia two sets of three full-thickness burns separated by two 5 × 30-mm zones were produced by applying brass probes heated to 100°C to the animals' backs for 30 sec. Cutaneous blood flow determinations were obtained for 72 hr. Blood flow measurements were performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ). There were five experimental groups; controls given saline alone, n = 12; animals given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n = 6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in the marginal “zone of stasis” between burn contact sites was significantly higher in the antibody-treated animals and administration of the antibodies 30 min after injury was as effective as preburn administration in preserving blood flow. At 72 hr post-burn all antibody-treated animals had blood flow in the areas at risk for progression (i.e., the zone of stasis) at or above baseline levels while the control animals had levels equal to 34.7 ± 12% of baseline (P < 0.05 by analysis of variance and Mann-Whitney U test). These results suggest that PMNs play an important role in the pathogenesis of burn wound progression, and that this progression can be attenuated by modulating PMN-EC adherence.

Background The use of antimicrobial solutions for irrigation in appendicitis is controversial. Numerous antiseptic and antibiotic solutions have been suggested for use as an intraoperative irrigant. We sought to determine whether there was a difference in postoperative surgical site infections (SSIs) comparing normal saline (.9%), antiseptic solution (Dakin's, .25%), and an antibiotic solution (imipenem 1 mg/mL). Methods We performed a retrospective study of adult appendectomies from January 1997 through November 2007 at a single institution The data were evaluated by multivariate logistic regression analysis and chi-square test. The incidences of postoperative overall SSI, wound infection, and abdominal abscess were compared. Results A total of 1,063 cases were identified. Saline (n = 661) had an SSI rate of 9.8% (65/661), a wound infection rate of 7.3% (48/661), and an abdominal abscess rate of 4.2% (28/661). Dakin's (n = 208) had an SSI rate of 20.7% (43/208), a wound infection rate of 15.9% (33/208), and an abdominal abscess rate of 9.1% (19/208). Imipenem (n = 194) irrigation had an SSI rate of .5% (1/194), a wound infection rate of .5% (1/194), and an abdominal abscess rate of .5% (1/194). Conclusions These results suggest that abdominal irrigation with an antibiotic solution (imipenem 1 mg/mL) is superior to both normal saline and Dakin's solution.

Interferon-γ (IFN-γ) has been proposed for use following severe trauma to reverse depressed macrophage (Mφ) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by Mφs and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis-induced MOFS by stimulating Mφs and leukocytes (WBC). This study addresses the following question: Does IFN-γ predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits ( n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO 2 , and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 μg/kg of Escherichia coli LPS iv, Group III (IFN-γ alone) was given recombinant rabbit IFN-γ (5.0 μg/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-γ + LPS) received 3 days of IFN-γ followed by LPS. One hour prior to sacrifice 5.0 μCi of 125 I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125 I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO 2 , and WBC counts, and increased lavage/plasma ratio of 125 I-albumin when compared to all other groups ( P t test). Neither LPS alone nor IFN-γ alone had a significant effect on measured variables. In contrast to immunosuppressed animals, IFN-γ pretreatment of normal animals increases the host pathophysiologic response to endotoxin.

Introduction: Motorcycles have become an increasingly popular mode of transportation despite their association with a greater risk for injury compared with automobiles. Whereas the recent incidence of annual passenger vehicle fatalities in the United States of America (USA) has progressively declined, motorcycle fatalities have steadily increased in the past 11 years. Although motorcycle injuries (MIs) have been studied, to the author’s knowledge there are no published reports on MIs in the USA during this 11-year period.Methods: Study data were derived from a prospectively collected Level I trauma center database. Data sampling included motorcycle crash injury evaluations for the 10-year period ending on 31 August 2008. This retrospective analysis included patient demographic and medical data, helmet use, Glasgow coma scale (GCS) score, injury severity score (ISS), length of hospital stay (LOS), specific injury diagnosis, and death. Data statistics were analyzed using the Spearman correlation coefficient, Kruskal-Wallis tests, and logistic regression.Results: The study identified 1252 motorcycle crash injuries. Helmets were worn by 40.7% of patients for which helmet data were available. The rates of the most common orthopedic injuries were tibia/fibula (19.01%), spine (16.21%), and forearm (10.14%) fractures. The most common non-orthopedic motorcycle crash injuries were concussions (21.09%), skull fractures (8.23%), face fractures (13.66%), and hemo- and pneumothorax (8.79%). There was a significant correlation between greater age and higher ISS (r=0.21, PConclusion: Compared with historical reports, the prevalence of skull, face, spine, and pelvis fractures have increased in American motorcycle crashes. Compared to recent European studies, the incidence of USA skull and face fractures is much higher, while the incidence of USA spine and pelvis fractures is more comparable; however, this is not associated with increased in-hospital mortality.

Transesophageal echocardiography has become a commonly used screening tool for traumatic tears of the descending aorta. The role of transesophageal echocardiography for ascending aortic tears is not yet well-defined. We report an ascending aortic tear imaged by aortography but missed on transesophageal echocardiography.

Alveolar macrophages from New Zealand white rabbits were incubated with twice the MIC of amikacin, ciprofloxacin, aztreonam, ceftazidime and imipenem and exposed to either 10 4 , 10 5 or 10 6 cfu/mL live Pseudomonas aeruginosa ATCC 27853 or 0.1, 1 or 10 mg/L purified lipopolysaccharide (LPS) derived from P. aeruginosa to determine the effects of different classes of antimicrobial agent on production of tumour necrosis factor (TNF). Incubation of macrophages with ciprofloxacin and amikacin resulted in less TNF activity after exposure to live P. aeruginosa than was found for saline, aztreonam, ceftazidime or imipenem (P < 0.05). However, no significant differences were found between any of the agents after macrophages had been exposed to purifi ed LPS. Different antimicrobial agents therefore appear to exert different effects in vitro on the TNF response of macrophages to bacterial stimulation.

Background: Burn injury, it was hypothesized, may induce changes in resistin expression that contribute to postburn metabolic derangements. This study examined resistin gene expression, serum levels of resistin protein, and glucose levels in burned mice. Methods: Ten male Balb-c mice were anesthetized and then given a 30% total burn surface area using heated probes. Burned and sham-burned mice were killed at 2, 4, 24, and 48 hours. The total ribonucleic acid from gonadal fat tissues was isolated for the measurement of resistin gene expression using real-time reverse transcriptase-polymerase chain reaction. Serum levels of resistin, insulin, and glucose were measured. Statistical analysis was performed by two-way analysis of variance using Bonferroni's test to find differences between groups. All p values less than 0.05 were considered significant. Results: Increases in resistin gene expression and serum resistin levels were detected in the burned animals, and these correlated with relative insulin resistance. Conclusion: The findings suggest a potential role for resistin in the pathophysiology of the metabolic response to injury.

Traditional methods of judging burn depth by clinical evaluation of the wound based on appearance and sensation remain in wide use but are subject to individual variation by examiner. In addition to the clinical difficulties with burn wound management, observer dependency of wound assessment complicates clinical trials of burn wound therapy. A laser Doppler flowmeter with a multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. Serial measurement with laser Doppler flowmetry had an 88% specificity and a positive predictive value of 81% for identifying nonhealing wounds. These results suggest that laser Doppler flowmetry is a potentially useful tool for burn wound assessment.

Background: A randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial was performed to determine whether inhibition of leukocyte adherence by administration of monoclonal antibody directed against intercellular adhesion molecule-1 would improve burn wound healing. Methods: One hundred ten patients with burn injury ranging from 10% to 30% total body surface area were enrolled. Fifty-six patients received placebo (saline) and 54 patients received murine monoclonal antibody to the human intercellular adhesion molecule-1 (enlimomab). Treatment was initiated within 6 hours of injury. Patients had three distinct partial-thickness wound sites assessed. Laser Doppler flowmetry was used to stratify wounds on the day of injury. Wounds were assessed for healing status on day 21 postburn and categorized as healed, non-healed, or grafted. Results: Patients treated with enlimomab had a significantly increased percentage of wounds that healed spontaneously in less than 21 days overall and when stratified by burn wound laser Doppler blood flow readings for those wounds at greatest risk for nonhealing. Conclusion: These results support the concept that leukocyte adherence is involved in the pathogenesis of burn wound necrosis and suggest a therapeutic mechanism for modulating the inflammatory response after the burn injury that may improve wound healing.

A 77-year-old woman with osteogenesis imperfecta was admitted with symptomatic choledocholithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) was carried out and mild resistance was encountered in the distal esophagus with “red out” during intubation. The duodenoscope was withdrawn and gastroscopy revealed a tear in the distal esophagus (● " Fig.1). As a perforation was suspected, a nasogastric tube was deployed, intravenous antibiotics were started, and surgery was consulted. An esophagogram confirmed the esophageal leak (● " Fig.2) and thoraco-abdominal computed tomography (CT) showed a 0.7-cm esophageal perforation and air– fluid collection (3cm×10cm) in the posterior mediastinum (● " Fig.3). Conservative management was decided on due to clinical stability and poor operative candidacy. Within 48 hours the liver function tests normalized and parenteral nutrition was started. The day 7 esophagogram showed partial healing. Enteral feeding was started with a nasojejunal tube placed fluoroscopically. An esophagogram on day 27 showed complete healing (● " Fig.4). The patient started an oral diet and was discharged with plan for elective cholecystectomy. Osteogenesis imperfecta is an autosomal dominant disorder of collagen synthesis (1 in 10000 births). Gastrointestinal manifestations in osteogenesis imperfecta are rare although spontaneous colon perforation has been reported, where histopathological examination showed absence of muscle layers in the perforated segment [1]. Murine models of osteogenesis imperfecta showed thinner esophageal submucosa and muscularis compared with wild mice [2]. ERCP-related perforations are infrequent (0.4%) and are commonly related to improper guidewire insertion or sphincterotomy [3]. Esophageal perforation in ERCP is rare and is attributed to use of sharp accessories [3,4]. This is the first reported case of esophageal perforation in osteogenesis imperfecta. We believe that perforation in our patient occurred due to abnormal esophageal submucosa and muscularis and limited view with duodenoscope. Esophageal perforations are traditionally managed surgically; however, good outcomes are reported with conservative management in smaller perforations and contained leaks [5]. The present case highlights the propensity for esophageal perforation in osteogenesis imperfecta. We recommend caution and low threshold to suspect perforation during gastrointestinal endoscopy in osteogenesis im

DNA containing unmethylated CpG motifs is intrinsically immunostimulatory, inducing the production of a variety of cytokines and chemokines by immune cells. The strong Th1 response triggered by CpG oligodeoxynucleotide (ODN) inhibits the development of Th2-mediated allergic asthma in mice. This work documents that CpG ODN-induced IL-12 production plays a critical role in this process, because intrapulmonary CpG ODN inhibits allergic inflammation in wild-type but not IL-12−/− mice. CpG ODN rapidly localized to alveolar macrophages (AM), thereby triggering the phosphorylation of p38 mitogen-activated protein kinase (MAP kinase). AM cultured with CpG but not control ODN up-regulated IL-12 p40 expression and release, and these effects were blocked by the highly specific p38 MAP kinase inhibitor SB202190. Intrapulmonary administration of this inhibitor blocked the ability of CpG ODN to produce IL-12 in the lungs and reversed the anti-inflammatory effects of CpG ODN on allergic lung inflammation. These findings indicate that IL-12 production by AM is stimulated by intrapulmonary CpG ODN administration through a p38 MAP kinase-dependent process, and IL-12 is a key cytokine that mediates CpG ODN-induced protection against allergic lung inflammation.

The clinical benefit of aeromedical transportation of injured patients in the civilian population has been debated. The purpose of this study was to examine the effects of discontinuing a hospital-based helicopter transport program on trauma patient outcomes, with the hypothesis that the loss of an air ambulance would result in increased transport time and increased mortality among severely injured patients.Data on injury severity and patient outcomes were collected prospectively for the 12 months immediately preceding and 24 months following discontinuation of the helicopter ambulance service. Transport time, mortality rate, and hospital length of stay was compared.The number of trauma patient admissions decreased 12%, with a 17% decrease in admissions of severely injured patients. Transport time decreased, with no change in mortality.Discontinuation of a hospital-based air ambulance service did not increase transport time or increase mortality for trauma patients.

Trauma produces dysfunction in immunity, which appears to be partially related to alterations in the cytokine response. Signal transducer and activator of transcription proteins (STATs) mediate activation of several cytokine genes. However, the effect of STAT proteins on tumor necrosis factor-alpha (TNFalpha) activation is not fully defined. We identified binding sites for STAT 3 and STAT 5/6 within the promoter region of TNFalpha and hypothesize that alterations in these sites would affect TNFalpha expression. The TNFalpha promoter was inserted into the luciferase reporter vector, and binding sites for STAT 3, STAT 5/6, and activator protein-1 (AP-1) were mutated using site-directed mutagenesis. Murine macrophages were transfected with the resultant plasmids, then incubated with and without lipopolysaccharide (LPS) or IFNalpha. Gene expression was measured by dual luciferase assay. Mutation of the STAT 3 binding site was associated with decreased LPS-inducible activity. Mutation of the AP-1 and STAT 5/6 consensus binding sites alone had no effect on TNFalpha expression. However, combined mutation of both STAT 5/6 and AP-1 was associated with increased LPS-inducible activity. Mutations of the STAT binding sites in the promoter region of TNFalpha affect TNFalpha gene expression. These results suggest a regulatory role for STATs in TNF gene transcription.

The evaluation of wound outcome after burn injury is a challenging problem in the performance of clinical trials evaluating potential impact on wound healing and scar formation. The purpose of this study was to determine whether an ocular tonometer could be adapted to provide an objective measurement of scar compliance. A pneumatonometer was used to perform measurements of cutaneous compliance at 8 anatomic areas (14 separate sites) on each of 17 normal volunteers and on 59 burn scars. Comparison of different anatomic sites showed there to be significant differences in the cutaneous compliance of different areas. The aggregate compliance of the burn scars in all sites was less than that of the control sites. These results indicate that the pneumatonometer can discern differences in the compliance of normal skin and differences between normal skin and scar and suggest that it may be a useful tool in the objective assessment of scar formation.

Cardiac dysfunction occurs after thermal injury but the pathogenesis is nuclear; leukocytes have been implicated in the pathogenesis of multiorgan dysfunction after burn injury. White blood cell activation and entry into tissue involve the use of a number of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, CD54. We asked the question: will administration of the monoclonal antibody (R6.5) directed against ICAM-1 alter the cardiac dysfunction which we have previously shown to occur after thermal injury? Previously instrumented New Zealand White rabbits were anesthetized and given a full-thickness burn over 30% of the total body surface area by applying brass probes heated to 100 degrees C to the animals' backs for 15 sec. Animals were monitored for 24 hr and given lactated Ringer's (LR) solution (4 cc/kg/% burn, Parkland formula) with additional LR given to maintain cardiac output and urine output. Three experimental groups were studied: sham burn controls had catheters placed and were monitored for 24 hr (N = 8); burn rabbits were divided into vehicle treated (saline, 1 ml/kg, N = 6) or R6.5 treated (2 mg/kg, N = 6). Vehicle or antibody was administered 30 min postburn and every 8 hr until 24 hr postburn; at this time, rabbits were sacrificed and hearts were harvested for in vitro assessment of contractile performance (Langendorff). Compared to values measured in sham burn controls, burn injury caused cardiac contractile depression as indicated by a fall in left ventricular pressure (LVP) (77 +/- 2 vs 56 +/- 3 mm Hg, P = 0.01), +dP/dt (1223 +/- 64 vs 842 +/- 64 mm Hg/sec, P = 0.001), and -dP/dt (973 +/- 63 vs 666 +/- 42 mm Hg/sec, P = 0.01). Administration of R6.5 significantly improved cardiac contractile function compared to the vehicle-treated burns as indicated by higher LVP (67 +/- 2 mm Hg, P > 0.05), +dP/dt (1017 +/- 33 mm Hg/sec, P > 0.05), and -dP/dt (858 +/- 40 mm Hg/ sec, P > 0.05) than values measured in vehicle-treated burns. These results suggest that ICAM-1-mediated WBC activation and/or tissue entry are involved in the pathogenesis of cardiac dysfunction following thermal injury.

Partial and full thickness burns with intervening zones of stasis were created on the backs on New Zealand White rabbits (n = 23). Either saline or the bradykinin receptor antagonist, NPC 17731, was administered. Skin blood flow was measured hourly using a laser Doppler blood flowmeter. After 4 h skin samples were harvested for assessment of tissue oedema (wet/dry weights) and leucocyte accumulation (immunohistochemistry). Statistical analysis was performed using Analysis of variance (ANOVA) and Mann-Whitney U test with a level of significance at P < 0.05. It was found that blood flow was decreased postburn in all groups. Bradykinin antagonist resulted in increased blood flow in partial thickness burns and zones of stasis compared to saline-treated animals (P < 0.05). Pretreatment with bradykinin antagonist showed reduced tissue oedema in full thickness burns (P < 0.05). No significant difference was observed in leucocyte accumulation between both groups. These data suggest a role for bradykinin in the pathogenesis of postburn microvascular changes which is independent of leucocyte-mediated injury.