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Anastomotic leak is the most dreaded complication following colonic resection. While patient frailty is increasingly being recognized as a risk factor for surgical morbidity and mortality, the current colorectal body of literature has not assessed the relationship between frailty and anastomotic leak.Evaluate the relationship between patient frailty and anastomotic leak as well as patient frailty and failure to rescue in patients who experienced an anastomotic leak.Retrospective cohort study.American College of Surgeons National Surgical Quality Improvement Program Database from 2015 to 2017.Patients with the diagnosis of colonic neoplasia undergoing an elective colectomy during the study time period.Anastomotic leak, failure to rescue.A total of 30,180 elective colectomies for neoplasia were identified. The leak rate was 2.9% (n = 880). Compared to nonfrail patients, frail patients were at increased odds of anastomotic leak (frailty score = 1: OR 1.34, 95% CI 1.10-1.63; frailty score = 2: OR 1.32, 95% CI 1.04-1.68; frailty score = 3: OR = 2.41, 95% CI 1.47-3.96). After an anastomotic leak, compared to nonfrail patient, a greater proportion of frail patients experienced mortality (3.4% vs 5.9%), septic shock (16.1% vs 21.0%), myocardial infarction (1.1% vs 2.9%), and pneumonia (6.8% vs 11.8%). Furthermore, the odds of mortality, septic shock, myocardial infarction, and pneumonia increased in frail patients with higher frailty scores.Potential misclassification bias from lack of a strict definition of anastomotic leak and retrospective design of the study.Frail patients undergoing colectomy for colonic neoplasia are at increased risk of an anastomotic leak. Furthermore, once a leak occurs, they are more vulnerable to failure to rescue. See Video Abstract at http://links.lww.com/DCR/B784.ANTECEDENTES:La fuga anastomótica es la complicación más temida después de la resección colónica. Si bien la fragilidad del paciente se reconoce cada vez más como un factor de riesgo de morbilidad y mortalidad quirúrgicas, la bibliografía colorrectal actual no ha evaluado la relación entre la fragilidad y la fuga anastomótica.OBJETIVO:Evaluar la relación entre la fragilidad del paciente y la fuga anastomótica, así como la fragilidad del paciente y la falta de rescate en pacientes que sufrieron una fuga anastomótica.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Base de datos del Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos de 2015 a 2017.PACIENTES:Pacientes con diagnóstico de neoplasia de colon sometidos a colectomía electiva durante el período de estudio.PRINCIPAL MEDIDA DE RESULTADO:Fuga anastomótica, falta de rescate.RESULTADOS:Se identificaron 30.180 colectomías electivas por neoplasia. La tasa de fuga fue del 2,9% (n = 880). En comparación con los pacientes no frágiles, los pacientes frágiles tenían mayores probabilidades de fuga anastomótica para (puntuación de fragilidad = 1: OR = 1,34, IC del 95%: 1,10-1,63; puntuación de fragilidad = 2: OR = 1,32, IC del 95%: 1,04- 1,68; puntuación de fragilidad = 3: OR 2,41; IC del 95%: 1,47-3,96). Después de una fuga anastomótica, en comparación con un paciente no frágil, una mayor proporción de pacientes frágiles experimentó mortalidad (3,4% frente a 5,9%), choque séptico (16,1% frente a 21,0%), infarto de miocardio (1,1% frente a 2,9%) y neumonía (6,8% vs 11,8%). Además, las probabilidades de mortalidad, choque séptico, infarto de miocardio y neumonía aumentaron en pacientes frágiles con puntuaciones de fragilidad más altas.LIMITACIONES:Posible sesgo de clasificación errónea debido a la falta de una definición estricta de fuga anastomótica, diseño retrospectivo del estudio.CONCLUSIÓN:Los pacientes frágiles sometidos a colectomía por neoplasia de colon tienen un mayor riesgo de una fuga anastomótica. Además, una vez que ocurre una fuga, son más vulnerables a fallas en el rescate. Consulte Video Resumen en http://links.lww.com/DCR/B784.

Backgrounds/Aims Post-operative pancreatic fistulas (POPF) are a major source of morbidity following pancreaticoduodenectomy (PD). This study aims to investigate if persistent lymphopenia, a known marker of sepsis, can act as an additional marker of POPF with clinical implications that could help direct drain management. Methods A retrospective chart review of all patients who underwent PD in a single hospital network from 2008 to 2018. Persistent lymphopenia was defined as lymphopenia beyond post-operative day #3. Results Of the 201 patients who underwent PD during the study period 161 patients had relevant laboratory data, 81 of whom had persistent lymphopenia. 17 patients with persistent lymphopenia went on to develop a POPF, compared to 7 patients without. Persistent lymphopenia had a negative predictive value of 91.3%. Multivariate analysis revealed only persistent lymphopenia as being independently associated with POPF (HR 2.57, 95% CI 1.07-6.643, p=0.039). Patients with persistent lymphopenia were more likely to have a complication requiring intervention (56.8% vs 35.0%, p

Background In order to better characterize outcomes of palliative surgery (PS), we evaluated patients that experienced top quartile survival to elucidate predictors of high impact PS. Methods All PS performed on advanced cancer patients from 2003 to 2017 were identified from a PS database. Results 167 patients were identified. Multivariate analysis demonstrated the ability to rise from a chair was independently associated with top quartile survival (HR 7.61, 95% CI 2.12–48.82, p=0.008) as was the need for re-operation (HR 2.81, 95% CI 1.26–6.30, p=0.0012). Patients who were able to rise from a chair had significantly prolonged overall survival (320 vs 87 days, p Conclusions Although not the primary goal, long-term survival can be achieved following PS and is associated with re-operation and the ability to rise from a chair. These patients experience the benefits of PS for a longer period of time, which in turn maximizes value and positive impact. Summary Long-term survival and symptom control can be achieved in highly selected advanced cancer patients following palliative surgery. The ability of the patient to independently rise from a chair and the provider to offer a re-operation when indicated are associated with long-term survival following a palliative operation.

IntroductionInhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury.MethodsData collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics.ResultsData from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (pConclusionsBurn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms.

The 80h work week has raised concerns that complications may increase due to multiple sign-outs or poor communication. Trauma Surgery manages complex trauma and acute care surgical patients with rapidly changing physiology, clinical demands and a large volume of data that must be communicated to render safe, effective patient care. Trauma Morning Report format may offer the ideal situation to study and teach sign-outs and resident communication.Surgery Residents were assessed on a 1-5 scale for their ability to communicate to their fellow residents. This consisted of 10 critical points of the presentation, treatment and workup from the previous night's trauma admissions. Scores were grouped into three areas. Each area was scored out of 15. Area 1 consisted of Initial patient presentation. Area 2 consisted of events in the trauma bay. Area 3 assessed clarity of language and ability to communicate to their fellow residents. The residents were assessed for inclusion of pertinent positive and negative findings, as well as overall clarity of communication. In phase 1, residents were unaware of the evaluation process. Phase 2 followed a series of resident education session about effective communication, sign-out techniques and delineation of evaluation criteria. Phase 3 was a resident-blinded phase which evaluated the sustainability of the improvements in resident communication.50 patient presentations in phase 1, 200 in phase 2, and 50 presentations in phase 3 were evaluated. Comparisons were made between the Phase 1 and Phase 2 evaluations. Area 1 (initial events) improved from 6.18 to 12.4 out of 15 (p0.0001). Area 2 (events in the trauma bay) improved from 9.78 to 16.53 (p0.0077). Area 3 (communication and language) improved from 8.36 to 12.22 out of 15 (P0.001). Phase 2 to Phase 3 evaluations were similar, showing no deterioration of skills.Trauma Surgery manages complex surgical patients, with rapidly changing physiologic and clinical demands. Trauma Morning Report, with diverse attendance including surgical attendings and residents in various training years, is the ideal venue for real-time teaching and evaluation of sign-outs and reinforcing good communication skills in residents.

Flame injuries are the primary cause of burns in young adults. Although drug and alcohol intoxication has been associated with other types of trauma, its role in burn injury has not been well described in this population. The purpose of this study was to investigate the association of intoxication and flame burn injuries in young adults in the United States. The 2014 Nationwide Emergency Department Sample was queried for burn injury visits of young adult patients, 13-25 years old. This data is weighted to allow for national estimates. Burn mechanism and intoxication status were determined by International Classification of Diseases, Ninth Revision codes. Multivariable logistic regression analysis was used to assess the association of intoxication and emergency department (ED) visits due to flame burns, adjusting for patient age, gender, zip code median income, zip code rural-urban designation, timing of visit, and hospital region. Further analyses assessed the odds of admission or transfer, as a possible proxy of injury severity, in patients with flame or other burns, with and without intoxication adjusting for patient age, gender, primary insurance, and hospital trauma designation. There were 20,787 visits for patients 13-25 years old with burn injuries and 12.9% (n = 2678) had a codiagnosis of intoxication. There was an increasing proportion of intoxication by age (5.8% 13-17 years old, 25% 18-20 years old, 69% 21-25 years old, P < .001). ED visits for burns with a codiagnosis of intoxication had 1.34 times ([95% confidence interval (CI): 1.18, 1.52], P < .01) higher odds of having flame burns compared to other burn mechanisms. Those with flame burns and intoxication were most likely to be admitted or transferred when compared to nonflame, nonintoxication visits in the adjusted model (odds ratio [OR] 5.49, [95% CI: 4.29, 7.02], P < .01). Furthermore, the odds of admission or transfer in visits with the combined exposure of intoxication and flame mechanism were significantly higher than visits due to nonflame burns and intoxication (OR 2.75, [2.25, 3.36], P < .01) or flame burns without intoxication (OR 3.00, [95% CI: 2.61, 3.42], P < .01). This study identified a significant association between flame-burn-related ED visits and intoxication in the young adult population in the United States. In addition, the combination of flame mechanism and intoxication appears to result in more substantial injury compared with either exposure alone. The relationship seen between intoxication and flame burn injury underscores a major target for burn prevention efforts in the young adult population.

Many studies have described the detrimental effect of lack of health insurance on trauma-related outcomes. It is unclear, though, whether these effects are related to pre-injury health status, access to trauma centers, or differences in quality of care after presentation. The aim of this study was to determine if patient and insurance type affect outcomes after trauma surgery.We conducted a retrospective chart review of prospectively collected data at the American College of Surgeons level 1 trauma registry in Rhode Island. All blunt trauma patients aged 18-45 observed from 2004 to 2014 were included. Patients were divided into one of four groups on the basis of their type of insurance: Private/commercial, Medicare, Medicaid, and uninsured. Co-morbidities and infections were recorded. Analysis of variance or the Mann-Whitney U test, as appropriate, was used to analyze the data.A total of 8,018 patients were included. Uninsured patients were more likely to be male and younger, whereas the Medicare patient group had significantly fewer male patients. Rates of co-morbidities were highest in the Medicare group (28.1%) versus the private insurance (16.7%), Medicaid (19.9%), and uninsured (12.9%) groups (p 0.05). However, among patients with any co-morbidity, there was no difference in the average number of co-morbidities between insurance groups. The rate of infection was highest in Medicaid patients (7.7%) versus private (5.6%), Medicare (6.3%), and uninsured (4.3%) patients (p 0.05). Only Medicaid was associated with a significantly greater risk of developing a post-injury infection (odds ratio 1.6; 95% confidence interval 1.1-2.3).The presence of insurance, namely Medicaid, does not equate to diagnosis and management of conditions that affect trauma outcomes. Medicaid is associated with worse pre-trauma health maintenance and a greater risk of infection.

Background Lymphocytes have become the target of cancer interventions through engineering or immune checkpoint antibodies. We previously found decreased lymphocyte counts to be a predictor of mortality and complications in trauma and cardiac surgery patients. We hypothesized lack of lymphocyte count recovery postoperatively would predict outcomes in esophagectomy patients. Methods A retrospective review of all patients undergoing esophagectomy for adenocarcinoma performed over 13 y at our center by a single surgeon after institutional review board approval was performed. Patients were grouped by postoperative lymphocytes counts: never low, low with recovery, and low without recovery. Resolution of lymphopenia was assessed by day 4. Primary end points were overall and recurrence-free survival. Results In total, 198 patients were included with a minimum 6-mo follow-up. Collectively the 5-y recurrence and overall survival rates were 36% and 50%, respectively. Recurrence was significantly higher at 5 y in patients with persistent lymphopenia (43%) compared with those who recovered (14% P = 0.0017) and those who never dropped (0% P = 0.0009). The persistent lymphopenia group had significantly lower survival (45%) compared with the two other groups (67% P = 0.0232). Conclusions There is a significant decrease in the overall and recurrence-free survival in those patients whose lymphocyte count drops without recovery after their esophagectomy. These data imply differences in immune responses to the stress of surgery that can be measured with routine postoperative laboratory values and are indicative of overall outcomes.

OBJECTIVE To describe the natural history of patients with traumatic brain injury (TBI) admitted to skilled nursing facilities (SNFs) following hospitalizations. SETTING Between 2005 and 2014. PARTICIPANTS Adults who had incident admissions to skilled nursing facilities (SNFs) with a diagnosis of TBI. DESIGN Retrospective review of the Minimum Data Set. MAIN MEASURES Main variables were cognitive and physical function, length of stay, presence of feeding tube, terminal condition, and dementia. RESULTS Incident admissions to SNFs increased annually from 17 247 patients to 20 787 from 2005 to 2014. The percentage of patients with activities of daily living score 23 or more decreased from 25% to 14% (P < .05). The overall percentage of patients with severe cognitive impairment decreased from 18% to 10% (P < .05). More patients had a diagnosis of dementia in 2014 compared with previous years (P < .05), and the presence of a terminal condition increased from 1% to 1.5% over the 10-year period (P < .05). The percentage of patients who stayed fewer than 30 days was noted to increase steadily over the 10 years, starting with 48% in 2005 and ending with 53% in 2013 (P < .05). CONCLUSION Understanding past trends in TBI admissions to SNFs is necessary to guide appropriate discharge and predict future demand, as well as inform SNF policy and practice necessary to care for this subgroup of patients.

Objective Operating room simulation exercises have been well established as an effective means of improving confidence, task engagement, and learning retention among surgical residents. We have established a cost-effective model and scoring system assessing resident skills to tie secure surgical knots with minimal tension. Design A circular grid divided into 18 segments was placed underlying an aluminum can. Trainees tie 20 surgical square knots scored for time and total knot length. Movement of the can outside the grid served as a scoring penalty. Recorded were time, length of the 20 knots, and number of segments exposed at exercise end. A score was developed to identify a progression of skills with PGY level. All outcomes were compared between classes using ANOVA. Setting Brown University/Rhode Island Hospital Department of Surgery. Participants Surgical residents (PGY1-PGY5) and participating attending surgeons employed by Rhode Island Hospital. Results Knot length and exposed segments showed trends of improved scores with ascending PGY level. Only average time attained statistical significance. Overall scores improved with PGY level: PGY1 (N = 9) PGY2 (N = 3) PGY3 (N = 6) PGY4 (N = 3) PGY5 (N = 3) Attending (N = 4) Composite 100.5 116.4 152.7 138.1 169.9 162.8 Composite scores significantly improved when comparing PGY1 to PGY3, PGY5, and Attending surgeons (p = 0.016, 0.011, and 0.011, respectively). Time significantly improved when comparing PGY1 to PGY3 and Attending surgeons (77vs. 50 and 47 seconds, p = 0.019 and 0.022 respectively). Composite scores were not significantly different above PGY3. Conclusions A low fidelity, high impact knot tying model has been developed to assess the ability to securely tie surgical knots while minimizing tension, with linear increases in scores that appear to plateau at the PGY3 level.

Background: The etiology of sepsis is broad. The peritoneal cavity displays compartmentalization with respect to inflammatory responses, so peripheral blood responses to sepsis of abdominal vs. non-abdominal origin are expected to be divergent. Lymphocytes and invariant natural killer T (iNKT) cells play important roles in survival from sepsis, as they dampen the neutrophil and macrophage responses. We assessed whether circulating iNKT cells display distinct phenotypic profiles depending on the presence of abdominal vs. non-abdominal infection with sepsis. Methods: Patients with sepsis, defined as infection confirmed microbiologically with a systemic inflammatory response syndrome (SIRS), were enrolled prospectively. They were categorized as having either exclusively sepsis of abdominal or exclusively non-abdominal origin. The white blood cell (WBC) count was recorded. Whole-blood staining with monoclonal antibodies to CD3, V-alpha-24 (to identify iNKT cells), and CD69 (marker of early activation) was applied. Results: Of the 53 enrolled patients, 18 had abdominal infection. Pneumonia was the most common non-abdominal type. There was no difference in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, WBC count, or CD3(+) T cells (7.1%±1.6% vs. 6.5%±0.9%; p=0.75) in the two groups. Patients with abdominal infection had a higher proportion of iNKT cells (2.7%±1.1% vs. 0.89%±0.14%; p=0.032). Correcting for WBC count, this translated into a higher absolute number of iNKT cells (3.4±1.8×10(7)/L vs. 0.74±0.15×10(7)/L; p=0.03). Patients with sepsis of abdominal origin had a lower percentage of CD69(+) iNKT cells (9.1%±3.1% vs. 27.2%±5.8%; p=0.028). In patients in shock vs. those who were not, patients with non-abdominal infection exhibited a greater number of iNKT cells (1.47±0.3 v. 0.62±0.1×10(7)/L; p=0.022) and percentage of activated iNKT cells (53±14.5% vs. 17.9±4.8%; p=0.04). Patients with non-abdominal infection who died had a lower absolute number of activated iNKT cells (0.8±1.2×10(7)/L vs. 0.34±0.1×10(7)/L; p=0.023); however, no such shock or death correlation was noted in patients with sepsis of abdominal origin. Conclusions: Divergent sepsis etiologies display distinct blood iNKT cell population changes. In non-abdominal infection, this difference was associated with septic shock and death. Elucidating the importance and basis for these changes relative to the response to sources of infection will help clarify appropriate diagnosis and management of the patient with sepsis.

Background Multi-organ failure occurs during critical illness and is mediated in part by destructive neutrophil-to-endothelial interactions. The β2 integrin receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the adhesion of activated neutrophils to inflamed endothelia which, when prolonged and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small molecule allosteric activator of CR3 and has been shown to promote adhesion of blood neutrophils to inflamed endothelium and restrict tissue infiltration. Therefore, LA-1 offers a novel mechanism of anti-inflammatory action by activation, rather than inhibition, of the neutrophil CR3 integrin. However, whether promotion of neutrophil-to-endothelial interaction by this novel therapeutic is of benefit or detriment to endothelial barrier function is not known. Methods Critically ill septic and trauma patients were prospectively enrolled from the surgical and the trauma ICU. Blood was collected from these patients and healthy volunteers. Neutrophils were isolated by dextran sedimentation and adhered to TNF-α (tumor necrosis factor-α)-activated human umbilical vein endothelial (HUVEC) monolayers in the presence or absence of fMLP (formylmethionine-leucine-phenylalanine) and/or LA-1. Electric cell-substrate impedance sensing (ECIS) and exposure of underlying collagen were used to quantify endothelial barrier function and permeability. Results Neutrophils from critically ill trauma and septic patients caused similar degrees of endothelial barrier disruption which exceeded that caused by cells obtained from healthy controls both kinetically and quantitatively. LA-1 protected barrier function in the absence and presence of fMLP which served as a secondary stimulant to cause maximal loss of barrier function. LA-1 protection was also observed by quantifying collagen exposure underlying endothelial cells challenged with fMLP-stimulated neutrophils. LA-1 treatment resulted in decreased migration dynamics of neutrophils crawling on an endothelial monolayer with reduced speed (μm/s = 0.25 ± 0.01 vs. 0.06 ± 0.01, p

Background Traumatic brain injury is a leading cause of death and disability in the United States. In survivors, traumatic brain injury remains a leading contributor to long-term disability and results in many patients being admitted to skilled nursing facilities for postacute care. Despite this very large population of traumatic brain injury patients, very little is known about the long-term outcomes of traumatic brain injury survivors, including rates of discharge to home or risk of death in long-term nursing facilities. We hypothesized that patient demographics and functional status influence outcomes of patients with traumatic brain injury admitted to skilled nursing facilities. Methods We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries aged 65 and older discharged alive and directly from hospital to a skilled nursing facility between 2011 and 2014 using the prospectively maintained Federal Minimum Data Set combined with Medicare claims data and the Centers for Medicare and Medicaid Services Vital Status files. Records were reviewed for demographic and clinical characteristics at admission to the skilled nursing facility, including age, sex, cognitive function, ability to communicate, and motor function. Activities of daily living were reassessed at discharge to calculate functional improvement. We used robust Poisson regression with skilled nursing facility fixed effects to calculate relative risks and 99% confidence intervals for mortality and functional improvement associated with the demographic and clinical characteristics present at admission. Linear regression was used to calculate adjusted mean duration of stay. Results Overall, 87,292 Medicare fee-for-service beneficiaries with traumatic brain injury were admitted to skilled nursing facilities. The mean age was 84 years, with 74% of patients older than age 80. Generally, older age, male sex, and poor cognitive or functional status at admission to a skilled nursing facility were associated with increased risk for poorer outcomes. Older patients (age ≥80 years) with traumatic brain injury had a 1.5 times greater risk of death within 30 days of admission compared with adults younger than 80 years (relative risk = 1.49, 99% confidence interval = 1.36, 1.64). Women were 37% less likely to die than men were (relative risk = 0.63, 99% confidence interval = 0.59, 0.68). The risk of death was greater for patients with poor cognitive function (relative risk = 2.55, 99% confidence interval = 2.32, 2.77), substantial motor impairment (relative risk = 2.44, 99% confidence interval = 2.16, 2.77), and patients with impairment in communication (relative risk = 2.58, 99% confidence interval = 2.32, 2.86) compared with those without the respective deficits. One year after admission, these risk factors continued to confer excess risk for mortality. Duration of stay was somewhat greater for older patients (30.1 compared with 27.5 average days) and patients with cognitive impairment (31.7 vs 27.5 average days). At discharge, patients with cognitive impairment (relative risk = 0.86, 99% confidence interval = 0.83, 0.88) and impairment in the ability to communicate (relative risk = 0.67, 99% confidence interval = 0.54, 0.82) were less likely to improve in physical function. Conclusion Our results suggest that among patients with traumatic brain injury admitted to skilled nursing facilities, the likelihood of adverse outcomes varies significantly by key demographic and clinical characteristics. These findings may facilitate setting expectations among patients and families as well as providers when these patients are admitted to skilled nursing facilities for rehabilitation after their acute episode.

Background and Objectives Optimal surgical decision-making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data. Elevated C-reactive protein (CRP) may help guide patient selection for palliative surgery. Methods Procedures to palliate symptoms of advanced cancer were identified from a prospective palliative surgery database. Patients with a recorded preoperative serum CRP were identified and observed for at least 180 days or until death. Results Fifty patients were identified who underwent an elective palliative procedure from July 2006 to June 2012. Presenting symptoms included gastrointestinal obstruction (40%), tumor-related pain (38%) or bleeding (12%), and other (10%). Symptom improvement was documented for 37 patients (74%). Palliative procedures were associated with 30-day postoperative morbidity (42%) and mortality (10%). CRP (range 1–144 mg/L, median 9.7 mg/L) was elevated in 27 patients (54%) and was independently associated with developing a major complication (P = 0.005) and decreased overall survival (166 vs. 659 days, P

Although nearly 18 million adults have been diagnosed as having a current alcohol abuse or dependence disorder, only 1 in 7 reports ever having received any kind of alcohol treatment (Grant et al., 2004; Cohen et al., 2007). At the same time, people with alcohol use problems are likely to be treated in trauma care centers and emergency departments (EDs) (Cohen et al., 2007) for problems related or unrelated to their alcohol use. People with alcohol-related problems are overrepresented in ED and primary care settings compared with those in the general population (Cherpitel, 1994). Furthermore, alcohol-related ED visits have increased significantly over the past 15 years (Cherpitel & Ye, 2012). Therefore, EDs provide an opportunity for screening and brief intervention for problematic alcohol use. Although it has been over three decades since a WHO Expert Committee first called for the development of methods that could be efficiently applied in primary care settings (World Health Organization, 1980), national goals for a reduction in substance-related ED visits (Healthy People 2010, U.S. Department of Health and Human Services, 2005) have not been realized (Cherpitel & Ye, 2012). A recent review (Nilsen et al., 2008) of 14 studies of brief motivational intervention (BMI) in EDs for alcohol indicates that although some studies have found that BMI reduced alcohol consumption, hazardous use of alcohol, and alcohol-related injuries (compared to usual ED care), approximately 35% of the reviewed studies found no effect (e.g. Daeppen, et al., 2007; D’Onofrio, et al., 2008). Also somewhat mixed are the results of a recent meta-analysis (Kaner et al., 2009) of 22 randomized controlled trials in primary care settings that confirmed the benefit of BMI for men but not women. Furthermore, even when positive treatment effects are reported, not all outcome measures are impacted similarly (e.g., Field et al., 2009; Monti et al., 1999). For example, past studies have identified BMI effects (i.e., group differences) in alcohol use but not in alcohol-related problems (Monti et al., 2007); others have found intervention group differences in alcohol-related problems, but not in drinking behaviors (Longabaugh et al., 2001; Monti et al., 1999). These discrepancies in results suggest the need for a more impactful approach. One possible avenue for enhancing the effects of BMI in emergency care might be to incorporate significant others (SO) into the treatment. Concerned SOs tend to be present soon after hospital admissions, and may be open to supporting their family member/friend’s behavior change. SOs can provide positive and/or negative influences on alcohol treatment process and outcome in various ways (Magill et al., 2010). For example, Havassy et al. (1991) found the social network can inhibit drinking; friends or family members can (a) provide feedback that might help motivate the problem drinker to change the drinking behavior; (b) affirm skills of the problem drinker that enhance the probability of successful change; (c) help set treatment goals; and (d) provide support for changes in drinking behavior (Miller et al., 1995a). On the negative side, an alcohol abuser’s social network is likely to include other heavy drinkers, and many will drink with their partners (e.g., Fernandez-Pol et al., 1986), which can make reducing alcohol intake or abstinence especially difficult (e.g., Havassy et al., 1991; Hunter-Reel et al., 2010), and can make it challenging to select an appropriate SO for intervention. Nevertheless, there is a basis for including SOs in brief alcohol treatment. There is a substantial literature establishing the efficacy of SO-enhanced interventions for alcohol problems (e.g., Epstein & McCrady, 1998; McCrady et al., 2009) although including SO’s in treatment does not always increase benefits (Monti, et al., 1990). Having family and friend networks that are supportive of alcohol use reduction is predictive of successful change (Longabaugh et al., 1995; Stout et al., 2012), with SO-involved alcohol interventions reliably increasing the likelihood that an at-risk drinker will initiate positive changes (O’Farrell, 1993). In a recent meta-analysis, a clear advantage was found for Behavioral Couples Treatment (BCT) over individual-based treatments for frequency and consequences of alcohol use as well as relationship satisfaction (Powers et al., 2008). Although the benefit of BCT with low severity problem drinkers has been studied less, there is some evidence for lower efficacy with these individuals (Powers et al., 2008). Miller and Rollnick (2002) support the notion that SOs are a natural support that can reinforce the identified patient’s change process. The Motivational Enhancement Therapy Manual created for Project MATCH (MET: Miller et al., 1992) suggests the inclusion of a SO in early treatment sessions to help patients resolve ambivalence regarding change. The premise was that SOs could describe alcohol-related consequences, offer support, comment on the feedback provided by the therapist, and generally contribute opinions that may be more positively received by the patient than if delivered by the therapist. Unfortunately, in Project MATCH only 17% of outpatient and 13% of aftercare MET patients elected to include SOs (Carroll et al., 1998), and only 2% did so in a subsequent study of MET (Miller et al., 2003a). Despite the number of studies examining and supporting BCT and couples treatment for alcohol use disorders, few studies incorporating SOs into motivational interviewing (MI) sessions have been conducted, and to date, such interventions have been delivered almost exclusively in individual format (cf. Cordova, et al., 2001). The efficacy of an enhanced MI that includes both the patient and a SO as a design element is unknown. Given the low rates of optional SO participation in prior research, any study designed to test the addition of SOs to MI sessions would necessarily have to require that both the patient and SO participate. It is likely that this requirement has been a deterrent to conducting this type of treatment study. Inherent difficulties and the additional work involved in recruiting appropriate SOs who are motivated to participate are indeed challenges. Nevertheless, given that SOs are often present and concerned about the patient in the hospital, recruitment and inclusion of SOs in such a study might be more successful in this “opportunistic setting.” Another variable that may influence outcomes is recruitment site. The efficacy of BMI has been studied most often in the ED, less often in the trauma unit, and very few studies have recruited patients from both sites. These treatment sites are distinct; trauma units treat more severely injured patients and over longer periods of time. Most trauma patients are hospitalized following acute treatment for the trauma; ED patients are not typically admitted to a trauma service. Both settings are appropriate for an opportunistic BMI as both provide a window of opportunity occasioned by a medical event (Field et al., 2010). Since the optimal application and practice of BIs in medical settings has been questioned (Field et al., 2010; Nilsen et al., 2009) this study enrolled patients from both sites. The objective of this study was to investigate the relative efficacy of a SO-enhanced Motivational Intervention (SOMI) compared to an Individual Motivational Intervention (IMI). Our primary aim was to test the hypothesis that patients who received SOMI would drink less alcohol and suffer fewer alcohol-related consequences in the year following their hospital visit as compared to patients assigned to IMI. Our secondary aim was to test the extent to which SOMI (compared to IMI) led to significant changes in SO behaviors related to patient drinking. Both sets of aims (primary and secondary) incorporated an exploration of the effects of intervention setting (trauma unit vs. ED) without a theoretical basis for hypothesizing any interaction.

We designed a simple, low-cost workshop to teach surgical residents the basic skills of vascular anastomosis. We studied our ability to identify objective procedural and end-product metrics that could be used to measure improvement in vascular anastomotic skill before and after training.Ten postgraduate year 2 residents without previous vascular surgery experience and four attending surgeons (expert) performed end-to-side anastomosis using a synthetic graft. The residents were taught the basic skills of vascular anastomosis during three didactic workshops. The objective metrics included volume leakage after saline perfusion (leak) and the time needed to complete the anastomosis. Penalty points were assigned for broken sutures, air knots, locking sutures, and failure to maintain an outside-in to inside-out technique. The leak, time, and penalties before and after training were compared.The mean leak was 70.4 ± 13.7 mL and the mean completion time was 18.7 ± 3 min for the pretraining group versus 45.3 ± 10.6 mL (P0.01) and 8.5 ± 1 min (P0.001), respectively, for the attending group. After training, significant improvement was seen in resident leak (46.7 ± 6.8 mL; P0.001) and completion time (14.4 ± 3 min; P0.01). Leak was similar between the post-training and expert groups (46.7 ± 6.8 mL and 45.3 ± 10.6 mL, respectively; P = 0.77); however, a significant difference for the completion time remained (14.4 ± 3.0 min and 8.5 ± 1 min, respectively; P0.01). The mean number of technical errors improved from 2.7 in the pretraining group to zero for the post-training group after completing the workshop.We have reported an easy to implement workshop for teaching surgical residents the basic skills of performing vascular anastomosis.

Introduction Ventilator-associated pneumonia (VAP) occurs in up to 25% of mechanically ventilated patients, with an associated mortality up to 50%. Early diagnosis and appropriate empiric antibiotic coverage of VAP are crucial. Given the multitude of noninfectious clinical and radiographic anomalies within trauma patients, microbiology from bronchioalveolar lavage (BAL) is often needed. Empiric antibiotics are administered while awaiting BAL culture data. Little is known about the effects of these empiric antibiotics on patients with negative BAL microbiology if a subsequent VAP occurs during the same hospital course. Methods This is a retrospective chart review of intubated trauma patients undergoing BAL for suspected pneumonia over a 3-y period at a Level 1 trauma center. All patients with suspected VAP undergoing a BAL receive empiric antibiotics. If microbiology data are negative at 72 h, all antibiotics are stopped; however, if the BAL returns with ≥10 5 colony-forming units per milliliter, the diagnosis of VAP is confirmed. We divided patients into three groups. Group 1 consisted of patients in whom the initial BAL was positive for VAP. Group 2 consisted of patients with an initial negative BAL, who subsequently developed VAP at a later point in the hospital course. Group 3 consisted of patients with negative BAL who did not develop a subsequent VAP. Results We obtained 499 BAL specimens in 185 patients over the 3-y period. A total of 14 patients with 23 BAL specimens initially negative for VAP subsequently developed VAP later during the same hospital stay. These patients did not have an increase in the hospital length of stay, intensive care unit days, ventilator days, or mortality compared with those who had a positive culture on the first suspicion of VAP. There was a significant increase in the percentage of Enterobacter (21% versus 8%) and Morganella (8% versus 0%) as the causative organism in these 14 patients when the VAP occurred. Furthermore, the profile of the top two organisms in each group changed. Enterobacter (21%) and Pseudomonas (17%) were the principal organisms in the initial BAL-negative group, whereas the two predominant strains in the initial positive BAL group were methicillin-sensitive Staphylococcus aureus (21%) and Haemophilus influenza (11%). Interestingly, methicillin-resistant S. aureus remained the third most common organism in both groups. Empiric antibiotics also did not seem to induce the growth of multidrug-resistant organisms, and there was no increased rate of secondary infections such as Clostridium difficile . Conclusions Ventilator-associated pneumonia remains a significant cause of morbidity and mortality in mechanically ventilated trauma patients. The diagnosis and treatment of VAP continue to be challenging. Once clinically suspected, empiric coverage decreases morbidity and mortality. Our data demonstrate that patients who receive empiric coverage exhibit a significantly different microbiologic profile compared with those who had an initial positive BAL culture. Initial empiric antibiotics in BAL-negative patients were not associated with an increase in multidrug-resistant organisms, hospital, or intensive care unit length of stay, ventilator days, and mortality or secondary infections.

Although seemingly disparate problems, patients with perforated peptic ulcers (PPU) and dislodged percutaneous endoscopic gastrostomies (PEGs) share several common features and the successful management of these patients requires considerable thought and attention to detail. Despite the development of potent medications to suppress gastric acid production and an appreciation of the critical role Helicobacter pylori plays in peptic ulcer disease as well as effective therapies to treat it, PPU remain a highly lethal condition particularly in the elderly. Patients with PEGs tend to be acutely ill or debilitated with limited physiologic reserves which may render them poor surgical candidates. Thus, patients with PPU and dislodged PEGS are both increased risk for peritonitis, complications, and death. In selected patients with either of these conditions, non-operative management may be successful but it is imperative that clinicians approach these patients cautiously since the risk of serious complications is so high. Advances in technology have created opportunities to manage patients with PPU or dislodged PEGs through minimally invasive, endoscopic, and other modalities but the best outcomes can only be realized when the right technology is employed in the right patient at the right time. Younger patients, those with minimal medical comorbidities and those without signs of systemic toxicity, are appropriate candidates for non-operative or minimally invasive techniques but the elderly those with established peritonitis or sepsis belong in the operating theater. Our understanding of H. Pylori and its role in peptic ulcer disease had dramatically impacted surgical care, altering the types of operations performed for PPU, and mandating detection and eradication of this organism in order to successfully treat the patient with complications due to this organism. The clinical presentation of an acute incarcerated paraesophageal hernia is a serious condition. There are clear clinical and radiographic signs that help in the diagnosis. The surgeon must quickly be able to determine whether the patient is sick or septic. The initial step should be to decompress the stomach with a nasogastric tube. The next step is to determine whether the patient requires emergent/urgent surgery or a semi-elective repair. Once the decision is made to go to the OR and there is no evidence of gastric perforation, an initial diagnostic laparoscopic approach can be used. If full thickness gastric necrosis or perforation is encountered, a staged resection and reconstruction should be considered if the patient is critically ill.

Background Despite advances in perioperative care, the rate of cardiac events in vascular patients remains high. We have previously shown that infections in trauma patients are associated with higher rates of subsequent cardiac complications, likely due to the additive effect of a second hit of an infection following the trauma. The aim of this study was to investigate whether there is an association between postoperative infections and subsequent cardiac events in vascular patients. Methods A 5-year retrospective review of demographics, comorbidities, operative interventions, infectious, and cardiac events in all vascular patients who underwent an operative intervention at a single tertiary referral center was performed. In patients with clinical suspicion of myocardial injury, myocardial damage was defined as troponin >0.15 ng/mL and myocardial infarction (MI) as troponin >1 ng/mL. Pneumonia was diagnosed using bronchoalveolar lavage (BAL) and considered positive if BAL fluid culture contained >10,000 colony-forming units (cfu). Urinary tract infection (UTI) was diagnosed if the urine culture contained >100,000 cfu. All other infections were diagnosed by culture data. Regression analysis was performed to assess risk of cardiac events as a function of infections adjusting for age, gender, and comorbidities. Results We analyzed 1,835 vascular operative interventions with the mean age of the cohort 65.5 years (65.9% male). The overall infection rate was 13.2%, with UTI being the most common (60.3%). The overall rate of myocardial damage was 8.1% and the rate of MI 3.8%. Rates of both myocardial damage (15.5 vs. 7.7%; P = 0.0015) and MI (7.1 vs. 3.4%; P = 0.018) were significantly higher in patients with infections, compared to those without infections. Adjusting for age, gender, medical comorbidities, open versus endovascular cases as well as statin and steroid use, patients with UTI were more likely to subsequently develop either myocardial damage (odds ratio [OR] = 3.57 [95% confidence interval = 1.51-8.45]) or MI (OR = 4.20 [1.23-14.3]). A similar association was noted between any infections and either myocardial damage (OR = 2.97 [1.32-6.65]) or MI (OR = 4.31 [1.44-12.94]). Conclusions We herein describe an association between postoperative infections, most commonly UTI, and subsequent cardiac events. Efforts should be made to minimize the risk of developing infections to ensure cardioprotection in vascular patients during perioperative period.

BACKGROUND Trauma produces profound inflammatory and immune responses. A second hit such as an infection further disrupts the inflammatory cascade. Inflammatory responses, following traumatic injuries, infections, or both, are emerging as biologic mediators of cardiac disease including myocardial ischemia and infarction. Inflammation-induced and stress-related cardiac damage are increasingly recognized in patients with critical illness. It is believed that cardiac dysfunction is the result of alterations in the inflammatory and immune cascades. Urinary tract infections (UTIs) and ventilator-associated pneumonia (VAP) are associated with increased mortality in trauma patients. UTIs and VAPs induced inflammatory responses. We postulate that increased mortality seen in trauma patients with infections is caused by increased rates of cardiac injury. METHODS This is a retrospective review of prospectively collected data. All trauma patients admitted to the intensive care unit at our Level I trauma center during 5 years were included in the analysis. Proportional hazard regression analysis was performed to predict suspicion of cardiac injury (troponin ordered), any cardiac injury (troponin > 0.15 ng/mL), or severe cardiac injury (troponin > 1 ng/mL) using age, sex, Injury Severity Score (ISS), pulmonary disease (chronic obstructive pulmonary disease), heart failure, hypertension, diabetes, and the presence of a UTI or VAP. A similar proportion hazard regression was performed to predict mortality. RESULTS In the model to predict any cardiac injury, chronic obstructive pulmonary disease (hazards ratio [HR], 1.9; p = 0.02), ISS (HR, 1.01; p = 0.04), VAP (HR, 5.6; p < 0.01), and UTI (HR, 2.4; p = 0.03) were significant. Neither VAP nor UTI predicted severe cardiac injury. In the model to predict death, any cardiac injury was not associated with mortality, but severe cardiac injury and UTI were associated with mortality as age increased. CONCLUSION Infectious complications have been associated with increased mortality in trauma patients. Our data demonstrate that development of VAP or UTI is associated with an increased risk of developing cardiac injury in trauma patients, which may contribute to subsequent increased mortality. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.

Obese women who become pregnant face many health risks, including gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia. These women also have a greater incidence of preterm labor, cesarean sections, and perioperative morbidity. Infants born to obese women have increased rates of macrosomia and congenital anomalies, as well as life-long complications such as obesity and its associated morbidities. With the increase in numbers of weight loss operations being performed in women of child-bearing age, physicians will have to address patient concerns regarding the safety of pregnancy after surgery. Many of the proposed health benefits of weight loss after surgery could translate to decreased rates of complications experienced by obese pregnant women. Case reports and small series have emerged documenting pregnancy courses after bariatric surgery. We reviewed the studies that reported pregnancy outcomes compiled from PubMed and Ovid databases to help draw conclusions regarding the maternal, fetal, and infant safety in women after bariatric surgery. The observations from these studies have shown that the health risks experienced by obese women during pregnancy are reduced after weight loss surgery. Additionally, there does not appear to be any increased risk regarding fetal or infant outcome.

Odontoid fractures are the most common cervical spine fractures in elderly patients. Treatment options included operative fixation (OP) or nonoperative management with either a halo-vest (HV) or rigid cervical orthosis (CO). Our previous study suggested increased morbidity and mortality with the use of HV in the treatment of elderly patients with cervical spine fractures. We review a series of odontoid fractures in elderly patients and evaluate for predictors for in-hospital morbidity and mortality.There were 78 patients65 years of age who sustained a type II or III odontoid fracture from January 1997 to June 2004 identified from the Rhode Island Hospital Trauma registry. Demographic, mechanism, injury pattern, treatment, and outcome data were recorded. Patients were analyzed according to treatment method.The mean age was 80.7 +/- 0.9 years. There were 50 type II, 17 type III, and 11 combined fractures. There were 38 (49%) patients treated with HV: 34 with halo alone, and 4 after OP; 40 (51%) patients were treated without HV: 27 with CO, and 13 with OP. There was no difference in injury severity or baseline medical condition between HV and non-HV patients. There were 24 (31%) patients who died during their hospital stay. Of the HV patients, 42% died compared with 20% in the non-HV group (p = 0.03). Major complications occurred in 66% of HV patients compared with 36% of non-HV patients (p = 0.003).Odontoid fractures are associated with significant morbidity and mortality in elderly patients. Outcomes after treatment with HV appear inferior to those achieved with CO or OP.

A phase I trial was conducted to determine the maximally tolerated dose of erlotinib with concurrent gemcitabine, paclitaxel, and radiation for patients with locally advanced pancreatic cancer and to gather preliminary data on maintenance erlotinib after chemoradiation.Patients received gemcitabine, 75 mg/m2, and paclitaxel, 40 mg/m, weekly for 6 weeks with 50.4 radiation to the primary tumor and draining lymph nodes with a 2- to 3-cm margin. Erlotinib was administered over 3-dose levels (50-100 mg/d) with chemoradiation then all patients received 150 mg/d maintenance until disease progression.Seventeen patients were assessable for toxicity; 13 with locally advanced disease and 4 who had undergone resection but had positive margins. At erlotinib dosagesor =75 mg/d with chemoradiation the dose-limiting toxicities were diarrhea, dehydration, rash, myelosuppression, and small bowel stricture. Maintenance erlotinib, 150 mg/d, was well tolerated. The median survival of the 13 patients with locally advanced disease was 14.0 months and 6 of 13 (46%) had a partial response.The maximum tolerated dose of erlotinib with gemcitabine, paclitaxel and concurrent radiation is 50 mg/d for patients with locally advanced pancreatic cancer. Full dose maintenance erlotinib is well tolerated. Promising preliminary activity and overall survival were demonstrated.

Background: Cervical spine fractures (CSFs) in elderly patients are increasingly common as the population ages. In many centers, halo vest immobilization (HVI) is the treatment of choice. Our anecdotal experience suggested that elderly patients treated with HVI have frequent bad outcomes. The purpose of this study was to compare the outcomes of elderly and younger CSF patients as related to treatment (HVI, surgery, or hard collar). Methods: Registry data from our Level I trauma center were reviewed to identify patients admitted with CSFs during an 80-month period. We excluded those with Glasgow Coma Scale (GCS) score of 3 at admission or death within 24 hours of admission. Patients were grouped as OLD (aged ≥ 66 years) or YNG (aged 18-65 years). Data were compared using X 2 and Student's t test, with p < 0.05 considered statistically significant. Results: One hundred twenty-nine OLD (aged 79.7 ± 0.7 years) and 289 YNG (aged 383 ± 0.8 years) patients met study criteria. Injury Severity Score was higher in YNG (18.9 ± 0.8 vs. 14.8 ± 1.0, p < 0.05), and GCS score was the same (OLD, 13.7 ± 0.2; YNG, 13.0 ± 0.2; p = 0.06) in both, but mortality was higher in OLD patients (21% vs. 5%, p < 0.05). OLD HVI patients had higher mortality than YNG HVI (40% vs. 2%). Among OLD patients, age, Injury Severity Score, GCS, and number of comorbidities were the same for each treatment subgroup. Despite this, mortality for the HVI subgroup was higher than either the surgery or collar subgroup. Of the OLD HVI patients that died, 14 died with pneumonia and 10 had a cardiac or respiratory arrest that preceded death. Conclusion: OLD patients with CSFs have higher mortality than YNG. HVI in OLD patients is associated with the worst outcomes, irrespective of injury severity, and should be considered a last resort. Further study is warranted to determine the optimal treatment for CSF in OLD patients.

The purpose of this study was to review our experience with interfacility transfers to identify problems that could be addressed in the development of a statewide trauma system.The fundamental tenet of a trauma system is to get the right patient to the right hospital at the right time. This hinges on well-defined prehospital destination criteria, interfacility transfer protocols, and education of caregivers. Patients arriving at local community hospitals (LOCs) benefit from stabilization and transfer to trauma centers (TCs) for definitive care. However, in the absence of a formalized trauma system, patients may not reach the TC in a timely fashion and may not be appropriately treated or stabilized at LOCs prior to transfer.Our facility is a level I TC and regional referral center for a compact geographic area without a formal trauma system. The Trauma Registry was queried for adult patients admitted to the trauma service between January 1, 2001 and March 30, 2003. Patients were divided into 2 groups: those received directly from the scene (DIR) and those transferred from another institution (TRAN). Medical records were reviewed to elucidate details of the early care. Data are presented as mean +/- SEM. Continuous data were compared using Student t test, and categorical data using chi2. Transfer times were analyzed by one-way ANOVA.A total of 3507 patients were analyzed. The TRAN group had a higher Injury Severity Score (ISS) (17.5 versus 11.0, P0.05), lower Glasgow Coma Score (GCS) (13.3 versus 14.1, P0.05), lower initial systolic blood pressure (SBP) (130 versus 140, P0.05), and higher mortality (10% versus 79%, P0.05) than the DIR group. The average time spent at the LOC was 162 +/- 8 minutes. The subgroup of patients with hypotension spent an average of 134 minutes at the LOC, often receiving numerous diagnostic tests despite unavailability of surgeons to provide definitive care. Severe head injury (GCS = 3) triggered more prompt transfer, but high ISS was underappreciated and did not result in a prompt transfer in all but the most severely injured group (ISS40). Some therapeutic interventions were initiated at the LOCs, but many were required at the TC. A total of 23 (8%) TRAN patients required critical interventions within 15 minutes of arrival; mortality in this group was 52%. Mortality among those requiring laparotomy after transfer was 33%.All but the most severely injured patients spend prolonged periods of time in LOCs, and many require critical interventions upon arrival at the TC. It is unreasonable to expect immediate availability of surgeons or operating rooms in LOCs. Thus, trauma system planning efforts should focus on 1) prehospital destination protocols that allow direct transport to the TC; and 2) education of caregivers in LOCs to enhance intervention skill sets and expedite transfer to definitive care.

Background My colleagues and I compared trauma patient demographics and outcomes between two time periods in the last 10 years in our Level I trauma center to evaluate the impact of the marked evolution in trauma care and determine additional opportunities for improvement. Methods Our trauma registry was queried for adult trauma patients admitted from 1991 to 1993 (EARLY) and 1999 to 2001 (LATE). The EARLY period predated creation and maturation of a dedicated trauma service and Level I trauma center verification. Continuous data were compared using Student's t-test, and categorical data using chi-square. Results Increased transfers of severely injured patients from regional hospitals, combined with fewer admissions for "observation," resulted in fewer, but sicker, patients admitted in the LATE period. Patients were considerably older in the LATE period and mortality was higher. Despite higher acuity of patients, hospital and ICU lengths of stay were shorter in the LATE period. Nonoperative management of solid organ injuries was more common in the LATE period, but the overall operative volume was similar. Nonsurvivors in the LATE period had higher Injury Severity Scores and were older compared with the EARLY period. Mortality attributable to blunt CNS injury was higher, and that attributed to late sepsis and multiple organ failure was lower in the LATE period. Conclusions Over the past decade, more older, severely injured patients have been admitted to our Level I trauma center. Overall mortality among these higher acuity patients has increased, with a marked shift in attributable mortality to CNS injury and away from late sepsis and multiple organ failure. This highlights the need for continued efforts to identify optimal management strategies for severe brain injury. Additional areas for improvement include enhancement of our regional trauma network and injury prevention initiatives.

PURPOSE: To conduct a phase I study incorporating trastuzumab with paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus. METHODS AND MATERIALS: Patients with adenocarcinoma of the esophagus without distant organ metastases were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation 50.4 Gy. HER-2/neu-positive patients (2+/3+ by immunohistochemistry) received weekly trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg, respectively. HER-2/neu-negative patients received the same chemoradiation without trastuzumab as a control for toxicity. Dose-limiting toxicities were defined as grade 3 esophageal, cardiac, or pulmonary toxicity. RESULTS: Twelve of 36 screened patients (33%) overexpressed HER-2/neu by immunohistochemistry (seven 3+ and five 2+). Eight of 12 patients with HER-2/neu overexpression by IHC had an increase in the number of HER-2/neu genes, six from amplification of the HER-2/ neu gene and two were hypderdiploid for chromosome 17. Thirty patients were enrolled (12 HER-2/neu-positive and 18 HER-2/neu-negative controls). No increase in toxicity was seen with the addition of trastuzumab. One of 12 patients in the trastuzumab arm and 8 of 17 in the control arm had grade 3 esophagitis (p < or = .026). Mean left ventricular ejection fraction for the trastuzumab group was 57% before treatment and 56% after treatment. CONCLUSION: HER-2/neu is overexpressed in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be added at full dose to cisplatin, paclitaxel, and radiation. Future studies of trastuzumab in esophageal adenocarcinoma are indicated.

Background: Missed injuries (MIs) adversely affect patient outcome and damage physician/institutional credibility. The primary and secondary surveys are designed to identify all of a patient's injuries and prioritize their management; however, MIs are prevalent in severely injured and multisystem trauma patients, especially when the patient's condition precludes completion of the secondary survey. We hypothesized that implementation of a routine tertiary trauma survey (TS) would reduce the incidence of MIs in a Level I trauma center. Methods: In mid 1999, a TS form was created and TS documentation was mandated on all trauma intensive care unit (TICU) patients within 24 hours of admission. Patient data, including TS documentation and injury patterns, were concurrently recorded in an institutional trauma registry. Data were compared for patients admitted in 1997 to 1998 (PRE period) and 2000 to 2001 (POST period) using X 2 or Student's t test. Results: MIs decreased from 2.4% to 1.5% overall, and from 5.7% to 3.4% in TICU patients, after TS implementation. Patients with MIs were slightly older (49 vs. 45 years; p > 0.05) and had higher Injury Severity Scores (21 vs. 10; p < 0.05) than patients without MIs. Sixty percent of MI patients had brain injuries, 56% were admitted to the TICU, and 26% went directly from the emergency department to the operating room. The large majority of MIs in the POST period were detected in patients not undergoing timely TS. Conclusion: ICU patients-particularly brain injury victims and those undergoing emergent surgical procedures-appear to be at highest risk for MI. Implementation of a standardized TS decreased MIs by 36% in our Level I trauma center, and more timely TS would likely have further reduced MIs. A TS should be routine in trauma centers.

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic cancer. Methods and Materials: Twenty patients with locally unresectable pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m 2 and paclitaxel 40 mg/m 2 weekly for 6 weeks. Concurrent radiation to 50.4 Gy was delivered in 1.8 Gy fractions. The radiation fields included the primary tumor, plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. Results: Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m 2 /week. An intermediate dose level of gemcitabine, 110 mg/m 2 /week, was added, but gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD therefore was gemcitabine 75 mg/m 2 /week with paclitaxel 40 mg/m 2 /week and concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4 toxicity. Four of 10 assessable patients treated at the MTD responded (40%), including one pathologic complete response. Conclusion: The maximum tolerated dosage of gemcitabine is 75 mg/m 2 /week with paclitaxel 40 mg/m 2 /week and conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology Group study is under way.

Background: After the onset of sepsis, there is a marked dysfunction in cell-mediated immunity that contributes to the morbidity and mortality seen in this condition. Although both nitric oxide (NO) from inducible NO synthase (iNOS) and the activation of p38 mitogen-activated protein kinase (p38 MAPK) appear to contribute to this immune dysfunction, the extent to which NO regulates p38 MAPK activity in sepsis remains unknown. Methods: To examine this, we induced sepsis by cecal ligation and puncture (CLP) in iNOS knockout (iNOS -/-) or C57BL/6 control mice. Twenty-four hours after CLP or sham operation, splenic T cells and macrophages were isolated and then stimulated with monoclonal antibody against the T-cell marker CD3 (anti-CD3) or lipopolysaccharide. At 4 or 24 hours after stimulation, cytokine release was determined by enzyme-linked immunosorbent assay, and p38 MAPK phosphorylation (activation) was determined by immunoblotting with antibody specific to phosphorylated p38 MAPK. Results: Splenic T-cell p38 MAPK activation and interleukin (IL)-10 release was increased by CLP, whereas Th1 cytokine (IL-2, interferon-y) release was depressed. iNOS gene deficiency inhibited p38 MAPK activation in splenic T cells taken from septic mice, and also suppressed IL-10 release in both sham and septic mice. Interestingly, although deficiency of iNOS restored IL-2 release after CLP, both sham and CLP T cells remained depressed in their ability to release interferon-y. Septic insult markedly suppressed C57BL/6 splenic macrophage release of proinflammatory agents tumor necrosis factor, IL-12, and IL-1, while augmenting the release of IL-10. However, although deficiency of iNOS concomitantly restored the ability to produce tumor necrosis factor while suppressing the rise in IL-10 release and p38 MAPK activation, it only partially restored IL-1 release and had no effect on IL-12 production seen after CLP. Conclusion: These data suggest that NO release from iNOS regulates aspects of sepsis-induced immune dysfunction by the activation of p38 MAPK.

A well-described array of metabolic derangements occurs after severe trauma or burn. This response includes hyperdynamic circulation, fever due to resetting of the hypothalamic temperature set point, immune deficiency, impaired wound healing, peripheral insulin resistance, alteration of hepatic protein synthesis, skeletal muscular protein catabolism, and elevated systemic energy expenditure. 1–9 During the flow phase after injury, survivors manifest a hyperdynamic circulation and begin to overtly display other systemic manifestations of global hypermetabolism. 10 Defects of both cellular and humoral immune function increase the likelihood of infection, hepatic protein synthesis shifts from storage and housekeeping proteins to acute phase response proteins, peripheral tissue insulin resistance with hyperglycemia occurs, and catabolism of proteins stores (predominantly skeletal muscle) leads to erosion of lean body mass. Fluxes of substrate fuels are altered with glucose, fat, and amino acids being supplied to the wound from hepatic gluconeogenesis, lipolysis, and auto-catabolized muscle protein. With the exception of circulatory physiologic parameters, these diverse systemic alterations are difficult to quantify. Associated with the hypermetabolic response is elevation in systemic energy expenditure. 11 This has been shown to correlate with the degree of muscle protein catabolism, impaired wound healing, and immune deficiency. 12-14 Resting energy expenditure as a correlate to total energy expenditure can be measured relatively easily at the bedside utilizing indirect calorimetry. Resting energy expenditure is determined from inspired and expired gases, measuring oxygen consumption and carbon dioxide production. It is noninvasive, reproducible, and immediately quantifiable (results are usually obtained within minutes). The general correlation between elevated energy expenditure and muscle catabolism has led to the notion that energy expenditure determines energy demand, which is required to offset catabolism. These demands, then, are met through the dietary delivery of calories. We hypothesize that muscle catabolism proceeds after severe burn regardless of caloric balance (caloric administration –measured energy expenditure). The goal of this study was twofold. First, we sought to determine the clinical relevance of elevated energy expenditure after burn, specifically whether elevated energy expenditure correlated with increased morbidity or mortality in the setting of severe burn. Second, we sought to determine whether energy expenditure could be used to define caloric demand to optimize attenuation of erosion of lean body mass. Our hypotheses were that 1) systemic energy expenditure is reflective of the degree of illness increasing to a point of exhaustion, after which decreases would correlate with mortality; and that 2) no optimal energy/caloric balance exists that abolishes catabolism of lean mass when at least 1.2 times the measured resting energy expenditure is delivered.

To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mphi) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis.Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage.Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 +/- 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mphi and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed.Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mphi from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mphi from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice.These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.

Background Current literature is controversial regarding the importance of obese BMI classifications as a risk factor for pulmonary complications after outpatient surgery. The objective of the current investigation was to evaluate predictors of pulmonary outcomes after outpatient surgery and to assess the importance of BMI weight classifications in risk assessment. Study Design Patients with "outpatient" recorded as their inpatient/outpatient status in the 2012 to 2013 NSQIP database were included. The primary outcome of interest was the occurrence of a new pulmonary complication (eg pneumonia, pulmonary embolism, unplanned intubation, or ventilator-assisted respiration for greater than 48 hours) within 30 days of surgery. Results There were 444,532 cases included in the final analysis. There were 996 (0.22%; 99% CI 0.21% to 0.24%) all-cause pulmonary complications. Binary logistic regression identified BMI as an independent predictor of a pulmonary complication, unadjusted odds ratio 1.091 (99.75% CI 1.026 to 1.160) per 5 kg/m 2 change in BMI, p 2 was 1.44 (99.75% CI 1.01 to 2.06; p = 0.002) and with a BMI of 40 to 49.99 kg/m 2 was 1.68 (99.75% CI 1.13 to 2.50; p 2 . Conclusions Obese classes II and III were associated with an independent risk of a pulmonary complication. The risk associated with obesity was low compared with the risk associated with advanced age, prolonged surgical duration, and the risk of comorbidities including congestive heart failure, COPD, and renal failure.

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer. Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m 2 by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments. Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%. Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.

More than 30 years ago, the clinical presentation of acute respiratory distress syndrome was reported by Ashbaugh et al 1 from a series of patients with the acute onset of tachypnea, hypoxemia, decreased pulmonary compliance, and diffuse bilateral infiltrates on a chest radiograph. Four years later, this clinical consortium of signs and symptoms was officially termed adult respiratory distress syndrome (ARDS). 2 Despite advances in critical care, death rates have remained high (>50%), 3–6 with recent reports suggesting only a small improvement in outcome. 7–9 The risk factors associated with the development of ARDS are sepsis, trauma, multiple transfusions, aspiration of gastric contents, pulmonary contusion, pneumonia, and near-drowning. 10 The current definition of ARDS has evolved from the five initial diagnostic criteria: acute respiratory failure from a known risk diagnosis, low respiratory compliance, a pulmonary artery occlusion pressure of 16 mmHg or less, diffuse bilateral infiltrates on a chest radiograph, and a decreased arterial-to-alveolar partial pressure of oxygen ratio (

"What's New in Surgery" evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons' Advisory Councils for the Surgical Specialties. This feature will be presented in issues of the Journal through the year beginning in 2001 (formerly published in one issue, February, of each volume of JACS) .

BACKGROUND Although depression in hepatocellular function occurs early after trauma and severe hemorrhage and persists despite fluid resuscitation, it remains unknown whether reactive oxygen species (ROS) play any role in the initiation of hepatocellular depression and damage under those conditions. We hypothesized that administration of a ROS scavenger at the beginning of resuscitation will attenuate organ injury after severe shock. METHODS Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i.e., induction of soft tissue trauma) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of maximal bleed-out with RL over 60 minutes. The ROS scavenger 2-mercaptopropionyl glycine (30 mg/kg) or vehicle was administered intravenously as a bolus at the beginning of resuscitation. At 2 hours after the completion of crystalloid resuscitation or the equivalent interval after sham-operation, cardiac index was measured by a dye dilution technique. Hepatocellular function, i.e., the maximum velocity of indocyanine green clearance (Vmax) and the efficiency of the active transport (Km), was determined using an in vivo hemoreflectometer. Serum levels of tumor necrosis factor (TNF)-alpha and alanine aminotransferase were determined with ELISA and colorimetrically, respectively. RESULTS The results indicate that at 2 hours after trauma hemorrhage and resuscitation, cardiac index and hepatocellular function were markedly depressed with concomitantly increased serum levels of TNF-alpha and alanine aminotransferase (p < 0.05). Administration of 2-mercaptopropionyl glycine, however, restored the depressed cardiac and hepatic function and markedly attenuated liver enzyme release and serum levels of TNF-alpha (p < 0.05). CONCLUSION Our data suggest that ROS play a role in producing the depression in organ functions after severe hemorrhagic shock. Thus, adjuncts that attenuate the detrimental effects of ROS may be useful for improving the depressed cardiac and hepatocellular functions after trauma hemorrhage and resuscitation.

Background. Although it is known that pentoxifylline (PTX) produces various beneficial effects during sepsis, it remains unknown whether this agent has any salutary effects on the depressed vascular responsiveness to adrenomedullin (ADM), a novel potent vasodilatory peptide, under such conditions. Materials and methods. Adult male Sprague–Dawley rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). One hour after CLP, PTX (50 mg/kg body wt) or vehicle (normal saline) was infused intravenously over 90 min. Twenty hours after CLP (i.e., the late, hypodynamic stage of sepsis), the thoracic aorta and small intestine were isolated and preconstricted by norepinephrine. Rat ADM (10−7 M) was applied, and the percentage of ADM-induced relaxation in the aortic rings and resistance vessels in the small intestine was determined. In addition, plasma ADM was determined by radioimmunoassay and tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 levels were measured by enzyme-linked immunosorbent assay. Results. The percentage of ADM-induced vascular relaxation in the aortic rings and resistance vessels of the isolated gut was significantly reduced 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented the decrease in vascular ADM responsiveness at the macro- and microcirculatory levels. Plasma ADM levels increased after CLP, irrespective of PTX infusion, indicating that the effect of PTX was not mediated by altering ADM release. The upregulated TNF-α, IL-1β, and IL-6 during late sepsis were, however, attenuated by PTX administration, suggesting that maintenance of ADM responsiveness by this agent appears to be due to downregulation of these cytokines. Conclusions. Since early administration of PTX maintains vascular ADM responsiveness even during the late stage of sepsis, this agent appears to be a useful adjunct in preventing the deterioration in hemodynamics and cardiovascular function during the progression of polymicrobial sepsis.

Studies indicate that immune responses after trauma-hemorrhage are significantly depressed in males compared with enhanced immune responses in females under such conditions. Although androgen depletion in male mice by castration before soft tissue trauma and hemorrhagic shock prevents the depression of cell-mediated immunity, the underlying mechanism responsible for this remains unclear. Because the thymus is the primary location of T-cell lymphopoiesis and thymocytes express a large number of androgen receptors, we investigated whether differences in thymic apoptosis might contribute to the divergent immune response in males versus females after trauma-hemorrhage. To study this, male and female C3H/HeN mice were subjected to sham operation or soft tissue trauma (laparotomy) and hemorrhagic shock followed by fluid resuscitation. Animals were killed 72 h thereafter and thymocytes were isolated. Thymocyte interleukin 3 (IL-3) release was significantly suppressed in males, but not females, after trauma-hemorrhage. A parallel increase in thymic apoptosis that was primarily in the CD8+ thymocyte subset was observed in the males. Furthermore, In vitro treatment of thymocytes with 5α-dihydrotestosterone (DHT) increased the rate of apoptosis and decreased IL-3 release in a dose-dependent manner. Thus, the gender-dependent dimorphic immune response after trauma-hemorrhage may be in part due to an androgen-induced increase in thymic apoptosis in males under such conditions.

Background: Studies indicate impaired wound healing after trauma. The underlying mechanism remains unknown. Methods: Mice were subjected to midline laparotomy, and polyvinyl alcohol sponges were implanted subcutaneously before hemorrhage (35 ± 5 mmHg for 90 minutes, resuscitated) or sham operation. Wound exudate cells from the sponges were harvested on the first, third, and fifth postoperative day and cultured for 24 hours. Interleukin (IL)-1β, IL-6, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and transforming growth factor (TGF)-β were determined in the supernatants. IL-1β and IL-6 were measured in the wound fluid. Results: Hemorrhage decreased collagen deposition in the wound. TGF-β release was significantly decreased on the first and third postoperative days after hemorrhage, whereas IL-1β and IL-6 release was increased at 3 and 5 days after hemorrhage. Similarly, IL-1β and IL-6 in the wound fluid were significantly increased at 3 days after hemorrhage. Conclusions: Because increased levels of pro-inflammatory cytokines and decreased amounts of TGF-β have been reported to impair the process of wound healing, the increased release of IL-1β and IL-6 and the decreased release of TGF-β after hemorrhage might contribute to the decreased collagen production in those animals. Thus, attempts to locally change the ratio of those cytokines in trauma victims might be useful for improving wound healing in those patients. (Surgery 1999;126:279-85.)

Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5α-dihydrotestosterone (DHT), 17β-estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 ± 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty-four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6 by splenic macrophage (−50 and −57%, respectively) and peritoneal macrophage (−51 and −52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased compared with that in sham-operated animals but was decreased in estrogen-treated mice under such conditions. These results suggest that male and female sex steroids exhibit divergent immunomodulatory properties with respect to cell-mediated immune responses after trauma-hemorrhage.

Although a profound depression in immune function occurs following injury, the mechanism responsible for this is not fully understood. Furthermore, steroid hormones are known to be important mediators in the regulation of immune function. Although dehydroepiandrosterone (DHEA), the most plentiful steroid hormone, has been shown to stimulate immune function in normal animals, it is unknown whether DHEA has any salutary or detrimental effects on immune responses after trauma and haemorrhage. To study this, male mice were subjected to trauma, haemorrhage and resuscitation, following which they received either DHEA or vehicle subcutaneously. DHEA administration restored the normally depressed splenocyte proliferation as well as interleukin 2, interleukin 3, and interferon gamma elaboration following trauma and haemorrhage. In an attempt to determine the mechanisms mediating this effect, T cells were stimulated in vitro in the presence of DHEA and a variety of hormone antagonists. The stimulatory effect of DHEA on splenocyte proliferation was unaltered by the testosterone receptor antagonist flutamide, while the oestrogen antagonist tamoxifen completely abrogated its effect. In addition, DHEA administration normalized the elevated serum corticosterone level typically seen following injury. These results indicate, therefore, that DHEA improves splenocyte function after trauma and haemorrhage by directly stimulating T cells and also by preventing a rise in serum corticosterone.