Total synthesis of (+)-pilosinine via a stereodivergent conjugate addition strategy.

In recent work, asymmetric conjugate addition reactions to chiral 4-phenyl-N-enoyl-1,3-oxazolidinones have been shown to give different stereochemical outcomes depending on the conditions employed. Through the application of stereodivergent reaction conditions, the total synthesis of (+)-pilosinine and the formal synthesis of (-)-pilosinine has been completed from a single enantiomer of the 1,3-oxazolidi-none auxiliary.

Major Barbara Stimson: A Historical Perspective on the American Board of Surgery Through the Accomplishments of the First Woman to Achieve Board Certification.

: Dr. Barbara Bartlett Stimson, AB, MD, MedScD, FACS (1898-1986) was a pioneering orthopedic surgeon from a prominent American family who, in 1940, became the first woman certified by the American Board of Surgery (ABS, certificate number 860). It would be another 7 years and approximately 2500 candidates before the next female surgeon would be certified. A member of the third class to admit women to Columbia Medical School and the second female surgical resident to complete training at Columbia-Presbyterian Medical Center, Dr. Stimson was a confident and exceptionally accomplished trailblazer for women in surgery. In this biographical sketch based upon documents from the ABS, and the archives of Vassar College and the College of Physicians and Surgeons at Columbia-Presbyterian Medical Center, Dr. Stimson's motivations, attitudes, and unique accomplishments emerge as testimony to the exceptional career of this driven, self-possessed woman. Stimson was undaunted by the sex-based conventions of her time, and achieved a notable career as a surgeon in the profession she loved; first honing her skills at a busy urban fracture service in New York, then serving with distinction in the Royal Army Medical Corps during World War II, and finally returning to the states to become a respected leader in her field. Her life story and unprecedented ABS certification affirm her conviction that proven skill and ability can be used as a means of overcoming unfounded biases, and helped pave the way for future generations of board certified female surgeons in the United States.

Long-term morbidity, pain, and disability after repair of severe chest wall injuries.

Long-term morbidity after severe chest wall injuries is common. We report our experience with acute chest wall injury repair, focusing on long-term outcomes and comparing our patients' health status with the general population. We performed a retrospective medical record review supplemented with a postal survey of long-term outcomes including the McGill Pain Questionnaire (MPQ) and RAND-36 Health Survey. RAND-36 outcomes were compared with reference values from the Medical Outcomes Study and from the general population. Forty-six patients underwent acute chest wall repair between September 1996 and September 2005. Indications included flail chest with failure to wean from the ventilator (18 patients), acute, intractable pain associated with severely displaced rib fractures (15 patients), acute chest wall defect/deformity (5 patients), acute pulmonary herniation (3 patients), and thoracotomy for other traumatic indications (5 patients). Three patients had a concomitant sternal fracture repair. Fifteen patients with a current mean age of 60.6 years (range 30-91) responded to our surveys a mean of 48.5 +/- 22.3 months (range 19-96) postinjury. Mean long-term MPQ Pain Rating Index was 6.7 +/- 2.1. RAND-36 indices indicated equivalent or better health status compared with references with the exception of role limitations due to physical problems when compared with the general population. The operative repair of severe chest wall injuries is associated with low long-term morbidity and pain, as well as health status nearly equivalent to the general population. Both the MPQ and the RAND-36 surveys were useful tools for determining chest wall pain and disability outcomes.

Surveyed opinion of American trauma, orthopedic, and thoracic surgeons on rib and sternal fracture repair.

INTRODUCTION: Rib and sternal fracture repair are controversial. The opinion of surgeons regarding those patients who would benefit from repair is unknown. METHODS: Members of the Eastern Association for the Surgery of Trauma, the Orthopedic Trauma Association, and thoracic surgeons (THS) affiliated with teaching hospitals in the United States were recruited to complete an electronic survey regarding rib and sternal fracture repair. RESULTS: Two hundred thirty-eight trauma surgeons (TRS), 97 orthopedic trauma surgeons (OTS), and 70 THS completed the survey. Eighty-two percent of TRS, 66% of OTS, and 71% of THS thought that rib fracture repair was indicated in selected patients. A greater proportion of surgeons thought that sternal fracture repair was indicated in selected patients (89% of TRS, 85% of OTS, and 95% of THS). Chest wall defect/pulmonary hernia (58%) and sternal fracture nonunion (>6 weeks) (68%) were the only two indications accepted by a majority of respondents. Twenty-six percent of surgeons reported that they had performed or assisted on a chest wall fracture repair, whereas 22% of surgeons were familiar with published randomized trials of the surgical repair of flail chest. Of surgeons who thought rib fracture or sternal fracture repair was rarely, if ever, indicated, 91% and 95%, respectively, specified that a randomized trial confirming efficacy would be necessary to change their negative opinion. CONCLUSIONS: A majority of surveyed surgeons reported that rib and sternal fracture repair is indicated in selected patients; however, a much smaller proportion indicated that they had performed the procedures. The published literature on surgical repair is sparse and unfamiliar to most surgeons. Barriers to surgical repair of rib and sternal fracture include a lack of expertise among TRS, lack of research of optimal techniques, and a dearth of randomized trials.

Early neurosurgical procedures enhance survival in blunt head injury: propensity score analysis.

BACKGROUND: Studies of trauma systems have identified traumatic brain injury as a frequent cause of death or disability. Due to the heterogeneity of patient presentations, practice variations, and potential for secondary brain injury, the importance of early neurosurgical procedures upon survival remains controversial. Traditional observational outcome studies have been biased because injury severity and clinical prognosis are associated with use of such interventions. OBJECTIVE: We used propensity analysis to investigate the clinical efficacy of early neurosurgical procedures in patients with traumatic brain injury. METHODS: We analyzed a retrospectively identified cohort of 518 consecutive patients (ages 18-65 years) with blunt, traumatic brain injury (head Abbreviated Injury Scale score of >or= 3) presenting to the emergency department of a Level-1 trauma center. The propensity for a neurosurgical procedure (i.e., craniotomy or ventriculostomy) in the first 24 h was determined (based upon demographic, clinical presentation, head computed tomography scan findings, intracranial pressure monitor use, and injury severity). Multivariate logistic regression models for survival were developed using both the propensity for a neurosurgical procedure and actual performance of the procedure. RESULTS: The odds of in-hospital death were substantially less in those patients who received an early neurosurgical procedure (odds ratio [OR] 0.15; 95% confidence interval [CI] 0.05-0.41). The mortality benefit of early neurosurgical intervention persisted after exclusion of patients who died within the first 24 h (OR 0.13; 95% CI 0.04-0.48). CONCLUSIONS: Analysis of observational data after adjustment using the propensity score for a neurosurgical procedure in the first 24 h supports the association of early neurosurgical intervention and patient survival in the setting of significant blunt, traumatic brain injury. Transfer of at-risk head-injured patients to facilities with high-level neurosurgical capabilities seems warranted.

Establishing the need for trauma center care: anatomic injury or resource use?

OBJECTIVE: It remains unclear whether the "need" for care at a trauma center should be based on anatomic injury (the current standard) or specialized resource use. We investigated whether anatomic injury severity scores adequately explain hospital resource use. METHODS: This was a retrospective cohort study including children and adults meeting statewide trauma criteria and transported to 48 hospitals from 1998 to 2003. The injury severity score (ISS) was considered as both continuous (range 0-75) and categorical (0-8, 9-15, and >or= 16) terms. Specialized resource use was defined as: major surgery (with and without orthopedic intervention), mechanical ventilation > 96 hours, blood transfusion, intensive care unit (ICU) stay >or= 2 days, or in-hospital mortality. Resource use was assessed as both a binary variable and a continuous term. Descriptive statistics and simple and multivariable linear regressions were used to compare ISS and resource use. RESULTS: 33,699 injured persons were included in the analysis. Within mild, moderate, and serious anatomic injury categories, 8%, 26%, and 69%, respectively, had specialized resource use. When the resource use definition included orthopedic surgery, 12%, 49%, and 76%, respectively, had specialized resource use. Whereas there was fair correlation between ISS and additive resource use (rho = 0.61), ISS explained only 37% of the variability in resource use (adjusted R-squared = 0.37). Resource use within anatomic injury categories differed by age group. CONCLUSIONS: The standard anatomic injury criterion for trauma center "need" (i.e., ISS >or= 16) misclassifies a substantial number of injured persons requiring critical trauma resources. Out-of-hospital trauma triage guidelines based on anatomic injury may need revision to account for patients with resource need.

Conscious sedation versus rapid sequence intubation for the reduction of native traumatic hip dislocation.

BACKGROUND: Traumatic hip dislocations (THD) are a medical emergency. There is debate whether the painful reduction of a dislocated hip should be first attempted using primary conscious sedation (PCS) or primary general anesthesia (PGA) METHODS: All cases of native THD from 2006 to 2015 in the trauma registry of a level 1 trauma center were reviewed. The primary outcome was successful reduction of the THD. RESULTS: 67 patients had a native, meaning not a hip prosthesis, THD. 34 (50.7%) patients had successful PCS, 12 (17.9%) failed PCS and underwent reduction following PGA. 21 (31.3%) underwent PGA. Patients in the PGA group were more severely injured. Time to reduction greater than 6 h was associated with PCS failure (Odds ratio (95% confidence interval) 19.75 (2.06,189.10) p = 0.01). CONCLUSION: Clinicians treating patients with a THD can utilize either PCS or PGA with many patients safely reduced under PCS. However, patients whose hip have been dislocated for more than 6 h are at risk for failure with PCS, and are good candidates for PGA.

Statewide assessment of injury and death rates among riders of off-road vehicles treated at trauma centers.

BACKGROUND: Injuries and deaths among riders of off-road motorized all-terrain vehicles are increasing in the US. We hypothesized that serious injuries in Oregon have increased among riders of both four-wheel and two-wheel vehicles. STUDY DESIGN: We analyzed the Oregon Trauma Registry. Seriously injured patients treated in the state's designated urban and rural trauma centers were identified using E-codes (821.0 to 821.9), which indicate whether patients were riding either an off-road all-terrain four-wheel vehicle (ATV) or off-road two-wheeled motorcycle (ORMC). Second, we performed a supplemental analysis of similar patients in the trauma registry of Oregon's University-based tertiary care trauma center. Patients in earlier time periods were compared with those in later time periods. RESULTS: Patients injured riding off-road vehicles and needing treatment in Oregon's trauma centers increased 76%. Sixty percent of patients were injured riding an ATV, and 35% were injured riding an ORMC. Children (aged younger than 15 years) were 20% and 23% of patients in the earlier and later years. At Oregon's University-based Level I trauma center, in the years 2002 to 2005, more than twice as many patients needed tertiary care for severe injuries caused by off-road vehicle crashes compared with the previous 4 years. CONCLUSIONS: There has been an alarming increase in the number of both ATV and ORMC riders requiring treatment in Oregon's trauma centers. Surgeons need to join a coalition of health care providers, citizens and public officials to implement a comprehensive injury-prevention response to this epidemic.

The benefit of higher level of care transfer of injured patients from nontertiary hospital emergency departments.

BACKGROUND: Although injured persons presenting to nontertiary hospitals are routinely transferred for further care, it is unknown whether there is an outcome benefit associated with this practice. We sought to assess whether the transfer of injured patients from nontertiary hospital emergency departments (EDs) is associated with improved survival. METHODS: This was a retrospective cohort analysis of all consecutive injured children and adults meeting state trauma criteria, presenting to 1 of 42 nontertiary hospital EDs (primarily rural) and requiring either admission or transfer (n = 10,176) from January 1998 through December 2003. Higher level of care transfer was defined as interhospital transfer from the ED to one of six Level I or II trauma centers. Propensity scores were used to adjust for the known nonrandom selection of patients for higher level of care transfer. The outcome measure was inhospital mortality. RESULTS: There were 10,176 trauma patients who presented to nontertiary hospital EDs and were included in the analysis, of which 3,785 (37%) were transferred to a tertiary hospital from the ED. Transfer patients had higher unadjusted mortality (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.06-3.89). After adjusting for the propensity to be transferred, transfer from the ED to a tertiary hospital was associated with a reduction in mortality (OR 0.67, 95% CI 0.48-0.94), which was strongest among patients transferred to Level I hospitals (OR 0.62, 95% CI 0.40-0.95). There was no measurable benefit for patients transferred to Level II hospitals (OR 0.82, 95% CI 0.47-1.43). CONCLUSIONS: After adjusting for injury severity and the nonrandom selection of patients for transfer, trauma patients transferred from nontertiary EDs to major trauma centers had lower inhospital mortality than patients remaining in nontrauma hospitals. Recognition and early transfer of at-risk rural trauma patients may improve survival in a regionalized trauma system.

Bicarbonate and mannitol treatment for traumatic rhabdomyolysis revisited.

BACKGROUND: A rhabdomyolysis protocol (RP) with mannitol and bicarbonate to prevent acute renal dysfunction (ARD, creatinine >2.0 mg/dL) remains controversial. METHODS: Patients with creatine kinase (CK) greater than 2,000 U/L over a 10-year period were identified. Shock, Injury Severity Score, massive transfusion, intravenous contrast exposure, and RP use were evaluated. RP was initiated for a CK greater than 10,000 U/L (first half of the study) or greater than 20,000 U/L (second half). Multivariable analyses were used to identify predictors of ARD and the independent effect of the RP. RESULTS: Seventy-seven patients were identified, 24 (31%) developed ARD, and 4 (5%) required hemodialysis. After controlling for other risk factors, peak CK greater than 10,000 U/L (odds ratio 8.6, P = .016) and failure to implement RP (odds ratio 5.7, P = .030) were independent predictors of ARD. Among patients with CK greater than 10,000, ARD developed in 26% of patients with the RP versus 70% without it (P = .008). CONCLUSION: Reduced ARD was noted with RP. A prospective controlled study is still warranted.

Optimizing physician skill development for medical students: The four-part assessment.

BACKGROUND: Medical student performance has been poorly correlated with residency performance and warrants further investigation. We propose a novel surgical assessment tool to determine correlations with clinical aptitude. METHODS: Retrospective review of medical student assessments from 2013 to 2015. Faculty rating of student performance was evaluated by: 1) case presentation, 2) problem definition, 3) question response and 4) use of literature and correlated to final exam assessment. A Likert scale interrater reliability was evaluated. RESULTS: Sixty student presentations were scored (4.8 assessors/presentation). A student's case presentation, problem definition, and question response was correlated with performance (r = 0.49 to 0.61, p ≤ 0.003). Moderate correlations for either question response or use of literature was demonstrated (0.3 and 0.26, p < 0.05). CONCLUSION: Our four-part assessment tool identified correlations with course and examination grades for medical students. As surgical education evolves, validated performance and reliable testing measures are required.

Correlation of central venous and arterial blood gas measurements in mechanically ventilated trauma patients.

HYPOTHESIS: Central venous blood gas (VBG) measurements of pH, PCO2, and base excess can be substituted for the same values obtained from an arterial blood gas (ABG) analysis in mechanically ventilated trauma patients, obviating the need for arterial puncture. DESIGN AND SETTING: Prospective comparison of 99 sets of VBGs and ABGs at a level 1 academic trauma center. PATIENTS: A consecutive sample of 25 trauma patients admitted to the intensive care unit who required mechanical ventilation and had both central venous and arterial catheters. MAIN OUTCOME MEASURES: Pearson correlations and Bland-Altman limits of agreement (LOAs) for pH, PCO2, and base excess values from each set of VBGs and ABGs. RESULTS: When VBG and ABG values were compared, pH had R = 0.92, P<.001, and 95% LOAs of -0.09 to 0.03; PCO2, R = 0.88, P<.001, and 95% LOAs of -2.2 to 10.9; and base excess, R = 0.96, P<.001, and 95% LOAs of -2.2 to 1.8. A receiver operating characteristic curve showed that a central venous PCO2 of 50 mm Hg had 100% sensitivity and 84% specificity for determining significant hypercarbia (arterial PCO2 > 50 mm Hg). CONCLUSIONS: Central venous and arterial PCO2, pH, and base excess values correlate well, but their LOAs represent clinically significant ranges that could affect management. Although VBGs cannot be substituted for ABGs in mechanically ventilated trauma patients during the initial phases of resuscitation, clinically reliable conclusions can be reached with VBG analysis.

Mortality benefit of transfer to level I versus level II trauma centers for head-injured patients.

OBJECTIVE: To determine whether head-injured patients transferred to level I trauma centers have reduced mortality relative to transfers to level II trauma centers. DATA SOURCE/STUDY SETTING: Retrospective cohort study of 542 patients with head injury who initially presented to 1 of 31 rural trauma centers in Oregon and Washington, and were transferred from the emergency department to 1 of 15 level I or level II trauma centers, between 1991 and 1994. STUDY DESIGN: A bivariate probit, instrumental variables model was used to estimate the effect of transfer to level I versus level II trauma centers on 30-day postdischarge mortality. Independent variables included age, gender, Injury Severity Scale (ISS), other indicators of injury severity, and a dichotomous variable indicating transfer to a level I trauma center. The differential distance between the nearest level I and level II trauma centers was used as an instrument. PRINCIPAL FINDINGS: Patients transferred to level I trauma centers differ in unmeasured ways from patients transferred to level II trauma centers, biasing estimates based on standard statistical methods. Transfer to a level I trauma center reduced absolute mortality risk by 10.1% (95% confidence interval 0.3%, 22.2%) compared with transfer to level II trauma centers. CONCLUSIONS: Patients with severe head injuries transferred from rural trauma centers to level I centers are likely to have improved survival relative to transfer to level II centers.

Blunt carotid artery injury: the futility of aggressive screening and diagnosis.

BACKGROUND: Blunt carotid artery injury (BCI) remains a rare but potentially lethal condition. Recent studies recommend that aggressive screening based on broad criteria (hyperextension-hyperflexion mechanism of injury, basilar skull fracture, cervical spine injury, midface fracture, mandibular fracture, diffuse axonal brain injury, and neck seat-belt sign) increases the rate of diagnosis of BCI by 9-fold. If this recommendation becomes a standard of care, it will require a major consumption of resources and may give rise to liability claims. The benefits of aggressive screening are unclear because the natural history of asymptomatic BCI is unknown and the existing treatments are controversial. HYPOTHESIS: The lack of an aggressive angiographic screening protocol does not result in delayed BCI diagnosis or BCI-related neurologic deficits. METHODS: A 10-year medical record review of patients with BCI was undertaken in 2 level I academic trauma centers. In both centers, urgent screening for BCI was performed in patients with focal neurologic signs or neurologic symptoms unexplainable by results of computed tomography of the brain as well as in selected patients undergoing angiography for another reason. RESULTS: Of 35 212 blunt trauma admissions, 17 patients (0.05%) were diagnosed as having BCI. Six showed no evidence of BCI-related neurologic symptoms during hospitalization or prior to death as a result of associated injuries. Eleven sustained a BCI-related stroke, 9 of whom had it within 2 hours of injury. The remaining 2 had a delayed diagnosis (9 and 12 hours after injury) and received only anticoagulation because the lesions were surgically inaccessible. Just 1 of these 2 patients met the criteria for BCI screening and could have been offered earlier treatment, of uncertain benefit, if we had adopted an aggressive screening policy. CONCLUSIONS: Of the few patients with BCI, most remain asymptomatic or develop neurologic deficits shortly after injury. Although a widely applied, resource-consuming screening program may increase the rate of early diagnosis of BCI, an improvement in outcome is uncertain. A cost-effectiveness analysis should be done before trauma surgeons accept an aggressive screening protocol as the standard of care.

Mechanism of acute ascites formation after trauma resuscitation.

BACKGROUND: Severely injured patients have been observed to acutely develop ascites; however, the pathogenesis of this rare phenomenon is poorly understood. OBJECTIVES: To report the factors common among severely injured patients developing ascites and to formulate a hypothesis regarding its origin. METHODS: Retrospective review of case series. RESULTS: We identified 9 injured patients between January 1, 1993, and December 31, 1998, who acutely developed significant amounts of ascites. The mean +/- SD estimated ascites volume was 2.0 +/- 0.8 L. All 9 patients had severe shock and were mechanically ventilated before abdominal decompression for the abdominal compartment syndrome. The mean +/- SD peak inspiratory pressure was 39.0 +/- 5.8 cm H2O. The mean +/- SD volumes of crystalloid and blood product infusion before decompression were 16.1 +/- 10.2 L and 5.2 +/- 4.8 L, respectively, in a mean +/- SD of 17 +/- 15 hours. In comparison, the mean +/- SD volumes of crystalloid and blood product transfusion among 100 contemporary, randomly selected patients undergoing trauma laparotomy were 5.1 +/- 5.5 L and 1.1 +/- 2.5 L, respectively (P<.001). Eight patients had only extra-abdominal injuries, while 1 patient had a combination of extra- and intra-abdominal injuries. Two patients were found to be cirrhotic by liver biopsy, but the other 7 patients had no known preexisting hepatic disease. Eight patients had absorbable mesh temporary abdominal closure, and 1 patient had primary fascial closure. There was persistent ascitic drainage in 5 patients; however, in all but 1 patient with cirrhosis, the drainage did not persist beyond 3 days. Two patients died, 1 of sepsis and the other of a closed head injury. CONCLUSIONS: Common denominators of posttraumatic ascites include shock, massive fluid resuscitation, and elevated intrathoracic pressure. The rapid onset of ascites in the setting of elevated intrathoracic pressure suggests that the patient's ability to clear ascitic fluid is overwhelmed.

Asymmetric conjugate addition reactions of allyl- and crotylstannanes.

The conjugate addition reactions of allylic stannanes have been investigated utilizing nonracemic N-enoyl-4-phenyl-1,3-oxazolidinones with Lewis acid precomplexation.

Advanced statistics: the propensity score--a method for estimating treatment effect in observational research.

Observational studies assessing the effect of a particular treatment or exposure may be subject to bias, which can be difficult to eliminate using standard analytic techniques. Multivariable models are commonly used in observational research to assess the relationship between a certain exposure or treatment and an outcome, while adjusting for important variables necessary to ensure comparability between the groups. Large differences in the observed covariates between two study groups may exist in observational studies in which the investigator has no control over who was allocated to each treatment group, and these differences may lead to biased estimates of treatment effect. When there are large differences in important prognostic characteristics between the treatment groups, adjusting for these differences with conventional multivariable techniques may not adequately balance the groups, and the remaining bias may limit valid causal inference. Use of a propensity score, described as a conditional probability that a subject will be "treated" based on an observed group of covariates, may better adjust covariates between the groups and reduce bias. The purpose of this article is to describe the use of propensity scores to adjust for bias when estimating treatment effects in observational research and to compare use of this technique with conventional multivariable regression. The authors present three methods for integrating propensity scores into observational analyses using a database collected on head-injured trauma patients. The article details the methods for creating a propensity score, analyzing data with the score, and explores differences between propensity score methods and conventional multivariable methods, including potential benefits and limitations. Graphical representations of the analyses are provided as well.

Injury mortality following the loss of air medical support for rural interhospital transport.

OBJECTIVES: This study evaluated variation in mortality among interfacility transfers three years before and after discontinuation of a rotor-wing transport service. METHODS: A retrospective cohort assessment was conducted among severely injured patients transferred from four rural hospitals to a single tertiary center in regions with continued versus discontinued rotor-wing service. Thirty-day mortality following discharge from the receiving tertiary facility served as the primary outcome measure. RESULTS: Discontinuation of rotor-wing transport decreased interfacility transfers and increased transfer time. Transferred patients were four times more likely to die after (compared with before) rotor-wing service was discontinued (p = 0.05). No difference was noted in the region with continued rotor-wing service [odds ratio (OR) = 0.53, p = 0.47]. CONCLUSIONS: Injury mortality increased with loss of air transport for interfacility transfer in a rural area.

Crush injury and rhabdomyolysis.

Crush injuries resulting in traumatic rhabdomyolysis are an important cause of acute renal failure. Ischemia reperfusion is the main mechanism of muscle injury. Intravascular volume depletion and renal hypoperfusion, combined with myoglobinuria, result in renal dysfunction. The infusion of intravenous fluids before extrication or soon after injury may lessen the severity of the crush syndrome. Serum CK levels can be used to screen patients with crush injuries to determine injury severity. Once intravascular volume has been stabilized, and the presence of urine flow has been confirmed, a forced mannitol-alkaline diuresis for prophylaxis against hyperkalemia and acute renal failure should be instituted. If an extremity compartment syndrome is suspected, one should have a low threshold for checking the intracompartmental pressures. Further studies are needed to demonstrate if any treatment regimen is truly superior to early, aggressive crystalloid infusion.