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.

Variability of the f-cell ratio after treatment of traumatic hemorrhagic shock.

PURPOSE: Measuring total blood volume (TBV) in critically ill patients, using isotope techniques to determine red cell volume (RBCV) and plasma volume (PV) is laborious. Recently, PV measurement using a single bolus dose of tracers has been validated, thus, allowing TBV calculation using large venous hematocrit (LVHCT). However, this technique relies on using a correlation factor, the f-cell ratio, to adjust for differences in LVHCT and total body hematocrit (TBHCT). The normal f-cell ratio is 0.9 but has never been studied in patients recovering from hemorrhagic shock (HS). This study assesses the f-cell ratio at different phases after HS to determine accuracy in calculating TBV. METHODS: 114 injured patients requiring immediate operation for HS were studied. All patients had measurements of PV and RBCV via isotope dilution enabling measurements of TBHCT. Correlation of LVHCT and TBHCT were used to calculate the f-cell ratio in the fluid sequestration (n = 81) and in the fluid mobilization period (n = 108). RESULTS: The f-cell ratio (mean ±â€¯SD) averaged 0.89 ±â€¯0.15 and 0.90 ±â€¯0.01 in the first and second halves of the fluid sequestration period versus 0.90 ±â€¯0.2 and 0.80 ±â€¯0.07 in the first and second 48 h of the fluid mobilization period. The f-cell ratio was significantly lower (p=<0.001) in the mobilization period. CONCLUSIONS: These data show for the first time that using PV and LVHCT to calculate TBV after HS is unreliable. The mechanisms causing this variation in f-cell ratio is unknown but likely related to capillary/interstitial dynamics and needs further scientific study.

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.

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.

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.

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.

Prospective clinical trial of surgical intervention for painful rib fracture nonunion.

We performed a prospective clinical trial of resection with or without plate fixation for symptomatic rib fracture nonunion three or more months postinjury with 6-month postoperative followup. The McGill Pain Questionnaire (MPQ) and RAND 36 Health Survey were administered and activity level (sedentary, ambulatory, moderately active, vigorous), functional status (disabled, nonphysical labor, physical labor), and work status (employed, unemployed, retired, student) were queried pre- and postoperatively. Twenty-four patients 4 to 197 months (median, 16 months) postinjury underwent surgical intervention for one to four rib fracture nonunions (median, two nonunions). Evidence of intercostal nerve entrapment was present in nine patients (38%). MPQ Present Pain Intensity and Pain Rating Index and RAND 36 Physical Functioning, Role Physical, Social Functioning, Role Social, Bodily Pain, Vitality, Mental Health, and General Health were significantly improved at six months compared with study entry (P < 0.05). Activity levels significantly improved (P < 0.0001) but functional and work status did not change. Twenty-four-hour morphine equivalent dosage of opioids at study entry was 20.3 ± 30.8 (mean ± standard deviation) and at study completion was 9.4 ± 17.5 (P = 0.054). Complications included one wound infection, two partial screw backouts, and one chest wall hernia at one year after resection of adjacent nonunions with significant gaps repaired with absorbable plates. Surgical intervention for rib fracture nonunion may improve chronic pain and disability but without change in functional or work status. Resection of adjacent nonunions with significant gaps may lead to chest wall hernia.

The contribution of rib fractures to chronic pain and disability.

BACKGROUND: The contribution of rib fractures to chronic pain and disability is not well described. METHODS: Two hundred three patients with rib fractures were followed for 6 months. Chronic pain was assessed using the McGill Pain Questionnaire Pain Rating Index and Present Pain Intensity (PPI) scales. Disability was defined as a decrease in work or functional status. RESULTS: The prevalence of chronic pain was 22% and disability was 53%. Acute PPI predicted chronic pain. Associated injuries, bilateral rib fractures, injury severity score, and number of rib fractures were not predictive of chronic pain. No acute injury characteristics were predictive of disability. Among 89 patients with isolated rib fractures, the prevalence of chronic pain was 28% and of disability was 40%. No injury characteristics predicted chronic pain. Bilateral rib fractures and acute PPI predicted disability. CONCLUSION: The contribution of rib fractures to chronic pain and disability is significant but unpredictable with conventional injury descriptors.

Prolonged pain and disability are common after rib fractures.

BACKGROUND: The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. METHODS: This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. RESULTS: One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). CONCLUSIONS: Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed.

Is futile care in the injured elderly an important target for cost savings?

BACKGROUND: This study proposes a definition of futile care and quantifies its cost in injured elders. METHODS: This was a retrospective study of Medicare patients with an International Classification of Diseases-9 injury diagnosis admitted to 171 Oregon and Washington facilities from January 1, 2001, through December 31, 2002, who died within 6 months of admission. Futile care was defined as death within 7 days of discharge from a hospitalization of at least 14 days. We compared health care costs in the last 6 months of life with those who did and did not meet our definition of futility. To simulate predicting and preventing futility early in the hospital course, we examined the effect of reducing spending on the futile care cohort to the level of those who survived 7 to 10 days after injury. RESULTS: There were 6,832 elders who died within 6 months of injury, of whom 230 (3.4%) met our definition of futility. The median cost of care in the last 6 months of life was $33,373 for those not meeting our definition of futility and $87,391 for the futile care group (p < 0.001). The 3.4% receiving futile care incurred 8.9% of total costs. Reducing expenditures in the futile care group to the level of those who died from 7 to 10 days after injury (median, $25,633) would result in an overall cost savings of 6.5%. CONCLUSION: End-of-life health care costs were significantly higher for those who received futile care. However, even aggressive reductions in futile care would result in small savings overall. LEVEL OF EVIDENCE: Economic analysis, level III.

Management of full-thickness duodenal laceration in the damage control era: evolution to primary repair without diversion or decompression.

The management of duodenal laceration (DL) is controversial. We sought to determine the influence of damage control (DC) on the use of decompression/diversion/exclusion (DDE) techniques and the risk of duodenal-related complications (DRC). We conducted a retrospective review of all patients with full-thickness DL surviving more than 72 hours in the years 1989 to 2009. Forty-one patients with a median duodenal organ injury scale of 3 and a mean abdominal trauma index (ATI) of 45 ± 24 underwent laparotomy. Twenty-five patients (61%) were treated with DC and 16 (39%) with fascial closure (FC). Although the ATI of the patients treated with DC was greater than the ATI of the patients treated with FC (56 ± 23 vs 28 ± 17, P < 0.001), DRCs were equivalent (two vs three, nonsignificant). Twenty-one patients were treated in the first decade and 20 in the second decade. Between the first and second decades, there were trends toward an increased use of DC (52 to 70%, nonsignificant) and a decreased use of DDE (52 to 35%, nonsignificant) with a significant reduction in DRC (5 vs 0, P = 0.04). Among the 18 patients (44%) who underwent DDE procedures there were 2 DRCs (11%) related to DDE. Among the 23 patients who did not have DDE, there were three DRCs (13%), including two obstructions, one partial and one complete. When DC is used after DL, DDE may be unnecessary. Diversion is recommended, however, when the duodenum is at risk for obstruction after primary repair.

Using hospital outcomes to predict 30-day mortality among injured patients insured by Medicare.

HYPOTHESIS: Survival until a fixed time after injury is a more useful outcome variable than survival until hospital discharge. DESIGN: We sought to determine whether 30-day survival could be accurately predicted by hospital discharge status. SETTING: Academic research. PATIENTS: We analyzed Medicare fee-for-service records for patients 65 years or older admitted with a principal diagnosis of injury (International Classification of Diseases, Ninth Revision, Clinical Modification codes 800-959, excluding 905-909, 930-939, and 958). MAIN OUTCOME MEASURES: Patients were classified by maximum Abbreviated Injury Score (range, 1-5) and Charlson comorbidity score (0, 1, 2, or ≥ 3). We modeled the conditional probability of survival at 30 days given hospitalization survival (P[S30SH]) as a function of census region, age, sex, maximum Abbreviated Injury Score, Charlson comorbidity score, length of stay, and discharge home or not. RESULTS: A total of 436 104 patients met inclusion criteria, and a model was created using half the sample. For northeastern women aged 65 to 69 years with a maximum Abbreviated Injury Score of less than 3, Charlson comorbidity score of 0, and discharge home with length of stay less than 3 days, the model predicted P (S30SH) to be 0.998. The P (S30SH) was lower for other census regions, male sex, older age, more severe injury, and greater comorbidity. The equation had modest predictive ability when applied to individuals in the other half of the sample (area under the receiver operating characteristic curve, 0.75) and closely predicted P (S30SH) within numerous subpopulations. CONCLUSION: For injured patients insured by Medicare, P (S30SH) can be estimated using administrative data known at the time of hospital discharge.

Development and implementation of a pharmacist-managed clinical pharmacogenetics service.

PURPOSE: The development and implementation of a pharmacist-managed clinical pharmacogenetics service are described. SUMMARY: A pharmacist-managed clinical pharmacogenetics service was designed and implemented at an academic specialty hospital to provide clinical pharmacogenetic testing for gene products important to the pharmacodynamics of medications used in the hospital's patients. A series of accredited educational seminars were conducted for our pharmacists to establish competencies in providing pharmacogenetic consults for the genes to be tested by the clinical pharmacogenetics service. The service was modeled after and integrated with an already-established clinical pharmacokinetics service. A steering committee was formed to evaluate the use of available tests, new evidence for implementation of additional tests, and other service quality metrics. All clinical pharmacogenetic test results are first reported to one of the pharmacists, who reviews the result and provides a written consultation. The consultation includes an interpretation of the result and recommendations for any indicated changes to therapy. In 2009, 136 clinical pharmacogenetic tests were performed. The service has been met with positive clinician feedback. The successful implementation of this service highlights the leadership role that pharmacists can take in moving pharmacogenetics from research to patient care. CONCLUSION: The development of and experience with a pharmacist-managed clinical pharmacogenetics service are described. The program's success has depended on collaboration between the clinical laboratory and pharmacists, and pharmacists' pharmacogenetic recommendations have been well accepted by prescribers.

Study of outcomes associated with hyponatremia and hypernatremia in children.

Sodium is usually included in hospitals' critical values lists; however, the values at which sodium is considered to be life threatening (critical) vary among hospitals. Studies of outcomes associated with hyponatremia and hypernatremia in pediatric patients have not been published. We performed a retrospective chart review of sodium values of <124 mmol/L and >155 mmol/L that occurred during a 6-month period. Univariate and multivariate analyses for mortality risk were performed with the different variables. A total of 702 (1.32%) sodium tests fell in the study reference range, with 166 being <124 mmol/L and 536 being >155 mmol/L. Although not statistically significant, mortality was higher (38.5%) in patients with sodium values ≤ 120 mmol/L than in those with values ≥ 170 mmol/L (25%) or in patients with other values (<14%). Underlying conditions prevented assessment of morbidity associated with hyponatremia or hypernatremia. Treatment was instituted within 4 hours in 80% of cases (50% within 1 hour). Multivariate analysis showed increased risk of death for hyponatremic patients if they were premature or had heart abnormalities, while for hypernatremic patients the risk increased when other critical values were present. In conclusion, sodium levels of ≤ 120 mmol/L and ≥ 170 mmol/L have increased mortality in children; however, the risk of death is not statistically different when compared to risk in patients with milder hyponatremia and hypernatremia. Risk factors for death in hyponatremic and hypernatremic patients may primarily reflect the severity of the underlying conditions present in these children, such as prematurity and heart abnormalities, rather than the sodium derangement.

The optimum follow-up period for assessing mortality outcomes in injured older adults.

OBJECTIVES: To compare mortality rates of hospitalized injured aged 67 and older across commonly used follow-up periods (e.g., in-hospital, 30-day, 1-year) and to determine the postinjury time after which mortality rates stabilize. DESIGN: Retrospective analysis of Medicare claims. SETTING: Oregon and Washington Medicare patients. PARTICIPANTS: Patients admitted to 171 Oregon and Washington facilities during 2001/02 with injuries identified according to International Classification of Diseases, Ninth Revision, code and followed for 1 year. MEASUREMENTS: The primary outcome was in-hospital mortality and mortality at 30, 60, 90, 180, and 365 days. Kaplan-Meier survival curves and daily postadmission mortality rates were also evaluated. The rate of change (slope) of the survival curves and daily mortality rates were analyzed to select the point after which mortality rates were no longer decreasing. RESULTS: There were 32,135 injured older adults hospitalized over the 2-year period, with a median age of 82 (interquartile range 77-88). Cumulative in-hospital mortality and at 30, 60, 90, 180, and 365 days was 4.1%, 9.7%, 13.6%, 16.1%, 21.3%, and 28.4%, respectively. Mortality rates stabilized by 6 months after injury, with 89% of the change occurring within 60 days. Although serious injuries, medical comorbidities, and preinjury nursing facility residence were all associated with higher mortality, they did not affect the pattern of mortality after injury. CONCLUSION: In-hospital mortality is much lower than postdischarge mortality in injured older adults, with a substantial portion of persons dying shortly after discharge from the hospital. Mortality appears to stabilize by 6 months after injury, although 60-day postadmission follow-up captures most of the excess daily mortality rate.

Process to evaluate hematological parameters that reflex to manual differential cell counts in a pediatric institution.

BACKGROUND: Each institution sets specific parameters obtained by automated hematology analyzers to trigger manual counts. We designed a process to decrease the number of manual differential cell counts without impacting patient care. METHODS: We selected new criteria that prompt manual counts and studied the impact these changes had in 2 days of work and in samples of patients with newly diagnosed leukemia, sickle cell disease, and presence of left shift. RESULTS: By using fewer parameters and expanding our ranges we decreased the number of manual counts by 20%. The parameters that prompted manual counts most frequently were the presence of blast flags and nucleated red blood cells, 2 parameters that were not changed. The parameters that accounted for a decrease in the number of manual counts were the white blood cell count and large unstained cells. Eight of 32 patients with newly diagnosed leukemia did not show blast flags; however, other parameters triggered manual counts. In 47 patients with sickle cell disease, nucleated red cells and red cell variability prompted manual review. Bands were observed in 18% of the specimens and 4% would not have been counted manually with the new criteria, for the latter the mean band count was 2.6%. CONCLUSIONS: The process we followed to evaluate hematological parameters that reflex to manual differential cell counts increased efficiency without compromising patient care in our hospital system.

The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents.

BACKGROUND: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated. METHODS: WHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGbeta), nicked beta subunit (hCGbetan), and beta core fragment (hCGbetacf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery of 90-110%. RESULTS: All assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGbeta (mean recovery 103.8%) but with high variation, and equimolar detection was observed only in four. The mean recovery of hCGbetan was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCGbetacf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays. CONCLUSIONS: hCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems.