Douglas Z. Liou

Breast-Conserving Therapy for Triple-Negative Breast Cancer

IMPORTANCE The aggressive triple-negative phenotype of breast cancer (negative for estrogen and progesterone receptors and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [ERBB2] [formerly human epidermal growth factor receptor 2 (HER2)]) is considered by some investigators to be a relative contraindication to breast-conserving therapy. OBJECTIVES To compare outcomes of breast-conserving therapy for patients with triple-negative breast cancer (TNBC) with those of patients with the luminal A, luminal B, and ERBB2 subtypes. DESIGN, SETTING, AND PARTICIPANTS Prospective database review at an academic tertiary medical center with a designated breast cancer center. We included 1851 consecutive patients ages 29 to 85 years with stages I to III invasive breast cancer who underwent breast-conserving therapy at a single institution from January 1, 2000, through May 30, 2012. Of these patients, 234 (12.6%) had TNBC; 1341 (72.4%), luminal A subtype; 212 (11.5%), luminal B subtype; and 64 (3.5%), ERBB2-enriched subtype. EXPOSURE Breast-conserving therapy. MAIN OUTCOMES AND MEASURES The primary outcome measure was local recurrence (LR). Secondary outcome measures included regional recurrence, distant recurrence, and overall survival. RESULTS Triple-negative breast cancer was associated with younger age at diagnosis (56 vs 60 years; P = .001), larger tumors (2.1 vs 1.8 cm; P < .001), more stage II vs I cancer (42.1% vs 33.6%; P = .005), and more G3 tumors (86.4% vs 28.4%; P < .001) compared with the non-TNBC subtypes. Multivariable analysis showed that TNBC did not have a significantly increased risk of LR compared with the luminal A (hazard ratio, 1.4 [95% CI, 0.6-3.3]; P = .43), luminal B (1.6 [0.5-5.2]; P = .43), and ERBB2 (1.1 [0.2-5.2]; P = .87) subtypes. Only tumor size was a significant predictor of LR (hazard ratio, 4.7 [95% CI, 1.6-14.3]; P = .006). Predictors of worse overall survival included tumor size, grade, and stage and TNBC subtype. CONCLUSIONS AND RELEVANCE Breast-conserving therapy for TNBC is not associated with increased LR compared with non-TNBC subtypes. However, the TNBC phenotype correlates with worse overall survival. Breast-conserving therapy is appropriate for patients with TNBC.

Impact of positive fluid balance on critically ill surgical patients: A prospective observational study

PURPOSE The purpose of this study is to determine the effect of postoperative fluid balance (FB) on subsequent outcomes in acute care surgery (ACS) patients admitted to the surgical intensive care unit (ICU). MATERIAL AND METHODS Acute care surgery patients admitted to the surgical ICU from 06/2012 to 01/2013 were followed up prospectively. Patients were stratified by FB into FB-positive (+) and FB-negative (-) groups by surgical ICU day 5 or day of discharge from the surgical ICU. RESULTS A total of 144 ACS patients met inclusion criteria. Although there was no statistically significant difference in crude mortality (11% for FB [-] vs 15.5% for FB [+]; P=.422], after adjusting for confounding factors, achieving an FB (-) status by day 5 during the surgical ICU stay was associated with an almost 70% survival benefit (adjusted odds ratio [95% confidence interval], 0.31 [0.13, 0.76]; P=.010). In addition, achieving a fluid negative status by day 1 provided a protective effect for both overall and infectious complications (adjusted odds ratio [95% confidence interval], 0.63 [0.45, 0.88]; P=.006 and 0.64 [0.46, 0.90]; P=.010, respectively). CONCLUSIONS In a cohort of critically ill ACS patients, achieving FB (-) status early during surgical ICU admission was associated with a nearly 70% reduction in the risk for mortality.

Gender impacts mortality after traumatic brain injury in teenagers

BACKGROUND Gender may influence outcomes following traumatic brain injury (TBI) although the mechanism is unknown. Animal TBI studies suggest that gender differences in endogenous hormone production may be the source. Limited retrospective clinical studies on gender present varied conclusions. Pediatric patients represent a unique population as pubescent children experience up-regulation of endogenous hormones that varies dramatically by gender. Younger children do not have these hormonal differences. The aim of this study was to compare pubescent and prepubescent females with males after isolated TBI to identify independent predictors of mortality. METHODS We performed a retrospective review of the National Trauma Data Bank Research Data Sets from 2007 and 2008 looking at all blunt trauma patients 18 years or younger who required hospital admission after isolated, moderate-to-severe TBI, defined as head Abbreviated Injury Scale (AIS) score 3 or greater. We excluded all individuals with AIS score of 3 or greater for any other region to limit the confounding effect of comorbidities. Based on the median age of menarche, we defined two age groups as follows: prepubescent (0–12 years) and pubescent (>12 years). Analysis was performed to compare trauma profiles and outcomes between groups. Our primary outcome measure was in-hospital mortality. RESULTS A total of 20,280 patients met inclusion criteria; 10,135 were prepubescent, and 10,145 were pubescent. Overall mortality was 6.9%, and lower mortality was noted among prepubescent patients compared with pubescent (5.2% vs. 8.6%, p < 0.0001). Although female gender did not predict reduced mortality in the prepubescent cohort (adjusted odds ratio, 1.05; 95% confidence interval, 0.85–1.30; p = 0.63), female gender was associated with reduced mortality in the pubescent (adjusted odds ratio, 0.78; 95% confidence interval, 0.65–0.93; p = 0.007). CONCLUSION In contrast to prepubescent female gender, pubescent female gender predicts reduced mortality following isolated, moderate-to-severe TBI. Endogenous hormonal differences may be a contributing factor and require further investigation. LEVEL OF EVIDENCE Prognostic study, level III.

Insurance-and race-related disparities decrease in elderly trauma patients

BACKGROUND Little focus is on health care disparities in the elderly, a population largely covered by public insurance. We characterized insurance type and race in elderly trauma patients to determine if lack of insurance or minority status predict increased mortality. METHODS The National Trauma Data Bank (version 7.0) was queried for all adult blunt trauma patients. We divided patients into two cohorts (15–64 or ≥65 years) based on age for universal Medicare eligibility. Our primary outcome measure was in-hospital mortality. Multiple logistic regression was used to control for confounding variables. RESULTS A total of 541,471 patients met inclusion criteria. Among younger patients, the most common insurance type was private (41.0%), with 26.9% uninsured. In contrast, the most common insurance type among older patients was Medicare (64.6%), with 6.0% uninsured. Within the younger cohort, private insurance (adjusted odds ratio [AOR], 0.6; p < 0.01) and other insurance (AOR, 0.8; p < 0.01) predicted reduced mortality, while Medicare predicted similar mortality (AOR, 1.1; p = 0.18) compared with no insurance. Black race (AOR, 1.4; p < 0.01) and Hispanic ethnicity (AOR, 1.4; p < 0.01) predicted higher mortality compared with white race. Within the older cohort, no insurance predicted similar mortality as Medicare (AOR, 1.0; p = 0.43), private insurance (AOR, 1.0; p = 0.51), and other insurance (AOR, 1.0; p = 0.71). Hispanic ethnicity predicted increased mortality (AOR, 1.4; p < 0.01), while Asian race was protective (AOR, 0.7; p = 0.01) compared with white race. CONCLUSION Elderly trauma patients present primarily with Medicare, while younger trauma patients are mostly privately insured; elderly patients are four times more likely to be insured. Disparities caused by lack of insurance and minority race are reduced in elderly trauma patients. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level III.

Prehospital hypertension is predictive of traumatic brain injury and is associated with higher mortality

BACKGROUND The purpose of the current study was to investigate the effect of early adrenergic hyperactivity as manifested by prehospital (emergency medical service [EMS]) hypertension on outcomes of traumatic brain injury (TBI) patients and to develop a prognostic model of the presence of TBI based on EMS and admission (emergency department [ED]) hypertension. METHODS This study is a retrospective review of the 2007 to 2008 National Trauma Data Bank including blunt trauma patients 15 years or older with available EMS and ED vital signs. Patients with head Abbreviated Injury Scale (AIS) score of 3 or greater were selected, and mortality was examined within EMS systolic blood pressure (SBP) groups: lower than 100 mm Hg, 110 mm Hg to 150 mm Hg, 160 mm Hg to 180 mm Hg, and 190 mm Hg to 230 mm Hg. A forward logistic regression model including the EMS heart rate, EMS SBP, EMS Glasgow Coma Scale (GCS) score, ED heart rate, and ED SBP was used to identify predictors of a TBI in patients with ED GCS score of less than or equal to 8, 9 to 13, and 14 to 15. RESULTS For the 5-year study period, 315,242 patients met inclusion criteria. Adjusted odds for mortality increased in a stepwise fashion with increasing EMS SBP compared with patients with normal EMS SBP (adjusted odds ratio [95% confidence interval], 1.33 [1.22–1.44], p < 0.001, for EMS SBP of 160–180 mm Hg and 1.97 [1.76–2.21], p < 0.001, for EMS SBP of 190–230 mm Hg). A 7-point scoring system was developed for each ED GCS score group to predict the presence of a TBI. EMS SBP of greater than 150 mm Hg and ED SBP of greater than 150 mm Hg were both predictive of the presence of a TBI in patients with ED GCS score of 8 or less and in patients with ED GCS score of 9 to 13 or 14 to 15, respectively. CONCLUSION Prehospital hypertension in TBI is associated with a higher mortality risk. Early hypertension in the prehospital setting and at admission can be used to predict the presence of such injuries. These findings may have important early triage and treatment implications. LEVEL OF EVIDENCE Prognostic study, level III.

Bicycle trauma and alcohol intoxication

INTRODUCTION As bicycling has become more popular, admissions after bicycle trauma are on the rise. The impact of alcohol use on bicycle trauma has not been well studied. The aim of this study was to examine the effect of alcohol intoxication on injury burden following bicycle-related crashes. METHODS A retrospective review of trauma patients presenting to a Level I trauma center after bicycle-related crashes from January 2002 to December 2011 was conducted. Demographics, injury data, alcohol intoxication, helmet use, and clinical outcomes were reviewed. Blood alcohol level (BAL) was considered positive if >0.01 g/dL. Variables were compared between patients based on BAL: negative, 0.01-0.16 g/dL, and >0.16 g/dL. RESULTS During the 10 year study period, 563 patients met study criteria; mean age was 33.5 ± 16.5 years, 87% were male, and mortality was 1%. On average, bicycle crashes increased over the study period by 4.4 collisions per year. BAL was tested in 211 (38%) patients. Mean BAL was 0.24 g/dL, with 37% of these patients being intoxicated (BAL ≥ 0.010 g/dL). Intoxicated patients were significantly less likely to wear a helmet (4.7% vs. 22.2%, p = 0.002) and to be involved in motor vehicle crash (59.0% vs. 81.2%, p < 0.001). There was no difference noted in the injury burden including ISS ≥ 16 (14.3% vs. 19.5%, p = 0.335) and AIS Head ≥ 3 (17.9% vs. 21.8%, p = 0.502). When comparing patients according to their BAL, there was a decreasing risk of motor vehicle collision with increasing BAL (81.2% for undetected, 76.5% for BAL ≤ 0.16 g/dL and 54.1% for BAL >0.16 g/dL, p < 0.001). The risk for a severe head injury (AIS Head ≥ 3) was significantly lower in helmeted patients (8.4% vs. 15.8%, p = 0.035). CONCLUSIONS The incidence of bicycle-related crashes is increasing and more than a third of patients tested for alcohol after bicycle-related crashes are found to be intoxicated. The injury burden in intoxicated patients, including head trauma, was not different compared to non-intoxicated patients. In addition, the risk for a collision with a motor vehicle was significantly lower. Nonetheless, these patients rarely utilize a helmet. The findings from this study can be used for the development and implementation of preventive strategies to minimize the injury burden associated with bicycle crashes and intoxicated cyclists.

Midodrine: A Novel Therapeutic for Refractory Chylothorax

Thoracic duct injury is a rare but serious complication following surgery of the neck or chest that leads to uncontrolled chyle leak. Conventional management includes drainage, nutritional modification, or aggressive surgical interventions such as thoracic duct ligation, flap coverage, fibrin glue, or talc pleurodesis; few successful medical therapeutics are available. We report a case of a high-output chylothorax refractory to aggressive medical and surgical interventions. Chyle output decreased substantially after initiating midodrine, an α1-adrenergic agonist that causes vasoconstriction of the lymph system, reducing chyle flow. This case report suggests that midodrine may be a novel therapeutic for refractory chyle leaks.

Support for blood alcohol screening in pediatric trauma

BACKGROUND Alcohol intoxication in pediatric trauma is underappreciated. The aim of this study was to characterize alcohol screening rates in pediatric trauma. METHODS The Los Angeles County Trauma System Database was queried for all patients aged ≤ 18 years who required admission between 2003 and 2008. Patients were compared by age and gender. RESULTS A total of 18,598 patients met the inclusion criteria; 4,899 (26.3%) underwent blood alcohol screening, and 2,797 (57.1%) of those screened positive. Screening increased with age (3.3% for 0-9 years, 15.1% for 10-14 years, and 45.4% for 15-18 years; P < .01), as did alcohol intoxication (1.9% for 0-9 years, 5.8% 10-14 years, and 27.3% for 15-18 years; P < .01). Male gender predicted higher mortality in those aged 15 to 18 years (adjusted odds ratio, 1.7; P < .01), while alcohol intoxication did not (adjusted odds ratio, .97; P = .84). CONCLUSIONS Alcohol intoxication is common in adolescent trauma patients. Screening is encouraged for pediatric trauma patients aged ≥10 years who require admission.

Impact of body mass index on injury in abdominal stab wounds: implications for management.

BACKGROUND Although it is assumed that obese patients are naturally protected against anterior abdominal stab wounds, the relationship has never been formally studied. We sought to examine the impact of body mass index (BMI) on severity of sustained injury, need for operation, and patient outcomes. MATERIALS AND METHODS We conducted a review of all patients presenting with abdominal stab wounds at an urban level I trauma center from January 2000-December 2012. Patients were divided into groups based on their BMI (<18.5, 18.5-29.9, 30-35, and >35). Data abstracted included baseline demographics, physiologic data, and characterization of whether the stab wound had violated the peritoneum, caused intra-abdominal injury, or required an operation that was therapeutic. The one-sided Cochran-Armitage trend test was used for significance testing of the protective effect. RESULTS Of 281 patients with abdominal stab wounds, 249 had complete data for evaluation. Chest and abdomen abbreviated injury scale trends decreased with increasing BMI, as did overall injury severity score, the percent of patients severely injured (injury severity score ≥ 25), and length of intensive care unit stay. Rates of peritoneal violation (100%, 84%, 77%, and 74%; P = 0.077), visceral injury (83%, 56%, 50%, and 30%; P = 0.022), and injury requiring a therapeutic operation (67%, 45%, 40%, and 20%; P = 0.034) all decreased with increasing BMI. Patients in the thinnest group required an operation three times more often than those in the most obese. CONCLUSIONS Increased BMI protects patients with abdominal stab wounds and is associated with lower incidence of severe injury and need for operation. Heavier patients may be more suitable to observation and serial examinations, whereas very thin patients are more likely to require an operation and be critically injured.

To swab or not to swab? A prospective analysis of 341 SICU VRE screens.

BACKGROUND Vancomycin-resistant Enterococcus (VRE) screening is routine practice in many intensive care units despite the question of its clinical significance. The value of VRE screening at predicting subsequent VRE or other hospital-acquired infection (HAI) is unknown. The purpose of this investigation was to examine the rate of subsequent VRE HAI in patients undergoing VRE screening. METHODS This study was conducted in a 24-bed surgical intensive care unit (SICU) at a Level I trauma center. Patients admitted to the SICU between February and August 2011 who had rectal swab for VRE screening within 72 hours were followed prospectively for the development of VRE and other HAIs. Demographics, clinical characteristics, and infection rates were compared between VRE-positive and VRE-negative patients. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of VRE screening for predicting subsequent VRE HAI were calculated. RESULTS A total of 341 patients had VRE screening within 72 hours of SICU admission, with 32 VRE-positive (9%) and 309 VRE-negative (91%) patients. VRE-positive patients had a higher incidence of any HAI (78% vs. 35%, p < 0.001). Eight VRE-positive patients (25%) developed VRE HAI compared with only 3 VRE-negative patients (1%) (p < 0.001). VRE screening had a 73% sensitivity, 93% specificity, 25% PPV, and 99% NPV for determining subsequent VRE HAI. CONCLUSION VRE colonization was present in 9% of SICU patients at admission. Negative VRE screen result had a high specificity and NPV for the development of subsequent VRE HAI. Empiric treatment of VRE infection may be unnecessary in VRE-negative patients. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III. Therapeutic study, level IV.