Linda A. Dultz

Follicular Variant of Papillary Thyroid Cancer Encapsulated, Nonencapsulated, and Diffuse: Distinct Biologic and Clinical Entities

OBJECTIVE To examine genotypic and clinical differences between encapsulated, nonencapsulated, and diffuse follicular variant of papillary thyroid carcinoma (EFVPTC, NFVPTC, and diffuse FVPTC, respectively), to characterize the entities and identify predictors of their behavior. DESIGN Retrospective medical chart review and molecular analysis. SETTING Referral center of a university hospital. PATIENTS The pathologic characteristics of 484 consecutive patients with differentiated thyroid cancer who underwent surgery by the 3 members of the New York University Endocrine Surgery Associates from January 1, 2007, to August 1, 2010, were reviewed. Forty-five patients with FVPTC and in whom at least 1 central compartment lymph node was removed were included. MAIN OUTCOME MEASURES Patients with FVPTC were compared in terms of age, sex, tumor size, encapsulation, extrathyroid extension, vascular invasion, central nodal metastases, and the presence or absence of mutations in BRAF, H-RAS 12/13, K-RAS 12/13, N-RAS 12/13, H-RAS 61, K-RAS 61, N-RAS 61, and RET/PTC1. RESULTS No patient with EFVPTC had central lymph node metastasis, and in this group, 1 patient (4.5%) had a BRAF V600E mutation and 2 patients (9%) had RAS mutations. Of the patients with NFVPTC, none had central lymph node metastasis (P > .99) and 2 (11%) had a BRAF V600E mutation (P = .59). Of the patients with diffuse FVPTC, all had central lymph node metastasis (P < .001), and 2 (50%) had a BRAF V600E mutation (P = .06). CONCLUSIONS FVPTC consists of several distinct subtypes. Diffuse FVPTC seems to present and behave in a more aggressive fashion. It has a higher rate of central nodal metastasis and BRAF V600E mutation in comparison with EFVPTC and NFVPTC. Both EFVPTC and NFVPTC behave in a similar fashion. The diffuse infiltrative pattern and not just presence or absence of encapsulation seems to determine the tumor phenotype. Understanding the different subtypes of FVPTC will help guide appropriate treatment strategies.

Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma

BACKGROUND BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.

Alcohol use by pedestrians who are struck by motor vehicles: How drinking influences behaviors, medical management, and outcomes

BACKGROUND Injuries to pedestrians struck by motor vehicles represent a significant public health hazard in large cities. The purpose of this study is to investigate the demographics of alcohol users who are struck by motor vehicles and to assess the effects of alcohol on pedestrian crossing patterns, medical management, and outcomes. METHODS Data were prospectively collected between December 2008 to September 2010 on all pedestrians who presented to a Level I trauma center after being struck by a motor vehicle. Variables were obtained by interviewing patients, scene witnesses, first responders, and medical records. RESULTS Pedestrians who used alcohol were less likely to cross the street in the crosswalk with the signal (22.6% vs. 64.7%) and more likely to cross either in the crosswalk against the signal (22.6% vs. 12.4%) or midblock (54.8% vs. 22.8%). Alcohol use was associated with more initial computed tomography imaging studies compared with no alcohol involvement. Alcohol use was associated with a higher Injury Severity Score (8.82 vs. 4.85; p < 0.001) and hospital length of stay (3.89 days vs. 1.82 days; p < 0.001) compared with those with no alcohol involvement. Patients who used alcohol had a lower average Glasgow Coma Scale score (13.80 vs. 14.76; p < 0.001) and a higher rate of head and neck, face, chest, abdomen, and extremity/pelvic girdle injuries (based on Abbreviated Injury Scale) than those with no alcohol involvement. CONCLUSION Alcohol use is a significant risk factor for pedestrians who are struck by motor vehicles. These patients are more likely to cross the street in an unsafe manner and sustain more serious injuries. Traffic safety and injury prevention programs must address irresponsible alcohol use by pedestrians.

Helmet use is associated with safer bicycling behaviors and reduced hospital resource use following injury

BACKGROUND While the efficacy of helmet use in the prevention of head injury is well described, helmet use as it relates to bicyclists’ behaviors and hospital resource use following injury is less defined. The objective of this study was to compare the demographics, behaviors, hospital workups, and outcomes of bicyclists based on helmet use. METHODS This study was a subset analysis of a 2.5-year prospective cohort study of vulnerable roadway users conducted at Bellevue Hospital Center, a New York City Level 1 trauma center. All bicyclists with known helmet status were included. Demographics, insurance type, traffic law compliance, alcohol use, Glasgow Coma Scale (GCS) score, initial imaging studies, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), admission status, length of stay, disposition, and mortality were assessed. Information was obtained primarily from patients; witnesses and first responders provided additional information. RESULTS Of 374 patients, 113 (30.2%) were wearing helmets. White bicyclists were more likely to wear helmets; black bicyclists were less likely (p = 0.037). Patients with private insurance were more likely to wear helmets, those with Medicaid or no insurance were less likely (p = 0.027). Helmeted bicyclists were more likely to ride with the flow of traffic (97.2%) and within bike lanes (83.7%) (p < 0.001 and p = 0.013, respectively). Nonhelmeted bicyclists were more likely to ride against traffic flow (p = 0.003). There were no statistically significant differences in mean GCS score, AIS score, and mean ISS for helmeted versus nonhelmeted bicyclists. Nonhelmeted patients were more likely to have head computed tomographic scans (p = 0.049) and to be admitted (p = 0.030). CONCLUSION Helmet use is an indicator of safe riding practices, although most injured bicyclists do not wear them. In this study, helmet use was associated with lower likelihood of head CTs and admission, leading to less hospital resource use. Injured riders failing to wear helmets should be targeted for educational programs. LEVEL OF EVIDENCE Epidemiologic study, level III.

Vulnerable roadway users struck by motor vehicles at the center of the safest, large US city

BACKGROUND Road safety constitutes an international crisis. In 2010, 11,000 pedestrians and 3,500 bicyclists were injured by motor vehicles in New York City. This study aims to identify the demographics, behaviors, injuries, and outcomes of vulnerable roadway users struck by motor vehicles in New York City’s congested central business district and surrounding periphery. METHODS A prospective, descriptive study of pedestrians and bicyclists struck by motor vehicles and treated at a Level I regional trauma center was performed. Data were collected between December 2008 and June 2011 by interviewing patients and first responders supplemented with imaging and outcomes variables. Main outcome measures included patient demographics, behavior patterns, scene-related data, Injury Severity Score (ISS), and outcomes including mortality. Multivariate ordinal logistic regression modeling was performed to isolate effects of predictor variables on outcome of ISS categories. RESULTS Injured pedestrians (n = 1,075) and bicyclists (n = 382) differ by age (p < 0.001), sex (p < 0.001), ethnicity/race (p < 0.001), and involved motor vehicle type (p < 0.001). Pedestrians sustain more severe/critical injuries (p < 0.001) and hospital admissions (p < 0.001). Bicyclists are more commonly struck by taxis (p < 0.001) and infrequently wear helmets (29.6%). Variables associated with low ISS include bicycling (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.29–0.63), above normal body mass index (AOR, 0.73; 95% CI, 0.54–0.99), Latino (AOR, 0.65; 95% CI, 0.46–0.94) or black (AOR, 0.63; 95% CI, 0.41–0.96) ethnicity/race, and struck by a taxicab (AOR, 0.50; 95% CI, 0.33–0.76) or turning vehicle (AOR,0.49; 95% CI, 0.34–0.70). Variables associated with high ISS include alcohol (AOR, 2.71; 95% CI, 1.81–4.05), age less than 18 years (AOR, 1.73; 95% CI, 1.05–2.86), hearing impairment (AOR, 2.24; 95% CI, 1.24–4.03), and struck by a truck or bus (AOR, 1.91; 95% CI, 1.18–3.10). Mortality was 1.2%. CONCLUSION Injured pedestrians and bicyclists represent distinct entities. Prevention modalities must be tailored accordingly with a focus on high-risk subgroups and compliance with traffic laws. Studying fatality or admissions data fail to capture the extent of the epidemic. LEVEL OF EVIDENCE Prospective epidemiologic study, level II.

Effect of Surgeon and Hospital Volume on Emergency General Surgery Outcomes

BACKGROUND Emergency general surgery (EGS) contributes to half of all surgical mortality nationwide, is associated with a 50% complication rate, and has a 15% readmission rate within 30 days. We assessed associations between surgeon and hospital EGS volume with these outcomes. STUDY DESIGN Using Marylands Health Services Cost Review Commission database, we identified nontrauma EGS procedures performed by general surgeons among patients 20 years or older, who were admitted urgently or emergently, from July 2012 to September 2014. We created surgeon and hospital volume categories, stratified EGS procedures into simple (mortality ≤ 0.5%) and complex (>0.5%) procedures, and assessed postoperative mortality, complications, and 30-day readmissions. Multivariable logistic regressions both adjusted for clinical factors and accounted for clustering by individual surgeons. RESULTS We identified 14,753 procedures (61.5% simple EGS, 38.5% complex EGS) by 252 (73.3%) low-volume surgeons (≤25 total EGS procedures/year), 63 (18.3%) medium-volume surgeons (26 to 50/year), and 29 (8.4%) high-volume surgeons (>50/year). Low-volume surgeons operated on one-third (33.1%) of all patients. For simple procedures, the very low rate of death (0.2%) prevented a meaningful regression with mortality; however, there were no associations between low-volume surgeons and complications (adjusted odds ratio [aOR] 1.07; 95% CI 0.81 to 1.41) or 30-day readmissions (aOR 0.80; 95% CI 0.64 to 1.01) relative to high-volume surgeons. Among complex procedures, low-volume surgeons were associated with greater mortality (aOR 1.64; 95% CI 1.12 to 2.41) relative to high-volume surgeons, but not complications (aOR 1.06; 95% CI 0.85 to 1.32) or 30-day readmission (aOR 0.99; 95% CI 0.80 to 1.22). Low-volume hospitals (≤125 total EGS procedures/year) relative to high-volume hospitals (>250/year) were not associated with mortality, complications, or 30-day readmissions for simple or complex procedures. CONCLUSIONS We found evidence that surgeon EGS volume was associated with outcomes. Developing EGS-specific services, mentorship opportunities, and clinical pathways for less-experienced surgeons may improve outcomes.

Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer

BACKGROUND The BRAF V600E (BRAF+) mutation activates the mitogen-activated protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC). Clinically, the behavior of BRAF+ PTC, however, varies from an indolent to an aggressive course. SPRY2 is a negative feedback regulator of the MAPK/ERK pathway. We hypothesize that the level of SPRY2 expression contributes to MAPK/ERK pathway output and accounts for BRAF+ and clinical heterogeneity. METHODS A tissue microarray with BRAF-positive PTCs (BRAF+ PTCs) was constructed and analyzed for SPRY2 expression and MAPK/ERK output. Data were studied in the context of clinicopathologic factors to develop a risk stratification system predictive of tumor biology. SPRY2 function was studied by silencing SPRY2 in BRAF+ PTC cells. These cells were treated with MAPK/ERK pathway inhibitors and assessed for growth effects. RESULTS BRAF+ PTCs with an intact MAPK/ERK feedback pathway do not exhibit lymph node metastases. BRAF+ PTCs with dysregulated feedback pathways have nodal metastasis. When SPRY2 is silenced, the BRAF+ PTC cells are significantly more sensitive to MAPK/ERK inhibition. CONCLUSION PTC behavior likely is dependent on both the driver of the MAPK/ERK pathway and its regulatory feedback. When the feedback pathway is intact, the tumor phenotype seems to be less aggressive. This observation has direct and important clinical implications and may alter our treatment strategies.

In-house trauma attendings: a new financial benefit for hospitals.

BACKGROUND There is an intuitive belief that in-house trauma attendings benefit patient outcome, although multiple studies have failed to prove this. However, no studies investigate the financial advantage for hospitals by having the attendings also perform urgent general surgery cases (GSC) during nights and weekends. The purpose of this study is to identify how an in-house attending program was used for urgent GSC and to see if it provided a financial benefit to the hospital. METHODS The in-house program began in October 2007. A retrospective study reviewed all cholecystectomies performed from October 2006 to September 2007 and October 2007 to September 2008. Total length of stay (LOS) was calculated. Total LOS for each group was multiplied by the daily cost for a medical-surgical bed (

The impact of alcohol in pedestrian trauma

2,530.00). The cost difference was calculated for the pre- and post-in-house groups. RESULTS Two hundred sixty-four cholecystectomies were performed before instituting an in-house attending program compared with 291 cases in the period after a 9% increase. Total LOS for cholecystectomies performed before the program was 6.4 days translating to

Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile -associated disease: An Eastern Association for the Surgery of Trauma multicenter trial

16,192.00 in room costs versus 5.24 days after and