77.03 Gendered Differences in Letters of Recommendation for Transplant Surgery Fellowship Applicants

Posted on January 18, 2018

A. L. Hoffman1, W. J. Grant1, M. F. McCormick1, E. E. Jezewski1, A. N. Langnas1  1University Of Nebraska Medical Center, Surgery, Omaha, NE, USA

Introduction: Recent studies have examined gender differences in letters of recommendation for men and women in academic positions, research grant applications, and residency programs. No published study has explored such gender differences in applications to surgical subspecialty fellowships.

Methods: We conducted a retrospective review of 317 letters of recommendation to a transplant surgery fellowship written for residents finishing United States general surgery residency programs. We created a dictionary of communal and agentic terms (Table 1) and determined whether there were differences in the terms, characteristics, and length of the letters based on applicant’s gender as well as the academic rank and gender of the author.

Results: Of the 317 reviewed letters, 235 were letters of recommendation written for male applicants. Male surgeons wrote 91.76% of letters written for female applicants and 93.2% of letters written for male applicants. Full professors wrote 58.7% of the letters, associate professors wrote 19.2% and assistant professors wrote 21.13%. Male applicant letters were significantly more likely to contain agentic terms than female applicant letters (p=0.00086).  Additionally, male applicant letters were significantly more likely to contain the term “future leader” than female letters (p=0.047). Letters containing the term “future leader” were more agentic (p=< 0.0001) and less communal (p=0.047) than letters that did not contain this term.  Letters written by full professors, division chiefs, and program directors were significantly more likely to describe female applicants using communal terms like compassionate, calm and delightful (p=0.0301, p=0.036,p= 0.036 respectively).  In letters written by assistant professors, female letters had significantly more references to the applicants family (p= 0.036) and were longer (p=0.00554) than male letters. We identified terms only found in male letters “no doubt will become extremely successful”, “is a great rarity”, “indestructible machine”, and “unlimited power”, as well as terms only found in female letters “successfully balancing work and family”, “blossomed”, “achieved without drama” and “lives the Girl Scout values”.

Conclusion: Gendered differences exist in letters of recommendation for transplant surgery fellowship applicants. This research may provide insight into the inherent gender bias that is revealed in letters supporting candidates entering the field.  This is the largest published study to identify differences in terms, length, and family references in a cohort of residents applying for a surgical fellowship.

77.04 Racial and Ethnic Disparities in Promotion and Retention of Academic Surgeons

Posted on January 18, 2018

G. Eckenrode1,2, M. Symer1, J. Abelson1, A. Watkins1, H. Yeo1,2  1Weill Cornell Medical College,Surgery,New York, NY, USA 2Weill Cornell Medical College,Healthcare Policy,New York, NY, USA

Introduction: Racial and ethnic diversity is low in academic surgery, especially in leadership positions. However, no study has quantified differences in the rates of retention and promotion of racial and ethnic minority surgeons in academia. We used the American Association of Medical Colleges (AAMC) Faculty Roster to track a large cohort of academic surgeons and evaluate their rates of promotion and retention by race.

Methods: The AAMC Faculty Roster is a comprehensive database which aggregates national, longitudinal data on academic faculty. All first-time assistant and associate professors appointed between January 1, 2003 and December 31, 2006 in surgery were included. Individuals were followed for up to 10 years from their initial appointment; until they were promoted, stayed at their current rank, or left full-time academia. Faculty who switched institutions were included in the analysis. Log-rank test was used to determine the impact of race and ethnicity on promotion (increase in academic rank) and retention (persistence in academic surgery regardless of rank). Individuals of Black, Hispanic, or Other race/ethnicity (such as American Indian or other/multiple/unknown) were grouped due to data limitations. 

Results:There were 3,966 academic surgeons who began academic appointments from 2003 to 2006, of whom 2,683 were assistant professors and 1,283 were associate professors. Faculty were predominantly White (n=2,617), followed by Asian (n=559), and Black, Hispanic, or Other race/ethnicity (n=790). There was a non-significant trend toward lower promotion of Black/Hispanic/Other assistant professors (Black/Hispanic/Other 26.7% promoted at 10 years, Asian 33.3%, White 34.4%, p=0.07). There was a similar difference in 10-year promotion rates of associate professors between these groups (Black/Hispanic/Other n=53, 28.8%; Asian n=43, 30.3%; White n=294, 30.7%; p=0.10). However, retention rates were significantly higher for White assistant professors (n=1,017, 61.3% retained at 10 years) than Asian (n=220, 52.8% retained) or Black/Hispanic/Other faculty (n=308, 50.8% retained; p<0.01). There was no significant difference in 10-year retention rates among associate professors based on race/ethnicity (Black/Hispanic/Other 71.2%, Asian 69.7%, White 69.3%, p=0.72).

Conclusion:Overall, promotion rates in academic surgery over a 10-year period were low, with a trend to lower rates among underrepresented minorities. In addition, there is a clear disparity in the retention of minority assistant professors of surgery. Other differences in the retention and promotion of minority faculty were not significant, possibly due to the small numbers of minority faculty even in this national study. Racial/ethnic minority faculty face unique barriers in remaining in academic surgery particularly at the start of their career. To build a diverse workforce in academic surgery, a renewed focus should be made on retaining early-career minority faculty.

77.02 Are Residents Really Burned Out? A Comprehensive Study of Surgical Resident Burnout and Well-Being

Posted on January 18, 2018

B. Hewitt1, J. W. Chung1, A. R. Dahlke1, A. D. Yang1, K. E. Engelhardt1, E. Blay1, J. T. Moskowitz2, E. O. Cheung2, F. R. Lewis3, K. Y. Bilimoria1  1Northwestern University,Surgical Outcomes And Quality Improvement Center,Chicago, IL, USA 2Northwestern University,Osher Center For Integrative Medicine,Chicago, ILLINOIS, USA 3American Board Of Surgery,Philadelphia, PENNSYLVANIA, USA

Introduction:  Despite great interest in resident wellness, little is known about actual rates of resident burnout as current data are limited by poor response rates, small sample sizes, or use of non-validated measures. Surgical residents are hypothesized to be at particular risk for burnout and poor well-being. We used novel national survey data with responses from nearly all U.S. general surgery residents to (1) examine burnout and poor well-being prevalence and (2) identify factors associated with burnout and well-being.

Methods:  All general surgery residents were surveyed (99% response rate) at the time of the January 2017 American Board of Surgery In-Training Examination (ABSITE) regarding wellness, duty hour violations, preparation for residency, and occupational safety. The main resident wellness outcomes were burnout (abbreviated Maslach Burnout Inventory – 6 items) and psychiatric well-being (General Health Questionnaire-12 which identifies those at risk for non-psychotic psychiatric illness). Hierarchical logistic regression analyses were performed to examine resident and program factors associated with burnout and well-being.

Results: Of 7,441 residents offered the survey, 7,387 residents (99.3%) in 260 surgical residency programs completed all items related to resident wellness. Overall, burnout was reported in 23.8% (n=1,756) of residents and poor psychiatric well-being in 44.3% (n=3,270). From the burnout assessment, 16.0% (n=1,184) of residents responded that they “do not really care what happens to some patients” at least a few times a month, and 18.1% (n=1,337) of residents responded that they daily “feel fatigued in the morning having to face another day on the job.” In multivariable models, burnout was more likely among male residents (OR 1.15 [95% CI 1.01-1.31]), those who felt unprepared for residency (OR 1.65 [95% CI 1.44-1.90]), and those who violated the 80 hour weekly average duty hour limit (violations in 1-4 of the past 6 months: OR 1.54 [95% CI 1.35-1.77]; violations in ≥5 months: OR 2.35 [95% CI 1.80-3.07]) compared to no violations. Burnout was not significantly associated with post graduate year (PGY). Poor psychiatric well-being was associated with similar factors with the exception of female residents (OR 1.25 [95% CI 1.12-1.38]) and PGY 1 residents (OR 1.19 [95% CI 1.04-1.35]) compared to PGY 4/5 residents who were more likely to report poor psychiatric well-being. There was no significant difference in burnout or psychiatric well-being between the Flexible and Standard arms of the FIRST Trial.

Conclusion: In this national survey including 99% of clinically active surgical residents in the U.S., burnout and poor psychiatric well-being were prevalent in surgical residents and more likely in residents who reported feeling unprepared for residency and those who violated duty hour limits. Solutions to improve resident wellness are needed and should address these associated factors.

76.05 Should Sentinel Lymph Node Biopsy Be Recommended to All Intermediate Thickness Melanoma Patients?

Posted on January 18, 2018

A. Hanna1, A. J. Sinnamon1, R. Roses1, R. Kelz1, D. Elder1, X. Xu1, B. Pockaj2, D. Fraker1, G. Karakousis1  1University Of Pennsylvania,Philadelphia, PA, USA 2Mayo Clinic,Phoenix, AZ, USA

Introduction:

Sentinel lymph node (SLN) biopsy is routinely recommended for patients with intermediate (1.01 – 4.00 mm) thickness melanoma. Prior institutional data from our group,however, suggested significant variation in the risk for SLN metastasis for these patients and we therefore sought to identify subgroups within this cohort with low risk for SLN positivity using a large national data set.

Methods:

Patients with intermediate thickness melanomas who underwent SLN biopsy from 2010 to 2013 were identified using the National Cancer Database. Clinical and pathologic variables associated with SLN positivity were analyzed using logistic regression. Classification and Regression Tree (CART) analysis was used to risk-stratify patients for SLN positivity.

Results:

Of the 23,440 study patients with intermediate thickness melanoma, 14.7% (95% CI, 14.2% – 15.1%) were found to have a positive SLN. Most (59.9%) patients were male and the median age was 62 years (IQR, 51 – 72 years old). In multivariate logistic regression, increased age (OR = 0.89/10 years, 95% CI 0.88 – 0.90), female gender (OR = 0.85, 95% CI 0.79 – 0.93), absence of lymphovascular invasion (LVI) (OR = 0.31, 95% CI 0.27 – 0.36), absent mitoses (OR = 0.61, 95% CI 0.54 – 0.70), a H&N, upper extremity, or shoulder primary site (OR = 0.55, 95% CI 0.49 – 0.63), decreased thickness (OR = 1.55/mm, 95% CI 1.48 – 1.63), and absent ulceration (OR = 0.74, 95% CI 0.68 – 0.81) all were significantly associated with having a negative SLN. In CART analysis, absent LVI, thickness < 1.7 mm, age < 56, and primary site were significant branch points (Figure 1). In patients 56 years of age or older with absent LVI and intermediate thickness lesions < 1.7 mm (29% of all patients analyzed), the rate of SLN positivity was < 5%.

Conclusion:

Despite a SLN positivity rate of 14.7% overall, there exists significant heterogeneity in the risk for SLN metastasis in patients with intermediate thickness melanoma. In a sizable group of patients (nearly 30% undergoing the procedure), the risk for SLN metastasis approximates that seen in lower risk thin melanomas, where the procedure is offered selectively. For these patients (56 years or older with lower depth intermediate lesions and absent LVI) careful consideration should be made weighing the risks and benefits of the SLN procedure.

76.06 Impact of ‘Take the Volume Pledge’ on Access & Outcomes for Gastrointestinal Cancer Surgery

Posted on January 18, 2018

R. C. Jacobs1, S. Groth1, F. Farjah2, M. A. Wilson3, L. A. Petersen4,5, N. N. Massarweh1,4  1Baylor College Of Medicine,Michael E. DeBakey Department Of Surgery,Houston, TX, USA 2University Of Washington,Division Of Cardiothoracic Surgery,Seattle, WA, USA 3VA Pittsburgh Healthcare System,Department Of Surgery,Pittsburgh, PA, USA 4Michael E. DeBakey Veterans Affairs Medical Center,VA HSR&D Center For Innovations In Quality, Effectiveness, And Safety,Houston, TX, USA 5Baylor College Of Medicine,Department Of Medicine,Houston, TX, USA

Introduction: The “Take the Volume Pledge” (TVP) initiative aims to regionalize complex cancer resections to hospitals meeting established annual volume thresholds. There is little data describing the potential impact on patient access if this initiative were broadly implemented or the relationship between TVP volume thresholds and quality of oncologic care.

Methods:  Hospitals performing esophagectomy (n=968), proctectomy (n=1,250), or pancreatectomy (n=1,068) in the National Cancer Data Base (2006-2012) were categorized into four groups based on frequency meeting TVP thresholds: always low volume (LV); low annual average and intermittently low volume (ILV); high annual average and intermittently high volume (IHV); always high volume (HV). Multivariable generalized estimating equations were used to evaluate the association between hospital TVP category and multimodality therapy (MMT) use, margin positive (R+) resection, and 30-day mortality.

Results: Over the study period, few hospitals met annual TVP thresholds (HV or IHV)—esophagectomy 1.6%; proctectomy 19.7%; pancreatectomy 6.6%. The majority of esophagectomy (77.8%) and pancreatectomy (53.4%) and 48.1% of proctectomy patients received care at hospitals not meeting annual TVP thresholds (LV or ILV). While unadjusted MMT, R+ resection, and 30-day mortality rates were better at ILV, IHV, and HV relative to LV hospitals, there were no consistent differences between non-LV (ILV, IHV, and HV) hospitals. The odds of receiving MMT was not different across TVP categories for esophagectomy or pancreatectomy (Table). For proctectomy, MMT use was significantly more likely (relative to LV hospitals) at ILV, IHV, and HV hospitals. For all three procedures, the odds of a R+ resection were lower (relative to LV hospitals) at IHV and HV hospitals (and at ILV hospitals for esophagectomy). However, there were no differences in R+ resection rates between ILV, IHV, and HV hospitals. The odds of 30-day mortality after esophagectomy was not different in any TVP category, except at HV (relative to LV) hospitals (OR 0.63 [0.42-0.94]). The odds of mortality were significantly lower (relative to LV hospitals) at ILV, IHV, and HV hospitals after proctectomy and pancreatectomy. But, there were no mortality differences comparing ILV, IHV, and HV hospitals.

Conclusion: Few hospitals meet TVP cancer resection volume thresholds with little difference in outcomes across non-LV hospitals. A policy to shift surgical care only to hospitals meeting TVP could compromise patient autonomy, limit access if patients are unable or unwilling to travel, and may not necessarily establish objective benchmarks for ensuring high-quality outcomes.

77.01 Gender and Self-concept in the General Surgery Trainee: Experiences that Shape Professional Identity

Posted on January 18, 2018

S. P. Myers1, K. J. Nicholson1, K. Hill1, E. B. Littleton2, G. Hamad1, M. Rosengart1  1University Of Pittsburgh Medical Center,General Surgery,Pittsburgh, PA, USA 2University Of Pittsburgh,School Of Medicine,Pittsburgh, PA, USA

Introduction:  Few studies focus on how gender affects the formation of professional identity during residency. Professional identity is integral to academic achievement and represents an essential component of the more comprehensive construct of self-concept. For surgeons, competence requires non-technical behaviors that support surgical learning and the development of professional identity. As residency is a formative period during which these intangible skills are acquired, we hypothesize that experiences during training diverge among genders and may be associated with differences in self-concept and professional identity.

Methods:  A qualitative mixed-methods study of general surgery residents at the University of Pittsburgh Medical Center was performed. General Surgery residents participated in two survey instruments, a questionnaire and interview, that interrogated domains of self-concept and professional identity. Transcribed interviews were coded for recurring content using inductive methods. Coded data were evaluated for emerging themes. Data and interrater reliability were analyzed using Fisher’s exact tests and Cohen’s Kappa respectively. A p-value <0.05 was considered significant.

Results: Study participants included forty-two (87.5%) general surgery residents (24 males, 18 females), and the kappa values for coded data ranged from (0.63-0.83). Fewer female residents self-identified as a ‘surgeon’ (11.1% vs. 37.5%, p<0.001). All subjects reported that patients more frequently dismissed female residents’ professional role (p<0.001), that support staff hostility was more commonly directed at women trainees (p=0.015), and that attendings preferred working with male residents (p=0.001). Significantly more females recounted episodes of another physician disregarding their professional title (p<0.001), being the target of unprofessional sexual conduct (p<0.001), and hostile behaviors from attendings (p>0.001).  All residents reported that women but not men were negatively stereotyped (p<0.001): cast as lacking confidence or authority, being physically or emotionally weak, having low professional or societal worth and being overly-aggressive. Significantly more female residents reported experiencing feelings of lack of mentorship, discomfort, feeling pressured to accept or participate in unprofessional behaviors, having difficulty completing tasks and having to adapt to overcome barriers (p<0.001). Nearly all the residents who communicated concern over barriers to career advancement were women. 

Conclusion: Key events in training perpetuate preconceived impressions that women are inferior to their male counterparts. These can be disruptive to the development of self-concept and professional identity.

 

76.04 Multi-institution Evaluation of Adherence to Comprehensive Postoperative VTE Chemoprophylaxis

Posted on January 18, 2018

B. Hewitt1, E. Blay1, L. J. Kreutzer1, K. Y. Bilimoria1, A. D. Yang1  1Northwestern University,Surgical Outcomes And Quality Improvement Center,Chicago, IL, USA

Introduction:  Venous thromboembolism (VTE) is the leading cause of preventable hospital mortality. Current quality measures for VTE prophylaxis are problematic due to surveillance bias, are not comprehensive, do not ensure appropriate administration, and cannot identify reasons why failures to provide chemoprophylaxis occur.

Methods:  We examined adherence to a novel process measure in patients who underwent elective or non-elective colectomy over an 18 month period at 36 hospitals in a statewide surgical collaborative. The process measure assessed comprehensive VTE chemoprophylaxis during a patient’s entire inpatient hospitalization, including reasons chemoprophylaxis was not given. Unadjusted and adjusted analyses were performed to identify reasons for failure to provide defect-free chemoprophylaxis and examine patient- and hospital-level factors associated with failure.

Results: Out of 4,086 total colectomies, the standard SCIP-VTE-2 prophylaxis measure publicly reported by CMS identified failure in care in only 1% of cases; however, the new measure unmasked failure to provide defect-free VTE chemoprophylaxis in 18% of cases. Reasons for failure included medication not ordered (29.6%), patient refusal (29.5%), incorrect dosage/frequency (7.9%), patient off unit (3.3%), and other (29.6%). Patients were more likely to fail the chemoprophylaxis process measure if treated at safety net hospitals (Odds Ratio [OR] 1.60, 95% Confidence Interval [CI] 1.06-2.41; p=0.03) or if they were ≤ 40 years old (OR 1.52, 95% CI 1.05-2.20; p=0.03 compared to age ≥ 75 years). Patients treated at Magnet nursing-accredited hospitals (OR 0.45, 95% CI 0.30-0.67; p<0.001) or undergoing elective colectomy (OR 0.77, 95% CI 0.62-0.96; p=0.02 compared to non-elective colectomy) were less likely to fail chemoprophylaxis. Patients ≤ 40 years old (OR 2.20, 95% CI 1.43-3.40; p<0.001), underweight patients (OR 2.19, 95% CI 1.28-3.77; p=0.004) or those that received treatment at safety net (OR 1.97, 95% CI 1.07-3.62; p=0.03 compared to non-safety net hospitals) or teaching hospitals (OR 2.82, 95% CI 1.37-5.84; p=0.005 compared to non-teaching hospitals) were more likely to refuse chemoprophylaxis.

Conclusion: This is the first multi-institution study examining failure patterns in providing comprehensive postoperative VTE chemoprophylaxis. In stark contrast to SCIP-VTE-2, our measure unmasked chemoprophylaxis failures in 18% of colectomies in a statewide surgical collaborative. Most chemoprophylaxis failures were due to patient refusals and ordering errors, occurring throughout the inpatient postoperative period. Thus, hospitals should focus improvement efforts on ensuring patients receive VTE prophylaxis throughout their entire hospitalization.

76.02 Editorial (Spring) Board?: Gender Composition in High-Impact General Surgery Journals

Posted on January 18, 2018

C. A. Harris1, T. Banerjee7, M. Cramer4, S. Manz6, S. Ward5, J. B. Dimick3, D. A. Telem2  1University Of Michigan,Division Of Plastic Surgery, Department Of Surgery,Ann Arbor, MI, USA 2University Of Michigan,Michigan Women’s Surgical Collaborative,Ann Arbor, MI, USA 3University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 4Cornell University,Ithaca, NY, USA 5University Of Michigan,Division Of Cardiac Surgery, Department Of Surgery,Ann Arbor, MI, USA 6University Of Michigan,Ann Arbor, MI, USA 7University Of Michigan,Institute For Health Policy And Innovation,Ann Arbor, MI, USA 8University Of Michigan,Institute For Health Policy And Innovation,Ann Arbor, MI, USA

Introduction: Serving on an editorial board is an important step in many surgeons’ careers; however, evidence suggests that access to these positions may differ based on gender. Analyses of medical journals indicate although women’s representation is improving, they remain a clear minority. Whether similar trends exist in surgery and whether women surgeons face different qualification thresholds for appointment remains unknown. To address this knowledge gap, we quantify the current gender composition of ten high-impact surgery journals, evaluate qualification metrics by gender, and delineate how board composition has changed over time.

Methods: Ten prominent general surgery journals were selected for inclusion based on impact factor. Editor characteristics were assigned using faculty websites, Scopus profiles, and the American Board of Surgery certification database. We performed cross-sectional analyses of editorial board composition by gender for 1997, 2007, and 2017 using univariate and logistic regression analysis. Variation in qualifications by gender was assessed by comparing H-index, academic rank, and number of additional degrees. Gender-based differences in editorial board member turnover and multiple board positions were evaluated for each time interval.

Results: Over 20 years, women’s editorial presence has increased from 5% to 19%. Initial univariate analysis demonstrated significant qualification differences. Compared to women, men had higher mean H-indices (39.1 vs 21.9; p<0.001) and more full professorships (70.2% vs 55.8% p=0.02); whereas, a higher percentage of women had additional degrees (36.1% vs 21.9% p=0.004). Following logistic regression controlling for length of time since board certification, these associations became non-significant (degrees p= 0.051; academic rank p=0.56; H-index p=0.35). Both women and men were equally likely to hold multiple board positions (1997 p=0.74; 2007 p=0.42; 2017 p=0.69). Journals retained higher proportions of men in each time interval (1997-2007 p=0.003; 2007-2017 p= <0.001; 1997-2017 p=0.01) and retention rates increased over time (Figure 1).

Conclusion: Women surgeons have a small but growing presence on surgical editorial boards, and any qualification differences by gender are likely attributable to practice length. Although this suggests improved gender parity, gaps remain, and may be perpetuated by inequitable retention. More importantly, rising retention rates may limit next-generation surgeons’ opportunities regardless of gender. Strategies such as imposing term limits or instituting merit-based performance reviews may help balance the need for high-level expertise with efforts to ensure that editorial boards capture the field’s changing demographics.

 

76.03 The Association of Enhanced Recovery Pathway and Acute Kidney Injury in Colorectal Surgery Patients

Posted on January 18, 2018

J. G. Wiener1, L. Goss1,2, D. I. Chu1, J. S. Richman1, J. A. Cannon1, T. S. Wahl1, G. D. Kennedy1, K. D. Cofer1, P. K. Patel1, M. S. Morris1  2Birmingham VA Medical Center,Surgery,Birmingham, ALABAMA, USA 1University Of Alabama at Birmingham,Surgery,Birmingham, Alabama, USA

Introduction:
Enhanced Recovery After Surgery (ERAS) pathways standardize preoperative, intraoperative, and postoperative care including goal directed fluid administration and multimodal pain management. ERAS is associated with shorter hospital lengths of stay, lower costs, and equivalent readmission rates. Since implementing ERAS at our institution in 2015, we sensed an increase in AKI. Although ERAS has benefits for patients and hospitals, little is known about its association with acute kidney injury (AKI). We hypothesize that incorporation of an ERAS pathway for elective colorectal surgery would be independently associated with an increased risk of AKI.

Methods:
A single-institution retrospective review of patients undergoing elective colorectal surgery before and after the implementation of ERAS was conducted. Patient-specific variables were recorded and our primary outcome was development of an AKI. AKI was operationalized using The Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging system. Patients with AKI or dialysis preoperatively were excluded from our analysis. Bivariate comparisons were made using chi-square and Wilcoxon rank sum tests for categorical and continuous variables, respectively. Variables with p<0.05 for bivariate comparisons were included in a multivariate logistic model for AKI.

Results:
Our study cohort included 974 total patients, 604 in the pre-ERAS group and 370 patients in the ERAS group. The two groups were similar except for significantly higher incidences in the pre-ERAS group of diabetes mellitus, hypertension requiring medication, ascites within 30 days prior to surgery, disseminated cancer, and contaminated or dirty wounds in the pre-ERAS group compared to the ERAS group (Table). There was no significant difference in age or BMI at the time of surgery between the two groups. Postoperatively, 9.7% of the ERAS group developed AKI compared to 5.8% of the pre-ERAS group (p=0.02).  After adjusting for significant covariates, our model showed that patients in the ERAS group were 2.4 times more likely to develop post-op AKI than patients in the pre-ERAS group (OR=2.41, CI 1.42-4.08, p < 0.01).

Conclusion:
Implementation of an Enhanced Recovery Protocol is associated with higher levels of acute kidney injury following elective colorectal surgery. Future studies will determine which aspects of the ERAS protocol, such as NSAID use in the multi-modal pain management or intraoperative goal directed fluid delivery, may be associated with this increased incidence of AKI.

76.01 The Affordable Care Act’s Medicaid Expansion and Utilization of Discretionary Inpatient Surgery

Posted on January 18, 2018

A. B. Crocker3, A. Zeymo2,3, D. Xiao3, L. B. Johnson4, T. DeLeire5, N. Shara2,4, W. B. Al-Refaie1,2,3  1MedStar-Georgetown University Medical Center,Department Of Surgery,Washington, DC, USA 2MedStar Health Research Institute,Washington, DC, USA 3MedStar-Georgetown Surgical Outcomes Research Center,Washington, DC, USA 4Georgetown-Howard Universities Center For Clinical And Translational Science,Washington, DC, USA 5Georgetown McCourt School Of Public Policy,Washington, DC, USA

Introduction: Pre-Affordable Care Act (ACA) Medicaid expansion has preferentially increased utilization of elective inpatient procedures. However, the impact of the ACA on such elective and preference-sensitive procedures (also known as discretionary procedures) vs. clinically essential and time-sensitive non-discretionary procedures remains unknown. We hypothesize that the ACA’s expansion led to increased utilization of inpatient discretionary procedures (DP) relative to non-discretionary surgical procedures (NDP) in expansion vs. non-expansion states. As such, we performed hospital-level quasi-experimental evaluations to measure the state-by-state differential effects of the ACA’s Medicaid expansion on utilization of DP vs. NDP.

Methods:  The State In-Patient Database (2012-2014) yielded 476 hospitals providing selected DP or NDP procedures performed on 275,131 non-elderly, adult patients (ages 18-64 years) across three expansion states (Kentucky, Maryland, and New Jersey) vs. two non-expansion control states (Florida and North Carolina). DP included non-emergent total knee arthroplasty and total hip arthroplasty, while NDP included a cohort of nine cancer surgeries. Mixed Poisson interrupted time series (ITS) analyses were performed to determine the impact of ACA’s Medicaid expansion on the number of DP vs. NDP provided: 1) across expanded versus non-expanded states overall, 2) among non-privately insured patients (Medicaid and uninsured payers).

Results: Substantial reductions in the number of uninsured DPs were observed in both expansion (-73%) and non-expansion states (-45%). While the number of Medicaid insured DPs in expansion states nearly doubled, the number of privately insured DPs in non-expansion states increased by 10%.  Observing no overall differential increase in the utilization of DPs in expansion and non-expansion states after 2014 (2.2% per quarter and 2.8% per quarter), subsequent analysis on the mean number of non-privately insured DP and NDP was performed. Mixed ITS estimated a differential increase in DP (+17.7% vs -3.5%) and NDP (+4.7% vs -5.0%) in expansion states compared to non-expansion states.  Additionally, a substantially larger increase in utilization of DP vs NDP was detected within expansion states after 2014 (Figure).

Conclusion: In this multi-state evaluation, ACA’s Medicaid expansion has preferentially increased utilization of DP in expansion vs non-expansion states among non-privately insured patients. This expansion has also differentially increased utilization of DP relative to NDP in expansion states. These preliminary findings suggest that expansion coverage increased use of inpatient surgery. Further research is merited to expand on these early results.

 

19.05 ATAC-seq and Reciprocal Transplantation Prove Scar-Forming Behavior is Cell Intrinsic

Posted on January 18, 2018

A. L. Moore1,3, C. Marshall1, U. Litzenburger4, R. C. Ransom4, L. Barnes4, B. Duoto4, D. Foster1, R. E. Jones2,4, S. Mascharak4, M. Hu4, H. Y. Chang4, H. P. Lorenz1, M. T. Longaker1  1Stanford University,Department Of Surgery,Palo Alto, CA, USA 2University Of Texas Southwestern Medical Center,Department Of Surgery,Dallas, TX, USA 3Brigham And Women’s Hospital,Department Of Surgery,Boston, MA, USA 4Stanford University,Palo Alto, CA, USA

Introduction:

Skin scarring poses a major financial and physiologic burden on patients and the US healthcare system. In 2015, our group discovered a subset of fibroblasts in the dorsal dermis identified by embryonic expression of the homeobox transcription factor Engrailed-1 that deposit the bulk of scar collagen in adult mice. These cells are also present in embryonic development around the time of phenotypic transition from regenerative scarless healing to fibrotic scarring. Given Engrailed-1 positive fibroblasts (EPFs) share a common precursor cell, we hypothesized that the EPFs accumulate epigenetic changes over time that result in their phenotypic change and result in a permanent cellular phenotype.

Methods:

Fibroblasts were isolated from En1Cre; R26mTmG mice using fluorescence-activated cell sorting (FACS) at gestational ages embryonic day (e)10, e16, e18, postnatal day (p)1, p30, and p30 wounded skin. Epigenetic regulation was analyzed using the assay for transposase accessible chromatin using sequencing (ATAC-seq). Fibroblasts were then transplanted from e16 embryos to p1 mouse pups, and vice versa, to observe scar forming behavior in vivo.

Results:

E10 fibroblasts are of a single lineage and were excluded from analysis. Time course analysis of e16-p30 EPFs and Engrailed-1 negative fibroblasts (ENFs) shows appropriate correlation between samples (Figure 1A). Grouping analysis of variance shows p30 EPFs and ENFs being the most dissimilar, and EPFs from p30 are most like e16 EPFs (Figure 1B). Most epigenetic changes in the EPF lineage occur in embryonic development between e16 and e18 with fewer epigenetic changes occurring postnatally between p1 and p30 (significant peaks = 124 vs. 20, Figure 1C). In contrast, the ENF lineage accumulates more epigenetic changes between p1 and p30 (significant peaks = 62 vs. >250, Figure 1C). Lastly, reciprocal transplantation of e16 fibroblasts into a p1 host and vice versa reveal a significant difference in collagen overlap (2.13% versus 24.18%) and morphologic changes suggestive of quiescence versus reactivity (Figure 1D).

Conclusions:

ATAC-seq analysis of EPF lineage cells reveals most epigenetic changes occurring at the time of phenotypic change from scarless to scarring (between e16 to e18). In future experiments, we will identify transcription factors to perturb using CRISPR-Cas9. Manipulated cells will be transplanted into fetal and postnatal hosts. These experiments will reveal if master regulators are involved in the scar forming phenotype of EPFs.

19.06 CCR2+ Monocytes Mobilized from Spleen Cause Neutrophil Extravasation During Lung Reperfusion Injury

Posted on January 18, 2018

R. Fernandez1, M. Akbarpour1, S. F. Chiu1, H. Sun1, A. Misharin1, G. S. Budinger1, A. Bharat1  1Northwestern University,Thoracic Surgery,Chicago, IL, USA

Introduction: Lung ischemia reperfusion injury (LIRI) is the primary cause of graft failure and mortality after lung transplant. LIRI is mediated by neutrophils. Neutrophil depletion ameliorates LIRI but is not clinically applicable due to their importance in pathogen clearance. Accordingly, we focused on elucidating trafficking of neutrophils. We identified a novel subset of bone marrow derived classical monocytes (CM) which, upon mobilization from the spleen, mediates neutrophil extravasation during LIRI in mice and humans.

Methods: LIRI was induced in mice by hilar clamping for 60 mins followed by 2 hours of reperfusion. Splenectomy and heterotopic spleen transplant were performed using standard techniques. Multipanel flow cytometry was used to quantify myeloid cell populations in tissues. Human lung samples were taken from lung grafts before and after reperfusion. Student’s t-tests and ANOVA were used for statistical analysis.

Results:LIRI induced an influx of CCR2+CM into the lung (29.3±4.7 vs. 3.9±0.7 cells/mg lung; p<0.001) which was associated with neutrophil extravasation into the alveoli compared to a resting state (16.0±3.1 vs. 2.3±0.3% extravasated, p<0.001). Depletion of all intravascular monocytes with clodronate-liposomes suppressed neutrophil extravasation compared to control (4.5±0.9 vs. 9.1±1.6%; p=0.03). Specific depletion of CM with anti-CCR2 antibody abrogated neutrophil extravasation compared to isotype control (15.4±1.4 vs. 20.7±1.8%; p=0.04). LIRI in Nr4a1-/- mice, which lack only non-classical monocytes, showed no difference in neutrophil extravasation. Splenectomy impaired neutrophil extravasation (6.8±0.6 vs. 16.6±2.2%; p=0.001) and reduced CM lung trafficking after LIRI (13.5±3.2 vs. 53.8±14.0 cells/mg lung; p=0.01). Heterotopic spleen transplant after native splenectomy restored CM trafficking (Figure 1A) (195.3±73.7 vs. 13.5±3.2 cells/mg lung; p=0.008) and neutrophil extravasation (Figure 1B) (14.1±1.2 vs. 6.8±0.6%; p<0.001) compared to spleen-lacking mice. Recipient bone marrow derived CCR2+CM repopulated the heterotopic spleen grafts and were recruited to the lungs during LIRI. Reconstitution with CCR2+CM did not restore neutrophil extravasation in splenectomized mice. Human lung allografts demonstrated over 2-fold increase in CCR2+CM influx immediately after reperfusion which showed linear correlation with neutrophil recruitment (p<0.001).

Conclusion:CCR2+ CM are responsible for neutrophil extravasation after LIRI but must pass through the spleen to mediate their function. As CCR2+CM are short-lived and replenished rapidly by the bone marrow, transient depletion using anti-CCR2 antibodies can ameliorate LIRI without affecting host pathogen response.

 

19.03 RON Kinase Inhibition Modulates the Pancreatic Cancer Microenvironment to Promote an Antitumor State

Posted on January 18, 2018

D. Sood1, A. Cazes1, D. Jaquish1, E. Mose1, R. French1, A. M. Lowy1  1University Of California – San Diego,Department Of Surgery, Division Of Surgical Oncology, Moores Cancer Center, La Jolla, CA, USA

Introduction:
RON, a receptor tyrosine kinase and c-Met proto-oncogene homolog, is over-expressed in pancreatic cancer relative to normal tissue. RON’s function in normal biology is to curtail the inflammatory response, such as in the terminal stages of wound healing. It does this in large part by regulating the transition of macrophages from a pro-inflammatory, tumor-suppressive (M1) state to an immunosuppressive, tumor-promoting (M2) state. In cancer, alternatively polarized macrophages secrete pro-tumorigenic cyto- and chemokines that suppress effector T cell activation and may prevent their access to the tumor microenvironment. In this study, we aim to determine if RON kinase inhibition can effectively modulate the pancreatic cancer microenvironment to promote antitumor activation states in macrophages.

Methods:
KPC (Pdx1-Cre; K-Ras+/LSLG12D; p53R172H/+) organoids were orthotopically injected into the pancreas of F1 hybrid B6-129S mice. LY2801653 is an orally bioavailable small molecule RON inhibitor in Phase II trials for advanced solid cancers. IPI549, a PI3Kγ  inhibitor in Phase I trials, shown to have potent preclinical antitumor activity and promote classical activation of macrophages to the M1 state, was selected as a positive control. Treatment was started one week after injection for the following groups: A) vehicle control (10% acacia gum/5% NMP), B) LY2801653 12 mg/kg, C) LY2801653 24 mg/kg, D) IPI549 15 mg/kg, and E) LY2801653 24 mg/kg + IPI549 15 mg/kg. Mice were treated daily via orogavage for 2 weeks. The tumors were harvested and dissociated into a single cell suspension. The cells were labeled with fluorescent-conjugated antibodies to markers of leukocytes and macrophage polarization for flow cytometry. One way ANOVA with a Bonferroni correction for multiple comparisons was used to analyze the results.

Results:
Macrophages were defined as cells that labeled positive for CD45, CD11b, MHC II, and F4/80. Within that population, cells that labeled positive for CD80 and CD86, but negative for MRC1 were considered M1 macrophages, whereas those that were MRC1 positive, but negative for CD80 and CD86 were considered M2 macrophages. Flow cytometry demonstrated a significant decrease in the M2 macrophage population in each of the four treatment groups when compared to the vehicle control (p < 0.001). There was also a corresponding increase in the M1 macrophage population; this was significant (p < 0.001) for all except group E. Finally, mice in all four treatment groups exhibited significantly suppressed tumor growth by weight, relative to the vehicle control-treated mice (p < 0.005).

Conclusion:
In this study, we demonstrate that inhibition of RON kinase signaling alters the immunosuppressive microenvironment of pancreatic cancer and can be effectively targeted to shift that environment toward an antitumor state. Further studies are underway to better understand RON’s potential as a therapeutic target in pancreatic cancer.

19.04 Whole-Food Enteral Nutrition Prevents Gut Dysbiosis and Improves Outcomes in a Mouse Colitis Model.

Posted on January 18, 2018

A. Yeh1, E. Conners2, B. Firek2, M. B. Rogers2, R. Cheek2, M. J. Morowitz2  1University Of Pittsburgh,Department Of Surgery,Pittsburgh, PA, USA 2Children’s Hospital Of Pittsburgh Of UPMC,Division Of Pediatric General And Thoracic Surgery,Pittsburgh, PA, USA

Introduction:

Critically ill patients have significantly deranged gut microbiota that may promote gastrointestinal and systemic inflammation. One major contributor to dysbiosis is the use of chemically-defined enteral formulas for nutrition that are composed of high sugar, low fiber, and artificial ingredients. Whole-food enteral formulas represent a healthy alternative that lacks these shortcomings. We hypothesize that whole-food enteral formulas will restore a healthy gut microbiota and reduce dysregulated inflammation in critically ill patients. To test this hypothesis, we used the DSS-induced colitis model in mice as a surrogate for the gut inflammation seen commonly during critical illness.

Methods:

C57BL/6 mice were fed standard chow, chemically-defined formulas Vital (V) or Pediasure (P; Abbott Nutrition), or plant-based whole-food formula Liquid Hope (LH; Functional Formularies) for 7 days. Mice were then given 4% DSS water or control water for 4 days. Weight and disease activity indices (DAI) were measured daily. Upon sacrifice, plasma was obtained for IL-6 analysis and colon length was measured as markers of inflammation. Stool samples were collected before starting the diet, after 7 days on the diet/before starting DSS water, and after DSS exposure. Bacterial 16S rRNA gene sequences in each sample were amplified, sequenced on the Illumina MiSeq, and analyzed with QIIME.

Results:

Weight loss was more severe (p<0.01) and DAI’s were higher (p<0.01) after DSS exposure in mice fed P or V (n=16 per group) compared to LH. IL-6 plasma levels and colon length were also significantly increased (p<0.01) and decreased (p<0.01), respectively, in mice fed V and P compared to LH indicating worse inflammation. Gut microbiome analysis demonstrated reduced species diversity and altered species composition in mice fed V and P compared to LH (p<0.05). Prior to DSS exposure, mice fed V and P compared to LH contained greater abundance of Enterobacteriaceae (p<0.05), a family containing Gram-negative pathogens associated with gut inflammation, and lesser abundance of Clostridiales (p<0.05), an order containing many commensal bacteria associated with immune homeostasis.

Conclusion:

LH significantly improved outcomes in mice exposed to DSS compared to standard formulas, V and P. LH also prevented gut dysbiosis, maintaining healthy commensal organisms, and preventing invasion of pathogenic organisms. Future work will need to determine if direct effects of the diet composition and/or indirect effects on the microbiome are responsible for the protective effect of whole-food nutrition, and whether its use in the ICU can improve outcomes for critically ill patients receiving enteral nutritional support.

19.01 E-selectin/AAV Gene Therapy Promotes Wound Healing in a Critical Limb Ischemia Mouse Model

Posted on January 18, 2018

P. P. Parikh1, R. Lassance-Soares1, H. Shao1, Z. Liu1, O. C. Velazquez1  1University Of Miami Miller School Of Medicine,Surgery,Miami, FL, USA

Introduction: Poor wound healing in critical limb ischemia (CLI) has been attributed to impaired neovascularization and diminished reperfusion. Optimizing the wound microenvironment by priming wound tissue with adhesion molecules to enhance stem and progenitor cell homing for wound healing may revolutionize the treatment of ischemic wounds. The primary aim of this study involves testing the efficacy of adhesion molecule E-selectin on ischemic wound healing in an ischemic mouse wound model, appraising the possibility of E-selectin-based gene therapy for wound care in CLI.

Methods: Eight-week-old male FVB mice underwent unilateral femoral artery ligation (FAL) to induce CLI. FAL was performed at two sites: immediately below the inguinal ligament and proximal to the sapheno-popliteal bifurcation. Subsequent to FAL, a 4-mm punch biopsy wound was created on the anterior thigh, below the proximal ligation site, to simulate ischemic wounds. Intra-lesion injection of either adenoassociated virus (AAV) carrying E-selectin gene (E-selectin/AAV, n=6) or LacZ gene as control (LacZ+/AAV, n=6) was performed immediately after FAL. Soft-ware assisted measurement of wound healing was performed sequentially for 10 days. Laser doppler imaging (LDI) quantified ischemic hindlimb reperfusion by mean perfusion of ligated:non-ligated limb on postoperative days (PODs) 2 and 8. Using live animal Dil perfusion, wound tissue neovascularization was evaluated by quantification of capillary density in the wound on POD 8. Immunofluorescence verified E-selectin transgene expression in wound vasculature using antibodies against E-selectin and CD31, an endothelial cell marker. Histology of tissues also observed for inflammation and micro-thrombi.

Results: Immunofluorescence confirmed highly effective E-selectin/AAV gene delivery in treatment vs control limbs.  No inflammation or micro-thrombi were noted on tissue histology. Wounds from E-selectin/AAV treated mice vs control revealed surface area healing of 55% vs 30% (P=0.005) on POD 1, 81% vs 58% on POD 4 (P=0.0007) and 93% vs 78% on POD 8 (P=0.0001), respectively. LDI revealed greater reperfusion in E-selectin/AAV treated mice vs control by POD 8 (0.2 vs 0.09, respectively; P=0.0006). Live animal Dil perfused ligated hindlimb in E-selectin/AAV treated vs control mice revealed mean neovascularization intensity score of 14 versus 6 (P=0.037) on POD 8.

Conclusion: This study demonstrates the E-selectin/AAV vector as an effective means to achieve elevated levels of E-selectin expression within ischemic wound tissue and blood vessels. Intra-lesion E-selectin/AAV gene therapy of ischemic wounds in mice significantly increased wound angiogenesis and limb reperfusion, expediting overall wound healing.

19.02 Bioengineered Human Pancreatic Islets for the treatment of Type-I Diabetes

Posted on January 18, 2018

M. Schmidt1, G. Loganathan1, S. Narayanan1, A. Jawahar1, J. Pradeep1, M. G. Hughes1, S. K. Williams1, B. N. Appakalai1  1University Of Louisville,Department Of Surgery,Louisville, KY, USA

Introduction:  Islet transplantation is one of the best approaches to restore insulin independence in Type-1 diabetic patients. Generally, the transplant recipients achieve insulin independence, however, the transplanted islets undergo cell death due to poor blood supply immediately after transplantation. Native islets in the pancreas have a rich vascular supply however, the current islet isolation technique completely severs the vasculature to islets. As such, these islets become avascular and many of them die immediately after transplantation. The creation of blood vessels around islets (Bioengineered islets –BEI) will enable islet cell survival and reverse diabetes efficiently. Our specific aim was to stimulate intra-islet endothelial cells (IIEC) to form peri-islet capillaries (PIC) in culture prior to transplantation. We tested our hypothesis and accelerated the formation of PIC to human islets by stimulating the IIEC with the addition of ECGS (a mixture of endothelial growth factors) in a 3D-culture system.

Methods:  Human islets cells were isolated from brain-dead donor pancreases (n=15) and the islets (200 per well) were cultured in a 3D system using rat-tail collagen-I gel with ECGS containing medium for 14 days. 2D cultured islets and 3D cultured islets without ECGS were used us control groups. Time-lapse microscopy (Cytation 5) was used to monitor islet-derived PIC growth every day for 14 days. After the sprout formation, human endothelium was identified via labeling with UEA-1 staining. To study diabetes reversal, the BEI were implanted in to diabetic nude mice at the subcutaneous site.

Results: These results indicate this approach induced cellular sprouting from human islets and were positive for endothelial cells. The bioengineered islets maintained >90% cell viability, high insulin secretory capacity when compared to control islets and importantly, BEI reversed diabetes in mice. Naked islets cultured in a 2D environment did not form any sprout. However, the presence of ECGS and 3D-culture system induced cellular sprouting from human islets within 7 days. UEA-1 FITC Green and RedDot 2 labeling indicated that several of these sprouts were endothelial. We speculate that our isolated islets gave rise to peri-islet sprouts. 3D-cultured islets maintained >90% cellular viability after 14 days, whereas 2D-cultured islets displayed disintegration of their borders as well as reduced viability. Statistically significant difference (P<0.05) was observed in number of sprouts when islets were cultured in 3D environment without ECGS.

Conclusion: We demonstrated that 3D matrix support and ECGS are required to elicit successful, spontaneous PIC formation in human islets. EGCS solution is essential for the stimulation of PIC. ECGS with 3D culture may provide unique avenues to accelerate islet neovascularization following transplantation. We conclude that creating BEI is a novel approach for the treatment of type-I diabetes.