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Item Bile Acids Conjugation in Human Bile Is Not Random: New Insights from 1H-NMR Spectroscopy at 800 MHz(Springer, 2009-06) Nagana Gowda, G. A.; Shanaiah, Narasimhamurthy; Cooper, Amanda; Maluccio, Mary; Raftery, Daniel; Department of Surgery, School of MedicineBile acids constitute a group of structurally closely related molecules and represent the most abundant constituents of human bile. Investigations of bile acids have garnered increased interest owing to their recently discovered additional biological functions including their role as signaling molecules that govern glucose, fat and energy metabolism. Recent NMR methodological developments have enabled single-step analysis of several highly abundant and common glycine- and taurine- conjugated bile acids, such as glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid. Investigation of these conjugated bile acids in human bile employing high field (800 MHz) (1)H-NMR spectroscopy reveals that the ratios between two glycine-conjugated bile acids and their taurine counterparts correlate positively (R2 = 0.83-0.97; p = 0.001 x 10(-2)-0.006 x 10(-7)) as do the ratios between a glycine-conjugated bile acid and its taurine counterpart (R2 = 0.92-0.95; p = 0.004 x 10(-3)-0.002 x 10(-10)). Using such correlations, concentration of individual bile acids in each sample could be predicted in good agreement with the experimentally determined values. These insights into the pattern of bile acid conjugation in human bile between glycine and taurine promise useful clues to the mechanism of bile acids' biosynthesis, conjugation and enterohepatic circulation, and may improve our understanding of the role of individual conjugated bile acids in health and disease.Item The Coalition for National Trauma Research supports the call for a national trauma research action plan(Lippincott, Williams, and Wilkins, 2017-03) Coimbra, Raul; Kozar, Rosemary A.; Smith, Jason W.; Zarzaur, Ben L.; Hauser, Carl J.; Moore, Frederick A.; Bailey, Jeffrey A.; Valadka, Alex; Jurkovich, Gregory J.; Jenkins, Donald H.; Davis, Kimberly A.; Price, Michelle A.; Maier, Ronald V.; Department of Surgery, School of MedicineItem Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2015-11) Unthank, Joseph L.; Miller, Steven J.; Quickery, Ariel K.; Ferguson, Ethan L.; Wang, Meijing; Sampson, Carol H.; Chua, Hui Lin; DiStasi, Matthew R.; Feng, Hailin; Fisher, Alexa; Katz, Barry P.; Plett, P. Artur; Sandusky, George E.; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P.; MacVittie, Thomas J.; Orschell, Christie M.; Department of Surgery, School of MedicineThe threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.Item Effect of Lean Processes on Surgical Wait Times and Efficiency in a Tertiary Care Veterans Affairs Medical Center(AMA, 2017-01) Valsangkar, Nakul P.; Eppstein, Andrew C.; Lawson, Rick A.; Taylor, Amber N.; Department of Surgery, School of MedicineImportance There are an increasing number of veterans in the United States, and the current delay and wait times prevent Veterans Affairs institutions from fully meeting the needs of current and former service members. Concrete strategies to improve throughput at these facilities have been sparse. Objective To identify whether lean processes can be used to improve wait times for surgical procedures in Veterans Affairs hospitals. Design, Setting, and Participants Databases in the Veterans Integrated Service Network 11 Data Warehouse, Veterans Health Administration Support Service Center, and Veterans Information Systems and Technology Architecture/Dynamic Host Configuration Protocol were queried to assess changes in wait times for elective general surgical procedures and clinical volume before, during, and after implementation of lean processes over 3 fiscal years (FYs) at a tertiary care Veterans Affairs medical center. All patients evaluated by the general surgery department through outpatient clinics, clinical video teleconferencing, and e-consultations from October 2011 through September 2014 were included. Patients evaluated through the emergency department or as inpatient consults were excluded. Exposures The surgery service and systems redesign service held a value stream analysis in FY 2013, culminating in multiple rapid process improvement workshops. Multidisciplinary teams identified systemic inefficiencies and strategies to improve interdepartmental and patient communication to reduce canceled consultations and cases, diagnostic rework, and no-shows. High-priority triage with enhanced operating room flexibility was instituted to reduce scheduling wait times. General surgery department pilot projects were then implemented mid-FY 2013. Main Outcomes and Measures Planned outcome measures included wait time, clinic and telehealth volume, number of no-shows, and operative volume. Paired t tests were used to identify differences in outcome measures after the institution of reforms. Results Following rapid process improvement workshop project rollouts, mean (SD) patient wait times for elective general surgical procedures decreased from 33.4 (8.3) days in FY 2012 to 26.0 (9.5) days in FY 2013 (P = .02). In FY 2014, mean (SD) wait times were half the value of the previous FY at 12.0 (2.1) days (P = .07). This was a 3-fold decrease from wait times in FY 2012 (P = .02). Operative volume increased from 931 patients in FY 2012 to 1090 in FY 2013 and 1072 in FY 2014. Combined clinic, telehealth, and e-consultation encounters increased from 3131 in FY 2012 to 3460 in FY 2013 and 3517 in FY 2014, while the number of no-shows decreased from 366 in FY 2012 to 227 in FY 2014 (P = .02). Conclusions and Relevance Improvement in the overall surgical patient experience can stem from multidisciplinary collaboration among systems redesign personnel, clinicians, and surgical staff to reduce systemic inefficiencies. Monitoring and follow-up of system efficiency measures and the employment of lean practices and process improvements can have positive short- and long-term effects on wait times, clinical throughput, and patient care and satisfaction.Item Efficacy of Local Anesthetic With Dexamethasone on the Quality of Recovery Following Total Extraperitoneal Bilateral Inguinal Hernia Repair A Randomized Clinical Trial(AMA, 2016-12) Sakamoto, Bryan; Harker, Gene; Eppstein, Andrew C.; Gwirtz, Kenneth; Department of Surgery, School of MedicineImportance Quality of recovery (directly associated with patient satisfaction) is an important clinical outcome measurement and a surrogate of anesthetic/surgical care quality. Objectives To compare the efficacy of a transversus abdominis plane (TAP) block with dexamethasone sodium phosphate and preperitoneal instillation of local anesthetic (PILA) with dexamethasone vs control on postoperative quality of recovery following a bilateral total extraperitoneal inguinal hernia repair (TEP-IHR) (>24 hours). Secondary objectives included efficacy of this technique on postoperative opioid use, nausea and vomiting, and pain scores. Design, Setting, and Participants Conducted from November 2013 to August 2015, this randomized, prospective, single-blinded study compared 2 groups (a TAP block and PILA) with a standard anesthetic technique with no regional technique (control) following bilateral TEP-IHR. This study at the Veterans Affairs Medical Center (Indianapolis, Indiana) included patients ages 18 to 80 years with an American Society of Anesthesiologists physical status of 1 to 3 scheduled for an outpatient bilateral TEP-IHR. Nurses assigning pain scores and administrating opioids for pain and staff anesthesiologists administering the Quality of Recovery–40 (QoR-40) questionnaire were blinded. Interventions Patients randomized to receive a TAP block with local anesthetics and dexamethasone, PILA with dexamethasone, or no regional technique (3 groups). Main Outcomes and Measures Patient’s response to the QoR-40 questionnaire following a TEP-IHR surgery. Results The mean (SD) ages in the TAP block (n = 19), PILA (n = 24), and control (n = 23) groups were 58.2 (9.4) years, 62.5 (8.1) years, and 62.9 (7.8) years, respectively. The global QoR-40 scores on postoperative day 1 for the TAP block group (median [interquartile range (IQR)], 178 [173-188]) were comparable with the control group (median [IQR], 174 [150-181]), while the PILA group had better global QoR-40 scores (median [IQR], 184 [175.5-190.75]) (P = .002). The effects of the TAP block and PILA on pain in the postoperative care unit (PACU) (median [IQR], 1 [0-5] and 3.5 [0-6.8], respectively), pain after discharge (median [IQR], 3 [2-5] and 3 [1-5.5], respectively), opiate use after discharge (median [IQR], 6.7 [5-10] and 6.7 [3.3-10], respectively), and incidence of nausea and vomiting in the PACU (4 of 19 [21.1%] and 6 of 24 [25%], respectively) were not significantly different from the control group (median [IQR], 4 [3-6] for pain scores in the PACU; 4 [3-7] for pain scores after discharge; 6.7 [3.3-10] for opioid use after discharge; and 6 of 23 [26.1%] for incidence of nausea/vomiting in the PACU). While there was a significant reduction of opioid use in the PACU in the TAP block group (median [IQR], 0 [0-1.3]) when compared with the control group (median [IQR], 4 [1.3-6.7]) (P = .001), this was not seen in the PILA group (median [IQR], 2 [0-6.4]). Conclusions and Relevance This study demonstrates a better quality of recovery in patients’ receiving PILA with dexamethasone compared with control for a TEP-IHR surgery.Item Impact of Integrated Vascular Residencies on Academic Productivity within Vascular Surgery Divisions(Elsevier, 2017-02) Kim, Bradford J.; Valsangkar, Nakul P.; Liang, Tiffany W.; Murphy, Michael P.; Zimmers, Teresa A.; Bell, Teresa M.; Davies, Mark G.; Koniaris, Leonidas G.; Department of Surgery, School of MedicineBackground Changing training paradigms in vascular surgery have been introduced to reduce overall training time. Herein, we sought to examine how shortened training for vascular surgeons may have influenced overall divisional academic productivity. Methods Faculty from the top 55 surgery departments were identified according to National Institutes of Health (NIH) funding. Academic metrics of 315 vascular surgery, 1,132 general surgery, and 2,403 other surgical specialties faculty were examined using institutional Web sites, Scopus, and NIH Research Portfolio Online Reporting Tools from September 1, 2014, to January 31, 2015. Individual-level and aggregate numbers of publications, citations, and NIH funding were determined. Results The mean size of the vascular divisions was 5 faculty. There was no correlation between department size and academic productivity of individual faculty members (R2 = 0.68, P = 0.2). Overall percentage of vascular surgery faculty with current or former NIH funding was 20%, of which 10.8% had major NIH grants (R01/U01/P01). Vascular surgery faculty associated with integrated vascular training programs demonstrated significantly greater academic productivity. Publications and citations were higher for vascular surgery faculty from institutions with both integrated and traditional training programs (48 of 1,051) compared to those from programs with integrated training alone (37 of 485) or traditional fellowships alone (26 of 439; P < 0.05). Conclusions In this retrospective examination, academic productivity was improved within vascular surgery divisions with integrated training programs or both program types. These data suggest that the earlier specialization of integrated residencies in addition to increasing dedicated vascular training time may actually help promote research within the field of vascular surgery.Item Management of the Pressure Injury Patient with Osteomyelitis: An Algorithm(Elsevier, 2017) Nicksic, Peter J.; Sasor, Sarah E.; Tholpady, Sunil S.; Wooden, William A.; Gutwein, Luke G.; Department of Surgery, School of MedicinePressure injury (PI) is a common complication of inpatient care, affecting an estimated 3 million patients annually in the US. Risk factors include immobility, compromised sensation, malnutrition, urinary or fecal incontinence, and chronic medical illness. Compliance with established guidelines (pressure off-loading, skin care, and frequent inspection) is imperative for the prevention of hospital-acquired PI. Unavoidable PI does occur at times, and is often related to advanced medical illness. Pressure injury complicated by osteomyelitis (OM) can develop in patients with physiologic, behavioral, or treatment-related risk factors, despite the adherence to current standards of prevention.Item Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasi(Elsevier, 2017) Yip-Schneider, Michele T.; Carr, Rosalie A.; Wu, Huangbing; Schmidt, C. Max; Department of Surgery, School of MedicineBackground With the increased frequency of diagnostic imaging, pancreatic cysts are now detected in >3% of American adults. Most of these are intraductal papillary mucinous neoplasms (IPMNs) with well-established but variable malignant potential. A biomarker that predicts malignant potential or dysplastic grade would help determine which IPMNs require removal and which can be observed safely. We previously reported that pancreatic fluid prostaglandin E2 (PGE2) levels might have promise as a predictor of IPMN dysplasia and we seek to validate those results in the current study. Study Design Pancreatic cyst/duct fluid was prospectively collected from 100 patients with IPMN undergoing pancreatic resection. Surgical pathology revealed 47 low-/moderate-grade, 34 high-grade, and 20 invasive IPMNs. The PGE2 levels were assessed by ELISA and correlated with IPMN dysplasia grade, demographics, clinical radiologic/pathologic variables, acute/chronic pancreatitis, and NSAID use. Results Mean pancreatic cyst fluid PGE2 levels in high-grade and invasive IPMNs were significantly higher than low-/moderate-grade IPMNs (3.5 and 4.4 pg/μL, respectively, vs 1.2 pg/μL; p < 0.0016). At a threshold of 1.1 pg/μL, PGE2 was 63% sensitive, 79% specific, and 71% accurate for detection of high-grade/invasive IPMNs. When tested in the subset of IPMN patients with preoperative pancreatic cyst fluid CEA >192 ng/mL, PGE2 at a threshold of 0.5 pg/μL demonstrated 78% sensitivity, 100% specificity, and 86% accuracy for detection of high-grade/invasive IPMN. Conclusions Our results validate pancreatic cyst fluid PGE2 as an indicator of IPMN dysplasia, especially in select patients with preoperative pancreatic cyst fluid CEA >192 ng/mL. The inclusion of PGE2/CEA in a diagnostic biomarker panel can facilitate more optimal treatment stratification of IPMN patients.Item The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation(Hindawi, 2017) Samy, Kannan P.; Butler, James R.; Li, Ping; Cooper, David K. C.; Ekser, Burcin; Department of Surgery, School of MedicinePig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical xenotransplantation. Costimulation blockade agents have been introduced in xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical xenotransplantation and the potential for future application.Item A Surgery Trainee’s Guide to Writing a Manuscript(Elsevier, 2017-09) Liang, Tiffany W.; Feliciano, David V.; Koniaris, Leonidas G.; Department of Surgery, School of MedicinePublishing clinical and research work for dissemination is a critical part of the academic process. Learning how to write an effective manuscript should be a goal for medical students and residents who hope to participate in publishing. While there are a number of existing texts that address how to write a manuscript, there are fewer guides that are specifically targeted towards surgery trainees. This review aims to direct and hopefully encourage surgery trainees to successfully navigate the process of converting ideas into a publication that ultimately helps understanding and improves the care of patients.