Timothy L Pruett

Case Western Reserve University, Cleveland, Ohio, United States

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Publications (290)1279.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). Background: Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. Methods: In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. Results: In our patients, the duration (mean ± SD) of CP before their TP-IAT was 7.1 ± 0.3 years and narcotic usage of 3.3 ± 0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. Conclusions: This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.
    Annals of surgery 09/2015; 262(4):610-622. DOI:10.1097/SLA.0000000000001453 · 8.33 Impact Factor
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    ABSTRACT: There are little data on long-term outcomes, health-related quality of life (HRQoL), and specifically issues related to living donor right hepatectomy. We studied Long-term health-related quality of life in 127 living liver donors. A donor specific survey (DSS) was used to evaluate the living liver-donor morbidity and the 36-item short form health survey (SF-36) was used to assess generic outcomes. The DSS was completed by 107 (84.3%) donors and the SF-36 by 62 (49%) donors. Median follow-up was 6.9 years. Twelve donors (11.2%) reported their health as better, while 84 (78.5%) reported their health the same as pre-donation. Ninety-seven (90.7%) are currently employed. The most common post-donation symptom was incisional discomfort (34%). Twenty-four donors (22.4%) self-reported depression symptoms post donation. Ninety-eight (91.6%) rated their satisfaction with the donation process ≥ 8 (scale of 1-10). Three factors, increased vitality (correlation 0.44), decreased pain (correlation 0.34), and a recipient who was living (correlation 0.44), were independently related to satisfaction with the donor experience. Vitality showed the strongest association with satisfaction with the donor experience. Mental and Physical Component Summary scale scores for donors were statistically higher compared to US population norm (p=<.001). Donors reported a high satisfaction rate with the donation process and almost all donors (n = 104, 97.2%) would donate again independent of experiencing complications. Our study suggests that long-term, liver donors continue to have above average HRQoL compared to the general population. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 08/2015; DOI:10.1002/lt.24304 · 4.24 Impact Factor
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    ABSTRACT: Total pancreatectomy with islet cell autotransplant (TPIAT) is a definitive therapeutic approach to pain management for patients with chronic pancreatitis that is non-responsive to maximum medical management. Total pancreatectomy (TP) results in brittle diabetes unless islet cell autotransplant (IAT) is concomitantly performed. Even with IAT, about 30 % of patients will require long-term basal-bolus insulin therapy due to significant endocrine insufficiency. The focus of this review is on the utility of whole organ pancreas transplantation toward improving quality of life, and decreasing the risk of mortality and overall cost of care for the subset of patients who experience endocrine and exocrine deficiency after pancreatic resection.
    06/2015; 2(2). DOI:10.1007/s40472-015-0057-6
  • Gastroenterology 04/2015; 148(4):S-977. DOI:10.1016/S0016-5085(15)33339-4 · 16.72 Impact Factor
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    Varvara A. Kirchner · Patty T Liu · Timothy L. Pruett
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    ABSTRACT: Twenty-one percent of transplants in the US come from live donors. Data show that live-donor transplantation is a safe practice, but is not completely risk free. Malignancy and infection transmission through live organ donation is extremely rare, but can be a devastating event for the recipient, donor and treatment team if it occurs. The donor evaluation is multifactorial, taking into the account the unique medical, social and family history of individual donors, needs of the recipient, and determination of the anatomic and functional suitability of the donor organ, and is further complicated by geographical and temporal components. While balancing all practical considerations can be complex, a thorough medical assessment for infection and malignancy of potential living donor is central in protecting the donor and the intended transplant recipient.
    03/2015; 2(1). DOI:10.1007/s40472-014-0049-y
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    ABSTRACT: Background: Chronic pancreatitis is a painful and often debilitating disease. Total pancreatectomy with intra-portal islet autotransplantation (TP-IAT) is a treatment option that allows for pain relief and preservation of beta-cell mass, thereby minimizing the complication of diabetes mellitus. Cultures of harvested islets are often positive for bacteria, possibly due to frequent procedures prior to TP-IAT, such as endoscopic retrograde cholangiopancreatography (ERCP), stenting, or other operative drainage procedures. It is unclear if these positive cultures contribute to post-operative infections. Hypothesis: We hypothesized that positive cultures of transplant solutions will not be associated with increased infection risk. Methods: We reviewed retrospectively the sterility cultures from both the pancreas preservation solution used to transport the pancreas and the final islet preparation for intra-portal infusion of patients who underwent TP-IAT between April 2006 and November 2012. Two hundred fifty-one patients underwent total, near-total, or completion pancreatectomy with IAT and had complete sterility cultures. All patients received prophylactic peri-operative antibiotics. Patients with positive pancreas preservation solution or islet sterility cultures received further antibiotics for 5-7 d. Patients' medical records were reviewed for post-operative infections and causative organisms. Results: Of the 251 patients included, 151 (61%) had one or more positive bacterial cultures from the pancreas preservation solution or final islet product. Seventy-three of the 251 patients (29%) had an infectious complication. Thirty-four of the 73 (22%) patients with a post-operative infectious complication also had positive cultures. Only seven of 151 patients with positive cultures (4.7%) had an infectious complication caused by the same organism as that isolated from their pancreas or islet cell preparation. Conclusions: In autologous islet preparations, isolation solutions frequently have positive cultures, but this finding is associated infrequently with clinical infection.
    Surgical Infections 02/2015; 16(2). DOI:10.1089/sur.2013.224 · 1.45 Impact Factor
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    ABSTRACT: An adult--to-adult living donor liver transplant (LDLT) has emerged as a possible option to help alleviate the organ shortage. We evaluated biliary complications in a cohort of 120 LDLT recipients at a single institution and studied the impact on long--term graft and patient survival. Of the 120 recipients, 26 (21.7%) developed biliary complications. Endoscopy was the initial choice of treatment for recipients with biliary complications. The median time for resolution of bile leaks was 37 days; for resolution of strictures, 82 days. A decreased risk of biliary complications was associated with an interrupted duct-to--duct (versus continuous choledocho---choledochostomy) (hazard ratio [HR] = 0.22, P = 0.002) and a Roux--en-Y hepaticojejunostomy (HR = 0.13, P < 0.001). In multivariate analysis of factors associated with graft failure and patient mortality, biliary complications were unrelated to long term (3yr and 5 year) graft failure or patient mortality. In conclusion, in our study, LDLT recipients had a 21.7% incidence of biliary complications, however, with successful endoscopic techniques, long-term patient and graft survival rates were not negatively affected.
    Minerva chirurgica 02/2015; · 0.68 Impact Factor
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    ABSTRACT: The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections and malignancies, to assess for donor transmitted events. Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.
    Transplantation 01/2015; 99(2). DOI:10.1097/TP.0000000000000584 · 3.83 Impact Factor
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    ABSTRACT: In a large cohort of subjects undergoing total pancreatectomy with islet autotransplantation (TPIAT), we assessed the prevalence and duration of gastrointestinal (GI) symptoms before and after the procedure to determine the impact of enzyme adherence on GI symptoms. Three hundred fifty-six preoperative and postoperative questionnaires were collected from 184 subjects between ages of 5 and 66 years who underwent TPIAT between 2008 and 2011 at the University of Minnesota. Questionnaires were analyzed for self-reported frequency and severity of GI symptoms, pancreatic enzyme usage, and glycemic variability index (GVI). After surgery, patient-reported steatorrhea increased whereas constipation decreased. Gastrointestinal symptoms interfered with daily activity in 44% to 69% of subjects, before and after surgery, despite high reported enzyme adherence. Postoperatively, more than 79% of subjects reported consistent use of enzymes at all meals. Presence of GI symptoms did not vary with adherence. The GVI of 2 had a 2.8-fold increased odds of steatorrhea (95% confidence interval, 1.1-7.0) compared with GVI of 0. Gastrointestinal symptoms were common after TPIAT; ongoing management is needed. Enzyme nonadherence was not a major contributor to diarrhea/steatorrhea in this cohort. Glycemic variability was closely associated with steatorrhea; poor response to enzyme replacement may complicate diabetes management.
    Pancreas 12/2014; 44(3). DOI:10.1097/MPA.0000000000000266 · 2.96 Impact Factor
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    ABSTRACT: The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.
    American Journal of Transplantation 11/2014; 15(1). DOI:10.1111/ajt.12978 · 5.68 Impact Factor
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    ABSTRACT: We utilized intravenous arginine with measurements of insulin, C-peptide, and glucagon to examine β-cell and α-cell survival and function in a group of 10 chronic pancreatitis recipients 1-8 years after total pancreatectomy and autoislet transplantation (TP/IAT). Insulin and C-peptide responses correlated robustly with the number of islets transplanted (correlation coefficients range = 0.81-0.91; p<0.01- 0.001). Since a wide range of islets were transplanted, we normalized the insulin and C-peptide responses to the number of islets transplanted in each recipient for comparison with responses in normal subjects. No significant differences were observed in terms of magnitude and timing of hormone release in the two groups. Three recipients had a portion of the autoislets placed within their peritoneal cavities, which appeared to be functioning normally up to 7 years post-transplant. Glucagon responses to arginine were normally timed and normally suppressed by intravenous glucose infusion. These findings indicate that arginine stimulation testing may be a means of assessing the numbers of native islets available in autologous islet transplant candidates and is a means of following post-transplant α- and β- cell function and survival.
    Diabetes 09/2014; 64(2). DOI:10.2337/db14-0690 · 8.10 Impact Factor
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    ABSTRACT: Background Solid organ transplant (SOT) recipients carry a high risk of developing Clostridium difficile-associated colitis (CDAC) and an increased risk for recurrence. Patients and methods Between December 1996 and September 2007, a total of 227 patients with CDAC were identified when querying our institutional surgical infection database. This included 169 nontransplant patients and 58 SOT recipients, including 1 cardiac, 19 renal, 2 pancreas, 5 renal/pancreas, and 31 liver recipients. Results Overall, we recorded 556 infectious episodes at any site in the 227 patients analyzed who eventually developed CDAC (2.4 episodes/patient); the total number of CDAC episodes was 255: 204 patients had a single episode and 23 patients had multiple episodes of CDAC. There were 19 patients with two episodes, 3 with three episodes, and 1 with four episodes. Of the 23 patients with recurrent CDAC, 11 (48 %) were SOT recipients. A total of 19 % of SOT recipients had recurrent CDAC as compared with only 7 % for nontransplant patients (p = 0.0197). Time to first CDAC recurrence was a median of 58 (range, 17-1372) days for SOT recipients and a median of 30 (range, 6-108) days for nontransplant patients (p = 0.047). Conclusions SOT recipients at our institution were found to be a high-risk group for CDAC and had an almost threefold risk for recurrent disease. Double-drug coverage, extended application of metronidazole, and profound reduction in the level of immunosuppression may help to cope with this emerging problem.
    European Surgery 08/2014; 46(4):160-164. DOI:10.1007/s10353-014-0279-3 · 0.27 Impact Factor
  • Timothy L. Pruett
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    ABSTRACT: The performance of organ transplantation requires healthcare providers with multiple skills and diverse institutional resources. To generate a sustainable transplant care delivery system, it is necessary to effectively compensate the individuals and the organizations necessary for this service. The payment structure for transplantation and organ donation services in the US has become highly intertwined with governmental regulation and oversight. Therefore, it is necessary to understand the nature and extent of governmental oversight and authority over the transplant system to better understand how governmental payments and private insurers are impacted. Furthermore, understanding how information enters the public domain, and the differences between the intended and actual use of those data has become necessary for transplant providers.
    Textbook of Organ Transplantation, 07/2014: pages 1673-1678; , ISBN: 9781118870143
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    ABSTRACT: Defective glucagon secretion during hypoglycemia after islet transplantation has been reported in animals and humans with type 1 diabetes. To ascertain whether this is true of islets from nondiabetic humans, subjects with autoislet transplantation in the intrahepatic site only (TP/IAT-H) or in intrahepatic plus nonhepatic (TP/IAT-H+NH) sites were studied. Glucagon responses were examined during stepped hypoglycemic clamps. Glucagon and symptom responses during hypoglycemia were virtually absent in subjects who received islets in the hepatic site only (glucagon increment over baseline = 1 ± 6, pg/mL, mean ± SE, n = 9, p = ns; symptom score = 1 ± 1, p = ns). When islets were transplanted in both intrahepatic + nonhepatic sites, glucagon and symptom responses were not significantly different than Control Subjects (TP/IAT-H + NH: glucagon increment = 54 ± 14, n = 5; symptom score = 7 ± 3; control glucagon increment = 67 ± 15, n = 5; symptom score = 8 ± 1). In contrast, glucagon responses to intravenous arginine were present in TP/IAT-H recipients (TP/IAT: glucagon response = 37 ± 8, n = 7). Transplantation of a portion of the islets into a nonhepatic site should be seriously considered in TP/IAT to avoid posttransplant abnormalities in glucagon and symptom responses to hypoglycemia.
    American Journal of Transplantation 07/2014; 14(8). DOI:10.1111/ajt.12776 · 5.68 Impact Factor
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    ABSTRACT: Objectives: Diagnosis of non-calcific chronic pancreatitis (NCCP) in patients presenting with chronic abdominal pain is challenging and controversial. Contrast-enhanced magnetic resonance imaging (MRI) with secretin-stimulated MRCP (sMRCP) offers a safe and noninvasive modality to diagnose mild CP, but its findings have not been correlated with histopathology. We aimed to assess the correlation of a spectrum of MRI/sMRCP findings with surgical histopathology in a cohort of NCCP patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). Methods: Adult patients undergoing TPIAT for NCCP between 2008 and 2013 were identified from our institution's surgery database and were included if they had MRI/sMRCP within a year before surgery. Histology was obtained from resected pancreas at the time of TPIAT by wedge biopsy of head, body, and tail, and was graded by a gastrointestinal pathologist who was blinded to the imaging features. A fibrosis score (FS) of 2 or more was considered as abnormal, with FS ≥6 as severe fibrosis. A multivariate regression analysis was performed for MRI features predicting fibrosis, after taking age, sex, smoking, alcohol, and body mass index (BMI) into consideration. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation coefficient (r) was calculated. Results: Fifty-seven patients (females=49, males=8) with NCCP and MRI/sMRCP were identified. ROC curve analysis showed that two or more MRI/sMRCP features provided the best balance of sensitivity (65%), specificity (89%), and accuracy (68%) to differentiate abnormal (FS≥2) from normal pancreatic tissue. Two or more features provided the best cutoff (sensitivity 88%, specificity 78%) for predicting severe fibrosis (FS≥6). There was a significant correlation between the number of features and severity of fibrosis (r=0.6, P<0.0001). A linear regression after taking age, smoking, and BMI into consideration showed that main pancreatic duct irregularity, T1-weighted signal intensity ratio between pancreas and paraspinal muscle, and duodenal filling after secretin injection to be significant independent predictors of fibrosis. Conclusions: A strong correlation exists between MRI/sMRCP findings and histopathology of NCCP.Am J Gastroenterol advance online publication, 15 September 2015; doi:10.1038/ajg.2015.297.
    Gastroenterology 05/2014; 146(5):S-2–S-3. DOI:10.1016/S0016-5085(14)60007-X · 16.72 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-1046. DOI:10.1016/S0016-5085(14)63814-2 · 16.72 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-3. DOI:10.1016/S0016-5085(14)60009-3 · 16.72 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-136-S-137. DOI:10.1016/S0016-5085(14)60483-2 · 16.72 Impact Factor
  • Gastrointestinal Endoscopy 05/2014; 79(5):AB443-AB444. DOI:10.1016/j.gie.2014.02.633 · 5.37 Impact Factor
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    ABSTRACT: Background Chronic-pancreatitis is a debilitating-disease resulting from many etiologies. The-subset with hereditary/genetic defects (HGP) not only has chronic-pain, but also an increased-risk for pancreatic-cancer. The long-term-outcomes of TP-IAT for chronic pancreatitis due-to-HGP are not clear. Study Design Review of a prospectively-maintained-database of 484 TP-IAT-from-1977-2012 at a single-center. The-outcomes (pain-relief, narcotic-use, β cell-function, health-related quality of-life-measures of patients-that-received TP-IAT for hereditary/genetic-defects (PRSS1 (n=38), SPINK1 (n=9), CFTR (n=14) and Familial (n=19) were-evaluated-and-compared to those with non-hereditary/genetic-etiology. Results All 80 patients with HGP were narcotic-dependent and failed-endoscopic-management or direct-pancreatic-surgery. Post TP-IAT, 90% of the patients-were-pancreatitis-pain-free with sustained-pain-relief; over 65% had partial or full β-cell-function. Compared to non-hereditary etiologies, HGP were-younger (22 yrs vs.38 yrs p=<0.001), had-pancreatitis-pain of longer-duration (11.6±1.1 vs. 9.0±0.4 yrs p=0.016) , had a higher-pancreas-fibrosis-score (7±0.2 vs. 4.8±0.1 p=<0.001), and-trended-toward-lower-Islet-yield (3,435 ± 361 IEQ vs. 3850± 128 IEQ p=0.28). Using-multivariate-logistic-regression, (1) non-HGP-etiology (p value=0.019) (2) lower severity-of-pancreas-fibrosis (p value < 0.001), (3) shorter-duration-of-years with pancreatitis (p value = 0.008) and (4) higher-transplant IEQ per KG body-weight (p value =<0.001) were-more likely-to-achieve-insulin-independence (p value < 0.001). There was a significant-improvement in HRQoL from-baseline, by SF-36, in physical-and-mental-component HRQoL scores (p <0.001). None-of-the-patients in the entire-cohort-developed-cancer of pancreatic-origin in the liver or elsewhere during 2,936 person-years of follow-up. Conclusions TP-IAT in patients with chronic pancreatitis due to HGP etiology provides long- term pain relief (90%) and preservation-of-beta-cell-function. Patients with chronic-painful pancreatitis due to HGP with a high-life-time-risk of pancreatic-cancer should be considered earlier for TP-IAT before pancreatic-inflammation results in higher-degree of pancreatic-fibrosis and islet-cell-function-loss.
    Journal of the American College of Surgeons 04/2014; 218(4). DOI:10.1016/j.jamcollsurg.2013.12.037 · 5.12 Impact Factor

Publication Stats

7k Citations
1,279.31 Total Impact Points


  • 2015
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 2011–2015
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
  • 2013
    • Saint Mary's University of Minnesota
      Minneapolis, Minnesota, United States
  • 1991–2011
    • University of Virginia
      • • Department of Surgery
      • • Department of Medicine
      Charlottesville, Virginia, United States
  • 2006–2009
    • Virginia Department of Health
      Richmond, Virginia, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2007–2008
    • University of Pittsburgh
      • Division of Infectious Diseases
      Pittsburgh, Pennsylvania, United States
  • 1995–2008
    • University of Michigan
      • • Department of Internal Medicine
      • • Department of Surgery
      Ann Arbor, Michigan, United States
  • 1992–2007
    • University of Rochester
      • • Department of Surgery
      • • School of Medicine and Dentistry
      Rochester, New York, United States
  • 2005
    • Baylor University
      Waco, Texas, United States
  • 1997
    • Indiana University-Purdue University Indianapolis
      • Department of Surgery
      Indianapolis, IN, United States
  • 1996
    • University of Louisville
      Louisville, Kentucky, United States
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States