Ergun Velidedeoglu
University of Pennsylvania
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Featured researches published by Ergun Velidedeoglu.
Transplantation | 2004
Niraj M. Desai; Kevin C. Mange; Michael D. Crawford; Peter L. Abt; Adam Frank; Joseph W. Markmann; Ergun Velidedeoglu; William C. Chapman; James F. Markmann
Background. The Model for End-Stage Liver Disease (MELD) has been found to accurately predict pretransplant mortality and is a valuable system for ranking patients in greatest need of liver transplantation. It is unknown whether a higher MELD score also predicts decreased posttransplant survival. Methods. We examined a cohort of patients from the United Network for Organ Sharing (UNOS) database for whom the critical pretransplant recipient values needed to calculate the MELD score were available (international normalized ratio of prothrombin time, total bilirubin, and creatinine). In these 2,565 patients, we analyzed whether the MELD score predicted graft and patient survival and length of posttransplant hospitalization. Results. In contrast with its ability to predict survival in patients with chronic liver disease awaiting liver transplant, the MELD score was found to be poor at predicting posttransplant outcome except for patients with the highest 20% of MELD scores. We developed a model with four variables not included in MELD that had greater ability to predict 3-month posttransplant patient survival, with a c-statistic of 0.65, compared with 0.54 for the pretransplant MELD score. These pretransplant variables were recipient age, mechanical ventilation, dialysis, and retransplantation. Recipients with any two of the three latter variables showed a markedly diminished posttransplant survival rate. Conclusions. The MELD score is a relatively poor predictor of posttransplant outcome. In contrast, a model based on four pretransplant variables (recipient age, mechanical ventilation, dialysis, and retransplantation) had a better ability to predict outcome. Our results support the use of MELD for liver allocation and indicate that statistical modeling, such as reported in this article, can be used to identify futile cases in which expected outcome is too poor to justify transplantation.
Annals of Surgery | 2003
James F. Markmann; Shaoping Deng; Xiaolun Huang; Niraj M. Desai; Ergun Velidedeoglu; Chengyang Lui; Adam Frank; Eileen Markmann; Maral Palanjian; Kenneth L. Brayman; Bryan A. Wolf; Ewan Bell; Marko Vitamaniuk; Nicolai M. Doliba; Franz M. Matschinsky; Clyde F. Barker; Ali Naji
ObjectiveTo restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. Summary Background DataThe recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. MethodsThe authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. ResultsIn each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. ConclusionsThis report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.
Nature Medicine | 2007
Chengyang Liu; Hooman Noorchashm; Jennifer A. Sutter; Mina Naji; Eline T. Luning Prak; Jean D. Boyer; Taryn Green; Michael R. Rickels; John E. Tomaszewski; Brigitte Koeberlein; Zhonglin Wang; Michelle Paessler; Ergun Velidedeoglu; Susan Y. Rostami; Ming Yu; Clyde F. Barker; Ali Naji
We found that an induction immunotherapy regimen consisting of rabbit anti-thymocyte globulin (Thymoglobulin) and the monoclonal antibody to CD20 rituximab (Rituxan) promoted long-term islet allograft survival in cynomolgus macaques maintained on rapamycin monotherapy. B lymphocyte reconstitution after rituximab-mediated depletion was characterized by a preponderance of immature and transitional cells, whose persistence was associated with long-term islet allograft survival. Development of donor-specific alloantibodies was abrogated only in the setting of continued rapamycin monotherapy.
Transplantation | 2002
Ergun Velidedeoglu; Noel N. Williams; Kenneth L. Brayman; Niraj M. Desai; Luis Campos; Maral Palanjian; Martin Wocjik; Roy D. Bloom; Robert A. Grossman; Kevin C. Mange; Clyde F. Barker; Ali Naji; James F. Markmann
Background. Minimally invasive donor nephrectomy has become a favored procedure for the procurement of kidneys from live donors. The optimal minimally invasive surgical approach has not been determined. In the current work, we compared the outcome of kidneys procured using the traditional open approach with two minimally invasive techniques: the standard laparoscopic procedure and a hand-assist procedure. Methods. The function of live-donor kidneys procured by open versus minimally invasive procedures was compared (procedures compared were the traditional open donor nephrectomy [ODN], the standard laparoscopic [LAP] approach, and the hand-assisted [HA] laparoscopic technique). The length of donor operation, donor length of stay in the hospital, surgical complications, and cost of hospitalization for three groups of patients were assessed in a series of 150 live-donor nephrectomies. Results. We found that both minimally invasive procedures yielded kidney allografts with excellent early function and a minimum of complications in the donor. The open procedure was associated with a reduced operative time but increased donor length of stay in the hospital. Resource utilization analysis revealed that both minimally invasive techniques were associated with a slight increase in costs compared with the open procedure, despite a shorter hospital stay. Conclusions. Minimally invasive donor nephrectomy is safe and effective for procuring normally functioning organs for live-donor transplantation. Of the two minimally invasive approaches examined, the hand-assisted technique was found to afford a number of important advantages, including facilitating teaching of residents and students, that it is more readily mastered by transplant surgeons, and that it may provide an additional margin of safety for the donor.
Transplantation | 2003
James F. Markmann; Shaoping Deng; Niraj M. Desai; Xiaolun Huang; Ergun Velidedeoglu; Adam Frank; Chengyang Liu; Kenneth L. Brayman; Moh Moh Lian; Bryan A. Wolf; Ewan Bell; Marko Vitamaniuk; Nicolai M. Doliba; Franz M. Matschinsky; Eileen Markmann; Clyde F. Barker; Ali Naji
Recent improvements in isolated islet transplantation indicate that this therapy may ultimately prove applicable to patients with type I diabetes. An obstacle preventing widespread application of islet transplantation is an insufficient supply of cadaveric pancreata. Non-heart-beating donors (NHBDs) are generally not deemed suitable for whole-organ pancreas donation and could provide a significant source of pancreata for islet transplantation. Isolated pancreatic islets prepared from 10 NHBDs were compared with those procured from 10 brain-dead donors (BDDs). The success of the isolation for the two groups was analyzed for preparation purity, quality, and recovered islet mass. The function of NHBD and BDD islets was evaluated using in vitro and in vivo assays. On the basis of the results of this analysis, an NHBD isolated islet allograft was performed in a type I diabetic. The recovery of islets from NHBDs was comparable to that of control BDDs. In vitro assessment of NHBD islet function revealed function-equivalent BDD islets, and NHBD islets transplanted to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice efficiently reversed diabetes. Transplantation of 446,320 islet equivalents (IEq) (8,500 IEq/kg of recipient body weight) from a single NHBD successfully reversed the diabetes of a type I diabetic recipient. Normally functioning pancreatic islets can be isolated successfully from NHBDs. A single donor transplant from an NHBD resulted in a state of stable insulin independence in a type I diabetic recipient. These results indicate that NHBDs may provide an as yet untapped source of pancreatic tissue for preparation of isolated islets for clinical transplantation.
Transplantation | 2004
Ergun Velidedeoglu; Kevin C. Mange; Adam Frank; Peter L. Abt; Niraj M. Desai; Joseph W. Markmann; Rajender Reddy; James F. Markmann
Background. Survival following liver transplantation for hepatitis C virus (HCV) is significantly poorer than for liver transplants performed for other causes of chronic liver disease. The factors responsible for the inferior outcome in HCV+ recipients, and whether they differ from factors associated with survival in HCV- recipients, are unknown. Methods. The UNOS database was analyzed to identify factors associated with outcome in HCV+ and HCV- recipients. Kaplan-Meier graft and patient survival and Cox proportional hazards analysis were conducted on 13,026 liver transplants to identify the variables that were differentially associated with outcome survival in HCV- and HCV+ recipients. Results. Of the 13,026 recipients, 7386 (56.7%) were HCV- and 5640 were HCV+. In HCV- and HCV+ recipient populations, five-year patient survival rates were 83.5% vs. 74.6% (P<0.00001) and five-year graft survival rates 80.6% vs. 69.9% (P<0.00001), respectively. In a multivariate regression model, donor age and recipient creatinine were observed to be significant covariates in both groups, while donor race, cold ischemia time (CIT), female to male transplants, and recipient albumin were independent predictors of survival of HCV- recipients. In the HCV+ cohort, recipient race, warm ischemia time (WIT), and diabetes also independently predicted graft survival. Conclusions. A number of parameters are differentially correlated with outcome in HCV- and HCV+ recipients of orthotopic liver transplantion. These findings may not only have practical implications in the selection and management of liver transplant patients, but also may shed new insight into the biology of HCV infection posttransplant.
Annals of Surgery | 2004
Adam M. Frank; Shaoping Deng; Xiaolun Huang; Ergun Velidedeoglu; Yong-Suk Bae; Chengyang Liu; Peter L. Abt; Robert Stephenson; Muhammad Mohiuddin; Thav Thambipillai; Eileen Markmann; Maral Palanjian; Marty T. Sellers; Ali Naji; Clyde F. Barker; James F. Markmann
Objective:We sought to compare the efficacy, risks, and costs of whole-organ pancreas transplantation (WOP) with the costs of isolated islet transplantation (IIT) in the treatment of patients with type I diabetes mellitus. Summary Background Data:A striking improvement has taken place in the results of IIT with regard to attaining normoglycemia and insulin independence of type I diabetic recipients. Theoretically, this minimally invasive therapy should replace WOP because its risks and expense should be less. To date, however, no systematic comparisons of these 2 options have been reported. Methods:We conducted a retrospective analysis of a consecutive series of WOP and IIT performed at the University of Pennsylvania between September 2001 and February 2004. We compared a variety of parameters, including patient and graft survival, degree and duration of glucose homeostasis, procedural and immunosuppressive complications, and resources utilization. Results:Both WOP and IIT proved highly successful at establishing insulin independence in type I diabetic patients. Whole-organ pancreas recipients experienced longer lengths of stay, more readmissions, and more complications, but they exhibited a more durable state of normoglycemia with greater insulin reserves. Achieving insulin independence by IIT proved surprisingly more expensive, despite shorter initial hospital and readmission stays. Conclusion:Despite recent improvement in the success of IIT, WOP provides a more reliable and durable restoration of normoglycemia. Although IIT was associated with less procedure-related morbidity and shorter hospital stays, we unexpectedly found IIT to be more costly than WOP. This was largely due to IIT requiring islets from multiple donors to gain insulin independence. Because donor pancreata that are unsuitable for WOP can often be used successfully for IIT, we suggest that as IIT evolves, it should continue to be evaluated as a complementary alternative to rather than as a replacement for the better-established method of WOP.
Transplantation | 2002
Ergun Velidedeoglu; Niraj M. Desai; Louis Campos; Kim M. Olthoff; Abraham Shaked; Frederick A. Nunes; Gillian Zeldin; Charmaine A. Stewart; Emily A. Blumberg; John D. Abrams; James F. Markmann
BACKGROUND The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. The survival of grafts from HCV+ donors has not been studied in detail. METHODS Two study populations were examined retrospectively to assess the survival of liver grafts procured from HCV+ donors. First, we evaluated the survival of all 13 HCV+ and 103 HCV- grafts that were transplanted at our institution to HCV+ recipients from January 1, 1995 to December 31, 1999. In parallel, we analyzed a subset of the United Network for Organ Sharing (UNOS) liver transplant database from the same 5-year time period that was comprised of 14,195 adult patients for whom donor and recipient HCV serologies were known. Kaplan-Meier graft survival for both patient populations was calculated based on donor and recipient HCV serologic status. A Cox proportional hazards analysis was performed on UNOS data to identify variables independently predicting graft survival. RESULTS For transplants performed at our institution, we found no statistically significant difference in the Kaplan-Meier graft survival of HCV+ and HCV- grafts transplanted to HCV+ recipients (P=0.68). The incidence of biopsy-proven, recurrent HCV posttransplant was similar in recipients receiving either HCV+ or HCV- grafts (4/13 vs. 18/103, chi-square P=0.211). Analysis of UNOS data revealed that the survival of HCV+ grafts in HCV+ recipients was equivalent to the survival of HCV- grafts in HCV+ recipients. Unexpectedly, the survival of grafts in HCV+ recipients in general was significantly inferior to that of grafts in HCV- recipients. Multivariate analysis of all patients found recipient but not donor HCV status to be independently predictive of graft survival. CONCLUSIONS Analysis of data from a single center and the national UNOS database suggests that transplantation of liver allografts from HCV+ donors to HCV+ recipients results in graft survival comparable to HCV- grafts transplanted to HCV+ recipients. In contrast, recipient HCV positivity is an independent predictor of graft failure compared with patients transplanted for other causes of liver disease.
Transplantation | 2004
Ergun Velidedeoglu; Roy D. Bloom; Michael D. Crawford; Niraj M. Desai; Luis Campos; Peter L. Abt; Joseph W. Markmann; Kevin C. Mange; Kim M. Olthoff; Abraham Shaked; James F. Markmann
Background. Acute and chronic renal dysfunction (ARD, CRD) are common complications after liver transplantation and are associated with poor outcome. Methods. We reviewed the results of 181 liver transplants performed in our institution between January 1, 1998 and December 31, 2000 in which the recipients were alive with good liver function at the end of the follow-up period (mean 2.7 years). Renal dysfunction was defined as a serum creatinine (Cr) greater than or equal to 2 mg/dL in both acute and chronic settings. Results. The incidence of ARD during the first posttransplant week was 39.2% (n=71), whereas late CRD occurred in 6.0% (n=11) of the patients by the end of the follow-up period. Among the variables we examined for association with CRD, five factors were found to be statistically significant in univariate analysis: pretransplant diabetes (PRTDM) (0.000), Cr greater than or equal to 2 during the first postoperative week (0.003), posttransplant diabetes (POTDM) (0.014), age greater than 50 (0.025), and tacrolimus level greater than 15 ng/mL at postoperative day 15 (0.058). In binary logistic regression analysis, PRTDM (odds ratio [OR]=5.7, 95% confidence interval [CI]) and early postoperative ARD (OR=10.2 95% CI) remained consistently significant. Nine of 11 patients with CRD also had a history of ARD during the first postoperative week. These patients progressed to CRD despite the fact that seven of nine had normalized their renal function by day 90 posttransplant. Conclusion. We suggest that a combination of events during the first postoperative week after liver transplant serve as a physiologic “stress test” for the kidneys. Patients who fail the test (peak Cr ≥2 mg/dL during the first postoperative week) as well as the patients with diabetes mellitus are at increased risk of CRD. In such cases, conversion to a less nephrotoxic regimen may be beneficial.
Journal of Immunology | 2006
Shaoping Deng; Daniel J. Moore; Xiaolun Huang; Mohammad Mohiuddin; Major K. Lee; Ergun Velidedeoglu; Moh-Moh Lian; Meredith Chiaccio; Samsher Sonawane; Anton Orlin; Jing Wang; Haiying Chen; Andrew J. Caton; Robert Zhong; James F. Markmann
Targeting of the CD45RB isoform by mAb (anti-CD45RB) effectively induces donor-specific tolerance to allografts. The immunological mechanisms underlying the tolerant state remain unclear although some studies have suggested the involvement of regulatory T cells (T-regs). Although their generative pathway remains undefined, tolerance promoting T-regs induced by systemic anti-CD45RB treatment have been assumed to originate in the peripheral immune system. We demonstrate herein that separable effects on the peripheral and central immune compartments mediate graft survival induced by anti-CD45RB administration. In the absence of the thymus, anti-CD45RB therapy is not tolerogenic though it retains peripheral immunosuppressive activity. The thymus is required for anti-CD45RB to produce indefinite graft survival and donor-specific tolerance, and this effect is accomplished through thymic production of donor-specific T-regs. These data reveal for the first time an Ab-based tolerance regimen that relies on the central tolerance pathway.