Risk Factor For Graft Failure Research Articles

Donation after cardiac death liver transplantation in primary sclerosing cholangitis: proceed with caution.

Primary sclerosing cholangitis (PSC) patients suffer from comorbidities unaccounted for by the model for end-stage liver disease scoring system and may benefit from the increased donor organ pool provided by donation after cardiac death (DCD) liver transplantation. However, the impact of DCD transplantation on PSC graft outcomes is unknown. We studied 41,018 patients using the United Network for Organ Sharing database from 2002 through 2012. Kaplan-Meier analysis and Cox regression were used to evaluate graft survival and risk factors for graft failure, respectively. The PSC patients receiving DCD livers (n=75) showed greater overall graft failure (37.3% vs. 20.4%, P = 0.001), graft failure from biliary complications (47.4% vs. 13.9%, P = 0.002), and shorter graft survival time (P = 0.003), compared to PSC patients receiving donation after brain death organs (n=1592). Among DCD transplants (n=1943), PSC and non-PSC patients showed similar prevalence of graft failure and graft survival time, though a trend existed toward increased biliary-induced graft failure among PSC patients (47.4 vs. 26.4%, P = 0.063). Cox modeling demonstrated that PSC patients have a positive graft survival advantage compared to non-PSC patients (hazard ratio [HR]=0.72, P < 0.001), whereas DCD transplantation increased risk of graft failure (HR = 1.28, P < 0.001). Furthermore, the interaction between DCD transplant and PSC was significant (HR = 1.76, P = 0.015), indicating that use of DCD organs impacts graft survival more in PSC than non-PSC patients. Donation after cardiac death liver transplantation leads to significantly worse outcomes in PSC. We recommend cautious use of DCD transplantation in this population.

Melody transcatheter valve: Histopathology and clinical implications of nine explanted devices

ObjectivesWe examined interventionally implanted valved Melody conduits after surgical explantation by means of histology and immunohistochemistry and matched these findings with clinical data in order to assess in vivo biocompatibility and to identify risk factors for graft failure. Methods9 Melody valves had been implanted in 8 patients (pulmonary n=7, tricuspid position n=1). Indication for explantation included significant obstruction in 7 patients and valve insufficiency in 1 patient. 4 of 8 patients had suffered from endocarditis. Mean interval between implantation and explantation was 3.2 (1.8–5.2) years. All explants were worked up using a uniform protocol with fixation in formalin and embedding in methylmethacrylate. ResultsAll but one valve of the explanted Melody grafts were thin and histologically intact without any pathological findings. Complete neo-endothelialization could be demonstrated by means of immunohistochemistry. All 4 Melody valves from patients with endocarditis showed dense granulocytic infiltrations, 3 of these showed thrombotic material within the valves. ConclusionThis report covers the first series of explanted Melody valves from humans applying a uniform protocol for histopathological examination. Good biocompatibility of the Melody valves could be demonstrated after a mid-term follow-up. Factors for graft failure included endocarditis, outgrowth, and residual stenosis. These findings may have significant implications for the implant procedure as well as care of the patients during long-term follow-up.

MP85-01 GRAFT OUTCOME DISPARITY IN A SINGLE RENAL TRANSPLANT CENTER BASED ON RECIPIENT GEOGRAPHIC ORIGIN

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II1 Apr 2015MP85-01 GRAFT OUTCOME DISPARITY IN A SINGLE RENAL TRANSPLANT CENTER BASED ON RECIPIENT GEOGRAPHIC ORIGIN Weikai Qu, Ryan Flynn, David Fumo, Timothy Suttle, Steven Selman, Michael Rees, and Jorge Ortiz Weikai QuWeikai Qu More articles by this author , Ryan FlynnRyan Flynn More articles by this author , David FumoDavid Fumo More articles by this author , Timothy SuttleTimothy Suttle More articles by this author , Steven SelmanSteven Selman More articles by this author , Michael ReesMichael Rees More articles by this author , and Jorge OrtizJorge Ortiz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1855AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The disparity in access to organs for kidney transplantation has led to inter-state “transplant tourism.” Our objective was to determine if recipients traveling over a state line for kidney transplantation experience different outcomes relative to recipients native to that state. METHODS The Scientific Registry of Transplant Recipients was analyzed to examine all deceased donor kidney transplants performed from 1987-2014 (n=1094). Those transplanted in their original state were labeled O (n=775). Those Nonnative recipients were labeled N (n=319). RESULTS Demographics: Both sets of recipients received similar donor allografts except for the following (p-value<0.05): The N group received more DCD (6.9% vs 3.1%, p=0.004) and CDC high-risk donors (19.4% vs. 7.6%, p<0.001), who were on average older (mean=36.7 vs. 34.2, p=0.016) and had a higher BMI (mean=26.8 vs 25.8, p=0.001). The N group had a shorter average cold ischemic time (mean=16.6 vs. 19.1 hours, p<0.001). However Donor KDPI median was not different between groups (38% vs 35%, p=0.478). Recipient demographics: The N group contained more Asians (5.6% vs 0.3%, p<0.001), an older population (mean=54.0 vs. 48.4, p<0.001) and fewer patients using Medicaid (0.7% vs 2.7%, p=0.042). The N group also had more patients with a current PRA higher than 20% (22.8% vs 17.5%, p=0.044) but fewer patients undergoing repeat transplantation (10.3% vs. 15.9%, P=0.018). Outcomes: Patient survival was not statistically significantly different (mean time in years=13.7 vs 12.9, p=0.707). However, the N group experienced less delayed graft function (13.3% vs. 20.9%, P=0.003), improved allograft survival (mean time in years=17.1 vs 12.9, p<0.05) and a lower rate of retransplantation (3.2% vs. 13%, P<0.001). Log Rank test showed a significant difference in graft survival between education levels (p=0.043). However, when analyzed with other possible risk factors in Cox Proportional Hazard test, education level was not an independent risk factor of graft failure (p=0.153). Additionally, the incidence of rejection and rejection as a cause of graft loss were not statistically significantly different. CONCLUSIONS In this single center study, those patients traveling from outside the state of transplantation (despite similar donor and recipient demographics) demonstrated superior allograft outcomes. These superior outcomes may be tied to socio-economic factors yet to be elucidated. Other confounding factors may exist to explain these discordant results. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1067 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Weikai Qu More articles by this author Ryan Flynn More articles by this author David Fumo More articles by this author Timothy Suttle More articles by this author Steven Selman More articles by this author Michael Rees More articles by this author Jorge Ortiz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Survival in pediatric lung transplantation: The effect of center volume and expertise

Institutional operative volume has been shown to impact outcomes of various procedures including lung transplantation (LTx). We sought to determine whether this holds true with pediatric LTx by comparing outcomes of adult centers (with larger overall volume) to those of pediatric centers (with smaller volume but more pediatric-specific experience). A retrospective analysis of the Organ Procurement and Transplant Network data was performed. Centers were categorized as either adult (LTx volume predominantly in adult patients), high-volume pediatric (HVP, ≥4 LTxs/year), or low-volume pediatric (LVP, <4 LTxs/year). Outcomes were compared in "younger children" (<12 years) and "older children and adolescents" (12 to 17 years). In total, 1,046 pediatric LTxs were performed between 1987 and 2012 at 62 centers (adult 51 [82%], HVP 3 [5%], LVP 8 [13%]). Although adult centers had larger overall LTx volume, their pediatric experiences were severely limited (median 1/year). In younger children, HVP centers were significantly better than LVP centers for patient survival (half-life: 7.3 vs 2.9 years, p = 0.002). Similarly, in older children and adolescents, HVP centers were significantly better than adult centers for patient survival (half-life: 4.6 vs 2.5 years, p = 0.001). Of note, even LVP centers tended to have longer patient survival than adult centers (p = 0.064). Multivariable analysis identified adult centers as an independent risk factor for graft failure (hazard ratio: 1.5, p < 0.001) as with LVP (hazard ratio: 1.3, p = 0.0078). Despite larger overall clinical volume, outcomes among pediatric LTx recipients in adult centers are not superior to those of pediatric centers. Not only center volume but pediatric-specific experience has an impact on outcomes in pediatric LTx.

Uric Acid and the Risk of Graft Failure in Kidney Transplant Recipients: A Re-Assessment

The association of hyperuricemia with kidney allograft outcomes remains controversial. We studied this problem in 1170 kidney transplants from January 2000 to December 2010. The primary endpoint was total graft failure (i.e. graft loss or death). Conventional, time-dependent and marginal structural Cox proportional hazards models were fitted, the latter accounting for kidney function as a time-varying confounder affected by prior uric acid levels. Uric acid level was associated with an increased risk of total graft failure in time-fixed and time-varying models (HR 1.02 [95% CI: 1.003-1.04] and HR 1.02 [95% CI: 1.01-1.03], respectively, for every 10 µmol/L increase in uric acid). In contrast, the marginal structural model showed a modestly protective effect (HR 0.90 [95% CI: 0.85-0.94] for every 10 µmol/L increase in uric acid). Similar results were observed for death-censored graft failure and death with graft function. In summary, the absence of a deleterious association between elevated uric acid and graft outcome after accounting for graft function as a time-varying confounder suggests that uric acid is not an independent risk factor for graft failure. The modestly protective effect of uric acid may be an indicator of nutritional status but further study is warranted.

Risk factors and long-term outcomes of delayed graft function in deceased donor renal transplantation

PurposeThe purpose of this study was to analyze the risk factors for delayed graft function (DGF) and determine its impact on the outcomes of deceased donor (DD) kidney transplantation (KT).MethodsBetween January 2000 and December 2011, we performed 195 DD renal transplants. After the exclusion of primary nonfunctional grafts (n = 4), the study recipients were divided into two groups-group I, DGF (n = 31, 16.2%); group II, non-DGF (n = 160, 83.8%). The following variables were compared: donor and recipient characteristics, patient and graft survival, postoperative renal function, acute rejection (AR) episodes, and the rates of surgical and infectious complications.ResultsDonor-related variables that showed significant differences included hypertension (P = 0.042), diabetes (P = 0.025), and prerecovery serum creatinine levels (P < 0.001). However, there were no significant differences in recipient-related factors. One significantly different transplant-related factor was positive panel reactive antibody (PRA > 20%, P = 0.008). On multivariate analysis, only the prerecovery serum creatinine level (P < 0.001; hazard ratio [HR], 1.814) was an independent risk factor for the development of DGF. A Cox multivariate analysis of risk factors for graft survival identified these independent risk factors for graft survival: nephron mass (donor kidney weight to recipient body weight ratio) index (P = 0.026; HR, 2.328), CMV infection (P = 0.038; HR, 0.114), and AR episode (P = 0.038; HR, 0.166).ConclusionIn DD KT, an independent risk factor for DGF was the prerecovery serum creatinine level. Although there was a significant difference in graft survival between the DGF and non-DGF groups, DGF was not an independent risk factor for graft failure in this study.

Race and ethnic differences in the epidemiology and risk factors for graft failure after heart transplantation

Contemporary epidemiology of chronic graft failure (GF) after heart transplantation (HT) is not well described. Moreover, differences in the epidemiology of GF based on race/ethnicity remain poorly understood, despite clear evidence of inferior survival of ethnic minorities after HT. The incidence of GF and the population-attributable risk (PAR) of independent risk factors for GF were assessed in 15,255 patients (76% men; mean age 52 ± 12 years) who underwent primary HT from 2004 to 2012. During a median follow-up of 4.7 years (interquartile range, 2.3-7.1 years), GF developed in 2,926 patients (19.2%), corresponding to an incidence rate of 39.8/1,000 person-years (95% confidence interval, 38.4-41.3). Blacks were more likely to develop GF than Hispanics or whites, with incidence rates of 55.1, 42.2, and 36.5/1,000 person-years, respectively. After multivariable adjustment, black race was associated with a higher risk of GF (hazard ratio, 1.4; 95% confidence interval, 1.2-1.6; p < 0.001). Blacks and Hispanics were more likely to have risk factors for GF, including low education, public insurance, allosensitization, higher human leukocyte antigen mismatch, non-adherence, and history of rejection requiring hospitalization (all p < 0.001). Rejection requiring hospitalization carried the highest population-attributable risk in all groups, with the highest fraction in blacks (25.8%) compared with whites (18.6%) and Hispanics (15.6%). Socioeconomic and donor risk factors conferred relatively less risk of GF. Black HT recipients have the highest risk of GF, with immunologic factors conferring the greatest proportion of that risk. Racial differences in risk factors for GF after HT require further study.

Risk Factors for Graft Failure with Busulfan/Fludarabine-Based Conditioning in Children Undergoing Allogeneic Hematopoietic Cell Transplantation for Nonmalignant Disorders

▪Background: Allogeneic hematopoietic cell transplantation (aHCT) is curative for a number of pediatric nonmalignant disorders. Toxicities related to conditioning, failure of engraftment, and GVHD remain obstacles to successful transplantation for these patients. Since 2000, our institution has prospectively studied busulfan/fludarabine (Bu/Flu)-based conditioning regimens with a goal to reduce complications associated with myeloablative conditioning while maintaining adequate, stable donor-derived hematopoiesis. While overall survival has remained excellent, graft failure rates remain high. Therefore, we performed a retrospective analysis to identify risk factors for graft failure in patients receiving Bu/Flu-based conditioning. In addition, we report results for second aHCTs following graft failure.Methods: Since 2000, our institution has performed 74 aHCTs with Bu/Flu-based conditioning for nonmalignant disorders. The most common diagnoses include Wiskott-Aldrich syndrome (n = 10), thalassemia (n = 9), Hurler syndrome (n = 7), hemophagocytic lymphohistiocytosis (HLH) (n = 6), sickle cell disease (n = 5), and aplastic anemia (n = 5). Three aHCTs were excluded due to relapse of the underlying disease (e.g. HLH) despite > 90% donor chimerism. Conditioning included a backbone of busulfan and fludarabine as previously described (Law J, et al, Biol Blood Marrow Transplant, 2012). Starting in 2012, four doses of clofarabine 10 mg/m2 (0.33 mg/kg for patients < 12 kg) were added for recipients of mismatched unrelated donors (MMUD). In addition, conditioning included either rabbit antithymocyte globulin (rATG) or alemtuzumab.Results: Twelve graft failures (17%) occurred between day +18 and +445 (median +66). Of the variables analyzed, only donor chimerism for whole blood and the CD3 subset were significantly correlated with graft failure (CD14/15 and CD19 subsets were not). Cord blood aHCTs were excluded from conditioning analysis since these transplantations exclusively used rATG rather than alemtuzumab.Table 1:Risk Factors for Graft FailureDurable EngraftmentGraft FailureOdds Ratio (95% CI)P-valueHLA MatchMatched457–Mismatched1452.30 (0.63 to 8.38)0.28DonorRelated222–Unrelated37102.97 (0.60 to 14.84)0.20ConditioningBu/Flu/rATG (+/–Clo)145–Bu/Flu/alemtuzumab (+/–Clo)4040.28 (0.07 to 1.19)0.11SourceMarrow418–Peripheral Blood1310.39 (0.04 to 3.46)0.67Cord Blood533.08 (0.61 to 15.54)0.17CMV Reactivation (Prior to Graft Failure)No425–Yes1242.80 (0.65 to 12.10)0.21Whole Blood Donor Chimerism (Day +30)> 90%485–< 90%966.40 (1.60 to 25.55)0.01CD3 Donor Chimerism (Day +30)> 50%322–< 50%7511.43 (1.83 to 71.45)0.009Among the 12 patients with aHCTs that resulted in graft failure, 7 were successfully rescued with a second transplantation, 1 declined a second transplantation, 1 is awaiting a second transplantation, and 3 died due to sequelae of graft failure despite a second transplantation.Table 2:Second TransplantationsConditioningFirst DonorSecond DonorDiagnosisDurable EngraftmentsCy 120, TBI 200, hATG 90MUD CBMUD PBHurlerCy 120, TBI 200, hATG 90MUD BMMUD PBHurlerCy 120, TBI 1200, hATG 90MMUD BMSameMannosidosisCy 120, TBI 1200, hATG 90MUD BMMUD PBAplastic anemiaMel 140, Flu 90, hATG 90MRD CBSame BM/PBThalassemiaMel 140, TT 10, alemtuzumabMUD BMSameWiskott-AldrichMel 140, TT 10, hATG 90MRD BMSameZAP-70 combined immunodeficiencySecond Graft FailuresCy 120, TBI 200, hATG 90MMUD BMMMUD PBCongenital neutropeniaCy 180, TT 10, rATG 8MMUD BMHaplo PBPorphyriaCy 120, alemtuzumabMUD PBSameAdrenoleukodystrophyMRD = matched related donor, MUD = matched unrelated donorConclusions: We have previously shown that reduced toxicity conditioning with busulfan, fludarabine, and either rATG or alemtuzumab is well tolerated with low rates of transplant-related morbidity and mortality. In our cohort, low early donor chimerism was significantly correlated with increased graft failure. Close monitoring and early interventions may benefit patients at high risk for graft failure. Notably, there was a trend towards reduction in graft failure with alemtuzumab (9%) compared to rATG (26%), which did not reach statistical significance possibly due to insufficient power. While graft failure remains an issue with Bu/Flu-based conditioning, rescue with second transplantation is feasible with a reasonable chance for success. DisclosuresNo relevant conflicts of interest to declare.

Intensified Myeloablative Unrelated Cord Blood Transplantation for High-Risk or Advanced Hematological Malignancies: Experience at a Single-Institution in China

Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center.Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age ＜14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age < 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG).Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27（7~89）months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively.Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. DisclosuresNo relevant conflicts of interest to declare.

Recipient-related risk factors for graft failure and death in elderly kidney transplant recipients.

BackgroundElderly patients with end-stage renal disease have become the fastest growing population of kidney transplant candidates in recent years. However, the risk factors associated with long-term outcomes in these patients remain unclear.MethodsWe retrospectively analyzed 166 recipients aged 60 years or older who underwent primary deceased kidney transplantation between 2002 and 2013 in our center. The main outcomes included 1-, 3- and 5-year patient survival as well as overall and death-censored graft survival. The independent risk factors affecting graft and patient survival were analyzed using Cox regression analysis.ResultsThe 1-, 3-, 5-year death-censored graft survival rates were 93.6%, 89.4% and 83.6%, respectively. Based on the Cox multivariate analysis, panel reactive antibody (PRA)>5% [hazard ratio (HR) 4.295, 95% confidence interval (CI) 1.321–13.97], delayed graft function (HR 4.744, 95% CI 1.611–13.973) and acute rejection (HR 4.971, 95% CI 1.516–16.301) were independent risk factors for graft failure. The 1-, 3-, 5-year patient survival rates were 84.8%, 82.1% and 77.1%, respectively. Longer dialysis time (HR 1.011 for 1-month increase, 95% CI 1.002–1.020), graft loss (HR 3.501, 95% CI 1.559–7.865) and low-dose ganciclovir prophylaxis (1.5 g/d for 3 months) (HR 3.173, 95% CI 1.063–9.473) were risk factors associated with patient death.ConclusionsThe five-year results show an excellent graft and patient survival in elderly kidney transplant recipients aged ≥60 years. PRA>5%, delayed graft function, and acute rejection are risk factors for graft failure, while longer duration of dialysis, graft loss and low-dose ganciclovir prophylaxis are risk factors for mortality in elderly recipients. These factors represent potential targets for interventions aimed at improving graft and patient survival in elderly recipients.

Donor-related risk factors and preoperative recipient-related risk factors for graft failure.

The aim of this study was to evaluate the outcome of penetrating keratoplasties, at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany, using organ-cultured donor corneas and to identify preoperative risk factors, which may influence the event of graft failure. In this study, 377 medical records of patients, who underwent penetrating keratoplasty between 2001 and 2011, were reviewed. Organ-cultured donor corneas were obtained from the eye bank, Ludwig-Maximilians-University, Munich, Germany. Donor-related and preoperative recipient-related risk factors for graft failure were analyzed by univariate and multivariate analyses. Graft failure occurred in 26% of patients. The following preoperative factors were significantly associated with graft failure by multivariate analyses: high donor age, low donor endothelial cell density, high patient age, indications of infectious keratitis, acute perforation of noninfectious keratitis, prior graft failure, chemical burn, trauma, glaucoma-associated corneal decompensation, high-risk graft indications, corneal edema, anterior chamber lens, diabetes mellitus, atopy, and autoimmune diseases. This study demonstrated a success rate of 74%, which is consistent with previous studies. Various preoperative recipient-related factors seem to influence the outcome of penetrating keratoplasties, whereas few donor-related factors have a significant association with graft failure.

Corneal Transplant Surgery for Keratoconus and the Effect of Surgeon Experience on Deep Anterior Lamellar Keratoplasty Outcomes

To investigate graft survival and surgical experience on clinical outcome following deep anterior lamellar keratoplasty (DALK). Multicenter cohort study. The United Kingdom Transplant Database was used to identify patients who had undergone a first DALK or penetrating keratoplasty (PKP) for keratoconus. Data were collected at the time of surgery and at 1, 2, and 5 years postoperatively. Graft survival, best-corrected visual acuity, and refractive error were analyzed for 3 consecutive time periods. DALK outcomes were analyzed according to surgeon experience. A total of 4521 patients were included. Graft survival was 92% (95% CI: 90-92) for PKP and 90% (95% CI: 88-92) for DALK (P = .09). For corneal transplants undertaken in the periods 1999-2002, 2002-2005, and 2005-2007, graft survival was 90%, 92%, and 88% following DALK, and 93%, 91%, and 92% following PKP, respectively. There was no evidence of a difference between surgeons in terms of case mix (P = .4) or outcome (P = .2). Surgeon experience, in terms of the number of previous DALK undertaken, had no significant effect on outcome. A donor recipient trephine size disparity of 0.5 mm was associated with an increased risk of graft failure for both DALK (P = .03) and PKP (P = .002), whereas ocular surface disease was a significant risk factor for DALK (P = .04) but not PKP. There has been little change in graft survival for DALK and PKP over the past decade. Ocular surface disease is an important risk factor for graft failure following DALK. A surgical learning curve for DALK could not be demonstrated in terms of clinical outcome.

Endothelial Keratoplasty After Failed Penetrating Keratoplasty: An Alternative to Repeat Penetrating Keratoplasty

To analyze graft survival of endothelial keratoplasty (EK) under a previous failed penetrating keratoplasty (PK) compared to repeat PK. Retrospective, comparative case series. Analysis involved consecutive patients who underwent either a repeat PK or EK under PK, after failed PK, whose primary surgical indication was pseudophakic bullous keratopathy at a single tertiary center. Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Study. Main outcome measure was graft survival up to 5 years follow-up. We included a total of 113 eyes that underwent a repeat PK (n = 81) or EK under a failed PK (n = 32). Cumulative graft survival probabilities comparing repeat PK with EK under PK were at 91.9% vs 96.2% (1 year), 82.6% vs 91.6% (2 years), 66.8% vs 86.4% (3 years), and 51.3% vs 86.4% up to 5 years follow-up, respectively (log-rank P value = .013). Multivariate Cox regression analysis was performed, which adjusted for: age, sex, risk factors for graft failure (corneal neovascularization, ocular surface disease, glaucoma, active corneal inflammation, anterior synechiae), donor endothelial cell count, and repeat donor size. Repeat PK was a significant risk factor for graft failure compared to performing an EK under PK (hazard ratio: 10.17; 95% CI 1.10-93.63; P = .041). In our study of eyes with bullous keratopathy, endothelial keratoplasty under a previously failed PK provided better graft survival outcomes than repeat PK, adjusting for potential confounders and risk factors for graft failure.

Perioperative and postoperative risk factors for corneal graft failure.

PurposeIn this study, we assessed the outcome of penetrating keratoplasties using organ-cultured corneal tissues at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany. The goal was to identify perioperative and postoperative risk factors that may affect graft survival.Patients and methodsThe medical records of 377 patients who underwent a penetrating keratoplasty between 2001 and 2011 were reviewed. Organ-cultured corneal tissue was obtained from the eye bank of Ludwig-Maximilians-University. Perioperative and postoperative risk factors for graft failure were evaluated by univariate and multivariate analyses.ResultsThe 5-year overall survival rate of penetrating keratoplasties was 68%. Graft failure occurred in 26% of patients. High-risk keratoplasties, such as repeat penetrating keratoplasties and emergency penetrating keratoplasties, as well as postoperative conditions, such as glaucoma, retinal surgery, suture problems, persistent epithelial defect, infectious keratitis, and graft rejection, were significantly associated with graft failure in the multivariate analyses.ConclusionThis study showed a similar graft-survival rate as demonstrated in previous studies. In addition, a number of perioperative and postoperative risk factors were identified in this specific patient population.

Cardiovascular risk factors contribute to disparities in graft outcomes in African American renal transplant recipients: A retrospective analysis

Data examining cardiovascular (CV) risk factors in renal transplant recipients (RTRs) and their contribution to the disparity in graft survival between African American (AA) patients and non-AAs is limited. A single-center, retrospective analysis of 1003 adult RTRs from January 1, 2000 to May 1, 2008 to inspect the impact of race on post-transplant CV events, treatment of CV risk factors and their independent influence on graft outcomes was performed. AAs experienced a higher incidence of late graft loss, with 1- and 5-year graft survival rates of 93% and 76% vs 95% and 84% in the non-AA group, respectively. AA patients had a higher prevalence of hypertension (HTN) and diabetes mellitus (DM) and demonstrated reduced control of DM post-transplant (AA 74% vs non-AA 82%, p = 0.053). Multivariate analysis for graft survival indicated acute rejection, delayed graft function (DGF) and incidence of CV events were significant risk factors for graft failure, while the use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were protective. In conclusion, after controlling for CV risk factors and events, race did not have an independent effect on outcomes, suggesting CV risk factors and events contribute to this disparity. Clinical summary. AAs experienced a higher rate of graft failure and CV events; after adjusting for multiple immunological and CV risk factors, race no longer remained an independent risk factor for post-transplant CV events or graft failure; although disparities in post-transplant outcomes remain, race alone does not account for the disparity; the racial disparity is due to the higher incidence of DGF and acute rejection, as well as traditional CV risk factors, including HTN and DM.

Impact of the Model for End-Stage Liver Disease Score On the Outcomes of Small-for-Size Grafts in the Setting of Pediatric Living Donor Liver Transplantation.

(Background) In the field of adult living donor liver transplantation (LDLT), it has generally reported that recipients receiving small-for-size grafts (SFSGs) exhibit poor outcomes and prognoses, whereas the outcomes and prognoses of pediatric recipients receiving SFSGs are unknown. The purpose of this study was to identify risk factors for graft failure in order to establish a preoperative strategy for SFSGs. (Patients & Methods) Among 225 LDLT procedures performed between May 2001 and December 2012, 13 LDLT (5.8%) were undertaken using SFSGs. A SFSG was defined as that having a graft volume (GV) of less than 40% of the standard liver volume (SLV). The original disease was biliary atresia in 9 patients (69.2%), graft failure in 1, Wilson disease in 1, ornithine transcarbamylase deficiency in 1, and a congenital extrahepatic portosystemic shunt in 1. The mean patient age and body weight were 12.9±2.0 years and 41.7±9.2 kg, respectively. We performed univariate analyses to identify factors associated with graft failure in patients receiving SFSGs. (Results) The graft survival of the patients without SFSGs (n=212) and those receiving SFSGs (n=13) was 93.4% and 76.9%, respectively (p<0.005). The univariate analysis showed that the model for end-stage liver disease (MELD) score to be an independent risk factor for graft failure among the patients receiving SFSGs (p=0.014). The preoperative MELD scores were significantly higher in the graft failure group than in the survival group (22.3±11.0 vs 10.6±2.3). According to the receiver operative characteristic analysis of the recipient survival and preoperative MELD scores, the area under the curve was 0.767 and the cut-off value for the MELD score was 15. The cause of graft failure was bacterial infections in all three recipients, and the timing of graft failure occurred at a median of 70 days postoperatively (14-88 days). (Conclusions) Pediatric LDLT using SFSGs is associated with poor outcomes and prognoses, especially in patients with a preoperative MELD score of more than 15.

Impact of Pre Transplant Cardiovascular Risk Factors On Patient and Graft Survival After Renal Transplantation.

Background Pre existing coronary artery disease (CAD) and coronary artery interventions (CAI) are not currently included in SRTR model used to calculate center specific outcomes in renal transplantation. The aim of this study is to evaluate if CAD impacts renal tx outcomes. Methods Pre-tx cardiovascular (CV) risk factors, CAD (defined as diagnosis of CAD in charts including angina, arrhythmia, CHF, MI, CAI), DM, HTN, and PVD were studied in 1547 kidney tx, done at a single center (2003-2014). Patient survival (PS), graft survival (GS) were calculated by Kaplan-Meier method. Pre-tx CAI included: stenting, PTCA and CABG. Cox proportional hazards regression model was used to evaluate independent effect of pre-tx CV risk factors and post-tx outcomes. Risk factors were assessed separately and in the form of summative index. Results CAD, DM and advancing age (in 10-year increments) were independent risk factors for 5-year pt mortality; CAD and re-trx were independent risk factors for 5-year graft failure.Table 1: No Caption available.CAI including stenting and PTCA were independent risk factors for 5-year pt mortality; whereas CABG was not.Table 2: No Caption available.There was no association between PVD and PS/GS. Multivariate model using individual risk factors provided a superior statistical model over an index based on summative number of risk factors (0 to 9). Conclusions Pre-tx CAD is an independent risk factor for graft failure and recipient mortality after kidney tx; coronary stenting and PTCA are independent risk factors for patient mortality after kidney transplantation. These factors should be included in SRTR model when calculating center specific outcomes so that centers are not discouraged from transplanting high CV risk recipients despite the ultimate benefit of transplantation. Perhaps, CABG lowers CV risk in kidney tx recipients compared to stenting/PTCA.

Ocular surface rehabilitation: Application of human amniotic membrane in high-risk penetrating keratoplasties

BackgroundHuman amniotic membrane is a versatile tool for management of ocular surface disorders. This study evaluates the effect of cryopreserved human amniotic membrane (hAM) on one-year survival of penetrating keratoplasties (PKP) in high-risk recipients. MethodThis is a retrospective noncomparative cohort study of 58 consecutive eyes undergoing PKP with concurrent placement of a self-retained cryopreserved hAM (PROKERA®) at a tertiary care center from January 2009 to July 2010. ResultsMean patient age was 66.7±17.2years and 30 (54%) were males. 51 eyes were pseudophakic and one aphakic. 27 eyes were glaucomatous; 24 had glaucoma drainage device and 2 had previous endocyclophotocoagulation. 12 patients had PKP for the first time and 46 had repeat PKP (average number of prior PKP=1.63±1.1, range: 1–5).Risk factors for graft failure included repeat PKP (79.3%), corneal neovascularization (51.7%), preexisting glaucoma (46.6%), and presence of anterior synechiae (37.9%). Both First Transplant and Repeat Transplant groups had similar survival rates until 6months after transplant (75% vs 74%, odds ratio=1.06, p=1.00). At 12months, First Transplant group showed a better survival rate (67% vs 43%, odds ratio=2.60, p=0.20). Eyes with >3 risk factors had a higher graft failure rate (odds ratio=5.81, p=0.003). ConclusionSurvey of the literature suggests that high-risk PKP with concurrent hAM placement demonstrate comparable graft survival. Presence of multiple risk factors is associated with poor survival.

Analysis of Early BK Viremia and Development of Antibodies to Self-Antigens (Fibronectin and Collagen IV) Following Kidney Transplantation: Effect On Long-Term Outcomes.

Background: Immune responses to tissue-restricted self-antigens (SAgs) are emerging as important risk factors for graft failure. We previously demonstrated that antibodies (Abs) to SAgs fibronectin (FN) and collagen type IV (ColIV) are associated with BK viremia and transplant (txp) glomerulopathy. The effect of early BK viremia and FN/ColIV Abs on long-term txp outcomes is unknown. We hypothesized that early BK viremia and FN/ColIV Abs portend worse long-term txp outcomes than either/no phenotype. Methods: We measured FN/ColIV Abs in plasmas from kidney txp recipients in a BK virus monitoring study (n=20). Subjects were monitored for BK viruria and/or viremia during year-1 post-txp with at least 5 years of follow-up. Non-txp patients with stage 3 chronic kidney disease (CKD, n=12) and kidney txp donors (Donors, n=12) served as controls. Using ELISA, we measured FN/ColIV Abs pre- and 1, 4, and 8 months post-txp, and in each control group. We compared trends in FN/ColIV Abs status between the BK viremic (n=10) and the BK negative group (n=10) and examined the association between BK status, FN/Col4 Abs status, and a composite outcome of acute rejection, graft failure, or death with a functioning graft. Results: Overall, 5/20 (25%) pre-txp, 5/20 (25%) post-txp, 3/12 (25%) CKD, and 0/12 Donors developed FN/ColIV Abs. By 8 months post-txp, 4/10 (40%) and 5/10 (50%) of BK viremic subjects developed FN and ColIV Abs, respectively. No BK negative subjects developed FN or ColIV Abs (p=0.03). The composite outcome was reached in 6/20 (30%) txp recipients; those who were double-positive for FN/ColIV Abs had higher risk for reaching the composite outcome than double-negative recipients, independent of BK status (Kaplan-Meier and Cox regression analysis, Figure).Figure: No Caption available.Conclusions: Abs to SAgs FN/ColIV are present in non-txp stage 3 CKD, pre- and post-kidney txp, but not healthy donors. Early immune responses to SAgs FN and ColIV are an independent predictor of long-term txp outcomes and may serve as important diagnostic and therapeutic targets in the early post-txp period.

Ob/ob mouse livers show decreased oxidative phosphorylation efficiencies and anaerobic capacities after cold ischemia.

BackgroundHepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation.MethodsLivers from 10-week old leptin-deficient obese (ob/ob, n = 9) and lean C57 mice (n = 9) were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity.Results Ob/ob and lean mice livers showed severe (>60%) macrovesicular and mild (<30%) microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP) levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers.ConclusionsSteatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in steatotic donor livers.