Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipient... more Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipients. The objective of this retrospective study is to reassess the use of anastomotic stents for biliary reconstruction while focusing on an end-to-end choledochocholedochostomy (EECC) in orthotopic liver transplantation (OLT). EECC for the biliary reconstruction in OLT was performed in 115 patients. Sixty-three had their bile duct reconstructed over a T-tube stent (S group) while the remaining 52 patients underwent the same procedure without the stent (non-S group). The two groups were compared in terms of biliary complications and the conversion rate to a hepaticojejunostomy (HJS). Twenty-three biliary complications were observed in the OLT patients. In the S group, the incidence of a biliary leak was 12.7%, 8 of 63 patients in which 5 patients showed a bile leak when T tubes were removed. The rate of biliary stricture in the S group was 25.4%, or 16 patients. This stricture rate was not ...
Background. National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antig... more Background. National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antigen mismatch) has improved outcome in the recipients of these kidneys despite increasing cold storage times. However, there may be limits to outcome improvement of matched kidneys based on age and cold storage time. Materials and methods. To determine if national sharing of kidneys based on matching improves outcome regardless of donor age and cold storage time, we evaluated the United Network for Organ Sharing (UNOS) Scientific Registry for all recipients of cadaveric kidney transplants between January 1, 1990 and July 31, 1998. We divided the recipients into four groups based on donor age and cold storage time. Group 1 comprised young donors (donor age <55 years) with average (<24 h) cold storage time; group 2, young donors with long (>24 h) cold storage time; group 3, older donors (donor age >55 years) with average cold storage time; and group 4, older donors with long cold storage time. Results. A total of 64,046 recipients were evaluated: 35,061 (55%) in group 1, 21,264 (33%) in group 2, 4308 (7%) in group 3, and 3414 (5%) in group 4. Early graft performance progressively decreased from group 1 to group 4. Delayed graft function (DGF: dialysis requirement in the first 7 days posttransplant) was 18, 29, 33, and 42% (P < 0.0001); serum creatinine at 3 years (in mg/dl) was 1.70 ؎ 0.8, 1.73 ؎ 0.9, 2.31 ؎ 1.0, and 2.42 ؎ 1.1 (P < 0.0001); 1-year graft survival was 87, 84, 79, and 77% (P < 0.0001); and 3-year graft survival was 77, 74, 63, and 62% (P < 0.0001, for groups 1 and 2 vs groups 3 and 4, respectively). The trends in DGF persisted through the groups in 0 antigen mismatched kidneys. Conclusions. Early function is adversely affected by prolonged cold storage, despite matching, in recipients of younger and older donor kidneys. Long-term function does not appear to be affected by prolonged cold storage. Recipients of kidneys from donors >55 years of age have significantly worse short-and longterm outcome and may not benefit from national sharing.
The relationship between liver regeneration and the induction of the immune response is uncertain... more The relationship between liver regeneration and the induction of the immune response is uncertain. We hypothesize that the altered environment of the regenerating liver allograft increases the immune response to the allograft. In DA (RT1a) to LEW (RT1I) rats, hepatectomized, small-for-size and whole, normal-for-size liver transplants were performed. Naive and 70% hepatectomized LEW served as controls. Animals were assessed for survival, mass restoration, and host alloresponses. Although 30% partial allografts regenerated well to achieve a volume nearly equal to that of recipient&#39;s native liver in 7 days, survival was significantly shorter than that of the recipients of whole grafts (8.8 +/- 0.4 vs 10.3 +/- 1.2 days, n = 6, P &lt; 0.02). When compared on Day 4 after transplantation, histologic examination revealed a more vigorous cellular infiltration in the sinusoidal area in the partial liver transplant group. Phenotypic analysis of thymocytes showed a predominance of more mature phenotypes in the partial group, including more prominent decrease in the frequency of CD4, CD8-double-positive cells and increase in that of alpha beta TCRhigh cells. Proliferative activity of thymocytes in response to Con A was higher in the partial group than in the whole group. MLR of splenocytes against donor-type antigens was higher in the partial group, whereas reactivity against third party was the same as in other groups. These data suggest that host cellular responses to the allograft are enhanced in the regenerating, small-for-size liver graft. These findings have implications in the clinical management of liver recipients with damaged or small for size livers.
The objective of our study was to determine whether acceptable long-term graft survival and funct... more The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. Materials and Methods: A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. Findings: Fifty-seven adult recipients with at least a 1year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)-or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5-and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0 ∫ 0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/ MMF had rejection. Nine patients (16%) had surgical complications. Conclusion: Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients.
This case report describes a patient who underwent orthotopic liver transplantation and developed... more This case report describes a patient who underwent orthotopic liver transplantation and developed extensive hyperacute venous and arterial intravascular thromboses and thromboemboli intraoperatively. The patient was receiving antifibrinolytic therapy with aprotinin. The safety of routine aprotinin therapy in liver transplantation is examined. The value of the thrombelastograph (TEG) as a qualitative assessment of the coagulation system is emphasized. (Liver Transpl 2004;10:310-314.
Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transpl... more Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transplant can negatively impact outcomes. In light of this, we created a low-cost bench-top kidney transplant surgery simulator to help residents practice vascular anastomoses. Methods We searched for inexpensive materials to design an iliac fossa and kidney allograft. Eighteen residents with real-life kidney transplant experience trialed the simulator and scored its fidelity and educational utility on a 0-100 visual analog scale (VAS) survey. Results A 35.9 x 19.4 x 12.4 cm plastic box mimicked the iliac fossa. Hooks attached to the box's sidewall held under tension 1.27 and 0.64 cm diameter Penrose drains to replicate the external iliac vein and artery. A modified kidney-shaped stress ball with 1.27 x 4, 0.64 x 4, and 0.64 x 15 cm Penrose drains replicated a kidney allograft with its vein, artery, and ureter, respectively. Residents performed and assisted in vascular anastomoses on the simulator. The iliac fossa and allograft cost $20.20 and each practice run cost $7.20. Residents thought that the simulator was less difficult than real-life procedure, had acceptable fidelity levels, and they highly rated its educational utility. Conclusion Our novel low-cost bench-top kidney transplant surgery simulator focusing on vascular anastomoses received positive educational feedback from residents.
Understanding the economic implications of induction and maintenance immunosuppression (ISx) is i... more Understanding the economic implications of induction and maintenance immunosuppression (ISx) is important in developing personalized kidney transplant (KTx) care. Using data from a novel integrated data set including financial records from the University Health System Consortium, Medicare, and pharmacy claims (2007‐2014), we estimated the differences in the impact of induction and maintenance ISx regimens on transplant hospitalization costs and Medicare payments from KTx to 3 years. Use of thymoglobulin (TMG) significantly increased transplant hospitalization costs ($12 006; P = .02), compared with alemtuzumab and basiliximab. TMG resulted in lower Medicare payments in posttransplant years 1 (−$2058; P = .05) and 2 (−$1784; P = .048). Patients on steroid‐sparing ISx incurred relatively lower total Medicare spending (−$10 880; P = .01) compared with patients on triple therapy (tacrolimus, antimetabolite, and steroids). MPA/AZA‐sparing, mammalian target of rapamycin inhibitors‐based, and cyclosporine‐based maintenance ISx regimens were associated with significantly higher payments. Alternative ISx regimens were associated with different KTx hospitalization costs and longer‐term payments. Future studies of clinical efficacy should also consider cost impacts to define the economic effectiveness of alternative ISx regimens.
Impacts of the prescription opioid epidemic have not yet been examined in the context of heart tr... more Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, 95% LCL aHR 95% UCL) with death and graft loss. Among 13,958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR 1.10 1.33 1.61) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR 1.46 1.70 1.98) over the subsequent 4 years (from >1 to 5 years posttransplant). While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Transplant international : official journal of the European Society for Organ Transplantation, Feb 7, 2017
To assess factors that influence the choice of induction regimen in contemporary kidney transplan... more To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass cor...
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 23, 2015
We integrated the United States transplant registry with administrative records from an academic ... more We integrated the United States transplant registry with administrative records from an academic hospital consortium (97 centers, 2008-2012) to identify pre-donation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14,964 living donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia-related injuries (2.4%), and 'other' complications (6.6%). Major Clavien ≥4 complications affected 2.5%. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR=1.26,...
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 25, 2015
The infrequent use ABO incompatible (ABOi) kidney transplantation in the US may reflect concern a... more The infrequent use ABO incompatible (ABOi) kidney transplantation in the US may reflect concern about the costs of necessary preconditioning and post-transplant care. Medicare data for 26,500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2-incompatilbe (A2i) recipients, were analyzed to assess pre-transplant, transplant episode, and 3 year post-transplant cost impacts. The marginal costs of ABOi and A2i vs. ABO compatible transplant (ABOc) were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient (93.2% vs 88.15, P=0.0009) and death-censored graft survival (85.4% vs 76.1%, P<0.05) at three years were lower after ABOi but not A2i. The average overall cost of the transplant episode was significantly higher for ABOi ($65,080) compared with A2i ($36,752) and ABOc ($32,039) transplantation (P<.001) excluding organ acquisition. ABOi was ind...
Purpose of Review A transdisciplinary systems approach to the design of an artificial intelligenc... more Purpose of Review A transdisciplinary systems approach to the design of an artificial intelligence (AI) decision support system can more effectively address the limitations of AI systems. By incorporating stakeholder input early in the process, the final product is more likely to improve decision-making and effectively reduce kidney discard. Recent Findings Kidney discard is a complex problem that will require increased coordination between transplant stakeholders. An AI decision support system has significant potential, but there are challenges associated with overfitting, poor explainability, and inadequate trust. A transdisciplinary approach provides a holistic perspective that incorporates expertise from engineering, social science, and transplant healthcare. A systems approach leverages techniques for visualizing the system architecture to support solution design from multiple perspectives. Summary Developing a systems-based approach to AI decision support involves engaging in ...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Mar 27, 2016
Implications of prescription opioid use for outcomes after liver transplant have not been describ... more Implications of prescription opioid use for outcomes after liver transplant have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n=26,925). Opioid fills on the waiting list were normalized to morphine equivalents (ME), and exposure was categorized as: >0 to 2 ME/day (level 1), >2 to 10 ME/day (level 2), >10 to 70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio, 95% LCL aHR 95% UCL ) of pre-transplant ME level with patient and graft survival over 5-years post-transplant were quantified by multivariable Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared to no use, level 3 (aHR 1.06 1.281.55 ) and 4 (aHR 1.16 1.521.98 ) opioid use during listing were associated with increased mortality over 5 years p...
Baylor University Medical Center Proceedings, 2008
Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the u... more Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the use of intraoperative fluorescence imaging with the SPY imaging device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as a means to assess patency of the vascular anastomoses. Intravenous indocyanine green 2.5 mg/mL was fluoresced with the device to create the intraoperative video sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on these two pancreas transplants did not demonstrate adverse effects on patients or the transplanted allografts. This method of vascular imaging could prove useful in improving short-term graft survival and possibly lowering the thrombosis rates seen with pancreas transplantation. Long-term correlation studies between intraoperative findings and graft survival must be performed to confirm the utility of this imaging method.
Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully ... more Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of ci...
Background. The outcomes and optimal management of cirrhotic patients who develop cryptococcosis ... more Background. The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known. Methods. We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care. Results. In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%. Conclusions. Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.
Methods. We reviewed our prospectively maintained database of 2005 liver transplantations. Therap... more Methods. We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. Results. Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P Ͼ .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. Conclusions. Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results. S IROLIMUS use in liver transplantation is becoming more common. Its mechanism of action and side effect profiles are distinct from calcineurin inhibitors (CNIs), and synergism with cyclosporine and tacrolimus has been identified. 1 It is a powerful immunosuppressant in vitro and in animal models. The use of sirolimus has also been shown to slow the progression of allograft vascular disease in kidneys. However, its use has not been universally accepted in the immediate post-liver transplant period. Despite its success in renal transplantation, its use in liver transplanta-
Since the pre-procurement hospitalization period of non-heart beating donors (NHBD) is apt to be ... more Since the pre-procurement hospitalization period of non-heart beating donors (NHBD) is apt to be longer than that of brain dead donors, the opportunity of bacterial or fungal infection of NHBD is significantly increased through the tracheal tubes, intravenous lines and urethral catheters. The purpose of this study is to detect serious bacterial / fungal infections of NHBD before the procurements or to detect bacterial / fungal contaminations of allografts before the transplants. The targeted organisms in this study are hardly treatable organisms such as methicillin resistant Staphyllococcus aureus (MRSA), Pseudomonas aeruginosa (P. aeruginosa) and Candida albicans. Methods: The pre-procurement blood samples from 86 possible renal donors were examined by PCR, and 158 kidneys from 83 donors in whom infection was denied by PCR and 23 renal grafts transferred from other centers were also tested. The preservation solution (PS) and renal pelvic urine (PU) obtained from a total of 181 grafts were examined by PCR. In PCR, appropriate primers were used to detect following genes; fem A specific for Staphylococcus aureus (S.aureus), mec A specific for methicillin resistant Staphylococcus species, P.aeruginosa gyr A specific for P.aerginosa and 18S rRNA specific for most of the clinically critical fungi. It takes 4 to 6 hours for making a definite diagnosis by PCR. In order to confirm the PCR diagnosis, rapid shaking culture (RSC) was also done in parallel with PCR and the result was judged at intervals of 6 hours. The pre-procurement clinical conditions of possible donors were as follows; ages ranging from 1 to 73 years (mean: 47.5), periods between admission and brain death ranging from 1 to 44 days (mean: 4.7) and periods between brain death and cardiac arrest ranging from 1 to 14 days (mean: 3.3). The values of inflammatory indices such body temperature, WBC and CRP elevated up to 37.9ϩ/-1.1°C, 12,600 ϩ/-6,300 /l, and 20.3 Ϯ11.6 mg/dl. Results: Two possible donors were diagnosed to have systemic MRSA infection by PCR and RSC, and one possible donor was diagnosed to have systemic bacteroides infection by RSC, and the procurements were cancelled immediately before the operations. Eight kidneys were discarded because of the diagnoses of PS / PU contamination with S.aureus (1), MRSA (2) and Candida albicans(5) by PCR and RSC. In 20 grafts, the PCR diagnoses of PS / PU were positive but the results of RSC at 6 or 12 hours were negative, and all the grafts were finally transplanted. The other 148 kidneys were transplanted without delay since all the specimens were negative by PCR. Following the 168 renal transplants, no infectious complication transmitted by the engrafted kidneys was noted. Conclusions: CONCLUSION; PCR combined with RSC is very useful for detecting donor infection or organ contamination with hardly treatable bacteria or fungi in a pretransplant limited time period. Moreover, the opportunity of organ donations from the marginal donors will be increased if the organ contamination is denied by applying PCR, even when the donor infection might be highly suspected by the elevated inflammatory indices values.
Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipient... more Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipients. The objective of this retrospective study is to reassess the use of anastomotic stents for biliary reconstruction while focusing on an end-to-end choledochocholedochostomy (EECC) in orthotopic liver transplantation (OLT). EECC for the biliary reconstruction in OLT was performed in 115 patients. Sixty-three had their bile duct reconstructed over a T-tube stent (S group) while the remaining 52 patients underwent the same procedure without the stent (non-S group). The two groups were compared in terms of biliary complications and the conversion rate to a hepaticojejunostomy (HJS). Twenty-three biliary complications were observed in the OLT patients. In the S group, the incidence of a biliary leak was 12.7%, 8 of 63 patients in which 5 patients showed a bile leak when T tubes were removed. The rate of biliary stricture in the S group was 25.4%, or 16 patients. This stricture rate was not ...
Background. National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antig... more Background. National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antigen mismatch) has improved outcome in the recipients of these kidneys despite increasing cold storage times. However, there may be limits to outcome improvement of matched kidneys based on age and cold storage time. Materials and methods. To determine if national sharing of kidneys based on matching improves outcome regardless of donor age and cold storage time, we evaluated the United Network for Organ Sharing (UNOS) Scientific Registry for all recipients of cadaveric kidney transplants between January 1, 1990 and July 31, 1998. We divided the recipients into four groups based on donor age and cold storage time. Group 1 comprised young donors (donor age <55 years) with average (<24 h) cold storage time; group 2, young donors with long (>24 h) cold storage time; group 3, older donors (donor age >55 years) with average cold storage time; and group 4, older donors with long cold storage time. Results. A total of 64,046 recipients were evaluated: 35,061 (55%) in group 1, 21,264 (33%) in group 2, 4308 (7%) in group 3, and 3414 (5%) in group 4. Early graft performance progressively decreased from group 1 to group 4. Delayed graft function (DGF: dialysis requirement in the first 7 days posttransplant) was 18, 29, 33, and 42% (P < 0.0001); serum creatinine at 3 years (in mg/dl) was 1.70 ؎ 0.8, 1.73 ؎ 0.9, 2.31 ؎ 1.0, and 2.42 ؎ 1.1 (P < 0.0001); 1-year graft survival was 87, 84, 79, and 77% (P < 0.0001); and 3-year graft survival was 77, 74, 63, and 62% (P < 0.0001, for groups 1 and 2 vs groups 3 and 4, respectively). The trends in DGF persisted through the groups in 0 antigen mismatched kidneys. Conclusions. Early function is adversely affected by prolonged cold storage, despite matching, in recipients of younger and older donor kidneys. Long-term function does not appear to be affected by prolonged cold storage. Recipients of kidneys from donors >55 years of age have significantly worse short-and longterm outcome and may not benefit from national sharing.
The relationship between liver regeneration and the induction of the immune response is uncertain... more The relationship between liver regeneration and the induction of the immune response is uncertain. We hypothesize that the altered environment of the regenerating liver allograft increases the immune response to the allograft. In DA (RT1a) to LEW (RT1I) rats, hepatectomized, small-for-size and whole, normal-for-size liver transplants were performed. Naive and 70% hepatectomized LEW served as controls. Animals were assessed for survival, mass restoration, and host alloresponses. Although 30% partial allografts regenerated well to achieve a volume nearly equal to that of recipient&#39;s native liver in 7 days, survival was significantly shorter than that of the recipients of whole grafts (8.8 +/- 0.4 vs 10.3 +/- 1.2 days, n = 6, P &lt; 0.02). When compared on Day 4 after transplantation, histologic examination revealed a more vigorous cellular infiltration in the sinusoidal area in the partial liver transplant group. Phenotypic analysis of thymocytes showed a predominance of more mature phenotypes in the partial group, including more prominent decrease in the frequency of CD4, CD8-double-positive cells and increase in that of alpha beta TCRhigh cells. Proliferative activity of thymocytes in response to Con A was higher in the partial group than in the whole group. MLR of splenocytes against donor-type antigens was higher in the partial group, whereas reactivity against third party was the same as in other groups. These data suggest that host cellular responses to the allograft are enhanced in the regenerating, small-for-size liver graft. These findings have implications in the clinical management of liver recipients with damaged or small for size livers.
The objective of our study was to determine whether acceptable long-term graft survival and funct... more The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. Materials and Methods: A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. Findings: Fifty-seven adult recipients with at least a 1year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)-or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5-and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0 ∫ 0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/ MMF had rejection. Nine patients (16%) had surgical complications. Conclusion: Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients.
This case report describes a patient who underwent orthotopic liver transplantation and developed... more This case report describes a patient who underwent orthotopic liver transplantation and developed extensive hyperacute venous and arterial intravascular thromboses and thromboemboli intraoperatively. The patient was receiving antifibrinolytic therapy with aprotinin. The safety of routine aprotinin therapy in liver transplantation is examined. The value of the thrombelastograph (TEG) as a qualitative assessment of the coagulation system is emphasized. (Liver Transpl 2004;10:310-314.
Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transpl... more Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transplant can negatively impact outcomes. In light of this, we created a low-cost bench-top kidney transplant surgery simulator to help residents practice vascular anastomoses. Methods We searched for inexpensive materials to design an iliac fossa and kidney allograft. Eighteen residents with real-life kidney transplant experience trialed the simulator and scored its fidelity and educational utility on a 0-100 visual analog scale (VAS) survey. Results A 35.9 x 19.4 x 12.4 cm plastic box mimicked the iliac fossa. Hooks attached to the box's sidewall held under tension 1.27 and 0.64 cm diameter Penrose drains to replicate the external iliac vein and artery. A modified kidney-shaped stress ball with 1.27 x 4, 0.64 x 4, and 0.64 x 15 cm Penrose drains replicated a kidney allograft with its vein, artery, and ureter, respectively. Residents performed and assisted in vascular anastomoses on the simulator. The iliac fossa and allograft cost $20.20 and each practice run cost $7.20. Residents thought that the simulator was less difficult than real-life procedure, had acceptable fidelity levels, and they highly rated its educational utility. Conclusion Our novel low-cost bench-top kidney transplant surgery simulator focusing on vascular anastomoses received positive educational feedback from residents.
Understanding the economic implications of induction and maintenance immunosuppression (ISx) is i... more Understanding the economic implications of induction and maintenance immunosuppression (ISx) is important in developing personalized kidney transplant (KTx) care. Using data from a novel integrated data set including financial records from the University Health System Consortium, Medicare, and pharmacy claims (2007‐2014), we estimated the differences in the impact of induction and maintenance ISx regimens on transplant hospitalization costs and Medicare payments from KTx to 3 years. Use of thymoglobulin (TMG) significantly increased transplant hospitalization costs ($12 006; P = .02), compared with alemtuzumab and basiliximab. TMG resulted in lower Medicare payments in posttransplant years 1 (−$2058; P = .05) and 2 (−$1784; P = .048). Patients on steroid‐sparing ISx incurred relatively lower total Medicare spending (−$10 880; P = .01) compared with patients on triple therapy (tacrolimus, antimetabolite, and steroids). MPA/AZA‐sparing, mammalian target of rapamycin inhibitors‐based, and cyclosporine‐based maintenance ISx regimens were associated with significantly higher payments. Alternative ISx regimens were associated with different KTx hospitalization costs and longer‐term payments. Future studies of clinical efficacy should also consider cost impacts to define the economic effectiveness of alternative ISx regimens.
Impacts of the prescription opioid epidemic have not yet been examined in the context of heart tr... more Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, 95% LCL aHR 95% UCL) with death and graft loss. Among 13,958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR 1.10 1.33 1.61) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR 1.46 1.70 1.98) over the subsequent 4 years (from >1 to 5 years posttransplant). While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Transplant international : official journal of the European Society for Organ Transplantation, Feb 7, 2017
To assess factors that influence the choice of induction regimen in contemporary kidney transplan... more To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass cor...
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 23, 2015
We integrated the United States transplant registry with administrative records from an academic ... more We integrated the United States transplant registry with administrative records from an academic hospital consortium (97 centers, 2008-2012) to identify pre-donation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14,964 living donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia-related injuries (2.4%), and 'other' complications (6.6%). Major Clavien ≥4 complications affected 2.5%. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR=1.26,...
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 25, 2015
The infrequent use ABO incompatible (ABOi) kidney transplantation in the US may reflect concern a... more The infrequent use ABO incompatible (ABOi) kidney transplantation in the US may reflect concern about the costs of necessary preconditioning and post-transplant care. Medicare data for 26,500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2-incompatilbe (A2i) recipients, were analyzed to assess pre-transplant, transplant episode, and 3 year post-transplant cost impacts. The marginal costs of ABOi and A2i vs. ABO compatible transplant (ABOc) were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient (93.2% vs 88.15, P=0.0009) and death-censored graft survival (85.4% vs 76.1%, P<0.05) at three years were lower after ABOi but not A2i. The average overall cost of the transplant episode was significantly higher for ABOi ($65,080) compared with A2i ($36,752) and ABOc ($32,039) transplantation (P<.001) excluding organ acquisition. ABOi was ind...
Purpose of Review A transdisciplinary systems approach to the design of an artificial intelligenc... more Purpose of Review A transdisciplinary systems approach to the design of an artificial intelligence (AI) decision support system can more effectively address the limitations of AI systems. By incorporating stakeholder input early in the process, the final product is more likely to improve decision-making and effectively reduce kidney discard. Recent Findings Kidney discard is a complex problem that will require increased coordination between transplant stakeholders. An AI decision support system has significant potential, but there are challenges associated with overfitting, poor explainability, and inadequate trust. A transdisciplinary approach provides a holistic perspective that incorporates expertise from engineering, social science, and transplant healthcare. A systems approach leverages techniques for visualizing the system architecture to support solution design from multiple perspectives. Summary Developing a systems-based approach to AI decision support involves engaging in ...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Mar 27, 2016
Implications of prescription opioid use for outcomes after liver transplant have not been describ... more Implications of prescription opioid use for outcomes after liver transplant have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n=26,925). Opioid fills on the waiting list were normalized to morphine equivalents (ME), and exposure was categorized as: >0 to 2 ME/day (level 1), >2 to 10 ME/day (level 2), >10 to 70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio, 95% LCL aHR 95% UCL ) of pre-transplant ME level with patient and graft survival over 5-years post-transplant were quantified by multivariable Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared to no use, level 3 (aHR 1.06 1.281.55 ) and 4 (aHR 1.16 1.521.98 ) opioid use during listing were associated with increased mortality over 5 years p...
Baylor University Medical Center Proceedings, 2008
Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the u... more Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the use of intraoperative fluorescence imaging with the SPY imaging device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as a means to assess patency of the vascular anastomoses. Intravenous indocyanine green 2.5 mg/mL was fluoresced with the device to create the intraoperative video sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on these two pancreas transplants did not demonstrate adverse effects on patients or the transplanted allografts. This method of vascular imaging could prove useful in improving short-term graft survival and possibly lowering the thrombosis rates seen with pancreas transplantation. Long-term correlation studies between intraoperative findings and graft survival must be performed to confirm the utility of this imaging method.
Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully ... more Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of ci...
Background. The outcomes and optimal management of cirrhotic patients who develop cryptococcosis ... more Background. The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known. Methods. We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care. Results. In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%. Conclusions. Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.
Methods. We reviewed our prospectively maintained database of 2005 liver transplantations. Therap... more Methods. We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. Results. Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P Ͼ .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. Conclusions. Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results. S IROLIMUS use in liver transplantation is becoming more common. Its mechanism of action and side effect profiles are distinct from calcineurin inhibitors (CNIs), and synergism with cyclosporine and tacrolimus has been identified. 1 It is a powerful immunosuppressant in vitro and in animal models. The use of sirolimus has also been shown to slow the progression of allograft vascular disease in kidneys. However, its use has not been universally accepted in the immediate post-liver transplant period. Despite its success in renal transplantation, its use in liver transplanta-
Since the pre-procurement hospitalization period of non-heart beating donors (NHBD) is apt to be ... more Since the pre-procurement hospitalization period of non-heart beating donors (NHBD) is apt to be longer than that of brain dead donors, the opportunity of bacterial or fungal infection of NHBD is significantly increased through the tracheal tubes, intravenous lines and urethral catheters. The purpose of this study is to detect serious bacterial / fungal infections of NHBD before the procurements or to detect bacterial / fungal contaminations of allografts before the transplants. The targeted organisms in this study are hardly treatable organisms such as methicillin resistant Staphyllococcus aureus (MRSA), Pseudomonas aeruginosa (P. aeruginosa) and Candida albicans. Methods: The pre-procurement blood samples from 86 possible renal donors were examined by PCR, and 158 kidneys from 83 donors in whom infection was denied by PCR and 23 renal grafts transferred from other centers were also tested. The preservation solution (PS) and renal pelvic urine (PU) obtained from a total of 181 grafts were examined by PCR. In PCR, appropriate primers were used to detect following genes; fem A specific for Staphylococcus aureus (S.aureus), mec A specific for methicillin resistant Staphylococcus species, P.aeruginosa gyr A specific for P.aerginosa and 18S rRNA specific for most of the clinically critical fungi. It takes 4 to 6 hours for making a definite diagnosis by PCR. In order to confirm the PCR diagnosis, rapid shaking culture (RSC) was also done in parallel with PCR and the result was judged at intervals of 6 hours. The pre-procurement clinical conditions of possible donors were as follows; ages ranging from 1 to 73 years (mean: 47.5), periods between admission and brain death ranging from 1 to 44 days (mean: 4.7) and periods between brain death and cardiac arrest ranging from 1 to 14 days (mean: 3.3). The values of inflammatory indices such body temperature, WBC and CRP elevated up to 37.9ϩ/-1.1°C, 12,600 ϩ/-6,300 /l, and 20.3 Ϯ11.6 mg/dl. Results: Two possible donors were diagnosed to have systemic MRSA infection by PCR and RSC, and one possible donor was diagnosed to have systemic bacteroides infection by RSC, and the procurements were cancelled immediately before the operations. Eight kidneys were discarded because of the diagnoses of PS / PU contamination with S.aureus (1), MRSA (2) and Candida albicans(5) by PCR and RSC. In 20 grafts, the PCR diagnoses of PS / PU were positive but the results of RSC at 6 or 12 hours were negative, and all the grafts were finally transplanted. The other 148 kidneys were transplanted without delay since all the specimens were negative by PCR. Following the 168 renal transplants, no infectious complication transmitted by the engrafted kidneys was noted. Conclusions: CONCLUSION; PCR combined with RSC is very useful for detecting donor infection or organ contamination with hardly treatable bacteria or fungi in a pretransplant limited time period. Moreover, the opportunity of organ donations from the marginal donors will be increased if the organ contamination is denied by applying PCR, even when the donor infection might be highly suspected by the elevated inflammatory indices values.
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Papers by Henry Randall