Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.

Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion in diabetic rhesus macaques. Induction therapy consisted of either basiliximab (n = 6) or rhesus-specific anti-thymocyte globulin (rhATG, n = 6), combined with a maintenance regimen using B7 costimulation blockade, tacrolimus with a delayed transition to sirolimus, and mycophenolate mofetil. Xenografts were monitored by blood glucose levels and porcine C-peptide measurements. Of the six receiving basiliximab induction, engraftment was achieved in 4 with median graft survival of 14 days. All six receiving rhATG induction engrafted with significantly longer xenograft survival at 40.5 days (P = 0.03). These data suggest that depletional induction provides superior xenograft survival to nondepletional induction, in the setting of a costimulation blockade-based maintenance regimen.

Decline of increased risk donor offers increases waitlist mortality in paediatric heart transplantation.

BACKGROUND: Increased risk donors in paediatric heart transplantation have characteristics that may increase the risk of infectious disease transmission despite negative serologic testing. However, the risk of disease transmission is low, and refusing an IRD offer may increase waitlist mortality. We sought to determine the risks of declining an initial IRD organ offer. METHODS AND RESULTS: We performed a retrospective analysis of candidates waitlisted for isolated PHT using 20072017 United Network of Organ Sharing datasets. Match runs identified candidates receiving IRD offers. Competing risks analysis was used to determine mortality risk for those that declined an initial IRD offer with stratified Cox regression to estimate the survival benefit associated with accepting initial IRD offers. Overall, 238/1067 (22.3%) initial IRD offers were accepted. Candidates accepting an IRD offer were younger (7.2 versus 9.8 years, p < 0.001), more often female (50 versus 41%, p = 0.021), more often listed status 1A (75.6 versus 61.9%, p < 0.001), and less likely to require mechanical bridge to PHT (16% versus 23%, p = 0.036). At 1- and 5-year follow-up, cumulative mortality was significantly lower for candidates who accepted compared to those that declined (6% versus 13% 1-year mortality and 15% versus 25% 5-year mortality, p = 0.0033). Decline of an IRD offer was associated with an adjusted hazard ratio for mortality of 1.87 (95% CI 1.24, 2.81, p < 0.003). CONCLUSIONS: IRD organ acceptance is associated with a substantial survival benefit. Increasing acceptance of IRD organs may provide a targetable opportunity to decrease waitlist mortality in PHT.

Predictors of nonuse of donation after circulatory death lung allografts.

OBJECTIVE: Despite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse. METHODS: All donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use. RESULTS: A total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO2/FiO2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO2/FiO2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001). CONCLUSIONS: Nontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool.

Transplant Center Variability in Organ Offer Acceptance and Mortality Among US Patients on the Heart Transplant Waitlist.

Importance: Under the current Centers for Medicare & Medicaid Services guidelines, there is incentivization to optimize posttransplant outcomes regardless of mortality among patients on the waitlist and transplant rates; few data exist with regard to transplant center acceptance practices and survival to heart transplant. Objectives: To evaluate the extent of variability in organ acceptance practices in the US and whether this center-level behavior is associated with heart transplant candidate survival. Design, Setting, and Participants: In this retrospective cohort study, the US National Transplant Registry was queried for all match runs of adult candidates listed for isolated heart transplant between May 1, 2007, and March 31, 2017. Data analysis was conducted from October 30, 2018, to May 1, 2019. The final cohort included 93 transplant centers, 19 703 donors, and 9628 candidates. Main Outcomes and Measures: Center acceptance rates for heart allografts offered to the highest-priority candidates, association between center acceptance rate and mortality among patients on the waitlist, and posttransplant outcomes between candidates who accepted their first-rank offers vs those who accepted previously declined offers. Results: Among 19 703 unique organ offers, 6302 hearts (32.0%) were accepted for first-rank candidates. After adjustment for donor, candidate, and geographic covariates, transplant centers varied in acceptance rates (12.3%-61.5%) of offers made to first-rank candidates. Higher acceptance rates were associated with lower cumulative incidence of 1-year mortality among patients on the waitlist. For every 10% increase in adjusted center acceptance rate, the risk of mortality decreased by 27% (subdistribution hazard ratio, 0.73; 95% CI, 0.67-0.80). No statistically significant difference was observed in 5-year adjusted posttransplant patient survival (adjusted hazard ratio, 1.02; 95% CI, 0.94-1.11) and graft failure (subdistribution hazard ratio; 0.95; 95% CI, 0.83-1.09) between hearts accepted at the first-rank compared with lower-rank positions. Conclusions and Relevance: Variability in heart allograft acceptance rates appears to exist among transplant centers, with candidates listed at lower acceptance rate centers being more likely to experience mortality while on the waitlist. Comparable posttransplant survival suggests that allografts that were declined as a first offer perform as well as those that were accepted at their first offer. These findings suggest that organ acceptance rate or time to transplant from being added to the waitlist may be an additional measure of heart transplant program performance.

Variability in donor organ offer acceptance and lung transplantation survival.

BACKGROUND: Lung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality. METHODS: We performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality. RESULTS: Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%-67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592-0.685). CONCLUSIONS: Variability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.

Failure to Rescue Contributes to Center-Level Differences in Mortality After Lung Transplantation.

BACKGROUND: The clinical response to postoperative complications after lung transplantation (LTx) may contribute to mortality differences among transplantation centers. The ability to avoid mortality after a complication-failure to rescue (FTR)-may be an effective quality metric in LTx. METHODS: The United Network for Organ Sharing database was queried for adult, first-time, lung-only transplantations from May 2005 to December 2015. Transplantation centers were stratified into equal-sized terciles on the basis of observed operative mortality rates. Several postoperative complications were identified, including stroke, acute rejection, acute kidney injury requiring hemodialysis, airway dehiscence, and extracorporeal membrane oxygenation 72 hours after surgery. Rates of FTR were calculated as the number of operative mortalities in patients who had complications divided by the number of patients who had any postoperative complications. RESULTS: Our study population included 16,411 LTx operations performed at 69 transplantation centers. LTx centers were stratified into terciles with average perioperative mortality of 4.0% for low-mortality centers, 6.9% for intermediate-mortality centers, and 12.4% for high-mortality centers. Low-mortality centers had slightly lower complication rates (low, 15.0% vs intermediate, 17.1% vs high, 19.1%; P < .001). Differences in FTR rate were significantly more pronounced (low, 14.9% vs intermediate, 23.9% vs high, 34.2%; P < .001). Multivariable logistic regression and generalized linear models demonstrated an independent association between high FTR rates and high mortality in LTx (P < .001). CONCLUSIONS: Differences in rates of FTR contribute significantly to per-center variability in mortality after LTx. FTR can serve as a quality metric to identify opportunities for improvement in management of perioperative adverse events.

Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients.

BACKGROUND: Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact. METHODS: To investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation. RESULTS: The group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection. CONCLUSIONS: Desensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.

Single lung transplantation in patients with severe secondary pulmonary hypertension.

BACKGROUND: The optimal transplant strategy for patients with end-stage lung disease complicated by secondary pulmonary hypertension (PH) is controversial. The aim of this study is to define the role of single lung transplantation in this population. METHODS: We performed a retrospective study of lung transplant recipients using the Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research registry. Adult recipients that underwent isolated lung transplantation between May 2005 and June 2015 for end-stage lung disease because of obstructive or restrictive etiologies were identified. Patients were stratified by mean pulmonary artery pressure ([mPAP] ≥ or < 40 mm Hg) and by treatment-single (SOLT) or bilateral (BOLT) orthotopic lung transplantation. The primary outcome measure was overall survival (OS), which was estimated using the Kaplan-Meier method and compared by the log-rank test. To adjust for donor and recipient confounders, Cox proportional hazards models were developed to estimate the adjusted hazard ratio of mortality associated with elevated mPAP in SOLT and BOLT recipients. RESULTS: A total of 12,392 recipients met inclusion criteria. Of recipients undergoing SOLT, those with mPAP ≥40 were shown to have lower survival, with 5-year OS of 43.9% (95% confidence interval 36.6-52.7; p = 0.007). Of recipients undergoing BOLT, OS was superior to SOLT, and no difference in 5-year OS between mPAP ≥ and <40 was observed (p = 0.15). In the adjusted analysis, mPAP ≥40 mm Hg was found to be an independent predictor for mortality in SOLT, but not BOLT recipients. This finding remained true on multivariable analysis. In patients undergoing SOLT, mPAP ≥40 was associated with an adjusted hazard ratio for mortality of 1.31 (1.08-1.59, p = 0.07). In BOLT, mPAP was not associated with increased hazard (adjusted hazard ratio 1.04, p = 0.48). CONCLUSIONS: There is a reduced survival when a patient with severe secondary PH undergoes SOLT. This increased mortality hazard is not seen in BOLT. It appears that a BOLT may negate the adverse effect that severe PH has on OS, and may be superior to SOLT in patients with mPAP over 40 mm Hg.

Impact of Donor Brain Death Duration on Outcomes After Lung Transplantation.

BACKGROUND: Donor brain death duration (BDD) may impact posttransplant graft function and survival in lung transplant. METHODS: We queried the 2007 to 2018 United Network for Organ Sharing Registry for adult recipients undergoing first-time isolated lung transplant. Cox proportional hazard modeling with splines enabled identification of 3 donor brain death intervals for subsequent analysis: short (<24 hours), reference (24-60 hours), and long (>60 hours). The primary outcome was posttransplant survival. RESULTS: In total, 19,721 donors and recipients met inclusion criteria. Median time from donor brain death until cross-clamp was 36.6 hours (interquartile range, 19.5). Unadjusted overall survival between cohorts was equivalent (log-rank P = .42); however, longer BDD was associated with improved bronchiolitis obliterans syndrome (BOS)-free survival (log-rank P < .001). On multivariable Cox proportional hazards regression, BDD was not associated with recipient survival (P > .05). Similarly, logistic regression did not identify an independent association between BDD and primary graft dysfunction (P > .05). Increased BDD was, however, associated with a decreased risk of acute rejection (long vs reference; adjusted odds ratio, 0.78; 95% confidence interval, 0.64-0.94) and improved BOS-free survival (long vs reference; adjusted hazard ratio, 0.88; 95% confidence interval, 0.81-0.96). CONCLUSIONS: Donor BDD is not associated with posttransplant survival or primary graft dysfunction. Long donor BDD, however, is associated with a decreased risk for acute rejection and improved BOS-free survival. Therefore, lung allografts from donors with a prolonged length of time from brain death until explant should not be viewed less favorably by donor selection centers.

The role of human CD46 in early xenoislet engraftment in a dual transplant model.

BACKGROUND: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value of human CD46 expression for islet xenotransplantation remains poorly defined. METHODS: This study attempted to delineate the role of CD46 in early neonatal porcine islet engraftment by comparing Gal-knocked out (GKO) and hCD46-transgenic (GKO/CD46) islets in a dual transplant model. Seven rhesus macaques underwent dual transplant and were sacrificed at 1 hour (n = 4) or 24 hours (n = 3). Both hemilivers were recovered and fixed for immunohistochemistry (CD46, insulin, neutrophil elastase, platelet, IgM, IgG, C3d, C4d, CD68, Caspase 3). Quantitative immunohistochemical analysis was performed using the Aperio Imagescope. RESULTS: Within 1 hour of intraportal infusion of xenografts, no differences were observed between the two types of islets in terms of platelet, antibody, or complement deposition. Cellular infiltration and islet apoptotic activity were also similar at 1 hour. At 24 hours, GKO/CD46 islets demonstrated significantly less platelet deposition (P = 0.01) and neutrophil infiltration (P = 0.01) compared to GKO islets. In contrast, C3d (P = 0.38) and C4d (P = 0.45) deposition was equal between the two genotypes. CONCLUSIONS: Our findings suggest that expression of hCD46 on NPIs potentially provides a measurable incremental survival advantage in vivo by reducing early thrombo-inflammatory events associated with instant blood-mediated inflammatory reaction (IBMIR) following intraportal islet infusion.

Challenging 30-day mortality as a site-specific quality metric in non-small cell lung cancer.

OBJECTIVE: The objective of this project was to assess the best measure for postoperative outcomes by comparing 30-day and 90-day mortality rates after surgery for non-small cell lung cancer using the National Cancer Database. Secondarily, hospital performance was examined at multiple postoperative intervals to assess changes in ranking based on mortality up to 1 year after surgery. METHODS: Patients who had undergone surgery for non-small cell lung cancer between 2004 and 2013 were identified in the National Cancer Database. Mortality rates at 30 days and 90 days were compared after adjusting for several patient characteristics, tumor variables, and hospital procedural volume using generalized logistic mixed models. Subsequently, mixed model logistic regression models were employed to evaluate hospital performance based on calculated mortality at prespecified time points. RESULTS: A total of 303,579 patients with non-small cell lung cancer were included for analysis. The 90-day mortality was almost double the 30-day mortality (3.0% vs 5.7%). Several patient characteristics, tumor features, and hospital volume were significantly associated with mortality at both 30 days and 90 days. Hospital rankings fluctuate appreciably between early mortality time points, which is additional evidence that quality metrics need to be based on later mortality time points. CONCLUSIONS: Thirty-day mortality is the commonly accepted quality measure for thoracic surgeons; however, hospital rankings may be inaccurate if based on this variable alone. Mortality after 90 days appears to be a threshold after which there is less variability in hospital ranking and should be considered as an alternative quality metric in lung cancer surgery.

Endoscopic cyclophotocoagulation (ECP) for childhood glaucoma: a large single-center cohort experience.

PURPOSE: To assess the factors associated with successful outcomes in the management of childhood glaucoma treated with endoscopic cyclophotocoagulation (ECP) as both primary and adjunctive surgery. METHODS: The medical records of consecutive children with glaucoma treated by a single surgeon at a single center over a 17-year period using ECP procedures were reviewed retrospectively. Treatment failure was defined as (1) intraocular pressure (IOP) >24 mm Hg at two consecutive examinations despite maximal medical treatment, (2) any additional glaucoma surgery, (3) sight-threatening complications, or (4) progression to no light perception visual acuity. Success was defined as the absence of treatment failure. RESULTS: A total of 107 ECP procedures on 80 eyes of 70 children were included. Glaucoma diagnoses included: following-cataract-surgery (60%), anterior segment dysgenesis (13%), primary congenital (9%), and other (19%). Most eyes (67 [84%]) had prior glaucoma surgery, and 73 (91%) were aphakic or pseudophakic at first ECP. Median follow-up was 2.2 years (IQR, 1.1-3.5) after initial ECP; mean number of ECP treatments per eye was 1.3 (range, 1-3). Success for a single ECP treatment at 1, 3, and 5 years (Kaplan-Meier analysis) was 64% (95% CI, 54-76), 36% (26-50), and 16% (7-37), respectively. Cumulative success (≥1 ECP) at 5 years was 34% (23-50). In multivariable analysis, of many risk factors considered, only a preoperative IOP of <32 mm Hg was significantly associated with treatment success. CONCLUSIONS: ECP represents a modestly effective long-term therapy for childhood glaucoma and may be most successful in patients with preoperative IOP of <32 mm Hg.

Secondary lymphoid tissue and costimulation-blockade resistant rejection: A nonhuman primate renal transplant study.

Naïve T cell activation requires antigen presentation combined with costimulation through CD28, both of which optimally occur in secondary lymphoid tissues such as lymph nodes and the spleen. Belatacept impairs CD28 costimulation by binding its ligands, CD80 and CD86, and in doing so, impairs de novo alloimmune responses. However, in most patients belatacept is ineffective in preventing allograft rejection when used as a monotherapy, and adjuvant therapy is required for control of costimulation-blockade resistant rejection (CoBRR). In rodent models, impaired access to secondary lymphoid tissues has been demonstrated to reduce alloimmune responses to vascularized allografts. Here we show that surgical maneuvers, lymphatic ligation, and splenectomy, designed to anatomically limit access to secondary lymphoid tissues, control CoBRR and facilitate belatacept monotherapy in a nonhuman primate model of kidney transplantation without adjuvant immunotherapy. We further demonstrate that animals sustained on belatacept monotherapy progressively develop an increasingly naïve T and B cell repertoire, an effect that is accelerated by splenectomy and lost at the time of belatacept withdrawal and rejection. These pilot data inform the role of secondary lymphoid tissues on the development of CoBRR and the use of costimulation molecule-focused therapies.

Implications of declining donor offers with increased risk of disease transmission on waiting list survival in lung transplantation.

BACKGROUND: Donors with characteristics that may increase the likelihood of disease transmission with transplantation are noted as increased risk via Public Health Service criteria. This study aimed to establish the implications of declining an increased-risk donor (IRD) organ offer in lung transplantation. METHODS: Adult candidates waitlisted for isolated lung transplantation in the United States using the Organ Procurement and Transplantation Network /United Network of Organ Sharing registry from 2007 to 2017 were identified. Individual match run files identified candidate recipients who matched to an IRD offer. Competing-risks analysis ascertained the likelihood of survival to transplantation. A stratified Cox model and restricted mean survival times estimated the survival benefit associated with the acceptance of an IRD organ. RESULTS: A total of 6,963 candidates met inclusion criteria, and 1,473 (21.2%) accepted an IRD offer. Candidates who accepted an IRD offer were older, more likely to be male, and had a higher lung allocation score at the time of listing (all p < 0.05). At 1 year after an IRD offer decline, 70.5% of candidates underwent a lung transplant, 13.8% died or decompensated, and 14.9% were still awaiting transplant. Compared with those who declined, candidates who accepted the IRD offer had significantly improved cumulative mortality at 1 year (14.1% vs 23.9%, p < 0.001) and 5 years (48.4% vs 53.8%, p < 0.001). CONCLUSIONS: IRD organ declination is associated with a decreased rate of lung transplantation and worse survival. Overall post-transplant survival rates for those who survive to transplantation are equivalent.

Simultaneous Versus Sequential Heart-liver Transplantation: Ideal Strategies for Organ Allocation.

BACKGROUND: Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research file was queried for adult recipients waitlisted for both heart and liver transplantation. The United Network for Organ Sharing thoracic and liver databases were linked to facilitate examination of waitlist and transplant characteristics for simultaneously listed patients. Univariate survival analysis was used to determine overall survival. RESULTS: Of the 236 patients meeting inclusion criteria, 200 underwent SHL, 7 sequentially underwent LAH, and 29 received heart transplantation only (isolated orthotopic heart transplantation [iOHT]). Recipients of SHL were less likely to have an episode of acute rejection before discharge (LAH, 14.2%; SHL, 2.4%; iOHT, 3.6%; P = .019) or be treated for acute rejection within 1 year after transplantation (LAH, 14.3%; SHL, 2.5%; iOHT, 13.8%; P = .007). Otherwise, postoperative hospital length of stay, stroke, need for dialysis, and need for pacemaker placement were comparable across groups. Ten-year survival similarly favored both LAH and SHL over iOHT (LAH: 100%, 71.4%, 53.6%; SHL: 87.1%, 80.4%, 52.1%, iOHT: 70.1%, 51.6%, 27.5% for 1-, 5-, and 10-year survivals, respectively, P = .003). However, median time between heart and liver transplant was 302 days in patients undergoing sequential transplantation. CONCLUSIONS: Although transplantation in a simultaneous or sequential fashion yields equivalent outcomes, a high fraction of patients undergoing initial heart transplant alone fail to proceed to subsequent liver transplantation. Therefore, in patients with combined heart and liver failure with a projected need for 2 allografts, simultaneous transplantation is associated with maximum benefit.

Elevated Donor Hemoglobin A1C Impairs Kidney Graft Survival From Deceased Donors With Diabetes Mellitus: A National Analysis.

OBJECTIVES: Kidney transplant is the optimal therapy for patients with end-stage renal disease. The presence of donor diabetes mellitus is a recognized risk factor for impaired kidney graft survival and is incorporated into the Kidney Donor Profile Index. At present, however, there are limited assessments of the severity of this risk factor. Hemoglobin A1c reflects glycemic control over the preceding 3 months, and we hypothesized that donor hemoglobin A1c levels could confer additional discriminatory power in assessments of deceased donors with diabetes mellitus. MATERIALS AND METHODS: The United Network for Organ Sharing/Organ Procurement and Organ Transplantation Network Standard Transplant Analysis Research file was queried for adult deceased-donor kidney transplants performed using allografts from donors with diabetes mellitus who had measurements of hemoglobin A1c before donation. RESULTS: The study cohort consisted of 1518 kidney transplants performed using allografts from deceased donors with diabetes mellitus. Kaplan-Meier survival analysis and log-rank test were performed to compare survival of grafts from donors with diabetes mellitus with elevated (≥ 6.5%) versus lower (< 6.5%) hemoglobin A1c levels. Graft survival at 5 years was significantly lower for recipients of donors with hemoglobin A1c ≥ 6.5% (58.9% vs 68.3%; P < .001). On multivariate analysis, hemoglobin A1c ≥ 6.5% was an independent predictor of diminished graft survival. CONCLUSIONS: Hemoglobin A1c has potential as an additional discriminatory test for estimating outcomes of grafts from donors with diabetes mellitus and should be routinely measured in this population.

Early experience with the use of hepatitis C antibody-positive, nucleic acid testing-negative donors in lung transplantation.

Historically, potential lung donors who have detectable antibodies to hepatitis C virus have been declined by most centers due to concern for possible disease transmission. We sought to evaluate hepatitis C viral transmission rates from donors who were known to be HCV Ab positive but HCV NAT negative. We performed a single-center retrospective review of a prospectively collected database for lung transplant recipients at our center including HCV Ab+NAT- donors (approved January 2017). Donor and recipient demographic data were compiled, and records were queried to ascertain rate of seroconversion. During the study period (1/1/17 to 8/9/17), a total of 64 recipients underwent lung transplantation. Thirteen (20%) donors were HCV Ab+NAT-. All recipients of HCV Ab+NAT- grafts were HCV Ab- at the time of transplant. Recipients of grafts from HCV Ab+NAT- donors underwent protocol NAT at 2 and 12 months and all are NAT- to date. One recipient developed reactive HCV Ab at 6 months post-transplant. Follow-up NAT showed HCV RNA to be undetectable. To date, use of HCV Ab+NAT- donors in lung transplantation has yielded favorable outcomes, with evidence of one transient seroconversion suggesting this practice may increase access to life-saving transplantation to those in need.

Improvement in Liver Transplant Outcomes From Older Donors: A US National Analysis.

OBJECTIVE: To investigate trends in long-term graft and patient outcomes following liver transplantation using grafts from donors ≥60 years old. SUMMARY BACKGROUND DATA: The scarcity of donor livers has led to increased utilization of organs from donors ≥60 years old. However, few studies have examined how long-term transplant outcomes from older donors have evolved over time. METHODS: The OPTN/UNOS database was queried for all first-time isolated adult liver transplants. We identified 14,796 adult liver transplant using donors ≧60-year-old suitable for analysis from 1990 to 2014. Cohorts were then developed based on 5-year intervals of transplant date. Kaplan-Meier analysis was used to compare graft and patient survival for recipients from older donor across each 5-year era. RESULTS: Utilization of donor grafts ≥60 years old increased steadily for the first 15 years of the study, but has leveled off over the last 10 years. Comparison of the earliest and latest eras in the study was notable for an increase in median recipient age (51 vs. 59, P < 0.001) and reduction in median cold ischemic time (10 vs. 6 h, P = 0.001). Unadjusted 5-year graft and patient survival has improved significantly over time (P < 0.0001). More importantly, the discrepancy in survival between older and younger grafts has narrowed substantially over time (P < 0.0001). CONCLUSIONS: This study demonstrates significant improvement in transplant outcomes with donor grafts ≥60-years old and supports increased but judicious use of extended criteria donors liver grafts. Improved patient selection and reduction in cold ischemia time appear to be contributing factors.

A Propensity-matched Survival Analysis: Do Simultaneous Liver-lung Transplant Recipients Need a Liver?

BACKGROUND: There is debate whether simultaneous lung-liver transplant (LLT) long-term outcomes warrant allocation of 2 organs to a single recipient. We hypothesized that LLT recipients would have improved posttransplant survival compared with matched single-organ lung recipients with an equivalent degree of liver dysfunction. METHODS: The Organ Procurement and Transplant Network/United Network for Organ Sharing STAR file was queried for adult candidates for LLT and isolated lung transplantation from 2006 to 2016. Waitlist mortality and transplant odds were calculated for all candidates. Donor and recipient demographic characteristics were compiled and compared. The LLT recipients were matched 1:2 with a nearest neighbor method to single-organ lung recipients. Kaplan-Meier methods with log-rank test compared long-term survival between groups. Univariate regression was used to calculate the association of LLT and mortality within 6 months of transplant. A proportional hazards model was used to calculate risk-adjusted mortality after 6 months posttransplantation. RESULTS: Thirty-eight LLT patients were matched to 75 single-organ lung recipients. After matching, no differences in baseline demographics or liver function were observed between cohorts. Length of stay was significantly longer in LLT recipients compared to isolated lung recipients (45.89 days vs 22.44 days, P < 0.001). There was no significant difference in survival probability between LLT and isolated lung transplant (1 y, 89.5% vs 86.7%; 5 y, 67.0% vs 64.6%; P = 0.20). CONCLUSIONS: After matching for patient characteristics and level of liver dysfunction, survival in simultaneous LLT was comparable to isolated lung transplantation. Although this population is unique, the clinical picture prompting liver transplant is not clear. National guidelines to better elucidate patient selection are needed.