Importance: Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. Objective: To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). Design, setting, and participants: This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. Exposure: DBD and DCD livers preserved on NMP or SCS. Main outcomes and measures: The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. Results: A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). Conclusions and relevance: In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Ruch, Brianna; Kumm, Kayla; Kirk, Wendy Van; Geraghty, PJ; Harbell, Jack W; Aqel, Bashar A; Reddy, Kunam S; Katariya, Nitin N; Mathur, Amit K Author Information

BACKGROUND:The Centers for Medicare and Medicaid Services is a major payer for abdominal transplant services. Reimbursement reductions could have a major impact on the transplant surgical workforce and hospitals. Yet government reimbursement trends in abdominal transplantation have not been fully characterized. METHODS:We performed an economic analysis to characterize changes in inflation-adjusted trends in Medicare surgical reimbursement for abdominal transplant procedures. Using the Medicare Fee Schedule Look-Up Tool, we performed a procedure code-based surgical reimbursement rate analysis. Reimbursement rates were adjusted for inflation to calculate overall changes in reimbursement, overall year-over-year, 5-year year-over-year, and compound annual growth rate from 2000 to 2021. RESULTS:We observed declines in adjusted reimbursement of common abdominal transplant procedures, including liver (-32.4%), kidney with and without nephrectomy (-24.2% and -24.1%, respectively), and pancreas transplant (-15.2%) (all, P < .05). Overall, the yearly average change for liver, kidney with and without nephrectomy, and pancreas transplant were -1.54%, -1.15%, -1.15%, and -0.72%. Five-year annual change averaged -2.69%, -2.35%, -2.64%, and -2.43%, respectively. The overall average compound annual growth rate was -1.27%. CONCLUSION:This analysis depicts a worrisome reimbursement pattern for abdominal transplant procedures. Transplant surgeons, centers, and professional organizations should note these trends to advocate sustainable reimbursement policy and to preserve continued access to transplant services.

Background. The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. Methods. Abdominal solid organs from SARS-CoV-2–infected donors were transplanted into uninfected recipients. Results. Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2–infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. Conclusions. Transplanting nonlung organs from SARS-CoV-2–infected donors into uninfected recipients demonstrated no evidence of virus transmission.

CONTEXT.—:It is unclear if preimplantation frozen section biopsy correlates with outcomes after deceased donor kidney transplantation.OBJECTIVE.—:To assess if chronic histologic changes on the preimplant frozen section correlates with graft loss and estimated glomerular filtration rate independently of kidney donor profile index (KDPI).DESIGN.—:Seven hundred three preimplantation biopsies were reviewed and a Banff sum score was calculated using glomerular sclerosis, interstitial fibrosis, vascular intimal thickening, and arteriolar hyalinosis. The posttransplant outcomes were compared for preimplantation biopsy Banff sum 0-1, 2-3, and 4-9. The cohort was also stratified by KDPI 85 or less versus more than 85.RESULTS.—:For the entire biopsy cohort, graft survival, estimated glomerular filtration rate at 1 year, and chronic changes on a 1-year posttransplant biopsy were superior in the group with preimplantation Banff sum 0-1. After stratifying by KDPI, the Banff sum no longer correlated with graft survival. In a univariate mode, using the Banff sum score as a continuous variable, a higher Banff sum score was significantly associated with graft failure (P = .03); however, after adjusting the KDPI, the Banff sum score no longer correlated with graft failure (P = .45). The 1-year estimated glomerular filtration rate and 1-year biopsy changes were superior in the group with Banff sum 0-1 only in the cohort with KDPI 85 or less.CONCLUSIONS.—:In donor kidneys used for transplant, preimplantation biopsy chronic changes correlate with estimated glomerular filtration rate and biopsy findings at 1 year, but biopsies with mostly mild chronicity and Banff sum scores less than or equal to 5 did not impact graft survival beyond KDPI.

The severe acute respiratory syndrome coronavirus 2 coronavirus disease 2019 (COVID-19) global pandemic has ushered in an era of hesitation in performing transplants in affected patients. This stems from the paucity of data regarding the testing modalities, long-term implications, and uncertain prognosis in this group of patients. Current guidance from the Centers for Disease Control recommends assessing symptoms rather than polymerase chain reaction (PCR) positivity. In light of these recommendations, we describe a case of an orthotopic liver transplant in a patient infected with COVID-19 with persistent PCR positivity for 40 days before retransplant. The patient's perioperative and postoperative course was uncomplicated. Our experience leads us to advocate for liver transplants in patients who are PCR positive for COVID-19 after careful individualized and multidisciplinary evaluation regarding their liver disease and COVID-19 symptomatology.

Patients undergoing kidney transplantation traditionally receive liberal amounts of fluid during surgery. However, excessive fluids can lead to fluid overload and ileus. In this retrospective cohort study, we compared the effect of restrictive versus liberal fluid therapy on kidney transplantation outcomes.

Early pancreas loss in simultaneous pancreas–kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients ( n = 218). Early pancreas allograft loss occurred in 12.8% ( n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications ( p = 0.12), or rejection episodes occurring in the first year ( p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post‐transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18–1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23–3.06, p = 0.77). One‐ and 2‐year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years ( p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

OBJECTIVE To evaluate the outcomes and perioperative complication rates following robot- assisted transplant nephrectomy ((RATN). METHODS All patients who underwent RATN at our institution were included. No exclusion criteria were applied. Clinical records were retrospectively reviewed and reported. This included preoperative, intraoperative, and postoperative outcomes. Complications were reported utilizing the Clavien-Dindo classification system. Descriptive statistics were reported using frequencies and percentages for categorical variables, means and standard deviation for continuous variables. RESULTS Between July 2014 and April 2018, 15 patients underwent RATN. Most patients had the transplant in the right iliac fossa (13/15). Ten patients underwent a concomitant procedure. The total operative time for the entire cohort was 336 (+/- 102) minutes (including cases who had concomitant procedures) and 259 (+/- 46 minutes) when cases with concomitant procedures were excluded. Mean estimated blood loss was 383 (+/- 444) mL. Postoperatively, 3 patients required blood transfusion. Average hospital stay was 4 (+/- 2.7) days. Most patients had finding consistent with graft rejection on final pathology. There were 5 complications; 3 of which were minor (grade 2 = 2 and grade 3 = 1); one patient had a wound infection requiring dressing (3A) and one patient died due to pulmonary embolism following discharge. Limitations include small series and retrospective nature of the study. CONCLUSION This case series demonstrate that RATN is technically feasible. With continued experience and larger case series, the robotic approach may provide a minimally invasive alternative to open allograft nephrectomy. (C) 2020 Elsevier Inc.

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post-kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2-3 and DBD AKIN stage 2-3. In comparing these groups, there were no short- or long-term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54-1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64-2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.

Purpose of review With an increasing demand for donor organs, strategies to increase the number of available donor organs have become more focused. Compensating donors for donation is one strategy proposed to increase the availability of organs for transplant. This has been implemented in several systems internationally, but debate continues in the United States with respect to appropriate strategies. The National Organ Transplant Act (NOTA) currently prohibits the transfer of any human organ ‘for valuable consideration’ for transplantation, but allows for the removal of financial disincentives. Recent findings Several proposals currently exist for compensating patients for living donation. Recent data have focused on studying and creating mechanisms for reimbursement of costs incurred as part of the donation process, which is related to the removal of disincentives to living donation. Others have advocated for the provision of actual incentives to patients for the act of donating, in an attempt to further expand living donation. The current debate focuses on what measures can reasonably be taken to increase donation, and whether additional incentives will encourage more donation or reduce the motivation for altruistic donation. Summary Currently, the transplant community broadly supports the removal of disincentives for living donors, including reimbursement of expenses for travel, housing and lost wages incurred during evaluation, surgery and after care. Others have advocated for financial incentives to further increase the number of donor organs available for transplant. Although the removal of disincentives is currently allowed under the existing legal structure of NOTA, providing financial incentives for living donation would require further evaluation of the economics, law, ethics and public readiness for a significant policy shift.

Prophylaxis for graft portal/splenic venous thrombosis following pancreas transplant varies between institutions. Similarly, treatment of venous thrombosis ranges from early re-exploration to conservative management with anticoagulation. We wished to determine the prevalence of graft splenic vein (SV) thrombosis, as well as the clinical significance of non-occlusive thrombus observed on routine imaging. Records of 112 pancreas transplant recipients over a 5-year period at a single center were reviewed. Venous thrombosis was defined as absence of flow or presence of thrombus identified in any part of the graft SV on ultrasound. Thirty patients (27%) had some degree of thrombus or absence of flow in the SV on postoperative ultrasound. There were 5 graft losses in this group. Four were due to venous thrombosis, and occurred within 20 days of transplant. All patients with non-occlusive partial SV thrombus but normal arterial signal on Doppler ultrasound were successfully treated with IV heparin followed by warfarin for 3-6 months, and remained insulin independent. Findings of arterial signal abnormalities, such as absence or reversal of diastolic flow within the graft, require urgent operative intervention since this finding can be associated with more extensive thrombus that may lead to graft loss.

Purpose To determine if ultrasonographic (US) findings, including Doppler US findings, are associated with subsequent pancreas transplant failure. Materials and Methods A cohort of adult patients who underwent pancreas transplantation at a tertiary institution over the course of 10 years (from 2003 to 2012) was retrospectively evaluated for failure, which was defined as return to insulin therapy or surgical graft removal. The institutional review board provided a waiver of informed consent. All US images obtained within the 1st postoperative year were reviewed for three findings: arterial flow (presence or absence of intraparenchymal forward diastole flow), splenic vein thrombus, and edema. These findings were correlated with pancreas graft failure within 1-year after surgery by using Cox proportional hazards models and hazard ratios. Results A total of 228 transplants were included (mean patient age, 41.6 years; range, 19-57 years; 122 men, 106 women). Absent or reversed arterial diastolic flow was identified in nine of 20 failed transplants (sensitivity, 45%; 95% confidence interval [CI]: 23, 68) and in 15 of 208 transplants that survived (specificity, 93% [193 of 208]; 95% CI: 89, 96). The Cox proportional hazard ratio was 6.2 (95% CI: 3.1, 12.4). Splenic vein thrombus was identified in 10 of 20 failed transplants (sensitivity, 50%; 95% CI: 27, 73) and in 25 of 208 transplants that survived (specificity, 88% [183 of 208]; 95% CI: 83, 92). The Cox proportional hazard ratio was 4.2 (95% CI: 2.4, 7.4). Edema had the lowest specificity (Cox proportional hazard ratio, 2.0; 95% CI: 1.3, 2.9). In the multivariate analysis, only absent or reversed arterial diastolic flow remained significantly associated with transplant failure (adjusted hazard ratio, 3.6; 95% CI: 1.0, 12.8; P = .045). Conclusion Absent or reversed diastolic arterial Doppler flow has a stronger association with transplant failure than does splenic vein thrombus or edema. (©) RSNA, 2016.

Human fibroblasts can be converted into hepatocytes capable of repopulating mouse livers by shortcutting reprogramming to pluripotency with factors promoting endoderm and hepatocyte differentiation. Previous studies have reported the production of liver cells from human embryonic and induced pluripotent stem (iPS) cells, but attempts to use them to repopulate liver tissue have been hampered by the failure of transplanted cells to proliferate. Holger Willenbring and colleagues adopted an alternative strategy for liver repopulation, converting human fibroblasts into mature hepatocytes capable of repopulating mouse livers. Their method bypasses an induced pluripotent state, instead reprogramming human fibroblasts to an induced multipotent progenitor cell (iMPC) state. From these cells the authors obtained endoderm progenitor cells (iMPC-EPCs) that generate surrogate hepatocytes capable of post-transplant maturation and proliferation. This work demonstrates the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, establishing the system as a possible model for research on autologous therapy of human liver diseases. Human induced pluripotent stem cells (iPSCs) have the capability of revolutionizing research and therapy of liver diseases by providing a source of hepatocytes for autologous cell therapy and disease modelling. However, despite progress in advancing the differentiation of iPSCs into hepatocytes (iPSC-Heps) in vitro1,2,3, cells that replicate the ability of human primary adult hepatocytes (aHeps) to proliferate extensively in vivo have not been reported. This deficiency has hampered efforts to recreate human liver diseases in mice, and has cast doubt on the potential of iPSC-Heps for liver cell therapy. The reason is that extensive post-transplant expansion is needed to establish and sustain a therapeutically effective liver cell mass in patients, a lesson learned from clinical trials of aHep transplantation4. Here, as a solution to this problem, we report the generation of human fibroblast-derived hepatocytes that can repopulate mouse livers. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs but cut short reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) state from which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. For this purpose we identified small molecules that aided endoderm and hepatocyte differentiation without compromising proliferation. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte function similar to those of aHeps. Unfractionated iMPC-Heps did not form tumours, most probably because they never entered a pluripotent state. Our results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy.