Declining Medicare reimbursement in abdominal transplantation from 2000 to 2021.

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.

Solid Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients: A Single-center Experience.

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.

Correlation of Chronic Histologic Changes on Preimplantation Frozen Section Biopsy With Transplant Outcomes After Deceased Donor Kidney Transplantation.

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.

Intraoperative fluid management and kidney transplantation outcomes: A retrospective cohort study.

BACKGROUND: 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. METHODS: Patients who underwent deceased-donor kidney transplantation at Mayo Clinic from January 2014 to March 2019 were included. Those who received <3 L of intravenous fluids intraoperatively were categorized as "restrictive;" those who received ≥3 L were categorized as "liberal." The primary outcome was incidence of delayed graft function (DGF). Secondary outcomes included length of stay, readmission within 30 days, time to return of bowel function, and incidence of postoperative complications. RESULTS: Of the 1171 patients included, 557 were in the restrictive group and 614 in the liberal group. The mean (SD) fluid intake was 2.17 (.54) L in the restrictive group and 3.67 (.68) L in the liberal group (P<.001). There was no difference in DGF (relative risk, 1.03; P = .56), length of stay (P = .34), readmission (P = .80), return of bowel function (P = .71), or other postoperative complications. CONCLUSIONS: Intraoperative restrictive fluid therapy during kidney transplantation was not associated with DGF or worse outcomes when compared with liberal fluid therapy.

Liver Transplant in a Polymerase Chain Reaction-Positive COVID-19 Recipient: A Case Report.

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.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft 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.

Robot Assisted Renal Allograft Nephrectomy: Initial Case Series and Description of Technique.

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.

Transplanting kidneys from donation after cardiac death donors with acute kidney injury.

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.

Financial compensation for organ 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.

US Findings in Patients at Risk for Pancreas Transplant Failure.

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.

Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.

Parthenogenesis is the development of an oocyte without fertilization. Mammalian parthenogenetic (PG) embryos are not viable, but can develop into blastocysts from which embryonic stem cells (ESCs) have been derived in mouse and human. PG ESCs are frequently homozygous for alleles encoding major histocompatibility complex (MHC) molecules. MHC homozygosity permits much more efficient immune matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a promising cell source for cell therapies requiring no or little immune suppression. However, findings of restricted differentiation and proliferation of PG cells in developmental chimeras have cast doubt on the potential of PG ESC derivatives for organ regeneration. To address this uncertainty, we determined whether PG ESC derivatives are effective in rescuing mice with lethal liver failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In developmental chimeras generated by injecting wild-type PG ESCs into Fah-deficient blastocysts, PG ESCs differentiated into hepatocytes that could repopulate the liver, provide normal liver function, and facilitate long-term survival of adult mice. Moreover, after transplantation into adult Fah-deficient mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading to high-level liver repopulation. Our results show that--despite the absence of a paternal genome--PG ESCs can form therapeutically effective hepatocytes.

Mouse liver repopulation with hepatocytes generated from human fibroblasts.

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 vitro, 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 transplantation. 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.

Solid organ transplants in HIV-infected patients.

There is a growing need for kidney and liver transplants in persons living with HIV. Fortunately, with the significant advances in antiretroviral therapy and management of opportunistic infections, HIV infection is no longer an absolute contraindication for solid organ transplantation. Data from several large prospective multi-center cohort studies have shown that solid organ transplantation in carefully selected HIV-infected individuals is safe. However, significant challenges have been identified including prevention of acute rejection, management of drug-drug interactions and treatment of recurrent viral hepatitis. This article reviews the selection criteria, outcomes, and special management considerations for HIV-infected patients undergoing liver or kidney transplantation.

Surgical complications in 275 HIV-infected liver and/or kidney transplantation recipients.

BACKGROUND: In this report, we examine the surgical safety and complications (SC) among 125 liver (L) and 150 kidney (K) HIV+ transplantation (TX) recipients in a prospective nonrandomized U.S. multicenter trial. METHODS: Subjects were required to have CD4+ T-cell counts >200/100 cells/mm3 (K/L) and undetectable plasma HIV-1 RNA (Viral Load [VL]) (K) or expected posttransplantation suppression (L). Impact of SCs (N ≥ 7) was evaluated by use of the proportional hazards models. Baseline morbidity predictors for SCs (N ≥ 7) were assessed in univariate proportional hazards models. RESULTS: At median 2.7 (interquartile range 1.9-4.1) and 2.3 (1.0-3.7) years after TX, 3-month and 1-year graft survival were [K] 96% (95% CI 91%-98%) and 91% (95% CI 85%-94%) and [L] 91% (95% CI 85%-95%) and 77% (95% CI 69%-84%), respectively. A total of 14 K and 28 L graft losses occurred in the first year; 6 K and 11 L were in the first 3 months. A total of 26 (17%) K and 43 (34%) L experienced 29 and 62 SCs, respectively. In the liver multivariate model, re-exploration was marginally associated (hazard ratio [HR] 2.8; 95% CI 1.0-8.4; P = .06) with increased risk of graft loss, whereas a greater MELD score before transplantation (HR 1.07 per point increase; 95% CI: 1.01-1.14; P = .02), and detectable viral load before TX (HR 3.6; 95% CI 0.9-14.6; P = .07) was associated with an increased risk of wound infections/dehiscence. CONCLUSION: The rates and outcomes of surgical complications are similar to what has been observed in the non-HIV setting in carefully selected HIV-infected liver and kidney TX recipients.

Activation of host translational control pathways by a viral developmental switch.

In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate.