Outcomes of Liver Transplantation From Hepatitis C Virus-positive DCD Donors and Its Utilization Among Centers in the United States.

BACKGROUND: Donation after circulatory death (DCD) or hepatitis C virus (HCV+) liver grafts are underused among transplant centers in the United States. The study aimed to evaluate organ utilization and outcomes of liver grafts from DCD donors with HCV infection. METHODS: National registry and local center data of all deceased donor liver transplants performed between November 2016 and December 2021 were analyzed. All transplants were divided into 4 groups: HCV- DCD, HCV- donation after brain death [DBD], HCV+ DCD, and HCV+ DBD. The outcome of interest was 1-y graft survival. RESULTS: Out of 146 liver transplant centers in the United States, liver transplants were not performed from DCD donors, HCV+ donors, and a combination of DCD and HCV+ donors by 28.7%, 27%, and 70%-72% of centers, respectively. In multivariate analysis, increasing center acceptance ratio was associated with increased utilization of liver grafts from DCD HCV- and DCD HCV antibody-positive nucleic acid test negative donors. Nationally, 1-y graft survival of HCV- DCD liver grafts was lower compared with other groups (89% versus 92% HCV+ DCD versus 93% HCV+ DBD versus 92% HCV- DBD, log rank P < 0.0001). There was no difference in 1-y graft survival among groups locally. CONCLUSIONS: Liver grafts from HCV+ DCD donors have 1-y patient and graft survival comparable with DBD liver grafts from donors with or without HCV infection. These results encourage the widespread use of liver grafts from DCD and HCV+ donors and standardization of practice in DCD donation to expand the donor pool without compromising short-term outcomes.

Determinants of Long Waiting Time to Kidney Transplantation.

BACKGROUND: Disparity in waiting time to kidney transplantation led to new policy (KAS250). Our aims were to identify variables associated with long wait time (LWT); assess the impact of KAS250 on WT; and analyze modifiable transplant center behaviors correlated with WT. METHODS: SRTR data for adult deceased donor kidney transplants were analyzed. Time-periods from 8/1/2018-7/31/2019 and 5/1/2021-4/30/2022 were chosen for pre- and post-KAS250 analyses. Transplant centers were categorized as LWT or SWT centers depending on whether pre-KAS250 median center waiting times were greater or less than the national pre-KAS250 median waiting time of 57.8 months. RESULTS: In multivariate analysis, transplantation with HCV NAT negative kidneys was associated with an additional 21.3 months of WT (CI: 18.5-24.2, P < .0001), and transplantation with KDPI <85% kidneys was associated with an additional 10.8 months (CI: 8.2-13.3, P < .0001). Post-KAS250 national kidney transplant waiting time decreased from 61-58 months (P < .0001) and waiting time at LWT centers decreased from 74-69 months (P < .0001). Cold ischemic times (CIT) increased (20.2 hours vs 18.3 hours, P < .0001) and DGF rates also increased (32.7% vs 31.0%, P < .0001). Centers generally displayed more aggressive transplantation practices post-KAS250 however significant differences in DCD utilization, organ offer acceptance ratios and tolerance for long CIT persist between SWT and LWT centers. CONCLUSION: KAS250 has reduced waiting time disparities between SWT and LWT centers at the cost of increased CIT and DGF and reduced allocation efficiency. Significant differences in transplant practice persist between SWT and LWT centers.

Variation in DCD Liver Transplant Protocols Among Transplant Centers in the United States.

Background: Variation in donation after circulatory death (DCD) organ recovery and liver transplant practices exist among transplant centers. This study aimed to evaluate these practices among centers in the United States. Methods: Scientific Registry of Transplant Recipients data were accessed to identify centers that performed liver transplantation in 2021 and 2022. Surveys were sent to transplant centers that consistently performed ≥5 DCD liver transplants per year. Results: DCD liver transplants were performed by 95 centers (65.1%) of the 146 liver transplant centers in the United States. Survey results were recorded from 42 centers that consistently performed ≥5 DCD liver transplants per year, with a 59.5% response rate. Withdrawal-to-asystole and agonal time were used to define donor warm ischemia time (WIT) in 16% and 84% centers, respectively. Fifty-six percent of the centers did not use oxygen saturation to define donor WIT. Systolic blood pressure cutoffs used to define agonal time varied between 50 and 80 mm Hg, donor age cutoffs ranged between 55 and 75 y, and cold ischemia times varied between 4 and 10 h. Seventy-six percent of centers used normothermic machine perfusion for DCD liver transplantation. Conclusions: This study highlights the wide variation in use, recovery, and definition of donor WIT. Using national data to rigorously define best practices will encourage greater utilization of this important donor resource.

Textbook outcome: A novel metric in heart transplantation outcomes.

OBJECTIVE: Assessing heart transplant program quality using short-term survival is insufficient. We define and validate the composite metric textbook outcome and examine its association with overall survival. METHODS: We identified all primary, isolated adult heart transplants in the United Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files from May 1, 2005, to December 31, 2017. Textbook outcome was defined as length of stay 30 days or less; ejection fraction greater than 50% during 1-year follow-up; functional status 80% to 100% at 1 year; freedom from acute rejection, dialysis, and stroke during the index hospitalization; and freedom from graft failure, dialysis, rejection, retransplantation, and mortality during the first year post-transplant. Univariate and multivariate analyses were performed. Factors independently associated with textbook outcome were used to create a predictive nomogram. Conditional survival at 1 year was measured. RESULTS: A total of 24,620 patients were identified with 11,169 (45.4%, 95% confidence interval, 44.7-46.0) experiencing textbook outcome. Patients with textbook outcome were more likely free from preoperative mechanical support (odds ratio, 3.504, 95% confidence interval, 2.766 to 4.439, P < .001), free from preoperative dialysis (odds ratio, 2.295, 95% confidence interval, 1.868-2.819, P < .001), to be not hospitalized (odds ratio, 1.264, 95% confidence interval, 1.183-1.349, P < .001), to be nondiabetic (odds ratio, 1.187, 95% confidence interval, 1.113-1.266, P < .001), and to be nonsmokers (odds ratio, 1.160, 95% confidence interval,1.097-1.228, P < .001). Patients with textbook outcome have improved long-term survival relative to patients without textbook outcome who survive at least 1 year (hazard ratio for death, 0.547, 95% confidence interval, 0.504-0.593, P < .001). CONCLUSIONS: Textbook outcome is an alternative means of examining heart transplant outcomes and is associated with long-term survival. The use of textbook outcome as an adjunctive metric provides a holistic view of patient and center outcomes.

Textbook Outcome as a Quality Metric in Living and Deceased Donor Kidney Transplantation.

BACKGROUND: Quality in kidney transplantation is measured using 1-year patient and graft survival. Because 1-year patient and graft survival exceed 95%, this metric fails to measure a spectrum of quality. Textbook outcomes (TO) are a composite quality metric offering greater depth and resolution. We studied TO after living donor (LD) and deceased donor (DD) kidney transplantation. STUDY DESIGN: United Network for Organ Sharing data for 69,165 transplant recipients between 2013 and 2017 were analyzed. TO was defined as patient and graft survival of 1 year or greater, 1-year glomerular filtration rate of greater than 40 mL/min, absence of delayed graft function, length of stay of 5 days or less, no readmissions during the first 6 months, and no episodes of rejection during the first year after transplantation. Bivariate analysis identified characteristics associated with TO, and covariates were incorporated into multivariable models. Five-year conditional survival was measured, and center TO rates were corrected for case complexity to allow center-level comparisons. RESULTS: The national average TO rates were 54.1% and 31.7% for LD and DD transplant recipients. The hazard ratio for death at 5 years for recipients who did not experience TO was 1.92 (95% CI 1.68 to 2.18, p ≤ 0.0001) for LD transplant recipients and 2.08 (95% CI 1.93 to 2.24, p ≤ 0.0001) for DD transplant recipients. Center-level comparisons identify 18% and 24% of centers under-performing in LD and DD transplantation. High rates of TO do not correlate with transplantation center volume. CONCLUSION: Kidney transplant recipients who experience TO have superior long-term survival. Textbook outcomes add value to the current standards of 1-year patient and graft survival.

Textbook Outcome as a Quality Metric in Liver Transplantation.

Quality in liver transplantation (LT) is currently measured using 1-y patient and graft survival. Because patient and graft survival rates now exceed 90%, more informative metrics are needed. Textbook outcomes (TOs) describe ideal patient outcomes after surgery. This study critically evaluates TO as a quality metric in LT. Methods: United Network for Organ Sharing data for 25 887 adult LT recipients were used to define TO as patient and graft survival >1 y, length of stay ≤10 d, 0 readmissions within 6 mo, absence of rejection, and bilirubin <3 mg/dL between months 2 and 12 post-LT. Univariate analysis identified donor and recipient characteristics associated with TO. Covariates were analyzed using purposeful selection to construct a multivariable model, and impactful variables were incorporated as linear predictors into a nomogram. Five-year conditional survival was tested, and center TO rates were corrected for case complexity to allow for center-level comparisons. Results: The national average TO rate is 37.4% (95% confidence interval, 36.8%-38.0%). The hazard ratio for death at 5 y for patients who do not experience TO is 1.22 (95% confidence interval, 1.11-1.34; P ≤ 0.0001). Our nomogram predicts TO with a C-statistic of 0.68. Center-level comparisons identify 31% of centers as high performing and 21% of centers as below average. High rates of TO correlate only weakly with center volume. Conclusions: The composite quality metric of TO after LT incorporates holistic outcome measures and is an important measure of quality in addition to 1-y patient and graft survival.

Dynamic impact of liver allocation policy change on donor utilization.

Liver allocation policy was changed to reduce variance in median MELD scores at transplant (MMaT) in February 2020. "Acuity circles" replaced local allocation. Understanding the impact of policy change on donor utilization is important. Ideal (I), standard (S), and non-ideal (NI) donors were defined. NI donors include older, higher BMI donors with elevated transaminases or bilirubin, history of hepatitis B or C, and all DCD donors. Utilization of I, S, and NI donors was established before and after allocation change and compared between low MELD (LM) centers (MMaT ≤ 28 before allocation change) and high MELD (HM) centers (MMaT > 28). Following reallocation, transplant volume increased nationally (67 transplants/center/year pre, 74 post, p .0006) and increased for both HM and LM centers. LM centers significantly increased use of NI donors and HM centers significantly increased use of I and S donors. Centers further stratify based on donor utilization phenotype. A subset of centers increased transplant volume despite rising MMaT by broadening organ acceptance criteria, increasing use of all donor types including DCD donors (98% increase), increasing living donation, and transplanting more frequently for alcohol associated liver disease. Variance in donor utilization can undermine intended effects of allocation policy change.

A Survey of Current Procurement Travel Practices, Accident Frequency, and Perceptions of Safety.

In 2018, 81% of the 36, 529 solid organs transplanted in the United States came from deceased donors. These organs were recovered through widespread use of aeromedical and emergency ground transportation systems. Urgently scheduled travel to remote hospitals at night and in varied weather conditions carries risk for the transplant professionals involved. A landmark survey conducted in 2007 demonstrated that 80% of respondents had experienced a "near-miss" event while on a procurement trip, and 15% had been involved in at least 1 accident. One decade later, we sought to revisit the issue of procurement related travel safety. METHODS: A 32 question survey designed to interrogate travel practice, accident frequency, and perceptions of safety was sent to the American Society of Transplant Surgeons membership. RESULTS: Our survey response rate was 20.6%. At least 1 travel accident with bodily injury was reported by 23% of respondents and yet only 7% of respondents reported feeling "unsafe" or "very unsafe" during procurement travel. Sixteen percent of respondents participated in a procurement at a dedicated organ procurement facility, and only 53% of procurement surgeons completed at least 1 deceased donor procurement at their own hospital facility within the preceding 12 months. CONCLUSIONS: In a field where increasingly aggressive organ utilization is the norm, the efficiency and safety of procurement travel merits ongoing consideration. Addressing these concerns takes on new significance as organ allocation policies change geographic distribution to expand the extent of travel required for surgical teams.

TGF-ß1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.

Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-ß1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases.

Surgical treatment of an extrarenal pseudoaneurysm after kidney transplantation.

A 69-year-old man who underwent a kidney transplantation developed a large pseudoaneurysm at the anastomosis between the right external iliac artery and renal transplant artery. After an unsuccessful attempt using percutaneous thrombin injection, the patient underwent open exploratory laparotomy and surgical ligation of the pseudoaneurysm with preservation of renal graft function.