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Background: Vascularized composite allograft transplantation is a treatment option for complex tissue injuries; however, ischemia reperfusion injury and high acute rejection rates remain a challenge. Hypothermic machine perfusion using acellular storage perfusate is a potential solution. This study evaluated the University of Wisconsin Kidney Preservation Solution-1 (KPS-1) compared with normal saline (NS) for preservation of donor rat hindlimbs subjected to 24 h of ex vivo perfusion cold storage., Methods: Hindlimbs were subjected to 24-h perfusion cold storage with heparinized KPS-1 (n = 6) or heparinized NS (n = 6). Flow, resistance, and pH were measured continuously. At the end of the 24-h period, tissue was collected for histological analysis of edema and apoptosis., Results: KPS-1 perfused limbs showed significantly less edema than the NS group, as evidenced by lower limb weight gain ( P  < 0.001) and less interfascicular space ( P  < 0.001). KPS-perfused muscle had significantly less cell death than NS-perfused muscle based on terminal deoxynucleotidyl transferase dUTP nick-end labeling ( P  < 0.001) and cleaved caspase-3 staining ( P  = 0.045). During hypothermic machine perfusion, a significant decrease in pH over time was detected in both groups, with a significantly greater decline in pH in the KPS-1 group than in the NS group. There were no significant differences overall and over time in flow rate or vascular resistance between the KPS and NS groups., Conclusions: Perfusion with KPS-1 can successfully extend vascularized composite allograft perfusion cold storage for 24 h in a rat hindlimb model without significant edema or cell death., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Aims: Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA., Methods: Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing., Results: Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p = 0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3 + M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm 2 , p = 0.03). The number of Galectin-3 + M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation., Conclusions: Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA., (© 2023 Japan Society of Hepatology.)

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants., Competing Interests: E. R. and C. L. E. are inventors on patents US10905780B2 and US11253613B2., (This journal is © The Royal Society of Chemistry.)

Background: Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study., Methods: Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival., Results: 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI ​= ​2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios., Conclusions: Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest. This content is the responsibility of the authors alone and does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This study uses data obtained from the public-use file of the National Longitudinal Mortality Study. The views expressed in this paper are those of the authors and do not necessarily reflect the view of the National Longitudinal Mortality Study, the Bureau of the Consensus, or the project sponsors: the National Heart, Lung, and Blood Institute, the National Cancer Institute, the National Institute on Aging, and the National Center for Health Statistics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatoblastoma (HBL). Although post-transplant outcomes have improved in the contemporary era, the impact of donor graft type on survival remains unclear., Methods: Using the United Network for Organ Sharing database (02/2002-06/2021), demographics, clinical characteristics, and patient and graft survival were analyzed in children (<18 years) who underwent LT for HBL according to donor graft type. The Kaplan-Meier method, log-rank tests, and Cox regression modeling were used to evaluate the effect of whole, partial, and split deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) on patient and graft survival., Results: A total of 590 pediatric HBL LT recipients (344 whole graft DDLT; 62 partial graft DDLT; 139 split graft DDLT; 45 LDLT) were included. During 2012-2021 the proportion of LDLTs for HBL decreased to about 5% compared with about 11% during 2002-2011. No significant differences were identified by donor graft type in either patient survival (log-rank test, p = .45) or graft survival (log-rank test, p = .69). The results remained similar during the 2002-2011 era, while during the 2012-2021 era, split graft DDLT was associated with decreased graft loss risk versus whole graft DDLT (hazard ratio: 0.48, 95% confidence interval: 0.23-0.99, p = .046) without any other significant between-group differences., Conclusions: Utilizing non-whole liver grafts can increase access to LT in children with unresectable HBL while ensuring favorable outcomes. LDLT is underutilized in children with HBL in the United States, and efforts to explore LDLT options should be undertaken., (© 2023 Wiley Periodicals LLC.)

Background: Hepatic undifferentiated embryonal sarcoma (HUES) is the third most common primary hepatic malignancy in children. If unresectable, liver transplantation (LT) is the only curative option. Historically, HUES LT outcomes were not favorable; however, modern-era data are lacking. We aimed to describe LT outcomes in children with HUES and compared with LT outcomes in children transplanted for hepatoblastoma (HBL) and non-malignancy indications., Methods: Children 18 years or younger with HUES who underwent LT from 1987 to 2021 were identified from the Scientific Registry of Transplant Recipients database. Graft and patient survival were studied in HUES and LT recipients with HBL and non-malignancy indications using Kaplan-Meier analysis. Cox regression was used to compare patient and graft survival among groups, controlling for confounders., Results: Twenty-one children with HUES underwent LT during the study period with a median age at LT of 10 years (IQR: 8-12 years). One and five-year patient survival for HUES recipients was not significantly different from that of recipients with HBL (p = .3) or non-malignancy diagnoses (p = .6). There were no deaths due to HUES recurrence. In multivariable Cox regression, HUES did not increase risk of either patient or graft loss as compared to HBL (HR 2.36, p = .2) or non-malignancy indications (HR 0.74, p = .7)., Conclusion: LT outcomes are more favorable in patients with HUES than historically described, and similar to LT outcomes of patients with HBL and non-malignancy indications. Transplant should be considered for HUES patients with unresectable localized tumors., (© 2023 Wiley Periodicals LLC.)

Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e. the amount of molecular oxygen present in the tissue is a direct result of supply (perfusion) and consumption. Thus, measurement of [Formula: see text] is an effective method to monitor tissue viability. However, tissue oximetry sensors commonly used in clinical practice instead rely on measuring oxygen saturation ([Formula: see text]), largely due to the lack of reliable, affordable [Formula: see text] sensing solutions. To address this issue we present a proof-of-concept design and validation of a low-cost, lifetime-based oxygen sensing fiber. The sensor consists of readily-available off-the shelf components such as a microcontroller, a light-emitting diode (LED), an avalanche photodiode (APD), a temperature sensor, as well as a bright in-house developed porphyrin molecule. The device was calibrated using a benchtop setup and evaluated in three in vivo animal models. Our findings show that the new device design in combination with the bright porphyrin has the potential to be a useful and accurate tool for measuring [Formula: see text] in tissue, while also highlighting some of the limitations and challenges of oxygen measurements in this context., (© 2023. Springer Nature Limited.)

Perioperative dysfunction of the fibrinolytic system may play a role in adverse outcomes for liver transplant recipients. There is a paucity of data describing the potential impact of the postoperative fibrinolytic system on these outcomes. Our objective was to determine whether fibrinolysis resistance (FR), on postoperative day one (POD-1), was associated with early allograft dysfunction (EAD). We hypothesized that FR, quantified by tissue plasminogen activator thrombelastography, is associated with EAD. Tissue plasminogen activator thrombelastography was performed on POD-1 for 184 liver transplant recipients at a single institution. A tissue plasminogen activator thrombelastography clot lysis at 30 minutes of 0.0% was identified as the cutoff for FR on POD-1. EAD occurred in 32% of the total population. Fifty-nine percent (n=108) of patients were categorized with FR. The rate of EAD was 42% versus 17%, p <0.001 in patients with FR compared with those without, respectively. The association between FR and EAD risk was assessed using multivariable logistic regression after controlling for known risk factors. The odds of having EAD were 2.43 times (95% CI, 1.07-5.50, p =0.03) higher in recipients with FR [model C statistic: 0.76 (95% CI, 0.64-0.83, p <0.001]. An additive effect of receiving a donation after circulatory determination of death graft and having FR in the rate of EAD was observed. Finally, compared with those without FR, recipients with FR had significantly shorter graft survival time ( p =0.03). In conclusion, FR on POD-1 is associated with EAD and decreased graft survival time. Postoperative viscoelastic testing may provide clinical utility in identifying patients at risk for developing EAD, especially for recipients receiving donation after circulatory determination of death grafts., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Compared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation., Methods: From January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients., Results: Rates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P < 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P < 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32)., Conclusion: Although initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts to report.

Background: Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT., Methods: The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance., Results: Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01)., Conclusions: ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed., (© 2022 Wiley Periodicals LLC.)

Introduction: High output, persistent ascites (PA) is a common complication following liver transplant (LT). Recent work has identified that platelets help maintain endothelial integrity and can decrease leakage in pathological states. We sought to assess the association of PA following LT with platelet count and platelet function., Methods: Clot strength (MA) is a measure of platelet function and was quantified using thrombelastography (TEG). Total drain output following surgery was recorded in 24-h intervals during the same time frame as TEG. PA was considered >1 L on POD7, as that much output prohibits drain removal., Results: 105 LT recipients with moderate or high volume preoperative ascites were prospectively enrolled. PA occurred in 28%. Platelet transfusions before and after surgery were associated with PA, in addition to POD5 TEG MA and POD5 MELD score. Patients with PA had a longer hospital length of stay and an increased rate of intraabdominal infections., Conclusion: Persistent ascites following liver transplant is relatively common and associated with platelet transfusions, low clot strength, and graft dysfunction., (Copyright © 2022. Published by Elsevier Inc.)

Background: Immediate extubation (IE) following pediatric liver transplantation is being increasingly performed. The aim of this study was to characterize the rate of IE at our institution and identify recipient factors predictive of IE., Methods: All pediatric liver transplants performed at our institution between January 1, 2015 and December 31, 2020 were reviewed. Retransplants and multi-organ transplants were excluded. IE was defined as extubation in the operating room following transplant. Backward stepwise logistic regression at a p-value threshold of .05 was performed to identify variables associated with IE., Results: IE was achieved in 58 (72%) of the 81 pediatric liver transplants. The IE cohort had significantly shorter ICU length of stay and overall hospital length of stay, though IE was not an independent predictor of posttransplant length of stay. Age <2 years, preoperative mechanical ventilation, and total intraoperative epinephrine and dopamine infusion requirements were significant, independent risk factors against IE. This multivariable model was highly predictive of IE (area under the curve = 0.89)., Conclusions: We describe the highest rate of IE postpediatric liver transplantation that has been reported to date and identified significant risk factors against successful IE., (© 2022 Wiley Periodicals LLC.)

Background: Infection is a leading cause of morbidity in liver transplant (LT). Considering that the fibrinolytic system is altered in sepsis, we investigated the relationship between fibrinolysis resistance (FR) and post-transplant infection., Methods: Fibrinolysis was quantified using thrombelastography (TEG) with the addition of tPA to quantify FR. FR was defined as LY30 = 0% and stratified as transient if present on POD1 or POD5 (tFR), persistent (pFR) if present on both, or no FR (nFR) if absent., Results: 180 LT recipients were prospectively enrolled. 52 (29%) recipients developed infection. 72 had tFR; 37 had pFR; and 71 had nFR. Recipients with pFR had significantly greater incidence of infections (51% vs. 26% tFR vs. 20% nFR, p = 0.002). pFR was independently associated with increased odds of post-transplant infection (adjusted OR 3.39, p = 0.009)., Conclusions: Persistent fibrinolysis resistance is associated with increased risk of post-transplant infection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Content available: Audio Recording., Competing Interests: C.L.M. consults for Albireo., (© 2022 American Association for the Study of Liver Diseases.)

Introduction: Kasai hepatoportoenterostomy is the standard of care for children with biliary atresia, but a majority of patients progress to end-stage liver disease and require a salvage liver transplant. Given the high failure rates of the hepatoportoenterostomy operation, some have advocated for primary liver transplantation as a superior treatment approach. The aim of this study was to compare outcomes of pediatric candidates with biliary atresia listed for primary vs. salvage liver transplantation., Methods: The SRTR/OPTN database was retrospectively reviewed for all children with biliary atresia listed for liver transplant between March 2002 and February 2021. Candidates were categorized as primary liver transplant if they had not undergone previous abdominal surgery prior to listing and salvage liver transplant if they had. Salvage transplants were further categorized as early failure if listed within the first year of life or late failure if listed at an older age., Results: 3438 children with biliary atresia were listed for transplant during the study period, with 15% of them listed for a primary transplant, 17% for salvage transplant after early failure, and 67% after late failure. Recipients of salvage liver transplant with late failure had lower bilirubin levels and were less critically ill as demonstrated by MELD/PELD scores and hospitalization status. Correspondingly, these recipients had higher waiting list and graft survival, though this did not remain statistically significant after adjustment in multivariable models. There were no differences in waiting list, recipient, or graft survival with primary vs. salvage liver transplant after early failure., Conclusion: Kasai hepatoportoenterostomy should remain the standard of care in biliary atresia as it may delay need for transplant beyond the first year of life in a subset of recipients and does not jeopardize subsequent transplant outcomes, even with early failure., Levels of Evidence: Retrospective cohort study (Level III)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pediatric living donor liver transplantation (LDLT) remains infrequently performed in the United States and localized to a few centers. This study aimed to compare pediatric waiting list and posttransplant outcomes by LDLT center volume., Methods: The Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network database was retrospectively reviewed for all pediatric (age <18 y) liver transplant candidates listed between January 1, 2009, and December 31, 2019. The average annual number of LDLT, deceased donor partial liver transplant (DDPLT), and overall (ie, LDLT + DDPLT + whole liver transplants) pediatric liver transplants performed by each transplant center during the study period was calculated., Results: Of 88 transplant centers, only 44 (50%) performed at least 1 pediatric LDLT during the study period. LDLT, DDPLT, and overall transplant center volume were all positively correlated. LDLT center volume was protective against waiting list dropout after adjusting for confounding variables (adjusted hazard ratio, 0.92; 95% confidence interval, 0.86-0.97; P  = 0.004), whereas DDPLT and overall center volume were not ( P  > 0.05); however, DDPLT center volume was significantly protective against both recipient death and graft loss, whereas overall volume was only protective against graft loss and LDLT volume was not protective for either., Conclusions: High-volume pediatric LDLT center can improve waiting list survival, whereas DDPLT and overall volume are associated with posttransplant survival. Expertise in all types of pediatric liver transplant options is important to optimize outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: One in four liver transplants (LT) require return to the operating room(R-OR) within 48 h of surgery. We hypothesize that donor, recipient, and intraoperative factors will predict R-OR., Methods: LT recipients were enrolled in an observational study to measure coagulation with thrombelastography (TEG) were assessed with transplant recipient and donor variables for risk of R-OR., Results: 160 recipients with a median age of 55 years and a MELD-Na of 22 were analyzed. R-OR occurred in 22%. Recipient BMI (p = 0.006), donor heavy alcohol use (p = 0.017), TEG MA (p = 0.013) during the anhepatic phase of surgery, TEG MA at anhepatic and 30-min after reperfusion (p < 0.05), and red blood cell transfusions (p < 0.001) were associated with R-OR., Conclusion: The vexing triad of recipient obesity, heavy donor alcohol use, and low TEG MA were associated with a high rate of R-OR. Strategies to reduce this sub-optimal combination of risk factors could reduce the frequency of unplanned re-operations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has affected all aspects of the US healthcare system, including liver transplantation. The objective of this study was to understand national changes to pediatric liver transplantation during COVID-19., Methods: Using SRTR data, we compared waitlist additions, removals, and liver transplantations for pre-COVID-19 (March-November 2016-2019), early COVID-19 (March-May 2020), and late COVID-19 (June-November 2020)., Results: Waitlist additions decreased by 25% during early COVID-19 (41.3/month vs. 55.4/month, p < .001) with black candidates most affected (p = .04). Children spent longer on the waitlist during early COVID-19 compared to pre-COVID-19 (140 vs. 96 days, p < .001). There was a 38% decrease in liver transplantations during early COVID-19 (IRR 0.62, 95% CI 0.49-0.78), recovering to pre-pandemic rates during late COVID-19 (IRR 1.03, NS), and no change in percentage of living and deceased donors. White children had a 30% decrease in overall liver transplantation but no change in living donor liver transplantation (IRR 0.7, 95% CI 0.50-0.95; IRR 0.96, NS), while non-white children had a 44% decrease in overall liver transplantation (IRR 0.56, 95% CI 0.40-0.77) and 81% decrease in living donor liver transplantation (IRR 0.19, 95% CI 0.02-0.76)., Conclusions: The COVID-19 pandemic decreased access to pediatric liver transplantation, particularly in its early stage. There were no regional differences in liver transplantation during COVID-19 despite the increased national sharing of organs. While pediatric liver transplantation has resumed pre-pandemic levels, ongoing racial disparities must be addressed., (© 2021 Wiley Periodicals LLC.)

Background: This study aimed to compare the outcomes of hepatitis C virus (HCV) positive (+) female liver transplant recipients to HCV negative (-) female and HCV+ male recipients before and after the direct-acting-antiviral (DAA) era., Methods: The United Network for Organ Sharing liver transplant database was retrospectively reviewed from 2002 to 2017. The DAA era was defined as ≥2014., Results: In the pre-DAA era, HCV+ female recipients had greater risk for graft failure compared with HCV+ male (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.03) and HCV- female (HR, 1.51; 95% CI, 1.43-1.60; P < 0.001) recipients. In the post-DAA era, HCV+ female recipients had lower risk for graft failure compared with HCV+ male recipients (HR, 0.82; 95% CI, 0.70-0.97; P = 0.02) and equivalent outcomes to HCV- female recipients. HCV+ female recipients with graft failure had increased likelihood of graft failure due to disease recurrence compared with HCV+ male recipients in the pre-DAA era (odds ratio, 1.23; 95% CI, 1.08-1.39; P = 0.001) but not in the post-DAA era., Conclusions: Although historically HCV+ female recipients were at disproportionately increased risk for graft failure and disease recurrence, this disparity has been eliminated in the DAA era., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to compare trends in use of drug overdose (DO) donors in adult versus pediatric liver transplants and the utilization of split liver transplantation in this donor population., Methods: The United Network for Organ Sharing database was reviewed for deceased donor liver transplants from March 2002 to December 2017. Recipients were categorized by donor mechanism of death. Donor splitting criteria was defined as age <40 y, single vasopressor or less, transaminases no >3 times the normal limit, and body mass index ≤ 28 kg/m2., Results: Adult liver transplants from DO donors increased from 2% in 2002 to 15% in 2017, while pediatric liver transplants from DO donors only increased from <1% to 3% in the same time. While 28% of DO donors met splitting criteria, only 3% of those meeting splitting criteria were used as a split graft. Both pediatric and adult recipients of DO donor livers achieved excellent patient and graft survival., Conclusions: DO donors are underutilized in pediatric liver transplantation. Increased splitting of DO donor livers could significantly decrease, if not eliminate, the pediatric liver waiting list., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Recently developed biofabrication technologies are enabling the production of three-dimensional engineered tissues containing vascular networks which can deliver oxygen and nutrients across large tissue volumes. Tissues at this scale show promise for eventual regenerative medicine applications; however, the implantation and integration of these constructs in vivo remains poorly studied. Here, we introduce a surgical model for implantation and direct in-line vascular connection of 3D printed hydrogels in a porcine arteriovenous shunt configuration. Utilizing perfusable poly(ethylene glycol) diacrylate (PEGDA) hydrogels fabricated through projection stereolithography, we first optimized the implantation procedure in deceased piglets. Subsequently, we utilized the arteriovenous shunt model to evaluate blood flow through implanted PEGDA hydrogels in non-survivable studies. Connections between the host femoral artery and vein were robust and the patterned vascular channels withstood arterial pressure, permitting blood flow for 6 h. Our study demonstrates rapid prototyping of a biocompatible and perfusable hydrogel that can be implanted in vivo as a porcine arteriovenous shunt, suggesting a viable surgical approach for in-line implantation of bioprinted tissues, along with design considerations for future in vivo studies. We further envision that this surgical model may be broadly applicable for assessing whether biomaterials optimized for 3D printing and cell function can also withstand vascular cannulation and arterial blood pressure. This provides a crucial step toward generated transplantable engineered organs, demonstrating successful implantation of engineered tissues within host vasculature., Competing Interests: JSM and BG are cofounders of and hold an equity stake in the startup company Volumetric, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Galván, Paulsen, Kinstlinger, Marini, Didelija, Yoeli, Grigoryan and Miller.)

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required., (© 2020 Wiley Periodicals LLC.)

Background: The separation of conjoined twins is a challenging and rare operation. Recent technological advances in imaging and three-dimensional printing (3DP) have allowed for enhancements in preoperative surgical planning and intraoperative anatomical orientation for complex operations. This report aims to consolidate the current clinical evidence utilizing 3DP models as an effective tool for surgical planning of conjoined twin separation and to detail our surgical approach for complex hepatic separation and management., Methods: A literature review was conducted for conjoined twin separations with preoperative use of 3D models including age at attempted separation, operative outcome, 3D modality, and postoperative course between 1998 and 2020. We also conducted a chart review of our electronic medical record for conjoined twin separations between January 2015 and December 2019., Results: We report two cases of conjoined twin separation with preoperative use of 3DP models from our institution: one set in the thoracoomphaloischiopagus orientation and the other set in the thoracoomphalopagus orientation with the presence of intrahepatic vascular anomalies. The literature review produced 10 case reports of conjoined twin separation with use preoperative 3D models accounting for 17 individual separation procedures. We summarize our preoperative radiological planning, the evidence of 3DP models as an educational and preoperative tool, ideal timing for separation, and our surgical approach for complex hepatic separation., Conclusions: Conjoined twin separation requires a multidisciplinary effort to address the multisystem surgical and medical needs of these patients. These complex patients require extensive preoperative imaging for planning separation, and we strongly recommend utilizing 3D printed models when possible for better surgeon understanding of complex variable anatomy. We have found numerous reports of successful conjoined twin separation using 3DP technology in preoperative planning. The use of three-dimensional printed models for preoperative assessments is an invaluable tool and is rapidly improving in fidelity., Type of Study: Operative technique and case series., Level of Evidence: Level IV., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Increasingly, for pediatric patients with short bowel syndrome (SBS), intestinal lengthening procedures such as serial transverse enteroplasty (STEP) are being offered with the hope of improving patients' chances for achieving enteral autonomy. However, it remains unclear to what extent STEP reduces the long-term need for intestinal transplant or improves survival., Methods: Based on existing literature, a decision analytic Markov state transition model was created to simulate the life of 1,000 pediatric SBS patients. Two simulations were modeled: 1) No STEP: patients were listed for transplant once medical management failed and 2) STEP: patients underwent STEP therapy and subsequent transplant listing if enteral autonomy was not achieved. Sensitivity analysis of small bowel length and anatomy was completed. Base case patients were defined as neonates with a small bowel length of 30cm., Results: For base case patients with an ostomy and a NEC SBS etiology, STEP was associated with increased rates of enteral autonomy after 10 years for patients with an ICV (53.9% [STEP] vs. 51.1% [No STEP]) and without an ICV (43.4% [STEP] vs. 36.3% [No STEP]). Transplantation rates were also reduced following STEP therapy for both ICV (17.5% [STEP] vs. 18.2% [No STEP]) and non-ICV patients (20.2% [STEP] vs. 22.1% [No STEP]). 10-year survival was the highest in the (+) STEP and (+) ICV group (85.4%) and lowest in the (-) STEP and (-) ICV group (83.3%)., Conclusions: For SBS patients, according to our model, STEP increases rates of enteral autonomy, reduces need for intestinal transplantation, and improves long-term survival., Type of Study: Economic/Decision Analysis or Modeling Studies LEVEL OF EVIDENCE: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Obesity has been associated with both increased progression of chronic kidney disease (CKD) as well as with a paradoxical improvement in survival among end-stage renal disease patients undergoing hemodialysis. As such, the optimal weight management strategy for obese CKD patients remains unclear., Objective: To estimate the outcomes of obese, CKD stage 3b patients after 3 weight loss interventions, including medical weight management, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), were followed to determine which strategy optimizes long-term survival., Setting: University hospital, Aurora, Colorado., Methods: A decision analytic Markov state transition model was created to simulate the life of 30,000 obese patients with CKD stage 3b, as they progressed to end-stage renal disease, transplantation, and death. Life expectancy after conservative medical weight management, RYGB, and SG were estimated. Base case patients were defined as being 50 years old and having a preintervention BMI of 40 kg/m 2 . Sensitivity analysis of initial BMI was performed. All Markov parameters were extracted from literature review., Results: RYGB and SG were associated with improved survival for patients with preintervention body mass index of >38 kg/m 2 . Compared with conservative weight management, base case patients who underwent RYGB gained 10.6 months of life, and gained 8.3 months of life after SG., Conclusions: Balancing progression of CKD with improved survival on end-stage renal disease for obese patients requires selective use of weight management strategies. RYGB and SG improved survival for CKD patients with Class II and III obesity, but not for patients with Class I obesity. As such, aggressive weight loss interventions should be reserved for patients with Class II and III obesity, while more conservative methods should be offered to those with Class I obesity., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation., Methods: A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling., Results: A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients., Conclusions: Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.

Introduction: The use of bariatric surgery has increased for morbidly obese patients with end stage renal disease (ESRD) for whom listing on the waitlist is often restricted until a certain BMI threshold is achieved. Effective weight loss for this population improves access to life-saving renal transplantation. However, it is unclear whether sleeve gastrectomy (SG) vs Roux-en-Y gastric bypass (RYGB) is a more effective therapy for these patients., Methods: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with ESRD who were deemed ineligible to be waitlisted for renal transplantation unless they achieved a BMI less than 35 kg/m 2 . Life expectancy following weight management (MWM), RYGB, and SG were estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m 2 . Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review., Results: RYGB improved survival compared with SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 1.3 additional years of life compared with patient's who underwent SG and 2.6 additional years of life compared with MWM., Conclusions: RYGB improves access to renal transplantation and thereby increases long-term survival compared with SG and MWM. The use of SG may be incongruent with the goal of improving access to renal transplantation for morbidly obese patients.

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post-transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy-two (22%) patients were measles non-immune, and 42/67 (63%) were varicella non-immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27-27.41) and technical variant graft (OR 0.07, 95% CI 0.01-0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non-immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30-11.01). This study demonstrates that non-immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non-immunity in this high-risk population., (© 2019 Wiley Periodicals, Inc.)

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor., (© 2019 Wiley Periodicals, Inc.)

The practice of uncontrolled donation after cardiac death (uDCD) has been met with tepid interest within the United States transplant community. Hesitancy stems largely from fears of eroding public trust due to complex ethical issues involving consent. Beyond ethical concerns, uDCD creates unique logistic challenges to obtain and to preserve organs within a short time frame. This mandates that organ recovery centers be able to rapidly mobilize, and that traditional cold preservation techniques may be inadequate. Proof of effective uDCD organ recovery comes from several European nations, and the frequency of its use is increasing due to early promising results. These scarce resources provide life-saving organs to desperate transplant candidates who otherwise experience high morbidity and mortality on a transplant waitlist. The objective of this review will be to provide an overview of the European experience with uDCD and discuss the unique ethical and logistic challenges associated with its implementation in the United States. Given existing models for it successful use, uDCD remains a poorly utilized source of donors in the United States at this time., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year., Summary of Background Data: Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success., Methods: We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression., Results: There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001)., Conclusion: In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.