Utilization Of Allografts Research Articles

Graft Failure and Contralateral ACL Injuries After Primary ACL Reconstruction: An Analysis of Risk Factors Using Interpretable Machine Learning.

Anterior cruciate ligament (ACL) reconstruction (ACLR) can be successful in restoring knee stability. However, secondary ACL injury, either through graft failure or contralateral injury, is a known complication and can significantly impact the ability of a patient to return successfully to previous activities. To develop and internally validate an interpretable machine learning model to quantify the risk of graft failure and contralateral ACL injury in a longitudinal cohort treated with ACLR. Case-control study; Level of evidence, 3. An established geographic database of >600,000 patients was used to identify patients with a diagnosis of ACL rupture between 1990 and 2016 with a minimum 2-year follow-up. Medical records were reviewed for relevant patient information and 4 candidate machine learning algorithms were evaluated for prediction of graft failure and contralateral ACL injury in patients after ACLR as identified either on magnetic resonance imaging or via arthroscopy. Performance of the algorithms was assessed through discrimination, calibration, and decision curve analysis. Model interpretability was enhanced utilizing global variable importance plots and partial dependence curves. A total of 1497 patients met inclusion criteria. Among them, 140 (9.4%) had graft failure and 128 (8.6%) had a contralateral ACL injury after index surgery at a median follow-up of 140.7 months (interquartile range, 77.2-219.2 months). The best performing models achieved an area under the receiver operating characteristics curve of 0.70 for prediction of graft failure and 0.67 for prediction of contralateral ACL injury, outperforming a logistic regression fitted on the identical feature set. Notable predictors for increased risk of graft failure included younger age at injury, body mass index (BMI) <30, return to sports <13 months, initial time to surgery >75 days, utilization of allograft, femoral/tibial fixation with suspension/expansion devices, concomitant collateral ligament injury, and active or former smoking history. Predictors of contralateral ACL injury included greater preoperative pain, younger age at initial injury, BMI <30, active smoking history, initial time to surgery >75 days, history of contralateral knee arthroscopies, and involvement in contact sports. Less than 18% of all patients who undergo ACLR should be expected to sustain either a graft failure or contralateral ACL injury. Machine learning models outperformed logistic regression and identified greater preoperative pain, younger age, BMI <30, earlier return to higher activity, and time to surgical intervention >75 days as common risk factors for both graft failure as well as contralateral ACL injury after ACLR. Surgeon-modifiable risk factors for graft failure included allograft and femoral/tibial fixation with a suspension/expansion combination.

Poster 290: Meniscus Transplants Delay Arthroplasty in Patients Over 50 Years of Age

Objectives: This study evaluates the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years of age previously advised to have a joint arthroplasty. The reason this study is important is because a 10-year delay in knee arthroplasty has been shown to reduce the lifetime revision rate. It was hypothesized that as opposed to debridement or meniscectomy alone, these subjects would benefit from a meniscus transplant in terms of improved knee symptoms, function, and delay of arthroplasty. Methods: One-hundred eight meniscus allograft transplants (MATs) using the arthroscopic 3-tunnel technique between 1997 and 2019 in patients over 50 were reviewed. Eighty-six of 108 (79.6%) patients met eligibility for this case series report. Inclusion criteria were patients recommended a knee arthroplasty with pain and preservation of some joint space by standing anterior-posterior and posterior-anterior flexion x-ray. Exclusion criteria were defined as lack of joint space, failure to comply with rehabilitation protocol or complete questionnaires. International Knee Documentation Committee and visual analog scale scores were obtained longitudinally. Time from meniscus transplantation to arthroplasty was measured with failure defined as allograft revision or excision, progression to arthroplasty, or same or increased pain. Results: Over the follow-up range of 2 to 25 years, 41 of 86 (47.6%) patients progressed to arthroplasty at a mean of 8.6 years. At the time of reporting, 41 of 86 (47.6%) patients had intact meniscus transplants. In subjects with intact meniscus allografts, significant improvements (p &lt; 0.05) were observed in pain and function. These improvements were sustained through ten years post-operatively, which correlated to a mean of 65.8 years of age. Conclusions: Meniscus allografts in combination with other arthroscopic knee treatments delay arthroplasty and improve symptoms of pain and function in a population over 50 who are otherwise candidates for knee arthroplasty. Limitations include the lack of a control population and the difficulty separating the relative contribution of concomitant procedures from meniscus transplantation alone to the clinical benefit observed. [Figure: see text][Figure: see text]

Diagnostic and Prognostic Value of Machine Perfusion Biomarkers in Kidney Graft Evaluation

BackgroundWith the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages. Materials and MethodsWe conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010. ResultsIn this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive. DiscussionThe review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes.

Meniscus Allograft Transplantation in Conjunction With Arthroscopic Biologic Knee Restoration Delays Arthroplasty in Patients Older Than 50 Years

The purpose of this study is to evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years of age previously advised joint arthroplasty. One hundred eight meniscus allograft transplants (MATs) using the arthroscopic three tunnel technique between 1997 and 2019 in patients over 50 years of age were retrospectively reviewed with two-year minimum follow-up period. Inclusion criteria were patients recommended knee arthroplasty with pain and preservation of some joint space by standing flexion x-rays. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol or complete research questionnaires. International Knee Documentation Committee (IKDC) composite and isolated pain scale were evaluated longitudinally. Time from MAT to arthroplasty was measured with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain. Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range of 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (p<0.001) in pain and function as assessed by IKDC. These improvements were sustained ten years post-operatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference (MCID) through 10 years post-operatively. Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates over 50 years of age. Influences of concomitant procedures cannot be defined.

INITIATION OF PROCESS STANDARDIZATION TO FABRICATE DEMINERALIZED BONE DIRECTED TOWARDS MAKING MATERIALS FOR BONE GRAFTING

Background: Bone tissue, a vital component for self-healing. This inherent regenerative capacity enables bones to repair themselves following injury or damage. Understanding the mechanisms behind bone tissue self-healing is of great significance in the field of medical research and has implications for the development of novel therapeutic approaches. In this article, we explore the fundamental characteristics and mechanisms underlying the self-healing properties of bone tissue. In certain instances of trauma or pathological conditions resulting in bone defects, the natural healing process may be insufficient. Consequently, the implementation of bone transplant interventions becomes imperative for successful bone regeneration. The predominant origins of bone grafts encompass autologous, homologous, and heterologous sources. The allograft, a widely utilized bone grafting technique, has gained significant popularity, and is currently in high demand within the medical field. The current state of allograft utilization in our nation has proven insufficient in meeting the demands of patients. Henceforth, a method has been devised and standardized for the procurement of demineralized osseous tissue, a crucial investigation in light of the insufficiency of allografts in meeting the requirements of patients. Objectives: Initially, standardizing an efficient procedure to obtain demineralized bone sources from human skull fragments from three different inclusion methods. Materials and Methods: Using three different types of solutions to obtain demineralized bone from human skull tissue including solutions of Formic Acid (10%), Hydrochloric Acid (5%), a mixture of solution: Formic Acid (10%) - Acid Hydrochloric (5%) (ratio 1:1,v/v). Demineralized bones were evaluated by comparing the mineral content extracted from bone samples, demineralization time, and analysis of ions concentration in bone samples (including Ca and P) before and after demineralization. Besides, demineralized bones were histologically stained before and after demineralization to assess the bone structure. Results: The Ca and P extraction rates of this method are high and standard, about 98% and 93%, respectively. The demineralization process only takes about five days. Relative bone tissue retains most of the structure of compact bone tissue. Conclusion: The procedure that our team has established is the right one for obtaining demineralized bone as bone replacement material and applies to a wide variety of human bone tissue.

Novel Study of SARS-CoV-2 RNA in Post-Reperfusion Liver Biopsies after Transplantation Using COVID-19-Positive Donor Allografts

The utilization of COVID-19-positive donors has expanded the donor pool for transplantation since the initiation of COVID allograft utilization protocols. However, the biopsy-proven PCR transmission rate of COVID-19 from these allografts has not been well documented. In August 2021, an institutional COVID-19-positive allograft protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA, and post-operative day 7 nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) swabs were collected. The primary endpoints evaluated included COVID-19 RNA on biopsy and COVID-19 detected via nasopharyngeal RT-PCR swab on post-operative day 7. A total of 20 vaccinated recipients underwent transplantation (17 liver only, 3 simultaneous liver and kidney) with whole liver allografts from 20 COVID-19-positive deceased donors between August 2021 and April 2022. 95% (19/20) of donors were asymptomatic at the time of donation. On post-reperfusion liver allograft biopsies, COVID-19 RNA was found in 10% (2/20) of the samples. All the recipients were COVID-19-negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. The use of COVID-19 allografts appears to be a safe practice, with no PCR-detectable transmission of COVID-19 despite 10% of the liver allografts having COVID-19 RNA present on post-reperfusion biopsy.

Generating strategies for a national comeback in pancreas transplantation: A Delphi survey and US conference report

In the United States, potential transplant candidates with insulin-dependent diabetes mellitus are inconsistently offered pancreas transplantation (PTx), contributing to a dramatic decline in pancreas allograft utilization over the past 2 decades. The American Society of Transplantation organized a workshop to identify barriers inhibiting PTx and to develop strategies for a national comeback. The 2-day workshop focused on 4 main topics: (1) referral/candidate selection, (2) organ recovery/utilization, (3) program performance/patient outcomes, and (4) enhanced education/research. Topics were explored through expert presentations, patient testimonials, breakout sessions, and strategic planning, including the identification of tasks for immediate focus. Additionally, a modified-Delphi survey was conducted among workshop members to develop and rate the importance of barriers, and the impact and feasibility of workgroup-identified improvement strategies. The panelists identified 16 barriers to progress and 44 strategies for consideration. The steps for a national comeback in PTx involve greater emphasis on efficient referral and candidate selection, better donor pancreas utilization practices, eliminating financial barriers to procurement and transplant, improving collaboration between transplant and diabetes societies and professionals, and increasing focus on PTx training, education, and research. Partnership between national societies, patient advocacy groups, and professionals will be essential to realizing this critical agenda.

The effect of an organ procurement organization surgeon on pediatric organ utilization.

Organ procurement organizations (OPO) have started to employ transplant-trained surgeons dedicated to organ procurement with the aim to increase allograft utilization and enhance the use of procured organs. We investigated the effects of an OPO-employed surgeon on the procurement and utilization of organs from pediatric donors within the Southwestern Transplant Alliance OPO. OPO data were obtained for all procurements that were performed between 2014 and 2019. The analysis was performed to see if the presence of an OPO donor surgeon impacted the utilization of pediatric livers. Donor and recipient demographic data were examined between allografts procured with the presence of an OPO surgeon (OPO-Present) and those without an OPO surgeon (OPO-Absent). A p-value of <.05 was considered significant. Of 149 pediatric procurements, 91 included an OPO-donor surgeon. In procurements with OPO-Present, donors were younger (8.2 vs. 11.2, p < .05) and had longer distances to travel to the recipient center (334 vs. 175 miles p < .05), but had comparable cold ischemic times. In terms of organ share type, more OPO-Present livers were shared nationally and there was no difference in discard rate between OPO-Present and OPO-Absent procurements. Finally, OPO-Present livers were more likely to be transplanted to pediatric recipients compared to OPO-Absent (47.3% vs. 24.1% p < .05). The presence of an OPO surgeon has impacted organ utilization, leading to increased transplantation of pediatric livers in pediatric recipients, and has expanded the geographical share of pediatric livers.

Utilization Trends of Nerve Autograft Alternatives for the Reconstruction of Peripheral Nerve Defects.

Autologous nerve grafting is the time-honored reconstruction method for peripheral nerve gaps. However, it is associated with donor-site morbidities. A growing number of studies have demonstrated the effective use of decellularized nerve allograft and synthetic conduits, which are convenient options with no donor deficit. The specific aim of this study was to characterize changes in practice trends for peripheral nerve defect reconstruction. The authors queried the 2015 to 2020 Merative MarketScan Databases for patients who underwent nerve autograft, allograft, synthetic conduit, and/or vein graft reconstruction. Patient demographic data (ie, location, indication) and hospital characteristics (ie, facility, provider type) were recorded. Regression analysis identified changes in trends over the study period. A total of 4331 patients underwent one or more nerve gap reconstructive procedures over the study period. Since the introduction of allograft CPT code in 2018, segmented mixed effect longitudinal modeling revealed that allograft utilization significantly increased from 21.5% to 29.6% after 2018 ( P < 0.001), whereas nerve autograft use decreased from 18.6% to 15.8% and conduit use decreased from 60% to 54.7% ( P = 0.09 and P = 0.03, respectively). When stratifying autograft by size, use of autograft less than or equal to 4 cm significantly decreased from 10.6% to 7.7% after 2018 ( P = 0.03), and autograft greater than 4 cm did not. When stratifying by state, there is heterogeneity in utilization rates of each product. After creation of a designated allograft CPT code in 2018, there was an increase in allograft use with concomitant decrease in conduit and short length autograft use, suggesting that allograft replaced a portion of procedures used in short nerve gap reconstruction.

722 Select Survey of Human Cadaver Skin Allograft Utilization by 21 Senior Academic Burn Surgeons

Abstract Introduction As of 2022, cryopreserved human cadaver skin allograft remains the gold standard by which all other skin substitutes used for burn care are compared. The 2015 Taiwan Color Dust Explosion burn mass casualty engendered the transfer of emergency tranches of skin allograft from reserves in both the US and EU to Taiwan. HHS/ASPR/BARDA/CBRN led an after-action fact-finding mission to Taiwan and concluded that skin allograft would still play a central role as a safety net in US national burn care preparedness, even as BARDA invested in the development of other burn medical countermeasures that would be part of the preparedness strategy. However, before investments in a skin allograft based national strategy could be built, it was critical that the leaders of the Disaster Committee and Organization and Delivery of Burn Care (ODBC) Committee of the American Burn Association (ABA) commission a survey to verify current practice patterns of senior academic burn surgeons on the use of skin allograft. Methods The committee chairs curated a list of 21 leading academic burn surgeons in North America. These surgeons’ credentials included having been an ABA president, a member of the ABA Board of Trustees, or having chaired a standing committee of the ABA. All 21 surgeons were actively practicing burn care daily. The survey contained 18 questions and was intentionally kept brief (Survey to be provided as Appendix). Results Of the 21 surgeons selected, there was 100% participation and completion of the survey. Most were in practice &amp;gt;15 years (62%) and manage &amp;gt;200 patients surgically per year (71%). The predominant use of allograft is to temporize the wound bed when there are inadequate donor sites (48% “Almost Always”). It is “Often” (48%) used to temporize wound beds prior to autografting. However, most are looking for alternatives to allograft (43% “Sometimes”, 43% “Often”). With ongoing development of skin substitutes, most indicated their allograft use will likely decrease, with only 19% indicating “Probably Not”. Conclusions Human skin allograft continues to play a central role in surgical burn care management. For the foreseeable future, new technologies are not likely to displace allograft use but rather blend with its use. This brief, select survey is not powered but provides a snapshot of the current role of skin allograft. In the future, we may conduct a broader survey to obtain a validated and more granular view of the use of allograft in modern burn care. Applicability of Research to Practice Armed with this information, the US Federal Government acted to increase preparedness after a burn mass casualty. In February 2022, a Request for Proposals for a large vendor-managed inventory of human cryopreserved skin allograft was answered by two separate tissue banks. As of September 2022, $38M was awarded to two partners for procurement and expansion of a vendor managed inventory of cryopreserved human skin allograft to ensure preparedness for rapid response to a burn mass casualty incident.

An Interrupted Time Series Analysis Measuring the Impact of Research and Education on Clinical Practice: Decreasing Allograft Use in Young Patients Using a Registry to Track Outcomes.

We sought to evaluate whether allograft utilization for primary anterior cruciate ligament reconstruction (ACLR) within our health-care system changed following the implementation of an allograft reduction intervention and whether revision rates within the health-care system changed following the initiation of the intervention. We conducted an interrupted time series study using data from Kaiser Permanente's ACL Reconstruction Registry. In our study, we identified 11,808 patients who were ≤21 years of age and underwent primary ACLR from January 1, 2007, through December 31, 2017. The pre-intervention period (15 quarters) was January 1, 2007, through September 30, 2010, and the post-intervention period (29 quarters) was October 1, 2010, through December 31, 2017. Poisson regression was used to evaluate trends over time in 2-year revision rates according to the quarter in which the primary ACLR was performed. Allograft utilization increased pre-intervention from 21.0% in 2007 Q1 to 24.8% in 2010 Q3. Utilization decreased post-intervention from 29.7% in 2010 Q4 to 2.4% in 2017 Q4. The quarterly 2-year revision rate increased from 3.0 to 7.4 revisions per 100 ACLRs pre-intervention and decreased to 4.1 revisions per 100 ACLRs by the end of the post-intervention period. Poisson regression found an increasing 2-year revision rate over time pre-intervention (rate ratio [RR], 1.03 [95% confidence interval (CI), 1.00 to 1.06] per quarter) and a decreasing rate over time post-intervention (RR, 0.96 [95% CI, 0.92 to 0.99]). In our health-care system, we saw a decrease in allograft utilization following the implementation of an allograft reduction program. During the same period, a decrease in the ACLR revision rate was observed. Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Japanese national survey on declined liver allografts from brain-dead donors: High decline rate but promising outcomes in allografts with moderate steatosis.

Liver allografts from brain-dead donors, which were declined and were eventually not transplanted due to accompanying marginal factors, have never been surveyed in Japan. We surveyed the declined allografts and discussed the graft potential focusing on various marginal factors. We collected data on brain-dead donors between 1999 and 2019 from the Japan Organ Transplant Network. We divided their liver allografts into declined (nontransplanted) and transplanted ones, and then characterized declined ones focusing on their timepoints of decline and accompanying marginal factors. For each marginal factor, we calculated the decline rate from the number of declined and transplanted allografts, and assessed the 1-year graft survival rate from transplanted allografts. A total of 571 liver allografts were divided into 84 (14.7%) declined and 487 (85.3%) transplanted ones. In the declined allografts, a majority was declined after laparotomy (n=55, 65.5%), most of which had steatosis and/or fibrosis (n=52). Out of the moderate steatotic (without F ≥ 2 fibrosis) allografts (n=33), 21 were declined and 12 were transplanted, leading to a 63.6% decline rate. The latter 12 achieved a 92.9% 1-year graft survival rate after transplantation. Comparison of donor background showed no significant difference between the declined and transplanted allografts. Pathological abnormalities of steatosis/fibrosis seem to be the most common donor factor leading to graft decline in Japan. Allografts with moderate steatosis were highly declined; however, transplanted ones achieved promising outcomes. This national survey highlights the potential utility of liver allografts with moderate steatosis.

Acuity circles allocation policy impact on waitlist mortality and donation after circulatory death liver transplantation: A nationwide retrospective analysis.

Acuity circles allocation policy impact on waitlist mortality and donation after circulatory death liver transplantation: A nationwide retrospective analysis.

Utilization of COVID-19 allografts without transmission to recipients in liver transplantation

Background: The utilization of COVID-19 positive donors has expanded the donor pool for liver and kidney transplantation in the United States since initiation of COVID allograft utilization protocols in 2020 and 2021. Utilization of these allografts has been demonstrated to be a safe practice and to reduce waitlist mortality; however, the transmission rate of COVID-19 from these allografts has not been well documented. Methods: In August 2021, an institutional COVID-19 positive serology donor protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA in the donor allografts. Post-operative management of recipients and immunosuppression were similar to standard protocols. All recipients were vaccinated per institutional protocol. Primary endpoint evaluated was transmission of COVID-19 to donors via nasopharyngeal RT-PCR swab on post-operative day 7. Results: 38 vaccinated recipients underwent transplantation with 17 livers, 3 liver-kidneys (SLK), and 18 kidneys from 33 COVID-19 positive deceased donors between August 2021 and April 2022. 90.9% of donors were asymptomatic at time of donation. On post-reperfusion allograft biopsies, COVID-19 RNA was found in only 10% (2/20) of samples. All recipients were COVID-19 negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. Respiratory complications were noted in 13% of the recipients; however, none were related to COVID-19. Conclusion: The safety of using COVID-19 allografts has been demonstrated in the literature and is again supported by this study which demonstrates no cases of clinically relevant or PCR-detectable transmission of COVID-19 from the positive allografts to recipients, despite 10% of allografts having COVID-19 RNA present on post-reperfusion biopsy. Further use of this underutilized donor source can continue to expand the donor pool in the US and decrease waitlist mortality.

A Novel National Program to Maximize Utilization of Heart and Lung Allografts from Donors After Brain Death (DBD) and Donors After Circulatory Death (DCD) for Transplantation

<h3>Purpose</h3> Build a national network of dedicated cardiothoracic surgical procurement and Organ Care System (OCS™) ex-vivo perfusion clinical experts to: Maximize cardiothoracic donor organ utilization for transplantation; overcome logistical and infrastructural burden of distant organ procurements and national allocation; standardize clinical quality of care of ex-vivo perfusion management of cardiothoracic allografts; and establish a better work-life balance for transplant teams across the U.S. <h3>Methods</h3> Leveraging the OCS, the only FDA approved portable perfusion technology for heart and lung transplantation, to build a national infrastructure to enable a turn-key service. This program comprehensively covers: donor screening, donor surgical procurement, OCS perfusion management and transportation of allografts from donor hospitals to any transplant program in the U.S. <h3>Results</h3> The National OCS Program (NOP) was initiated in 2021 for lung transplantation using the OCS Lung technology in 9 major regions across the U.S. Early experience is very encouraging and demonstrated the capabilities of NOP to significantly expand thoracic organ retrieval distance. Enabling cross-country thoracic organ sharing to benefit more patients awaiting transplants while unburdening transplant programs resources. The map below demonstrates actual NOP lung transplants. NOP is now expanding to include OCS Heart and provide similar service to heart transplant programs across the U.S. <h3>Conclusion</h3> The process of cardiothoracic donor organ procurement and related logistics are challenging and unscalable to meet the growing national demand for increased donor organ utilization for lung and heart transplantation. NOP was designed to create a collaborative partnership between industry, OPOs and transplant programs to provide solutions to overcome the existing challenges and transform the field of cardiothoracic transplantation in the U.S.

Liver allograft findings of donation after cardiac death versus brain death in recipients with hepatitis C related cirrhosis: a matched histologic comparison

As the demand for organ transplantation increases, utilization of liver allografts of donation after cardiac death (DCD) is becoming increasingly necessary. Althoughthe clinical outcomes of DCD allografts have been well described, the histologic features are not well characterized. Liver biopsies (n=131) from age-matched DCD (n=60) and donation after brain death (DBD; n=71) recipients with hepatitis C virus were compared. Histologic features were studied in a blinded fashion, subgrouped into time 0, 0-6 months, and >6 months. In time 0 biopsies, more DCD cases had zone 3 (43.8 vs 29%) and bridging necrosis (19 vs 0%), albeit not statistically significant. At 0-6 months, more DCD cases had portal edema (p=0.01). Pericholangitis (30.4% vs 18.8%) and acute cholestasis (21.7% vs 12.5%) were more common in DCD, but not statistically significant. At >6 months, pericholangitis (19% vs 4.5%) persisted in DCD, although not statistically significant. Overall, both groups had similar bile duct injury, portal inflammation, and fibrosis. Postoperative biliary complications were more common in DCD (19% vs 0%). Three-year and 10-year graft survival and patient outcomes were similar in both cohorts. Biliary alterations were more prevalent in the 0-6 month time period DCD biopsies, reflecting increased vulnerability of this group to biliary complications in the early post-orthotopic liver transplant (OLT) period. This finding may suggest poor graft perfusion despite comparable cold ischemia times. However, these features improved and DCD recipients have similar graft and overall survival compared to DBD recipients, indicating that carefully selected DCD liver allografts are a viable option for transplantation.

A Clinical Tool to Guide Selection and Utilization of Marginal Donor Livers With Graft Steatosis in Liver Transplantation.

Donor liver biopsy (DLBx) in liver transplantation provides information on allograft quality; however, predicting outcomes from these allografts remains difficult. Between 2006 and 2015, 16 691 transplants with DLBx were identified from the Standard Transplant Analysis and Research database. Cox proportional hazard regression analyses identified donor and recipient characteristics associated with 30-d, 90-d, 1-y, and 3-y graft survival. A composite model, the Liver Transplant After Biopsy (LTAB) score, was created. The Mini-LTAB was then derived consisting of only donor age, macrosteatosis on DLBx, recipient model for end-stage liver disease score, and cold ischemic time. Risk groups were identified for each score and graft survival was evaluated. P values <0.05 were considered significant. The LTAB model used 14 variables and 5 risk groups and identified low-, mild-, moderate-, high-, and severe-risk groups. Compared with moderate-risk recipients, severe-risk recipients had increased risk of graft loss at 30 d (hazard ratio, 3.270; 95% confidence interval, 2.568-4.120) and at 1 y (2.258; 1.928-2.544). The Mini-LTAB model identified low-, moderate-, and high-risk groups. Graft survival in Mini-LTAB high-risk transplants was significantly lower than moderate- or low-risk transplants at all time points. The LTAB and Mini-LTAB scores represent guiding principles and provide clinically useful tools for the successful selection and utilization of marginal allografts in liver transplantation.

Development of the Eurotransplant Discard Risk Index to Predict Acceptance of Livers for Transplantation: A Retrospective Database Analysis.

The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant. Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index. Of 11670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyltranspeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P < .001), respectively. Despite strong calibration, discard rates of 0.8% for overall donors and 6% of donors after circulatory death could be predicted with 80% accuracy. The Eurotransplant-developed Discard Risk Index showed a high prognostic ability to predict liver utilization in a European setting. The model could therefore be valuable for identifying livers at high risk of not being transplanted in an early stage. These organs might profit the most from modified allocation strategies or advanced preservation techniques.

Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry.

Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12-18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.

Allograft discard risk index for heart transplantation.

The numberof patients awaiting heart transplantation (HTx) substantially exceeds the number of donor hearts transplanted each year, yet nearly 65% of eligible donor hearts are discarded rather than transplanted. Deceased organ donors listed within the UNOS Deceased Donor Database between 2010 and 2020 were reviewed. Those greater than 10 years old and consented for heart donation were included and randomly separated into training (n=48435) and validation (n=24217) cohorts. A discard risk index (DSRI) was created using the results of univariable and multivariable analyses. Discard data were assessed at DSRI value deciles, and stratum-specific likelihood ratio (SSLR) analysis and Kaplan-Meier survival function were used for mortality data. Factors associated with higher DSRI values included donor age>45, LVEF, HBV-core antibodies, hypertension, and diabetes. The DSRI C-statistic was .906 in the training cohort and .904 in the validation cohort. The DSRI did not reliably predict 30-day or 1-year mortality after transplantation (C-statistic .539 and .532, respectively). The factors leading to heart allograft discard are not correlated to the same degree with post-transplant outcomes. This suggests that optimizing utilization of certain allografts with slightly higher risk of discard could increase the heart donor pool with limited impact on posttransplant mortality.