Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers.

Use of donation after circulatory death (DCD) donor livers for transplantation has remained cautious in the United States. The aim of this study was to demonstrate the expansion of a DCD liver transplantation (LT) program with the use of extended criteria donor (ECD) DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with 1 of the following factors: donor age >50 years, donor body mass index >35 kg/m2 , donor functional warm ischemia time >30 minutes, and donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush and efforts to minimize ischemia times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC), and change in DCD LT volume. Of 135 consecutive DCD LTs, 62 were ECD DCDs. In total, 24 ECD DCD LTs were performed before (era 1) and 38 after the institution of optimization protocol (era 2), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in era 2, with a significantly lower incidence of IC (5% versus 17% in era 1; P = 0.03) and better 1-year graft survival (93% versus 75% in era 1; P = 0.07). Survival outcomes for ECD DCD LT in era 2 were comparable to matched deceased donor LT. With the expansion of the DCD donor pool, the number of DCD LTs performed at our center gradually increased in era 2 to account for >20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.

Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal-derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole-organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi-xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end-stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression-free transplantation justifies the interest that the transplant community is committing to the field.

A prospective policy development to increase split-liver transplantation for 2 adult recipients: results of a 12-year multicenter collaborative study.

OBJECTIVE: To analyze in a multicenter study the potential benefit of a new prospective policy development to increase split-liver procedures for 2 adult recipients. BACKGROUND: Split-liver transplantation is an important means of overcoming organ shortages. Division of the donor liver for 1 adult and 1 pediatric recipient has reduced the mortality of children waiting for liver transplantation but the benefits or disadvantages to survival when the liver is divided for 2 adults (adult-to-adult split-liver transplant, AASLT) compared with recipients of a whole graft have not been fully investigated. METHODS: We developed a computerized algorithm in selected donors for 2 adult recipients and applied it prospectively over a 12-year period among 7 collaborative centers. Patient and graft outcomes of this cohort receiving AASLT either as full right grafts or full left grafts were analyzed and retrospectively compared with a matched cohort of adults who received a conventional whole-liver transplant (WLT). Univariate and multivariate analysis was done for selected clinical variables in the AASLT group to assess the impact on the patient outcome. RESULTS: Sixty-four patients who received the AASLT had a high postoperative complication rate (64.1% grade III and IV) and a lower 5-year survival rate than recipients of a WLT (63.3% and 83.1%) CONCLUSIONS: AASLT should be considered a surgical option for selected smaller-sized adults only in experimental clinical studies in experienced centers.

Organ shortage: the greatest challenge facing transplant medicine.

The success of organ transplantation as a treatment for end-stage organ disease has yielded a series of ethical quandaries originating from the issue of organ shortage. Scarcity of organs for transplantation necessitates formulation of just and fair allocation policies as well as ethically viable solutions to bridging the vast gap between organ supply and demand. The concept of "triage" provides a useful paradigm in which to contextualize the organ shortage issue. This entails subjugating the welfare of the individual patient for the benefit of the wider community as an ethically justified response to the challenge of scarcity.

The aggressive phenotype revisited: utilization of higher-risk liver allografts.

Organ shortage has led to increased utilization of higher risk liver allografts. In kidneys, aggressive center-level use of one type of higher risk graft clustered with aggressive use of other types. In this study, we explored center-level behavior in liver utilization. We aggregated national liver transplant recipient data between 2005 and 2009 to the center-level, assigning each center an aggressiveness score based on relative utilization of higher risk livers. Aggressive centers had significantly more patients reaching high MELDs (RR 2.19, 2.33 and 2.28 for number of patients reaching MELD>20, MELD>25 and MELD>30, p<0.001), a higher organ shortage ratio (RR 1.51, 1.60 and 1.51 for number of patients reaching MELD>20, MELD>25 and MELD>30 divided by number of organs recovered at the OPO, p<0.04), and were clustered within various geographic regions, particularly regions 2, 3 and 9. Median MELD at transplant was similar between aggressive and nonaggressive centers, but average annual transplant volume was significantly higher at aggressive centers (RR 2.27, 95% CI 1.47-3.51, p<0.001). In cluster analysis, there were no obvious phenotypic patterns among centers with intermediate levels of aggressiveness. In conclusion, highwaitlist disease severity, geographic differences in organ availability, and transplant volume are the main factors associated with the aggressive utilization of higher risk livers.

Under-utilization of donor hearts in the initial era of the heart transplant program in Korea- review of 13 years' experience from the Korea national registry.

BACKGROUND: Heart transplantation (HTPL) is the effective treatment option to improve quality of life as well as survival of terminal heart failure patients. Shortage of donors, however, limits HTPL to all indicated cases. The temporal trend and clinical characteristics of HTPL donors in Korea were therefore investigated. METHODS AND RESULTS: Among 2,001 brain-death donors registered in Korean Network for Organ Sharing from February 2000 to May 2012, a total of 28% of hearts (n=552) were utilized for HTPL. The mean age of Korean heart donors was 10 years younger than that of heart recipients (33.2 ± 12 years vs. 43.2 ± 17 years, respectively). The oldest was 56 years old, and donors aged over 50 accounted for only 6.2% (n=34) of total cases. Female donors were utilized less than male donors (23.6% vs. 29.6%, respectively). To determine characteristics of declined donor heart candidates, subgroup analysis of echocardiographic data was done, and 74.6% had normal ventricular function and structure, although only 42.3% were actually transplanted. The utilization rate of donor hearts with minor echocardiography abnormalities was only 15.2%. Clinical outcomes of marginal heart donors were not different from non-marginal donors. CONCLUSIONS: Although shortage of donor organs is an emerging issue, most donor hearts have been under-utilized in the past in Korea. In particular, aged and female donor hearts with minor echocardiographic abnormalities had a low rate of utilization.

[Deceased organ donors, legal regulations governing diagnosis of brain death, overview of donors and liver transplants in the Czech Republic]. / Zemrelí dárci orgánu, právní normy dia-gnostiky smrti mozku. Prehled dárcu a transplantací jater v Ceské republice.

The key restriction of transplantation medicine globally, as well as in the Czech Republic, concerns the lack of organs. The number of deceased donors, and thus the availability of organ transplants, has been stagnating in our country. The paper describes current legal regulations governing the dia-gnosis of brain death and primary legal and medical criteria for the contraindication of the deceased for organ explantation, gives an overview of the number of liver transplants, age structure, and diagnosis resulting in brain death of the deceased liver donors in the Czech Republic.

The use of back-up units to enhance the safety of unrelated donor cord blood transplantation.

The inability to obtain additional stem cells is a disadvantage of unrelated donor cord blood transplantation (CBT). Moreover, in the event of problems with unit shipment, compromised unit quality, thaw mishaps, or graft failure, the time to secure a back-up graft could be unacceptable. Emergent shipment of 1 to 2 back-up units that have been previously typed and reserved could overcome this limitation. However, the advantages of this approach are not established. Therefore, we present our use of back-up units over a 5.5-year period. Six of 121 CBT recipients (5%) required back-up unit infusion. Indications included shipment mishaps (n = 2), poor unit viability (n = 2), significant infusion reaction (n = 1), and graft failure (n = 1). Lack of back-up units would have caused transplantation delay or infusion of inferior-quality units. Five of the 6 patients achieved sustained donor engraftment. We demonstrate that back-up units are emergently required in a significant minority of patients, supporting the incorporation of at least 1 back-up unit in cord blood (CB) selection algorithms to enhance CBT safety.

Organ transplantation--how much of the promise has been realized?

Since the introduction of organ transplantation into medical practice, progress and optimism have been abundant. Improvements in immunosuppressive drugs and ancillary care have led to outstanding short-term (1--3-year) patient and graft survival rates. This success is mitigated by several problems, including poor long-term (>5-year) graft survival rates, the need for continual immunosuppressive medication and the discrepancy between the demand for organs and the supply. Developing methods to induce transplant tolerance, as a means to improve graft outcomes and eliminate the requirement for immunosuppression, and expanding the pool of organs for transplantation are the major challenges of the field.

Local versus distant lung donor procurement does not influence short-term clinical outcomes.

OBJECTIVE: The purpose of this study was to recognize clinically meaningful differences in lung transplant outcomes based on local or distant lung procurement. This could identify if the lung allocation policy change would influence patient outcomes. METHODS: This single-center retrospective cohort study analyzed adult patients who underwent lung transplant from 2006 to 2017. Donor and recipient data were abstracted from a collaborative, prospective registry shared by our local organ procurement organization, and tertiary medical center. Short-term outcomes, 1-year survival, and hospitalization costs were compared between local and distant lung transplants defined by donor service area. RESULTS: Of the 722 lung transplants performed, 392 (54%) had local donors and 330 (46%) had distant donors. Donors were similar in age and cause of death. Recipients were significantly different in diagnosis and local recipients had lower median lung allocation scores (local, 37.3 and distant, 44.9; P < .01). Distant lung transplants had longer total ischemic times (local, 231 ± 52 minutes and distant, 313 ± 48 minutes; P < .01). The rate of major complications, length of hospital stay, and 1-year survival were similar between groups. Distant lung transplants were associated with higher median overall cost (local, $183,542 and distant, $229,871; P < .01). Local lung transplants were more likely to be performed during daytime (local, 333 out of 392 [85%] and distant, 291 out of 330 [61%]; P < .01). CONCLUSIONS: Local lung transplants are associated with shorter ischemic times, lower cost, and greater likelihood of daytime surgery. Short- and intermediate-term outcomes are similar for lung transplants from local and distant donors. The new lung allocation policy, with higher proportion of distant lung transplants, is likely to incur greater costs but provide similar outcomes.

Cadaveric Organ Donation in Lebanon: Proposed Suggestions for Improvement.

Organ transplantation is the treatment of choice for most end-stage diseases, despite the continuous advancements in the medical and surgical field. The dilemma of the shortage between supply and demand of organs for transplantation has been an ongoing debate and concern. The well-known "Spanish Model" was established in 1989 and adopted by the National Transplant Organization. The main commitment of the National Transplant Organization is to increase organ donation and transplantation rates. The program was also successfully adopted in countries such as Australia and Great Britain as well as Latin-American countries. The system is based on recruitment of cadaveric organs by a specialized team in hospitals at the regional and national level. Lebanon hopes to initialize a model similar to the Spanish Model but faces several obstacles. Adopting such a model could help increase cadaveric organ donation in Lebanon.

Suboptimal Donors Do Not Mean Worse Results: A Single-Center Study of Extending Donor Criteria for Lung Transplant.

BACKGROUND: Lung transplant remains the only viable treatment for most of the end-stage lung diseases. It is believed that extending criteria for donor lungs would increase the number of lung transplants. The aim of the study was to compare the graft function by means of oxygenation index among recipients who received the lungs from donors of extended criteria with those whose received lungs from donors who met the standard criteria. METHODS: This retrospective study analyzed 71 donors whose lungs where transplanted into 71 first-time double lung recipients of 2 groups: patients who received transplants before and after 2018. The objective was to assess whether there is a significant difference in quality of the donor pool after applying extended criteria. The second objective was to compare results of recipients with lungs from donors of oxygenation index > 400 mm Hg with those obtained among recipients with this parameter < 400 mm Hg. RESULTS: In the case of transplants performed in 2018 to 2019, oxygenation indices were significantly lower in donors but significantly higher in recipients on the first day than those observed in 2015 to 2017. The number of transplants increased from 9 per year to 22 per year. Irrespective of whether the donor had PaO2/fraction of inspired oxygen above or below 400 mm Hg, recipients showed similar oxygenation index values after transplant (mean oxygenation index, 462 vs 412 mm Hg, respectively). Short-term mortality did not differ either. CONCLUSIONS: Extended criteria of lungs suitability as a potential grafts not only increases the donor pool but also proves that suboptimal donors are not associated with producing inferior results of the recipients.

Expanded Criteria Donor Kidneys With Kidney Donor Profile Index ≤ 85%: Are We Doing Enough to Counsel Our Patients?

BACKGROUND: Kidneys at higher risk for allograft failure are defined by the Kidney Donor Profile Index (KDPI) > 85% in the current kidney allocation system (KAS), replacing the historical concept of expanded criteria donor (ECD) kidneys in the previous KAS. Discrepancies exist in the classification of "high-risk kidneys" between the 2 KAS. In the current KAS, only recipients of KDPI > 85% kidneys are counseled about the high risk of allograft failure and are required to sign a consent. In this study, we evaluated the outcomes and allocation of kidneys with discordant classification. METHODS: Using the Scientific Registry of Transplant Recipients, kidneys transplanted between 01/2002 and 09/2016 were classified according to the old (standard criteria donor [SCD]/ECD) and current (KDPI) KAS. We then grouped them as concordant (KDPI ≤ 85% + SCD or KDPI > 85% + ECD) and discordant (KDPI ≤ 85% + ECD or KDPI > 85% + SCD) kidneys. RESULTS: Approximately 11% of transplanted kidneys were discordant in classification. Among kidneys with KDPI ≤ 85%, ECD status conferred a 64% (95% CI: 56%-73%) higher risk of allograft failure compared to SCD status. However, SCD/ECD status was not associated with differential outcomes in KDPI > 85% kidneys. These ECD kidneys have KDPIs > 50% and have been transplanted across all estimated post-transplant survival (EPTS) deciles. CONCLUSION: Adequate counseling about the risk and benefit of accepting ECD kidneys with KDPI ≤ 85% versus waiting on dialysis should be explored with the patients, especially those with lower EPTS.

Hypothermic preservation of rat hearts using antifreeze glycoprotein.

Antifreeze proteins are an effective additive for low-temperature preservation of solid organs. Here, we compared static hypothermic preservation with and without antifreeze glycoprotein (AFGP), followed by nonfreezing cryopreservation of rat hearts. The heart was surgically extracted and immersed in one of the cardioplegia solutions after cardiac arrest. Control rat hearts (n=6) were immersed in University of Wisconsin (UW) solution whereas AFGP-treated hearts (AFGP group) (n=6) were immersed in UW solution containing 500 ?g/ml AFGP. After static hypothermic preservation, a Langendorff apparatus was used to reperfuse the coronary arteries with oxygenated Krebs-Henseleit solution. After 30, 60, 90, and 120 min, the heart rate (HR), coronary flow (CF), cardiac contractile force (max dP/dt), and cardiac diastolic force (min dP/dt) were measured. Tissue water content (TWC) and tissue adenosine triphosphate (ATP) levels in the reperfused preserved hearts were also assessed. All the parameters were compared between the control and AFGP groups. Compared with the control group, the AFGP group had significantly (p<0.05) higher values of the following parameters: HR at 60, 90, and 120 min; CF at all four time points; max dP/dt at 90 min; min dP/dt at 90 and 120 min; and tissue ATP levels at 120 min. TWC did not differ significantly between the groups. The higher HR, CF, max dP/dt, min dP/dt, and tissue ATP levels in the AFGP compared with those in control hearts suggested that AFGP conferred superior hemodynamic and metabolic functions. Thus, AFGP might be a useful additive for the static/nonfreezing hypothermic preservation of hearts.

São Paulo State Liver Transplantation Supply Chain Study.

BACKGROUND: The number of liver transplantations is increasing worldwide, and Brazil ranks in the second position. It has one of the biggest public health care systems, which is responsible for the coordination and financial funding of transplantation procedures. Meeting the demands of such a large system of transplantation has become a challenge, particularly when attempting to minimize costs of scarce and expensive resources. The aim of this study was to investigate the process of donation, the retrieval of organs, and the transplantation itself using engineering methods based on logistics analyses. METHODS: Three steps were used: study planning, data gathering, and data analysis. Researchers surveyed professionals to acquire raw information based on their observations, experience, and knowledge. Then, a data analysis was conducted, putting together all the information gathered during the previous steps. Bias was removed, and conflicting perceptions were resolved in order to have a standard view on the transplantation process. RESULTS: Data was gathered between 2014 and 2018 and included 5502 liver donors and 2678 (48.7%) patients who received liver transplants organs. A total of 2824 organs were refused because of logistics issues (transport and handling). Interviews of health care professionals enabled the design of a process map in which 4 stakeholders were identified: patient, physician, organ, and information. CONCLUSIONS: The liver transplantation process is analyzed based on a supply chain methodology applying this knowledge and putting together medical and engineering sciences to promote better efficiency and outcomes for the transplantation program. Future studies should focus on the implementation of these ideas aiming to promote optimization gains in any step of the process.

Donation after circulatory death liver transplantation: What are the limits for an acceptable DCD graft?

The utilization of donation after circulatory death (DCD) livers has been growing over the last decade. In large-volume centers, survival outcomes have improved and are comparable to outcomes with brain death donor (DBD) liver transplantation (LT). The relatively concentrated success with DCD LT demonstrated by high-volume transplant centers has rekindled international enthusiasm. The combination of increasing expertise in DCD LT and ongoing shortage in transplantable organs has promoted expansion of the DCD donor pool with regards to donor age, body mass index and donor warm ischemia time. In this review, we focused on the practice patterns in DCD liver graft utilization in the last decade, along with the possibilities for further expansion of DCD liver graft utilization and new technologies, such as machine perfusion.

Why NOTTO? The National Organ and Tissue Transplant Organisation and Why It Is Crucial to Regulate Organ Donation and Transplantation in India.

OBJECTIVES: This study addresses the establishment of the National Organ and Tissue Transplant Organisation (NOTTO) and its impact on organ donation and transplantation in India. METHODS: Yearly data, 2013 to 2018, from all the states and union territories of India as per the World Health Organization-Global Observatory on Donation and Transplantation (WHO-GODT) format, were analyzed and tabulated. The various national and international legislation, advisories, and reports that mandated establishment of national regulatory bodies were studied. Comparisons were drawn, noting points of similarity and contrast between analogous organizations. RESULTS: In the WHO Madrid Report 2004, the international advisory highlighted the need for a national transplantation agency for effective integrated development of donation and transplantation. Its parallel in India was the 2011 Amendment of the Transplantation of Human Organs Act 1994 to set NOTTO up with its first director in 2014, and also with a national donor and recipient registry to achieve transparent allocation. A challenging task for NOTTO was to collect from all transplant and/or retrieval centers their real-time data of donors, recipients, and transplants in the National Organ and Tissue Transplant Registry (NOTTR). However, NOTTO succeeded in collecting data offline from all 29 states and 7 union territories and submitted to GODT in 2019. There was a greater than 2-fold increase of deceased organ donors from 340 in 2013 (pre-NOTTO) to 875 in 2018 (post-NOTTO). The deceased organ donation rate went up from 0.27 to 0.65, and the total number of transplants went up from 4990 to 10,340 in the same period. All the outcome measures doubled or tripled, establishing the role of NOTTO. Albeit having differences, NOTTO is analogous to the National Transplant Organization of Spain and United Network of Organ Sharing of the United States. CONCLUSION: The 2011 Amendment of THOA 1994 provided the basis for the establishment of NOTTO, which has been crucial in regulating organ donation and transplantation in India with the setting up of the NOTTR in 2015. NOTTO has been instrumental in augmenting all outcomes.

Split-liver transplantation in the high-MELD adult patient: are we being too cautious?

The fear that patients with high-mathematical model for end stage liver disease (MELD) score may not be suitable candidates for segmental grafts because of their need for greater liver mass has continued to push the transplant community toward the use of whole LT (WLT) in preference to split LT (SLT). In order to define the outcome of segmental liver transplantation in a better manner in high-MELD patients (score > or =26), we queried the UNOS registry for graft and patient survival results according to MELD score in adult patients receiving WLT and SLT in the United States from the inception of MELD allocation (February 27, 2002) through March 9, 2007. A total of 316 adult patients received a SLT as compared with 20 778 WLTs. Patient and graft survival rates at 6 and 12 months were comparable for all MELD ranges, including the 'high-MELD' recipients (e.g. at MELD score 31-35, patients' and grafts' survival rates at 12 months was 87.5% in SLT group vs. 84.4% and 76.7% in WLT group respectively). The results even at higher MELD scores (i.e. >35) were more than acceptable. In conclusion, patient and graft survival rates for SLT in high-MELD adult patients are comparable to the same for WLT.

Lung Allocation Score System: First Italian Experience.

BACKGROUND: Lung transplantation is an established therapeutic option for patients with end-stage pulmonary disease. In May 2005, the lung allocation score (LAS) was introduced in the United States to maximize the benefit to the recipient population and reduce waiting list mortality. The LAS has been applied in a region of Italy since March 2016 on a provisional basis. The aims of the study were describing waiting list characteristics and short-term outcomes after lung transplantation before and after LAS introduction. METHODS: All the patients who received transplants between January 1, 2011, and March 15, 2017, were included in our retrospective study. The study population was divided into 2 cohorts (historical cohort and post-LAS cohort) and a comparison among the main perioperative data was performed. RESULTS: The historical cohort consisted of 415 patients on the waiting list with 91 deaths and 199 lung transplants; the post-LAS cohort consisted of 134 patients with 10 deaths on the waiting list and 51 transplants. Median waiting time and mortality on the list decreased from 223 to 106 days (P = .03) and from 11.2% to 7.5% (P > .05), respectively. The transplantation rate increased from 25% to 38% (P = .001) and the probability to receive a transplant in the first year in the post-LAS era increased significantly (P = .004). CONCLUSIONS: The results of the introduction of the LAS system in our region are encouraging and have not shown any adverse short-term effects. The regional coordination decided to prolong the experimental application of LAS in order to accumulate more data and to evaluate medium-term outcomes.