Heart transplantation candidacy.

PURPOSE OF REVIEW: Timely referral of eligible candidates for consideration of advanced therapies, such as a heart transplantation or mechanical circulatory support is essential. The characteristics of heart transplantation candidates have changed significantly over the years, leading to a more complex evaluation process. The present review summarizes recent advances in the evaluation process for heart transplantation eligibility. RECENT FINDINGS: The heart transplantation allocation policy was recently reviewed in the USA in an effort to reduce waitlist mortality and to ensure fair geographic allocation of organs to the sickest patients. Moreover, patients with chronic infectious diseases, as well as malignancies, are being currently considered acceptable candidates for transplantation. Listing practices for heart transplantation vary between programmes, with a greater willingness to consider high-risk candidates at higher-volume centres. SUMMARY: The ultimate decision to place high-risk candidates on the heart transplantation waitlist should be based on a combination of quantitative and qualitative data analysis informed by clinical judgement, and the chronic shortage of organ donors makes this process an important ethical concern for any society. Future guidelines should discuss approaches to achieve fair organ allocation while preserving improved outcomes after transplantation.

Supply and Demand of Domestic Corneal Tissue and Its Implications on Export Potential-Using Australia as an Example.

PURPOSE: Corneal tissue importation is only possible if another country is able to export corneas without impacting its own domestic demand. Currently, there is little evidence to indicate whether export nations have such surplus capacity and in a position to export. To explore this concept, we examined our nation, Australia, which is reported to routinely decline donations because of its ability to meet domestic corneal transplant demand. Our research offers insights and opportunities for Australia and other nations to evaluate their domestic and international supply and allocation of corneal tissue in this space. METHOD: We collated 12 months of data on collected and noncollected donations, through participating Australian Eye Banks. The explanation of why some known donors were declined or not pursued indicated if demand was met and potential surplus-for-export levels. RESULTS: There were 7.5% (n = 11,889) of deaths in Australia that were notified to Australian Eye Banks during our reporting period. Of those, 9.3% (n = 1106/11,889) were recovered and allocated, 15.7% (n = 1863/11,889) were known but declined, and 75% (n = 8920/11,889) were not pursued. Of those that were declined, 64.3% (n = 1197/1863) were declined because of limitations with service/manpower at the eye bank, whereas 35.7% (n = 666/1863) were declined because demand was met. CONCLUSIONS: Australia did not meet demand all the time, during our data period. There were adequate quantities of potential donors to support increasing recovery for domestic allocation and provide for exportation without hindrance to Australian demand. Further examination of domestic supply and demand cycles and the export process is required before routine exportation.

Deceased Donor-initiated Chains: First Report of a Successful Deliberate Case and Its Ethical Implications.

BACKGROUND: It has been suggested that deceased donor kidneys could be used to initiate chains of living donor kidney paired donation, but the potential gains of this practice need to be quantified and the ethical implications must be addressed before it can be implemented. METHODS: The gain of implementing deceased donor-initiated chains was measured with an algorithm, using retrospective data on the pool of incompatible donor/recipient pairs, at a single center. The allocation rules for chain-ending kidneys and the characteristics and quality of the chain-initiating kidney are described. RESULTS: The benefit quantification process showed that, with a pool of 69 kidneys from deceased donors and 16 pairs enrolled in the kidney paired donation program, it was possible to transplant 8 of 16 recipients (50%) over a period of 3 years. After obtaining the approval of the Veneto Regional Authority's Bioethical Committee and the revision of the Italian National Transplant Center's allocation policies, the first successful case was completed. For the recipient (male, aged 53 y), who entered the program for a chain-initiating kidney with a Kidney Donor Risk Index of 0.61 and a Kidney Donor Profile Index of 3%, the waiting time was 4 days. His willing donor (female, aged 53 y) with a Living Kidney Donor Profile Index of 2, donated 2 days later to a chain-ending recipient (male, aged 47 y) who had been on dialysis for 5 years. CONCLUSIONS: This is the first report of a successfully completed, deliberate deceased donor-initiated chain, which was made possible after a thorough assessment of the ethical issues and the impact of allocation policies. This article includes a preliminary efficacy assessment and describes the development of a dedicated algorithm.

Assessment of Postdonation Outcomes in US Living Kidney Donors Using Publicly Available Data Sets.

Importance: There are limited resources providing postdonation conditions that can occur in living donors (LDs) of solid-organ transplant. Consequently, it is difficult to visualize and understand possible postdonation outcomes in LDs. Objective: To assemble an open access resource that is representative of the demographic characteristics in the US national registry, maintained by the Organ Procurement and Transplantation Network and administered by the United Network for Organ Sharing, but contains more follow-up information to help to examine postdonation outcomes in LDs. Design, Setting, and Participants: Cohort study in which the data for the resource and analyses stemmed from the transplant data set derived from 27 clinical studies from the ImmPort database, which is an open access repository for clinical studies. The studies included data collected from 1963 to 2016. Data from the United Network for Organ Sharing Organ Procurement and Transplantation Network national registry collected from October 1987 to March 2016 were used to determine representativeness. Data analysis took place from June 2016 to May 2018. Data from 20 ImmPort clinical studies (including clinical trials and observational studies) were curated, and a cohort of 11 263 LDs was studied, excluding deceased donors, LDs with 95% or more missing data, and studies without a complete data dictionary. The harmonization process involved the extraction of common features from each clinical study based on categories that included demographic characteristics as well as predonation and postdonation data. Main Outcomes and Measures: Thirty-six postdonation events were identified, represented, and analyzed via a trajectory network analysis. Results: The curated data contained 10 869 living kidney donors (median [interquartile range] age, 39 [31-48] years; 6175 [56.8%] women; and 9133 [86.6%] of European descent). A total of 9558 living kidney donors with postdonation data were analyzed. Overall, 1406 LDs (14.7%) had postdonation events. The 4 most common events were hypertension (806 [8.4%]), diabetes (190 [2.0%]), proteinuria (171 [1.8%]), and postoperative ileus (147 [1.5%]). Relatively few events (n = 269) occurred before the 2-year postdonation mark. Of the 1746 events that took place 2 years or more after donation, 1575 (90.2%) were nonsurgical; nonsurgical conditions tended to occur in the wide range of 2 to 40 years after donation (odds ratio, 38.3; 95% CI, 4.12-1956.9). Conclusions and Relevance: Most events that occurred more than 2 years after donation were nonsurgical and could occur up to 40 years after donation. Findings support the construction of a national registry for long-term monitoring of LDs and confirm the value of secondary reanalysis of clinical studies.

Infections and associated behaviors among deceased organ donors: Informing the assessment of risk.

BACKGROUND: For infectious disease risk assessment among deceased organ donors, pre-donation clinical, microbiological, and behavioral information are reviewed; however, uncertainty may arise due to false negative screening results of recently acquired infections. METHOD: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and residual risks (RR) of undetected virus was estimated, with the impact of more sensitive screening. RESULTS: For United Kingdom potential deceased organ donors between 2010 and 2014, prevalence of HBsAg was 0.1%, HIV 0.06% and HCV 0.9%, increasing to 25.7% in people who injected drugs (PWID). Incidence, derived from new blood donors, was multiplied by duration of screening assay window periods to give RR per 100 000 donors as 0.43 (95% confidence interval [CI] 0.03-3.99) for HBV, 0.08 (95% CI 0.02-0.21) for HIV, and 5.96 (95% CI 0.82-37.89) for HCV. For PWID, HCV RR was 163.3 (95% CI 22.8-1107.8) compared to 2.76 (95% CI 0.35-17.36) for non-PWID. RR decreased significantly with nucleic acid testing (NAT), and, for HCV, antigen testing had a similar impact. CONCLUSION: While the burden of HCV risk lies within PWID, these are in small numbers therefore few HCV antigen or NAT tests would be needed to more accurately assess risk.

A retrospective study to assess the evaluation of living related kidney donors and their outcomes following nephrectomy at Kenyatta National Hospital.

BACKGROUND: Kidney transplantation is the renal replacement therapy of choice for end stage renal disease. To ensure safety regular audit of the donation process is necessary. The aim of this study was to assess the evaluation of potential living related kidney donors and document their outcomes following nephrectomy. METHODS: This was a retrospective descriptive study involving all living related kidney donors seen at Kenyatta National Hospital (KNH) renal unit from 2010 to 2014. Upon approval by KNH/ERC, the records of all kidney donors were retrieved. Demographic characteristics, number of potential and actual donors, their clinical, laboratory and radiological data as well as documented complications and deaths were recorded. SPSS version 17(Chicago, Ilinois) was used for data entry and analysis. Chi square test and Mann Whitney U test were used as tests of association for categorical and continuous data respectively, with P value set at <0.05. RESULTS: Median age of the donors was 34 years (IQR 31-39). First-degree relatives were majority(84.5%). Renal function assessment was done using mean glomerular filtration rate (GFR) from the radionuclide scan (DTPA) and serum creatinine levels. The donors had a mean GFR of 99.2 ± SD 6.6. All the haematological and biochemical tests were within normal. Majority(42.9%) were HLA compatible, but data on HLA typing was missing for 22% of the patients records. On CT angiogram, single renal artery and single renal vein were found in 94 and 88% respectively. Immediate complications included excessive bleeding(2%) and breach of other cavities (4%). Paralytic ileus (32%) and atelectasis (27%) were the most common early postoperative complications. There was no mortality. CONCLUSION: Our study reports no fatality but significant post-operative complications. These are significant findings that may be used to review and improve care and to educate potential kidney donors on the safety of this procedure in our centre, in a bid to widen the pool of potential living kidney donors.

Impact of single centre kidney paired donation transplantation to increase donor pool in India: a cohort study.

In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single-centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross-match (n = 59) and better matching (n = 19). A total of 124 two-way (n = 248), 14 three-way (n = 42), one four-way (n = 4) and one six-way exchange (n = 6) yielded 300 KPD transplants. Death-censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow-up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high-volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-centre LDKT via KPD when national programmes do not exist.

Anatomists' views on human body dissection and donation: an international survey.

A survey was conducted to test three hypotheses: anatomists believe that dissection by students conveys not just anatomical knowledge but also essential skills and attitudes, including professionalism; anatomists approve of the donation of their own bodies or body parts/organs for medical/health-care training and research; attitudes towards body dissection and donation are not dependent upon gender or upon the extent of teaching experience, but are related to transcendental convictions relating to beliefs in the afterlife. Eighty-one anatomists, from 29 countries responded to the survey; 80% indicated that they required medical/health-care students to dissect human cadavers (60% females-86% males, p=0.02). Most teachers recorded that dissection was an instrument for training undergraduate students, an instrument for the development of professional skills, and an instrument to help to control emotions in the future doctor rather than being only a means of teaching/learning anatomy facts. Males were more receptive to the concept that dissection helps to control emotions in the future doctor (p=0.02). Most teachers (75%) said they were willing to donate their bodies, 41% saying they would donate body organs only, 9% would donate their entire bodies only, 25% would separately donate organs and also the entire body. The willingness to donate increased significantly with the years of teaching experience (p=0.04). Teachers who were not believers in the afterlife were more likely to donate their organs/bodies than were believers (p=0.03). Our findings showed that anatomists' attitudes towards body dissection and donation are dependent upon gender, upon the extent of teaching experience, and upon transcendental convictions.

Asian immigrants to the United States are less likely to donate cryopreserved embryos for research use.

OBJECTIVE: To determine whether there are ethnic differences in the proportion of IVF patients donating excess cryopreserved embryos for use in research. DESIGN: Retrospective. SETTING: University clinic. PATIENT(S): Four hundred consecutive patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo disposition plan reported on the cryopreservation consent form (disposal, donation for research, or donation for therapeutic use). RESULT(S): Compared with Europeans or Asians born in the U.S., Asians born outside the U.S. were less likely to opt to donate excess embryos. Research donation was highly associated with interest in participation in clinical research. CONCLUSION(S): Decreased donation of excess embryos for research among Asians born outside the U.S. may relate to religious, sociocultural, language, or other undescribed factors. Targeted educational strategies may be critical to the development of a diverse pool of embryos available for research.

Percepción y disposición a donar órganos en Chile / Perception and disposition to donate organs in Chile

Como orientación a la política pública de salud, el presente documento determina la percepción y la disposición de las personas a la donación de órganos. El instrumento de indagación fue un cuestionario aplicado a una muestra de 204 personas localizadas en 10 ciudades de Chile. La varianza del estudio fue 18,8 por ciento, el error un 2,58 por ciento, la confiabilidad, medida por Alfa de Cronbach, fue de 0,777. Las variables se identificaron mediante el método de grupo foco, se midieron por escalas nominales y ordinales. En general se concluye que tanto quienes están inscritos como donantes como aquellos que no lo están tienen una buena disposición a donar órganos y perciben que la decisión de donación debe ser tomada en forma personal, pero en conocimiento de la familia.

Virtual crossmatch approach to maximize matching in paired kidney donation.

We developed and tested a new computer program to match maximal sets of incompatible live donor/recipient pairs from a national paired kidney donation (PKD) registry. Data of 32 incompatible pairs included ABO and 4 digit-high-resolution donor and recipient HLA antigens and recipient's HLA antibodies. Three test runs were compared, in which donors were excluded from matching to recipients with either donor-specific antibodies (DSA) >8000MFI (mean fluorescent intensity) at low-resolution (Run 1) or >8000MFI at high-resolution (Run 2) or >2000MFI and high-resolution (Run 3). Run 1 identified 22 703 possible combinations, with 20 pairs in the top ranked, Run 2 identified 24 113 combinations, with 19 pairs in the top ranked and Run 3 identified 8843 combinations, with 17 pairs in the top ranked. Review of DSA in Run 1 revealed that six recipients had DSA 2000-8000MFI causing a possible positive crossmatch resulting in breakdown of two 3-way and three 2-way chains. In Run 2, four recipients had DSA 2000-8000MFI, also potentially causing breakdown of three 2-way chains. The more prudent approach of excluding from matching recipients with DSA with >2000MFI reduces the probability of matched pairs having a positive crossmatch without significantly decreasing the number of possible transplants.

Análise bioética do diagnóstico de morte encefálica e da doação de órgãos em hospital público de referência do Distrito Federal / Bioethics analysis of the diagnosis of brain death and organs donation in apublic hospital of reference in the Federal District, Brazil

O estudo faz uma análise bioética do diagnóstico de morte encefálica (ME) no contexto da captação de órgãos para transplantes na instituição de referência regional, o Hospital de Base do Distrito Federal (HBDF), tendo por base a Resolução 1.480/97 do Conselho Federal de Medicina (CFM), quanto a: i) grau de conhecimento médico; ii) confiabilidade; iii) dificuldades para seguimento; iv) eficácia e segurança; v) adequação da estrutura e dos recursos do hospital para a adoção desses critérios. A pesquisa mostrou baixo índice de doação efetiva (15,8 por cento); significativoíndice de recusa familiar (27,2 por cento); outras causas de perda (parada cardiorrespiratória, sorologia positiva etc.), 57 por cento. A aplicação e interpretação de questionários respondidos por 30 médicos neurologistas e intensivistas do HBDF, indicaram os seguintes resultados: os critérios preconizados pelo CFM são conhecidos por mais de 93 por cento dos entrevistados e considerados confiáveis por 86,6 por cento deles; por falta de recursos tecnológicos e humanos, 63,4 por cento acham que o hospital não estáestruturado para prover um diagnóstico de ME seguro; 80 por cento dos entrevistados não assinariam um TDME baseado exclusivamente no exame clínico; 73,3 por cento indicaram a angiografia cerebral como o exame complementar mais seguro para diagnosticar ME, embora o eletroencefalograma fosse o meio mais utilizado na instituição.

European survey on clinical use of cord blood for hematopoietic and non-hematopoietic indications.

This report describes the evolution of Cord Blood (CB) hematopoietic stem cell transplants (HSCTs) in Europe over time and its current status. There were 687 patients with a first CB HSCT and a total of 763 allogeneic CB HSCT but no autologous CB HSCT reported in the year 2008. The 687 first transplants correspond to 6% of the total 11,408 allogeneic HSCT. All CB HSCT were for haematological indications; there were no CB transplants reported amongst the 598 cellular transplants listed for non-hematopoietic use. Indications were different depending on donor type. Main indications for the 48 HLA identical family donors CB HSCT were non-malignant disorders (36; 75%) and acute leukaemia (8; 17%). Main indications for the 639 unrelated first CB HSCT were acute leukaemia (337;53%), non-malignant disorders (115;18%) and lymphoproliferative disorders (53; 8%). 159 teams out of the 368 teams performing allogeneic HSCT (43%) reported 1 to 37 CB HSCT (median 3). There were significant differences in use of CB in the participating European countries with a median CB transplant number of 6.5 (range 1-207), transplant rate (number of CB HSCT/10 million inhabitants) of 6.3 (range 0.1-234.6) and a proportion of CB amongst allogeneic HSCT from 0.7% to 18.2% (median 5.4%). These data document the established role of CB HSCT in Europe but point to significant differences in its use.

Should we neglect or nurture replacement blood donors in sub-Saharan Africa?

Lack of blood is common in SSA but quantification of the overall shortfall is hampered by a lack of evidence-based targets for blood collection. Despite recommendations that all blood donors should be voluntary and non-remunerated, replacement donors are common throughout sub-Saharan Africa (SSA). Voluntary donors are generally recruited through centralised systems whereas replacement donors are recruited by families and donate through hospitals. Blood from a centralised service is more expensive than from a hospital-based service due to the higher costs of donor recruitment, quality assurance processes and the maintenance of distribution networks. Information about the contribution of replacement donors to the blood supply is scanty and inconsistent but it is likely that they currently provide over half of the blood in SSA. WHO's guidelines for transfusion services deal exclusively with voluntary donors and neglect the substantial contribution made by replacement donors. Examples of how the supply and quality of blood from the replacement donors can be improved have been published but need to be evaluated and disseminated. Political will and open-mindedness to innovative ways to improve supply and safety of blood from all types of donors are essential to promote more evidence-based approaches to blood transfusion practice in low-income countries.

Blood donation in Chile: Replacement and volunteer donors.

In recent years, the Chilean Health Ministry has developed a strategy in order to improve the safety and opportunity of the blood supply through the creation of a nationally co-ordinated blood transfusion service, centralizing collection management, production and testing in three Blood Centers along the country and promoting voluntary, regular, blood donation. In 2007, a comprehensive study of the situation of Blood Transfusion Services in Chile concluded that several critical factors make it difficult to achieve a safe and adequate access to blood and blood components in the country. For example there is a low donation rate (14.3/1000 inhabitants), very low percentage of voluntary donors (10%), excessive amount of blood banks collecting, processing and testing blood revealing an atomized non-centralized system, lack of a national IT system and insufficient national standards. There are two regions in the country, Bio Bio and Valparaíso, where Regional Blood Centers are located, that have put in place several strategies in order to obtain better results.

The blood donor in sub-Saharan Africa: a review.

The high prevalence of numerous endemic and epidemic diseases such as malaria, HIV infection and viral hepatitis in some areas of sub-Saharan Africa (SSA) affects the health status of blood donors. Considering the difficulties in ensuring sufficient and safe blood supply, analysing epidemiological factors that impact blood donors in this community may further bring light on issues of supply and safety, and help in planning for its rational use. This review does not aim to propose new strategies but describes the main characteristics of blood donors in SSA as collected from different reports. Data were mainly obtained from the reports of the World Health Organization and national blood transfusion programmes and also from relevant literature and conference reports. Several characteristics are common in blood donors, such as the predominance of young adult males, the high frequency of Transmission-transmitted Infections (TTIs) and some erythrocytic phenotypes. The data indicate variations in the level of improvement of blood collection and blood safety from one area to another, particularly in the field of donor motivation or screening strategies for TTIs. These data could be useful to supplement previous reports and to provide updates for governments and international organizations' programs involved in the improvement of blood safety in Africa.

Stranger donors: a key link in transplant chains.

Living donation to strangers is a complex issue that has caused some transplant centers to ban the practice altogether. Most prominent of the troublesome issues is the common source of these donors; namely, the Internet. These "stranger donors," however, are critical to both paired kidney transplants and chain kidney transplants. This article presents the ethical complexities of donors in these transplant arrangements and offers 2 case examples from our facility. Rigorous donor screening and informed consent processes are crucial, and together they help make transplant pairs and chains ethically feasible.

Barriers to implementing protocols for kidney paired donation and desensitization: survey of U.S. transplant programs.

CONTEXT: Special types of kidney transplant exist for patients who have willing but incompatible donors. Two types of transplants that circumvent donor-recipient incompatibility are "kidney paired donation" and "desensitization." Lack of access to these protocols limits living donations and shortens the life span of patients with willing but incompatible donors. OBJECTIVE: To understand potential barriers to implementing kidney paired donation and desensitization, as well as attitudes toward nondirected donation and compatible type O donation, which would maximize the number of kidney paired donation transplants performed via chains. DESIGN: We created a 56-question Web-based survey to elicit information from US transplant program directors about 24 potential barriers to implementing these protocols. PARTICIPANTS: Of 166 programs contacted, 96 responded, including 88 complete and 8 partial responses. After pediatric-only programs and multiple responses from the same program were removed, 84 total (78 complete) remained. MAIN OUTCOME MEASURES: Respondents were asked to designate each barrier as "major," "minor," or "not a barrier". RESULTS: Availability of dedicated nurse coordinators and the United Network for Organ Sharing's variance request process (although kidney paired donation does not actually require a variance) were significant barriers to kidney paired donation. Most respondents (54%, 42/78) would prefer to participate in a regional rather than a national protocol for kidney paired donation. Risk of complications was the most significant barrier to desensitization. University affiliation, region, and training (nephrologist vs surgeon) had little effect on perception of barriers. Most (92%, 71/78) would evaluate nondirected donations; 53% (41/78) would encourage compatible type O donors to enter kidney paired donation.