Zika virus and its implications on cord blood banking and transplantation.

Umbilical cord blood is an important cellular therapy product used for hematopoietic stem cell transplantation, but the US Food and Drug Administration guidance regarding donor screening to reduce the risk of Zika transmission has decreased the number of licensed, eligible cord blood units available for transplantation. There is a crucial need for updated travel risk assessment for Zika virus transmission, validated screening tests for Zika virus in umbilical cord blood, and further research on Zika virus transmissibility due to umbilical cord blood products to ensure that umbilical cord blood and related tissues are safe and available for transplantation.

Mitigating Racial and Sex Disparities in Access to Living Donor Kidney Transplantation: Impact of the Nation's Longest Single-center Kidney Chain.

OBJECTIVE: In this study, we sought to assess likelihood of living donor kidney transplantation (LDKT) within a single-center kidney transplant waitlist, by race and sex, after implementation of an incompatible program. SUMMARY BACKGROUND DATA: Disparities in access to LDKT exist among minority women and may be partially explained by antigen sensitization secondary to prior pregnancies, transplants, or blood transfusions, creating difficulty finding compatible matches. To address these and other obstacles, an incompatible LDKT program, incorporating desensitization and kidney paired donation, was created at our institution. METHODS: A retrospective cohort study was performed among our kidney transplant waitlist candidates (n = 8895). Multivariable Cox regression was utilized, comparing likelihood of LDKT before (era 1: 01/2007-01/2013) and after (era 2: 01/2013-11/2018) implementation of the incompatible program. Candidates were stratified by race [white vs minority (nonwhite)], sex, and breadth of sensitization. RESULTS: Program implementation resulted in the nation's longest single-center kidney chain, and likelihood of LDKT increased by 70% for whites [adjusted hazard ratio (aHR) 1.70; 95% confidence interval (CI), 1.46-1.99] and more than 100% for minorities (aHR 2.05; 95% CI, 1.60-2.62). Improvement in access to LDKT was greatest among sensitized minority women [calculated panel reactive antibody (cPRA) 11%-49%: aHR 4.79; 95% CI, 2.27-10.11; cPRA 50%-100%: aHR 4.09; 95% CI, 1.89-8.82]. CONCLUSIONS: Implementation of an incompatible program, and the resulting nation's longest single-center kidney chain, mitigated disparities in access to LDKT among minorities, specifically sensitized women. Extrapolation of this success on a national level may further serve these vulnerable populations.

Development of a Clinical Decision Support System for Living Kidney Donor Assessment Based on National Guidelines.

BACKGROUND: Live donor nephrectomy is an operation that places the donor at risk of complications without the possibility of medical benefit. Rigorous donor selection and assessment is therefore essential to ensure minimization of risk and for this reason robust national guidelines exist. Previous studies have demonstrated poor adherence to donor guidelines. METHODS: We developed a clinical decision support system (CDSS), based on national living donor guidelines, to facilitate the identification of contraindications, additional investigations, special considerations, and the decision as to nephrectomy side in potential living donors. The CDSS was then tested with patient data from 45 potential kidney donors. RESULTS: The CDSS comprises 17 core tasks completed by either patient or nurse, and 17 optional tasks that are triggered by certain patient demographics or conditions. Decision rules were able to identify contraindications, additional investigations, special considerations, and predicted operation side in our patient cohort. Seventeen of 45 patients went on to donate a kidney, of whom 7 had major contraindications defined in the national guidelines, many of which were not identified by the clinical team. Only 43% of additional investigations recommended by national guidelines were completed, with the most frequently missed investigations being oral glucose tolerance testing and routine cancer screening. CONCLUSIONS: We have demonstrated the feasibility of turning a complex set of national guidelines into an easy-to-use machine-readable CDSS. Comparison with real-world decisions suggests that use of this CDSS may improve compliance with guidelines and informed consent tailored to individual patient risks.

Organ donor screening practices for Strongyloides stercoralis infection among US organ procurement organizations.

BACKGROUND: Targeted donor screening for strongyloidiasis performed at the time of organ procurement can prevent this life-threatening donor-derived infection. METHOD: The Association of Organ Procurement Organizations surveyed members to determine the number of US organ procurement organizations (OPOs) performing donor screening for Strongyloides infection and their screening practices. RESULTS: All 58 OPOs responded to the survey. Only 6 (10%) currently screen donors for strongyloidiasis; most OPOs started 6-36 months before the survey and one started 6 years prior. All used risk-based criteria to determine which donors to screen, though the criteria varied among OPOs. A median of 56 donors have been screened at each OPO since initiating their screening programs, with a median of 2 infected donors (range 0-13) identified. Overall, 53 organs have been transplanted from 22 infected donors, including hearts, lungs, kidneys, and livers. Of 52 OPOs not currently screening, 20 had considered screening and one plans to start screening in the near future. Of those considering risk-based screening, most had not decided on the criteria. Uncertainty about the benefits of and guidelines for screening and misconceptions about the interpretation of test results were concerns shared by non-screening OPOs. CONCLUSION: Continued education and advocacy on the importance of targeted donor screening are needed.

[Donor and recipient selection in living donor kidney transplantation: eligibility]. / La selezione del donatore e del ricevente nel trapianto di rene da donatore vivente: iter di idoneità.

This review is intended to be a guide for the physician to evaluate and prepare a donor / recipient couple for living kidney transplantation. Although it is intended to be exhaustive, it will not be able to respond at all possible and different cases, but it may apply at most of them. Renal transplantation is considered the choice treatment for patients with chronic renal failure and if the kidney transplant is performed pre-emptive it is associated with better organ and patient survival. The main aim of the program is to evaluate the risks of donor and recipient and to ensure the donor safety and well-being. Eligibility for living transplant can only be granted when the risks are acceptable, well defined and the couple is adequately informed. The review includes clinical and legal procedures needed to transplantation. Early conditions that contraindicate the transplant must be removed, to avoid unnecessary exams, excessive waste of time, money. The sequence of the exams has been ordered so that costly and invasive surveys are carried out only after other simple and essential investigations have confirmed the transplant suitability. Special attention should be paid to the renal function measurement, proteinuria, hematuria, hypertension, obesity, pre diabetes, renal calculus, and cancers. To give eligibility for living transplant is often not easy, but a careful study can avoid many complications and improve the transplant outcome.

Fifteen years of Nucleic Acid Testing in France: Results and lessons.

Of the 40 million donations screened with Nucleic acid testing (NAT) between July 2001 and December 2015 in France, 20 HIV-positive, 13 HCV-positive and 17 HBV (HBV-NAT was initiated in 2005 and extended to the whole country in 2010) donations were discarded thanks to NAT. The main benefit in terms of discarded donations is related to HBV with a yield of 0.88 per million donations, which is 12.5 and 1.8 times higher than for HCV and HIV respectively. The main risk factor found in these donors during the post donation interview was having sex with men for males (n=11, all repeat blood donors), having a partner HCV positive (n=6) or at-risk partner (originated from endemic area or HBV positive) for HBV (n=8) for HIV, HCV and HBV, respectively. Although the mean viral load was high for HIV (5.6 log copies/mL) and HCV (7 log IU/mL), HBV cases show low level of DNA (1.8 log IU/mL) demonstrating the need of a highly sensitive NAT assay. Overall, the clinical benefit for recipients remains those related to the prevention of HIV contaminations since HCV avoided transmissions are extremely rare (only one case in the last 5 years thanks to NAT) and the potential infectivity of HBV-NAT only positive cases is questionable due to the low level of HBV DNA and the presence of anti-HBs in more than a half of DNA positive/HBsAg and anti-HBc negative donors.

Impact of a Full-Time Donor Management Protocol on Donors' Liver Biopsy Findings: Progress to Date.

OBJECTIVES: This study investigated a fixed coordinator-directed donor management strategy's impact on donated liver quality, as determined by definitive biopsy results. MATERIALS AND METHODS: We collected donated liver biopsy results from donations both before and after implementing a fixed coordinator-directed donor management strategy. This strategy involved full-time attendance by a donor coordinator and continued resuscitation of brain-dead donors. All donations took place in a single organ procurement unit. We also followed up results of biopsies from the Liver Transplantation Center database of Namazi Hospital in Shiraz, Iran. RESULTS: We compared biopsy findings of 192 livers donated from 2012 to 2013 (group A) with 276 livers donated from 2015 until August 2016 (group B). Data analysis showed that 67 livers (34.9%) in group A were rejected for transplant owing to severe steatosis in 17 (8.9%), moderate/severe fibrosis in 9 (4.7%), moderate/severe necrosis in 28 (14.6%), and 13 (6.8%) rejected for other pathologies. Among group B livers, 59 (21.4%) were not deemed suitable for transplant owing to severe steatosis in 37 (13.5%), moderate/severe fibrosis in 6 (2.1%), and moderate/ severe necrosis in 16 (5.7%). Overall, steatosis was found in 94 livers (49.2%) in group A versus 175 livers (63.3%) in group B (P = .007). Donor age in group A averaged 36.5 years versus 47.9 years in group B (P = .02). Necrosis was found in 33 livers (17.2%) in group A and 22 livers (7.9%) in group B (P = .008). One-month survival rates were 95.3% and 96.3% for groups A and B (P = .08). CONCLUSIONS: Donated liver disqualification before transplant noticeably decreased despite the shift in demographic patterns from 2012 to 2016. In group A, brain-dead liver donors were younger and more often died from trauma, whereas group B donors had more cerebrovascular accident-induced deaths. This achievement took place alongside increased rates of steatosis and decreased rates of necrosis.

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care.

The History and Challenges of Blood Donor Screening in China.

Since the establishment of People's Republic of China in 1949, the Chinese government has encountered several catastrophes related to transfusion transmitted diseases. The government's increasing attention to blood safety has prompted the initiation of a series of policies and measures that have enhanced the level of safety for the blood supply and met the basic clinical demands of blood for 1.3 billion people in the country. Blood donation screening strategies in China predominantly comprise donor screening and donor testing. Donor screening includes selection of low-risk blood donors by the use of a donor history questionnaire, predonation physical examination, and initial rapid donor testing. Donor testing includes direct pathogen detection and serology tests. The year 1998 marked the most transformative change in blood donor selection and screening policies in China. Before 1998, paid donation was the predominant mode of blood donation. Donor screening and donor testing were conducted before donation, and only those who were eligible were allowed to donate. To ensure the safety of blood, donor testing was performed again after donation. After the implementation of the Blood Donation Law in 1998, to promote voluntary and unpaid donation, predonation donor testing was eliminated to reduce the amount of waiting time and to provide a more convenient donation experience for blood donors. However, it is the national requirement that donated blood should undergo 2 rounds of testing using different equipment or reagents, conducted by different personnel. Donor selection has transitioned from paid donation and obligatory donation to voluntary donation with fixed volunteer groups, as the latter mode of donation provides the lowest risks. Donations are currently screened for syphilis, hepatitis C virus, HIV, and hepatitis B virus (HBV). Units, previously typed only for ABO, are now routinely tested for both ABO and Rh(D). Innovations in testing technologies and methods have also brought changes to screening parameters. For instance, screening for HBV pathogens evolved from the early use of hemagglutination method to the later use of radioimmunoassay, independent enzyme-linked immunosorbent assay, and now the widespread application of nucleic acid test (NAT). Since 2010, the Chinese government has established NAT capacity in several blood centers; and in 2015, the government invested 900 million RMB on the nationwide expansion of NAT. Although the Chinese government has worked to enhance blood safety, many challenges remain. Concern exists for rising rates of HIV infection. The existence of occult HBV infection and the transmission of emerging blood-borne diseases continue to challenge the safety of the blood supply.

Fundamental Principles of Stem Cell Banking.

Stem cells are highly promising resources for application in cell therapy, regenerative medicine, drug discovery, toxicology and developmental biology research. Stem cell banks have been increasingly established all over the world in order to preserve their cellular characteristics, prevent contamination and deterioration, and facilitate their effective use in basic and translational research, as well as current and future clinical application. Standardization and quality control during banking procedures are essential to allow researchers from different labs to compare their results and to develop safe and effective new therapies. Furthermore, many stem cells come from once-in-a-life time tissues. Cord blood for example, thrown away in the past, can be used to treat many diseases such as blood cancers nowadays. Meanwhile, these cells stored and often banked for long periods can be immediately available for treatment when needed and early treatment can minimize disease progression. This paper provides an overview of the fundamental principles of stem cell banking, including: (i) a general introduction of the construction and architecture commonly used for stem cell banks; (ii) a detailed section on current quality management practices; (iii) a summary of questions we should consider for long-term storage, such as how long stem cells can be stored stably, how to prevent contamination during long term storage, etc.; (iv) the prospects for stem cell banking.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction / Ampliando o pool de doadores de rim: utilização de órgãos com disfunção renal aguda

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

RESUMO Diante da escassez de órgãos para transplante, algumas estratégias têm sido adotadas pela comunidade transplantadora, no sentido de ampliar a oferta de órgãos. Uma delas é a utilização de rins de doadores com critérios expandidos, ou seja, doadores com idade >60 anos ou entre 50 e 59 anos, e que atendem a dois ou mais dos seguintes critérios: história de hipertensão, creatinina sérica terminal >1,5mg/dL e acidente vascular cerebral como causa de morte do doador. Nesta revisão, foi dada ênfase à utilização de doadores com disfunção renal aguda, condição considerada por muitos uma contraindicação para a aceitação de órgãos e, portanto, uma das principais causas de descarte de órgãos. Desde que sejam doadores bem selecionados e que não tenham doença renal crônica, como hipertensão ou diabetes, muitos trabalhos mostraram que o uso de doadores com disfunção renal aguda deve ser encorajado, pois, em geral, a disfunção renal aguda é de caráter reversível. Embora, a maioria dos estudos tenha demonstrado que há uma maior taxa de função retardada do enxerto com a utilização desses órgãos, os resultados de sobrevida do enxerto e do paciente após o transplante são muito semelhantes aos resultados obtidos da utilização de doadores padrão. Os achados clínicos e morfológicos do doador, a utilização da máquina de perfusão e a análise de seus parâmetros, principalmente a resistência intrarrenal, são importantes ferramentas de apoio para tomada de decisão no momento da oferta de órgãos com disfunção renal.

The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry.

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10-562) days. The ADP is a viable method to support time limited donors in a KPD network.

Assessing the potential of international organ exchange--the Swiss experience.

OBJECTIVE: Little is known about the impact of international organ exchange on national transplant programmes. This study evaluates the relevance of hearts and lungs offered by the European Organ Exchange Organisations to Swisstransplant, Switzerland's national organ procurement organisation. METHODS: The study is a retrospective analysis of donor characteristics of 290 hearts and 199 lungs, offered by the European Organ Exchange Organisations between 1 January 2004 and 31 December 2008 to Swisstransplant. It assesses the responses (acceptance/reasons for refusal) from the Swiss heart and lung transplant centres. RESULTS: Among the 290 hearts offered by the foreign transplant organisations, eight (2.8%) were accepted by a Swiss transplant centre. This corresponds to 5.8% of the Swiss heart transplant activity during the observation period. In the lung group (n = 199), five (2.5%) were accepted, equalling 2.8% of the transplant activity. As for the reasons for refusal, approximately one-fifth and one-sixth of both the heart and lung offers were refused for medical and logistic reasons, respectively. For more than half of the offers, there was either no compatible recipient on the Swiss waiting list, or the reason for refusal was not specified. Notably, 47.6% of the offers in the heart group and 46.7% of the lung offers originated from donors aged less than 16 years. CONCLUSIONS: International organ exchange is a very valuable and effective way to allocate a maximum of medically suitable organs to recipients on the waiting list. Organ exchange is lifesaving, especially in children, and also in patients with rare blood groups. A professional structure within the national organ procurement organisations, and a close cooperation between them on an international level, is crucial to achieve organ exchange on a high-quality level in Europe.

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Stem cells are miraculous things. These primitive undifferentiated cells are normally present in the bone marrow and develop into red cells, white cells and platelets. The bone marrow can be stimulated to produce more stem cells than needed through the use of stimulating factors, for example, Granulocyte Colony Stimulating Factor or GCSF. These extra stem cells spill out from the bone marrow into the peripheral circulation. Using a blood cell separator they can be collected from the circulating blood and given to a recipient.

Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood.

Since the first successful transplantation of umbilical cord blood in 1988, cord blood has become an important source of hematopoietic stem and progenitor cells for the treatment of blood and genetic disorders. Significant progress has been accompanied by challenges for scientists, ethicists, and health policy makers. With the recent recognition of the need for a national system for the collection, banking, distribution, and use of cord blood and the increasing focus on cord blood as an alternative to embryos as a source of tissue for regenerative medicine, cord blood has garnered significant attention. We review the development of cord blood banking and transplantation and then discuss the scientific and ethical issues influencing both established and investigational practices surrounding cord blood collection, banking, and use.