Outcome analysis of brain-death referral to NOD-Lb: A retrospective chart review of a single hospital experience over 3 years.

BACKGROUND: Organ donation shortage and in particular organ procurement is an international concern as the gap between the number of donors and recipients is steadily growing. Organ procurement is a chain of steps with donor identification and referral (ID&R) as the very first link in this chain. Failure of this step hinders the progress in the organ transplantation program. OBJECTIVES: Our study was conducted to evaluate and highlight the gap between the national system and the practice at the identification and referral (ID&R) step of the organ procurement chain in a single tertiary-care academic health center in Beirut: the Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), and to appraise the literature for challenges at this step and for possible interventions for improvement based on the international experience. MATERIALS AND METHODS: This retrospective study was a descriptive case series of ICU and ED deceased patients at a single tertiary-care university hospital in Beirut. Patients' characteristics were collected from medical records for all patients who died between 2017 and 2019 while in the ICU or the ED and shared with the National Organization for Organ and Tissue Donation and Transplantation (NOD-Lb), for each subject separately, to decide on the donor status. All data collected from the patient cohort was analyzed using R version 3.6.1. Wilcoxon signed-rank test, chi-squared, and fisher-exact tests were used to compare differences in clinical characteristics in terms of donor status when appropriate. RESULTS: This study served as 3 years audit of a single hospital experience, and it demonstrates failure to make any referrals to NOD-Lb and zero actual organ and tissue donations over the study period. The review of 295 deceased subjects' charts demonstrates 295 missed alerts to NOD-Lb and the overall missing of 5 organ and tissue donors and 24 cornea donors assuming the organ procurement chain of steps will continue uninterrupted after ID&R. CONCLUSION: The data gathered suggests the presence of an inefficient identification and referral system that is translated into a complete failure of reporting to NOD-Lb from LAUMC-RH. A systematic evidence-based approach to evaluate for the most cost-effective intervention to increase identification and referral rates is needed with a serious effort to examine and account for any inefficient implantation.

How does the methodological clinical evaluation impact organ donation? Experience from 4 Organ Procurement Organizations (OPO)

INTRODUCTION: The lack of a clear and reproducible methodology for evaluating potential organ donors, which ensures traceability in the process, can compromise the number of utilized organ donors and the transplantation quality. METHODOLOGY: We developed a reproducible and safe method for the evaluation and validation of Potential Organ Donors (PD) based on 2 principles:1) Updated knowledge of absolute contraindications for organ donation and, 2) Decision making supported by 3 questions. The first principle was absolute contraindications. They were categorized into 4 groups: A) Serologies, B) Tumors, C) Infections, and D) Biological risk for transmission of infectious diseases and cancer. The second principle was the decision-making questions: A) What is the cause of death? B) Are there absolute contraindications to organ donation? and, C) Are there relative contraindications to organ donation? Each PD was subjected to the same methodology. The questions were answered after knowing the PD's clinical file. The PD was valid only if the set of answers adhered to an established matrix respecting different guidelines. The same physician evaluated each PD in all OPO. We applied in 4 different OPO, 3 of them in the State of São Paulo/Brazil and one in the United Arab Emirates, in different periods, including the SARS-COV 2 pandemic. RESULTS: OPO­SCSP, before the methodology (2007): 62 utilized donors, 205 transplants. After the methodology has been started (2008/2009/2010): 117, 154, 186 utilized donors and 348, 533, 487 transplants, respectively. 2) OPO-BTU, before the methodology (2009): 9 utilized donors and 19 transplants. After the methodology has been started (2010/2011/2012): 17, 36, 49 utilized donors and 38, 90, 143 transplants, respectively. 3) OPO-IDPC, before the methodology (2017): 93 utilized donors and 202 transplants. After the methodology has been started (2018/2019/2020): 107, 177, 187 utilized donors and 219, 395, 356 transplants, respectively. 4) UAE OPO, before the methodology (2020): 9 utilized donors and 35 transplants. After the methodology has been started (2021/2022): 39, 55 utilized donors and 147, 203 transplants, respectively. The percentage increase after the beginning of the methodology, considering the last year evaluated: 1) OPO-SCSP: 195% (Utilized donors) and 137% (Transplants); 2) OPO-BTU: 444% (Utilized donors) and 652% (Transplants); C) OPO-IDPC: 101% (Utilized Donors) and 76% (Transplants); 4) OPO-EOTC (United Arab Emirates): 511% (Utilized donors) and 480% (Transplants). CONCLUSION: The methodology used demonstrates that it can directly contribute to increasing the percentage of effective donors and transplants. The increase in donors ranged from 101% to 444%. The percentage growth of transplantation ranged from 76% to 652%. Indirectly, an increase the referrals was observed, motivated by frequent contact with OPO members and ICU professionals.

Ethical aspects of organ donation activities.

Renal transplant remains the treatment of choice for patients with end-stage renal disease. Human organs can be harvested from 2 main sources: living and deceased donors. Preference should be given to deceased-donor transplants since they represent the only source of organs for several nonrenal solid-organ transplants and the only modality where there is no risk to the donor. Unfortunately, even the most well-developed deceased-donor program (eg, the Spanish program) can barely cover 50% of its waiting list because the demand for deceased-donor organs far exceeds supply. The success of transplant surgery has created a waiting list dilemma. Despite all efforts, deceased-donor donation cannot meet current needs and therefore, living donation demands serious consideration. This is supported by the fact that the risk to live donors is minimal, graft survival is significantly better than that of deceased-donor kidneys regardless of HLA matching, and professional ethical philosophers have fewer difficulties with voluntary living donations than with the removal of an organ from a cadaver. This is especially true in our region. Living-related donation has always been acceptable ethically. It is, however, limited by the number of willing and qualified donors, the high incidence of familial renal diseases, and donor coercion (especially in our area). Living-unrelated donation increases the availability of donors, decreases the chances of coercion, and eliminates the problem of consanguinity. It raises, however, the ethical issues of commercialism, transplant tourism, and organ trafficking. The arguments for and against living-unrelated donation are innumerable. They have been the subject of several international forums and have raised endless discussions. We have set long ago a series of rules and regulations that are in close agreement with the recent Amsterdam and Kuwait resolutions. We have been continually modifying them over the last 15 years to try to implement our ideal, which is to protect the interest of the living donor and avoid commercialism.

A novel approach in clinical immunosuppression monitoring: drug lymphocyte level.

Like others, we have shown a weak correlation between drug blood levels and clinical outcome and immune response. We recently established that in contrast to blood levels, drug lymphocyte levels are strongly associated with therapeutic efficacy. The discordance between the 2 methodologies regarding clinical outcome and immune response is related mainly to the weak association between drug blood level and target-cell content. This weak association explains the intra- and interindividual variabilities of the therapeutic response. These variations are related mainly to genetic and environmental factors including age, sex, body mass index, organ function, food and subsequent drug absorption, drug interactions, and the availability of extra-target-cell binding sites. These factors seem to influence the modes of action of immunosuppressive agents including drug absorption, metabolism, elimination, transport, extra-target-cell sites, as well as target-cell receptor expression and its binding affinity and specific enzyme baseline activity. Therefore, the cellular fraction of a drug at a fixed dosage is the result of the integration of out-fluxing and in-fluxing forces that are affected by genetic and environmental factors. Any redistribution of the drug between the different binding sites will ultimately affect its bioactivity with no change to its extracellular bioavailability (which is currently determined by pharmacokinetic measurements). Compared with whole-blood or plasma-level measurements, monitoring immunosuppression therapy at the site of action appears to be not only more clinically and immunologically relevant (since it measures the free fraction of the drug at its effector site), but this method also bypasses the potentially complex extracellular factors that affect bioactivity. Since the intracellular content of a drug strongly correlates with its biological effect, monitoring immunosuppression therapy at the site of action is comparable to pharmacodynamic monitoring. It is cost effective and easy to perform in clinical practice and could be used for all immunosuppressive drugs. Since it allows maximal reduction of adverse effects through dosage reduction while maintaining an optimal level of immunosuppression, it should offer a new alternative for immunosuppressive therapy monitoring and tailoring to the individual patient.