Organ Donation Research Articles

Human iPSC-liver organoid transplantation reduces fibrosis through immunomodulation.

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver-like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC-liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163+ M2-macrophage polarization. Next, we created midgestational fetal liver-like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163+ phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis.

Predicting outcomes after transplantation of deceased donor kidneys of marginal quality within the Eurotransplant service area.

Kidneys of marginal quality are increasingly being used to overcome the shortage of donor organs. However, accurate prediction of outcome is needed to optimise the use of these kidneys. We aimed to test the performance of a recently proposed score consisting of delayed graft function (DGF), renal function recovery (RFR), and glomerular filtration rate (GFR) <30 ml/min per 1.73 m2 90 days after transplantation for risk assessment of patient and graft survival. A total of 221 adult brain death donors with marginal kidneys, transplanted into 223 recipients within Eurotransplant were included in the analysis. Multivariable Cox proportional hazards models were constructed to assess death-censored and all-cause censored graft failure and recipient mortality at one and three years. Recipients with DGF had a higher risk of death-censored graft loss (HR, 95%CIs: 3.058 (1.195 - 7.825)). Recipients with a GFR <30ml/min/1.73m² at 90 days after transplantation had a higher risk of death censored and all-cause graft failure (HR, 95%CIs: 2.122 (1.129-3.990 and 2.122 (1.129 - 3.990)). None of the three components of the proposed score was associated with a higher risk of mortality. DGF and eGFR <30 ml/min/1.73m² but not RFR at 90 days predicted graft failure after transplantation of marginal kidneys. However, no combination of these factors was able to predict short-term patient and graft survival.

Do ethical views of end-of-life patients' family members impact organ donation decisions?

Background: The relatives of patients who decide to donate their loved one's organs experience dilemmas about organ donation and are affected by culture, religion, and individual views.Aim: The aim of this study was to determine the relationship between the ethical position and personal characteristics of the family members of the patients receiving end-of-life care and their thoughts about organ donation in Turkey.Research design and participants: The study was completed with 158 family members. For data collection, a personal information form and the Ethics Position Questionnaire were used.Ethical considerations: This study was obtained from the ethics committee of the faculty of medicine in Turkey. It was based on voluntary participation, informed consent, confidentiality, and anonymity.Results: All participants in the study shared the same faith and were Muslims. The idealism and relativism tendencies of the participants tended to be high. The number of children, the participants have, participants' status of waiting for an organ transplant, the view that the clergy and health personnel will increase interest in organ donation were identified as factors associated with idealism tendencies. Participants' status of having children, the number of children participants have, participants' status of organ transplant waiting, the view that the health personnel will increase interest in organ donation were identified as factors associated with relativism tendencies (p < 0.0.5).Conclusion: The results of this study demonstrated a relationship between participants' idealism and relativism tendencies, among those with a large number of children, waiting for organ donation, advocating for clergy guidance to increase organ donations, and believing healthcare professionals need not guide to increase organ donations. In light of this finding, it may be recommended to establish a multidisciplinary team, including healthcare professionals and clergy, and to inform the society with accurate information to increase the number of organ donations.

Brain Death and the Role of the Anaesthesiologist: A Review

Brain death is a critical and complex diagnosis in the medical field, necessitating precise and methodical evaluation. Anaesthesiologists play a pivotal role in this process, ensuring that the determination of brain death is accurate and ethically sound. This review examines the criteria and protocols for diagnosing brain death, the physiological and clinical challenges involved, and the crucial contributions of anaesthesiologists. We discuss the integration of neuroimaging and electrophysiological studies, the management of potential confounders such as intoxication or hypothermia, and the importance of maintaining homeostasis in potential organ donors. The involvement of anaesthesiologists in organ donation procedures, including maintaining optimal organ function and coordinating with transplant teams, is also explored. By highlighting the multi-faceted responsibilities of anaesthesiologists in the context of brain death, this review underscores their essential role in ensuring that diagnoses are made with the highest degree of accuracy and ethical consideration.

Categorization challenges in research on organ donation after euthanasia: Determining somatic or psychiatric origins of suffering

This perspective article discusses the classification challenges encountered in organ donation after euthanasia (ODE) among individuals with psychiatric disorders, as highlighted in our recent case series. In cases involving &amp;ldquo;somatic symptoms and related disorders,&amp;rdquo; somatic symptoms are connected to excessive thoughts, feelings, and behaviors, causing distress or dysfunction. Conditions such as tinnitus and chronic pain often co-occur with psychiatric disorders. The recent Dutch guideline on ODE eliminated the requirement to distinguish between somatic and psychiatric causes of suffering. This updated guideline encourages a holistic approach to patient care, emphasizing the importance of addressing patients&amp;rsquo; overall suffering rather than specific categorizations. To avoid errors in classification, categorization in research on ODE should recognize the overlap between somatic and psychiatric diagnoses, thereby eliminating the risk of misclassification, avoiding the stigmatization of patients, and optimizing future treatment options.

Proprotein convertase subtilisin/kexin type 9 as a drug target for abdominal aortic aneurysm.

There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth. This review summarizes evidence suggesting that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) may be a drug target to limit AAA growth. Mendelian randomization studies suggest that raised LDL and non-HDL-cholesterol are causal in AAA formation. PCSK9 was reported to be upregulated in human AAA samples compared to aortic samples from organ donors. PCSK9 gain of function viral vectors promoted aortic expansion in C57BL/6 mice infused with angiotensin II. The effect of altering PCSK9 expression in the aortic perfusion elastase model was reported to be inconsistent. Mutations in the gene encoding PCSK9, which increase serum cholesterol, were associated with increased risk of human AAA. Patients with AAA also have a high risk of cardiovascular death, myocardial infarction and stroke. Recent research suggests that PCSK9 inhibition would substantially reduce the risk of these events. Past research suggests that drugs that inhibit PCSK9 have potential as a novel therapy for AAA to both limit aneurysm growth and reduce risk of cardiovascular events. A large multinational randomized controlled trial is needed to test if PCSK9 inhibition limits AAA growth and cardiovascular events.

Family-Oriented Living Organ Donation in Bangladesh: A Bioethical Defence.

This study focuses on issues related to living organ donation for transplantation in Bangladesh. The policy and practice of living organ donation for transplantation in Bangladesh is family-oriented: close relatives (legal and genetic) are the only ones allowed to be living donors. Unrelated donors, altruistic donors (directed and non-directed), and paired/pooled or non-directed altruistic living donor chains-as many of these are implemented in other countries-are not legally allowed to serve as living donors in Bangladesh. This paper presents normative arguments explaining why the family-oriented nature of regulations and practices surrounding living organ donation for transplantation is essential for Bangladesh. In this article, I specifically argue that if the Bangladesh government revises the current biomedical policy robustly beyond relatives and allows unrelated donors to donate organs legally, this may foster organ selling due to the poverty and corruption problems in Bangladesh. The family-oriented requirement of the living organ donation policy and practice is defensible and morally justifiable as it preserves common notions of the family unit and family bonding in Bangladesh. Maintaining the current living-donation regulations and promoting deceased donation is the way forward, as this safely preserves the family values, protects against organ selling, and increases access to organ transplantation.

Organ Donation and Transplantation Coordinators' Experience and needs for ethics education.

Transplant coordinators face ethical conflicts in various situations, such as deciding who should receive organ donations and how to consider patient costs and such conflicts are expected to be more frequent in Korea, as organ transplant coordinators in the country perform both organ acquisition and transplantation. This study aims to develop an ethics education program to enhance organ transplant coordinators' ethical competence and address the ethical conflicts faced by them during clinical practice. A descriptive study. An online survey was conducted from March 22 to May 28, 2021. The study was conducted among 160 registered members of the Korea Organ Transplant Coordinators Association. Ultimately, 87 participants agreed to participate in the study. Permission to conduct the study was obtained from the Institutional Review Board. The study revealed variations in the degree of ethical conflict based on the participants' general characteristics. Furthermore, organ transplant coordinators exhibited high levels of ethical competence and expressed a need for ethics education. The findings also indicated a positive correlation between higher ethical competence and greater demand for ethics education. Based on the findings, developing standardized ethics education programs tailored to organ transplant coordinators is recommended. These programs should focus on improving ethical decision-making skills and establishing professional ethics. The education provided should be practical, applicable in the clinical setting, and responsive to the participants' awareness and concerns regarding ethics education.

Organ donation and transplantation in the Russian Federation in 2023. 16th Report from the Registry of the Russian Transplant Society

Organ donation and transplantation in the Russian Federation in 2023. 16th Report from the Registry of the Russian Transplant Society

Case Series: Fibula Free Flap with Bone Allograft as the Gold Standard in Lower Limb-Salvage Surgery for Adolescent Patients with Primary Bone Tumors Located within Tibial Diaphysis: Technical Modifications and Short-Term Follow-Up.

Background: Primary malignant bone tumors are most commonly associated with mutilating surgical procedures that can significantly disturb the motor development of a young patient and are frequently affiliated with major postoperative complications. Unfortunately, despite available autologous tissue donor sites, artificial materials are still most commonly used for the reconstruction of post-resection defects. Reconstructive microsurgery is increasingly recognized as an effective method of functional reconstruction, creating the possibility of performing limb-sparing surgery (LSS) with significant limitation of major postoperative complications at the same time. Methods: The study group consisted of 9 pediatric patients diagnosed with primary malignant bone tumor in the limb location. In order to perform microvascular reconstruction, 9 free fibula flaps were used in combination with a bone allograft (Capanna method). The functional outcome of the reconstruction was assessed on the basis of the MSTS (Musculoskeletal Tumor Society Scoring System) scale. Results: The presented analysis proves the effectiveness of this reconstructive procedure and the possibility of performing LSS with reasonable functional outcomes after appropriate patient qualification. In this study, all limbs included were spared. In all cases, the R0 surgical margins were achieved and no reports of local recurrences were reported during the follow-up. The average score on the MSTS scale was 27/30 points. Conclusions: Microvascular reconstructive surgery is an individually personalized and highly effective method of treating patients with primary bone tumors in the limb location and provides satisfactory functional outcomes.

Organ Utilization From Donors Following Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review of Graft and Recipient Outcome.

The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR. We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024. From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%). Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Awareness and Willingness towards Organ Donation among Riyadh Residents: A Cross-Sectional Study.

The increasing prevalence of chronic diseases in Saudi Arabia has heightened the need for organ transplantation; however, the donor pool remains insufficient. This study explored awareness and willingness towards organ donation among Riyadh residents and examined the sociodemographic factors influencing these attitudes. A cross-sectional survey using convenience sampling was conducted among adults in Riyadh. The survey assessed demographic characteristics, awareness, willingness to donate, and sociodemographic factors. Statistical analyses included descriptive statistics and logistic regression. Among the 645 respondents, 56.4% were willing to donate organs, with females showing a higher propensity than males (OR 2.9, 95% CI 1.7-5.1, p < 0.001). Awareness of organ donation centers was linked to increased willingness to donate (OR 1.5, 95% CI 1.1-2.5, p < 0.001). Higher educational level was strongly associated with donor registration (OR 36.8, 95% CI 14.7-91.9, p < 0.001). Despite their high willingness, only 9.5% were registered as donors, highlighting the gap between intention and action. Riyadh residents showed a significant willingness to donate organs, influenced by gender, education, and awareness. Low registration rates suggest barriers such as religious beliefs and lack of information. Targeted educational campaigns and policy evaluations, including an opt-out system, are recommended to enhance registration rates.

Computed Tomography Angiography as Ancillary Testing for Death Determination by Neurologic Criteria: A Technical Review.

The determination of death by neurological criteria (DNC) stands as a pivotal aspect of medical practice, involving a nuanced clinical diagnosis. Typically, it comes into play following a devastating brain injury, signalling the irreversible cessation of brain function, marked by the absence of consciousness, brainstem reflexes, and the ability to breathe autonomously. Accurate DNC diagnosis is paramount for adhering to the 'Dead donor rule', which permits organ donation solely from deceased individuals. However, complexities inherent in conducting a comprehensive DNC examination may impede reaching a definitive diagnosis. To address this challenge, ancillary testing such as computed tomography angiography (CTA) has emerged as a valuable tool. The aim of our study is to review the technique and interpretation of CTA for DNC diagnoses. CTA, a readily available imaging technique, enables visualization of the cerebral vasculature, offering insights into blood flow to the brain. While various criteria and scoring systems have been proposed, a universally accepted standard for demonstrating full brain circulatory arrest remains elusive. Nonetheless, leveraging CTA as an ancillary test in DNC assessments holds promise, facilitating organ donation and curbing healthcare costs. It is crucial to emphasize that DNC diagnosis should be exclusively entrusted to trained physicians with specialized DNC evaluation training, underscoring the importance of expertise in this intricate medical domain.

Outcomes in solid organ transplant recipients receiving organs from a donor with Fusarium solani species complex meningitis.

Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS. Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-β-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis.

Perspectives of relatives of patients with end-stage kidney disease on kidney sources, commercial kidney donation, and barriers to living kidney donation in Nigeria: a qualitative study.

Kidney transplantation is the best mode of kidney replacement therapy. However, the shortage of organ donations has been a major challenge globally. Relatives of patients with end-stage kidney disease (ESKD) are potential kidney donors. We explored their perspectives about kidney donation, kidney commercialisation, and barriers to kidney donation. In-depth interviews were conducted among 28 relatives of ESKD patients across the six geopolitical zones and Federal Capital Territory of Nigeria. The interview focused on potential sources of kidney donors, kidney commercialisation and barriers to kidney donation. ATLAS.ti version 9.0.22.0 was used for data analysis. Mean age of the study participants was 41.57 ± 14.55years; 54% were females, 60.7% were married, 93% had tertiary education and 75% were first degree relatives of ESKD patients. There were 7 themes and 28 subthemes generated in this study. The potential sources of kidney donors identified by the study participants included commercial, hospital, family and non-family member donors. While some opined that a family member is the best choice as a kidney donor, others preferred a commercial donor. The majority of those interviewed do not believe that it is wrong to purchase a kidney, and would be willing to do so. Identified factors that promote kidney commercialisation were unwillingness of a family member to donate, having the financial capacity to purchase a kidney, non-fitness of family members to donate. Identified barriers to kidney donation were age, poor health status, polygamy, perceived poor expertise of the medical team, perceived risk of the procedure, parental influence and religious beliefs. The majority of participants lacked correct information about kidney donation. Implementation of educational programpolicies and laws regulating and reinforcing ethical principles of kidney donation and transplantation should be ensured.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation

PurposeIn an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications.MethodsaNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range.ResultsThe liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301–451) µg/kg/h versus those who did not 105 (70–158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = − 0.755) and aspartate transaminase (AST; R = − 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346–453) µg/kg/h) from those who were discarded (155 (87–206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels.ConclusionsThis study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients.

Is Family-Priority Rule the Right Path? An Experimental Study of the Chinese Organ Allocation System

Abstract China is experiencing an organ shortage crisis. We experimentally test the effectiveness of the family-priority allocation rule on organ donation and argue that such incentive would be highly motivating in Chinese family-oriented culture. Results of our experiment show that introducing the family-priority rule can not only increase donor registration but also promote family consent. Such priority rule would be particularly effective to increase deceased organ donation in China, as it will significantly promote donor registration and meanwhile generate a consistent higher family consent rate in a more family-orientated culture.

Cadaveric organ donation: Indian perspective

Cadaveric organ donation in India, although started long back; its present status is not favourable. The percentage gain is very slow in comparison to most of the country even after having proper legislation. There are many reasons for this, lack of awareness being the most common. Most of the people does not know the concept of brain death. Although government and many NGOs are attached with it and are trying their level best to communicate with people for this noble cause, they have not yet reached the expected goal.To boost up the process of cadaveric organ donation, the hospitals and their staff including doctors must play a vital role. Hence, knowledge and orientation of such potential group is important for further processing because in most of the hospitals even doctors are not well-informed about the legal and ethical aspects of organ donation. If all the weak locus are addressed properly, we can definitely achieve the goals within a short span of time.

Cardiac surgery during wartime in Israel

BackgroundThe war that began on October 7th, 2023, has impacted all major tertiary medical centers in Israel. In the largest cardiac surgery department in Israel there has been a surprising increase in the number of open-heart procedures, despite having approximately 50% of surgeons recruited to military service. The purpose of this study is to characterize this increase in the number of operations performed during wartime and assess whether the national crisis has affected patient outcomes.MethodsThe study was based on a prospectively collected registry of 275 patients who underwent cardiac surgery or extracorporeal membrane oxygenation (ECMO) during the first two months of war, October 7th 2023 – December 7th 2023, as well as patients that underwent cardiac surgery during the same period of time in 2022 (October 7th, 2022 – December 7th, 2022).Results120 patients (43.6%) were operated on in 2022, and 155 (56.4%) during wartime in 2023. This signifies a 33.0% increase in open-heart procedures (109 in 2022 vs. 145 in 2023, p-value 0.26). There were no significant differences in the baseline characteristics of patients when comparing the 2022 patients to those in 2023. No significant differences between the two groups were found with regards to intraoperative characteristics or the type of surgery. However, compared to 2022, there was a 233% increase in the number of transplantations in the 2023 cohort (p-value 0.24). Patient outcomes during wartime were similar to those of 2022, including postoperative complications, length of stay, and mortality.ConclusionsPatients who underwent cardiac surgery during wartime presented with comparable outcomes when compared to those of last year despite the increase in cardiac surgery workload. There was an increase in the number of transplants this year, attributed to the unfortunate increase in organ donors.