Dead Donors Research Articles

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Uterus procurement from deceased donor for transplantation.

Women with absolute uterine factor infertility cannot get pregnant. The current experience in uterine transplantation is limited and the use of a deceased donor uterus in this area is incipient after some initial unsuccessful attempts. The birth of healthy babies through this modality in four different centers has given a new impetus to the use of this transplantation technique. We aimed to develop a technique for uterus procurement and preparation for transplantation from a brain dead donor. Fifteen uteri were retrieved from multi-organ donor patients, 10 of these were used in bench surgeries with the proposed technique. All procedures were performed after obtaining family's consent. This study allowed the clinical use of two of the 15 organs that were procured for transplantation. One of these organs resulted in the first live birth worldwide using a uterus transplanted from a deceased donor, a landmark in reproductive medicine. Another outcome was the optimization of the surgical technique involving less manipulation of the uterine vascular pedicles. The success of this novel technique suggests that the proposed model can be replicated and optimized further to facilitate the transplantation of uterus from deceased donors.

Assessment of Deceased Brain Dead Donor Liver Grafts via Normothermic Machine Perfusion: Lactate Clearance Time Threshold Can Be Safely Extended to 6 Hours.

The incorporation of machine preservation technology into clinical solid-organ transplantation is becoming a routine procedure in many institutions around the globe. As experience with these modalities accrues over time, it is important to refine their application. In combination with laboratory based NMP experiments, early patient series allowed us to establish NMP viability criteria that were applied in the VITTAL trial.

Perioperative management of the brain-dead organ donor : Anesthesia between ethics and evidence

HintergrundDie Anzahl postmortal gespendeter Organe ist in Deutschland weit geringer als der Bedarf. Dies unterstreicht die Wichtigkeit einer optimalen Versorgung während des gesamten Prozesses der Organspende.FragestellungEs existieren internationale Leitlinien und nationale Empfehlungen zu intensivmedizinischen organprotektiven Maßnahmen beim Organspender. Für das anästhesiologische Management fehlen evidenzbasierte Empfehlungen. Ziel dieser Übersichtsarbeit ist es, anhand der vorhandenen Evidenz die pathophysiologischen Veränderungen des irreversiblen Hirnfunktionsausfalls zu rekapitulieren und sich kritisch mit den empfohlenen Behandlungsstrategien und therapeutischen Zielgrößen auseinanderzusetzen. Auch auf ethische Aspekte der Betreuung des postmortalen Organspenders wird eingegangen.MethodeDiese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche in PubMed (Suchwörter: „brain dead donor“, „organ procurement“, „organ protective therapy“, „donor preconditioning“, „perioperative donor management“, „ethical considerations of brain dead donor“). Internationale Leitlinien und nationale Empfehlungen wurden besonders berücksichtigt.ErgebnisseInsgesamt ist die Evidenz für optimale intensivmedizinische und perioperative organprotektive Maßnahmen beim postmortalen Organspender sehr gering. Nationale und internationale Empfehlungen zu Zielwerten und medikamentösen Behandlungsstrategien unterscheiden sich teilweise erheblich: kontrollierte randomisierte Studien fehlen. Der Stellenwert einer Narkose zur Explantation bleibt sowohl unter pathophysiologischen Gesichtspunkten als auch aus ethischer Sicht ungeklärt.SchlussfolgerungenDie Kenntnisse über die pathophysiologischen Prozesse im Rahmen des irreversiblen Hirnfunktionsausfalls und die organprotektiven Maßnahmen sind ebenso Grundvoraussetzung wie die ethische Auseinandersetzung mit dem Thema postmortale Organspende. Nur dann kann das Behandlungsteam in dieser herausfordernden Situation sowohl dem Organempfänger als auch dem Organspender und seinen Angehörigen gerecht werden.

Association Between ACOX1 and NRF1 Gene Expression and Hepatitis B and C Virus Infections and Hepatocellular Carcinoma in Liver Transplant Patients (Shiraz, Iran).

Liver transplantation is used to treat both patients with end-stage liver diseases and those with hepatocellular carcinoma; in Iran, these patients are commonly infected with hepatitis B and C viruses. In the present study, for the first time, we investigated the association between ACOX1 and NRF1 gene and protein expression and presence of hepatitis B virus, hepatitis C virus, and hepatocellular carcinoma in liver transplant patients in South-Central Iran. In this cross-sectional study, we included 200 patients who were seen between 2008 and 2017 for liver transplant at the Namazi Hospital, Shiraz University of Medical Sciences (Shiraz, Iran). All patients received liver grafts from brain dead donors. Donors and recipients were unrelated. ABO compatibility blood group analyses for donor-recipient pairs were conducted. Liver transplant recipients were divided into 3 different groups: hepatitis B virus infected, hepatitis C virus infected, and presence of hepatocellular carcinoma. We also had a control group that included 30 healthy individuals. NRF1 and ACOX1 gene expression levels were evaluated using the SYBER green real-time polymerase chain reaction method. NRF1 and ACOX1 protein expression levels were evaluated using enzymelinked immunosorbent analyses. We used SPSS software for statistical analyses (version 19.0). NRF1 gene expression was increased in all 3 liver transplant recipient groups compared with the control group (not significant, P > .05). Furthermore, ACOX1 gene expression was decreased in all patients compared with control (P > .05). However, we found ACOX1 and NRF1 protein expression to be significantly decreased in all 3 liver transplant recipients groups compared with the control group (P < .05). NRF1 and ACOX1 genes and their protein expressions could affect the development of chronic liver disease.

Hemodynamic management in brain dead donors

Donor management is the key in the complex donation process, since up to 20% of organs of brain death donors (DBD) are lost due to hemodynamic instability. This challenge is made more difficult due to the lack of strong recommendations on therapies for hemodynamic management in DBDs and more importantly to the epidemiologic changes in these donors who are becoming older and with more comorbidities (marginal donors). In the present manuscript we aimed at summarizing the available evidence on therapeutic strategies for hemodynamic management (focusing on vasoactive drugs) and monitoring (therapeutic goals). Evidence on management in elderly DBDs is also summarized. Donor management continues critical care but with different and specific therapeutic goals since the number of donor goals met is related to the number of organs retrieved and transplanted. Careful monitoring of selected parameters (possibly including serial echocardiography) is the clinical tool able to guarantee the achievement and maintaining of therapeutic goals. Despide worldwide differences, norepinephrine is the vasoactive of choice in most countries but, whenever higher doses (> 0.2 mcg/kg/min) are needed, a second vasoactive drug (vasopressin) is advisable. Hormonal therapy (desmopressin, corticosteroid and thyroid hormone) are suggested in all DBDs independently of hemodynamic instability. In the single patient, therapeutic regimen (imprimis vasoactive drugs) should be chosen also according to the potential organs retrievable (i.e. heart vs liver and kidneys).

Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry.

Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12-18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.

Normothermic with or without hypothermic oxygenated perfusion for DCD before liver transplantation: European multicentric experience.

Grafts from donors with cardiac death (DCD) are subject to warm ischemia time (WIT) due to the no-touch-period (20min in Italy and 5min in France). These livers (LT) have higher rates of early allograft dysfunction (EAD), primary non-function (PNF), and ischemic cholangiopathy (IC) compared to LT from brain dead donors (DBD). Normothermic regional perfusion (NRP) is a beneficial strategy to mitigate organ damage; a further approach is the application of ex vivo hypothermic oxygenated perfusion (HOPE) after cold storage (CS). We retrospectively analyzed LTs performed from 2016 to 2019 at three transplant centers using NRP-DCD grafts: Bologna and Milan treated with HOPE (group A), Rennes preserved using CS (group B). No-flow period, total and functional WIT were significantly higher in group A than in group B (30.5±7.7vs. 20.5±4.1; 56.5±20.4vs. 39.1±21.6; 41.9±12.5vs. 25.5±3.7; respectively, P<.05), without differences in the postoperative course. In particular, the two groups had similar rates of EAD (21.1%vs. 25.0%), PNF (5.3%vs. 6.3%), IC (0%vs. 12.5%, P=.112), and non-IC biliary complications (0%vs. 6.3%, P=.457), re-LT (10.5%vs.12.5%). This occurred despite a high rate of UK DCD risk score>10 (63.2% A vs. 17.6% B, P=.000), which theoretically would make a large number of these transplants "futile." In conclusion, Italian and French groups had similar post-LT outcomes, probably related to the use of HOPE after CS in the case of long WIT.

Double-Effect Donation Disputed.

In "Double Effect Donation," Camosy and Vukov argue that "there are circumstances in which it is morally permissible for a healthy individual to donate their organs even though their death is a foreseeable outcome". They propose that a living donor could ethically donate an entire, singular, vital organ while knowing that this act would result in death. In reply, I argue that it is not ethical for a living person to donate an entire, singular, vital organ. Moreover, mutatis mutandis, it is not ethical for surgeons and others to perform such a deadly operation. For to do so is "intentionally to cause the death of the donor in disposing of his organs". Such an act violates the dead donor rule which holds that an entire, singular, vital organ may be taken only from a corpse. Contrary to Camosy and Vukov's claims, double-effect reasoning does not endorse such organ donation.

Proteomic analysis of machine perfusion solution from brain dead donor kidneys reveals that elevated complement, cytoskeleton and lipid metabolism proteins are associated with 1-year outcome.

SUMMARYAssessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1‐year post‐transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP‐citrate synthase and fatty acid‐binding protein 5 (T1) and immunoglobulin heavy variable 2‐26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1‐year post‐transplantation. Furthermore, it provides insights into mechanisms that could play a role in post‐transplant outcomes.

May I give my heart away? On the permissibility of living vital organ donation.

The dead donor rule (DDR) regulates current practice for vital organ donation, which means that organs may only be retrieved from people who are already dead (or brain dead). However, several authors criticize the DDR and argue that we should instead adopt a rule that allows us to retrieve vital organs before people are dead. They call this proposal organ donation euthanasia (ODE). While I am sympathetic to this proposal I do not think it goes far enough. In this paper, I show that the key reasons put forward in favor of permitting ODE actually justify a more far-reaching suggestion for regulation, permitting people to become living vital organ donors even when they are not about to die for other reasons. Further, I argue that only accepting imminently dying people as eligible donors for living vital organ donation would be objectionably paternalistic.

Assessment of Oxidative Stress Markers in Hypothermic Preservation of Transplanted Kidneys

Ischemia-reperfusion injury (IRI) after renal transplantation is a complex biochemical process. The first component is an ischemic phase during kidney storage. The second is reperfusion, the main source of oxidative stress. This study aimed to analyze the activity of enzymes and concentrations of non-enzymatic compounds involved in the antioxidant defense mechanisms: glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione transferase (GST), thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), measured in preservation fluid before transplantation of human kidneys (KTx) grafted from brain dead donors. The study group (N = 66) was divided according to the method of kidney storage: Group 1—hypothermic machine perfusion (HMP) in LifePort perfusion pump, n1 = 26, and Group 2—static cold storage (SCS), n2 = 40. The measurements of kidney function parameters, blood count, and adverse events were performed at constant time points during 7-day hospitalization and 3-month follow-up. Kidney perfusate in Group 2 was characterized by significantly more acidic pH (p < 0.0001), higher activity of GPX [U/mgHb] (p < 0.05) and higher concentration of MDA [μmol/L] (p < 0.05). There was a statistically significant improvement of kidney function and specific blood count alterations concerning storage method in repeated measures. There were aggregations of significant correlations (p < 0.05) between kidney function parameters after KTx and oxidative stress markers: diuresis & CAT, Na+ & CAT, K+ & GPX, urea & GR. There were aggregations of significant correlations (p < 0.05) between recipient blood count and oxidative stress markers: CAT & MON, SOD & WBC, SOD & MON. Study groups demonstrated differences concerning the method of kidney storage. A significant role of recipient’s gender, gender matching, preservation solution, and perfusate pH was not confirmed, however, basing on analyzed data, the well-established long-term beneficial impact of HMP on the outcome of transplanted kidneys might partially depend on the intensity of IRI ischemic phase and oxidative stress, reflected by the examined biomarkers.

Evaluation of changes in plasma vitamin C levels in brain-dead organ donors

Introduction: Inflammatory events after brain death (BD) generally influence the quality of donated organs and adversely affect the outcome of transplant surgeries. Vitamin C is a natural organic compound with potent antioxidant properties. Changes in serum levels of vitamin C (ascorbic acid) following BD are still unknown. Objectives: This study aimed to assess the changes in serum vitamin C levels in brain dead donors in the time elapsed between BD diagnosis and at once before procurement procedure of donated organs. Patients and Methods: In this experimental study, serum vitamin C levels were measured in 37 brain-dead donors (BDDs) at two time points, primarily on admission (R1) and just before organ procurement (R2). The difference between mean values of R1-R2 was analyzed according to the parameters of brain dead donor’s, which consisted of gender, cause of BD, and type of blood group. Results: A total of 37 BDDs (62.2% male) with a mean age of 26.48±18.1 years were included. Time interval between the two samplings was 40.09±12.10 hours. Overall, there was a statistically significant difference between serum ascorbic acid (AA) levels at admission (R1) and immediately before organ procurement (R2) (P=0.016). However, in terms of the cause of BD and blood type, no significant difference in serum AA at the two-time points was detected (P=0.85 and P=0.79 respectively). Conclusion: Significant differences were observed between serum vitamin C levels in the duration between BD diagnosis and immediately before procurement surgery. Therefore, determining the most effective dose of vitamin C supplementation and the best time to administer it to the patients is highly recommended for future studies.

Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors.

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

Training Experiences of American Society of Transplant Surgeons Fellows in Deceased Donor Organ Procurement.

Training Experiences of American Society of Transplant Surgeons Fellows in Deceased Donor Organ Procurement.

Poor Organ Donation in Vietnam: Resulting from Beliefs, Religions, and Traditional Culture? How to Promote Organ Donation and to Deal with Organ Trading from a Legal Perspective?

In Vietnam, organs are always in great demand while the organ supply from brain dead donors is extremely small, prompting the search for organs supplied by living people. People in need of an organ transplant either have to wait for a legally supplied organ (coming from any voluntary and non-commercial donation) or resort to an illegal supplied one (through organ trading). Therefore, increasing the number of legally supplied organs and controlling illegal source of supply are problems to be solved by Vietnam. This paper discovers whether religions, beliefs, traditional culture, and current legislation impede the organ donation or not. In addition, this paper also aims to find out legal loopholes resulting in ineffective handling of organ trading, then proposing solutions to improve the law to promote the legal supply of organs and effectively combat crimes related to organs illegally supplied by organ trading.

Donor and Recipient Matching in Facial Vascularized Composite Allotransplantation: A Closer Look at the Donor Pool.

Identifying a donor for facial vascularized composite allotransplant recipients can be a lengthy, emotionally challenging process. Little is known about the relative distribution of key donor characteristics among potential donors. Data on actual wait times of patients are limited, making it difficult to estimate wait times for future recipients. The authors retrospectively reviewed charts of nine facial vascularized composite allotransplant patients and provide data on transplant wait times and patient characteristics. In addition, they analyzed the United Network for Organ Sharing database of dead organ donors. After excluding donors with high-risk characteristics (e.g., active cancer or risk factors for blood-borne disease transmission), the authors calculated the distribution of relevant donor-recipient matching criteria (i.e., ethnicity, body mass index, age, ABO blood group, cytomegalovirus, Epstein-Barr virus, hepatitis C virus) among 65,201 potential donors. The median wait time for a transplant was 4 months (range, 1 day to 17 months). The large majority of United Network for Organ Sharing-recorded deaths from disease were white (63 percent) and male (58 percent). Female donors of black, Hispanic, or Asian descent are underrepresented, with 7, 5, and 1 percent of all recorded deaths from disease, respectively. Potential donors show cytomegalovirus and Epstein-Barr virus seropositivity of 65 and 95 percent, respectively. The number of annual hepatitis C-positive donors increased over time. Actual facial vascularized composite allotransplant wait times vary considerably. Although most patients experience acceptable wait times, some with underrepresented characteristics exceed acceptable levels. Cytomegalovirus-seropositive donors present a large portion of the donor pool, and exclusion for seronegative patients may increase wait time. Hepatitis C-seropositive donors may constitute a donor pool for underrepresented patient groups in the future.

Liver Transplantation in Croatia: "David Among Goliaths".

Liver Transplantation in Croatia: "David Among Goliaths".

Changes in Clinical Features and Demographics in Donors After Brain Death Over the Past 20 Years: A Single-Center Experience in the Republic of Korea.

We investigated clinical characteristics and demographics of brain death in patients from a single center in Korea to identify possible changes in organ procurement by comparing early and late periods. Potential donors diagnosed as brain dead and who had provided organ donation consent from May 2000 to May 2020 were considered. Donors were divided into 2 categories: early period (2000-2010) and late period (2011-2020).Demographic data, clinicalrisk factors, cause of death, use ofinotropic and vasoconstrictor agents, laboratory findings, intensive care unit stay data, loss of donors, and number of donated organs were analyzed. Mean age of donors significantly increased in the late period (36.0 ± 12.0 vs 46.0 ± 15.1 years), but there were no significant differences in the proportion of females and the number of pediatric donors (<18 years). The number of donors who smoked decreased (61% vs 41%), but hypertension rate increased significantly in the late period (17.4% vs 31.0%). In the late period, fewer brain dead donors were lost (19.0% vs 7.59%) and use of vasoconstrictor agents was more frequent (25.3% vs 64.5%) than use of inotropic agents (73.1% vs 49.3%). In the late period, heart(19.0% vs 37.3%) and lung (0% vs 18.3%) procurement rates increased and the number of transplanted organs per donorincreased (2.58 ± 1.6 vs 3.14 ± 1.50; P = .016). Causes of death were primarily from head traumas (34.4%), cerebral aneurysms (21.7%), spontaneous intracerebral hemorrhage (21.3%), and asphyxia/hanging (16.3%). Head trauma decreased in the late period (46% vs 29.7%; P = .021) but still constituted the most common cause of death. We found no definite demographic changes in brain dead donors. Donors with cerebrovascular disease increased annually, but trauma was still the most common cause of brain death, with suicides being highly frequent.

Acts that Kill and Acts that Do Not

In response to recent debates on the need to abandon the Dead Donor Rule (DDR) to facilitate vital-organ transplantation, I claim that, through a detailed philosophical analysis of the Uniform Determination of Death Act (UDDA) and the DDR, some acts that seem to violate DDR in fact do not, thus DDR can be upheld. The paper consists of two parts. First, standard apparatuses of the philosophy of language, such as sense, referent, truth condition, and definite description are employed to show that there exists an internally consistent and coherent interpretation of UDDA which resolves the Reduction Problem and the Ambiguity Problem that allegedly threaten the UDDA framework, and as a corollary, the practice of Donation after the Circulatory Determination of Death (DCDD) does not violate DDR. Second, an interpretation of the DDR, termed ‘No Hastening Death Rule’ (NHDR), is formulated so that, given that autonomy and non-maleficence principles are observed, the waiting time for organ procurement can be further shortened without DDR being violated.