David Paredes

Normothermic recirculation reduces primary graft dysfunction of kidneys obtained from non-heart-beating donors.

Abstract Our aim was to analyze the short‐ and long‐term function of kidneys procured from non‐ heart‐beating donors (NHBD) by means of three techniques: in situ perfusion (ISP), total body cooling (TBC) and normothermic recirculation (NR). Fifty‐seven potential NHBD were included. Mean warm ischemia time was 68.9 ± 35.6 min. Forty‐four kidneys were obtained from donors perfused with ISP, 8 with TBC, and 8 with NR. Eighteen kidneys (32%) started functioning immediately, 29 (52 %) showed delayed graft function (DGF) and 9 (16%) showed primary non function (PNF). The actuarial graft survival rate was 76.4 % at 1 year and 56 % at 5 years. The patient survival rate was 89.3 % at 5 years. Incidence of DGF and PNF was significantly lower in kidneys perfused with NR than those with ISP or TBC (P < 0.01). Duration of DGF was shorter in kidneys obtained through TBC than in kidneys obtained with ISP (P < 0.05). In conclusion, NR reduces the incidence of DGF and may be considered the method of choice for kidney procurement from NHBD.

Applicability and Results of Maastricht Type 2 Donation After Cardiac Death Liver Transplantation

Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5‐min no‐touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end‐stage liver disease and cold and reperfusion warm ischemic times were 55 years (49–60), 19 (14–21) and 380 (325–430) and 30 min (26–35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One‐year recipient and graft survivals were 82% and 70%, respectively (median follow‐up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.

Success factors and ethical challenges of the Spanish Model of organ donation

1These data account for WHO’s strategy to extend the so-called Spanish Model across the globe, and for the European Parliament’s decision to incorporate some of the elements of the Spanish model into its 2010 action plan on organ donation and transplantation. 2 In this Viewpoint, we explore the success factors of the Spanish system and look at whether these factors can be implemented in other countries. We also identify inherent ethical issues. Success factors of the Spanish Model include its legal approach and a comprehensive programme of education, communication, public relations, hospital reimbursement, and quality improvement. These factors have occasionally been implemented by other regions with success. 3

Persistence of intracranial diastolic flow in transcranial Doppler sonography exploration of patients in brain death.

OBJECTIVE The persistence of cerebral blood flow (CBF) in patients with whole brain death (BD) diagnosis is an unusual phenomenon. We describe patients with whole BD diagnosed despite persistence of intracranial blood flow on transcranial Doppler sonography (TDS). MATERIALS AND METHODS From January 2001 to December 2002, we reviewed the records of 11 patients. Etiology of BD was craniocephalic trauma in 2 cases, schemic cerebrovascular accident (CVA) in 4 cases, Hemorrhagic CVA in 3 cases, subaracnoid hemorrhage in 1 case, and acute hydrocephalus in 1 case. Six patients had a cerebral decompressive mechanism. In all patients, TDS was used to confirm BD after clinical diagnosis. Additionally, all patients underwent an electroencephalogram (EEG). In 3 patients cerebral angiography (CA) and in 2 others radionuclide angiography (RA) with Tc99m HMPAO were done. RESULTS All TDS studies showed persistent telediastolic positive flow in at least 1 artery. Because the TDS did not confirm the clinical diagnosis of BD, EEG tests were performed showing silence of bioelectrical activity. Those cases showed CA or RA results with a complete absence of CBF. CONCLUSION The TDS technique directly evaluates the intracranial but not the intracerebral circulation. For this reason, during the BD diagnosis for patients with previous decompressive techniques, it was possible to find persistence of intracranial telediastolic flow using TDS. In those cases, it is advisable to use other tests to confirm the clinical diagnosis of BD.

The organs crisis and the Spanish model: theoretical versus pragmatic considerations

In the United Kingdom, the debate about how best to meet the shortfall of organs for transplantation has persisted on and off for many years. It is often presumed that the answer is simply to alter the law to a system of presumed consent. Acting perhaps on that presumption in his annual report launched in July, the Chief Medical Officer, Sir Liam Donaldson, advocated a system of organ donation based on presumed consent, the so-called “opt-out” system.1 He is calling for a change in the law in England and Wales whereby consent to organ donation is presumed, making a person’s organs automatically available for transplantation after death, unless they registered objections to this while alive. Subsequently, the British Medical Association (BMA) lent its support to the introduction of such a system.2 The BMA contends that “the practice of presumed consent legislation has had a significant effect on the number of cadaveric donors per million population.”2 It is often taken for granted that there must be a correlation between the enactment of legislation on presumed consent and an increase in organ donation and procurement. However, the correlation is not as straightforward as it might seem. It may be that other practical measures to encourage organ donation could be implemented without changing the Human Tissue Act 2004, an Act which has been in force for barely a year. An analysis by Abadie and Gay demonstrated that “presumed consent legislation has a positive and sizeable effect on organ donation rates”(p599),3 but they themselves admitted that the correlation between rates of donation and presumed consent legislation is “not completely unequivocal”(p606).3 It is true that among the most successful cases in procurement rates are countries with presumed consent legislation (Spain, Austria, Belgium, France and Italy). However, since some of the …

EULID Project: European Living Donation and Public Health

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) projects (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

Attitude of Health Professionals Toward Cadaveric Tissue Donation

INTRODUCTION A positive attitude toward organ donation would be expected among health professionals from transplant centers with active donor activities. However, acceptance and knowledge about cadaveric tissue donation has been insufficiently studied. OBJECTIVE The objective of this study was to analyze the knowledge and attitude of health professionals toward cadaveric tissue donation. METHODS An anonymous survey composed of 23 questions was given to health professionals from 2 university hospitals with donation experience. Sociodemographic and professional characteristics were described to analyze knowledge and acceptance of cadaveric tissue donation. RESULTS Among 600 distributed questionnaires we collected 514 completely answered surveys. Gender distribution was 399 females/115 males of ages ranging from 18-65 years, namely 18-28 years, 27%; 29-39 years, 31%; 40-50 years, 32%; and 51-65 years, 10%. Among the sample, 31% of health professionals had never been in contact with a transplant recipient. In this study 99.4% had knowledge about cadaveric organ donation compare with 89.7% about tissue donation. The knowledge about various types of tissue donation was as follows: eye, 96%; musculoskeletal, 87%; skin, 72%, and cardiovascular, 67%. In the sample, 93% and 92% accepted the opportunity to receive an organ or tissue transplantation, respectively. The acceptance of a tissue varied according to the type: cardiovascular, 93%; ocular, 94%; skin, 89%; and musculoskeletal, 87%. Participant acceptance of a relatives tissue donation was 74%, refusal was 22%, and with doubts was 4%. CONCLUSIONS Insufficient knowledge about cadaveric tissue was demonstrated among health professionals more exposed to the donation process. These results highlighted the importance of health professionals education to facilitate public information about organ and tissue donation.

Differential Pharmacologic Properties of the Two C75 Enantiomers: (+)-C75 Is a Strong Anorectic Drug; (−)-C75 Has Antitumor Activity

C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identifying it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential different biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that (-)-C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.

Kidneys from donors with incidental renal tumors: should they be considered acceptable option for transplantation?

Background The increase in the prevalence of end-stage renal disease in developed countries and the shortage of deceased donors has made it necessary to increase the graft pool by means of several strategies, such as live donation, non–heart-beating donors, and expanded criteria donors. Frequently, and because of the increasing acceptance of older donors, we find a higher percentage of incidental renal masses in these donors as a result of the inherent epidemiology of this disease. These kidneys can be considered suitable grafts after bench surgery to remove the tumor. Methods Retrospective analysis of donors with a diagnosis of incidental small renal mass before implantation and their corresponding recipients was performed between January 2007 and September 2012. All cases underwent an ex vivo tumorectomy with a preoperatory pathologic analysis. Recipients were followed up according to our standard renal tumor protocol. Results Eight donors with incidental renal mass were detected (four live and four deceased donors). The mean age was 47.8 years. Eleven transplantations were performed. Eight cases received the kidney after tumor exeresis, and three, the contralateral one. The recipient mean age was 53.8 years. The mean tumor diameter was 14.8 mm, with pathologic stages pT1a in seven cases and pT1b in one case (five clear cell renal carcinoma, two chromophobe type, and one lipoma). Surgical margins were negative. Mean follow-up was 32.34 months; none of the patients presented tumor recurrence, and all had correct renal function. Conclusions Kidneys with small incidental tumors can be considered an option for kidney transplantation in selected patients.

Coagulation Profiles of Unexpected DCDD Donors Do Not Indicate a Role for Exogenous Fibrinolysis

It has been suggested that vascular stasis during cardio‐circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out‐of‐hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98–100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted.