Global transplantation:Lessons from organ transplantation organizations worldwide

Although national transplant organizations share common visions and goals,the creation of a unified global organization remains impractical.Differences in ethnicity,culture,religion,and education shape local practices and infrastructure,making the establishment of a single global entity unfeasible.Even with these social disparities aside,logistical factors such as time and distance between organ procurement and transplantation sites pose significant challenges.While technological advancements have extended organ preservation times,they have yet to support the demands of transcontinental transplantations effectively.This review presents a comparative analysis of the structures,operational frameworks,policies,and legislation governing various transplant organizations around the world.Key differences pertain to the administration of these organizations,trends in organ donation,and organ allocation policies,which reflect the financial,cultural,and religious diversity across different regions.While a global transplant organization may be out of reach,agreeing on best practices for the benefit of patients is essential.

Patients admitted in the intensive care unit after solid organ or bone marrow transplantation:Retrospective cohort study

BACKGROUND Solid organ transplantation(SOT)and hematopoietic stem cell transplantation(HSCT)revolutionized the survival and quality of life of patients with malignant diseases,various immunologic,and metabolic disorders or those associated with a significant impairment in a patient's quality of life.AIM To investigate admission causes and treatment outcomes of patients after SOT or HSCT treated in a medical intensive care unit(ICU).METHODS We conducted a single-center,retrospective epidemiological study in the medical ICU at the University Hospital Centre Zagreb,Croatia covering the period from January 1,2018 to December 31,2023.RESULTS The study included 91 patients with either SOT[28 patients(30.8%)]or HSCT[63 patients(69.2%)].The median age was 56(43.2-64.7)years,and 60.4%of the patients were male.Patients with SOT had more comorbidities than patients after HSCT[χ^(2)(5,n=141)=18.513,P<0.001].Sepsis and septic shock were the most frequent reasons for admission,followed by acute respiratory insufficiency in patients following HSCT.Survival rate significantly differed between SOT and HSCT[χ^(2)(1,n=91)=21.767,P<0.001].ICU survival was 57%in the SOT and 12.7%in the HSCT group.The need for mechanical ventilation[χ^(2)(1,n=91)=17.081,P<0.001]and vasopressor therapy[χ^(2)(1,n=91)=36.803,P<0.001]was associated with survival.The necessity for acute renal replacement therapy did not influence patients'survival[χ^(2)(1,n=91)=0.376,P=0.54].In the subgroup of patients with infection,90%had septic shock,and the majority had positive microbiological samples,mostly Gram-negative bacteria.The ICU survival of patients with sepsis/septic shock cumulatively was 15%.The survival of SOT patients with sepsis/shock was 45%.CONCLUSION Patients with SOT or HSCT are frequently admitted to the ICU due to sepsis and septic shock.Despite advancements in critical care,the mortality rate of patients with refractory septic shock and multiorgan failure in this patient population is extremely high.Early recognition and timely ICU admittance might improve the outcome of patients,especially after HSCT.

Machine learning in solid organ transplantation:Charting the evolving landscape

BACKGROUND Machine learning(ML),a major branch of artificial intelligence,has not only demonstrated the potential to significantly improve numerous sectors of healthcare but has also made significant contributions to the field of solid organ transplantation.ML provides revolutionary opportunities in areas such as donorrecipient matching,post-transplant monitoring,and patient care by automatically analyzing large amounts of data,identifying patterns,and forecasting outcomes.AIM To conduct a comprehensive bibliometric analysis of publications on the use of ML in transplantation to understand current research trends and their implications.METHODS On July 18,a thorough search strategy was used with the Web of Science database.ML and transplantation-related keywords were utilized.With the aid of the VOS viewer application,the identified articles were subjected to bibliometric variable analysis in order to determine publication counts,citation counts,contributing countries,and institutions,among other factors.RESULTS Of the 529 articles that were first identified,427 were deemed relevant for bibliometric analysis.A surge in publications was observed over the last four years,especially after 2018,signifying growing interest in this area.With 209 publications,the United States emerged as the top contributor.Notably,the"Journal of Heart and Lung Transplantation"and the"American Journal of Transplantation"emerged as the leading journals,publishing the highest number of relevant articles.Frequent keyword searches revealed that patient survival,mortality,outcomes,allocation,and risk assessment were significant themes of focus.CONCLUSION The growing body of pertinent publications highlights ML's growing presence in the field of solid organ transplantation.This bibliometric analysis highlights the growing importance of ML in transplant research and highlights its exciting potential to change medical practices and enhance patient outcomes.Encouraging collaboration between significant contributors can potentially fast-track advancements in this interdisciplinary domain.

Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation

BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Development of organ transplantation in China and organ donation

This article provides a concise overview of the development of organ transplantation in China.Inspired by international advancements in organ transplantation,China embarked on its own organ transplantation research journey in 1958.The clinical evaluation phase is marked by the first cadaveric kidney transplant in 1960 and the first living-donor kidney transplant in 1972.By 1989,the annual number of successful kidney transplants had surpassed 1000.However,57 liver transplants were performed between 1977 and 1983;limitations in technology and the scarcity of cyclosporine A resulted in unfavorable outcomes for most recipients,with the majority succumbing within 3 months of surgery.These factors led to a near-complete halt in liver,heart,and lung transplants for the following decade.With all 4 conditions met-(1)mature surgical techniques,(2)powerful immunosuppressive agents available for clinical use,(3)new organ preservation solutions that ensure the quality and transportation of donor organs,and(4)reasonable and legal sources of organs-China's organ transplantation field has experienced rapid development.In 2014,there were 9652 organ transplants,and this number grew to 20,225 by 2022.Despite the progress,China's organ donation rate per million remains relatively low,3.86 ranking 48th globally in 2022,underscoring the need for increased public awareness and support for organ donation.

Critical care specialists,the missing link in organ procurement for transplantation

The procurement process for organ donation begins with the identification of potential organ donors in emergency or critical care units(CCU),followed by their clinical evaluation,diagnostic procedures,and therapeutic interventions,mostly conducted in CCUs.It concludes with the request for organ donation and,if accepted,the retrieval of organs.Despite most interventions occurring in detection units,there has been a neglect of the strategic role played by critical care specialists(CCS)in managing and caring for brain-dead or near-brain-death patients.Questions arise:Are they willing to undertake this responsibility?Do they fully comprehend the nature of organ procurement?Are they aware of the specific interventions required to maintain possible organ donors in optimal physiological condition?Our objective is to examine the role of CCS in organ procurement and propose ways to enhance it,ultimately aiming to increase and enhance organ donation rates.

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Cryopreserved Fibroblast and Mesenchymal Stem Cells (MSCs) Being Alternative Mitochondrial Donors for Mitochondrial Organelle Transplantation (MOT)

Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, traumatic brain and spinal cord injuries, cerebral stroke, and neurodegenerative diseases. The earlier MOT results in better efficacy in animal models of urgent diseases such as ischemic stroke, and traumatic brain and spinal cord injuries. There is no long-term method to preserve mitochondria. Routine MOT procedure from cell growth to mitochondrial injection often takes serval weeks and is not satisfactory for urgent use cases. Hypothesis: Cryopreserved cells might be mitochondrial donors for MOT. Methods: We isolated mitochondria from cryopreserved human fibroblasts and mesenchymal stem cells (MSCs) in cell banks and compared the mitochondrial viability and transplantation with the mitochondria from fresh cells. Key findings: We found that mitochondria from fresh and cryopreserved cells are comparable in mitochondrial viability and transplantation. We also obtained data showing that mitochondria of fibroblasts and MSCs had similar membrane potential and transfer ability, but MSC’s mitochondria had higher ATP content than fibroblast’s mitochondria. In addition, oxygen consumption rates (OCRs) were higher in MSC’s mitochondria compared to fibroblast’s mitochondria and did not change between fresh and frozen cells. Conclusion: Cryopreserved fibroblasts and MSCs are alternative mitochondrial donors for MOT to fresh cells. MSCs could provide higher ATP-produced mitochondria than fibroblasts.

Machine perfusion in abdominal organ transplantation: Current use in the Netherlands

Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death.Due to the suboptimal outcomes of these donor organs,there is an increased interest in better preservation methods,such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes.This state-ofthe-art review aims to discuss the available types of perfusion techniques,its potential benefits and the available evidence in kidney,liver and pancreas transplantation.Additionally,translational steps from animal models towards clinical studies will be described,as well as its application to clinical practice,with the focus on the Netherlands.Despite the lack of evidence from randomized controlled trials,currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation.For ex vivo machine perfusion in kidney transplantation,hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial,while normothermic machine perfusion is currently under investigation.For ex vivo machine perfusion in liver transplantation,normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction.In response to clinical studies,hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.

Is the near coming xenotransplantation era relieving us from needing to look for more non-living organ donors?

Despite organ transplantation being the most successful treatment for end-stage organ dysfunction,the number of annual solid organ transplantations is much lower than that required to satisfy the demand of patients on waiting lists.The explanation for this phenomenon is the relative scarcity of non-living organ donors due to several factors,such as:(1)Late arrival of patients with a neurocritical condition to an emergency service;(2)lack of detection of those patients as possible organ donors by health professionals dedicated to procurement or by clinicians at emergency and intensive care units,for instance;(3)late transfer of the patient to an intensive care unit to try to recover their health and to provide hemodynamic,ventilatory,and metabolic support;(4)lack of confirmation of the physiological status of the possible donor;(5)late or incorrect positive diagnosis of the subject’s death,either due to brain or cardiac death;(6)difficulty in obtaining legal authorization,either by direct relatives or by the authority,for the extraction of organs;and(7)deficient retrieval surgery of the organs actually donated.The recent reports of relatively successful xenotransplants from genetically modified pigs open the possibility to fix this mismatch between supply and demand,but some technical(organ rejection and opportunistic infections),and economic issues,still remain before accepting a progressive replacement of the organ sources for transplantation.An approximate economic cost analysis suggests that the hypothetical acquisition cost of any genetically modified pig derived organ is high and would not even satisfy the solid organ demand of the wealthiest countries.

China organ donation and transplantation update: the Hangzhou Resolution

The much-anticipated change in the practice of organ donation and transplantation in China is now underway and affirmed by an important Hangzhou Resolution promulgated at the 2013 China Transplant Congress.Support of the National Health and Family Planning Commission On October 29,2013,in a meeting of the National Health and Family Planning Commission (NHFPC)officials with Jie-Fu Huang,Head of National Organ Transplant Committee(OTC), Hai-Bo Wang,Director of China Organ Transplant Response System (COTRS)

Cryptosporidium infection in solid organ transplantation

Diarrhea is a common complication in solid organ transplant(SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.

Liver transplantation using organs from deceased organ donors: a single organ transplant center experience

BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.

The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation

There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate＇s adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for 〉 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans- plantation are already in progress. Future developments will involve further genetic manipulations of the organ- source pig, with most of the genes that are likely to be beneficial already identified.

Organ assessment and repair centers: The future of transplantation is near

Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.

Current status of glucocorticoid usage in solid organ transplantation

Glucocorticoids(GCs)have been the mainstay of immunosuppressive therapy in solid organ transplantation(SOT)for decades,due to their potent effects on innate immunity and tissue protective effects.However,some SOT centers are reluctant to administer GCs long-term because of the various related side effects.This review summarizes the advantages and disadvantages of GCs in SOT.PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering“transplantation”and“glucocorticoids”.GCs are used in transplant recipients,transplant donors,and organ perfusate solution to improve transplant outcomes.In SOT recipients,GCs are administered as induction and maintenance immunosuppressive therapy.GCs are also the cornerstone to treat acute antibody-and T-cell-mediated rejections.Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols,to reduce ischemia-reperfusion injury peri-transplant.GCs with low bioavailability and high potency for GC receptors,such as budesonide,nanoparticle-mediated targeted delivery of GCs to specific organs,and combination use of dexamethasone with inducers of immuneregulatory cells,are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression.Various side effects involving different non-targeted organs/tissues,such as bone,cardiovascular,neuromuscular,skin and gastrointestinal tract,have been noted for GCs.There are also potential drug-drug interactions for GCs in SOT patients.

Bioengineered functional humanized livers： An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

End stage liver diseases （ESLD） represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.

Extended criteria brain-dead organ donors:Prevalence and impact on the utilisation of livers for transplantation in Brazil

BACKGROUND Despite its association with higher postoperative morbidity and mortality,the use of extended criteria donor(ECD)livers for transplantation has increased globally due to the high demand for the procedure.AIM To investigate the prevalence of ECD in donation after brain death(DBD)and its impact on organ acceptance for transplantation.METHODS Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre.The incidence of the Eurotransplant risk factors to define an ECD(ET-ECD)among DBD donors and the likelihood of organ acceptance over the years were analysed.The relationship between organ refusal for transplantation,the occurrence,and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment.RESULTS A total of 1619 organ donors were evaluated.Of these,78.31%(n=1268)had at least one ET-ECD criterion.There was an increase in the acceptance of ECD DBD organs for transplantation(1 criterion:from 23.40%to 31.60%;2 criteria:from 13.10%to 27.70%;3 criteria:From 6.30%to 13.60%).For each addition of one ETECD variable,the estimated chance of organ refusal was 64.4%higher(OR 1.644,95%CI 1.469-1.839,P<0.001).Except for the donor serum sodium>165 mmol/L(P=0.310),all ET-ECD criteria increased the estimated chance of organ refusal for transplantation.CONCLUSION A high prevalence of ECD DBD was observed.Despite the increase in their utilisation,the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation

Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.