Scarcity Of Organs Research Articles

Proposed hypothesis of GSK-3 β inhibition for stimulating Wnt/β-catenin signaling pathway which triggers liver regeneration process.

Almost every human organ has a poor ability to regenerate, notable exceptions are liver, skin, gut, etc. Molecular and cellular underpinnings of liver regeneration might pave the way for novel treatments concerned with chronic liver disorder. Such treatments would eliminate the disadvantages of liver transplantation, such as a scarcity of donor organs, a lengthy waitlist, significant medical expenses, surgical complications, and the necessity for lifelong immunosuppressive medications. Advancement in the development of regenerative therapy is giving hope to those suffering from end-stage liver disorder. The regeneration process is unique, intricate, and well coordinated, which involve the interaction of numerous signaling pathways, cytokines, and growth factor. Various signaling pathways for liver regeneration are HO-1/BER pathway, Tweak/Fn14 signaling pathway, Hippo pathway, Wnt/beta-catenin pathway, Hedgehog signaling pathway, bile acids repairing pathway, serotonin (5HT) pathway, estrogen pathway, thyrotropin-releasing hormone (TRH) pathway, insulin repairing pathway, etc. The in vitro scientific literature revealed that numerous GSK-3 β inhibitors (LY 2090314, AR-A014418, Tideglusib, Solasodine, CHIR99021, 9-ING-41, SB-216763) play an important role in stimulating the liver regeneration process. Similarly, from the above discussion, the direction is highlighted to emphasize the proposed molecular Wnt/β-catenin signaling pathway which is associated with GSK-3 β inhibition for the induction of the repairing and regeneration process.

Waiting Time for Second Kidney Transplantation and Mortality.

The median kidney transplant half-life is 10-15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list. In this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980-2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies "retransplant" versus "remain waitlisted with maintenance dialysis" are reported for different waiting times after first graft loss. Second kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, -14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively. Second kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death

Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015–2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy performed after declaration of death. Hepatocyte isolation was performed by three-step collagenase perfusion. Hepatocyte viability, yield, and function were assessed using fresh and cryopreserved cells. Engraftment and maturation of cryopreserved neonatal hepatocytes were assessed by transplantation into an immunodeficient mouse model and analysis of the gene expression of phase I, phase II, and liver-specific enzymes and proteins. Twelve livers were procured. Median warm ischemia time (WIT) was 190 [interquartile range (IQR): 80–210] minutes. Median viability was 86% (IQR: 71%–91%). Median yield was 6.9 (IQR: 3.4–12.8) x106 viable hepatocytes/g. Transplantation into immunodeficient mice resulted in good engraftment and maturation of hepatocyte-specific proteins and enzymes. A neonatal organ donation program including preterm born infants was found to be feasible. Hepatocytes isolated from neonatal donors had good viability, function, and engraftment despite prolonged WIT. Therefore, neonatal livers should be considered as a donor source for clinical hepatocyte transplantation, even in cases with extended WIT.

II. Dynamics of Function and Regulation of the Endoplasmic Reticulum.

Diabetes results from insufficient production of the hormone insulin from beta cells in pancreatic islets. Islet transplantation can replace the lost beta cells in patients but is limited by the scarcity of available donor organs. Our aim is to differentiate pluripotent stem cells into functional islets that can serve as an unlimited source for transplantation to treat diabetes. We have investigated the therapeutic potential of pancreatic endoderm cells derived from human embryonic stem cells. Several weeks following transplant into diabetic rodents, these cells mature and secrete sufficient human insulin, in a regulated manner, to reverse diabetes. In rats, we observed inconsistent survival of pancreatic endoderm cells implanted subcutaneously in macroencapsulation devices designed to be immunoprotective via use of a cell impermeable layer, but this was rectified by the addition of portals designed to enable direct capillary vascular permeation into the device interior. In contrast both device types supported cell survival, differentiation and function in mice, with more rapid C-peptide release and better glucose tolerance observed using the devices containing portals. Kidney capsule grafts often contained ductal cells and cysts, whereas cells implanted subcutaneously within macroencapsulation devices differentiated predominantly to endocrine cells. In collaboration with Aspect Biosystems, we are also exploring the feasibility of using 3D bioprinting as an approach to both contain implanted islet cells and protect them from immune attack. As part of a ViaCyte clinical trial (clinicaltrial.gov identifier: NCT03163511), we investigated the safety and efficacy of pancreatic endoderm cells implanted in nonimmunoprotective macroencapsulation devices for the treatment of patients with type 1 diabetes and hypoglycemic unawareness. Patients underwent subcutaneous implant of cell products combined with an immunosuppressive regimen. After implant, patients had increased fasting Cpeptide levels, increased glucose-responsive C-peptide levels, and developed mixed meal-stimulated C-peptide secretion. Patients had reduced insulin requirements, increased time in target blood glucose range, and improved hypoglycemic awareness. Explanted grafts contained cells with a mature beta cell phenotype that were immunoreactive for insulin, islet amyloid polypeptide, and MAFA. Collectively, these findings support future investigation into optimizing cell therapies for diabetes.

Heterogeneity of liver fibrosis in patients with congestive hepatopathy: A biopsy and explant comparison series

PurposePatients with end-stage heart failure and concomitant irreversible liver injury may be candidates for combined heart liver transplant (CHLT). Determining appropriate candidates for CHLT is essential given organ scarcity. Transjugular liver biopsy (TJLB) is used to evaluate the severity of parenchymal liver injury in transplant candidates. In patients with congestive hepatopathy (CH), the fibrosis pattern may be heterogenous. MethodsWe reviewed all CHLT cases between 2007 and 2017, as well as lone-heart transplant cases with post-mortem autopsy. Pre-transplant TJLB was compared to explant to assess the performance of biopsy fibrosis staging. Results12 patients were included. Median age at time of transplant was 58 and the cohort was predominantly male (75%). Seven (64%) TJLB were predominantly stage 4 fibrosis and 4 (36%) were stage 1. Advanced fibrosis was the dominant pattern in 7 (70%) explants and 5 (50%) explants had heterogenous fibrosis. In 50% of CH cases, there was discordance between the TJLB and explant. In the autopsy cases, the TJLB and autopsy findings differed. ConclusionsIn this series of matched TJLB and explanted livers, we found variable performance of TJLB in predicting the predominant fibrosis stage present in the liver.

Translational Control in Liver Disease

Chronic liver disease is one of the biggest threats to public health worldwide. Worryingly, the incidence of liver disease is dramatically rising due to the aging of the population and the global epidemics of obesity. Both are major risk factors for chronic liver disease and adverse prognostic factors, causing an increase in mortality rate. It is of great concern that 80–95% of obese people have non-alcoholic fatty liver disease, the major precursor for liver failure and a global health challenge. Currently, the only curative treatment for advanced chronic liver disease is liver transplantation, which is, however, hampered by high treatment costs and the scarcity of donor organs. New strategies are therefore urgently needed to prevent and reverse chronic liver disease. And for that it is essential to understand better the molecular mechanisms underlying human disease. This review focuses on the abnormalities in the regulation of translation by RNA-binding proteins during chronic liver disease and their pathological impact on portal hypertension, fibrosis, steatosis, neovascularization, and cancer development.

Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings.

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). Patients and Methods: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000–2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan−Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). Results: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60’s and their 70’s. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). Conclusions: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient’s comorbidity and predicted life expectancy.

Urgent Liver Transplantation from Deceased Donor With a Calcified Hydatid Cyst: A Case Report

Liver transplantation is the final treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The large gap between the growing list of patients awaiting liver transplantation and the scarcity of donor organs has fueled efforts to maximize the existing donor pool and identify new avenues. We treated a 13-year-old boy who had acute liver failure, due to Wilson's disease, with transplantation of a liver from a deceased liver donor with a calcified hydatid cyst. After 3 years of follow-up, liver function tests remained normal, hydatid cyst serology was negative, and no hydatid cyst or other problems were observed.

Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis.

Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Values Not Our Own: Interrogating Psychosocial Suitability in the Transplant Social Work Assessment.

A primary role of social workers in North American transplant programs is to assess potential organ recipients’ psychosocial suitability for a life-saving transplantation (Sas, 2019). In a context of organ scarcity, the social work assessment is part of a larger multidisciplinary evaluation that aims to prevent waste (Gordon, 2000). Neglected in this focus on waste prevention is social work’s professional mandate for social justice. Although a biomedical perspective presents organ allocation as an objective, pragmatic, and fair decision-making process, transplantation is laden with Western values of personal responsibility and efficiency, which, in practice, conflict with social work’s values of fair and equitable treatment and access to resources, including life-saving organs. In this column, I critically reflect on social work assessments for determining psychosocial suitability for transplant, illustrating how the values for personal responsibility and efficiency individualize systemic health inequities and constrain our practice. Given our professional...

Machine Learning Applications in Solid Organ Transplantation and Related Complications.

The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems.

Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.

Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long‐term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell‐replacement strategies. Induction of local immunotolerance to prevent allo‐rejection against islets and stem cell derived β cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non‐encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/β cell modification, immunomodulatory biomaterial platforms, and co‐transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.

Health-Related Quality of Life and Mental Health after Surgical Treatment of Hepatocellular Carcinoma in the Era of Minimal-Invasive Surgery: Resection versus Transplantation.

Laparoscopic liver resection (LLR) is an increasingly relevant treatment option for patients with resectable hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) has been considered optimal treatment for HCC in cirrhosis, but is challenged by rising organ scarcity. While health-related quality of life (HRQoL) and mental health are well-documented after OLT, little is known about HRQoL in HCC patients after LLR. We identified all HCC patients who underwent LLR at our hospital between 2014 and 2018. HRQoL and mental health were assessed using the Short Form 36 and the Hospital Anxiety and Depression Scale, respectively. Outcomes were compared to a historic cohort of HCC patients after OLT. Ninety-eight patients received LLR for HCC. Postoperative morbidity was 25% with 17% minor complications. LLR patients showed similar overall HRQoL and mental health to OLT recipients, except for lower General Health (p = 0.029) and higher anxiety scores (p = 0.010). We conclude that LLR can be safely performed in patients with HCC, with or without liver cirrhosis. The postoperative HRQoL and mental health are comparable to that of OLT recipients in most aspects. LLR should thus always be considered an alternative to OLT, especially in times of organ shortage.

MO923PREDICTING POST-TRANSPLANT HRQOL TO OPTIMIZE OUTCOMES IN OLDER KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Kidney transplantation (KT) is the optimal treatment for older patients in need for kidney replacement therapy, with favorable outcomes both on survival, and health-related quality of life (HRQoL). Given the current organ scarcity, allocation of transplants should prioritize patients who are expected to benefit most from KT and identifying reliable predictors of post-transplant HRQoL outcomes is essential to optimize the selection process. Method Patients ≥ 65 years, who were enlisted for KT between January 2013 and November 2016 at the Norwegian national transplant center, were asked to participate. Self-reported HRQoL was assessed using the Kidney-Disease Quality of Life Short Form version 1.3 (KDQOL-SF) survey. Pre-transplant comorbidity was assessed by the Liu comorbidity index (LCI). Linear mixed-effect models were used to detect HRQoL changes over time (pre-KT, at -6, -12 and -36 months post-KT), and to identify pre-transplant predictors of post-transplant outcomes. Results By November 2020, 220 (76%) out of 289 enrolled participants, were transplanted. The mean age at KT was 71.8 (4.1) years, 154 (70%) were males, 57 (26%) were transplanted pre-emptively and 30 (13.6%) received a transplant from a living donor. Longer dialysis vintage was independently associated with impaired physical function post-transplantion (Figure 1). Pre-transplant LCI score ≥ 7 consistently predicted poorer HRQoL outcomes at baseline and after 3-years, compared with LCI score &amp;lt; 7 (Figure 2). At 3- years post-transplant, increasing LCI score was lineary associated with decreasing SF-36 scores. Recipients on dialysis for ≥ 1 year with LCI ≥ 7 experienced the worst outcomes, with a marked and sustained post-transplant physical deterioration (Figure 3). Conclusion Older wait-listed candidates either on dialysis for &amp;gt;1 year or with elevated pre-transplant LCI are at high risk for impaired HRQoL post-transplant outcomes and should be re-evaluated with respect to transplantability on a regular basis. The identification of criteria to optimize the selection of older transplant candidates should be the scope of future studies

Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis.

Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce. A retrospective double case control matched pair analysis (60 months follow-up) was carried out and RTx-recipients were stratified for history of PTM. First, PTM-RTx recipients were matched according to age, sex and duration of immunosuppressive therapy. Next, PTM-RTx recipients were matched 1:1 for age, sex and cause of end-stage renal disease. Five-year patient and graft survival as well as oncological outcomes were analyzed. A total of 65 PTM-RTx recipients were identified. Post-RTx recurrence rate was 5%, while 20% developed second de novo malignancy, comparable to 14% in the control group. PTM-RTx recipients had a noticeable lower five-year death-censored as well as overall graft survival and Cox proportional hazard modeling showed a correlation between PTM and inferior graft survival. Although underlying reasons remain not fully understood, this study is the first to show inferior graft survival in PTM-RTx recipients and advocates necessity to focus on more meticulous graft monitoring in PTM recipients in addition to heightened surveillance for cancer recurrence.

Factors Associated With Access to and Receipt of Liver Transplantation in Veterans With End-stage Liver Disease

Organ scarcity means few patients with advanced liver disease undergo a transplant, making equitable distribution all the more crucial. Disparities may arise at any stage in the complex process leading up to this curative therapy. To examine the rate of and factors associated with referral, wait-listing, and receipt of liver allografts. This retrospective cohort study used linked data from comprehensive electronic medical records and the United Network of Organ Sharing. Adult patients with cirrhosis and a Model for End-Stage Liver Disease with addition of sodium score of at least 15 points between October 1, 2011, and December 31, 2017, were included in the study. Patients were from 129 hospitals in the integrated, US Department of Veterans Affairs health care system and were followed up through December 31, 2018. Statistical analyses were performed from April 28, 2020, to January 31, 2021. Sociodemographic (eg, age, insurance, income), clinical (eg, liver disease etiology, severity, comorbidity), and health care facility (eg, complexity, rural or urban, presence of a liver transplant program) factors were evaluated. Referral, wait-listing, and liver transplantation. Of the 34 494 patients with cirrhosis (mean [SD] age, 62 [7.7] years; 33 560 men [97.29%]; 22 509 White patients [65.25%]), 1534 (4.45%) were referred, 1035 (3.00%) were wait-listed, and 549 (1.59%) underwent a liver transplant within 3 years of meeting clinical criteria for transplantation. Patient age of 70 years or older was associated with lower rates of referral (hazard ratio [HR], 0.09; 95% CI, 0.06-0.13), wait-listing (HR, 0.07; 95% CI, 0.04-0.12), and transplant (HR, 0.08; 95% CI, 0.04-0.16). Alcohol etiology for liver cirrhosis was associated with lower rates of referral (HR, 0.38; 95% CI, 0.33-0.44), wait-listing (HR, 0.32; 95% CI, 0.27-0.38), and transplant (HR, 0.30; 95% CI, 0.23-0.37). In addition, comorbidity (none vs >1 comorbidity) was associated with lower rates of referral (HR, 0.47; 95% CI, 0.40-0.56), wait-listing (HR, 0.38; 95% CI, 0.31-0.46), and transplant (HR, 0.28; 95% CI, 0.21-0.38). African American patients were less likely to be referred (HR, 0.82; 95% CI, 0.70-0.95) and wait-listed (HR, 0.73; 95% CI, 0.61-0.88). Patients with lower annual income and those seen in facilities in the West were less likely to be referred (HR, 0.70; 95% CI, 0.53-0.93), wait-listed (HR, 0.48; 95% CI, 0.36-0.64), or undergo a transplant (HR, 0.50; 95% CI, 0.34-0.74). In a review of the medical records for 333 patients who had limited comorbidity but were not referred, organ transplant was considered as a potential option in 176 (52.85%). When documented, medical and psychosocial barriers explained most of the deficits in referral. In this cohort study, few patients with advanced liver disease received referrals, were wait-listed, or underwent a transplant. The greatest deficits occurred at the referral step. Although health systems routinely track rates and disparities for organ transplants among wait-listed patients, extending monitoring to the earlier stages may help improve equity and manage potentially modifiable barriers to transplantation.

Functional joint models for chronic kidney disease in kidney transplant recipients.

This functional joint model paper is motivated by a chronic kidney disease study post kidney transplantation. The available kidney organ is a scarce resource because millions of end-stage renal patients are on the waiting list for kidney transplantation. The life of the transplanted kidney can be extended if the progression of the chronic kidney disease stage can be slowed, and so a major research question is how to extend the transplanted kidney life to maximize the usage of the scarce organ resource. The glomerular filtration rate is the best test to monitor the progression of the kidney function, and it is a continuous longitudinal outcome with repeated measures. The patient's survival status is characterized by time-to-event outcomes including kidney transplant failure, death with kidney function, and death without kidney function. Few studies have been carried out to simultaneously investigate these multiple clinical outcomes in chronic kidney disease stage patients based on a joint model. Therefore, this paper proposes a new functional joint model from this clinical chronic kidney disease study. The proposed joint models include a longitudinal sub-model with a flexible basis function for subject-level trajectories and a competing-risks sub-model for multiple time-to event outcomes. The different association structures can be accomplished through a time-dependent function of shared random effects from the longitudinal process or the whole longitudinal history in the competing-risks sub-model. The proposed joint model that utilizes basis function and competing-risks sub-model is an extension of the standard linear joint models. The application results from the proposed joint model can supply some useful clinical references for chronic kidney disease study post kidney transplantation.

The Human Organ Transplantation Act in Bangladesh: Towards Proper Family-Based Ethics and Law.

The Human Organ Transplantation Act came into officially force in Bangladesh on April 13, 1999, allowing organ donations from both living and brain-dead donors. The Act was amended by the Parliament on January 8, 2018, with the changes coming into effect shortly afterwards on January 28. The Act was revised to extend a living donor pool from close relatives (e.g., parents, adult sons and daughters, adult brothers and sisters, uncles and aunts from both the paternal and maternal sides, and spouses) to include certain other relatives such as grandparents, grandchildren, and first cousins (Section 2:4). The Act was also revised to allow individuals to prioritize family members in receiving their organs after their death (Section 7c:3). The aim of this paper is not to carry out an ethical analysis of the Act as a whole but only to focus on aspects relating to priority access for family members to organs. Despite Islam encouraging Muslims to be sympathetic, and to save the life of any member of humankind (Quran 5:32), saving the life of a relative through organ donation is even more highly valued. The collective and extended structure of the family impacts on the provisions of the Act that only allows Bangladeshis to legally donate their organs to save the lives of relatives and allows individuals to prioritize family members. Recent progress in the practice of organ transplantation raises a number of ethical dilemmas around the allocation of available organs in the context of organ scarcity. A key purpose of introducing incentive into the system of organ allocation is to increase the number of donations from living relatives and initiation of vital organ donations from brain-dead donors. However, allocation criteria based on a living organ donation incentive system would appear to be unethical because there is no provision in the Act with regard to financial compensation for a distant relative donor’s post-operative care in the absence of healthcare coverage. Receiving organs from a distant relative without giving financial compensation for post-operative care places them in a grave health condition and violates the biomedical principle of non-maleficence. An incentive system around brain-dead donors would appear to be ethical as the amended Act allows individuals to prioritize relatives in receiving their organs after death. This provision is intended to initiate the transplantation of vital organs (e.g., kidney, liver, heart, pancreas, bone marrow) from brain-dead donors as families might bear the cost of keeping the organs alive for transplantation. Regular reassessment of the impact of the Act is necessary to maximize the donation rate of transplantable organs using ethical means.

Trapianto renale da donatore vivente

Kidney transplant is the best therapy to manage end-stage kidney failure. The main barriers limiting this therapy are scarcity of cadaveric donors and the comorbidities of the patients with end-stage kidney failure, which prevent the transplant. Living kidney donor transplant makes it possible to obviate the problem of scarcity of cadaveric donor organs and also presents better results than those of cadaveric transplant. The principal indication of living kidney donor transplant is preemptive transplant. This allows the patient to avoid the complications of dialysis and it has also been demonstrated that it has better results than the transplant done after dialysis has been initiated. Priority indications of living donor transplant are also twins and HLA identical siblings. We also have very favorable conditions when the donor is young and male. On the contrary, the living donor transplant will have worse results if the donors are over 60-65 years and the recipients are young, and this can be a relative contraindication. There is an absolute contraindication for the living donation when the recipient has diseases with high risk of aggressive relapse in the grafts: focal and segmental hyalinosis that had early relapse in the first transplant; atypical hemolytic uremic syndrome due to deficit or malfunction of the complement regulatory proteins; early development of glomerulonephritis due to anti-glomerular basement membrane antibody in patients with Alport syndrome; primary hyperoxaluria.&#x0D; Extreme caution should also be taken in the evaluation of the kidney donors. The risks of developing renal failure or other complications are low if an adequate pre-donation evaluation has been made according to the international guidelines.

Native Lung Complications in Single Lung Transplant Recipients

Purpose Single lung transplants are performed less frequently around the world. Associated with better survival, bilateral lung transplantation is prefered. However, in the setting of scarce organ supply, single lung transplant is still a viable choice as it expands the donor pool.We aimed to describe native lung complications in single lung transplant recipients. Methods We performed a retrospective cohort study at a single lung transplant center in Buenos Aires, Argentina. We evaluated all single lung transplants performed from 2010 to 2019. Demographic characteristics and native lung complications, classified as infections, neoplasm and hyperinflation are presented. Results During the study period, 81 lung transplants were performed. 68% (n=55) were single lung transplants. 45% were performed in women. Mean age was 54 years.Cause of transplantation was as follow: COPD in 25 cases (45%), IPF in 22 cases (40%) and silicosis in 5 cases (9%).Native lung transplant complications were determined in 23 cases (36%). Infections were recorded in 13 ( 24%), neoplasm in 2 (4%) cases and hyperinflation in 8 (15%) cases. Both cases of neoplasm and one case of infection were determined as cause of death. Conclusion Native lung complications were common and were determined as cause of death in 15% of cases.