De Novo Belatacept in a Human Immunodeficiency Virus-Positive Kidney Transplant Recipient.

Benefits of belatacept-based immunosuppressive regimens in human immunodeficiency virus (HIV)-positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new-onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV-positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV-positive renal transplant recipient.

The Long-Term Follow-up and Support for Living Organ Donors: A Center-Based Initiative Founded on Developing a Community of Living Donors.

Transplant professionals recognize that the long-term follow-up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, because the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative, which sets several priorities we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long-term follow-up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow-up, and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on joint recognition by our transplant team and our hospital leadership that supporting the long-term welfare of living donors is essential to accomplishing the goal of expanding living donor transplantation. The transplant team and hospital missions are aligned, and both contribute resources to the initiative.

Simultaneous Liver-Kidney Allocation Policy: A Proposal to Optimize Appropriate Utilization of Scarce Resources.

The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based.

Early changes in liver distribution following implementation of Share 35.

In June 2013, a change to the liver waitlist priority algorithm was implemented. Under Share 35, regional candidates with MELD ≥ 35 receive higher priority than local candidates with MELD < 35. We compared liver distribution and mortality in the first 12 months of Share 35 to an equivalent time period before. Under Share 35, new listings with MELD ≥ 35 increased slightly from 752 (9.2% of listings) to 820 (9.7%, p = 0.3), but the proportion of deceased-donor liver transplants (DDLTs) allocated to recipients with MELD ≥ 35 increased from 23.1% to 30.1% (p < 0.001). The proportion of regional shares increased from 18.9% to 30.4% (p < 0.001). Sharing of exports was less clustered among a handful of centers (Gini coefficient decreased from 0.49 to 0.34), but there was no evidence of change in CIT (p = 0.8). Total adult DDLT volume increased from 4133 to 4369, and adjusted odds of discard decreased by 14% (p = 0.03). Waitlist mortality decreased by 30% among patients with baseline MELD > 30 (SHR = 0.70, p < 0.001) with no change for patients with lower baseline MELD (p = 0.9). Posttransplant length-of-stay (p = 0.2) and posttransplant mortality (p = 0.9) remained unchanged. In the first 12 months, Share 35 was associated with more transplants, fewer discards, and lower waitlist mortality, but not at the expense of CIT or early posttransplant outcomes.

"Don't Look Up": Eco-anxiety presenting in a Community Mental Health Service.

This case report discusses a 25-year-old male who was referred to community mental health services from primary care with symptoms of anxiety and depression related to climate change, which the referring clinician believed were of delusional intensity. This case report gives the history of his interaction with the service. A literature review is performed noting the dearth of case reports in this area and a subsequent discussion charts the emerging literature on mental health issues related to climate change. Finally the paper makes some broad recommendations for mental health practitioners on how to approach these issues.

A consolidated biovigilance system for blood, tissue and organs: one size does not fit all.

Biovigilance systems to assess and analyze risks for disease transmission through the transfer of organs, tissue, cells and blood between people is part of administrative oversight and has impact upon clinical practice and policy. In 2009, a formal recommendation by the Public Health Service requested that Health and Human Services fund and support efforts to consolidate national biovigilance efforts. There are differences in the biovigilance issues involved in organ and tissue donation/transplantation. If disease avoidance is made the dominant principle guiding organ donor testing, an unintended consequence may be an increase in deaths on the waiting list. We propose that overall benefit for the organ transplant recipient, tempered by patient informed awareness of limited organ availability and assessment processes, should be the guiding principle of such a system.

Open sphincteroplasty for benign ampullary stricture after pancreas transplantation.

Ampullary and proximal pancreatic duct strictures are well known to result in recurrent episodes of pancreatitis in the native pancreas, which when benign in origin can often be treated with sphincteroplasty (open or endoscopic) and stenting in the native pancreas. However, recurrent episodes of pancreatitis in a transplanted pancreas allograft can have multiple potential etiologies, and if the diagnosis of pancreatic duct stricture is made, treatment with preservation of the pancreatic allograft can be challenging. This is the first case report to describe the open sphincteroplasty of a short benign ampullary stricture in a transplant pancreas allograft.

An approach to teaching psychiatry to medical students in the time of Covid-19.

In this time of Covid-19, life in healthcare has changed immeasurably. It has rapidly been injected with an 'all hands-on deck' approach, to facilitate the necessary adaptations required to reduce the spread of the virus and deliver frontline clinical care. Inevitably aspects of these changes have disrupted the delivery of medical education, notably clinical placements have been cancelled and social distancing guidelines prohibit face-to-face teaching. The training of future doctors is an essential part of this effort. Indeed, the emergence of a global health threat has underlined its continued importance. For medical educators and students alike, we have been presented with a challenge. Concurrently, this presents us with an impetus and opportunity for innovation. For some time now, a transformation in medical education has been called for, with an increasing recognition of the need to prepare students for the changing landscape of healthcare systems. This has included a focus on the use of technology-enhanced and self-directed learning. As a team of educators and clinicians in psychiatry, working in the School of Medicine and Medical Sciences (SMMS) in University College Dublin (UCD), we will share how we have responded. We outline the adaptations made to our 'Psychiatry' module and consider the influence this may have on its future delivery. These changes were informed by direct student input.

Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients.

Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1-year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1-year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1-year biopsy (OR 6.62, 95% CI 2.68-16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.

Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report.

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

Deceased donor kidney transplantation from donors with acute renal failure due to rhabdomyolysis.

With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4-25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7-1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function.

ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation.

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

Outcomes of simultaneous kidney-pancreas transplantation with positive cross-match.

We studied 72 consecutive simultaneous pancreas kidney transplant (SPKT) recipients. There were 14 patients with positive pretransplant cross-matches (positive CDC- B cell and/or positive flow T or B cross-match). The control group included all 58 SPKT recipients with a negative crossmatch. The study group received induction with low dose intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG; total dose 6 mg/kg), or alemtuzumab (30 mg single dose) and maintenance with tacrolimus, mycophenolate mofetil (MMF), and corticosteroids. The control group was treated similarly, but with steroid avoidance and no IVIg. Biopsy-proven acute rejection (BPAR) of the kidney allograft occurred in 7 study patients (50%) compared with 10% in the control group (P = .022). One patient experienced acute cellular rejection (ACR); the other 6 (43%), antibody-mediated rejection (AMR). None of the cross-match negative patients had AMR (P = .001). The mean follow-up period was 18.7 months in the study group, and 18.3 months in the control group. The 1-year actuarial patient survival was 91.7% in the study group and 97% in the control group. Kidney allograft survival was 91.7% in the study group and 95.2% in the control group. Pancreas allograft survival was 76.9% in study group and 89.6% in the control group (P = .088). We concluded that patients with a positive pretransplant CDC-B cross-match and/or positive flow cross-match have an increased risk of AMR; more intensive desensitization is needed with low-dose IVIg and induction with either rATG or alemtuzumab.

Acute rejection risk in kidney transplant recipients on steroid-avoidance immunosuppression receiving induction with either antithymocyte globulin or basiliximab.

Immunosuppression with rapid discontinuation of corticosteroids, usually with induction therapy, is safe in kidney transplant recipients. In 89 patients, we induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17 and 72 patients, respectively). Selection criteria for basiliximab were age (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes mellitus (eligible for pancreas transplant). Steroids were administered through posttransplantation day 4 (five doses); maintenance immunosuppression was with tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%). Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The overall risk of biopsy-proven acute rejection was 12%. At 6 months posttransplantation, acute rejection-free survival was 93% for antithymocyte globulin, 65% for basiliximab (P<.001). Median time to biopsy-proven acute rejection was 27 and 71 days, respectively. The low incidence of biopsy-proven acute rejection with steroid-avoidance immunosuppression may be further reduced with antithymocyte globulin.

Partners in Crime: Kidney Transplantation and Seizure Disorder.

Seizure disorder is a common neurologic complication of kidney transplantation and often presents as a complex management challenge. Little is known about the risks mutually conferred by the 2 clinical entities and the effects of such risks on clinical outcomes. Using the National Inpatient Sample, our goal was to examine the effects of kidney transplantation and seizure disorder on mortality, hospitalization statistics, clinical complications, and cost of care. A history of kidney transplantation was shown to negatively affect the care of seizure disorder, and a history of seizure disorder also negatively affected the clinical outcomes of kidney transplantation. Our findings are important for initiating discussions and prompting future studies to further examine disease-specific risks of kidney transplantation.

Belatacept and Eculizumab for Treatment of Calcineurin Inhibitor-induced Thrombotic Microangiopathy After Kidney Transplantation: Case Report.

Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.