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  • Schmucki K
  • Hofmann P
  • Fehr T
  • Inci I
  • Kohler M
  • et al.
Transplantation. 2023 Jan 1;107(1):53-73 doi: 10.1097/TP.0000000000004336.
BACKGROUND:

Chronic kidney disease (CKD) after lung transplantation is common and limits the survival of transplant recipients. The calcineurin inhibitors (CNI), cyclosporine A, and tacrolimus being the cornerstone of immunosuppression are key mediators of nephrotoxicity. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used in combination with reduced CNI dosage after lung transplantation.

METHODS:

This systematic review examined the efficacy and safety of mTOR inhibitors after lung transplantation and explored their effect on kidney function.

RESULTS:

mTOR inhibitors are often introduced to preserve kidney function. Several clinical trials have demonstrated improved kidney function and efficacy of mTOR inhibitors. The potential for kidney function improvement and preservation increases with early initiation of mTOR inhibitors and low target levels for both mTOR inhibitors and CNI. No defined stage of CKD for mTOR inhibitor initiation exists, nor does severe CKD preclude the improvement of kidney function under mTOR inhibitors. Baseline proteinuria may negatively predict the preservation and improvement of kidney function. Discontinuation rates of mTOR inhibitors due to adverse effects increase with higher target levels.

CONCLUSIONS:

More evidence is needed to define the optimal immunosuppressive regimen incorporating mTOR inhibitors after lung transplantation. Not only the indication criteria for the introduction of mTOR inhibitors are needed, but also the best timing, target levels, and possibly discontinuation criteria must be defined more clearly. Current evidence supports the notion of nephroprotective potential under certain conditions.

  • Wall SP
  • Castillo P
  • Shuchat Shaw F
  • Norman E
  • Martinez-Lopez N
  • et al.
Health Educ Behav. 2022 Jun;49(3):424-436 doi: 10.1177/10901981211022240.

We assessed whether videos with medical footage of organ preservation and transplantation plus sad, unresolved, or uplifting stories differentially affect deceased organ donor registration among clients in Latinx-owned barbershops and beauty salons. In a 2 × 3 randomized controlled trial, participants (N = 1,696, mean age 33 years, 67% female) viewed one of six videos. The control portrayed a mother who received a kidney (uplifting), excluding medical footage. Experimental videos included medical footage and/or showed a mother waiting (unresolved) or sisters mourning their brother's death (sad). Regression models assessed relative impact of medical footage and storylines on: (1) registry enrollment, (2) donation willingness stage of change, and (3) emotions. Randomization yielded approximately equal groups relative to age, sex, education, religion, nativity, baseline organ donation willingness, beliefs, and emotions. Overall, 14.8% of participants registered. Neither medical footage, sad, nor unresolved stories differentially affected registration and changes in organ donation willingness. Sad and unresolved stories increased sadness and decreased positive affect by ~0.1 logits compared with the uplifting story. Educational videos about organ donation which excluded or included medical footage and varying emotional valence of stories induced emotions marginally but did not affect viewers' registration decisions differently. Heterogeneity of responses within video groups might explain the attenuated impact of including medical footage and varying emotional content. In future work, we will report qualitative reasons for participants' registration decisions by analyzing the free text responses from the randomized trial and data from semistructured interviews that were conducted with a subset of participants.

  • Weiss MJ
  • van Beinum A
  • Harvey D
  • Chandler JA
Transplant Rev (Orlando). 2021 Dec;35(4):100635 doi: 10.1016/j.trre.2021.100635.
AIM:

Pre-mortem interventions (PMIs) are performed on patients before the determination of death in order to preserve or enhance the possibility of organ donation. These interventions can be ethically controversial, and we thus undertook a scoping review of the ethical issues surrounding diverse PMIs.

METHODS:

Using modified scoping review methods, we executed a search strategy created by an information specialist. Screening and iterative coding of each article was done by two researchers using qualitative thematic analysis, and narrative summaries of coded themes were presented.

RESULTS:

We identified and screened 5365 references and coded 196 peer-reviewed publications. The most frequently cited issues were related to possible harms to the patient who is a potential donor, and legitimacy of consent. The most controversial issue was that PMIs may place patients at risk for physical harm, yet benefit is accrued mainly to recipients. Some authors argued that lack of direct medical benefit to the still living patient precluded valid consent from surrogate decision makers (SDMs), while many stated that some medical risk could be approved by SDMs if it aligns with non-medical benefits valued by the patient.

CONCLUSION:

PMIs require consensus that benefit includes concepts beyond medical benefit to the patient who is a potential donor. Informed consent must be confirmed for each PMI and not assumed to be part of general consent for donation. Risk must be proportionate to the potential benefit and newly proposed interventions should be reviewed carefully for medical efficacy and potential risks.

  • Tang J
  • Kerklaan J
  • Wong G
  • Howell M
  • Scholes-Robertson N
  • et al.
Am J Transplant. 2021 Oct;21(10):3369-3387 doi: 10.1111/ajt.16613.

Medicine-taking among transplant recipients is a complex and ubiquitous task with significant impacts on outcomes. This study aimed to describe the perspectives and experiences of medicine-taking in adult solid organ transplant recipients. Electronic databases were searched to July 2020, and thematic synthesis was used to analyze the data. From 119 studies (n = 2901), we identified six themes: threats to identity and ambitions (impaired self-image, restricting goals and roles, loss of financial independence); navigating through uncertainty and distrust (lacking tangible/perceptible benefits, unprepared for side effects, isolation in decision-making); alleviating treatment burdens (establishing and mastering routines, counteracting side effects, preparing for the unexpected); gaining and seeking confidence (clarity with knowledge, reassurance through collective experiences, focusing on the future outlook); recalibrating to a new normal posttransplant (adjusting to ongoing dependence on medications, in both states of illness and health, unfulfilled expectations); and preserving graft survival (maintaining the ability to participate in life, avoiding rejection, enacting a social responsibility of giving back). Transplant recipients take medications to preserve graft function, but dependence on medications jeopardizes their sense of normality. Interventions supporting the adaptation to medicine-taking and addressing treatment burdens may improve patient satisfaction and capacities to take medications for improved outcomes.

  • de Sousa SG
  • Nascimento da Silva GV
  • Costa Rodrigues AM
  • Meireles Fernandes da Silva TM
  • Costa FC
  • et al.
Exp Clin Transplant. 2021 Jun;19(6):511-521 doi: 10.6002/ect.2020.0506.
OBJECTIVES:

Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABOincompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant.

MATERIALS AND METHODS:

This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update.

RESULTS:

We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year.

CONCLUSIONS:

The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABOincompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

  • Spoletini G
  • Bianco G
  • Graceffa D
  • Lai Q
BMC Gastroenterol. 2020 Aug 6;20(1):259 doi: 10.1186/s12876-020-01401-0.

The global health crisis due to the fast spread of coronavirus disease (COVID-19) has caused major disruption in all aspects of healthcare. Transplantation is one of the most affected sectors, as it relies on a variety of services that have been drastically occupied to treat patients affected by COVID-19. With this report from two transplant centers in Italy, we aim to reflect on resource organization, organ allocation, virus testing and transplant service provision during the course of the pandemic and to provide actionable information highlighting advantages and drawbacks.To what extent can we preserve the noble purpose of transplantation in times of increased danger? Strategies to minimize risk exposure to the transplant population and health- workers include systematic virus screening, protection devices, social distancing and reduction of patients visits to the transplant center. While resources for the transplant activity are inevitably reduced, new dilemmas arise to the transplant community: further optimization of time constraints during organ retrievals and implantation, less organs and blood products donated, limited space in the intensive care unit and the duty to maintain safety and outcomes.

  • van Rijn R
  • van den Berg AP
  • Erdmann JI
  • Heaton N
  • van Hoek B
  • et al.
BMC Gastroenterol. 2019 Mar 12;19(1):40 doi: 10.1186/s12876-019-0956-6.
CET Conclusion
Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Conclusion: This is the study protocol for the DHOPE-DCD trial, a multicentre, inferiority, randomized controlled trial which will compare cold storage plus two hours of dual, end-ischemic hypothermic oxygenated machine perfusion versus cold storage alone in donation after circulatory death liver transplantation. The power calculation is based the primary outcome non-anastomotic biliary strictures (NAS) at 6 months and showed that 154 are needed plus 1 patient in each arm to allow for dropouts for 80% power. The procurement surgeon and the patients will be blinded to group assignment and the primary outcome NAS will be assessed by a blinded adjudication committee. Randomisation will be done using a web-based tool and patients will not be randomised until a liver is deemed suitable for transplantation. Data will be analysed according to the intention to treat principle.
Aims: To determine the efficacy of end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) in reducing the incidence of non-anastomotic biliary strictures (NAS) after donation after circulatory death (DCD) liver transplantation.
Interventions: Liver grafts will either be preserved with static cold storage (SCS) followed by 2 hours of DHOPE (intervention group) or SCS alone without any further intervention (control group).
Participants: 156 patients undergoing DCD liver transplantation (>18 years).
Outcomes: Primary outcome will be measured as symptomatic NAS. Secondary outcomes will be measured as incidence of asymptomatic NAS, severity of NAS, graft and recipient survival, liver failure requiring retransplantation or leading to death, initial poor function based on a modification of the Olthoff criteria, graft function and ischaemia-reperfusion injury measured by alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AlkP), gamma-glutamyl transferase (γGT), and total bilirubin at postoperative day 0–7 and 1, 3, and 6months, ICU and hospital stay following live
Follow Up: 6 months.
BACKGROUND:

The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation.

METHODS:

This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation.

DISCUSSION:

DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial.

TRIAL REGISTRATION:

The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 .

  • Czerwiński J
  • Haberko J
  • Dębska-Ślizień A
  • Bicki J
  • Bohatyrewicz R
  • et al.
Transplant Proc. 2018 Sep;50(7):1971-1974 doi: 10.1016/j.transproceed.2018.03.130.

Due to increasing global mobility, the number of non-residents who are potential deceased organ donors is likely to increase as well. Since 2014, 14 deceased foreigners have been referred as potential organ donors in Poland. There are, however, no precise international agreements between Poland and other countries regulating this issue. The aim of this paper is to provide guidelines on this subject for transplant coordinators. While there are no differences in the algorithms of potential donor identification, death diagnosis, donor management, organ procurement and preservation, allocation, transportation and transplantation, and the medical evaluation of a foreigner as a potential organ donor may differ. In certain cases, the risk of tropical or endemic infections should be evaluated. The authorization of the procurement may differ as well-foreigners who are not listed in the Polish Electronic System for Registration of Population cannot be registered in Polish Central Registry of Objection. They may have also not expressed refusal or consent for donation due to different legal solutions in their home countries. The donor's family and the proper diplomatic representative must be involved in donation process in order to obtain authorization for organ donation, to acquire essential medical information about the donor, and to ensure the transparency of the process. The procurement of organs, tissues and cells from foreigners deceased in Poland may be performed provided that a proper donor qualification process is conducted, the deceased had not objected to donation, there is no objection on the part of the donor's family or the prosecutor (if required), and the donation and procurement are properly described in medical documentation.