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  • Rinaldi M
  • Bonazzetti C
  • Gatti M
  • Caroccia N
  • Comai G
  • et al.
Transpl Infect Dis. 2022 Dec;24(6):e13979 doi: 10.1111/tid.13979.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This manuscript reports a systematic review and meta-analysis investigating the impact of positive perfusion fluid on risk of graft arteritis. Data from 21 observational studies are included, and the authors found that identification of high-risk pathogens in the perfusion fluid results in a significant increase in the odds of graft arteritis, especially fungal contamination. The review is very well conducted and reported, but perhaps slightly limited by the observational nature of the underlying studies. Risk of bias is high, and there is evidence of publication/reporting bias as might be expected in observational studies of this nature. Definitions of graft arteritis are unclear and not standardised. Nonetheless, routine culture of the preservation fluid is relatively inexpensive, and the results presented would support screening and consideration for prophylactic treatment of high-risk pathogens.
Aims: The aim of this study was to examine the effect of positive preservation fluid (PF) on graft-site arteritis among solid organ transplant recipients.
Interventions: A literature search was performed on PubMed, MEDLINE, EMBASE, and Scopus databases. Study selection and data extraction were conducted independently by two pairs of authors. The methodological quality of the included studies was assessed using the the risk of bias in non-randomised studies of interventions (ROBINS-I) tool.
Participants: 21 studies were included in the review.
Outcomes: The main outcome of interest was graft arteritis development.
Follow Up: N/A
BACKGROUND:

The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear.

METHODS:

Systematic literature search retrieving observational studies comparing solid organ transplant (SOT) recipients with culture-positive PF versus culture-negative PF. The quality of included studies was independently assessed according to the ROBINS-I tool for observational studies. Meta-analysis was performed using Mantel-Haenszel random-effect models. Graft site arteritis within 180 days from transplant was selected as the primary outcome.

RESULTS:

Twenty-one observational studies (N = 2208 positive PF vs. 4458 negative) were included. Among positive PF, 857 (38.8%) were classified as high-risk group pathogens and 1351 (61.2%) as low-risk pathogens. Low-risk and negative PF showed similar odds ratios. A significant higher risk of graft arteritis was found in SOT recipients with a PF yielding a high-risk pathogen (odds ratio [OR] 18.43, 95% confidence interval [CI] 7.83-43.40) compared to low-risk and negative PF, with low heterogeneity (I2 = 2.24%). Similar results were found considering separately high-risk bacteria (OR 12.02, 95%CI 4.88-29.60) and fungi (OR 71.00, 95%CI 28.07-179.56), with no heterogeneity (I2 = 0%), and in the subgroup analyses of the liver (OR 16.78, 95%CI 2.95-95.47) and kidney (OR 19.90, 95%CI 4.78-82.79) recipients. However, data about diagnostic features of graft arteritis were very limited, indeed for only 11 of the 93 events histological or microbiological results were reported.

CONCLUSIONS:

Our results may support the performance of PF culturing and a preemptive diagnostic or therapeutic management upon isolation of high-risk pathogens. Further studies based on a reliable diagnosis of graft arteritis are needed.

  • 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.

  • De Beule J
  • Vandendriessche K
  • Pengel LHM
  • Bellini MI
  • Dark JH
  • et al.
Transpl Int. 2021 Nov;34(11):2046-2060 doi: 10.1111/tri.14121.

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.

  • Jochmans I
  • Hessheimer AJ
  • Neyrinck AP
  • Paredes D
  • Bellini MI
  • et al.
Transpl Int. 2021 Nov;34(11):2019-2030 doi: 10.1111/tri.13951.

Normothermic regional perfusion (NRP) in donation after circulatory death (DCD) is a safe alternative to in situ cooling and rapid procurement. An increasing number of countries and centres are performing NRP, a technically and logistically challenging procedure. This consensus document provides evidence-based recommendations on the use of NRP in uncontrolled and controlled DCDs. It also offers minimal ethical, logistical and technical requirements that form the foundation of a safe and effective NRP programme. The present article is based on evidence and opinions formulated by a panel of European experts of Workstream 04 of the Transplantation Learning Journey project, which is part of the European Society for Organ Transplantation.

  • 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.

  • van de Leemkolk FEM
  • Schurink IJ
  • Dekkers OM
  • Oniscu GC
  • Alwayn IPJ
  • et al.
Transplantation. 2020 Sep;104(9):1776-1791 doi: 10.1097/TP.0000000000003345.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This paper reports a systematic review on abdominal normothermic regional perfusion (ANRP) in donation after circulatory death. The systematic review was conducted to good standards, following the PRISMA guidelines, pre-registering a protocol and searching multiple databases. Titles and abstracts were also screened in duplicate by independent reviewers, and risk of bias assessed independently, although it is not clear if data was also extracted in duplicate. Twenty-four studies were included, and all were observational in design, 7 with no control group. A particular strength of the paper is the clear presentation of the bias assessment, with 11 studies judged to have a serious risk of overall bias, and 5 more a moderate risk of overall bias. The studies were published between 1986 and the current date, and included between 5 and 186 donors. The 2 largest studies were national registry analyses. The included studies were heterogeneous and so a narrative review has been conducted. In both kidney and liver transplantation there was no consistent evidence of increased organ utilisation rate or 1-year graft survival compared to standard retrieval practice. Only 3 studies presented results for pancreas or islet transplantation with no conclusive comparative outcomes. This is a good quality systematic review that shows ANRP is both feasible and safe. However, there is little evidence from within studies that ANRP is superior to standard practice, it is only when comparing between studies that there may be some benefit. The paper finishes with guidance for the design of studies of ANRP and acknowledges that a randomised controlled trial comparing to standard cold preservation is needed in controlled DCD. In uncontrolled DCD a trial like this may be of less significance and more difficult to achieve.
Aims: This study aimed to investigate the recent evidence on the added benefit of using abdominal normothermic regional perfusion (aNRP) as compared to local standard perfusion techniques.
Interventions: An electronic database search was carried out on Pubmed, Web of Science, MEDLINE, Cochrane library, ScienceDirect, Emcare, Google Scholar and Academic Search Premier. Study screening, data extraction and quality assessment were performed by two independent reviewers. The risk of bias was assessed using the Risk of Bias In Nonrandomized Studies of Interventions tool.
Participants: 24 studies were included
Outcomes: The primary outcomes were 1-year patient and graft survival, and the organ utilization rate (OUR). The secondary outcomes were primary nonfunction (PNF), early allograft dysfunction, delayed graft function, estimated glomerular filtration rate (eGFR), serum creatinine and biliary complications.
Follow Up: not applicable
BACKGROUND:

Abdominal normothermic regional perfusion (aNRP) for donation after circulatory death is an emerging organ preservation technique that might lead to increased organ utilization per donor by facilitating viability testing, improving transplant outcome by early reversal of ischemia, and decreasing the risk of unintentional surgical damage. The aim of the current review is to evaluate the recent literature on the added value of aNRP when compared to local standard perfusion technique.

METHODS:

The Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline for systematic reviews was used, and relevant literature databases were searched. Primary outcomes were organ utilization rate and patient and graft survival after 1 year. Secondary outcomes included delayed graft function, primary nonfunction, serum creatinine, and biliary complications.

RESULTS:

A total of 24 articles were included in this review. The technique is unanimously reported to be feasible and safe, but the available studies are characterized by considerable heterogeneity and bias.

CONCLUSIONS:

Uniform reported outcome measures are needed to draw more definitive conclusions on transplant outcomes and organ utilization. A randomized controlled trial comparing aNRP with standard procurement technique in donation after circulatory death donors would be needed to show the added value of the procedure and determine its place among modern preservation techniques.

  • 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.

  • Angelico R
  • Trapani S
  • Manzia TM
  • Lombardini L
  • Tisone G
  • et al.
Am J Transplant. 2020 Jul;20(7):1780-1784 doi: 10.1111/ajt.15904.

The spread of Coronavirus Disease 2019 (COVID-19) has already reached a pandemic dimension within a few weeks. Italy has been one of the first countries dealing with the outbreak of COVID-19, and severe measures have been adopted to limit viral transmission. The spread of COVID-19 may have several implications in organ transplant activity that physicians should be aware of. The initial experience gained during the COVID-19 outbreak shows that around 10% of infected patients in Italy need intensive care management to overcome the acute respiratory distress syndrome. Due to the exponential rise of infected patients we are now facing an actual risk of saturation of intensive care unit (ICU) beds. A restriction in the number of ICU beds available for both donors and transplant recipients may unfavorably influence the overall donation activity, and eventually lead to a reduced number of transplants. Preliminary Italian data show that a 25% reduction of procured organs has already occurred during the first 4 weeks of COVID-19 outbreak. This underlines the need to closely monitor what will be further happening in ICUs due to the COVID-19 spread in the attempt to preserve transplant activity, especially in Western countries where deceased donors represent the major organ resource.