Trends and Patterns in Reporting of Patient Safety Situations in Transplantation

Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a “culture of safety.” The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de‐identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self‐reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety‐related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.     

A Registry Analysis of Damage to the Deceased Donor Pancreas During Procurement

Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety‐six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement‐related injuries.     

Pathogen Stimulation History Impacts Donor‐Specific CD8+ T Cell Susceptibility to Costimulation/Integrin Blockade–Based Therapy

Recent studies have shown that the quantity of donor‐reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade‐based immunosuppression. Using a murine skin graft model of CD8⁺ memory T cell–mediated costimulation blockade resistance, we elicited donor‐reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor‐reactive memory T cell response. Intriguingly, the most immunosuppression‐sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi‐cytokine producers. These data, therefore, demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor‐reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation.     

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem‐Resistant Gram‐Negative Bacteria

Donor‐derived infections due to multidrug‐resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2‐year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem‐resistant gram‐negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor‐derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high‐risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high‐risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug‐resistant bacteria requires intra‐ and inter‐institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.     

HLA‐G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06～UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04～UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.     

Successful Transplantation of Kidneys From Elderly Circulatory Death Donors by Using Microscopic and Macroscopic Characteristics to Guide Single or Dual Implantation

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual‐implanted kidney; its pair continued to function satisfactorily. Death‐censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual‐implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased‐donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.     

Superior Sensitivity of Ex Vivo IFN‐γ Release Assays as Compared to Skin Testing in Immunocompromised Patients

Comparative assessment of the tuberculin skin testing (TST) and commercial IFN‐γ release‐assays (IGRAs) is hampered by the use of different antigens (tuberculin PPD in TST vs. ESAT‐6/CFP‐10 in IGRAs). Thus, PPD was used as a common stimulus to compare performance of the TST and three IGRAs in 72 controls, 101 hemodialysis patients and 100 renal transplant recipients. Results of the TST were compared with PPD‐induced IFN‐γ induction in vitro detected by ELISPOT, ELISA or a flow‐cytometric FACS assay. Percentages of positive tests were significantly lower in TST (9.2%) compared to ELISA (55.3%), ELISPOT (45.3%) and FACS (44.9%, p < 0.0001). Agreement between TST and IGRAs was highest for controls (κ = 0.19–0.32) and poor in immunocompromised patients (κ = 0 for transplant patients, κ = 0.06–0.13 for hemodialysis patients). Discrepant results were largely TST negative and IGRA positive. Among IGRAs, agreement was highest between ELISPOT and FACS (κ = 0.61). Unlike TST, all IGRAs were associated with variables of mycobacterial exposure. Among IGRAs, the FACS assay was least affected by the level of immunosuppression. In conclusion, both the percentage of positive results and between‐test‐agreement were higher with IGRAs as compared to TST. This indicates superiority of IGRAs in detecting a PPD‐specific immune response which may also apply for immunity toward Mycobacterium tuberculosis–specific antigens.