Characterisation of the novel HLA-C*15:274 allele using short and long-read sequencing technologies.

The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.

Multi-centre analytical performance verification of an IVD assay to quantify donor-derived cell-free DNA in solid organ transplant recipients.

Donor-derived cell-free DNA (dd-cfDNA) has been widely studied as biomarker for non-invasive allograft rejection monitoring. Earlier rejection detection enables more prompt diagnosis and intervention, ultimately improving patient treatment and outcomes. This multi-centre study aims to verify analytical performance of a next-generation sequencing-based dd-cfDNA assay at end-user environments. Three independent laboratories received the same experimental design and 16 blinded samples to perform cfDNA extraction and the dd-cfDNA assay workflow. dd-cfDNA results were compared between sites and against manufacturer validation to evaluate concordance, reproducibility, repeatability and verify analytical performance. A total of 247 sample libraries were generated across 18 runs, with completion time of <24 h. A 96.0% first pass rate highlighted minimal failures. Overall observed versus expected dd-cfDNA results demonstrated good concordance and a strong positive correlation with linear least squares regression r2 = 0.9989, and high repeatability and reproducibility within and between sites, respectively (p > 0.05). Manufacturer validation established limit of blank 0.18%, limit of detection 0.23% and limit of quantification 0.23%, and results from independent sites verified those limits. Parallel analyses illustrated no significant difference (p = 0.951) between dd-cfDNA results with or without recipient genotype. The dd-cfDNA assay evaluated here has been verified as a reliable method for efficient, reproducible dd-cfDNA quantification in plasma from solid organ transplant recipients without requiring genotyping. Implementation of onsite dd-cfDNA testing at clinical laboratories could facilitate earlier detection of allograft injury, bearing great potential for patient care.

Case report: Preventive infusion of donor-derived CD7 chimeric antigen receptor T cells after allogeneic hematopoietic stem cell transplantation.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.

Characterisation of the novel HLA-C*08:275 allele, first identified in a Brazilian individual.

The novel HLA-C*08:275 allele, first described in a potential bone marrow donor from Brazil.

Organ donation after extracorporeal cardiopulmonary resuscitation: a nationwide retrospective cohort study.

BACKGROUND: Limited data are available on organ donation practices and recipient outcomes, particularly when comparing donors who experienced cardiac arrest and received extracorporeal cardiopulmonary resuscitation (ECPR) followed by veno-arterial extracorporeal membrane oxygenation (ECMO) decannulation, versus those who experienced cardiac arrest without receiving ECPR. This study aims to explore organ donation practices and outcomes post-ECPR to enhance our understanding of the donation potential after cardiac arrest. METHODS: We conducted a nationwide retrospective cohort study using data from the Japan Organ Transplant Network database, covering all deceased organ donors between July 17, 2010, and August 31, 2022. We included donors who experienced at least one episode of cardiac arrest. During the study period, patients undergoing ECMO treatment were not eligible for a legal diagnosis of brain death. We compared the timeframes associated with each donor's management and the long-term graft outcomes of recipients between ECPR and non-ECPR groups. RESULTS: Among 370 brain death donors with an episode of cardiac arrest, 26 (7.0%) received ECPR and 344 (93.0%) did not; the majority were due to out-of-hospital cardiac arrests. The median duration of veno-arterial ECMO support after ECPR was 3 days. Patients in the ECPR group had significantly longer intervals from admission to organ procurement compared to those not receiving ECPR (13 vs. 9 days, P = 0.005). Lung graft survival rates were significantly lower in the ECPR group (log-rank test P = 0.009), with no significant differences in other organ graft survival rates. Of 160 circulatory death donors with an episode of cardiac arrest, 27 (16.9%) received ECPR and 133 (83.1%) did not. Time intervals from admission to organ procurement following circulatory death and graft survival showed no significant differences between ECPR and non-ECPR groups. The number of organs donated was similar between the ECPR and non-ECPR groups, regardless of brain or circulatory death. CONCLUSIONS: This nationwide study reveals that lung graft survival was lower in recipients from ECPR-treated donors, highlighting the need for targeted research and protocol adjustments in post-ECPR organ donation.

Characterisation of the novel HLA-B*35:593 allele using short and long-read sequencing technologies.

The novel HLA-B*35:593 allele, first described in a potential bone marrow donor from Brazil.

Bilateral orthotopic lung transplant via a clamshell thoracosternotomy from a donor with extended cold static lung preservation.

In this video tutorial, we present a comprehensive step-by-step operative technique for a bilateral orthotopic lung transplant using a bilateral transverse thoracosternotomy in a patient with idiopathic pulmonary fibrosis lung disease. The donor lungs were exposed to extended cold static ischaemic storage at 10° C for the semi-elective operation.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

Impact of Asian and Black Donor and Recipient Ethnicity on the Outcomes After Deceased Donor Kidney Transplantation in the United Kingdom.

Patients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the UK, because of lack of human leucocyte antigen and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts from Asian and black donors. The UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed between 2001 and 2015. Asian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors. On Cox-regression analysis, Asian donor and black recipient ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor-white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black recipient, Asian donor-white recipient, and white donor-black recipient combinations in decreasing order of worse unadjusted 5-year graft survival. Increased deceased donation among ethnic minorities could benefit the recipient pool by increasing available organs. However, it may require a refined approach to enhance outcomes.

Integrated transcriptomics and histopathology approach identifies a subset of rejected donor livers with potential suitability for transplantation.

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Active Donor Management Goals in Serial Donors After Brain Death.

OBJECTIVES: Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. MATERIALS AND METHODS: In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years). RESULTS: In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period. CONCLUSIONS: Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.

Outcomes of Kidneys Transplanted From Hepatitis C Viremic Donors to Naive Recipients From an Appalachian Rural Kidney Transplant Program.

OBJECTIVES: Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis C virus is now amenable to effective treatment with excellent seronegativity rates. In this study, we review the outcomes of hepatitis C viremic kidneys transplanted into hepatitis C-naive recipients. MATERIALS AND METHODS: In this retrospective observational study, we examined 6 deceased donor kidneys with hepatitis C viremia that were transplanted into hepatitis C-naive recipients between March 2020 and April 2021 at a single center. Because of health insurance constraints, patients were treated for hepatitis C virus with glecaprevir/pibrentasvir for 8 weeks following seroconversion posttransplant. Primary outcome measured was viral seroconversion; secondary outcomes included graft function, posttransplant complications, and all-cause mortality. RESULTS: On average, patients seroconverted 6 days (range, 4-10 d) after transplant and began treatment 26 days (range, 15-37 d) after seroconversion. An 8-week course of antiviral treatment was successful in preventing acute hepatitis C virus infection in all patients. Posttransplant median creatinine was 1.96 mg/dL (range, 1-4.55 mg/dL), whereas median estimated glomerular filtration rate was 41.33 mL/min/1.73 m2 (range, 17-85 mL/min/1.73 m2). Patient survival rate was 66.7%, and death-censored graft survival rate was 100%. Two patients died from unrelated reasons: 1 from acute respiratory failure secondary to SARS-CoV-2 infection and 1 from posttransplant lymphoproliferative disorder. Two patients developed allograft rejection posttransplant (1 developed antibody mediated rejection, 1 developed borderline T-cell-mediated cellular rejection). Other major complications included neutropenia, fungal rash, SARS-CoV-2 infection, cytomegalovirus, BK virus, and Epstein-Barr virus reactivation. CONCLUSIONS: Use of hepatitis C-viremic donor kidneys for transplant is a safe option and has great potential to increase the kidney donor pool, as long as high index of suspicion is maintained for allograft rejection and opportunistic infections.

Deceased Donor Liver Transplantation With Hepatic Artery Aneurysm.

Few case reports have documented the long-term outcomes of liver donor aneurysms, illustrating the apprehension of transplant surgeons about using these grafts. However,the presence of an aneurysm in the donor liver should not be an absolute contraindication for its use. As shown in our described patient, such grafts have the potential to achieve good results.

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model.

Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

Tacrolimus's Time Below Therapeutic Range Is Associated With Acute Pancreatic Graft Rejection and the Development of De Novo Donor-specific Antibodies.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

The novel HLA-DPB1*05:01:20 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.