Ophthalmologists' perspectives on corneal transplantation and donation: a survey from Türkiye.

PURPOSE: To evaluate ophthalmologists' interest and opinions regarding corneal transplantation and donation in Türkiye. MATERIAL AND METHODS: An online questionnaire was prepared using Google Forms, and the electronic link to this questionnaire was sent via WhatsApp to ophthalmologists working in Türkiye. Eighteen open-ended/multiple-choice questions were asked about ophthalmologists' demographic information and their opinions regarding corneal transplantation and donation. The answers were analyzed by transferring the data to Excel. RESULTS: A total of 195 ophthalmologists participated in the survey. While 68.6% of them stated that they wanted to donate their corneas, 21.1% stated that they were undecided, and 10.3% did not want to donate their corneas. While 93.8% of the participants agreed to have a cornea transplant in case of need, 5.7% of them stated that they were undecided, and 0.5% said that they would not accept a cornea transplant. The most frequent (90.5%) reason for being willing to donate one's cornea was to give hope to patients with low vision. The most frequent (46.2%) reason for not wanting to donate one's cornea was the unwillingness to have one's body/eye integrity impaired. The vast majority (80.8%) of the participants thought that there was not enough corneal donation in Türkiye and that this was mostly (85.9%) due to cultural and/or religious reasons. CONCLUSIONS: Even in a sample with a high level of education and the most knowledge about corneal transplantation, the willingness to donate corneas may remain below the expected rates. Therefore, it is necessary to alleviate unrealistic concerns and prejudices about corneal donation and transplantation.

Impact of Age of Heart Transplant Program on Patient Survival and Post-Transplant Outcomes.

BACKGROUND: The relationship between age of a heart transplant (HT) program and outcomes has not been explored. METHODS: We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. RESULTS: Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p < 0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p < 0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p < 0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p < 0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). CONCLUSION: Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.

The Spread Pattern of New Practice in Liver Transplantation in the United States.

BACKGROUND: Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States. METHODS: The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated. RESULTS: LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p = 0.05) and significantly improved graft survival rates (p = 0.02). Facilities adopting new practices often overlap across different practices. DISCUSSION: Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution.

Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival.

BACKGROUND: Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes. METHODS: A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens. RESULTS: High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival. CONCLUSIONS: P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.

[The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation].

Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Donor Kidney With Complete Duplication of Ureter: Is It Safe for Transplantation?

Renal transplantation is the best modality of treatment for patients with end-stage renal disease. Donor shortage remains a substantial problem, for which different strategies are employed, including acceptance of marginal donors and donor kidneys with anatomic variations. We performed a successful kidney transplant of a donor kidney that had complete duplication of the ureter. After transplant, the recipient had no urinary complications.

Impact of Pulsatile Machine Perfusion on Posttransplant Recovery in Asystole Donation: Organ Optimization and the Future of Renal Transplantation.

OBJECTIVES: With the increase in life expectancy and the aging of the population, chronic kidney disease has become increasingly prevalent in our environment. Kidney transplantation remains the gold standard treatment for end-stage renal disease, but the supply of renal grafts has not been able to keep pace with growing demand. Because of this rationale, organ selection criteria have been extended (expanded criteria donation), and alternative donation types, such as donation after circulatory death, have been evaluated. These approaches aim to increase the pool of potential donors, albeit with organs of potentially lower quality. Various forms of donations, including donation after circulatory death, have also undergone assessment. This approach aims to augment the pool of potential donors, notwithstanding the compromised quality of organs associated with such methods. Diverse strategies have been explored to enhance graft function, with one of the most promising being the utilization of pulsatile machine perfusion. MATERIALS AND METHODS: We conducted a retrospective analysis on 28 transplant recipients who met the inclusion criterion of sharing the same donor, wherein one organ was preserved by cold storage and the other by pulsatile machine perfusion. We performed statistical analysis on posttransplant recovery parameters throughout the patients' hospitalization, including admission and discharge phases. RESULTS: Statistically significant differences were noted in delayed graft function (P = .04), blood transfusions requirements, and Clavien-Dindo complications. Furthermore, an overall trend of improvement in discharge parameters and hospital stay was in favor of the pulsatile machine perfusion group. CONCLUSIONS: The use of pulsatile machine perfusion as a method of renal preservation results in graft optimization, leading to earlier recovery and fewer complications compared with cold storage in the context of donation after circulatory death.

Chronological and Geographical Variations in the Incidence and Acceptance of COVID-19-Positive Donors and Outcomes Among Abdominal Transplant Patients.

INTRODUCTION: Given the importance of understanding COVID-19-positive donor incidence and acceptance, we characterize chronological and geographic variations in COVID-19 incidence relative to COVID-19-positive donor acceptance. METHODS: Data on deceased donors and recipients of liver and kidney transplants were obtained from the UNOS database between 2020 and 2023. Hierarchical cluster analysis was used to assess trends in COVID-19-positive donor incidence. Posttransplant graft and patient survival were assessed using Kaplan-Meier curves. RESULTS: From among 38 429 deceased donors, 1517 were COVID-19 positive. Fewer kidneys (72.4% vs. 76.5%, p < 0.001) and livers (56.4% vs. 62.0%, p < 0.001) were used from COVID-19-positive donors versus COVID-19-negative donors. Areas characterized by steadily increased COVID-19 donor incidence exhibit the highest transplantation acceptance rates (92.33%), followed by intermediate (84.62%) and rapidly increased (80.00%) COVID-19 incidence areas (p = 0.016). Posttransplant graft and patient survival was comparable among recipients, irrespective of donor COVID-19 status. CONCLUSIONS: Regions experiencing heightened rates of COVID-19-positive donors are associated with decreased acceptance of liver and kidney transplantation. Similar graft and patient survival is noted among recipients, irrespective of donor COVID-19 status. These findings emphasize the need for adaptive practices and unified medical consensus in navigating a dynamic pandemic.

Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients.

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.

Effect of Donor Cigarette Smoking in Kidney Transplantation: Re-Evaluation of Long-Term Outcomes.

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor (n = 276) and those who received a graft from a non-smoking donor (n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft.

Characterisation of the novel HLA-C*01:273 allele, first identified in a Brazilian individual.

The novel HLA-C*01:273 allele, first described in a potential bone marrow donor from Brazil.

The novel HLA-C*04:01:01:182 allele identified in a candidate bone marrow donor by next-generation sequencing.

HLA-C*04:01:01:182 differs from the HLA-C*04:01:01:06 allele by one nucleotide substitution in the 5'UTR.

The novel HLA-C*14:02:01:31 allele identified in a candidate bone marrow donor by next-generation sequencing.

Characterisation of the novel HLA-C*14:02:01:31 allele in a 21-year-old Greek bone marrow donor.

Impact of Recipient and Donor Body Mass Index on Survival Outcomes After Intestinal Transplantation: A United Network for Organ Sharing Database Analysis.

BACKGROUND Long-term patient survival after intestinal transplantation (IT) remains low compared with other organ transplants despite years of advancement in clinical experience. While patients with extremely high or low body mass index (BMI) are often considered ineligible for IT, the impact of BMI on post-transplant IT survival remains understudied. MATERIAL AND METHODS Using the United Network for Organ Sharing Standard Transplant database, we conducted a retrospective cohort study on patients who underwent IT between April 11, 1994, and September 29, 2021. We assessed the association of recipient and donor BMI at transplant with post-transplant mortality using Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses. RESULTS A total of 1541 patients were included in our final sample. Of these patients, 806 were females (52.5%) and most were in the normal-weight BMI subgroup (54.2%). Obese class II (mean; 36.8±10.92 years) and underweight patients (mean; 37.6±13.37 years) were significantly younger than patients in other BMI categories. The adjusted multivariate model demonstrated an increased risk of mortality in underweight IT recipients compared to normal-weight IT recipients (aHR=1.25, 95% confidence interval [CI], 1.02-1.54; P=0.032).There was no significant association between donor BMI categories and survival in IT recipients. CONCLUSIONS Recipient BMI below normal is associated with an increased risk of mortality after intestinal transplantation and represents a potentially modifiable patient characteristic to improve survival outcomes.

[Guidelines for clinical application of tissue matching techniques for kidney transplantation in China].

Tissue matching is one of the key factors affecting the success of kidney transplantation and long-term graft survival. At present, the development of tissue matching technology and its application in the laboratory of transplant centers in China is different. In order to promote the standardization of clinical diagnosis and treatment of kidney transplantation tissue matching, the Chinese Transplantation Branch of the Chinese Medical Association, the Kidney Transplantation Branch of the China Medical Care International Exchange Promotion Association, and the Transplantation Technology Branch of the Chinese Medical Biotechnology Association jointly initiated the guidelines for clinical application of tissue matching techniques for kidney transplantation in China. This guide grades the quality of evidence and the strength of recommendation for each clinical issue using the 2009 Oxford Centre for Evidence-Based Medicine Grading and Strength of Recommendation criteria. Aiming at 15 clinical problems related to the laboratory detection technology and clinical application of kidney transplantation tissue matching, a total of 21 recommendations were put forward in line with China's clinical diagnosis and treatment practice, aiming at promoting tissue matching before kidney transplantation, improving the long-term survival time of recipients and transplanted kidneys, and giving play to the application value of precision medicine in the field of kidney transplantation.

[Effect of donor and recipient HLA mismatched locus on the prognosis of childhood with leukemia after umbilical cord blood transplantation].

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.

BOMS: blockchain-enabled organ matching system.

This work proposes a Blockchain-enabled Organ Matching System (BOMS) designed to manage the process of matching, storing, and sharing information. Biological factors are incorporated into matching and the cross-matching process is implemented into the smart contracts. Privacy is guaranteed by using patient-associated blockchain addresses, without transmitting or using patient personal records in the matching process. The matching algorithm implemented as a smart contract is verifiable by any party. Clinical records, process updates, and matching results are also stored on the blockchain, providing tamper-resistance of recipient's records and the recipients' waiting queue. The system also is capable of handling cases in which there is a donor without an immediate compatible recipient. The system is implemented on the Ethereum blockchain and several scenarios were tested. The performance of the proposed system is compared to other existing organ donation systems, and ours outperformed any existing organ matching system built on blockchain. BOMS is tested to ascertain its compatibility with public, private, and consortium blockchain networks, checks for security vulnerabilities and cross-matching efficiency. The implementation codes are available online.