Rejection Episodes Research Articles

Impact of HLA eplet mismatch load in immunological outcomes after living donor kidney transplantation

IntroductionHLA eplets mismatches (eMM) have been associated with negative kidney outcomes after transplantation, such as the development of de novo donor-specific antibody (dnDSA), antibody-mediated rejection (ABMR), and early graft loss. This study aimed to evaluate the clinical effects of the HLA eMM load on dnDSA development, ABMR, renal function, allograft survival and graft loss. Material and methodsThis retrospective study involved 159 living donor kidney transplant patients categorized into groups based on antigen HLA mismatches assessed traditionally and HLA eMM load. Patients had followed for at least one year. The EpViX online program was used to evaluate the HLA eMM load. Cox models were constructed to assess the risk of graft loss. Kaplan-Meier survival curves were carried out. The analyses had performed using the R program and p < 0.05 was considered significant. ResultsFrom all 159 patients, 28 (17.6%) lost their allografts. Rejection episodes occurred in 37.1% of patients, 13.6% of whom were ABMR. Patients with rejection episodes had higher HLA-AB (p = 0.032) and HLA-DR (p = 0.008) HLA eMM load, HLA-AB (p = 0.006) and HLA-DR (p = 0.009) antigens mismatches, and higher proportions of the following eMM in the HLA-DR locus: 70R eMM (p = 0.015), 70RE (p = 0.015), 74E (p = 0.015) and 48Q (p = 0.047). In multiple models, the presence of HLA-DR 70qq eMM (HR 3.75, 95% CI 1.47; 9.55) add an increase in creatinine levels at 1-year (HR 3.87, 95% CI 2.30, 6.53) were associated with the risk of graft loss. ConclusionThe HLA eMM load was related to episodes of rejection and allograft loss. The HLA-DR eMM was most strongly associated with a worse immunologic outcome than eMM mismatches for HLA-AB.

When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Contemporary Biomarkers for Renal Transplantation: A Narrative Overview.

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.

Descemet Stripping Automated Endothelial Keratoplasty versus Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy: A National Registry-Based Comparison

To compare the outcome between posterior lamellar corneal transplant procedures for Fuchs endothelial corneal dystrophy, taking preoperative patient characteristics in consideration. Surgical methods compared were Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and DSAEK with concomitant cataract surgery (phacoemulsification plus DSAEK). Registry-based study with propensity score matching. One thousand six hundred seventy-seven patients from all Swedish corneal transplantation units treated from 2012 through2019. All patients undergoing endothelial keratoplasty performed from 2012 through 2019 with completed 2-year follow-up data reported to The Swedish Corneal Transplant Register were included, totaling 1677 patients. Three comparable groups (DMEK, DSAEK, and phacoemulsification plus DSAEK) with 216 patients in each group were generated with propensity score matching based on preoperative visual acuity, age, sex, year of surgery, and preoperative risk factors such as inflammation, vascularization, and glaucoma. Best-corrected visual acuity (BCVA) at the 2-year follow-up, frequency of graft dislocation, graft rejection episodes, and graft failure within 2 years including primary graft failure. The preoperative corneal status was affected more severely in the DSAEK group before matching. In the matched groups, the median BCVA 2 years after surgery was 0.1 logarithm of the minimum angle of resolution (logMAR) in both the DMEK and the phacoemulsification plus DSAEK groups and 0.15 logMAR in the DSAEK group (P= 0.001). The frequency of graft dislocation was higher among the patients undergoing phacoemulsification plus DSAEK, but the frequency of graft failure and primary graft failure was higher in the DMEK group. Visual acuity improved in most patients (90%) with all 3 surgical methods. However, DMEK and phacoemulsification plus DSAEK reached higher levels of visual acuity 2 years after surgery, and phacoemulsification plus DSAEK was superior considering graft survival rate. All 3 surgical procedures showed both strengths and weaknesses, suggesting that the choice of surgical method should be individualized, taking into consideration not only the cornea, but each patient's complete medical status as well as the entire course of postoperative medical care. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Current Therapies in Kidney Transplant Rejection.

Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy.

Long-Term Endothelial Cell Viability After Deep Anterior Lamellar Versus Penetrating Keratoplasty for Keratoconus.

We compared long-term endothelial cell survival after penetrating versus after deep anterior lamellar keratoplasty for keratoconus. We retrospectively compared 64 eyes of 55 patients who had penetrating keratoplasty and 40 eyes of 37 patients who had deep anterior lamellar keratoplasty for keratoconus (October 2003-February 2021). Best-corrected visual acuity, Goldmann applanation tonometry, fundus examination with 90D lens, and specular microscopy with CEM-530 (Nidek) were performed preoperatively and every 6 months postoperatively. Main outcomes were endothelial cell density, central corneal thickness, and visual acuity. Secondary outcomes were coefficient of variation, hexagonality, graft rejection episodes, and graft clarity. We found no significant differences between the 2 treatment groups regarding patient age, donor age, preoperative vision, central corneal thickness, and recipient-donor trephine diameters. Mean follow-up was 92.5 months. In deep anterior lamellar keratoplasty, the endothelium was preserved significantly better for 10 years versus for penetrating keratoplasty. Mean endothelial density in penetrating versus deep anterior lamellar keratoplasty was 2006.7 versus 2354.7 cells/mm2 at 1 year (P = .010), 1170.5 versus 2048.2 at 5 years (P <.001), and 972.5 versus 1831.6 at 10 years (P < .001). Cumulative endothelial cell loss was 43% and 19.7% at 10 years for penetrating and anterior lamellar keratoplasty, respectively. Significantly more thickening of central cornea was shown in penetrating keratoplasty after 7 years. Corneal thickness was 583.0 µm in penetrating and 545.1 µm in deep anterior lamellar keratoplasty (P = .002) at 10 years. Vision gain and coefficient of variation were similar. Hexagonality decreased significantly in both groups at 10 years. Rates of rejection were 12.5% in penetrating and 7.5% in deep anterior lamellar keratoplasty. Graft survival rates were 97.5% and 96.9%, respectively. In keratoconus, endothelial vitality is better preserved with deep anterior lamellar keratoplasty than with penetrating keratoplasty over a 10-year follow-up.

Rituximab administration one week before ABO-incompatible liver transplantation due to drug-induced acute liver failure with hepatic coma: a case report.

In cases of acute liver failure (ALF) with hepatic coma, early liver transplantation, including ABO-incompatible (ABOi) living donor liver transplantation (LDLT), should be considered. The ABO antibody barrier can be reduced using plasma exchange (PE) and the anti-CD20 antibody rituximab. Plasma exchange is also performed for drug-induced ALF and is effective for desensitization. Rituximab treatment usually requires 14days. There is presently no established desensitization protocol for ABOi-LDLT for ALF. Here, we report a case of drug-induced ALF with hepatic coma, which was treated with ABOi-LDLT using PE and rituximab 8days prior to surgery. A 33-year-old female, with a history of headaches for which she was taking analgesics daily, developed drug-induced ALF with hepatic coma. Her ABOi sister desired to become a liver donor. We initiated desensitization using rituximab (500mg) and mycophenolate mofetil (MMF, 2000mg/day), followed by five sessions of PE. Eight days after rituximab administration, ABOi-LDLT with splenectomy was performed. Postoperatively, the patient received local infusion via portal vein for 14days and immunosuppression with tacrolimus, methylprednisolone, and MMF. No episode of cellular or antibody-mediated rejection (AMR) was observed. The patient was discharged uneventfully 56days after ABOi-LDLT with no problems up to 15months after the transplant.

Mapping children by ALT 4-5 years after liver transplant: Potential individual and population applications.

Although clinicians repeatedly measure ALT to assess allograft health in children with liver transplants, they generally make decisions based on single values or qualitative trends without quantitative aggregation or synthesis. We therefore aimed to derive and test a holistic ALT metric for the 5th post-transplant year (Yr 4-5) that may better guide clinical decision-making and/or population comparisons. We derived the "adjusted mean Yr 4-5 ALT" for children transplanted in 2005-2016 by averaging the median ALT from each month. Patients in quartiles (Q1-4) defined by the adjusted mean Yr 4-5 ALT were compared by clinical variables, Yr 5-8 outcomes, and tacrolimus standard deviation (MLVI). For 97 children [49 male; 77 deceased donors; median (IQR) age at LT 2.5 (0.8-11.7) years], the 25th, 50th, and 75th percentile thresholds for adjusted mean Yr 4-5 ALT were 19, 28, and 47 U/L, respectively. Age, donor type, LT indication, rejection history, and mean tacrolimus levels did not differ between quartiles (Q). Children in Q4 had more Yr 4-5 acute rejection episodes (p < .01), higher Yr 4-5 MLVI (p < .01), and more Yr 5-8 for-cause liver biopsies (p < .01) than those in Q1 + Q2. Children in Q3 also had higher Yr 4-5 MLVI than Q1 + Q2 (p = .047). Rates of chronic rejection and therapeutic liver-related procedures were higher in Q4 but the difference did not reach significance. An integrated ALT metric calculated utilizing all available ALT values correlates with MLVI and future for-cause biopsies. Further study of this novel ALT metric as a predictor of clinical outcomes and descriptor of populations is warranted.

BK Virus Infection and Its Management in Renal Transplantation: An Update

BK virus (BKV) is a common opportunistic pathogen in kidney transplant recipients and one of the most challenging causes of allograft dysfunction and loss. Although over-immunosuppression remains the primary risk factor for BKV infection after transplantation, male gender, older recipient age, prior rejection episodes, degree of human leukocyte antigen mismatching, prolonged cold ischemia time, BK virus serostatus and ureteral stent placement have all been implicated as risk factors. Routine screening post-renal transplant is important to prevent allograft loss in patients with BK viruria or viremia. Reduction of immunosuppression remains the mainstay of BKV nephropathy treatment and is the most studied intervention. In this review, we are going to discuss the epidemiology of BK virus infection, screening strategies, treatment options and new studies or evidence in the future.

Immune surveillance and humoral immune responses in kidney transplantation - A look back at T follicular helper cells.

T follicular helper cells comprise a specialized, heterogeneous subset of immune-competent T helper cells capable of influencing B cell responses in lymphoid tissues. In physiology, for example in response to microbial challenges or vaccination, this interaction chiefly results in the production of protecting antibodies and humoral memory. In the context of kidney transplantation, however, immune surveillance provided by T follicular helper cells can take a life of its own despite matching of human leukocyte antigens and employing the latest immunosuppressive regiments. This puts kidney transplant recipients at risk of subclinical and clinical rejection episodes with a potential risk for allograft loss. In this review, the current understanding of immune surveillance provided by T follicular helper cells is briefly described in physiological responses to contrast those pathological responses observed after kidney transplantation. Sensitization of T follicular helper cells with the subsequent emergence of detectable donor-specific human leukocyte antigen antibodies, non-human leukocyte antigen antibodies their implication for kidney transplantation and lessons learnt from other transplantation "settings" with special attention to antibody-mediated rejection will be addressed.

Immunosuppression regimen modification during COVID-19 infection in kidney transplant recipients

BackgroundCOVID-19 pandemic had tremendously affected all the aspects of human life during the past 3 years. In this study, we focused on kidney transplant patients' course from the COVID-19 diagnosis, immunosuppressive medication modification, hospitalization, and COVID-19 complications and how the COVID-19 infection affected the kidney and patients' quality of life during the hospitalization and after the discharge. Material and methodA retrospective analysis of a prospectively collected database of all kidney transplants adult patients who had a positive COVID-19 PCR from 1 January 2020 to 30 December 2022, and had a history of kidney transplant at the SUNY Upstate Medical Hospital was done to identify the cases. Results188 patients met the inclusion criteria and were included in the study. Based on the immunosuppressive regimen modification during COVID-19 infection, patients divided into two groups; in 143 (76%) patients, the immunosuppressive medication was reduced, and in 45 (24%) of patients, the immunosuppressive regimen continued as before during the COVID-19 infection. The mean time from the transplant to the diagnosis of COVID-19 was 67 months in the group we reduced the IM regimen, and 77 months in the group without changes in IM regimen. The mean recipients' age was 50.7 ± 12.9 years in the group we reduced the IM regimen, and 51.8 ± 16.4 years in the group without changes in IM regimen (P = 0.64). The vaccination rate against COVID-19 with at least 2 doses of either the CDC recommended Moderna or Pfizer vaccines was 80.2% in the group we reduced the IM regimen, and 84.8% in the group without changes in IM regimen (P = 0.55). The hospitalization rate due to COVID-19 related symptoms was 22.4% % in the group we reduced the IM regimen, and 35.5% in the group without changes in IM regimen (P = 0.12). However, the ICU admission rate was higher in the group we reduced the IM regimen, but the difference was not significant (26.5% Vs.6.25%, P = 0.12). 6 episodes of biopsy-proven rejection in the group with IM reduction was observed, which were 3 episodes of acute antibody-mediated rejections (ABMR) and 3 episodes of acute T-Cell-mediated rejections (TCMR), and 3 episodes in the group without any change in IM regimen, which were 2 episodes of ABMR and 1 episode of TCMR (P = 0.51). No significant difference was mentioned in the eGFR and serum creatinine after the comparison between the groups after 12 months of follow up.124 patients responded to the post-COVID-19 questionnaires and were included in the data analysis. The response rate was 66%. Fatigue and exertion were the most reported symptom with a 43.9% prevalence. ConclusionsWe found that immunosuppressive regimen minimization did not impact the kidney function in the long-term and it might be a helpful strategy to minimize the effect of COVID-19 infection on patients' condition during the hospital stay. With all the treatments, vaccinations, and precautions, still some patients did not achieve the complete recovery compared to their pre-COVID-19 health status. Fatigue was the main reported symptom amongst all the reported symptoms.

Donor antigen-specific regulatory T cell administration to recipients of live donor kidneys: A ONE Study consortium pilot trial

Regulatory T cells (Tregs) can inhibit cellular immunity in diverse experimental models and have entered early phase clinical trials in autoimmunity and transplantation to assess safety and efficacy. As part of the ONE Study consortium, we conducted a phase I-II clinical trial in which purified donor antigen reactive (dar)-Tregs (CD4+CD25+CD127lo) were administered to 3 patients, 7 to 11 days after live donor renal transplant. Recipients received a modified immunosuppression regimen, without induction therapy, consisting of maintenance tacrolimus, mycophenolate mofetil, and steroids. Steroids were weaned off over 14 weeks. No rejection was seen on any protocol biopsy. Therefore, all patients discontinued mycophenolate mofetil 11 to 13 months posttransplant, per protocol. An early for-cause biopsy in 1 patient, 5 days after dar-Treg infusion, revealed absence of rejection and accumulation of Tregs in the kidney allograft. All patients had Treg-containing lymphoid aggregates evident on protocol biopsies performed 8 months posttransplant. The patients are now all >6 years posttransplant on tacrolimus monotherapy with excellent graft function. None experienced rejection episodes. No serious adverse events were attributable to Treg administration. These results support a favorable safety profile of dar-Tregs administered early after renal transplant, suggest early biopsy might be an instructive research endpoint and provide preliminary evidence of potential immunomodulatory activity.

Urine CXCL10 to Assess BK Polyomavirus Replication After Kidney Transplantation.

Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication. We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d. Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol. Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty.

Monoclonal gammopathy of unknown significance in kidney transplanted patients: novel insights into long-term outcomes.

Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, little is known about the consequences of MGUS on long-term outcomes. We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls. Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P=.03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P=.007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P=.04) and a trend for more bacterial infections (63% vs 48%, P=.08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival. MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression.

Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients. Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux. We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation. Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection (r=0.8, P=0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return. The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

One Year Experience of the Hand Allotransplantation First Performed after Korea Organ Transplantation Act (KOTA) Amendment.

The revision of the Korea Organ Transplantation Act (KOTA) in 2018 included hand/arm among the organs that can be transplanted. The first hand transplantation since the revision of KOTA took place in January 2021. A 62-year-old male patient experienced hand amputation on July 13, 2018, by a catapult injury. The patient first visited our institute 3 months after the injury. After serial interviews and an overall evaluation, the patient was registered on the hand transplantation waiting list in January 2020. On January 9, 2021, the patient underwent hand transplantation at the right distal forearm level. The total operation time was 17 hours 15 minutes, and the cold ischemic time was 4 hours 9 minutes. Postoperative immunosuppression was administered based on the protocol used for kidney transplantation. Two acute rejection episodes occurred, on postoperative days 33 and 41. Both rejection episodes were reversible with rescue therapy of a higher tacrolimus trough level, steroid pulse therapy, and topical immunosuppressants. Controlled passive range of motion exercise was started on postoperative day 10. Dynamic splint was applied on postoperative day 18. At 1 year, graft maintenance and functional improvement were satisfactory, and the patient showed a Disabilities of Arm, Shoulder and Hand score of 25.8. We successfully performed the first hand transplantation surgery under the KOTA amendment. It came from the organic and effective cooperation of plastic, orthopaedic, and transplantation departments and we believe it will guarantee the future ongoing success.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p<.001). The duration of dialysis was longer in Hispanics (640 vs. 473days, p=.02), and fewer patients received preemptive transplants (10% vs. 29%, p<.01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Incidence of Graft Rejection in Descemet Membrane Endothelial Keratoplasty After COVID-19 mRNA Vaccination.

The aim of this study was to investigate the Descemet membrane endothelial keratoplasty (DMEK) rejection rate after COVID-19 vaccination with an mRNA vaccine. This was a multicenter, retrospective cohort study. A total of 198 patients who underwent DMEK between January 2006 and December 2020 were divided into 2 cohorts: consecutive patients who received at least 1 COVID-19 vaccination in 2021 (vaccination started from February 2021 in Japan) and nonvaccinated patients (control cohort). Patients who had a postoperative observation period of less than 90 days were excluded. The main outcome measurement was the incidence of graft rejection. A Cox proportional hazards regression model was used for comparisons with the nonvaccinated group. Six rejection episodes were observed in 198 patients (124 nonvaccinated and 74 vaccinated patients), with 1 occurring in the nonvaccinated group and 5 in the vaccinated group. In the univariate model, vaccination had a significant effect on rejection episodes (P = 0.003). The effect of vaccination was also significant (P = 0.004) after adjusting for covariates. This study suggests that there may be a higher rejection rate after COVID-19 vaccination in patients who underwent DMEK. Patients should be warned of the rejection risk and its typical symptoms before receiving an mRNA COVID-19 vaccine, although further larger studies are needed to confirm the involvement of vaccination.

Subset-specific Retention of Donor Myeloid Cells After Major Histocompatibility Complex-matched and Mismatched Liver Transplantation.

During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail. Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed. Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved. Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes.

Introduction of machine perfusion of donor hearts in a single center in Germany

IntroductionOrgan shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center. MethodsIn a retrospective single-center study, data from a prospectively collected database were analysed. From July 2018 to August 2021, fourteen hearts were retrieved and perfused using the Organ Care System (OCS), 12 hearts were transplanted. Criteria to use the OCS were based on donor/recipient characteristics. Primary objective was 30-day survival, secondary objectives were major cardiac adverse events, graft function, rejection episodes as well as overall survival in the follow-up and assessment of MP technical reliability. ResultsAll patients survived the procedure and the postoperative 30-day interval. No MP related complications were noted. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsy showed excellent results with no or mild rejection. Two donor hearts were rejected after OCS perfusion and evaluation. ConclusionEx vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options increased the number of acceptable donor hearts. Additional clinical trials are necessary to develop guidelines regarding the application of MP.