Transplant Recipients Research Articles

Interaction between ischemia-reperfusion injury and intestinal microecology in organ transplantation and its therapeutic prospects

Organ transplantation is a vital intervention for end-stage organ failure; however, ischemia-reperfusion injury is a complication of transplantation, affecting the prognosis and survival of transplant recipients. As a complex ecosystem, recent research has highlighted the role of the intestinal microecology in transplantation, revealing its significant interplay with ischemia-reperfusion injury. This review explores the interaction between ischemia-reperfusion injury and intestinal microecology, with a special focus on how ischemia-reperfusion injury affects intestinal microecology and how these microecological changes contribute to complications after organ transplantation, such as infection and rejection. Based on a comprehensive analysis of current research advances, this study proposes potential strategies to improve transplant outcomes, offering guidance for future research and clinical practice.

Early Hospital Readmission After Pediatric Liver Transplant: A Retrospective Analysis of the Society of Pediatric Liver Transplantation (SPLIT) Database.

Incidence of and risk factors for early hospital readmission (EHR) are poorly defined in pediatric liver transplant recipients. Therefore, we evaluated EHR incidence and risk factors for pediatric liver recipients in a nationally representative sample. Using the Society of Pediatric Liver Transplantation database, we retrospectively analyzed 2808 pediatric liver-only recipients transplanted 2011-2022. Recipient-, donor-, and center-level characteristics were evaluated as possible risk factors for EHR within 30 days of hospital discharge using multivariable modified Poisson regression. Overall, 23% (N = 642) of pediatric recipients experienced EHR. Independent risk factors for EHR include diabetes (adjusted relative risk [aRR] 2.33, 95% CI: 1.41-3.86, p = 0.001), history of malignancy (aRR 1.59, 95% CI: 1.19-2.11, p = 0.002), and shorter length of transplant hospitalization. Recipients in the shortest length of stay quartile (median [IQR] 8 [7-9] days) had a ninefold increased risk for EHR compared with recipients in the longest length of stay quartile (34 [28-48] days) (aRR 8.86, 95% CI: 5.68-13.81, p < 0.001). Incidence of EHR did not vary by transplant center and was not associated with other characteristics of the donor (DCD vs. not DCD), recipient (age, race, sex, and diagnosis), procedure (whole vs. split liver, ischemic time), or transplant center. We found the 30-day readmission rate for pediatric liver transplant recipients was 23%. Shorter hospital stays were a major risk factor for EHR, highlighting that longer initial transplant hospital stays may be beneficial for predischarge optimization and coordination of their complex care.

Recurrent Outbreak of Carbapenem-Resistant IMP-1-Producing Pseudomonas aeruginosa in Kidney Transplant Recipients: The Impact of Prolonged Patient Colonization.

Infections by carbapenem-resistant Pseudomonas aeruginosa (CRPA) have been associated with high morbidity and mortality among solid organ recipients. To delineate the epidemiological and molecular characteristics of a recurrent outbreak of imipenem (IMP)-producing P. aeruginosa (CRPA) among kidney transplant (KT) recipient METHODS: We described a recurring CRPA outbreak in a KT ward, divided into two periods: before unit closure (Feb 2019-2020) and after reopening (Aug 2020-Dec 2023). Routine surveillance cultures (SCs) were performed using axillary-perineum-rectal swabs with immunochromatographic tests. A case-control study identified risk factors for CRPA acquisition. Pulsed-field gel electrophoresis and whole genome sequencing characterized the strains. After reopening, new cases arose from patients previously colonized, peaking 18 months later. A total of 67 KT recipients with CRPA-IMP-producing strains were identified. All except one sequenced strain belonged to the ST446 clone, differing by a maximum of 110 single nucleotide polymorphisms. Forty-five (67.2%) cases were identified through SC, with 45.7% showing intermittent SC positivity. Patients remained colonized for up to 623 days. Twenty-four (35.8%) patients had infections, with the most common site being the urinary tract. Identified risk factors included older age, deceased donor, re-transplantation, reoperation, carbapenem or quinolone use, lymphopenia, hospital stay >10 days, and the first 60 days post-KT. KT recipients can harbor CRPA for extended periods, and detecting CRPA-colonized patients is challenging. These characteristics highlight the patient as the major source and a critical point in outbreak control.

Extracorporeal Photopheresis for the prevention of rejection after lung transplantation - a prospective randomized controlled trial.

Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). To investigate the efficacy of ECP as a prophylactic treatment to prevent acute cellular rejection (ACR), CMV infections and reduce the risk of CLAD. Single-center prospective randomized controlled trial conducted at Medical University of Vienna between 2018 and 2020. It included 31 COPD recipients per group. Treatment group underwent extracorporeal photopheresis in addition to standard triple-drug immunosuppression protocol after lung transplantation. Control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation. In the control group, 19 patients (61.3%) achieved the primary combined endpoint, compared with only 6 patients (19.4%) in the treatment group (p<0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44 versus 0.56±0.94, p<0.05) and at 12 months (0.25±0.48 versus 1.0±1.45, p=0.002). The rate of infections was lower in the ECP group with 5 cases and 67 cumulative hospital days compared to 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at three years was significantly greater in the ECP group (p=0.015). Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.

Severe SARS-CoV-2 infection is associated with increased risk of De novo HLA antibody production in lung transplant recipients: Single-center study.

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcomes. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR. We performed a retrospective chart review of 63 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 l of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 l of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. A total of 11, 43, and 9 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively. We observed no significant differences in the CPRA pre-COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 6/11 (54.5 %), 18/43 (41.8 %), and 6/9 (66.9 %) LTR with mild (p = 0.66), moderate (p = 0.74), and severe (p = 0.22) COVID-19 respectively. HLA class I and II DSA were detected pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis in 2/11 (p = 0.93), 7/43 (p = 0.71), and 0/9 LTR with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSA were detected within 6 months post-COVID-19 diagnosis in 0/11 (0 %), 1/43 (2.3 %), and 3/9 (33.3 %%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.001). Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.

Telehealth and Telemedicine in the Management of Adult Patients after Liver Transplantation: A Scoping Review.

Introduction: Telemedicine can support home-based self-care for liver transplant recipients after discharge from the hospital. This study aimed to (1) provide an overview of the forms of home care for liver transplant patients; (2) identify the content elements of telemedicine in the home care of liver transplant patients; and (3) summarize the effect and outcome indexes of using telemedicine in liver transplantation patients. Methods: A search was performed in the electronic databases of PubMed, CINAHL, Web of Science, Cochrane Library, Embase, Google Scholar, CNKI, Wan Fang data and Wei Pu database through March 1, 2024. Subject heading and keywords were used to reflect the concepts of telemedicine, hepatic transplantation. Studies of tele-home care after transplantation in liver transplant recipients over 18 years of age and the form, content elements, and outcome assessments of telemedicine were included. Results: A total of 16 articles met the inclusion criteria, and from this, the application form of telemedicine in liver transplantation patients, intervention elements and evaluation outcome indexes were identified. The forms of application include internet platform, applications, network communication software, and portable devices; and the elements of intervention include telemonitoring, remote health guidance, telerecordings, teleconsultation, and telerehabilitation; and the outcome indicators include physiological indicators, psychological status, Quality of life, self-management ability, compliance, satisfactory degree, complication rate, readmission rate, and feasibility. Conclusion: Telemedicine is active and feasible in the home-based self-care of patients after liver transplantation, but its application is immature and there are still some problems.

Risk factors for SARS-CoV-2 pneumonia among renal transplant recipients in Omicron pandemic—a prospective cohort study

BackgroundThe coronavirus disease (COVID-19) pandemic is a global health emergency, and SARS-CoV-2 pneumonia poses significant challenges to health systems worldwide. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. However, few studies have elucidated the risk factors of SARS-CoV-2 pneumonia in RTRs infected with COVID-19. This study aimed to build a risk prediction model for SARS-CoV-2 pneumonia among RTRs based on demographic and clinical information.MethodsWe conducted a prospective cohort study among 383 RTRs (age ≥ 18 years) diagnosed with COVID-19 from December 21, 2022, to March 26, 2023. Patients’ demographic and clinical information was collected through a questionnaire survey combined with electronic medical records. A stepwise logistic regression model was established to test the predictors of SARS-CoV-2 pneumonia. We assessed the diagnostic performance of the model by calculating the area under the curve (AUC) of the receiver operating characteristic (ROC) and calibration using the Hosmer–Lemeshow (HL) goodness-of-fit test.ResultsOur study showed that the incidence of SARS-CoV-2 pneumonia among RTRs was 31.1%. Older age (OR = 2.08–3.37,95%CI:1.05–7.23), shorter post-transplantation duration (OR = 0.92,95% CI: 0.87,0.99), higher post-transplant Charlson Comorbidity Index (CCI) (OR = 1.84, 95%CI: 1.14,2.98), pulmonary infection history (OR = 3.44, 95%CI: 1.459, 8.099, P = 0.005), fatigue (OR = 2.11, 95%CI: 1.14, 3.90), cough (OR = 2.03, 95%CI: 1.08, 3.81), and lower estimated glomerular filtration rate (eGFR) at COVID-19 diagnosis (OR = 0.98, 95%CI:0.97,0.99) predicted a higher risk for SARS-CoV-2 pneumonia. The model showed good diagnostic performance with Chi-Square = 10.832 (P > 0.05) and AUC = 0.839 (P < 0.001).ConclusionsOur study showed a high incidence of SARS-CoV-2 pneumonia among RTRs, and we built a risk prediction model for SARS-CoV-2 pneumonia based on patients’ demographic and clinical characteristics. The model can help identify RTRs infected with COVID-19 at high risk of SARS-CoV-2 pneumonia to inform timely, targeted, and effective prevention and intervention efforts.

Interstitial pneumonitis due everolimus in a liver transplant recipient.

This is a case report of a patient with a history of liver transplant who developed interstitial pneumonitis due to immunosuppressive treatment. Everolimus-induced pneumonitis in liver transplant recipients is a rare condition. This observation aims to highlight the significance of being aware of this condition, being suspicious of it, and getting a proper diagnosis and treatment.

Evaluating the use of glucagon‐like peptide‐1 receptor agonists in a matched cohort of kidney and liver transplant recipients

AbstractBackgroundDiabetes mellitus (DM) and obesity are common among solid organ transplant recipients, but are associated with an increased risk of graft failure.AimAlthough glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are effective for managing both conditions in the general population, there is limited evidence regarding their use among transplant recipients.MethodThe effect of GLP‐1 RAs on post‐transplant glucose control (defined as haemoglobin A1c [HbA1c]) among 37 liver and kidney transplant patients was compared to a control cohort. Secondary outcomes included change in total daily insulin requirements and oral DM agents, estimated glomerular filtration rate (eGFR), weight, and body mass index (BMI). Adverse events attributed to GLP‐1 RAs, hypoglycaemia, incidence of pancreatitis, biopsy‐proven acute rejection, graft loss, and death were assessed. Ethical approval was granted by the Henry Ford Health Institutional Review Board (Reference no: 15959) and the study conforms with the US Federal Policy for the Protection of Human Subjects.ResultsWe observed that patients receiving GLP‐1 RAs had a median reduction in HbA1c of 0.5% and reduction in insulin and oral anti‐DM agents compared to the control group without GLP‐1 RAs. There were statistically significant reductions in both weight and BMI in the GLP‐1 RA group. Our observed incidence of adverse events was similar to previous literature. Unlike other smaller studies, a decline in eGFR was observed in the GLP‐1 RA group. There were no differences in incidence of biopsy‐proven acute rejection, graft loss, or death.ConclusionWhen compared to patients without GLP‐1 RA therapy, GLP‐1 RAs modestly reduced HbA1c and insulin requirements and statistically reduced weight/BMI review at 6 months. GLP‐1 RAs, even if initiated early post‐transplant, were seemingly safe and effective. Larger, prospective studies are warranted to evaluate the safety and efficacy of GLP‐1 RAs in this population.

Epidemiological and Clinical Characteristics of the Course of COVID-19 Among Vaccinated and Unvaccinated Heart Transplant Recipients in Slovenia

Background: Patients receiving heart transplantation require lifelong immunosuppression and compared to the general population, they have a more than five times higher chance of acquiring COVID-19, and their mortality rates are higher. The aim of the present study was to estimate the epidemiological and clinical characteristics of COVID-19 in heart transplant recipients (HTRs) in Slovenia to estimate the vaccination rate and evaluate possible vaccination-hesitant subgroups. Methods: All SARS-CoV-2-positive HTRs (N = 79) between 1 March 2020 and 31 December 2023 at the Infectious Diseases Department, University Medical Centre Ljubljana, Slovenia, were included retrospectively. Demographic, clinical and vaccination data were extracted from medical documentation and a statistical evaluation was performed. Results: The observed vaccination rate was 63.3%, but among patients who received transplants before the pandemic, it was statistically significantly higher (p = 0.027). Vaccinated HTRs were statistically significantly older (p = 0.004) and had a significantly higher Charlson Comorbidity Index (p = 0.018). Our results indicate no significant differences between vaccinated and unvaccinated HTRs regarding acute respiratory insufficiency (p = 0.135), length of hospital stay (p = 0.106), intensive care unit admission (0.414) and in-hospital mortality (p = 0.317), but we observed statistically more frequently an asymptomatic course in those vaccinated (p = 0.050), and a longer length of stay in vector vaccine recipients (p = 0.011) and in those not re-vaccinated (p = 0.030). There was a significantly higher re-vaccination rate in males (p = 0.005). Conclusions: An asymptomatic course of COVID-19 was more often observed in vaccinated HTRs. Our findings suggest statistically significant differences in COVID-19 vaccine acceptance rates; younger HTRs and those transplanted after the pandemic are more hesitant to vaccinate, while females accept booster doses less frequently.

Treatment Response of Donor Specific Antibodies and Forced Expiratory Volume in Lung Transplant Recipients With Antibody Mediated Rejection

Antibody-mediated rejection (AMR) is an evolving diagnosis in lung transplantation. The presence of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) does not always correlate with clinical picture, leading to variation in treatment. This study sought to examine anti-HLA DSA response and lung allograft stabilization following AMR treatment. A single-center, retrospective case series was conducted in adult lung transplant recipients treated for clinical and subclinical AMR. The primary outcome was anti-HLA DSA reduction (≥ 25% decrease in mean fluorescence intensity [MFI]). The secondary outcome was forced expiratory volume (FEV1) stabilization (≤ 10% decline) at peak FEV1 and at 6-months post-treatment. Fifteen bilateral lung transplant recipients were included. Eight (53%) patients achieved the primary outcome with median MFI reduction of -56.7% (interquartile range [IQR] = -41.3 to -69.5). Statistical significance was found on matched pairs analysis between 3 and 6 months post-treatment for anti-HLA DSA reduction. Of the subjects with available data, 7 of 9 (78%) patients had FEV1 stabilization from diagnosis to peak FEV1, and 5 of 7 (71%) patients had stabilization from diagnosis to 6 months post-treatment. A statistically significant decline was found from peak FEV1 post-treatment to 6 months post-treatment (-0.4 L ± 0.2, P = .05). Univariate analysis did not identify predictors affecting anti-HLA DSA response. Anti-HLA DSA response was achieved in approximately half the cohort. A statistically significant decline in FEV1 was seen from peak FEV1 post-treatment but stabilized in most patients by 6 months. These results highlight the difficulty of DSA management and recovering lung function once lost, however, the finding of FEV1 stabilization after treatment is notable.

COVID-19 clinical phenotypes in vaccinated and nonvaccinated solid organ transplant recipients: a multicenter validation study

Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2 < 95% at admission. All-cause mortality occurred in 105 (21.5%) cases. It was higher in nonvaccinated versus vaccinated SOTR (23.4% vs 13.8%, P = 0.04). Patients in the entire cohort were classified into phenotypes A (n = 149, 30.5%), B (n = 187, 38.3%), and C (n = 152, 31.1%), with mortality rates of 8.7%, 16.6%, and 40.1%, respectively, which were similar to those of nonvaccinated SOTR (9.5%, 16.7%, and 52.0%) and lower in vaccinated SOTR (4.4%, 15.8%, and 17.3%, respectively), with difference between nonvaccinated and vaccinated in the phenotype C (P < 0.001). In conclusion, COVID-19 clinical phenotypes are useful in SOTR, and all-cause mortality decreases in vaccinated patients.

Emerging concepts of CMV in transplantation

AbstractCytomegalovirus (CMV) infections continue to be associated with significant morbidity and mortality following solid organ transplantation and haemopoietic stem cell transplantation. Advances in understanding the biology of CMV in the immunosuppressed host will translate into improved management approaches and better clinical outcomes. Updated definitions of resistant and refractory CMV infections will lead to more consistent reporting of CMV outcomes, better inform appropriate antiviral strategies and influence clinical trial design. Improved knowledge of the immunological control of CMV in the immunosuppressed host has led to novel diagnostics, emerging therapeutic cellular therapies and the development of an informed rationale for prophylactic and pre‐emptive strategies. As the boundaries of transplantation are extended, new patterns of CMV infection are being recognised. Finally, recent studies support the use of novel antiviral therapies in transplant recipients in the appropriate clinical setting. In this review, we provide an update on important new and emerging concepts in the management of CMV in immunosuppressed transplant recipients.

Knockout of B2M in combination with PD-L1 overexpression protects MSC-derived new islet β cells from graft rejection in the treatment of canine diabetes mellitus

BackgroundThe immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect.MethodsIn this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained.ResultsThe immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site.ConclusionsNew islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.

Timeline and Incidence of Infectious Complications in Older Transplant Recipients During the First Year Post-Transplantation

The number of older adults undergoing organ transplantation, and waiting lists are increasing. The epidemiological data on infections in older transplant patients are scarce. The objective of the study was to investigate the incidence and distribution of infectious complications in older patients according to post-transplant periods. This retrospective study was conducted in a university hospital between 1 January 2018 and 31 March 2023. All infectious episodes were analyzed over three post-transplant periods. Forty-four patients were enrolled. The median age was 67 years (min: 65 and max: 87 years). Patients experienced a total of 98 infectious episodes. The median number of infectious events per patient was 1.0 (min: 0 and max: 8). The overall incidence rate of infectious events was 2.18 infectious episodes per 1000 transplant days. Of the patients at risk, 18.2% had 12 (12.4% of all infections) infections in the first month (9.09 episodes per 1000 transplant days), 56.8% had 52 (53.1%) infections between 1 and 6 months (7.88 episodes per 1000 transplant days), and 40.9% had 34 (35%) infections &gt;6–12 months post-transplant (0.92 episodes per 1000 transplant days) The most prevalent type of infection was bacterial (79.6%, n = 78) followed by viral (18.4%, n = 18) and fungal (2.0%, n = 2) infections. The overall mortality rate of the 44 patients was 13.6%. The bacterial infections were more prevalent, and the incidence of infection was high during all post-transplant periods. These results may guide infection management in older transplant patients.

Using Machine Learning for Personalized Prediction of Longitudinal COVID-19 Vaccine Responses in Transplant Recipients

The COVID-19 pandemic has underscored the importance of vaccines, especially for immunocompromised populations like solid organ transplant (SOT) recipients, who often have weaker immune responses. The purpose of this study was to compare deep learning architectures for predicting SARS-CoV-2 vaccine responses 12 months post-vaccination in this high-risk group. Utilizing data from 303 SOT recipients from a Canadian multicenter cohort, models were developed to forecast anti-receptor binding domain (RBD) antibody levels. The study compared traditional machine learning models—logistic regression, epsilon-support vector regression, random forest regressor, and gradient boosting regressor—and deep learning architectures, including long short-term memory (LSTM), recurrent neural networks, and a novel model, routed LSTM. This new model combines capsule networks with LSTM to reduce the need for large datasets. Demographic, clinical, and transplant-specific data, along with longitudinal antibody measurements, were incorporated into the models. The routed LSTM performed best, achieving a mean square error (MSE) of 0.02±0.02 and a Pearson correlation coefficient (PCC) of 0.79±0.24, outperforming all other models. Key factors influencing vaccine response included age, immunosuppression, breakthrough infection, BMI, sex, and transplant type. These findings suggest that AI could be a valuable tool in tailoring vaccine strategies, improving health outcomes for vulnerable transplant recipients.

Prostate cancer in solid organ transplant recipients: results from a multicenter series

Prostate cancer incidence in immunosuppressed transplant recipients increases as life expectancy improves in this population. However, the management of treatments and immunosuppressive (IS) regimens for solid organ transplant recipients diagnosed with prostate cancer remains poorly defined. Therefore, we conducted a multicentric study to investigate these parameters more thoroughly. This multicentric, retrospective study includes all kidney, heart, liver, or combined transplant recipients, diagnosed with prostate cancer between 1998 and 2020. IS regimen management, demographic, oncological and survival outcomes were studied here. A prostate cancer was diagnosed among 87 SOTRs: 70 RTRs, 10 HTRs, 2 LTRs and 5 combined transplant recipients. The mean age at diagnosis was 64.3 years with 10,7 years mean time from transplantation to PCa. A 38% low risk, 45% intermediate risk and 11% high risk were recorded at diagnosis. 56 patients underwent radical prostatectomy, 11 patients underwent radiotherapy combined with ADT, 4 patients underwent radiotherapy alone, 6 patients underwent ADT alone, 1 patient underwent brachytherapy, 3 patients underwent watchful waiting, 1 patient was treated by HIFU and 5 patients were under active surveillance. 16 patients had complementary treatment following biochemical recurrence or positive margins. IS regimen was modified for 69% of patients. 12 deaths occurred in total (14%) with a 92% and 86%, 3 and 5-year overall survival respectively. 3 and 5-year progression-free survival were 89% and 83% respectively. There was no significant PFS difference between patients treated with radiotherapy and prostatectomy (p=0.94), and patients with or without a change in immunosuppressants (p=0.88). Guidelines for diagnosis and management of prostate cancer in the general population appears to apply in SOTRs with good oncological outcomes. Active surveillance should also be considered in this population.

Impact of Immunosuppressive Therapy, Vaccination, and Monoclonal Antibody Use With Outcomes in Liver and Kidney Transplant Recipients With COVID-19: A Retrospective Study.

Patients who have undergone solid organ transplantation are at an elevated risk of severe coronavirus disease (COVID-19) because of post-transplantation immunosuppressive therapy. However, optimization of vaccination, modification of immunosuppression, and implementation of monoclonal antibody (mAb) therapy in transplant recipients with COVID-19 is uncertain. A retrospective cross-sectional study was conducted on patients who underwent liver or kidney transplants and were diagnosed with COVID-19. The association of several vaccine doses, mycophenolate therapy, and mAB therapy with mortality outcomes after COVID-19 diagnosis (3 and 6 months), hospitalization, and length of hospital stay were assessed. This study included 255 patients with a median age of 59 (23-89) were included. Many COVID-19 vaccine doses were not associated with any outcome; however, patients with a liver transplanted with mycophenolate had higher 3-month (19% vs. 0%; p = 0.02) and 6-month (21% vs. 0%; p = 0.01) mortality rates than those who did not. In addition, transplant recipients who received mAb therapy for COVID-19 were less likely to be hospitalized (37% vs. 68%; p < 0.001). For organ transplant recipients with COVID-19, vaccination alone may not be an optimal strategy for preventing serious outcomes. Rather, the types of organ transplant, immunosuppressive therapy (particularly mycophenolate), and COVID-19 treatment strategy should be synergistically considered to promote an optimal therapeutic dynamic for a vulnerable population.

Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants

BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical. Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes. BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19-2.91, compared to non-viraemic recipients' median logIC50 values of 2.13-3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p<0.001). Notably, a mismatch against donor serotype Ic and II associated with adjusted odds ratios of 8.12 (95% CI 2.10 to 35.61; p=0.002) and 4.52 (95% CI 1.19 to 19.23; p=0.03) respectively. 21 recipients demonstrated broadly neutralising responses against all the serotypes, none of whom developed BKV DNAaemia post-transplant. In contrast, there was poor concordance with PsV-specific ELISA data that quantified the total antibody response against different serotypes. BKV nAb mismatch predicts post-transplant BKV DNAaemia. Specific mismatches in nAb, rather than total seroreactivity, are key indicators of BKV risk post-transplant. This has the potential to risk-stratify individuals and improve clinical outcomes by influencing the frequency of monitoring and individualised tailoring of immunosuppression. Furthermore, detailed examination of individuals with broadly neutralising responses may provide future therapeutic strategies. The research was funded by St. Peters Trust, Royal Free Hospital Charity and Wellcome Trust (grant numbers RFCG1718/05, SPT97 and 204870/Z/WT_/Wellcome Trust/United Kingdom).

Lung Transplant Outcomes in Recipients of Advanced Age: Are Two Always Better Than One?

Lung transplantation has become more common in patients aged 65 years and older. We aimed to examine outcomes across age groups and identify risk factors for decreased survival. United Network for Organ Sharing data for all primary lung transplants from 1/1/2006 to 3/8/2023 was retrospectively reviewed. Impact of recipient age on survival was analyzed. Of the 33,644 lung transplant recipients that were identified, 23,125 (69%), 7,270 (21%), 2,895 (9%), and 354 (1%) were aged 12-64, 65-69, 70-74, and 75-79 years, respectively. Older patients underwent single lung transplantation more often (12-64: 19%, 65-69: 41%, 70-74: 57%, 75-79: 75%, p<0.001). Median survival was higher in bilateral compared to single lung transplant in all groups except 75-79 (12-64: 7.6 vs. 5.6, p < 0.001; 65-69: 5.8 vs. 4.8, p < 0.001; 70-74: 5.0 vs. 3.9, p < 0.001; 75-79: 4.0 vs. 3.9 years, p = 0.919). Prior cardiac surgery was associated with increased hazard of death (HR: 1.27, 95% CI, 1.14-1.41, p<0.001) and higher likelihood of receiving a single lung transplant with older age (12-64 years: 45.3%, 65-79 years: 71.0%, p < 0.001). Bilateral lung transplantation offers a survival advantage over single lung transplantation in recipients up to 74 years of age. Recipients aged 75 to 79 have poor long-term survival. Prior cardiac surgery is associated with worse long-term survival, necessitating careful patient selection, especially in older patients being offered a single lung transplant.