Selection Of Patients For Transplantation Research Articles

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Erratum: Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

Erratum: Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

Management and Outcomes of Kidney Transplant Candidates With Severe Pulmonary Hypertension: A Single-center Strategy and Experience.

Severe pulmonary hypertension (PH) is associated with high mortality posttransplant and thus is considered a contraindication to kidney transplantation. In this study, we describe the pretransplant management and posttransplant outcomes in patients with severe PH using a multidisciplinary approach. Between 11 of 2013 and 8 of 2022, we identified all patients with severe PH on initial pretransplant workup who underwent ultrafiltration (UF) or medical therapy for PH before transplant. Posttransplant we evaluated the perioperative course, renal function, graft, and patient survival. We compared survival to those who remained waitlisted or were delisted. Three-two patients (mean age = 55.03 ± 10.22 y) diagnosed with severe PH on pretransplant screening echocardiogram. Thirty patients (94%) were subjected to a median of 4 (range, 3-8) UF sessions with an average weight loss of 4.33 ± 2.6 kg. Repeat assessment of PH revealed a decline in mean pulmonary artery systolic pressure from 67 ± 12 mm Hg to 43 ± 13 mm Hg (P < 0.0001). Seventeen patients (53%) received a kidney transplant. The mean estimated Glomerular Filtration Rate at 3, 6, 9, and 12 mo was 72 ± 27, 72 ± 28, 75 ± 29, and 75 ± 29 mL/min/1.73 m2. Among, those who underwent transplantation both graft and patient survival was 100% at 1-y posttransplant. Overall, since the UF intervention, at a median follow-up of 88 ± 12 mo those transplanted had a patient survival of 88% while those who remained on dialysis had a survival of 53% (P = 0.0003). In this single-center study, we report postcapillary PH can be a significant contributor to elevations in pulmonary artery systolic pressure. Using a multidisciplinary approach, PH can improve with volume removal and phosphodiesterase 5 inhibitors therapy leading to a successful posttransplant outcome.

Kidney transplantation in patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

Outcomes of Kidney Transplantation Among COVID-19 Recovered Patients in a Single Transplant Center

The COVID-19 pandemic significantly lowered kidney transplantation (KT) rates worldwide, and studies regarding outcomes of patients who developed COVID-19 infection before KT are limited, especially in low to middle-income countries. To determine the 1-year graft and patient survival of kidney transplant recipients who recovered from COVID-19 infection before KT. We retrospectively reviewed all adult end-stage renal disease patients who underwent KT at the National Kidney and Transplant Institute from June 2020 through October 2021. Transplant parameters, graft and patient survival, pretransplant COVID-19 infection, and post-KT infectious complications were recorded. Data was analyzed using two-tailed descriptive statistical tests. Of the 219 recipients, 23 (11%) had COVID-19 infection within 1 to 16 months before KT. The mean age of KT recipients was 36 years (range, 25-57), and 61.9% had chronic glomerulonephritis as primary renal disease. The mean duration from COVID-19 recovery to KT was 79 days (range, 21-207). There was no significant difference in the 1-year biopsy-proven acute rejection in the 2 groups, at 4.5% vs 12.5% for the COVID-19 and non-COVID-19 group, respectively. Both the 1-year graft and patient survival were similar in the COVID-19 and non-COVID-19 groups at 98.4% vs 100% and 100% vs 98.44%, respectively. There was no significant difference in biopsy-proven acute rejection, 1-year graft, and patient survival among patients who had a prior COVID-19 infection vs those who did not. Kidney transplantation appears safe when performed at least 1 month from COVID-19 infection.

Spliced CEACAM1: A Potential Novel Biomarker and Target for Ameliorating Liver Ischemia-reperfusion Injury.

Hepatic ischemia-reperfusion injury remains a significant challenge in liver transplantation potentially leading to delayed graft function, primary nonfunction, and sometimes rejection. Understanding the underlying mechanisms and implementing mitigation strategies are essential for improving transplant outcomes and patient survival. A recent study published by Dery et al shows that alternative splicing of carcinoembryonic antigen-related cell adhesion molecule 1 regulated by hypoxia inducible factor 1 alpha under stress enhances hepatic ischemia tolerance in mice and humans. The authors identified a direct binding of hypoxia inducible factor 1 alpha to the promoter region of polypyrimidine tract-binding protein 1 splicing enzyme, resulting in carcinoembryonic antigen-related cell adhesion molecule 1-short induction and improved posttransplant outcomes. This study has notably elucidated a potential biomarker pertaining to the quality of liver transplant donor grafts.

Performance of risk prediction models for post-liver transplant patient and graft survival over time.

Given liver transplantation organ scarcity, selection of recipients and donors to maximize post-transplant benefit is paramount. Several scores predict post-transplant outcomes by isolating elements of donor and recipient risk, including the donor risk index, Balance of Risk, pre-allocation score to predict survival outcomes following liver transplantation/survival outcomes following liver transplantation (SOFT), improved donor-to-recipient allocation score for deceased donors only/improved donor-to-recipient allocation score for both deceased and living donors (ID2EAL-D/-DR), and survival benefit (SB) models. No studies have examined the performance of these models over time, which is critical in an ever-evolving transplant landscape. This was a retrospective cohort study of liver transplantation events in the UNOS database from 2002 to 2021. We used Cox regression to evaluate model discrimination (Harrell's C) and calibration (testing of calibration curves) for post-transplant patient and graft survival at specified post-transplant timepoints. Sub-analyses were performed in the modern transplant era (post-2014) and for key donor-recipient characteristics. A total of 112,357 transplants were included. The SB and SOFT scores had the highest discrimination for short-term patient and graft survival, including in the modern transplant era, where only the SB model had good discrimination (C ≥ 0.60) for all patient and graft outcome timepoints. However, these models had evidence of poor calibration at 3- and 5-year patient survival timepoints. The ID2EAL-DR score had lower discrimination but adequate calibration at all patient survival timepoints. In stratified analyses, SB and SOFT scores performed better in younger (< 40 y) and higher Model for End-Stage Liver Disease (≥ 25) patients. All prediction scores had declining discrimination over time, and scores relying on donor factors alone had poor performance. Although the SB and SOFT scores had the best overall performance, all models demonstrated declining performance over time. This underscores the importance of periodically updating and/or developing new prediction models to reflect the evolving transplant field. Scores relying on donor factors alone do not meaningfully inform post-transplant risk.

CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis

AbstractCPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as “7 + 3” combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs “7 + 3” combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and “7 + 3” combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with “7 + 3” combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor–interleukin-22 (IL-22)–IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.

Reduced graft survival in renal transplant patients with urinary tract infections - a meta-analysis.

Renal transplant patients are prone to developing urinary tract infections (UTIs). However, the potential effect of a UTI on renal graft loss remains unclear. We systematically surveyed the literature for a potential association between UTI and graft loss. Articles were identified in online databases using a specific search string, followed by post selection for meta-analysis following four inclusion criteria: 1) a clear definition of UTI and recurrent UTI, 2) n > 200, 3) patient age > 16 years and 4) inclusion of data on graft loss. Data on UTI and graft loss were extracted from the included studies for calculation of a combined weighted odds ratio (OR) using the Mantel-Haenszel method. This review was conducted according to the PRISMA 2020 statement. Unfortunately, only eight of 108 papers met the inclusion criteria. These studies reported between 276 and 2,368 patients, primarily male, aged around 50 years. The two-year incidence of overall UTI varied from 16.5% at a 27.5-month follow-up to 30.1% at a 24-month follow-up from transplantation. Seven papers were included in the OR analysis; two found an association between UTI and graft loss and five did not. However, in the meta-analysis, the weighted OR for all seven studies was 1.340 (95% confidence interval: 1.050-1.720). Filtering the literature for a strict definition of UTI allowed us to establish an association between UTI and graft loss in renal transplant patients. However, further investigation and stronger studies using the Goldman criteria are needed to allow stratification for UTI severity and effect on graft loss.

Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin

BackgroundThe treatment of tacrolimus-induced post-transplantation diabetes mellitus (PTDM) has become a hot topic to improve the long-term survival of organ transplant patients, however whose pathogenesis has not been fully elucidated. In pancreas, the up-regulation of NF-κB has been reported to stimulate cytokine IL-1β/TNF-α secretion, inducing pancreatic injury, meanwhile other studies have reported the inhibitory effect of rapamycin on NF-κB. PurposeThe aim of this study was to clarify the mechanism of tacrolimus-induced pancreatic injury and to explore the potential effect from small dose of sirolimus. MethodsWistar rats were randomly divided normal control (NC) group, PTDM group, sirolimus intervention (SIR) group. Transcriptomic analysis was used to screen potential mechanism of PTDM. Biochemical index detections were used to test the indicators of pancreatic injury. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot were used to verify the underlying mechanism. ResultsCompared with NC group, the level of insulin was significant reduction (P < 0.01), inversely the level of glucagon was significantly increase (P < 0.01) in PTDM group. Transcriptomic analysis indicated Syk/BLNK/NF-κB signaling was significantly up-regulated in PTDM group. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot verified Syk/BLNK/NF-κB and TNF-α/IL-1β were all significantly increased (P < 0.05 or P < 0.01), demonstrating the mechanism of tacrolimus-induced pancreatic injury via Syk/BLNK/NF-κB signaling. In addition, compared with PTDM group, the levels of weight, FPG, AMY, and GSP in SIR group were significant ameliorative (P < 0.05 or P < 0.01), and the expressions of p-NF-κB, TNF-α/IL-1β in SIR group were significantly reduction (P < 0.05 or P < 0.01), showing Syk/BLNK/NF-κB signaling promoted pancreatic injury induced by tacrolimus and potential protective effect from rapamycin reducing NF-κB. ConclusionSyk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and rapamycin has a potentially protective effect by down-regulating NF-κB. Further validation and clinical studies are needed in the future.

The value of functional magnetic resonance imaging in evaluating renal allograft function

BackgroundTo explore the value of arterial spin labeled (ASL) and blood oxygen level dependent (BOLD) imaging in evaluating allogeneic kidney function after renal transplantation. MethodsOne hundred and thirty-five renal transplant patients were included. Demographic and imaging data were collected. Transplanted renal function, pathology, ASL and BOLD parameters were obtained. The patients were divided into normal, mild and severe injury group. The correlation between BOLD/ASL parameters and clinical data were evaluated. The prediction models were based on ASL and BOLD parameters using multivariate logistic analysis. Cox proportional hazards regression model was used to analyze the effects of gender, age, ASL and BOLD on the survival of renal transplant patients. ResultsASL and BOLD parameters were independently associated with renal function injury and renal allograft positive pathology. The AUC of prediction model for renal allograft function based on ASL and BOLD parameters was 0.85, while the AUC based on BOLD parameters was 0.70. Renal transplantation time showed a positive correlation with age, BOLD parameters and SCr，while a negative correlation with ASL parameters and eGFR. ASL parameter was positively correlated with eGFR and negatively correlated with Scr. BOLD parameter was negatively correlated with eGFR, ASL and positively correlated with Scr. Cox proportional hazards regression model showed that the increase of age could reduce the risk of renal function injury and positive pathology. ConclusionsASL and BOLD were associated with renal function injury and renal allograft positive pathology. ASL and BOLD had some value in predicting renal allograft function.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients.

The prevalence of malnourished patients before transplantation and the influence of malnutrition on graft and patient outcomes remain underestimated, despite being associated with higher postoperative morbidity and mortality. This study aimed to develop an easy nutritional screening tool and evaluate the impact of nutritional status on clinical outcome, graft survival (GS) and mortality risk in kidney transplant patients (KTP). In this retrospective cohort study including 451 KTP, we developed a score by using anthropometric, clinical, and laboratory measures performed in the pretransplant evaluation. The patients were stratified into 3 groups according to the final score: G1 (0 or 1 point)=low risk, G2 (2 to 4 points)=moderate risk, and G3 (>5 points)=high risk of malnutrition. The patients were monitored after transplantation at least 1 to 10 years. Stratifying the 451 patients based on the pretransplant risk score, G1, G2, and G3 were composed of 90, 292, and 69 patients, respectively. Patients from G1 maintained the lowest serum creatinine levels at hospital discharge when compared with others (p = 0.012). The incidence of infection in the patients from G3 was higher than patients from G1 and G2 (p = 0.030). G3 recipients showed worse GS than G1 patients (p = 0.044). G3 patients showed almost threefold higher risk for graft loss (HR 2.94, 95% CI 1.084-7.996). KTP with higher malnutrition risk score were associated with worse outcomes and GS. The nutritional screening tool is easy to be used in clinical practice to evaluate the patient in preparation for kidney transplant.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients

RESUMO Antecedentes: A prevalência de pacientes desnutridos antes do transplante e a influência da desnutrição nos desfechos do enxerto e do paciente permanecem subestimadas, embora estejam associadas a maior morbimortalidade pós-operatória. Este estudo buscou desenvolver uma ferramenta simples de triagem nutricional e avaliar o impacto do estado nutricional no desfecho clínico, sobrevida do enxerto (SE) e risco de mortalidade em pacientes transplantados renais (PTR). Métodos: Neste estudo de coorte retrospectivo incluindo 451 PTR, desenvolvemos um escore usando medidas antropométricas, clínicas e laboratoriais tomadas na avaliação pré-transplante. Os pacientes foram estratificados em 3 grupos segundo a pontuação final: G1 (0-1 ponto) = baixo risco, G2 (2-4 pontos) = risco moderado e G3 (&gt;5 pontos) = alto risco de desnutrição. Eles foram monitorados por pelo menos 1 a 10 anos após o transplante. Resultados: Os 451 pacientes foram estratificados em G1, G2 e G3, que consistiram em 90, 292 e 69 pacientes, respectivamente. Os pacientes do G1 mantiveram os menores níveis de creatinina sérica na alta hospitalar em relação aos demais (p = 0,012). A incidência de infecção nos pacientes do G3 foi maior que nos pacientes do G1 e G2 (p = 0,030). Os pacientes do G3 apresentaram SE pior do que os pacientes do G1 (p = 0,044) e um risco quase três vezes maior de perda do enxerto (HR 2,94; IC 95% 1,084-7,996). Conclusões: PTR com maior escore de risco de desnutrição foram associados a piores desfechos e menor SE. A ferramenta de triagem nutricional é fácil de usar na prática clínica para avaliar pacientes em preparação para transplante renal.

Phase Angle and Body Composition As a Prognostic Factor in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukaemia (ALL) is a malignant proliferation of lymphoid cells blocked at an early stage of differentiation that can invade bone marrow, blood, and extramedullary sites. Age specific incidence is highest in children aged 1-4 years, then drops sharply through childhood (5-14 years), adolescence and young adulthood (AYA) (15-39 years), reaching the lowest point between 25 years and 45 years. Bioelectrical impedance analysis (BIA) is a method used to estimate body composition and cell membrane integrity. BIA is a useful tool as it is non-invasive, relatively inexpensive, can be performed on nearly any patient, does not expose the patient to ionizing radiation, is painless, and has both high intra and inter observer precision (coefficient of variation = 2.7%-4.0%). Phase angle (PhA) is obtained by BIA and is associated with cellular function. It is considered a reliable marker of malnutrition. PhA has been shown to predict survival in solid malignancies and hematopoietic stem cell transplant patients. To date, no studies have evaluated the usage of PhA in ALL patients. Therefore, this retrospective study sought to establish the prognostic significance of baseline PhA and lean mass index on OS and LFS in newly diagnosed ALL patients receiving intensive chemotherapy. Retrospective, cross-section, observational and descriptive study. The records of patients who received intensive chemotherapy from January 2019 to January 2023 were reviewed. Statistical analysis The qualitative variables were studied in frequencies and proportions, the quantitative variables were grouped into medians and ranges. OS and LFS were determined using Kaplan-Meier survival curves with log-Rank with a significant p &amp;lt;0.05 value. Statistical analysis was performed with SPSS version 25 and GraphPad Prism version 9.5.0. Results 85 patients were included, 56.7% (48) men and 43.5% (37) women. 79 patients with ALL-B and 6 patients ALL-T. The mean age was 25 years. 68 were AYA population and 17 not-AYA. The CR was 89%, ND MRD was 57%. The chemotherapy for AYA was CALGB 10403, and not AYA was Hyper-CVAD. Relapse was documented in 38%. The mean body mass index was 26.98±5.27 kg/m 2. The mean PhA was 4.547±0.9983°. The mean lean mass index was 17.8 (12.9-35.5) kg/m 2. The mean fat mass index was 9.195±4.425 kg/m 2. The mean OS was 86% at 1 year and OS at 3 years was 64.5%. The results that were statistically significant in LFS compared by Kaplan Meier curves were: male vs female p=0.0344, PhA &amp;gt;4, p=0.0235, lean mass index ≥16, p=0.0111. Conclusions In conclusion, our findings suggest that in newly diagnosed ALL patients undergoing intensive induction chemotherapy, PhA may provide important prognostic information for LFS and OS. PhA is an objective, repeatable, high-precision measure in ALL patients and, unlike other prognostic factors in this population, is potentially subject to intervention. Future studies of PhA in ALL patients should address the content validity of phase angle while further exploring the promising findings of the effect of strength training and nutritional supplementation on PhA and patient outcomes.

High pretransplant FGF23 level is associated with persistent vitamin D insufficiency and poor graft survival in kidney transplant patients

Vitamin D3 (25[OH]D3) insufficiency and fibroblast growth factor 23 (FGF23) elevation are usually attenuated after kidney transplantation (KT). However, elevated FGF23 may be associated with poor graft outcomes and vitamin D insufficiency after KT. This study investigated the effect of pretransplant FGF23 levels on post-KT 25(OH)D3 status and graft outcomes. Serum FGF23 levels from 400 participants of the KoreaN Cohort Study for Outcome in Patients With Kidney Transplantation were measured. Annual serum 25(OH)D3 levels, all-cause mortality, cardiovascular event, and graft survival were assessed according to baseline FGF23 levels. Serum 25(OH)D3 levels were initially increased 1 year after KT (12.6 ± 7.4 vs. 22.6 ± 6.4 ng/mL). However, the prevalence of post-KT vitamin D deficiency increased again after post-KT 3 years (79.1% at baseline, 30.8% and 37.8% at 3 and 6 years, respectively). Serum FGF23 level was decreased 3 years post-KT. When participants were categorized into tertiles according to baseline FGF23 level (low, middle, high), 25(OH)D3 level in the low FGF23 group was persistently low at a median follow-up of 8.3 years. Furthermore, high baseline FGF23 level was a risk factor for poor graft survival (HR 5.882, 95% C.I.; 1.443–23.976, P = 0.013). Elevated FGF23 levels are associated with persistently low post-transplant vitamin D levels and poor graft survival.

Abstract 19190: The Impact of Donor Age on Long-Term Survival After Heart Transplantation: A Modern Analysis of the Unos Database

Introduction: Despite innovations in organ procurement and preservation, heart transplantation (HT) remains challenged with paucity of donor organs. Data is limited regarding the influence of donor age on long term outcomes of HT. Hypothesis: Our aim was to investigate the impact of donor age on long-term survival of transplant recipients between the past two decades. We hypothesized that the probability of survival has increased significantly over the most recent decade with significant increases in survivability for donor hearts aged 55+ years. Methods: The UNOS heart transplant registry was used to analyze survival of heart transplant patients between 2000-2009 (N= 10178) and 2010-2019 (N=20990). These were further separated into three donor age groups: 18-34, 35-54, and over 55 years. Kaplan-Meier survival curves were generated over a 10-year period. Log-ranked statistical testing was used to test the survival curves for significance. Results: Between 2000-2009, 5895 (58%) HT were performed from donors aged 18-34, 3862 (38%) HT from ages 35-54, and 422 (4%) HT from age 55+ group. The chance of 10-year survival was 62%, 52% and 40% respectively.In the 2010-2019 era, there were 12993 (62%) HT performed from donors aged 18-34, 7363 (35%) from ages 35-54, and 634 (3%) from age 55+ group. The 10-year survival was 81%, 77% and 73% respectively.In the donor group age 55+, there was significant difference (p&lt;0.0001) between the head trauma and cerebrovascular cause of death prior to 2010, but no difference in the new era. Conclusions: Our study of the UNOS database finds that the donor age of transplanted hearts significantly impacted long-term survival during 2000-2009. These significant differences carry for transplants from 2010-2019, however, we find that long-term survivability for all donor groups increased to over 70%. The largest increase was observed for donor hearts 55+ years where the chance of 10-year survival improved from 40% before 2010 to 73% after 2010.

The outcomes of patients with kidney failure due to focal segmental glomerulosclerosis (FSGS) in Australia and New Zealand: A cohort study using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA).

The outcomes of patients with focal segmental glomerulosclerosis (FSGS) on kidney replacement therapy (KRT) have not been well described. This study evaluated the outcomes of patients with kidney failure due to FSGS on KRT including dialysis and kidney transplantation. All adult patients with kidney failure who commenced KRT in Australia and New Zealand from 15th of May 1963 to 31st of December 2018 were retrospectively extracted from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Outcomes of patients with FSGS were compared to those with other causes of kidney failure (non-FSGS). 85,052 patients commenced KRT during the study period, of whom 2991 (3.5%) were patients with FSGS. Compared to patients with non-FSGS, patients with FSGS experienced similar mortality on dialysis (adjusted hazard ratio [aHR] 0.98, 95% CI 0.90-1.06, p = 0.55) and following kidney transplantation (aHR 0.92, 95% CI 0.73-1.15, p = 0.47). The risk of first kidney allograft loss was higher in patients with FSGS (aHR 1.20, 95% CI 1.04-1.37, p = 0.01). However, when death was analysed as a competing risk, the survival in both groups was similar (sub-hazard ratio [SHR] 1.09, 95% CI 0.94-1.28, p = 0.26). Patients with FSGS had a longer waiting time for kidney transplantation (aHR 0.92, 95% CI 0.86-0.98, p = 0.02) and experienced an increased risk of disease recurrence in the allograft (aHR 1.73, 95% CI 1.35-2.21, p<0.001). Compared to patients with other forms of glomerular disease, patients with FSGS experienced similar dialysis and transplant patient survival and death-censored rate of kidney transplantation and allograft loss but higher rates of primary kidney disease recurrence. FSGS was associated with similar dialysis and transplant patient survival and death-censored first allograft loss compared to non-FSGS and other forms of glomerular disease.

Real-World Comparison of Venetoclax-Based Treatment Versus Intensive Chemotherapy As Bridging to Allogeneic Stem Cell Transplantation in MDS-IB2 Patients

Background Allogeneic stem cell transplantation (alloSCT) is the cornerstone therapy for myelodysplastic syndromes with increased blasts-2 (MDS-IB2). However, the optimal induction therapy before transplantation remains unclear. Herein, we compared our single-center experience of non-intensive Venetoclax (Ven)-based regimens versus standard intensive chemotherapy (IC) as bridging to alloSCT in MDS-IB2 patients. Methods We have performed an observational, retrospective, single-center study. All patients were at least 18 years of age, had newly diagnosed, previously untreated MDS-IB2 based on the 5 th edition of the WHO diagnostic criteria, were considered transplant-eligible at diagnosis, and had received either Ven-based therapies or IC for induction. All patients provided informed consent for data collection. The Ven-based regimens were either Ven14+Aza7 (Venetoclax 400mg/d on days 1-14 with Azacitidine 75mg/m 2 on days 1-7) or ACTIVE (Venetoclax 600mg/d on days 1-14, Cytarabine 20mg/m 2 on days 1-10 and Actinomycin D 12.5mcg/kg on days 1-3). IC regimens were 7+3 or FLAG-Ida. After 1 or 2 cycles of induction therapy transplant-eligible responders proceeded to alloSCT. We evaluated baseline characteristics, IPSS-M, IPPS-R values, CR, CRh and marrow CR (mCR) rates, time to ANC&amp;gt;1x10 9 and PLT&amp;gt;100x10 9 recovery, CTCAE v5.0 grade 3-5 non-hematological adverse events, overall survival (OS) and day-30 mortality. Results Detailed baseline characteristics are summarized in Table 1. 18 patients (13 female) had received Ven-based therapies and 15 patients (7 female) had undergone IC. The median age was 59 (27-71) in comparison to 56 (24-66) in Ven and IC patients, respectively (p=0.104). The median ECOG value was 1 (0-2) in the Ven group and was significantly higher compared to 0 (0-2) in the IC cohort (p=0.042). The median IPSS-R and IPSS-M values were 6.5 (5.5-10) and 2.19 (0.78-4.73) compared to 7.25 (4.5-10) and 3.15 (0.93-4.52) in Ven and IC patients, respectively (p=0.746, p=0.79). The mCR rate was 82% in Ven patients compared to 87% in the IC group (p=0.741). The CR+CRh rates were 59% and 73% in Ven and IC groups, respectively (p=0.396). Sixty-three percent of Ven patients were allotransplanted compared to 73% in the IC group (p=0.526). Grade 3-5 non-hematological toxicity was lower in the Ven group compared to the IC patients (44% vs 87%, p=0.013). The median times to neutrophil and platelet recovery were 44 (4-165) and 34 (21-94) days compared to 30 (21-110) and 32 (21-36) days in the Ven and IC groups, respectively (p=0.285, p=0.775). The median OS was 15.1 months (3.2-22.1) and 13 months (6.7-40.3) in the Ven and IC groups, respectively (p=0.637). Survival data are shown in Figure 1. The day-30 mortality rate was 11% in the Ven group compared to 7% in the IC patients (p=0.663). Conclusions We did not observe significant differences between low-intensity Ven-based regimens and IC in terms of responses, overall survival, and number of transplanted patients in this high-risk MDS-IB2 cohort. Non-hematological grade 3-5 toxicity was lower in Ven-treated patients. Our real-life, single-center results should be interpreted with caution.

Trichosanthin-derived peptide Tk-PQ attenuates immune rejection in mouse tracheal allotransplant model by suppressing PI3K-Akt and inducing type II immune polarization

Obliterative bronchiolitis (OB) is one of the main complications affecting long-term survival of post-lung transplantation patients. In this study, we evaluated the efficacy of Tk-PQ (a peptide derived from trichosanthin) in alleviating OB in a mouse ectopic tracheal transplant model. We found that post-transplantation treatment of Tk-PQ significant ameliorated OB symptoms including luminal occlusion, epithelial cells loss and fibrosis in the allograft. In addition, Tk-PQ promoted immune suppressive environment by inducing Th2 polarization and increasing Treg population which in turn led to elevated levels of anti-inflammatory cytokines IL-4, IL-10, IL-33 and decreased levels of pro-inflammatory IL-1β. Mechanistically, we used transcriptome analysis of splenic T cells from allografted mice to show that Tk-PQ treatment down-regulated the PI3K-Akt signaling pathway. Indeed, the immune suppression phenotypes of Tk-PQ was recapitulated by a PI3K inhibitor LY294002. Taken together, Tk-PQ regulates post-transplantation immuno-rejection by modulating the balance of T cell response via the PI3K-Akt pathway, making it a promising peptide based immune rejection suppressant for patients receiving allotransplant.

Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens.

Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown. To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge ("Change" group). A p-value < 0.05 was considered statistically significant. Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates. This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.