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Combined liver–kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli's disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients. [ABSTRACT FROM AUTHOR]

Summary: The global pandemic has resulted in the common occurrence of SARS‐CoV‐2 infection in the population. In the post‐pandemic era, it is imperative to understand the influence of donor SARS‐CoV‐2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). We retrospectively analysed allo‐HSCTs from donors with mild SARS‐CoV‐2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo‐HSCT from donors without prior SARS‐CoV‐2 infection as group 0 (n = 194). Transplants from donors with different SARS‐CoV‐2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft‐versus‐host disease (aGvHD), grade II–IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III–IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II–IV (hazard ratio [HR] 2.307, p = 0.010) and grade III–IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS‐CoV‐2 infection were associated with higher incidences of aGvHD in transplants from related donors. [ABSTRACT FROM AUTHOR]

Introduction: Donation after circulatory death (DCD) donors are becoming an important source of organs for heart‐transplantation (HT), but there are limited data regarding their use in multiorgan‐HT. Methods: Between January 2020 and June 2023, we identified 87 adult multiorgan‐HTs performed using DCD‐donors [77 heart–kidney, 6 heart–lung, 4 heart–liver] and 1494 multiorgan‐HTs using donation after brain death (DBD) donors (1141 heart–kidney, 165 heart–lung, 188 heart–liver) in UNOS. For heart–kidney transplantations (the most common multiorgan‐HT combination from DCD‐donors), we also compared donor/recipient characteristics, and early outcomes, including 6‐month mortality using Kaplan–Meier (KM) and Cox hazards‐ratio (Cox‐HR). Results: Use of DCD‐donors for multiorgan‐HTs in the United States increased from 1% in January to June 2020 to 12% in January–June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart–kidney transplantations, recipients of DCD heart–kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06% vs. 69.59%) and had lower inotrope use (22.08% vs. 43.30%), lower IABP use (2.60% vs. 26.29%), but higher durable CF‐LVAD use (19.48% vs. 12.97%), all p < 0.01. Compared to DBD‐donors, DCD‐donors used for heart–kidney transplantations were younger [28(22–34) vs. 32(25–39) years, p = 0.004]. Recipients of heart–kidney transplantations from DCD‐donors and DBD‐donors had similar 6‐month survival using both KM analysis, and unadjusted and adjusted Cox‐HR models, including in propensity matched cohorts. Rates of PGF and in‐hospital outcomes were also similar. Conclusions: Use of DCD‐donors for multiorgan‐HTs has increased rapidly in the United States and early outcomes of DCD heart–kidney transplantations are promising. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI‐D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI‐D in pediatric heart transplant recipients. Methods: We retrospectively identified all pediatric first‐time, single‐organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI‐D, and unadjusted time‐to‐event analyses were used to determine the association between AKI‐D and survival free of kidney failure. Results: Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI‐D with median time from transplant to dialysis initiation of 6 days (IQR 3–13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04–1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI‐D, whereas patient demographics and pretransplant kidney function were not associated with AKI‐D. AKI‐D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure. Conclusions: The incidence of AKI‐D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI‐D even in adjusted models. Further research is needed to improve the prediction and management of AKI‐D in this population. [ABSTRACT FROM AUTHOR]

Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease. [ABSTRACT FROM AUTHOR]

In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, p = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, p = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, p = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) is the only curative therapy for adult T‐cell leukaemia/lymphoma (ATL). Specific HLAs are associated with outcomes of immunotherapy and allo‐HSCT. We hypothesised that individual HLAs would affect the clinical outcomes of ATL patients after allo‐HSCT. Using data from a Japanese registry, we retrospectively analysed 829 patients with ATL who received transplants from HLA‐identical sibling donors or HLA‐A, ‐B, ‐C or ‐DRB1 allele‐matched unrelated donors between 1996 and 2015. We evaluated the overall mortality risk of HLA‐A, ‐B and ‐DR antigens with frequencies exceeding 3%. Outcomes were compared between transplants with or without specific HLA antigens. Of the 25 HLAs, two candidates were identified but showed no statistically significant differences by multiple comparison. HLA‐B62 was associated with a lower risk of mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.51–0.90; p = 0.008), whereas HLA‐B60 was associated with a higher risk of mortality (HR, 1.64; 95% CI: 1.19–2.27; p = 0.003). In addition, HLA‐B62 was associated with a lower risk of transplant‐related mortality (TRM) (HR, 0.52; 95% CI: 0.32–0.85, p = 0.009), whereas HLA‐B60 was associated with a higher risk of grades III–IV acute graft‐versus‐host disease (HR, 2.63; 95% CI: 1.62–4.27; p < 0.001). Neither HLA influenced relapse. The higher risk of acute GVHD in HLA‐B60‐positive patients and the lower risk of TRM in HLA‐B62‐positive patients were consistent with previously obtained results from patients with other haematological malignancies. Consideration of HLA in ATL patients may help to predict risk and outcomes after allo‐HSCT. [ABSTRACT FROM AUTHOR]

Background: CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2–4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target. Study design and Methods: In this retrospective, single‐center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft‐versus‐host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes. Results: There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85–1.22), relapse (aRR = 1.10, 95% CI = 0.85–1.42), or overall survival by Kaplan–Meier analysis (p =.44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II–IV, aRR = 1.18 grades III–IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 =.073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132). Discussion: We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction. [ABSTRACT FROM AUTHOR]

Background and hypothesis: Frailty has emerged as an important factor in the pre-transplant evaluation process as studies have shown that it is associated with increased waitlist mortality, lower rates of transplant listing, and higher rates of delisting. There have not been many studies on frailty in elderly pre-transplant patients. In this study, we determined the common frailty phenotypes in an elderly population, and its effects on transplant success. Methods: Over a 3-year period, frailty was determined for all patients evaluated at our center. Patient characteristics were summarized using descriptive statistics, overall and by level of frailty. Differences in patient characteristics by level of frailty were assessed for statistical significance using analysis of variance for age and chi-square or Fisher's exact test. Transplant outcomes such as listing success, transplant rates and post-transplant outcomes were tied to initial frailty assessments as well as the changes in frailty over time. Results: A total of 375 patients were evaluated over the study period. The mean age was 64±9 years. African American patients were less likely to be frail. After adjusting for age and race, the most significant predictors of listing were the walk test (aOR: 0.42, 95 % CI: 0.22–0.79) and physical activity (aOR: 0.45, 95 % CI: 0.28–0.74). A total of 30 patients (8 %) with a pre-listing frailty evaluation died prior to transplantation. Frail walk test and physical activity assessment led to a 2-fold increase in pre-transplant mortality (7 % vs 17 %; 6 % vs 13 %). Conclusion: Our study is the first to focus on a purely geriatric population and shows the importance of frailty on listing success, transplant rates and mortality prior to listing. These data point to the need for the development of tools to target frailty as a guide for improving transplant success in elderly patients.

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

Management of patients with posterior urethral valves (PUV) is commonplace for many pediatric urologists, however adult providers may be far less familiar with this diagnosis, its management and long-term ramifications. As urologic management of these patients has evolved, clinical outcomes have substantially improved with many more patients now surviving into adulthood. These patients remain at increased risk of morbidity due to their condition and therefore are likely to benefit from long term follow-up with adult providers. In this review we analyze the psychosocial impacts of PUV on adults, evaluate long term transplant outcomes in PUV patients and discuss effective clinical management strategies of bladder dysfunction in adult PUV patients. A retrospective literature review was performed using the MEDLINE (Pubmed) electronic database using key words such as "posterior urethral valve", "quality of life", "sexual function", "transplant outcomes", "bladder dysfunction", "mitrofanoff" etc. to identify relevant studies. Generally, the quality of life of PUV patients is good, those suffering from renal insufficiency or lower urinary tract symptoms, specifically incontinence, appear to be a group that may benefit from more intensive follow-up. Good long-term kidney transplant (KT) function and survival can be achieved in patients with PUV. Rigorous management to optimize bladder function and close follow-up, are key for long term graft survival after KT. The chronicity of PUV warrants adult providers to be not only well versed in the pathophysiology of the disease, but well prepared to care for these patients as they transition into adulthood. Additional studies addressing psychosocial, clinical and transplant outcomes of adults with PUV are necessary to develop optimal long-term follow-up regimens for these patients. [ABSTRACT FROM AUTHOR]

BackgroundChildren undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed.MethodsSingle center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes.ResultsProphylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p

In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75–1.33, p = 0.99, liver; HR 0.92, 95% CI 0.66–1.28, p = 0.61, pancreas: HR 1.16; 95% CI 0.16–8.68, p = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.

Background: Early in the COVID-19 pandemic, positive COVID-19 status often disqualified potential organ donors due to perceived risks, despite limited evidence. Subsequent studies have clarified that the COVID-19 status of donors, particularly when incidental and not the cause of death, does not adversely affect non-lung transplant outcomes. This study quantifies the potential loss of eligible organ donors and the corresponding impact on organ availability during the initial phase of the pandemic. Methods: In this retrospective analysis, we examined deceased donor referrals to a major organ procurement organization from June 2020 to January 2022. Referrals were categorized as All Referrals, Medically Ruled Out (MRO), or Procured Donors (PD). We used Chi-square tests for categorical comparisons and logistic regression to model additional donors and organs, contrasting COVID-negative and positive cases within age-matched cohorts. Results: Among 9478 referrals, 23.4 % (2221) were COVID-positive. Notably, COVID-positive referrals had a substantially higher MRO rate (80.6 % vs. 29.6 %, p

Combined liver–kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli’s disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients.

Key Clinical Message: Proper diagnosis and treatment of vascular stenosis which is a possible complication of renal transplant is important in improving patients' quality of life and prognosis. One known consequence among recipients of renal transplants is graft renal artery stenosis. Early identification and therapy are crucial to avoid graft malfunction and the serious consequences that might arise due to elevated hypertension in several organs. We report a rare case of transplant renal artery stenosis in a mid‐aged woman who presented with edema, hypertension, and increased creatinine 2 months after kidney transplant. The patient had normal renal arterial resistive index (RI) and perfusion index (PI), and there was only a modest decrease in perfusion on duplex ultrasound. Following the patient's renal stenting treatment, angiographic resolution was observed. After 14 days of regulated blood pressure following renal artery stenting, she was discharged from the hospital with her edema resolved. Considering complications in patients with clinical manifestations such as hypertension resistant to treatment and graft dysfunction, vascular stenosis is a notable issue to consider even in the context of normal renal arterial RI, PI, and duplex ultrasound. Proper diagnosis and treatment are of importance to improve patients' quality of life and prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Kidney transplantation is the optimal treatment option for most patients with end-stage kidney disease given the significantly lower morbidity and mortality rates compared to remaining on dialysis. Rejection and graft failure remain common in transplant recipients with limited improvement in long-term transplant outcomes despite therapeutic advances. There is an unmet need in the development of non-invasive biomarkers that specifically monitor graft function and predict transplant pathologies that affect outcomes. Despite the potential of proteomic investigatory approaches, up to now, no candidate biomarkers of sufficient sensitivity or specificity have translated into clinical use. The aim of this review was to collate and summarise protein findings and protein pathways implicated in the literature to date, and potentially flag putative biomarkers worth validating in independent patient cohorts. Methods This review followed the Joanna Briggs’ Institute Methodology for a scoping review. MedlineALL, Embase, Web of Science Core Collection, Scopus and Google Scholar databases were searched from inception until December 2022. Abstract and full text review were undertaken independently by two reviewers. Data was collated using a pre-designed data extraction tool. Results One hundred one articles met the inclusion criteria. The majority were single-centre retrospective studies of small sample size. Mass spectrometry was the most used technique to evaluate differentially expressed proteins between diagnostic groups and studies identified various candidate biomarkers such as immune or structural proteins. Discussion Putative immune or structural protein candidate biomarkers have been identified using proteomic techniques in multiple sample types including urine, serum and fluid used to perfuse donor kidneys. The most consistent findings implicated proteins associated with tubular dysfunction and immunological regulatory pathways such as leukocyte trafficking. However, clinical translation and adoption of candidate biomarkers is limited, and these will require comprehensive evaluation in larger prospective, multicentre trials.

Background: Restrictive cardiomyopathy (RCM) comprises diverse etiologies with overall poor prognosis. Emerging therapies have significantly impacted some of these entities. However, these therapies may have limited impact in the end-stages and have only recently become available. We sought to assess outcomes before and after transplant in the RCM population stratified into 3 distinct time periods from the recent era. Methods: Retrospective analysis of the United Network of Organ Sharing registry (n = 62,709) for all patients transplanted between 1987 and March 1, 2022, were stratified by RCM status with 1157 patients with RCM. Populations were grouped temporally into classic (1987-2000), contemporary (2000-2013), and current (2014-2022) eras. Multiorgan and repeat transplants were excluded from the analysis. Baseline demographics, listing status, hemodynamics, donor information, and life support methods were compared using Kruskal-Wallis and Pearson’s tests. Longitudinal survival was assessed via Kaplan-Meier survival analysis. Univariate and multivariate analyses using Cox modeling and competing outcomes analyses were performed. Results: RCM patients were older, female, with older donors and longer ischemic times (p

Key Clinical Message Proper diagnosis and treatment of vascular stenosis which is a possible complication of renal transplant is important in improving patients' quality of life and prognosis. Abstract One known consequence among recipients of renal transplants is graft renal artery stenosis. Early identification and therapy are crucial to avoid graft malfunction and the serious consequences that might arise due to elevated hypertension in several organs. We report a rare case of transplant renal artery stenosis in a mid‐aged woman who presented with edema, hypertension, and increased creatinine 2 months after kidney transplant. The patient had normal renal arterial resistive index (RI) and perfusion index (PI), and there was only a modest decrease in perfusion on duplex ultrasound. Following the patient's renal stenting treatment, angiographic resolution was observed. After 14 days of regulated blood pressure following renal artery stenting, she was discharged from the hospital with her edema resolved. Considering complications in patients with clinical manifestations such as hypertension resistant to treatment and graft dysfunction, vascular stenosis is a notable issue to consider even in the context of normal renal arterial RI, PI, and duplex ultrasound. Proper diagnosis and treatment are of importance to improve patients' quality of life and prognosis.

Background: Kidney transplantation is the optimal treatment option for most patients with end-stage kidney disease given the significantly lower morbidity and mortality rates compared to remaining on dialysis. Rejection and graft failure remain common in transplant recipients with limited improvement in long-term transplant outcomes despite therapeutic advances. There is an unmet need in the development of non-invasive biomarkers that specifically monitor graft function and predict transplant pathologies that affect outcomes. Despite the potential of proteomic investigatory approaches, up to now, no candidate biomarkers of sufficient sensitivity or specificity have translated into clinical use. The aim of this review was to collate and summarise protein findings and protein pathways implicated in the literature to date, and potentially flag putative biomarkers worth validating in independent patient cohorts. Methods: This review followed the Joanna Briggs' Institute Methodology for a scoping review. MedlineALL, Embase, Web of Science Core Collection, Scopus and Google Scholar databases were searched from inception until December 2022. Abstract and full text review were undertaken independently by two reviewers. Data was collated using a pre-designed data extraction tool. Results: One hundred one articles met the inclusion criteria. The majority were single-centre retrospective studies of small sample size. Mass spectrometry was the most used technique to evaluate differentially expressed proteins between diagnostic groups and studies identified various candidate biomarkers such as immune or structural proteins. Discussion: Putative immune or structural protein candidate biomarkers have been identified using proteomic techniques in multiple sample types including urine, serum and fluid used to perfuse donor kidneys. The most consistent findings implicated proteins associated with tubular dysfunction and immunological regulatory pathways such as leukocyte trafficking. However, clinical translation and adoption of candidate biomarkers is limited, and these will require comprehensive evaluation in larger prospective, multicentre trials. [ABSTRACT FROM AUTHOR]

Background: Infections by multidrug‐resistant organisms (MDRO) are a major hurdle in hematopoietic stem‐cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in‐turn leads to transmigration of gut bacteria and sepsis. Pre‐transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre‐transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. Methods: A single‐center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre‐transplant stool/throat surveillance cultures, and their impact on overall 100‐day and post‐100‐day to 6‐month post‐transplant survival were analyzed. Results: Sixty‐four patients were included in the study. Pre‐transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase‐producing genes (mainly New Delhi metallo‐beta‐lactamase‐1 [NDM‐1] and oxacillinase‐48 [OXA‐48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri‐engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All‐cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post‐HSCT, respectively. The 100‐day and post‐100‐day all‐cause mortality rates were higher in patients with Gram‐negative MDRO bloodstream infections (p <.012 and <.008, respectively). Conclusion: MDRO infections can adversely affect HSCT outcomes. Pre‐transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes. [ABSTRACT FROM AUTHOR]

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a frequent adverse outcome following liver transplantation (LT) with a multifactorial etiology. It is critical to identify modifiable risk factors to mitigate the risk. One key area of interest is the role of intraoperative hypotension, which remains relatively unexplored in liver transplant cohorts. Methods: This was a retrospective observational cohort study of 1292 adult patients who underwent LT (between 2009 and 2019). Multivariable logistic regression analysis was used to explore the association between intraoperative hypotension, quantified by time duration (in min) under various mean arterial pressure (MAP) thresholds, and the primary outcome of early postoperative AKI according to the KDIGO criteria. Results: AKI occurred in 40% of patients and was independently associated with greater than 20 min spent below MAP thresholds of 55 mm Hg (adjusted OR = 1.866; 95% CI = 1.037–3.44; P = 0.041) and 50 mm Hg (adjusted OR = 1.801; 95% CI = 1.087–2.992; P = 0.023). Further sensitivity analyses demonstrated that the association between intraoperative hypotension and postoperative AKI was accentuated after restricting the analysis to patients with a normal preoperative renal function. Conclusions: Prolonged (>20 min) intraoperative hypotension (below a MAP of 55 mm Hg) was independently associated with AKI following LT, after adjusting for several known confounders. [ABSTRACT FROM AUTHOR]

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute’s Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency’s qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.

BackgroundWe sought to understand how safety culture may evolve during disruption, by using the COVID-19 pandemic as an example, to identify vulnerabilities in the system that could impact patient outcomes.MethodsA cross-sectional analysis of transplant personnel at a high-volume transplant center was conducted using the Safety Attitudes Questionnaire (SAQ). Survey responses were scaled and evaluated pre- and post-COVID-19 (2019 and 2021).ResultsTwo-hundred and thirty-eight responses were collected (134 pre-pandemic and 104 post-pandemic). Represented organ groups included: kidney (N = 89;38%), heart (N = 18;8%), liver (N = 54;23%), multiple (N = 66;28%), and other (N = 10;4%). Responders primarily included nurses (N = 75;34%), administration (N = 50;23%), and physicians (N = 24;11%). Workers had high safety, job satisfaction, stress recognition, and working conditions satisfaction (score >75) both before and after the pandemic with overlapping responses across both timepoints. Stress recognition, safety, and working conditions improved post-COVID-19, but teamwork, job satisfaction, and perceptions of management were somewhat negatively impacted (all p > 0.05).ConclusionsDespite the serious health care disruptions induced by the pandemic, high domain ratings were notable and largely maintained in a high-volume transplant center. The SAQ is a valuable tool for healthcare units and can be used in longitudinal assessments of transplant culture of safety as a component of quality assurance and performance improvement initiatives.

BackgroundDonation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization and patient and allograft outcomes. Given the increasing US experience with TA-NRP DCD recovery, we evaluated outcomes of DCD liver allografts transplanted after TA-NRP.MethodsLiver allografts transplanted from DCD donors after TA-NRP were identified from 5/1/2021 to 1/31/2022 across 8 centers. Donor data included demographics, functional warm ischemic time (fWIT), total warm ischemia time (tWIT) and total time on TA-NRP. Recipient data included demographics, model of end stage liver disease (MELD) score, etiology of liver disease, PNF, cold ischemic time (CIT), liver function tests, intensive care unit (ICU) and hospital length of stay (LOS), post-operative transplant related complications.ResultsThe donors' median age was 32 years old and median BMI was 27.4. Median fWIT was 20.5 min; fWIT exceeded 30 min in two donors. Median time to initiation of TA-NRP was 4 min and median time on bypass was 66 min. The median recipient listed MELD and MELD at transplant were 22 and 21, respectively. Median allograft CIT was 292 min. The median length of follow up was 257 days. Median ICU and hospital LOS were 2 and 7 days, respectively. Three recipients required management of anastomotic biliary strictures. No patients demonstrated IC, PNF or required re-transplantation.ConclusionLiver allografts from TA-NRP DCD donors demonstrated good early allograft and recipient outcomes.

Supplemental Digital Content is Available in the Text. Purpose: Functional recovery after lung transplant is crucial to long-term outcomes. Despite rehabilitation, few reach the threshold of healthy function. The purpose of this study was to assess the potential benefit of rehabilitation in the Center of Life for Thoracic Transplant (COLTT) program by (1) measuring time to functional recovery, (2) identifying factors associated with functional recovery, (3) examining program outcomes, and (4) examining COLTT impact on unplanned hospital readmission. Methods: The study retrospectively examined 105 patients in COLTT after hospital discharge. Functional measures collected at enrollment and completion included 6-minute walk distance, walking speed, 1-minute sit-to-stand test, and single-leg stance. Demographic and hospital stay data were examined for associations between time to achieve COLTT goals and readmissions. Results: The median number of visits in COLTT was 18 (9–53). Significant functional gains were made across all outcome measures and near thresholds for healthy individuals. Age, hospital and intensive care unit (ICU) length of stay (LOS), lung disease type, and ventilation time were significantly associated with COLTT visits. The 30-day hospital readmission free rate after hospital discharge was 71.4%. Conclusions: Healthy adult functional outcomes were achieved in 18 visits. Age, hospital and ICU LOS, lung disease type, and prolonged ventilation are associated with functional recovery. [ABSTRACT FROM AUTHOR]

There is a paucity of data on heart transplantation (HT) using COVID-19 donors. This study investigated COVID-19 donor use, donor and recipient characteristics, and early post-HT outcomes. Between May 2020 and June 2022, study investigators identified 27,862 donors in the United Network for Organ Sharing, with 60,699 COVID-19 nucleic acid amplification testing (NAT) performed before procurement and with available organ disposition. Donors were considered "COVID-19 donors" if they were NAT positive at any time during terminal hospitalization. These donors were subclassified as "active COVID-19" (aCOV) donors if they were NAT positive within 2 days of organ procurement, or "recently resolved COVID-19" (rrCOV) donors if they were NAT positive initially but became NAT negative before procurement. Donors with NAT-positive status >2 days before procurement were considered aCOV unless there was evidence of a subsequent NAT-negative result ≥48 hours after the last NAT-positive result. HT outcomes were compared. During the study period, 1,445 "COVID-19 donors" (COVID-19 NAT positive) were identified; 1,017 of these were aCOV, and 428 were rrCOV. Overall, 309 HTs used COVID-19 donors, and 239 adult HTs from COVID-19 donors (150 aCOV, 89 rrCOV) met study criteria. Compared with non-COV, COVID-19 donors used for adult HT were younger and mostly male (∼80%). Compared with HTs from non-COV donors, recipients of HTs from aCOV donors had increased mortality at 6 months (Cox HR: 1.74; 95% CI: 1.02-2.96; P = 0.043) and 1 year (Cox HR: 1.98; 95% CI: 1.22-3.22; P = 0.006). Recipients of HTs from rrCOV and non-COV donors had similar 6-month and 1-year mortality. Results were similar in propensity-matched cohorts. In this early analysis, although HTs from aCOV donors had increased mortality at 6 months and 1 year, HTs from rrCOV donors had survival similar to that seen in recipients of HTs from non-COV donors. Continued evaluation and a more nuanced approach to this donor pool are needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: We compared posttransplant outcomes between patients bridged from temporary mechanical circulatory support to durable left ventricular assist device before transplant (bridge-to-bridge [BTB] strategy) and patients bridged from temporary mechanical circulatory support directly to transplant (bridge-to-transplant [BTT] strategy). Methods: We identified adult heart transplant recipients in the Organ Procurement and Transplantation Network database between 2005 and 2020 who were supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device as a BTB or BTT strategy. Kaplan-Meier survival analysis and Cox regressions were used to assess 1-year, 5-year, and 10-year survival. Posttransplant length of stay and complications were compared as secondary outcomes. Results: In total, 201 extracorporeal membrane oxygenation (61 BTB, 140 BTT), 1385 intra-aortic balloon pump (460 BTB, 925 BTT), and 234 temporary ventricular assist device (75 BTB, 159 BTT) patients were identified. For patients supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device, there were no differences in survival between BTB and BTT at 1 and 5 years posttransplant, as well as 10 years posttransplant even after adjusting for baseline characteristics. The extracorporeal membrane oxygenation BTB group had greater rates of acute rejection (32.8% vs 13.6%; P = .002) and lower rates of dialysis (1.6% vs 21.4%; P

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major strategy to cure patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate whether isolated flow cytometry (FCM)-positive central nervous system (CNS) involvement before allo-HSCT is clinically significant. Methods: The effects of isolated FCM-positive CNS involvement prior to transplantation on the outcomes of 1406 ALL patients with complete remission (CR) were retrospectively investigated. Results: Patients were classified into isolated FCM-positive CNS involvement (n=31), cytology-positive CNS involvement (n = 43), and negative CNS involvement (n = 1332) groups. Among the three groups, the 5-year cumulative incidence of relapse (CIR) values were 42.3%, 48.8%, and 23.4%, respectively (P<0.001). The 5-year leukemia-free survival (LFS) values were 44.7%, 34.9%, and 60.8%, respectively (P<0.001). Compared with the negative CNS group (n=1332), the 5-year CIR of the pre-HSCT CNS involvement group (n=74) was higher (46.3% vs. 23.4%, P<0.001], and the 5-year LFS was inferior (39.1% vs. 60.8%, P<0.001). Multivariate analysis indicated that four variables, Tcell ALL, in second complete remission or beyond (CR2+) at HSCT, pre-HSCT measurable residual disease positivity, and pre-HSCT CNS involvement, were independently associated with a higher CIR and inferior LFS. A new scoring system was developed using the following four variables: low-risk, intermediate-risk, high-risk, and extremely high-risk groups. The 5-year CIR values were 16.9%, 27.8%, 50.9%, and 66.7%, respectively (P<0.001), while the 5-year LFS values were 67.6%, 56.9%, 31.0%, and 13.3%, respectively (P<0.001). Conclusion: Our results suggest that ALL patients with isolated FCM-positive CNS involvement are at a higher risk of recurrence after transplantation. Patients with pre-HSCT CNS involvement had higher CIR and inferior survival outcomes. [ABSTRACT FROM AUTHOR]

Aims: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post‐heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non‐CHD patients before (Era‐1) and after (Era‐2) pediatric heart allocation policy implementation. Methods: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era‐1 and Era‐2. Results: 5551 patients were listed for HT, of whom 2447(44%) were in Era‐1 and 3104(56%) were in Era‐2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era‐2, whereas the number of non‐CHD patients listed as status 1A decreased, but status 1B increased. In Era‐2 compared to Era‐1, both temporary (1% to 4%, p <.001) and durable VAD (13.6% to 17.8%, p <.001) utilization increased, and the transplantation rate per 100‐patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p =.06), whereas for non‐CHD patients it decreased from 61 to 54 days (p <.001). Adjusted 90‐day WL survival increased from 84% to 88%, p =.016 in CHD, but there was no significant change in non‐CHD patients (p =.57). There was no significant difference in 1‐year post‐HT survival in CHD and non‐CHD patients between Era‐1 and Era‐2. Conclusions: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non‐CHD cohort, and 90‐day WL survival probability improved in children with CHD without significant change in 1‐year post‐HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post‐HT survival. [ABSTRACT FROM AUTHOR]

The current understanding of the safety of heart transplantation from COVID-19+ donors is uncertain. Preliminary studies suggest that heart transplants from these donors may be feasible. We analyzed 1-year outcomes in COVID-19+ donor heart recipients using 1:3 propensity matching. The OPTN database was queried for adult heart transplant recipients between 1 January 2020 and 30 September 2022. COVID-19+ donors were defined as those who tested positive on NATs or antigen tests within 21 days prior to procurement. Multiorgan transplants, retransplants, donors without COVID-19 testing, and recipients allocated under the old heart allocation system were excluded. A total of 7211 heart transplant recipients met the inclusion criteria, including 316 COVID-19+ donor heart recipients. Further, 290 COVID-19+ donor heart recipients were matched to 870 COVID-19− donor heart recipients. Survival was similar between the groups at 30 days (p = 0.46), 6 months (p = 0.17), and 1 year (p = 0.07). Recipients from COVID-19+ donors in the matched cohort were less likely to experience postoperative acute rejection prior to discharge (p = 0.01). National COVID-19+ donor heart usage varied by region: region 11 transplanted the most COVID-19+ hearts (15.8%), and region 6 transplanted the fewest (3.2%). Our findings indicate that COVID-19+ heart transplantation can be performed with safe early outcomes. Further analyses are needed to determine if long-term outcomes are equivalent between groups.

Background The prevalence of obesity among kidney transplant recipients is rising. We sought to determine the association between recipient body mass index (BMI) and post-transplant complications. Methods Single-center, retrospective cohort study of all adult kidney transplant recipients from 2004 to 2020. Recipients were stratified into four BMI categories: normal-weight (BMI 18.5–24.9 kg/m2, n  = 1020), overweight (BMI 25–29.9 kg/m2, n  = 1002), moderately obese (BMI 30–34.9 kg/m2, n  = 510) and severely-to-morbidly obese (BMI ≥35 kg/m2, n  = 274). Logistic regression was used to estimate the association between BMI category and surgical site infections (SSIs). Results Recipients with BMI ≥35 kg/m2 had significantly higher rates of SSIs (P  < .0001) compared with recipients in all other categories. On multivariable analysis, recipients with BMI ≥35 kg/m2 had increased odds of SSIs compared with normal-weight recipients [odds ratio (OR) 3.34, 95% confidence interval (CI) 1.55–7.22, P  = .022). On multivariable and Kaplan–Meier analyses, no BMI groups demonstrated increased odds for death-censored graft failure. Conclusion Severe obesity in kidney transplant recipients is associated with increased SSIs, but not kidney allograft failure. [ABSTRACT FROM AUTHOR]

Obesity has become a global epidemic, adding to the burden of chronic diseases and disabilities. Metabolic syndrome, especially obesity, is a significant risk factor for nonalcoholic fatty liver disease, which is the most common indication for liver transplant (LT). The prevalence of obesity among the LT population is growing. Obesity increases the necessity of LT by playing a role in the development of nonalcoholic fatty liver disease, decompensated cirrhosis, and hepatocellular carcinoma, and it can also coexist with other diseases requiring LT. Therefore, LT teams must identify key aspects required to manage this high-risk population, but there are currently no defined recommendations for managing obesity in LT candidates. Although body mass index is often used to assess the weight of patients and classify them as overweight or obese, this measure may be inaccurate to use in patients with decompensated cirrhosis, as fluid overload or ascites can significantly add to the weight of patients. Diet and exercise remain the cornerstone of obesity management. Supervised weight loss before LT, without worsening frailty and sarcopenia, may be beneficial in reducing surgical risks and improving long-term LT outcomes. Bariatric surgery is another effective treatment for obesity, with sleeve gastrectomy currently conferring the best outcomes in LT recipients. However, evidence supporting the timing of bariatric surgery is lacking. Long-term patient and graft survival data in individuals with obesity following LT are scarce. Class 3 obesity (body mass index ≥40) further complicates the treatment of this patient population. This article discusses the impact of obesity on the outcome of LT. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames.200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation.The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration.Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival. [ABSTRACT FROM AUTHOR]

[Display omitted] • High tacrolimus exposure within the initial weeks post-HSCT can lead to a reduced overall survival (p < 0.01) and increased risk of chronic GVHD (p < 0.0001). • Elevated tacrolimus levels are associated with decreased incidence of early transplant-related events (p < 0.01), including acute GVHD and reduced post-transplant infections (p < 0.0001). • In patients younger than two years, the C 0 /D ratio is significantly higher than in oldest children. Acute graft-versus-host disease (GVHD) is a common life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), ranking as the second leading cause of death among recipients, surpassed only by disease relapse. Tacrolimus is commonly used for GVHD prophylaxis, but achieving therapeutic blood levels is challenging, particularly in pediatrics, due to the narrow therapeutic window and the high interindividual variability. The retrospective study conducted at IRCCS "Burlo Garofolo" in Italy aimed to assess the impact of early post-HSCT tacrolimus levels on transplant-related outcomes in pediatric recipients. The population pharmacokinetic model (POP/PK) was set up to describe tacrolimus pharmacokinetics. Elevated tacrolimus (>12–15 ng/ml) levels within the initial weeks post-HSCT are associated with reduced post-transplant infections (p < 0.0001) and decreased incidence of early transplant-related events (p < 0.01), including a lower incidence of acute GVHD (p < 0.05 on day 0). High tacrolimus exposure can lead to an increased risk of chronic GVHD (p < 0.0001) and reduced overall survival (p < 0.01). Personalized dosing and therapeutic monitoring of tacrolimus are crucial to ensure optimal outcomes. POP/PK could help achieve this goal, giving us a model by which we can balance immunosuppression while looking at the patient's general well-being and providing the necessary treatment. [ABSTRACT FROM AUTHOR]

BackgroundAlthough individuals classified as nonresident aliens, including undocumented immigrants, are entitled to receive emergency dialysis in the United States regardless of their ability to pay, most states do not provide them with subsidized care for maintenance dialysis or kidney transplantation. We explored whether nonresident aliens have similar outcomes to US citizens after receiving kidney transplants covered by Medicaid, a joint federal and state health insurance program.Study designRetrospective observational cohort study.Setting & participantsAll adult Medicaid patients in the US Renal Data System who received their first kidney transplant from 1990 to 2011.PredictorCitizenship status, categorized as US citizen, nonresident alien, or permanent resident.OutcomeAll-cause transplant loss.MeasurementsHRs and 95% CIs estimated by applying Cox proportional hazards frailty models with transplantation center as a random effect.ResultsOf 10,495 patients, 8,660 (82%) were US citizens, 1,489 (14%) were permanent residents, and 346 (3%) were nonresident aliens, whom we assumed were undocumented immigrants. Nonresident aliens were younger, healthier, receiving dialysis longer, and more likely to have had a living donor. 71% underwent transplantation in California, and 61% underwent transplantation after 2005. Nonresident aliens had a lower unadjusted risk for transplant loss compared with US citizens (HR, 0.48; 95% CI, 0.35-0.65). Results were attenuated but still significant when adjusted for demographics, comorbid conditions, dialysis, and transplant-related factors (HR, 0.67; 95% CI, 0.46-0.94).LimitationsCitizenship status was self-reported, possible residual confounding.ConclusionsOur study suggests that the select group of insured nonresident aliens who undergo transplantation with Medicaid do just as well as US citizens with Medicaid. Policymakers should consider expanding coverage for kidney transplantation in nonresident aliens, including undocumented immigrants, given the associated high-quality outcomes in these patients.

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: Studies evaluating the prevalence and impact of recurrent rejection (RR) in pediatric heart transplant (HT) are sparse., Objectives: The purpose of this study was to describe prevalence and impact of RR on cardiac allograft vasculopathy (CAV) and graft loss after pediatric HT., Methods: Data on HT from January 1, 2000, to June 30, 2020, in the Pediatric Heart Transplant Society database were included. Freedom from RR (≥2 rejection episodes) was compared by era (early: 2000-2009; current: 2010-2020). Outcomes for children experiencing RR were compared with those experiencing 0 or 1 rejection episodes and by type of RR (antibody-mediated rejection [AMR], acute cellular rejection [ACR], mixed [ACR/AMR])., Results: Of 6,342 HT recipients, 1,035 (17%) experienced RR. In the current era, pediatric HT recipients were less likely to experience RR (P < 0.001). Freedom from CAV was similar for those experiencing RR to those experiencing 0 or 1 episode (96.6% vs 95.3% vs 96.6%); and similar regardless of the type of RR (AMR, ACR, or mixed) (65.5% vs 82.9% vs 100%) (P > 0.05). Freedom from graft loss was significantly lower for those experiencing RR to those experiencing 0 or 1 episode (56.3% vs 72.3% vs 82.3%) and lower for those experiencing recurrent mixed rejection or recurrent AMR compared with those experiencing recurrent ACR (65.3% vs 50% vs 81.8%). Black children experiencing RR subsequently had lower freedom from CAV and graft loss than White children (P < 0.05 for all)., Conclusions: Although prevalence of RR has decreased, children experiencing RR are at greatly increased risk for losing their graft, particularly those who have recurrent mixed or antibody-mediated rejection., Competing Interests: Funding Support and Author Disclosures Dr Amdani is the site principal investigator for a multicenter study led by the University of Michigan and has received no salary support. Dr Kirklin has received royalties related to IT software development in registry database design developed at and licensed from the University of Alabama at Birmingham; has received payments from Kirklin Solutions Co database development and analytics and partial salary support in his role as Director of the data center for STS Intermacs/Pedimacs Registries; and serves as Chair of the Data and Safety Monitoring Board for Xeltis cardiac conduit clinical trial and Chair of the Data and Safety Monitoring Board for Carmat TAH clinical trial. Dr Lal is a site PI for the TEAMMATE trial, with grant funding from the United States Department of Defense (W81XWH-17-1-0532). Dr Edelson has received grant support from Enduring Hearts and the University of Pennsylvania McCabe Award; and has received honoraria from Abbott Technologies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A previous cancer diagnosis can preclude patients from consideration for solid organ transplantation. Statistical models may improve candidate selection. We fitted statistical cure models and estimated 5-year cancer-specific survival (5yCSS) for colorectal cancer patients in the United States using registry data. The median cure probability at cancer diagnosis for patients in the general population was 0.67. Among 956 colorectal cancer patients who underwent solid organ transplantation, the median time since diagnosis was 6.3 years and the median 5yCSS at transplantation was 0.96. Patients with a 5yCSS below 0.90 had increased posttransplant cancer-specific mortality (hazard ratio 3.31, 95% CI 1.52-7.21). Compared with recently published guidelines, our models suggested shorter wait times for some groups of colorectal cancer patients (eg, stage IIA cancers) and longer wait times for others (stages IIB, IIIB, IIIC, IV). In conclusion, colorectal cancer patients undergoing solid organ transplantation had excellent prognoses, reflecting selection incorporating existing guidelines and clinical judgment. Nonetheless, 5yCSS probabilities estimated from cure models offer additional prognostic information for patients considered for transplantation and identify situations where current guidelines might be revised. We developed a web-based tool for clinicians to calculate 5yCSS probabilities for use in transplant evaluation for individual colorectal cancer patients (https://dceg.cancer.gov/tools/risk-assessment/calculator-of-colorectal-cancer-survival-probability)., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Published by Elsevier Inc.)

Objective: To compare the outcomes of livers donated after circulatory death (DCD) and undergoing either in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) with livers undergoing static cold storage (SCS). Summary of Background Data: DCD livers are associated with increased risk of primary nonfunction, poor function, and nonanastomotic strictures (NAS), leading to underutilization. Methods: A single center, retrospective analysis of prospectively collected data on 233 DCD liver transplants performed using SCS, NRP, or NMP between January 2013 and October 2020. Results: Ninety-seven SCS, 69 NRP, and 67 NMP DCD liver transplants were performed, with 6-month and 3-year transplant survival (graft survival non-censored for death) rates of 87%, 94%, 90%, and 76%, 90%, and 76%, respectively. NRP livers had a lower 6-month risk-adjusted Cox proportional hazard for transplant failure compared to SCS (hazard ratio 0.30, 95% Confidence Interval 0.08–1.05, P = 0.06). NRP and NMP livers had a risk-adjusted estimated reduction in the mean model for early allograft function score of 1.52 (P < 0.0001) and 1.19 (P < 0.001) respectively compared to SCS. Acute kidney injury was more common with SCS (55% vs 39% NRP vs 40% NMP; P = 0.08), with a lower risk-adjusted peak-to-baseline creatinine ratio in the NRP (P = 0.02). No NRP liver had clinically significant NAS in contrast to SCS (14%) and NMP (11%, P = 0.009), with lower risk-adjusted odds of overall NAS development compared to SCS (odds ratio = 0.2, 95%CI 0.06–0.72, P = 0.01). Conclusion: NRP and NMP were associated with better early liver function compared to SCS, whereas NRP was associated with superior preservation of the biliary system. [ABSTRACT FROM AUTHOR]

Background: The impact of posttransplant red blood cell transfusion (RBCT) and their potential immunomodulatory effects on kidney transplant recipients are unclear. We examined the risks for adverse graft outcomes associated with post-kidney transplant RBCT. Methods: We conducted a retrospective cohort study of all adult kidney transplant recipients at The Ottawa Hospital from 2002 to 2018. The exposure of interest was receipt of an RBCT after transplant categorized as 1, 2, 3 to 5, and >5 RBC. Outcomes of interest were rejection and death-censored graft loss (DCGL). Cox proportional hazards models were used to calculate hazard ratios (HR) with RBCT as a time-varying, cumulative exposure. Results: Among 1258 kidney transplant recipients, 468 (37.2%) received 2373 total RBCTs, 197 (15.7%) had rejection and 114 (9.1%) DCGL. For the receipt of 1, 2, 3 to 5, and >5 RBCT, compared with individuals never transfused, the adjusted HRs (95% confidence interval [CI]) for rejection were 2.47 (1.62–3.77), 1.27 (0.77–2.11), 1.74 (1.00–3.05), and 2.23 (1.13–4.40), respectively; DCGL 2.32 (1.02–5.27), 3.03 (1.62–5.64), 7.50 (4.19–13.43), and 14.63 (8.32–25.72), respectively. Considering a time-lag for an RBCT to be considered an exposure before an outcome to limit reverse causation, RBCT was not associated with rejection; the HRs for DCGL attenuated but remained similar. RBCT was also associated with a negative control outcome, demonstrating possible unmeasured confounding. Conclusion: RBCT after kidney transplant is not associated with rejection, but may carry an increased risk for DCGL.

Introduction: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. Methods: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. Results: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). Conclusion: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

Background: The long-term benefits of conversion from calcineurin inhibitors (CNIs) to belatacept in kidney transplant recipients (KTr) are poorly documented. Methods: A single-center retrospective work to study first-time CNI to belatacept conversion as a rescue therapy [eGFR <30 ml/min/1.73m2, chronic histological lesions, or CNI-induced thrombotic microangiopathy (TMA)]. Patient and kidney allograft survivals, eGFR, severe adverse events, donor-specific antibodies (DSA), and histological data were recorded over 36 months after conversion. Results: We included N = 115 KTr. The leading cause for switching was chronic histological lesions with non-optimal eGFR (56.5%). Three years after conversion, patient, and deathcensored kidney allograft survivals were 88% and 92%, respectively, eGFR increased significantly from 31.5 ± 17.5 to 36.7 ± 15.7ml/min/1.73m2 (p < 0.01), the rejection rate was 10.4%, OI incidence was 5.2 (2.9-7.6) per 100 person-years. Older age was associated with death, eGFR was not associated with death nor allograft loss. No patient developed dnDSA at M36 after conversion. CNI-induced TMA disappeared in all cases without eculizumab use. Microvascular inflammation and chronic lesions remained stable. Conclusion: Post-KT conversion from CNIs to belatacept, as rescue therapy, is safe and beneficial irrespective of the switch timing and could represent a good compromise facing organ shortage. Age and eGFR at conversion should be considered in the decision whether to switch. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical characteristics, risk factors, and overall survival outcomes in adults with congenital heart disease (ACHD) bridged to transplantation with a ventricular assist device (VAD) versus no‐VAD. Methods: The study included 894 ACHD patients aged ≥18 years listed for primary heart transplantation between 2010 and 2019 from the United Network for Organ Sharing database. Primary outcomes were waitlist and 1‐year post‐transplant mortality between VAD and no‐VAD ACHD patients. Results: Of 894 ACHD patients included in the study, 91(10.1%) had VAD support at the time of listing. Patients who needed VAD support were mostly males, heavier, and had higher pulmonary artery pressure than the no‐VAD group at the listing. The overall waitlist mortality was 38% in the VAD group than 17% in the no‐VAD group (p < 0.01). ECMO use was associated with significantly higher mortality than either group. There was no significant difference in 1‐year post‐transplant mortality between VAD versus no‐VAD at the time of transplant (15% vs. 17%; p = 0.66). Multivariate regression analysis found that BMI <20 kg/m2 (hazard ratio (HR) 1.1; p = 0.01), bilirubin >2 mg/dl (HR 1.1; p = 0.03), creatinine >2 mg/dl (HR 1.3; p = 0.04) and ECMO at transplant (HR 1.4; p = 0.03) increased early post‐transplant mortality. Conclusions: The one‐year post‐transplant mortality rate was no different for ACHD patients that received VAD versus no‐VAD. These findings suggest that a VAD should be considered an option to support ACHD patients as a bridge to heart transplantation. [ABSTRACT FROM AUTHOR]