Transplantation最新文献

Background: Early extubation after liver transplantation can decrease cost and intensive care unit lengths of stay, but its adoption remains limited because of safety concerns. We assessed the feasibility and safety of early extubation at a liver transplant center with a high early extubation rate. We analyzed subgroups of high-risk patients, including high model for end-stage liver disease-sodium (MELD-Na) score, high intraoperative blood loss, and patients undergoing simultaneous liver-kidney transplantation.

Methods: We included all adult liver transplantations performed at a single center between June 2012 and July 2022. Patients were divided into 2 groups: (1) those extubated early (ie, in the operating room or within the first hour of intensive care unit admission) and (2) those who underwent delayed extubation. The primary outcome was reintubation within 48 h after early extubation. Rates of early extubation were analyzed separately for quartiles of MELD-Na score and intraoperative blood loss.

Results: Of 1555 patients, 969 (62%) were extubated early. Of these, 31 patients (3.2%) required mechanical ventilation within 48 h postoperatively: 11 patients (1.1%) were reintubated for respiratory failure and 20 (2.1%) remained intubated after reoperation. There was no difference in postoperative pneumonia between the groups (P = 0.059). Early extubation rates inversely correlated with the quartiles of MELD-Na score and estimated blood loss. In the highest quartile for MELD-Na (>34) and estimated blood loss (>5 L), 34% of patients were extubated early.

Conclusions: Early extubation of properly selected patients after liver transplantation is safe and associated with a low rate of reintubation, even among select groups of high-risk patients.

Background: The introduction of posttransplant cyclophosphamide (PTCy) for prophylaxis against graft-versus-host disease (GVHD) has led to an increase in the number of transplants from haploidentical donors. Accordingly, we aimed to understand the impact of HLA epitope mismatch on the outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) with prophylaxis against GVHD.

Methods: This retrospective study included 1037 patients who underwent their first HSCT for hematologic malignancies from haploidentical peripheral blood donors in a Japanese registry between 2011 and 2019. In total, 542 patients received PTCy and 495 received antithymocyte globulin-based GVHD prophylaxis.

Results: In patients with high-risk disease who received PTCy, higher class I Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-I) scores were associated with a significantly lower risk of relapse, leading to a higher overall survival (OS: high PIRCHE-I patients compared with low PIRCHE-I patients: relapse: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P = 0.040; mortality: HR, 0.69; 95% CI, 0.46-0.99; P = 0.042). In patients with standard-risk disease who received antithymocyte globulin, a significant association between class II PIRCHE (PIRCHE-II) and a lower incidence of nonrelapse mortality (NRM) leading to higher OS was observed (high PIRCHE-II patients compared with low PIRCHE-II patients, NRM: HR, 0.41; 95% CI, 0.19-0.86; P = 0.019; OS: HR, 0.55; 95% CI, 0.32-0.94; P = 0.030).

Conclusions: These findings suggest the differential effects of T-cell epitope matching based on GVHD prophylaxis after haploidentical HSCT. Pretransplant disease status may also be important for understanding the graft-versus-leukemia effect of mismatched HLA in haploidentical HSCT using PTCy.

Chronic graft-versus-host disease (cGVHD) is an immune-mediated, heterogeneous, multiorgan complication affecting allogeneic hematopoietic cell transplantation recipients, leading to increased morbidity, mortality, and decline in health-related quality-of-life. Advances in understanding the complex disease pathophysiology, and collaborative efforts lead by the National Institutes of Health to standardize criteria for clinical trials, led to bench-to-bedside efforts resulting in the development of 4 US Food and Drug Administration-approved agents for the treatment steroids-refractory cGVHD since 2017. Despite the remarkable advances in the field of hematopoietic cell transplantation in prevention of cGVHD, and more treatment options, the outcome of patients with moderate-severe cGVHD remains suboptimal. Essential to successful cGVHD management is to recognize the disease at early stages before the onset of irreversible damage, allowing for personalized multidisciplinary specialized interventions that include pharmacologic therapies and additional supportive care measures. The aim of this review is to summarize key areas of active clinical research and new developments in cGVHD therapeutic approaches, with focus on (1) preemptive therapy, (2) upfront therapy beyond corticosteroids, (3) treatment refractory cGVHD novel agents, role of combination therapies, and organ-specific approaches, and (4) challenges, gaps, and future directions.

Background: Current investigation indicates that nuclear factor (erythroid-derived 2)-like 2 (NRF2) possesses both proinflammatory and anti-inflammatory capabilities in T cells, yet its exact function in acute graft-versus-host disease (aGVHD) CD4+ T cells remains unexplored.

Methods: This study aims to determine NRF2 levels within CD4+ T cells of patients with or without aGVHD and analyze the correlation between T-cell receptor activation and NRF2 expression. RNA sequencing was used to detect changes in the expression profile of CD4+ T cells after overexpression of NRF2, and functional enrichment analysis was performed on the sequencing results. Finally, after treating aGVHD CD4+ T cells with NRF2 inhibitor, the expression of related pathway molecules was detected.

Results: Our findings demonstrated a significant upregulation of NRF2 expression in CD4+ T cells from patients in the aGVHD group compared with patients in the non-aGVHD group, and its expression level is correlated with the severity of aGVHD. Additionally, T-cell receptor activation in CD4+ T cells elevates NRF2 expression. Postactivation of NRF2-inhibited CD4+ T cells, the expression levels of T-cell activation markers were notably lower than those in non-NRF2-inhibited CD4+ T cells. Sequencing analysis identified 904 genes that changed after NRF2 overexpression. These genes were categorized into 288 gene subsets, encompassing pathways such as T-cell receptor signaling transduction, Janus kinase 1/signal transducer and activator of transcription 1 (JAK1-STAT1) signaling, T helper cell 17 (Th17) cell differentiation, etc. Ultimately, treating CD4+ T cells of aGVHD patients with an NRF2 inhibitor led to a significant downregulation of JAK1-STAT1 signaling and Th17 cells.

Conclusions: Elevated NRF2 expression in CD4+ T cells of patients with aGVHD initiates and exacerbates aGVHD by potentiating T-cell activation, amplifying JAK1/STAT1 signaling, and instigating Th17/regulatory T-cell ratio imbalance.

Kidney disease is a common complication in heart transplant recipients and requires a comprehensive and personalized approach. The interplay between preexisting kidney disease, perioperative factors, immunosuppression, and cardiovascular complications makes the management of kidney dysfunction challenging in these patients. The objective of this expert consensus was to look for agreements for the management of chronic kidney disease in heart transplant recipients. A panel of Spanish cardiologists and nephrologists with expertise in heart and kidney transplantation reviewed the evidence related to the current management of chronic kidney disease in heart transplant recipients and consensus statements were developed using a 2-round Delphi methodology. Consensus statements were proposed covering key topics, including the identification and management of kidney disease in heart transplant recipients and the indications for kidney transplantation. These statements provide additional expert guidance for the management of kidney disease in patients undergoing heart transplantation where published clinical evidence is scarce.