Transplantation最新文献

The resection and partial liver segment 2/3 transplantation with delayed total hepatectomy (RAPID) represents an innovative fusion of 2 of the most challenging procedures of modern liver surgery: auxiliary partial orthotopic liver transplantation and associating liver partition and portal vein ligation for staged hepatectomy. By combining the principles of auxiliary partial orthotopic liver transplantation of partial graft implantation with staged parenchymal modulation of associating liver partition and portal vein ligation for staged hepatectomy, RAPID enables sequential hypertrophy of the transplanted graft followed by complete native liver removal, addressing critical limitations in donor-recipient size matching. Current evidence highlights its primary application in treating unresectable hepatic malignancies, demonstrating advantages over conventional strategies in preserving functional liver volume, minimizing the risk of small-for-size syndrome, and accelerating graft regeneration. However, the procedure faces unresolved challenges, including ethical debates over living donor utilization in oncological contexts, necessity and feasibility of portal inflow modulation, optimal timing for delayed hepatectomy, insufficient long-term oncological outcome data and so on. This review provides an overview of the past and current status of RAPID, especially with respect to its evolution, indication, and technical details, as well as the potential challenges that have been discussed. Additionally, future directions of this surgical paradigm are outlined.

Background: Disparities in posttransplant outcomes persist and worsened during the COVID-19 pandemic, disproportionately affecting individuals with social risk factors. This study examined the total and residual (ie, direct) associations between individual- and neighborhood-level income and posttransplant outcomes among deceased donor kidney transplant (DDKT) and living donor kidney transplant recipients transplanted in the United States in 2020.

Methods: This retrospective cohort study linked Organ Procurement and Transplantation Network data with estimated individual annual income from LexisNexis and neighborhood median annual household income from the American Community Survey. Multivariable Cox models assessed associations between income and 3-y all-cause graft survival, patient survival, and death-censored graft survival.

Results: Among 14 091 DDKT recipients, lower individual income was associated with higher all-cause graft failure (adjusted hazard ratio [aHR] for lowest quartile [Q1] versus highest [Q4]: 1.37; 95% confidence interval [CI], 1.20-1.56) and death (aHR, 1.47; 95% CI, 1.26-1.72). Neighborhood income had weaker associations, though Q1 recipients still had higher all-cause graft failure (aHR, 1.17; 95% CI, 1.03-1.33) and death (aHR, 1.21; 95% CI, 1.04-1.41). In models including both income measures, only individual income remained significant. Censoring COVID-19 deaths attenuated associations for individual income, while neighborhood income was no longer significant. Among 4565 living donor kidney transplant recipients, income was not significantly associated with outcomes.

Conclusions: Lower individual income predicts higher all-cause graft failure, primarily because of increased mortality in DDKT recipients. Neighborhood income has a weaker effect, particularly when censoring COVID-19 deaths. Targeted interventions are needed to improve equity in kidney transplantation, especially during public health crises.

Physical frailty and sarcopenia are increasingly associated with morbidity and 2-fold mortality in patients with advanced chronic liver disease awaiting liver transplantation (LT). Furthermore, they significantly affect post-LT recovery and patients' ability to return to independent daily living, including employment. The increased prevalence of metabolic risk factors (ie, obesity, diabetes) and the aging population have contributed to the prevalence of physical frailty and the complexity of the multidisciplinary team decision-making that surrounds LT. Therefore, it is essential that physical frailty is identified early in the LT clinical pathway to provide targeted nutritional (1.2-2.0 g/kg protein intake, pancreatic exocrine replacement therapy) and individualized exercise (both aerobic and resistance) interventions in the form of (p)rehabilitation. A variety of clinical tools currently exist to assess the nutritional status of LT recipients, sarcopenia, and physical frailty, including patient questionnaires (ie, Royal Free Hospital Global Assessment, Duke Activity Status Index), easy-to-use "by the bedside" tests (ie, liver frailty index, 6-min walk test), and the more specialist investigations (ie, computer tomography, cardiopulmonary exercise testing). This overview aims to briefly summarize these tools, focusing on their varying ease of use, accessibility, and efficacy in a field that lacks consensus and continuity among LT centers. In addition, the overview highlights the benefits and future challenges of implementing pre- and post-LT rehabilitation programmes.

Background: Eplets, acting as specificity determinants on donor HLA antigen molecules, may induce the formation of de novo donor-specific antibodies (dnDSAs) by the recipient's B cells posttransplantation. HLA-DQ DSAs are the most common type of DSAs that target mismatched donor HLA-DQ antigens. The HLA-DQ protein exists as a heterodimer, consisting of HLA-DQA1 and HLA-DQB1 molecules. The specific risk of each mismatched HLA-DQ dimer contributing to dnDSA formation remains underexplored.

Methods: A total of 434 kidney transplant donor/recipient pairs from Zheng Zhou University First Affiliated Hospital, who underwent the transplant procedure between September 2016 and November 2020, were included in this analysis. All were DSA-negative pretransplant. For each HLA-DQ heterodimer, the total incidence of dnDSA, alpha chain-specific dnDSA, and beta chain-specific dnDSA after kidney transplant was analyzed. The dnDSA formation rates of different mismatched HLA-DQ dimers were compared and their haplotype association with specific HLA-DRB1 protein were determined.

Results: In this study, 38 HLA-DQ dnDSAs were detected, with 28 to HLA-DQB1 and 10 to HLA-DQA1. HLA-DQA1*03:02-DQB1*03:03 dimer had the highest dnDSA formation rate of 28.3%. The HLA-DQA1*05:xx-DQB1*03:01 and HLA-DQA1*05:xx-DQB1*02:xx, which are known for their high immunogenicity in previous studies, showed a relatively low DSA formation rate of 4.3%. The common DQB1*01:xx-DQB1*05:xx and DQA1*01:xx-DQB1*06:xx dimers had DSA formation rates of 1.8% and 3.9%, respectively. The high immunogenic HLA-DQA1*03:02-DQB1*03:03 dimer formed haplotype with DRB1*09:01 (98%), whereas the low immunogenic HLA-DQA1*02:01-DQB1*03:03 dimer formed exclusively haplotype with DRB1*07:01.

Conclusions: The DQA1*03:02-DQB1*03:03 dimer and the HLA-DRB1*09:01-HLA-DQA1*03:02-DQB1*03:03 haplotype turned out to be the most immunogenic in inducing HLA-DQ dnDSA in this Northern Han Chinese cohort.

Cardiac allograft vasculopathy (CAV) is a leading contributor to late allograft failure, mortality, and morbidity after heart transplantation. The prevalence of moderate to severe CAV over time has not changed significantly, and CAV remains an important contemporary consideration in post-heart transplantation management. The diagnosis and surveillance of CAV include both established and emerging invasive and noninvasive modalities, with a growing interest in understanding microvascular function and coronary physiology. The management of CAV is primarily focused on the prevention of CAV progression and optimizing traditional cardiovascular risk factors. Although mammalian target of rapamycin inhibitors and statins are central to the prevention of CAV progression, there is a lack of novel therapeutics for CAV. The development of new therapies for CAV will require a better understanding of the immune mechanisms underlying the initiation and perpetuation of this condition. CAV is mediated through a complex process involving cells and soluble factors of both innate and adaptive immune systems. Animal studies demonstrated that T cells play a central role in CAV. Both alloreactive T cells, which recognize donor major histocompatibility complex peptides (indirect allorecognition), and autoreactive T cells directed against heart tissue-specific antigens such as cardiac myosin have been shown to trigger CAV in mice. These processes involve the production of donor-specific antibodies and autoantibodies, respectively. Other studies suggest that CAV could be mediated by bystander T cells in a T cell receptor-independent manner and that CAV requires cooperation between T cells and natural killer cells. In addition, the essential role of interferon-γ in CAV has been documented. Whether any of these mechanisms pertain to CAV observed in transplanted patients has not been thoroughly investigated. Gaining insights into this question will be instrumental to the design of immune-based therapies for CAV.

Background: Hepatic ischemia-reperfusion injury (HIRI) significantly affects liver function in liver transplantation, primarily through dysregulated metabolism and inflammation. Although serine and glycine (SG) have been identified as potential therapeutic targets in various diseases, the mechanisms by which SG influences HIRI remain unclear. This study aimed to investigate the effects of SG deficient (-SG) dietary intervention on HIRI.

Methods: We established an in vivo and in vitro HIRI model under the -SG condition. RNA sequencing, coupled with bioinformatics analysis, identified key targets modulated after -SG intervention. Biochemical and histological analyses were used to evaluate the effects of -SG on HIRI. Furthermore, plasmid-based transient overexpression of CYP2S1 and CYP26B1 was induced to explore the mechanistic role of -SG in regulating cell apoptosis and inflammatory responses.

Results: Histological and liver enzyme analyses confirmed that SG deficiency worsened ischemia-reperfusion-induced liver necrosis and impaired liver function. Furthermore, SG deficiency exacerbated hepatocyte apoptosis, immune responses, and inflammatory responses caused by ischemia-reperfusion injury in vivo and in vitro experiments. RNA sequencing revealed a correlation between CYP family signaling pathway and liver injury resulting from SG deficiency.

Conclusions: SG deficiency exacerbated apoptosis, as well as immune and inflammatory responses in a liver injury model. The lack of these amino acids can promote inflammation and worsen HIRI by downregulating CYP2S1 and CYP26B1 expression. Conversely, SG supplementation may exhibit a protective effect against liver injury after transplantation.