Frontiers in transplantation最新文献

This paradox emphasizes the urgent need to re-engineer transplant systems around pediatric-adult split liver transplantation (SLT). Despite being as effective as whole-liver transplants, SLT remains underutilized due to logistical and policy barriers. We believe that expanding SLT is not only clinically acceptable but a just and effective moral necessity. We propose a five-point action plan, including centralized splitting hubs, NMP-enabled transport, and global pilot programs, to transform SLT from an exception into standard practice.

Since the standardization of the grading system for pathologic diagnosis of antibody-mediated and acute cellular rejection, endomyocardial biopsy has remained the gold-standard. However, biopsies are invasive, costly, and limited by sampling error. As such, adjuvant non-invasive methods including cardiac biomarkers, imaging including cardiac magnetic resonance and echocardiography, and donor-specific antibodies and non-HLA antibodies have been traditionally used. However, all these techniques are limited by either sensitivity or specificity. More recently, there has been a shift to other contemporary non-biopsy surrogate markers for rejection surveillance including donor-derived cell free DNA, gene expression profiling, and messenger RNA and micro-RNA in tissue. Herein we review the methods currently utilized to diagnose rejection and their limitations. We find that while there have been significant advancements in technology and non-invasive techniques, no current method alone adequately diagnoses rejection (Central Image). Thus, future studies are warranted to investigate new strategies involving a multi-modal approach that incorporates non-invasive diagnostic methods and personalized medicine to monitor postoperative progression in heart transplant patients.

Background: Mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial DNA disorder that, in severe cases, can result in insulin-dependent diabetes and end-stage renal disease (ESRD). While organ transplantation is a potential treatment, documented cases remain scarce.

Methods: A 40-year-old patient with dialysis-dependent ESRD and diabetes secondary to MELAS underwent simultaneous pancreas-kidney transplantation. The perioperative and postoperative periods were uncomplicated with only targeted MELAS-specific adaptations to standard protocols.

Results: During the 5-year follow-up, the patient maintained excellent kidney allograft function and sustained insulin independence, with no need for dialysis or exogenous insulin therapy. At 5 years, creatinine was 77 µmol/L with an estimated GFR above 90 mL/min/1.73 m², and glycated hemoglobin was 40 mmol/mol.

Conclusions: SPK transplantation may be feasible in carefully selected patients with MELAS, ESRD, and diabetes, providing durable renal and metabolic graft function at 5 years. To our knowledge, this is the first reported SPK case in MELAS, with extended follow-up.

Background: Cerebral autoregulation (CA)-the brain's ability to maintain stable cerebral blood flow (CBF) despite changes in mean arterial pressure (MAP)-may be disrupted during orthotopic liver transplantation (OLT) due to profound metabolic, inflammatory, and hemodynamic alterations. Such impairment could increase the risk of cerebral hypoperfusion or hyperemia, yet its perioperative evolution and clinical implications remain unclear. This systematic scoping review aimed to synthesize current evidence on CA monitoring during OLT and to identify methodological gaps and potential clinical applications.

Methods: A systematic scoping review was conducted according to Joanna Briggs Institute (JBI) guidelines. Studies including adult patients undergoing OLT with quantitative perioperative CA assessment were identified across PubMed, Embase, Scopus, Web of Science, and Medline.

Results: Six studies (n = 99) met inclusion criteria. CA was assessed using diverse methods, including transcranial Doppler (TCD), near-infrared spectroscopy (NIRS), and derived indices such as the pressure reactivity index (PRx), mean flow index (Mx), cerebral oximetry index (COx), static cerebral autoregulation index (SCAI), and transfer function analysis (TFA). Monitoring phases and definitions of impaired CA varied widely. In acute liver failure, CA was commonly impaired pre-transplant and improved postoperatively, whereas findings in chronic liver disease were inconsistent. Only a few studies explored associations with neurological outcomes, yielding inconclusive results.

Conclusions: CA appears to be dynamically affected during OLT, particularly in acute liver failure, but evidence remains limited by methodological heterogeneity and small sample sizes. Standardized, prospective studies are needed to clarify the role of CA monitoring and to determine whether individualized blood pressure management could improve neurological outcomes.

Cholangiocytes-the epithelial cells lining the biliary tree-are especially vulnerable to ischemic injury, particularly in the setting of orthotopic liver transplantation (OLT). This susceptibility stems from their reliance on an arterial blood supply and limited anaerobic capacity, predisposing them to hypoxia-induced damage. While significant research has focused on hepatocellular ischemia-reperfusion injury (IRI), the specific biology of cholangiocyte injury and regeneration remains underexplored. Recent evidence highlights purinergic signaling as a key regulatory axis in the liver's response to ischemia. Upon hypoxic stress, extracellular ATP is released as a damage-associated molecular pattern (DAMP), activating pro-inflammatory P₂ receptors. Enzymatic degradation of ATP by CD39 and CD73 shifts the signaling balance toward adenosine, a potent anti-inflammatory and cytoprotective molecule acting through P₁ receptors (A₁, A₂A, A₂B, A₃). This review synthesizes emerging data on purinergic signaling in cholangiocyte biology, emphasizing its role in modulating inflammatory injury, cellular crosstalk, and regeneration. We discuss how A₂A and A₂B receptor pathways suppress immune-mediated damage and promote cholangiocyte proliferation, with downstream effects on IL-6 secretion, vascular remodeling, and bile duct survival. As biliary complications remain a major cause of graft dysfunction post-transplant, harnessing purinergic mechanisms may offer a novel therapeutic frontier in improving cholangiocyte resilience and overall transplant outcomes.

Sex hormones profoundly shape immune responses and influence outcomes after heart transplantation. Estrogen enhances allosensitization and is associated with a higher incidence of acute rejection in female recipients. Beyond its immunological effects, estrogen also modulates the pharmacokinetics and pharmacodynamics of calcineurin inhibitors-particularly cyclosporine A-thereby influencing immunosuppressive efficacy and early graft performance. Donor-recipient sex mismatch further modulates transplant outcomes. Female-to-male transplants in particular exhibit the poorest short- and long-term survival and show increased rates of primary graft failure and cardiac allograft vasculopathy. Mechanistic and experimental data provide a biological basis for these observations: estrogen protects the myocardium against ischemia-reperfusion injury and preserves vascular integrity through both nuclear estrogen receptors and GPER-mediated signaling. Abrupt withdrawal of this estrogen-mediated protection in male recipients of female donor hearts may therefore increase susceptibility to early graft dysfunction and chronic vasculopathy. Integrating sex and hormonal status into transplant medicine-through hormonal profiling, receptor-specific mechanistic studies, and sex-adapted immunosuppressive strategies-may pave the way toward more individualized and effective therapeutic approaches in heart transplantation.

Background: Based on clinical observations, we hypothesized that tacrolimus (TAC) exposure and acute kidney injury (AKI) are associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx).

Methods: Of 827 lung transplant recipients treated between 2000 and 2018, 509 with complete data sets from the University Hospital of Munich (LMU) were included in this study. In the context of a 10% reduction in FEV₁ (CLAD10), tacrolimus and renal function were examined descriptively, inferentially, and through confounder analysis with regard to the occurrence of CLAD10.

Results: Of 509 LTx patients, 67 (13%) died within the first 2 years after LTx. Among these 67 patients, 38 (57%) developed CLAD10 within 2 years of LTx. In these patients, we observed a temporal pattern characterized by a peak in TAC levels, followed by AKI, and subsequently subtherapeutic TAC concentrations, which occurred a few weeks before the onset of CLAD10. The confounder analysis demonstrated a significant influence of renal failure and tacrolimus fluctuations on the hazards ratio for developing CLAD10.

Conclusion: Our data suggest that a transient decline in TAC serum concentrations, often caused by a TAC-induced AKI, may trigger the onset of CLAD10 and subsequently elevate the risk of premature death.

Experts in transplantation medicine and AI innovation came together to showcase advancements in AI applications with the potential to improve transplant outcomes. Ethical deployment, consolidation of multimodal data and supporting clinical decision making were among the themes addressed. Experts presented foundational models such as MedSAM for universal medical image segmentation, scPGT for single-cell genomics and Clinical Camel for clinical decision support, each demonstrating high capability and adaptability across transplant specialities. Experts highlighted future directions, considerations, and challenges for integrating these tools into clinical practice in an ethical and safe manner. We will summarize these themes as discussed at the Ajmera Transplant Centre's second annual Transplant AI Symposium.

Introduction: Vascularized composite allotransplantation (VCA) has achieved significant clinical success, but lifelong immunosuppression remains essential to prevent rejection. Despite potent regimens, including tacrolimus, mycophenolate mofetil, and steroids, rejection episodes frequently occur within the first postoperative year. The side effects of immunosuppressive drugs must be carefully balanced against the risks of insufficient therapy. This review specifically aims to evaluate current immunosuppressive regimens and infection prophylaxis in VCA to identify evidence based approaches that attempt to mitigate rejection, prevent infections, and improve long-term graft survival.

Methods: A systematic review was conducted across PubMed/MEDLINE, EMBASE, and Web of Science databases, adhering to PRISMA 2020 guidelines. Inclusion criteria focused on studies reporting immunosuppressive regimens, dosages, and infection prophylaxis in VCA surgery. Non-VCA, animal, feasibility studies, and non-English publications were excluded.

Results: Of 1,150 screened articles, 42 met inclusion criteria. Upper extremity and facial VCAs represented 50% and 29% of cases, respectively, with traumatic amputation as the primary indication (37%). Antithymocyte globulin was the most common induction drug, while tacrolimus, mycophenolate mofetil, and steroids were predominant for maintenance therapy in 33% and 11% of cases, respectively. Infection prophylaxis was used in 31% of cases. Drug dosages varied widely, and no standardized immunosuppressive protocols were identified.

Conclusion: Current immunosuppressive strategies in VCA lack standardization, leading to variability in outcomes and increased risks. Infection prophylaxis remains underutilized despite recipient vulnerability. There is a critical need for standardized and tailored guidelines to optimize immunosuppressive therapy and infection control, ensuring graft survival and improved patient outcomes.