Frontiers in transplantation最新文献

Transplant surgery encompasses two primary branches: solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA). As the global population ages, elderly transplant patients become a more pressing clinical challenge. Elderly transplant recipients require specialized care that addresses their unique needs, including increased comorbidities and frailty. Despite the growing recognition of these challenges, there is a paucity of studies that synthesize the current knowledge on this patient cohort, from immunological changes over translational challenges to tailored clinical care. This review highlights the individual needs of elderly transplant patients, emphasizing the importance of understanding their clinical profiles to develop specialized perioperative management strategies. The clinical need for tailored therapeutic concepts contrasts with the current lack of established, integrated care models specifically designed for older adults undergoing SOT and VCA. Overall, future research is warranted to provide individualized and cross-disciplinary care models for aging transplant patients and broaden the access to transplant surgery for this patient population.

Introduction: Our objective was to model Ischemia-Reperfusion (IR) injuries by ex-vivo perfusion of porcine lungs with whole blood containing the inflammatory cells.

Methods: Lungs and whole blood were collected from 12 pigs and submitted to cold ischemia time (CIT) of 1 or 18 h. The lungs were then ventilated and perfused for 6 h at 37°C using donor whole blood. Pulmonary pressure was 20 mmHg.

Results: Compared to the short CIT group, the long CIT group had a lower maximum perfusion flow rate (mean difference in % cardiac output, -39%; 95% CI, -66 to -12; P = 0.005) and higher pulmonary vascular resistance (mean difference, 1,077 dyne·s·cm^-⁵; 95% CI, 685-1,469; P < 0.001). Neutrophils decreased more in the long CIT group (mean difference, -744.02 cells/mm³; 95% CI, -1,343.11 to -144.92; P = 0.017), suggesting sequestration in the lung parenchyma. Interleukin-6 and -8 levels after 6 h were significantly higher in the long CIT group (mean differences, 1.1 pg/ml; 95% CI, 0.39-1.8; P = 0.003; and 29.31 pg/ml; 95%CI, 16.00-42.61; P < 0.001; respectively). Progressive microvasculopathy resulting in lymphangiectasia and peribronchovascular inflammatory infiltrates were seen in both groups.

Conclusion: After 18 h of CIT, ex-vivo whole-blood perfusion for 6 h replicated features of IR injuries.

Introduction: Studies evaluating cell-free DNA (cfDNA) in kidney allograft dysfunction have primarily focused on detection of rejection by donor-derived cfDNA (ddcfDNA). The utility of ddcfDNA as a marker of longer-term outcomes has not been examined.

Methods: This study investigated the prognostic value of plasma total cfDNA, fractional ddcfDNA and absolute ddcfDNA, quantified in 49 adult kidney transplant recipients (KTRs) at the time of indication allograft biopsy between 2014 and 2017. Primary outcomes were death, death-censored graft loss (DCGL), and all graft loss (AGL).

Results: During a median follow-up of 6.3 years, 7 patients died, 7 experienced DCGL, and 14 had AGL. Death was predicted by high total cfDNA [>4,034 copies/ml, hazard ratio (HR) 5.94, 95% CI 1.40-25.13, P = 0.008] and low fractional ddcfDNA (<0.67%, HR 10.85, 95% CI 1.32-1,408.19, P = 0.03), and DCGL was predicted by high fractional ddcfDNA (>0.72%, HR 4.93, 95% CI 1.12-21.72, P = 0.04), on univariate analysis. AGL was predicted by high total cfDNA (>4,034 copies/ml, HR 642, 95% CI 1.15-3.56 × 10⁵, P = 0.045) on multivariate analysis. Absolute ddcfDNA was not associated with survival outcomes.

Discussion: This study demonstrates potential prognostic utility of total cfDNA and fractional ddcfDNA in KTRs with allograft dysfunction. Incorporation of these biomarkers could enhance personalised care, beyond non-invasive detection of rejection.

Background: Social determinants of health (SDOH) and transplant center characteristics have been associated with access to liver transplantation (LT) for Hispanic individuals. The aim of this study was to identify waitlist characteristics and correlates of odds of LT and waitlist removal by Hispanic ethnicity.

Methods: This was a single-center cohort study of adults listed for LT between January 2018-December 2020. Demographic, clinical, and SDOH were analyzed using logistic regression.

Results: 375 patients were included. 52.5% (N = 197) were Hispanic. At time of listing, Hispanic patients had significantly higher BMI, prevalence of diabetes and metabolic dysfunction associated steatohepatitis. Rates of substance use were significantly lower and time of last drink to listing was significantly longer (641 vs. 391 days, p = 0.0007) in Hispanic adults. Rates of LT and waitlist removal did not significantly differ by Hispanic ethnicity (46.9% vs. 46.1% and 35% vs. 36.5%, respectively). Hepatocellular carcinoma (OR 3.28) was associated with odds of LT whereas employment status predicted waitlist removal.

Conclusions: Distribution on the waitlist, LT and waitlist removal did not differ by Hispanic ethnicity. Hispanic patients had significantly longer time from last drink to listing, suggesting referral bias. Public health interventions to optimize LT referral are needed to increase health equity.

Despite significant advances in organ preservation, surgical techniques, and immunosuppressive regimens, rejection continues to pose a major challenge in the care of heart transplant patients. Endomyocardial biopsy (EMB) remains the gold standard test for surveillance and diagnosis of rejection, but is limited by its invasiveness, interobserver variability, procedural risk, and cost thus prompting the widespread use of non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA). Due to its high negative predictive value, dd-cfDNA is often routinely used for surveillance of asymptomatic patients. However, it is a non-specific marker of allograft injury and elevated levels in the presence of a reassuring EMB creates a diagnostic dilemma. This review explores the pathophysiological basis and clinical utility of dd-cfDNA in monitoring of heart transplant recipients with particular focus on evaluation and management of discordant findings.

Building on the established success of hypothermic machine perfusion (HMP) and emerging normothermic platforms, machine perfusion is poised to guide a journey toward 2040, transforming organ transplantation into an era of integrated preservation, viability assessment, and ex situ therapy. While renal HMP today reduces delayed graft function and improves graft survival, the next two decades will centre on adaptive platform trials in normothermic perfusion, predictive AI-driven biomarkers, and unified registries to validate robust surrogate endpoints. Centralised Assessment and Reconditioning Centres (ARCs) will streamline 24/7 workflows, combining advanced imaging, molecular assays, and gene or cell therapies to repair and optimise grafts ex-vivo. Health economics will shift toward dynamic, value-based reimbursement, addressing equity and cost-effectiveness across diverse systems. Regulatory frameworks will adapt through CONSORT-style reporting and direct device-to-registry data integration, ensuring transparency and reproducibility. By 2040, these convergent advances in HMP, normothermic machine perfusion (NMP), along with translational research will not only enhance graft utilisation and patient outcomes but will redefine transplantation paradigms through precision graft management, optimised logistics, and new indications such as extracorporeal organ support.

Introduction: Islet transplantation offers a potential curative treatment for patients with type 1 diabetes (T1D). To make this therapy widely available, a stable supply chain of human islets is essential. Developing techniques like cryopreservation and culture for long-term islet storage, or islet banking, with minimal functional loss would strengthen this supply chain. This study provides a systematic review of the current methods for long-term human islet storage.

Methods: A search strategy and query were developed according to the PICO framework. We included studies published on PubMed, Embase, and Web of Science from inception until August 2024.

Results: 6,945 studies were screened with 47 meeting criteria for full text extraction. The primary outcomes recorded were measures of islet viability and glucose stimulated insulin secretion. Optimization of culture parameters such as temperature, medium selection, and scaffolds can extend islet viability and function.

Discussion: Recent studies on human islet cryopreservation report promising results for long-term storage; however, the field remains underexplored. Several cytoprotective supplements with potential utility across both culture and cryopreservation conditions have also been reviewed. Although long-term islet storage has been a critical focus since the advent of the Edmonton protocol, the literature lacks the rigor needed to drive clinical translation. Notably, we observe substantial variability in experimental design and reported outcomes, which complicates meaningful comparison between interventions.

Background/objectives: Heart transplantation remains the definitive treatment for end-stage heart failure. However, donor shortages and the increasing age of candidates present significant challenges. This report aims to highlight the feasibility and successful outcome of heart transplantation in an elderly patient, questioning traditional age-based eligibility criteria.

Methods: A 76-year-old male with idiopathic dilated cardiomyopathy and severe heart failure underwent orthotopic heart transplantation. Preoperative assessments included right heart catheterization, echocardiography, and cardiac index evaluation. A suitable 66-year-old female donor was identified, and transplantation was performed using the bicaval technique. Postoperative outcomes were monitored through echocardiography and biopsy analysis.

Results: The patient had an uneventful postoperative course, with extubation on day 1 and discharge on postoperative day 30. Follow-up at 14 months showed excellent clinical recovery, with an improved left ventricular ejection fraction (LVEF) of 58% and global longitudinal strain (GLS) of -20.8%. No signs of rejection were observed on biopsy.

Conclusions: This case represents the oldest documented successful heart transplant recipient discharged home. The findings suggest that age alone should not be a limiting factor in transplantation eligibility. Expanding criteria to include well-selected elderly patients could help address the growing demand for donor hearts.

This case report highlights the management of recurrent urinary tract infections (UTIs) caused by multidrug-resistant (MDR) Pseudomonas aeruginosa in a post-renal transplant patient. Despite the challenges posed by antibiotic resistance, the patient was successfully treated with an extended infusion of meropenem, underscoring the efficacy of this approach in such difficult cases. The patient's recurrent infections required multiple hospitalizations and adjustments in treatment protocols, including the use of alternative antibiotics like fosfomycin and tailored immunosuppressive management to control both infection and rejection. This case is noteworthy for demonstrating the successful management of recurrent UTIs in the immunocompromised patient population, providing valuable insights into the treatment strategies that can be employed in similar clinical scenarios.