Frontiers in transplantation最新文献

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.

Introduction: Lung transplantation has seen strides in survival over the past few decades, though long-term survival remains poor. Chronic lung allograft dysfunction (CLAD) is a leading cause of graft failure and mortality beyond the first year. Anti-thymocyte globulin (ATG) is commonly used for treating refractory CLAD, though its efficacy remains uncertain.

Methods: This retrospective study evaluated the impact of ATG on lung function decline and mortality among lung transplant recipients diagnosed with CLAD, defined as a persistent >20% decline in forced expiratory volume (FEV1) from baseline. Patients treated with ATG were compared to those who did not receive ATG, using mixed effects modeling for FEV1 decline and Fine-Gray competing risk modeling for mortality.

Results: Of the 124 patients with CLAD, 55 (44%) received ATG. Administration was not associated with a significant change in FEV1 decline when compared to rate of decline prior to ATG administration [-0.0881 L/year, 95% CI (-0.21, 0.034)] or compared to non-ATG recipients [0.0599 L/year, 95% CI (-0.057, 0.18)]. However, ATG was associated with a lower hazard of all-cause mortality [subhazard ratio 0.66, 95% CI (0.39-1.14)].

Discussion: While ATG improved survival, it did not alter lung function decline, affirming the need for prospective randomized studies.

Introduction: Lung transplantation (LT) is the standard treatment for end-stage chronic respiratory failure that does not respond to other therapies. Advances in surgical techniques and perioperative care have improved survival rates. However, postoperative complications, particularly atrial arrhythmias (AA) remain clinically significant. Although AAs are frequently observed in the early postoperative period, data regarding their incidence and impact on outcomes are scarce. This observational study aims to: (i) assess the incidence of new-onset postoperative AA within one month of bilateral LT; (ii) evaluate their impact on short- and mid-term outcomes; and iii) identify potential predictors.

Materials and methods: We retrospectively reviewed all consecutive bilateral LT recipients admitted to the Intensive Care Unit (ICU) of the University Hospital of Padua between October 2021 and December 2023. Clinical variables, perioperative right heart catheterization data, and echocardiographic measurements were collected.

Results: A total of 85 LT recipients were enrolled. Postoperative AA occurred in 27 patients (32%), with atrial fibrillation emerging as the most common arrhythmia (55.6%). The remaining 58 (68%) patients did not develop any arrhythmic disorder. Many AA patients (22, 81.5%) required treatment with antiarrhythmic drugs or electrical cardioversion. Compared to the control group, AA patients were older (p-value 0.002) and usually affected by coronary heart disease (18.5% vs. 5.2%, p-value 0.05) and obstructive respiratory disease (55.5% vs. 27.7%, p-value 0.004). AA patients more frequently experienced difficult weaning from mechanical ventilation, a higher incidence of postoperative V-A ECMO, more frequent anastomotic complications, and longer ICU stays, as compared to controls. Multivariate analysis identified older age (OR 1.11, 95% CI 1.01-1.25, p-value 0.047) and higher postoperative dobutamine dosage (OR 2.25, 95% CI 1.15-5.01, p-value 0.026) as the only significant predictors of new-onset AA within one month of LT.

Conclusions: In our cohort, the incidence of new-onset AAs was 32% after bilateral LT. AA patients experienced worse short- and mid-term outcomes compared to controls. Furthermore, this study highlights older age and postoperative dobutamine administration as significant predictors of new-onset AA following bilateral LT. Further research is needed to clarify the causal relationships and long-term implications of AA on the clinical course of LT recipients.

Background: Alcohol use disorder (AUD) treatment in liver transplant (LT) recipients requires multidisciplinary management. We aim to analyze post-LT patients' perceptions of the transplant clinic, local community resources, desired supports and barriers for AUD recovery resources.

Methods: A survey of adult recipients who received a LT within the last ten years with a history of AUD at a single Transplant Center was conducted. The survey consisted of five categories: demographics, strategies for AUD treatment used before and after LT, recent alcohol use, and challenges faced in AUD treatment. Results were reported using descriptive statistics.

Results: Forty-one of 203 approached participants completed the questionnaire over a 3-month period [median age 56 years (45.5-62), 68.3% male, 90.2% white, median time since transplant 21 months (9.4-50.7)]. Thirty-three (80.5%) had a period of abstinence from alcohol prior to LT: 17 (41.5%) 1-5 years, 7 (17%) 6-12 months, and 7 (17%) < 6 months. 88.9% reported their goal for alcohol was complete abstinence. Useful strategies for AUD management before LT included exercise (73.1%), family support (63.4%), and therapy (58.5%). Exercise was most effective post-LT resource to prevent return to alcohol use, followed by social work assistance (51.2%), and finding a new hobby (48.8%). Social support and difficulties with availability of AUD treatment resources were the main challenges perceived by survey participants.

Conclusion: Exercise, social support, social work assistance, finding new hobbies, and therapy were the preferred resources for AUD management. Future interventions should facilitate access to resources to assist with sobriety and incorporate their outside support network in assisting with recovery from AUD.

Introduction: Acute cellular rejection of transplanted lung allografts involves activated cytotoxic T cells and reduced Regulatory T (Treg) cell function. Calcineurin inhibitors, the cornerstone of immunosuppressive regimens, suppress T cell cytotoxicity but inhibit Treg proliferation. The DNA hypomethylating agent decitabine (DAC) can abrogate T cell cytotoxicity while stimulating Treg proliferation.

Methods: We sought to determine the effects of DAC treatment in a murine MHC-mismatched orthotopic lung transplant model.

Results: Rescue treatment with DAC maintains lung allograft gross and histologic integrity with a reduction in cytotoxic T cell responses. CD4+FoxP3+ T cell depletion in Foxp3DTR mice exacerbated rejection lung injury compared to CD4+FoxP3+ T cell sufficient mice and failed to abolish the protective effect of DAC in this model. The protective effect of DAC was associated with a reduction in cytokine production from host T-cells.

Discussion: Decitabine could offer a new line of treatment for acute lung allograft rejection, in part via its effects on Tregs.