Transplant International最新文献

The prevention of hepatic artery thrombosis (HAT) is pivotal for graft survival immediately after liver transplantation (LT). This study aimed to identify risk factors (RF) for early HAT (eHAT) and assess the benefit of antiplatelet prophylaxis (AP). This retrospective single-center study included 836 adult patients who underwent LT between 2007 and 2022. AP was administered for 3 months in N = 127 patients for surgical reasons. In total, 836 patients underwent LT, of whom 5.5% developed eHAT. In multivariable analysis, arterial anastomotic redo (aHR = 4.33), arterial reconstruction (aHR = 3.72) and cryptogenic liver cirrhosis (aHR = 4.25) were independent RFs for eHAT and AP appeared to be protective (aHR = 0.18). Indeed, in patients with at least one RF who received AP (RF+AP+, n = 94), the eHAT rate was significantly lower (3.2% vs. 21.3%, p < 0.001) than in those with RF who did not receive AP (RF+AP-, n = 89). The effect was even more pronounced when focusing on surgical RF alone (i.e., redo and/or reconstruction) with an additional improvement in 1 year graft survival of 85.3% vs. 70.4%, p = 0.02. AP did not pose an increased risk of bleeding. In conclusion, the main RFs for eHAT include arterial anastomotic redo, arterial reconstruction and cryptogenic liver cirrhosis as LT indications. Our results suggest that AP may protect against eHAT development in these high-risk patients.

The molecular HLA epitope mismatch is an advanced measure for developing de novo donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus. At 1 year post-transplant, SPKTRs exhibited an increased dnDSA incidence (11.2% vs. 3.1%, p = 0.011); but not at 10 years post-transplant. In SPKTRs, preformed DSA (HR 2.872, p = 0.039) and younger donor age (HR 0.943, p = 0.017) were independent risk factors for developing dnDSA. PIRCHE-II scores for HLA-DQ correlated with dnDSA development upon univariate analysis (p = 0.044). Among 455 KTRs/SPKTRs, multivariate analysis identified PIRCHE-II scores for HLA-DQ (HR 1.023, p = 0.025) and ciclosporine use (HR 2.440, p = 0.001) as independent predictors of dnDSA development. Simultaneous pancreas/kidney transplantation (SPK) was an independent risk factor in case of preformed DSA only (HR 2.782, p = 0.037). High PIRCHE-II scores for HLA-DQ are crucial for dnDSA development in both SPKTRs and KTRs. The lack of an independent association of total PIRCHE-II scores urges caution in implementing it in post-transplantation risk assessment.

Heart failure is a serious and challenging medical condition characterized by the inability of the heart to pump blood effectively, leading to reduced blood flow to organs and tissues. Several underlying causes may be linked to this, including coronary artery disease, hypertension, or previous heart attacks. Therefore, it is a chronic condition that requires ongoing management and medical attention. HF affects >64 million individuals worldwide. Heart transplantation remains the gold standard of treatment for patients with end-stage cardiomyopathy. The recruitment of marginal donors may be considered an asset at the age of cardiac donor organ shortage. Primary graft dysfunction (PGD) is becoming increasingly common in the new era of heart transplantations. PGD is the most common cause of death within 30 days of cardiac transplantation. Mechanical Circulatory Support (MCS), particularly venoarterial extracorporeal membrane oxygenation (V-A ECMO), is the only effective treatment for severe PGD. VA-ECMO support ensures organ perfusion and provides the transplanted heart with adequate rest and recovery. In the new era of heart transplantation, early use allows for increased patient survival and careful management reduces complications.

Clinical pancreatic islet xenotransplantation will most probably rely on genetically modified pigs as donors. Several lines of transgenic pigs carrying one and more often, multiple modifications already exist. The vast majority of these modifications aim to mitigate the host immune response by suppressing major xeno-antigens, or expressing immunomodulatory molecules that act locally at the graft site. While these modifications are essential and have proven beneficial in preclinical trials, ensuring good intrinsic islet secretory function is equally important to achieve normoglycemia in recipients. Neonatal and even adult porcine islets are known for their low secretory response to physiological stimulation, a shortcoming that is often overcome by implanting extremely large numbers of such islets to compensate for insulin requirement incompatibilities between donor pigs and rodent, non-human primate or human recipients. Recent studies have revealed the existence of secretory amplifying pathways in porcine beta-cells previously identified in murine and human cells. Building upon these findings, a new line of transgenic pigs where these pathways are activated specifically in beta-cells has been created. Compared to their wild-type counterparts, islets from these transgenic pigs have proven to be better insulin secretors in their native pancreas environment, in vitro after isolation and most importantly in vivo after transplantation to diabetic mice.

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study. 580 kidney allograft recipients from 3 referral centers were included for 603 total evaluations. Correlation between assays was evaluated using r-squared (r ²) and Spearman's rank correlation test, and associations with rejection using logistic regression analyses and discrimination using area under the curve. Mean dd-cfDNA levels from decentralized and centralized tests were 0.51% ± 0.81% and 0.43% ± 0.78%, respectively. The assays were highly correlated, with r ² = 0.95 and Spearman's rank correlation 0.88 (p < 0.0001). Both tests showed significant association with allograft rejection (p < 0.0001) and good and similar discriminations to predict rejection (AUC: 0.758 for the decentralized and AUC: 0.760 for the centralized dd-cfDNA; p = 0.8466). Consistency between the assays was also confirmed across clinical scenarios including post-transplant timepoint, allograft stability, and allograft rejection subcategories. This decentralized dd-cfDNA assessment demonstrates high accuracy and value to non-invasively monitor kidney recipients.

The scarcity of donors has prompted the growing utilization of steatotic livers, which are susceptible to injuries following orthotopic liver transplantation (OLT). This study aims to assess the efficacy of multidrug donor preconditioning (MDDP) in alleviating injuries of steatotic grafts following rat OLT. Lean rats were subjected to a Western-style diet with high-fat (HF) and high-fructose (HFr) for 30 days to induce steatosis. Both lean and steatotic livers were implanted into lean recipients fed with a chow diet after OLT. The HF + HFr diet effectively elevated blood triglyceride and cholesterol levels and induced fat accumulation in rat livers. Our results demonstrated a significant decrease in alanine aminotransferase levels (p = 0.003), aspartate aminotransferase levels (p = 0.021), and hepatic Suzuki scores (p = 0.045) in the steatotic rat liver allograft group following MDDP treatment on post-operation day (POD) 7. Furthermore, the survival rates of steatotic rat liver allografts with MDDP (19/21, 90.5%) were significantly higher than those in the steatotic control (12/21, 57.1%, *p = 0.019). These findings indicate that MDDP treatment improves steatotic rat liver allograft function and recipient survival following OLT.

The Council of Europe (CoE) and the European Union (EU) share the same fundamental values, i.e., human rights, democracy and the rule of law, but are separate entities which perform different, yet complementary, roles. The CoE brings together governments from across Europe, and beyond, to agree minimum legal standards in a wide range of areas. CoE monitors how countries apply the standards that they have chosen to sign up to. It provides technical assistance, often working together with the EU. The EU refers to those same European values as a key element of its political and economic integration processes. It often builds upon CoE standards when drawing up legal instruments and agreements which apply to the member states, furthermore, monitoring work in its dealings with neighbouring countries, many of which are CoE member states. At CoE, the European Committee on Organ Transplantation (CD-P-TO) is the steering committee in charge of organ transplantation activities. In the EU, the regulation on Substances of Human Origin (SoHO) was endorsed in 2024. The CoE and the EU thave concluded an agreement expanding their co-operation in the field of SoHO. In the BTC regulation, xenotransplantation is not included.

Intestinal microsporidiosis caused by Enterocytozoon bieneusi is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication. We aimed to describe therapeutic management of E. bieneusi infections in this context. We conducted a French nationwide observational retrospective study on reported cases of E. bieneusi infections in SOT recipients. We identified 154 cases: 64 (41.6%) were managed by simply modifying the immunosuppressive regimen, 54 (35.1%) were given fumagillin, and 36 (23.4%) were given nitazoxanide. Clinical remission rate ranged from 77.8% to 90.7% and was not significantly different between therapeutic strategies but tended to be lower with nitazoxanide. Stool negativization rate was highest with fumagillin (91.7%) and lowest with nitazoxanide (28.6%). Relapses occurred in 6.9% of cases and were more frequent with nitazoxanide (14.3%). This study shows that tapering immunosuppression can result in a satisfactory remission rate but is sometimes accompanied by relapses. Nitazoxanide had limited effectiveness, whereas fumagillin had good results that provide a solid rationale for bringing fumagillin back to market.

Trial registration number: ClinicalTrials.gov ID: NCT05417815.

While the Banff classification dichotomizes kidney allograft rejection based on the localization of the cells in the different compartments of the cortical kidney tissue [schematically interstitium for T cell mediated rejection (TCMR) and glomerular and peritubular capillaries for antibody-mediated rejection (AMR)], there is a growing evidences that subtyping the immune cells can help refine prognosis prediction and treatment tailoring, based on a better understanding of the pathophysiology of kidney allograft rejection. In the last few years, multiplex IF techniques and automatic counting systems as well as transcriptomics studies (bulk, single-cell and spatial techniques) have provided invaluable clues to further decipher the complex puzzle of rejection. In this review, we aim to better describe the inflammatory infiltrates that occur during the course of kidney transplant rejection (active AMR, chronic active AMR and acute and chronic active TCMR). We also discuss minor components of the inflammatory response (mastocytes, eosinophils, neutrophils, follicular dendritic cells). We conclude by discussing whether the over simplistic dichotomy between AMR and TCMR, currently used in clinical routine, remains relevant given the great diversity of immune actors involved in rejections.