Clinical Transplantation最新文献

Background

Endomyocardial biopsies (EMB) remain the reference standard for detection of acute rejection in heart transplant (HTx) patients. Recent studies evaluating novel noninvasive tests have sparked a renewed discussion in the HTx community about revising acute rejection surveillance policies. However, patient and provider perspectives remain underexplored. This single-center study examined both HTx patient and provider perspectives on replacing EMBs earlier with noninvasive blood tests.

Methods

We performed semi-structured interviews with 28 HTx patients to explore their perspectives on replacement of EMBs with donor-derived cell-free DNA (dd-cfDNA) early post-HTx. We subsequently conducted a survey of 118 HTx patients using self-administered online questionnaires. We also performed semi-structured interviews with 18 HTx providers to explore their perspectives. Thematic analysis was performed on interview and open-ended survey responses using deductive and inductive approaches. Patient quantitative survey responses were analyzed with descriptive statistics.

Results

Our study identified three key themes: patient anxiety related to EMBs, importance of patient-provider communication, and strong interpersonal trust in providers by HTx patients. Although 78.4% of patients experienced EMB-related anxiety, they prioritized testing accuracy to ensure “the health of their new heart.” Consequently, patients favored the most accurate testing protocol and trusted providers to make this decision (91.1%). HTx providers raised concerns about the accuracy and safety of noninvasive surveillance testing for high-risk patients.

Conclusion

HTx patients trusted their providers to determine the most accurate acute rejection surveillance policy. Additionally, our study provides important patient-centered priorities to guide the implementation of early noninvasive testing into clinical practice.

Trial Registration: ClinicalTrials.gov identifier: NCT06414603

Background

Uncontrolled donors after circulatory death (uDCDs) are recognized as a potential donor pool. No data are so far available on liver biopsy findings in uDCDs. We aimed at assessing liver biopsy findings in uDCDs consecutively admitted to our Center from 2019 to 2023.

Methods

Twenty nine utilized uDCD consecutively admitted at our Center from 2019 to 2023 were included. Liver biopsies were performed during organ procurement in all uDCDs.

Results

The median time from cardiac arrest to normothermic regional perfusion (NRP) run was 144 min, while the median NRP duration was 6 h. The liver was retrieved but not transplanted in 12 donors (12/29, 41%) and transplanted in 10 donors (10/29, 35%). In 7 uDCDs, livers were not retrieved (24%). Ishak grading score 1–2 was observed in most biopsies (21/29, 72%). The incidence of microsteatosis <50% and macrosteatosis <30% was prevalent in our series (24/29, 82% and 22/29, 76%). Lobular infiltration was found in most biopsies (15/24, 63%), while hepatocellular focal necrosis was documented in the 45% (11/24). Severe IRI was found in a small percentage of uDCDs (4/24, 16%).

Conclusion

In our series, liver biopsy in uDCDs may provide clinicians with two different kinds of information. The first one may be mainly related to comorbidities and chronic damages, as indicated by the presence (and percentages) of micro/macrosteatosis and Ishak grading/score. The second one might provide insights into the ischemic-reperfusion injury of the liver, that is it might be related to the uDCD process itself.

Background

The UK Kidney Allocation Scheme (KAS) prioritizes organ allocation based on HLA mismatches, assigning the greatest weight to HLA-DR compatibility. However, the clinical relevance of this approach across different ethnicities in the era of modern immunosuppression remains uncertain.

Methods

We conducted a retrospective cohort study of 25 094 adult deceased donor kidney transplants in the United Kingdom between 2008 and 2020. Using competing risk Cox regression, we evaluated the impact of individual HLA locus mismatches and grouped mismatch levels (as defined by UK-KAS) on graft survival. Subgroup analyses by ethnicity were performed, and the relationship between HLA mismatches and acute rejection was assessed using logistic regression.

Results

A single HLA-DR mismatch was significantly associated with graft failure (SHR 1.119, 95% CI 1.035–1.211, p = 0.005), while mismatches at the A, B, and DQ loci were not. In subgroup analyses, HLA-DR mismatching was predictive of graft failure in Asian recipients but not in Black recipients. Black patients also exhibited higher rates of mismatching at all loci. DQ mismatches were associated with early acute rejection but did not predict long-term graft failure. Ten-year graft survival was 13% less with one HLA DR mismatch, and 17% less with 2 HLA DR mismatch, in comparison to zero DR mismatch. The four-level HLA mismatch grouping used by UK-KAS stratified risk incrementally, with levels 3 and 4 associated with 13% and 19% higher failure risk, respectively.

Conclusions

HLA-DR matching improves graft survival overall but offers limited benefit in Black recipients, likely due to low-resolution typing inadequately capturing immunological compatibility across ethnic lines. The current UK-KAS scoring system may inadvertently disadvantage ethnic minorities by delaying transplantation for matches that confer minimal benefit. Our findings support incorporating ethnicity-specific considerations into kidney allocation policy to promote equity and optimize outcomes.

Background and Aims

Primary sclerosing cholangitis recurrence (rPSC) after liver transplantation (LT) is common; however, the factors contributing to rPSC are poorly understood. This study aimed to identify the risk factors for rPSC after LT and determine whether donor type affects rPSC.

Methods

A multicenter retrospective cohort analysis was conducted on 174 patients with PSC who underwent LT between January 2000 and January 2024. Multivariable Cox models were used to evaluate risk factors for rPSC. The rPSC risk for living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) recipients was compared using Kaplan-Meier survival curves and log-rank tests.

Results

Of the 174 recipients, 144 (83%) underwent LDLT and 30 (17%) underwent DDLT. Sixty-four (37%) had inflammatory bowel disease (IBD) prior to LT. Thirty-three patients (19%) had rPSC after LT. The median time to rPSC was 28 months (IQR 6-252). Patients with rPSC were younger at the time of PSC diagnosis, and had a higher prevalence of biliary complications after LT and concomitant IBD than those without recurrence. Multivariable Cox regression identified LDLT (HR 3.92, 95% CI 1.06–14.51, p = 0.041), biliary complications (HR 2.18, 95% CI 1.05–4.54, p = 0.037), IBD (HR 2.42, 95% CI 1.20–4.89, p = 0.013), and acute cellular rejection (HR 2.43, 95% CI 1.08–5.48, p = 0.032) as independent risk factors for rPSC.

Conclusions

This multicenter study identified LDLT, acute cellular rejection, IBD, and biliary complications as independent risk factors for rPSC. These findings underscore the need for individualized post-transplant surveillance and provide important considerations for graft selection and perioperative management in patients with PSC, particularly in settings where LDLT is predominant.

Background

Warfarin, the anticoagulant of choice for durable left ventricular assist devices (LVADs), has a narrow therapeutic index and extensive pharmacologic interactions that make dose optimization challenging. Inadequate time in the therapeutic range increases the risk of thrombotic and hemorrhagic complications. We sought to evaluate the safety and efficacy of apixaban as an alternative anticoagulant for HeartMate (HM) 3 LVADs.

Methods

We analyzed data for patients with HM3 LVADs treated at our center between 2018 and 2024, comparing thromboembolic and hemorrhagic events between patients receiving warfarin and those who transitioned to apixaban due to adverse events or labile therapeutic responses on warfarin.

Results

We included 47 patients, 16 of whom remained on warfarin, while 31 transitioned to apixaban. Both cohorts had identical baseline characteristics. Rates of all-cause bleeding per 100 patient-years were similar for warfarin (33) and apixaban (29), p = 0.24. The relative risk (RR) of major bleeding within the first 3 months of anticoagulation was significantly lower with apixaban—RR 0.08 (95% CI, 0.01–0.65, p = 0.01), with an incidence rate of 6.4% on apixaban versus 43.8% on warfarin. All-cause bleeding occurred less frequently with apixaban at 32% compared to 68.8%—RR 0.14 (95% CI 0.03–0.62, p = 0.009). Hemocompatibility improved in the apixaban group, evidenced by an increase in hemoglobin (11 ± 2 to 12 ± 2 g/dL, p < 0.001) and a decrease in lactate dehydrogenase (427 ± 129 to 221 ± 83 U/L, p < 0.001). Thrombotic events were identical.

Conclusion

In patients with HM3 LVADs, apixaban may be a safe and clinically effective alternative to warfarin.

Purpose

To evaluate the association between tacrolimus intra-patient variability (IPV) and the prognosis of cardiac transplant recipients.

Methods

Tacrolimus trough concentrations (C₀) from cardiac transplant recipients were collected during the postoperative months 3–6. Dose-adjusted IPV values were calculated, and recipients were divided into high-IPV and low-IPV groups. The composite endpoint was defined as the occurrence of any one of the following: infection, rejection, or mortality.

Results

A total of 202 recipients were included. The incidence of infections was significantly higher in the high-IPV group (34.8% vs. 21.1%, χ² = 4.480, p = 0.034). The risk of infection and composite endpoint occurrence was approximately 2.2 and 2.1 times higher, respectively, in the high-IPV group than in the low-IPV group, with hazard ratios (HR) and 95% CIs of 2.215 (1.175–3.842) and 2.061 (1.258–3.378). No significant differences were observed between the two groups in terms of rejection or mortality (p > 0.05). Cox regression analysis revealed that the relative risk of composite endpoint occurrence in the high-IPV group was 2.024 times higher than in the low-IPV group. The cumulative event-free survival rates for the composite endpoint differed significantly between the two groups. Log-rank testing of the survival curves yielded p = 0.004 and HR = 2.061 (95% CI: 1.258–3.378).

Conclusion

Cardiac transplant recipients with high tacrolimus IPV may be at increased risk of adverse events such as infections. Tacrolimus IPV, which is simple to calculate, can serve as a useful follow-up tool for predicting postoperative adverse outcomes.

Background

Mycophenolic acid (MPA) is a common immunosuppressant used in children post-orthotopic heart transplant (OHT). Multiple MPA dosing strategies exist, with limited reports of comparisons between dosing strategies and patient outcomes.

Methods

We performed a retrospective review of heart transplant recipients ≤ 21 years from 2014 to 2022, comparing dose concordance and clinical outcomes of weight-based mycophenolate dosing (15 mg/kg/dose every 12 h) to body surface area (BSA)-based dosing (600 mg/m²/dose every 12 h).

Results

We analyzed 109 patients total (56% in the BSA-based cohort and 44% in the weight-based cohort). The BSA-based cohort received a higher total milligram dose (480 (IQR 200–563) vs. 636 (IQR 320–1000), p = 0.005), mg/kg dose (14.5 (IQR 13.7–16.1) vs. 20.7 (IQR 16.4–25.8), p < 0.001) and mg/m² dose (382 (IQR 333–470) vs. 596 (IQR 572–612), p < 0.001) compared to the weight-based cohort. The BSA-based cohort experienced a lower hazard of rejection (HR 0.2, 95% CI 0.1–0.4 vs. weight-based) and a greater hazard for overall infection (HR 2.2, 95% CI 1.2–3.9). There was no significant difference in 1-year post-transplant mortality and incidence of post-transplant lymphoproliferative disorder (PTLD).

Conclusions

This study demonstrates the discordance between two common mycophenolate dosing strategies (1200 mg/m²/day vs. 30 mg/kg/day) and its resultant impact on pediatric heart transplant-related outcomes. Further multicenter data would be useful to elucidate the impact on post-heart transplant morbidity and mortality.