Clinical Transplantation最新文献

Background

The heart transplant allocation policy change in 2018 was intended to help ameliorate differences in waiting times for heart transplantation across UNOS regions. We sought to examine the regional variability in waitlist times and post-transplant outcomes since these changes were implemented.

Methods

The adult patients in the United Network for Organ Sharing registry from October 2018 to December 2022 were included. Regional trends in waitlist time, waitlist events, and post-transplant outcomes were assessed. Differences in regional variability of successful transplantation over years since policy change were described.

Results

A total of 8029 patients were included. The cumulative incidence of successful transplant after 30 days was significantly different across regions (p < 0.001). There was no difference in 30-day post-transplant mortality across regions. In each year since the policy change, there continues to be a significant difference in the lowest and highest cumulative incidence of successful transplant at 30 days across regions using difference of difference analysis, suggesting regional variation has not improved over time (p = 0.49).

Conclusions

Since the allocation policy change, there continues to be significant variation in time to successful transplantation across geographic regions.

Background

Substance use is common among lung transplant donors, but concerns persist about graft damage. Stimulant drugs such as cocaine and methamphetamine can induce pulmonary arterial hypertension, while smoked products such as cannabis and crack cocaine can produce airway and parenchymal diseases. We sought to characterize donor substance use at our center and evaluate the associations with recipient survival as well as chronic lung allograft dysfunction (CLAD), severe primary graft dysfunction (PGD3), and baseline lung allograft dysfunction (BLAD).

Methods

We studied patients with double lung transplants in our program between 2004 and 2016, including a history of donor substance use with nine pre-specified agents. We modeled the association with time to death or retransplant, CLAD, severe PGD, and BLAD.

Results

Of 473 recipients, 186 (39%) received lungs from a donor with a history of substance use with at least one of the pre-specified substances. There was no overall relationship between donor substance use and any outcome. Heavy donor smoking was associated with an increased risk of death or retransplant (hazard ratio 1.47; p = 0.032), PGD3 (odds ratio [OR]: 2.13; p = 0.014), and BLAD (OR 2.56; p < 0.001). Donor crack cocaine use (n = 24) was also associated with worse survival (HR 2.16; 95% CI 1.16–3.66; p = 0.017) but not CLAD or BLAD. We noted no CLAD associations with any drug.

Conclusion

A history of donor substance use was common and in general not associated with worse outcomes, aside from heavy donor smoking. These findings may have implications for allocation and post-transplant graft dysfunction.

Background

Human donor kidneys release (pro)renin, erythropoietin (EPO), active vitamin D, and urodilatin during normothermic machine perfusion (NMP). However, whether the endocrine function of donor kidneys is associated with post-transplant kidney function is unclear.

Methods

We studied 28 donor kidneys, including seven from donation after brain death (DBD) donors and 21 from donation after circulatory death (DCD) donors. Prior to transplantation, we measured levels of (pro)renin, EPO, 1,25(OH)₂D in the perfusate, and urodilatin in urine during NMP. Hormone release rates were compared between kidneys with and without delayed graft function (DGF), and correlations were assessed between hormone release rates and donor characteristics and transplant outcome, including DGF duration, serum creatinine levels at 1-week post-transplant, and estimated glomerular filtration rate at 1-month post-transplant.

Results

DBD kidneys secreted significantly less EPO and more active vitamin D than DCD kidneys. Kidneys with DGF exhibited significantly higher release rates of active vitamin D and lower release rates of urodilatin compared to those without DGF. In addition, EPO release rate was positively correlated with serum creatinine levels at 1-week post-transplant. Finally, urodilatin release rates were negatively correlated with DGF duration and positively correlated with urine output.

Conclusions

Urodilatin release in urine and EPO and active vitamin D release in perfusate during NMP may serve as potential biomarkers for predicting early post-transplant outcomes.

Trial Registration: ClinicalTrials.gov identifier: NCT04882254

Introduction

Little is known about the epidemiology and management of gram-negative bloodstream infections (GN-BSIs) in patients after solid organ transplant (SOT). We describe epidemiology, treatment approaches, and outcomes in a subset of patients with SOT from a larger cohort with GN-BSI.

Methods

This was a multicenter, retrospective cohort study that enrolled unique, consecutive adults with GN-BSI hospitalized at any of 24 participating hospitals between January and December 2019.

Results

Of 4581 adults in the overall cohort, 298 (6.5%) were SOT recipients, including kidney (177, 59%), liver (67, 22%), heart (23, 8%), lung (12, 4%), and multiorgan (19, 6%) recipients. The most common organisms were Escherichia coli (45%), Klebsiella pneumoniae (20%), and Pseudomonas aeruginosa (15%). Twenty-two percent of E. coli, Klebsiella spp., or Proteus spp. isolates had extended-spectrum beta-lactamase phenotype. Sixty-six (22%) subjects did not receive active empirical therapy within the first 48 h. Median treatment duration was 15 days (IQR 12–18 days). Transition to oral therapy occurred in 161 (54%) patients at a median of 4 days (IQR 3–7 days). Thirty-one patients (10%) had recurrent bacteremia, and 10% of the cohort died within 90 days.

Discussion

In this large cohort of SOT patients with GN-BSI, durations exceeded 14 days in most patients, while more than half transitioned to oral antibiotics. Approximately 1 in 5 did not receive active empirical antibiotics, highlighting the impact of drug resistance and the importance of access to rapid diagnostic tools in this patient population. Mortality aligned with published estimates from other studies.

Introduction

Previous cardiothoracic surgery (CTS) is associated with a significant risk of perioperative bleeding in lung transplantation (LT). The types of prior surgery have not been well-defined. We aimed to quantify the risk of perioperative bleeding in LT based on a history of previous CTS.

Methods

We conducted a retrospective study of adult patients who underwent bilateral LT and stratified recipients into no prior CTS (No-CTS), minimally invasive CTS (Mi-CTS), or open/invasive CTS (I-CTS). The primary outcome was the occurrence of severe/massive bleeding or worse bleeding by the modified universal definition of perioperative bleeding (UDPB). Multivariable analysis was performed with p value <0.05 for statistical significance.

Results

507 recipients were included. I-CTS had 3.93 higher odds of severe/massive bleeding (95% CI [1.98–7.98]; p < 0.001) and 4.37 higher odds of worse bleeding than No-CTS (95% CI [2.27–8.70]; p < 0.001). I-CTS had 2.38 higher odds of worse bleeding than Mi-CTS (95% CI [1.14–5.11]; p = 0.023). Mi-CTS had a higher risk of severe/massive bleeding and worse bleeding than No-CTS.

Conclusion

Patients with more invasive prior CTS had an increased risk of perioperative bleeding and worse outcomes. More invasive previous surgery predicts bleeding risk and requires more transfusion and hospital resources. Centers should examine opportunities for preoperative optimization, intraoperative management, and intraoperative extracorporeal life support (ECLS) strategies to mitigate this risk.

Aims

Coronary artery disease (CAD) is a frequent comorbidity in lung transplant (LuTx) candidates. The impact of allogenic organ transplantation and the corresponding alterations in immune response on the progression of CAD remains poorly understood. In this study, we sought to analyze the effect of donor-recipient overall human leukocyte antigen (HLA) and HLA-DQ mismatch on cardiovascular outcomes following LuTx.

Methods and Results

This retrospective analysis of adult patients receiving lung transplantation at the LMU University Hospital between 2012 and 2018 included 310 patients, the majority of whom (67.4%) had undergone double lung transplantation. There were no significant differences in the incidence of the primary composite endpoint between patients with high/low HLA mismatches (22 [7.9%] vs. 4 [12.9%]; p = 0.311). Numerically higher rates of the primary endpoint, myocardial infarction, and cardiovascular death in the low HLA mismatch group can partially be explained by differences in baseline rates of CAD and coronary sclerosis. Notably, neither HLA-DQ mismatch nor the occurrence of rejection episodes or cytomegalovirus (CMV) infection was associated with the occurrence of cardiovascular events following transplantation.

Conclusion

In this study cohort, high HLA mismatch and HLA-DQ mismatch were not associated with increased adverse cardiovascular events. Furthermore, neither transplant rejection nor CMV infection increased the risk for cardiovascular events. The high cardiovascular event rates following LuTx necessitate meticulous cardiovascular follow-up, irrespective of immunological matching.

Background and Aim

Liver transplant (LT) recipients may succumb to graft-related pathologies, contributing to graft fibrosis (GF). Current methods to diagnose GF are limited, ranging from procedural-related complications to low accuracy. With recent advances in machine learning (ML), we aimed to develop a noninvasive tool using demographic, clinical, laboratory, and B-mode ultrasound (US) features to predict significant fibrosis (METAVIR≥F2).

Methods

We used a nested 10-fold cross-validation approach with grid-search for hyperparameter fine-tuning to train an artificial neural network (ANN) and a support vector machine (SVM) to classify mild fibrosis (F0-F1) and significant fibrosis (F2-F4) on 1131 patients. We calculated Shapley values to identify top-ranked features, determining the contribution of each feature to model predictions. For the imaging-based model, we used 4819 images with 892 studies trained on the residual network 18 (ResNet18) model to classify F0-F1 versus F3-F4.

Results

We determined the ANN performed the best when compared to the SVM and standard biomarkers, with an AUC ranging from 0.77 to 0.81. The ResNet18 model was unable to diagnose advanced GF, leading to the training AUCs ranging from 0.89 to 0.97, while the validation and testing AUCs were 0.43–0.63. Shapley analysis highlighted the following top-ranked features associated with significant GF: hepatitis C at transplant, recipient age, recipient sex, and certain blood markers such as creatinine and hemoglobin.

Conclusion

Noninvasive approaches using ML for predicting significant GF perform well when considering demographic, clinical, and laboratory data; however, this performance is not enhanced with the use of US images.

Background

End-stage renal disease (ESRD) is associated with significant left ventricular (LV) remodeling. However, the impact of renal transplantation on LV remodeling has not been adequately elucidated.

Methods

A comprehensive echocardiography was performed before and after (median time interval 239 days, interquartile range 149–328 days) renal transplantation in 42 patients (mean age 39.1 ± 11.0 years, 79% men). Forty-five apparently healthy age- and gender-matched controls were also included.

Results

The patients with ESRD had significantly increased LV mass index, left atrial volume index (LAVI), and the ratio of early diastolic mitral inflow velocity to mitral annular velocity (E/e’), whereas LV global longitudinal strain (GLS), circumferential strain, apical rotation, and twist were reduced. LV ejection fraction (LVEF) was also lower, but the LV global radial strain (GRS) was not different between the two groups. Most of these abnormalities showed improvement after renal transplantation. Nearly one-third of all patients had at least a 10% improvement in LVEF, and roughly half had a 10% or more improvement in the mitral E/e’ ratio and the LV global longitudinal and circumferential strain.

Conclusion

This study shows that renal transplantation results in a significant regression of LV hypertrophy and an improvement in LV myocardial deformation translating into an improvement in the LV systolic and diastolic function. Further larger and long-term studies are needed to identify the predictors and the clinical significance of these changes.