Transplantation Direct最新文献

Background: Abdominal wall (AW) closure after solid organ transplantation (SOT) is challenging in case of loss of abdominal domain and/or large-for-size grafts. Primary closure is crucial to avoid open abdomen-associated morbidity and mortality. Several techniques have been developed to address this challenge, including nonvascularized rectus fascia transplantation (NVRF Tx). Long-term outcome is missing.

Methods: We designed a multicenter survey to analyze the worldwide experience after NVRF Tx. International Intestinal Rehabilitation And Transplantation Association members were invited to participate to a questionnaire. The survey included all NVRF Tx performed after SOT. Questions were classified into pre-, intra-, and postoperative data.

Results: Of the 29 responding centers, 8 performed NVRF Tx, comprising 98 patients in total. Thirty-two patients underwent multivisceral Tx (33.3%), 27 isolated intestinal Tx (28.1%), 21 combined liver-intestinal Tx (21.9%), 8 liver Tx (8.3%), 8 other SOT (8.3%), and 2 (2.0%) not reported. Thirty NVRF (30.9%) were from third-party donors. Thirty patients (31.3%) had surgical site infections. Seventy-one (74.0%) patients had reoperations, of them 18 (26.1%) patients had NVRF removal. Median follow-up time was 31 mo (10.0-63.5). Seventeen patients presented with bulging of the AW (18.7%), 5 with herniation (5.9%). No NVRF graft rejection was reported.

Conclusions: This survey reports long-term outcome after NVRF Tx, with herniation in a limited number of patients, no suspicion of clinical rejection and no additional infection and mortality. NVRF Tx has proven to be a useful option, belonging to the standard armamentarium for AW closure after SOT.

Background: Despite considerable advancement in surgical and immunological management in pancreas transplantation, graft pancreatitis remains a feared complication after pancreas transplantation. Identification of molecular mechanisms of underlying ischemia/reperfusion injury (IRI) in pancreas transplantation could, therefore, pave the path for targeted therapy to improve surgical outcomes. The aim of the study was to identify and validate the genes differentially expressed in the early period (24 h) of graft reperfusion in pancreas transplantation.

Methods: A porcine pancreas allotransplant model (n = 4) was used to identify and validate the genes aberrantly expressed in 60 min postreperfusion tissue samples (phase 1). Trends of expression of selected genes from phase 1 and corresponding protein product levels in serum were validated at defined time points for >24 h in a technically replicated external cohort (n = 3; phase 2).

Results: A total of 104 genes were found to be upregulated at 60 min after pancreas graft reperfusion. The most consistently overexpressed genes were IL6, THBS1, and MIR-21 (micro-RNA) mapped to protein kinase and intracellular signaling molecular pathways. Levels of expression of these genes correlated significantly with serum interleukin-6 (R = 0.60-0.81; P < 0.01) and tumor necrosis factor-alpha levels (R = 0.34-41; P > 0.05) at corresponding time points.

Conclusions: The results provide new insights into biomolecular pathways (THBS1-IL6-MIR-21 crosstalk and hydroxymethylglutarate coenzyme A reductase-linked nuclear factor kappa B activation) linked to pancreatic IRI in porcine transplantation model. Identification and validation of some novel molecular pathway interactions in human pancreas transplantation could pave the path for potential targeted therapy in alleviating graft injury in the early phases of pancreatic IRI.

Background: Optimal and maintained adherence to immunosuppressive medication is essential to kidney graft success.

Methods: We analyzed the longitudinal course of immunosuppressant adherence as measured with the Basel Assessment of Adherence to Immunosuppressive Medication Scale interview for up to 3-y duration of the Kidney Transplantation 360° study. Additionally, we examined putative baseline predictors of adherence trajectories. During the investigation period, patients participated in a multidisciplinary aftercare program consisting of case management, psychosocial and exercise assessments and interventions, including telemedicine support.

Results: The analysis sample with at least 1 valid information on the Basel Assessment of Adherence to Immunosuppressive Medication Scale consisted of 838 adult patients (41.3% women) aged 52.3 y (SD 13.5). Adherence to immunosuppressants improved significantly during the Kidney Transplantation 360° aftercare program; however, at each assessment point, 17%-25% of the patients still reported suboptimal adherence. Baseline predictors for a better improvement of adherence were younger age, male sex, and a longer duration since transplantation. Those variables were associated with a lower adherence at baseline, and we detected a "catch-up effect" over time, which might have been supported by the comprehensive aftercare program.

Conclusions: We believe that our aftercare program has supported the "catch-up effect" in adherence in younger male patients with a longer time after transplantation. However, the lack of a control group limits causal interpretations.

Background: Utilizing older donors (≥65 y) in lung transplantation can greatly expand donor availability while potentially maintaining typical survival outcomes in certain subpopulations, such as older recipients, especially compared to survival with single lung transplants (which comprise ~20%-25% of US lung transplants according to recent data).

Methods: This study included US adult lung transplants from 2010 to 2021 in the Scientific Registry for Transplant Recipients. To compare patient groups defined by donor age (D < 65 or D ≥ 65) and transplant type (single or double), stratified by recipient age (R18-39, R40-64, R ≥ 65), Inverse probability of treatment weighting was used to generate Kaplan-Meier survival estimates adjusted for >15 available covariates.

Results: In R40-64, survival with D ≥ 65 double (adjusted median survival [aMS] = 7.1 [3.3-12.0] y, n = 150, P = 0.15) at least equaled survival with D < 65 single (aMS = 5.7 [2.5-10.2] y, n = 2926), whereas D ≥ 65 single use was uncommon (n = 23), and survival was highest with D < 65 double (aMS = 7.7 [3.0-13.4] y, n = 10 934, P < 0.01). In R ≥ 65, survival with D ≥ 65 double (aMS = 5.0 [2.2-10.8] y, n = 90, P = 0.53) or D ≥ 65 single (aMS = 5.3 [1.9-8.4] y, n = 73, P = 0.72) was not significantly different from survival with D < 65 single (aMS = 4.7 [2.1-8.1] y, n = 3913), whereas survival was highest with D < 65 double (aMS = 5.8 [2.0-10.2] y, n = 4209, P < 0.01). In R18-39, D ≥ 65 were uncommon (n = 15).

Conclusions: Among lung recipients aged 40-64 y, donor age ≥65 y double transplants yield survival at least matching that of donor age <65 y single transplants. Among recipients aged ≥65 y, donor age ≥65 y double or single transplants yield survival comparable to that of donor age <65 single transplants. Compared with donor age <65 y double transplants, donor age ≥65 y double transplants had only ≤10 mo shorter adjusted median survival, within recipients aged ≥40 y. Judiciously increasing utilization of donors aged ≥65 y within recipients aged ≥40 y can reduce deaths among patients needing a lung transplant by decreasing donor scarcity, while maintaining favorable posttransplant survival.

Background: The effectiveness of mitigating performance status decline on the liver transplant (LT) waitlist and the impact of dynamic performance status changes on posttransplant outcomes remain understudied.

Methods: This US nationwide retrospective cohort study analyzed adult LT candidates listed between 2015 and 2023. Trends in the proportion of low Karnofsky Performance Status (KPS) at listing and LT were analyzed. The trend in ΔKPS, representing the change in KPS between waitlisting and LT, was evaluated using linear regression, and its impact on post-LT mortality was estimated using Cox proportional hazards models. Inverse probability censoring weighting accounted for selection bias from death or dropout before LT.

Results: Among 57 917 LT candidates, 39.5% had a low KPS (10%-40%) at listing. The likelihood of low KPS at waitlisting increased during the study period; however, there was a significant improvement in KPS at LT (P < 0.001). Amount of improvement in KPS (ΔKPS) significantly increased over time, by 0.5 points per month (P < 0.001), with the effect being approximately 3 times greater in patients with Model for End-Stage Liver Disease (MELD) score of <30 than those with MELD score of ≥30. A 10% increase in KPS between waitlisting and LT reduced the hazard of death post-LT by 5% (hazard ratio, 0.95; 95% confidence interval, 0.93-0.97).

Conclusions: Although the transplant community has mitigated low KPS on the LT waitlist, optimizing post-LT outcomes, only modest improvement was seen in patients with high (≥30) MELD scores at listing. These findings highlight the need to enhance functional status in LT candidates and ensure timely transplants for patients with high MELD scores.

Background: Graft-versus-host-disease (GvHD) is an infrequent but serious complication of small intestinal transplantation in children, which is associated with a very poor prognosis. This study evaluated a novel strategy of managing GvHD in these patients through a reduction in immunosuppression.

Methods: We conducted a retrospective review 108 consecutive pediatric patients at our center between 2005 and 2021, who had small intestinal transplantation. We assessed clinical features and outcomes as well as laboratory chimerism studies in cohorts of patients before and following a change in treatment strategy for GvHD from intensification to reduction in immunosuppression.

Results: Fourteen percent of pediatric patients developed GvHD after small intestinal transplantation. A change in treatment strategy to a reduction in immunosuppression led to significantly improved overall survival (log rank P = 0.015). This improved survival correlated biologically with altered T-cell chimerism dynamics in blood; in patients who had a reduction in immunosuppression, there was abrogation of the rise in donor T-cell chimerism over time seen in the blood of patients who instead had intensification of their immunosuppression. This may be because of permitting recipient lymphocytes to have a host-versus-graft effect and outcompete donor-derived lymphocytes.

Conclusions: Our results demonstrate that that altering the immunosuppressive therapy strategy, following clinical manifestations of GvHD such as a typical skin rash, from intensification to a reduction in immunosuppression led to significantly improved survival.

Background: Although small bowel transplantation is generally a highly effective treatment for patients with irreversible intestinal failure, and it is the only viable recourse for the restoration of intestinal function, the quantity of individuals awaiting a transplant surpasses that of accessible donors. With the advent of living donor small bowel transplantation, the small bowel transplant donor pool has been expanded to include parental donors. However, its global implementation is constrained by concerns regarding remaining donor safety and long-term prognoses. To help the donor recover better in the future, we have used 3-dimensional (3D) laparoscopic live donor ileal resection.

Methods: This study reviews 7 cases at our hospital involving living parental donors for small bowel transplantation. Each donor, being a close relative of the recipient, voluntarily provided a portion of their intestine. We used 3D laparoscopic ileal resection under general anesthesia to enable minimally invasive procedures, reduce surgical trauma, and expedite recovery. Comprehensive preoperative evaluations included psychological counseling to ensure informed consent, whereas postoperative care focused on tailored rehabilitation, nutritional support, bowel function monitoring, and psychological health.

Results: All donors recovered successfully without severe perioperative complications. At 6 mo postsurgery, all donors had normal bowel function and reported no issues with malabsorption or gastrointestinal health. Psychological assessments indicated good mental health and high satisfaction with their decision to donate.

Conclusions: Three-dimensional laparoscopic ileal resection for living parental donors is both feasible and safe, offering a minimally invasive approach with favorable donor outcomes. One-year follow-ups confirm that this technique provides high-quality grafts for recipients while preserving donor health and well-being. These findings support the potential for broader adoption of 3D laparoscopic ileal resection in living donor small bowel transplantation, with larger cohort studies recommended to validate these outcomes and refine donor care practices.

Background: Hilar cholangiocarcinoma has limited treatments, with transplantation emerging as a curative option. During the era of regional patient review, it was suggested that transplant centers performing a higher volume of transplants for cholangiocarcinoma had improved outcomes. However, it is unknown whether this association persists since the national standardization of guidelines in May 2019.

Methods: Transplant candidates listed in the United Network of Organ Sharing database using cholangiocarcinoma exception points from May 2019 to December 2022 were included. Experienced centers were defined as performing at least 10 transplants during the time period. Recipient and donor characteristics, graft and patient survival, and hospital length of stay were compared between more and less experienced centers. The Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier curves, log-rank tests, and Cox hazards analyses were used where appropriate.

Results: Between May 2019 and December 2022, 166 transplants for cholangiocarcinoma were performed at 37 centers, with "more experienced" centers accounting for 59% (n = 98). Unadjusted graft survival (P = 0.03) and patient survival (P = 0.047) were lower at less experienced centers. In addition to center experience, univariable Cox analyses recipient age (0.02), diabetes (0.18), and donor age (0.08) had a P value of ≤0.2. In a covariate-adjusted model, more experienced centers were associated with a 70% lower hazard of graft failure (hazard ratio, 0.29; 95% confidence interval, 0.12-0.70; P = 0.006) and 72% lower hazard of mortality (hazard ratio, 0.27; confidence interval, 0.11-0.69; P = 0.007).

Conclusions: These data suggest that experienced centers have improved posttransplant survival. Variations in selection and postoperative care not captured by this study may underlie this association. More granular studies are warranted to elucidate the impact of center experience on outcomes in transplantation for cholangiocarcinoma.

Background: Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution remain inadequate. It is unknown whether the degree of molecular allograft injury after treatment of AR/OP modulates the risk of CLAD and death.

Methods: To evaluate the association of molecular allograft injury after AR/OP with the incidence of CLAD/death, we conducted a multicenter prospective cohort study that included 93 patients who underwent lung transplantation between 2015 and 2022. The degree of molecular allograft injury after AR/OP was quantified by the mean area under the curve of longitudinal measures of plasma donor-derived cell-free DNA (dd-cfDNA).

Results: Over a median follow-up of 5 y, patients who developed CLAD/death had persistently higher levels of dd-cfDNA in the months after AR/OP. In multivariable Cox regression analysis adjusting for patient and transplant risk factors, mean dd-cfDNA levels after AR/OP were independently associated with an increased risk of CLAD/death (adjusted hazard ratio, 2.84; 95% confidence interval, 1.67-4.83; P < 0.001) and remained consistent when accounting for changes in pulmonary function after AR/OP events (hazard ratio, 2.62; 95% confidence interval, 1.53-4.47; P < 0.001).

Conclusions: The degree of allograft injury on the molecular level after AR/OP events in lung transplant recipients is associated with the risk of developing CLAD or death. This study demonstrates the potential of dd-cfDNA for improving risk stratification and monitoring the resolution and treatment responses of lung allograft injury.