Pediatric Transplantation最新文献

Background: POLG is one of several nuclear genes associated with mitochondrial DNA maintenance defects and is a group of diseases caused by mitochondrial DNA deficiency that results in impaired adenosine triphosphate production and organ dysfunction. Myocerebrohepatopathy spectrum (MCHS) is the most severe and earliest presentation of POLG mutations, and liver transplantation (LT) for MCHS has never been reported.

Case presentation: The patient was a 3-month-old boy with acute liver failure and no neurological manifestations (e.g., seizures). We performed a living donor LT using a left lateral segment graft from his father. The postoperative course was uneventful. Subsequently, a homozygous POLG mutation (c.2890C>T, p. R964C) was identified by multigene analysis of neonatal/infantile intrahepatic cholestasis. Moreover, respiratory chain complex I, II, and III enzyme activities and the ratio of mtDNA to nuclear DNA in the liver were reduced. Therefore, we considered that these clinical manifestations and examination findings met the definition for MCHS. During meticulous follow-up, the patient had shown satisfactory physical growth and mental development until the time of writing this report.

Conclusion: We presumed that the absence of remarkable neurologic manifestations prior to LT in patients with MCHS is a good indication for LT and contributes to a better prognosis in the present case.

Background: Recent studies demonstrate high offer decline and organ non-utilization rates are associated with increased pediatric heart transplant waitlist mortality. We sought to determine which donor, candidate, and offer specific variables most importantly influenced these decisions using only data available at the time of each offer.

Methods: Retrospective review of pediatric (<18 years) heart donor offers made to pediatric candidates in the United States between 2010 and 2020. In addition to standard donor, candidate, and offer data available in UNOS, we extracted objective and qualitative valvar and myocardial function data from all available donor echocardiogram reports.

Results: During the study period, 5625 pediatric donor hearts produced 30 156 offers to 4905 unique candidates, of which 88.7% of all offers were declined and 39.2% of organs were not utilized by pediatric waitlisted candidates. Of the 60.8% utilized hearts, 89.7% had a 'cumulatively' normal echocardiogram at the time of offer acceptance; 62.9% of hearts not utilized for a pediatric candidate also had a cumulatively normal final echocardiogram. Random forest and logistic regression modeling demonstrated good predictive performance (AUROC ≥0.83) of likelihood to accept when utilizing donor, candidate, and offer specific variables. SHAP variable importance scores demonstrated number of prior offer declines and candidate institution's prior year acceptance rates as the two most important variables influencing offer decisions.

Conclusions: Behavioral economics appear to play a significant role in pediatric heart transplant candidate institutions' acceptance practices, even when considering the arguably healthier pediatric donor population. Removal of prior institution's decisions from DonorNet may help increase donor utilization.

Background: A serial multiple mediator analysis was conducted to test the predictive effects of heart disease symptoms on pediatric heart transplant recipients health-related quality of life (HRQOL) from their perspective with patient-perceived cognitive problems, patient health communication, and treatment anxiety as hypothesized mediators.

Methods: One hundred and nineteen pediatric heart transplant recipients aged 8-18 completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Cardiac Module Heart Disease Symptoms Scale, Cognitive Problems Scale, Communication Scale and Treatment Anxiety Scale. The serial multiple mediator analysis tested the hypothesized sequential mediation of the cross-sectional association between patient-perceived heart disease symptoms and their perceived HRQOL.

Results: Heart disease symptoms indirect effects on HRQOL were sequentially mediated through cognitive problems, with cognitive problems' indirect effects mediated through patient health communication and treatment anxiety. A predictive analytics analysis consisting of age, gender, and time since transplant demographic covariates, demonstrated that heart disease symptoms, cognitive problems, patient health communication, and treatment anxiety accounted for 66 percent of the variance in patient-perceived HRQOL (p < .001), representing a large effect size.

Conclusions: Patient-perceived heart disease symptoms indirect effects on HRQOL in pediatric heart transplant recipients was explained by patient-perceived cognitive problems, patient health communication, and treatment anxiety. Delineating heart disease symptoms indirect effects on HRQOL from the perspective of pediatric patients may inform targeted clinical interventions to improve daily functioning in pediatric heart transplant recipients.

Background: The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring.

Methods: This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed.

Results: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II.

Conclusion: Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.

Background: The process of transition to adult-based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long-term outcome.

Methods: This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic. We investigated changes in these constructs over time. We further investigated the relationship between the change in these constructs over time spent in a focused transition program with adherence.

Results: The primary component underlying our transition readiness survey for patients and parents represented self-efficacy. Time spent in the transition program was an independent predictor of change in self-efficacy (rho 0.299, p = .015); however, the magnitude of that change had no relationship to adherence. Change in parent-proxy self-efficacy was found to have a statistically significant relationship with tacrolimus standard deviation (rho -0.301, p = .026). There was disagreement identified between patient and parent responses on the survey. Neither change in patient nor parent reports of self-efficacy was found to have a relationship with post-transfer adherence.

Conclusions: This study reaches the novel conclusion that self-efficacy and parent-proxy self-efficacy are dynamic concepts that change over time spent in a focused transition program. The patient-parent disagreement and the relationship between parent-proxy self-efficacy and adherence stress the importance of involving parents/guardians in the transition process as well.

Background: This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD).

Methods: A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri-transplant including pre-transplant, Day +3, and Day +30.

Results: By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p = .029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0-I° aGVHD and II-III° aGVHD indicates that children with II-III° aGVHD had more Bilophila before transplantation than children with 0-I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed.

Conclusions: This study has synthetically shown the distribution of intestinal flora after allo-HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease.

Background: Hepatic artery thrombosis (HAT) is a reported complication of 5%-10% of pediatric liver transplantations, rates 3-4 times that seen in adults. Early HAT (seen within 14 days after transplant) can lead to severe allograft damage and possible urgent re-transplantation. In this report, we present our analysis of HAT in pediatric liver transplant from a national clinical database and examine the association of HAT with anticoagulant or antiplatelet medication administered in the post-operative period.

Methods: Data were obtained from the Pediatric Health Information System database maintained by the Children's Hospital Association. For each liver transplant recipient identified in a 10-year period, diagnosis, demographic, and medication data were collected and analyzed.

Results: Our findings showed an average rate of HAT of 6.3% across 31 centers. Anticoagulant and antiplatelet medication strategies varied distinctly among and even within centers, likely due to the fact there are no consensus guidelines. Notably, in centers with similar medication usage, HAT rates continue to vary. At the patient level, use of aspirin within the first 72 h of transplantation was associated with a decreased risk of HAT, consistent with other reports in the literature.

Conclusion: We suggest that concerted efforts to standardize anticoagulation approaches in pediatric liver transplant may be of benefit in the prevention of HAT. A prospective multi-institutional study of regimen-possibly including aspirin-following transplantation could have significant value.

Background: Children frequently undergo routine Doppler-ultrasound (DUS) after liver transplantation (LT) for which they are fasted, but this may cause hunger and discomfort.

Objective: To determine if DUS measurements, with focus on the portal vein (PV), are affected by prandial changes, and if this affects distress and feasibility of the DUS.

Materials and methods: Children were prospectively included to undergo a pre- and postprandial DUS on the same day at 6 months after LT. Pre- and anastomotic PV peak systolic velocity (PSV), and hepatic artery and hepatic vein DUS measurements were obtained. Pre- and postprandial measurements, and relative postprandial change of PV velocity ratio (VR) compared to PV anastomotic PSV, were compared using paired-sample t-tests and intraclass correlation coefficients (ICC). Obscuration by bowel gas, difficulty of DUS, and impact of fasting were assessed using 5-point rating scales.

Results: Twenty-eight children (median age 3.5 years, IQR 1.6-10.8) were included; four were subsequently excluded because they were not fasted (N = 2) or withdrew consent for the second DUS (N = 2). Measurements between pre- and postprandial DUS, and relative postprandial change of VR compared to PV anastomotic PSV, were not significantly different (p > .05). Test consistency was good (ICC = 0.69, 95% CI = 0.29-0.67) for PV anastomotic PSV, and excellent (95% CI = 0.61-0.93) for PV VR. Obscuration by bowel gas or ease of DUS did not change after eating (p > .05). The majority (16/28, 57.2%) found fasting difficult, and several (13/28, 46.4%) got upset when fasted.

Conclusion: Children with an LT do not need to be fasted for routine DUS, which may decrease the burden of the examination.