Local competition influences donor heart acceptance practice.
Ontology highlight
ABSTRACT:
SUBMITTER: Clerkin KJ
PROVIDER: S-EPMC7721478 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Disparities in organ acceptance practices exacerbate donor heart nonuse and lead to increased waiting times and mortality for heart transplant candidates. We studied disparities in donor heart acceptance among US transplant centers and their relations to posttransplant outcomes. Candidate, potential transplant recipient match run, and deceased donor data were obtained from the United Network for Organ Sharing. We analyzed donor, candidate, and transplant center characteristics with respect to organ acceptance, offer acceptance, number of offers before acceptance (organ sequence number), and association with posttransplant mortality. A total of 693 420 donor heart offers made between April 2007 and December 2015 were included. We identified great variability in donor heart acceptance practices among US heart transplant centers. We identified donor and recipient characteristics that were strongly associated with heart organ and offer acceptance, and organ sequence number, and identified inconsistencies among centers with respect to how these characteristics influenced acceptance decisions. Finally, we identified characteristics that were highly predictive of donor heart nonuse and were not associated with increased recipient mortality, which may guide future efforts aimed at increasing use of available hearts for transplantation.
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Project description:BACKGROUND: The purpose of our research was to examine the relationship between male age and semen parameters in a range of ages (from 20s to 60s) in Egg Donation Program (EDP) cycles. EDP provides a pool of high quality oocytes, thus allowing better analysis of the sperm efficacy. DISCUSSION: The retrospective study population consisted of 484 male partners of patients undergoing EDP in in-vitro fertilization (IVF) treatments. A comparison was made of male age and sperm parameters within two groups: cycles resulting in a pregnancy (pregnant group) and cycles which failed to achieve a pregnancy (non-pregnant group). The men involved in the pregnant group were found to be significantly younger 43.2 +/- 8.1 than those of the nonpregnant group 46.81 +/- 7.8 (p = 0.003). Analysis of sperm morphology revealed a significant prevalence of teratozoospermia in males of the non-pregnant group, as compared to the males of the pregnant group (29% vs. 11%, respectively). The results also demonstrate that sperm parameters are apparently not diminished until men reach the age of 40. However, between 40-50 years old semen parameters deteriorate. Male age was found to be related to a reduction in sperm strict criteria: 44.8 in normozoospermia, 47.9 (p = 0.02), 48.4 (p = 0.04) and 51.9 (p = 0.001) years old in mild teratozoospermia, moderate teratozoospermia and severe teratozoospermia, respectively. Additionally, the results showed that the percentage of "healthy" embryos on day 3 of embryo culture was lower in the non-pregnant group (26%), as compared with the pregnant group (34%; p = 0.01). CONCLUSION: Our study confirms that sperm parameters are reduced by age and suggests that this age-dependent effect could be a reason for failures in IVF cycles even in EDP couples.
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Project description:Background. Organ shortage has liberalised the acceptance criteria of grafts for heart transplantation, but which donor characteristics ultimately influence the decision to perform transplantation? For the first time this was evaluated using real-time donor data from the German organ procurement organization (DSO). Observed associations are discussed with regard to international recommendations and guidelines. Methods. 5291 German donors (2006-2010) were formally eligible for heart donation. In logistic regression models 160 donor parameters were evaluated to assess their influence on using grafts for transplantation (random split of cases: 2/3 study sample, 1/3 validation sample). Results. Successful procurement was determined by low donor age (OR 0.87 per year; 95% CI [0.85-0.89], P < 0.0001), large donor height (OR 1.04 per cm; 95% CI [1.02-1.06], P < 0.0001), exclusion of impaired left ventricular function or wall motion (OR 0.01; 95% CI [0.002-0.036], P < 0.0001), arrhythmia (OR 0.05; 95% CI [0.009-0.260], P = 0.0004), and of severe coronary artery disease (OR 0.003; 95% CI [<0.001-0.01], P < 0.0001). Donor characteristics differed between cases where the procedure was aborted without and with allocation initiated via Eurotransplant.
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Project description:Background: While heart transplantation is the standard treatment for heart failure, both acute and chronic transplant rejection frequently occur. Since the modulation of protein phosphatase PP2A activity is critical for tissue and organ homeostasis under physiological and pathophysiological conditions, PP2A may also affect the ability to tolerate transplanted organs. Here we demonstrate that administration of a novel class of small molecule activators of PP2A (SMAPs) prolonged cardiac allograft survival in a mouse heterotopic heart transplantation model. Mechanistically, SMAPs effectively suppressed the inflammatory immune response while increasing Treg population in the allografts, findings corroborated by functional analysis of RNAseq data derived from Tregs of treated splenic tissue. Importantly, SMAPs further prolonged CTLA4-Ig (an immunosuppressive agent utilized in organ transplantation)-induced cardiac rejection tolerance and extended allograft survival. SMAPs also strongly mitigated cardiac allograft vasculopathy as evidenced by a marked reduction of neointimal hyperplasia and smooth muscle cell proliferation. Mechanistic studies implicate SMAPs elicited suppression of MEK/ERK pathways as a unifying mechanism for the aforementioned effects in Tregs and SMCs. These findings highlight the potential of PP2A activation in improving alloengraftment in heart transplantation and add knowledge to the phosphatase driven regulation of the immune system in the context of organ transplantation.
2023-07-20 | GSE236206 | GEO
Project description:BackgroundLung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality.MethodsWe performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality.ResultsOf 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%-67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592-0.685).ConclusionsVariability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.
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