Unfair Advantages for Hepatocellular Carcinoma Patients Listed for Liver Transplant in Short-Wait Regions Following 2015 Hepatocellular Carcinoma Policy Change.
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SUBMITTER: Brondfield MN
PROVIDER: S-EPMC8751234 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti-human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%-19%, PRA 20%-79%, and PRA 80%-100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study.
| S-EPMC4731107 | biostudies-literature
Project description:BackgroundGeographic disparities in access to deceased donor kidney transplantation persist in the United States under the Kidney Allocation System (KAS) introduced in 2014, and the effect of transplant center practices on the probability of transplantation for wait-listed patients remains unclear.MethodsTo compare probability of transplantation across centers nationally and within donation service areas (DSAs), we conducted a registry study that included all United States incident adult kidney transplant candidates wait listed in 2011 and 2015 (pre-KAS and post-KAS cohorts comprising 32,745 and 34,728 individuals, respectively). For each center, we calculated the probability of deceased donor kidney transplantation within 3 years of wait listing using competing risk regression, with living donor transplantation, death, and waiting list removal as competing events. We examined associations between center-level and DSA-level characteristics and the adjusted probability of transplant.ResultsCandidates received deceased donor kidney transplants within 3 years of wait listing more frequently post-KAS (22%) than pre-KAS (19%). Nationally, the probability of transplant varied 16-fold between centers, ranging from 4.0% to 64.2% in the post-KAS era. Within DSAs, we observed a median 2.3-fold variation between centers, with up to ten-fold and 57.4 percentage point differences. Probability of transplantation was correlated in the post-KAS cohort with center willingness to accept hard-to-place kidneys (r=0.55, P<0.001) and local organ supply (r=0.44, P<0.001).ConclusionsLarge differences in the adjusted probability of deceased donor kidney transplantation persist under KAS, even between centers working with the same local organ supply. Probability of transplantation is significantly associated with organ offer acceptance patterns at transplant centers, underscoring the need for greater understanding of how centers make decisions about organs offered to wait-listed patients and how they relate to disparities in access to transplantation.
| S-EPMC7790218 | biostudies-literature
Project description:The debate around the potential superiority of quantum annealers over their classical counterparts has been ongoing since the inception of the field. Recent technological breakthroughs, which have led to the manufacture of experimental prototypes of quantum annealing optimizers with sizes approaching the practical regime, have reignited this discussion. However, the demonstration of quantum annealing speedups remains to this day an elusive albeit coveted goal. We examine the power of quantum annealers to provide a different type of quantum enhancement of practical relevance, namely, their ability to serve as useful samplers from the ground-state manifolds of combinatorial optimization problems. We study, both numerically by simulating stoquastic and non-stoquastic quantum annealing processes, and experimentally, using a prototypical quantum annealing processor, the ability of quantum annealers to sample the ground-states of spin glasses differently than thermal samplers. We demonstrate that (i) quantum annealers sample the ground-state manifolds of spin glasses very differently than thermal optimizers (ii) the nature of the quantum fluctuations driving the annealing process has a decisive effect on the final distribution, and (iii) the experimental quantum annealer samples ground-state manifolds significantly differently than thermal and ideal quantum annealers. We illustrate how quantum annealers may serve as powerful tools when complementing standard sampling algorithms.
| S-EPMC5430793 | biostudies-literature
Project description:Unfair advantages can be created either intentionally (e.g., cheating) or unintentionally (e.g., unintended benefit). Little is known regarding how children evaluate different types of advantages in situations where group identity and group membership are made salient. To investigate how children's group identity influences their evaluations and attribution of intentions in intergroup contexts, children were presented with three hypothetical advantages (unintentionally unfair, intentionally unfair, and fair) in a competitive context created by either an in-group member or an out-group member. Children (N = 120) were 4-6 years of age (n = 59; Mage = 5.29 years) and 7-10 years of age (n = 61; Mage = 8.34 years), including 64 girls and 56 boys. Participants were 67% European American, 18% African American, 11% Asian American, and 4% Hispanic. All participants were assigned to one of two teams in a contest in order to create an in-group/out-group manipulation prior to their evaluation of the actions. Out-group members viewed unintentional unfair and fair advantages as less acceptable than in-group members, but in-group and out-group members were equally negative in their assessment of an intentional transgression. When reasoning about unintentional and intentional unfair advantages, older children referenced the intentions of the advantage creator to justify their decisions more than younger children, whereas younger children reasoned about the impact of the behavior on their team more than older children. These novel findings shed light on developmental and social factors influencing children's understanding of fairness and intentionality in everyday contexts.
| S-EPMC8608754 | biostudies-literature
Project description:Cancer cells preferentially utilize glucose and glutamine, which provide macromolecules and antioxidants that sustain rapid cell division. Metabolic reprogramming in cancer drives an increased glycolytic rate that supports maximal production of these nutrients. The folate cycle, through transfer of a carbon unit between tetrahydrofolate and its derivatives in the cytoplasmic and mitochondrial compartments, produces other metabolites that are essential for cell growth, including nucleotides, methionine, and the antioxidant NADPH. Here, using hepatocellular carcinoma (HCC) as a cancer model, we have observed a reduction in growth rate upon withdrawal of folate. We found that an enzyme in the folate cycle, methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L), plays an essential role in support of cancer growth. We determined that MTHFD1L is transcriptionally activated by NRF2, a master regulator of redox homeostasis. Our observations further suggest that MTHFD1L contributes to the production and accumulation of NADPH to levels that are sufficient to combat oxidative stress in cancer cells. The elevation of oxidative stress through MTHFD1L knockdown or the use of methotrexate, an antifolate drug, sensitizes cancer cells to sorafenib, a targeted therapy for HCC. Taken together, our study identifies MTHFD1L in the folate cycle as an important metabolic pathway in cancer cells with the potential for therapeutic targeting.
| S-EPMC5409797 | biostudies-literature
Project description:BackgroundOur goal was to clarify the comparison between elective neck dissection (END) and the wait-and-see policy in neck management for cT1N0 buccal squamous cell carcinoma (SCC).MethodsThis was a retrospective comparison of 175 prospectively enrolled patients with cT1N0 buccal SCC. The patients were divided into two groups based on the nonrandomized management of the neck: 125 patients received END, and 50 patients were exposed to the wait-and-see policy. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). Patients were asked to complete the shoulder domain in the University of Washington quality of life questionnaire, version 4, 1?year postoperatively.ResultsTen of the patients undergoing END developed recurrence, and the 5-year LRC rate was 92%. Five patients undergoing the wait-and-see policy developed recurrence, and the 5-year LRC rate was 90%. The difference was not significant (p?=?0.668). There were 6 deaths in patients undergoing END, and the 5-year DSS rate was 94%. There were 3 deaths in patients undergoing the wait-and-see policy, and the 5-year DSS rate was 94%; the difference was not significant (p?=?0.777). The mean shoulder scores of patients undergoing END and the wait-and-see policy were 93.9 and 100, respectively, and the difference was not significant (p?=?0.284).ConclusionElective neck dissection does not carry a survival benefit compared to the wait-and-see policy, and it is not suggested for patients with cT1N0 buccal SCC.
| S-EPMC7285468 | biostudies-literature
Project description:Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.
| S-EPMC9293618 | biostudies-literature
Project description:Background Early kidney transplantation (KT) is the best option for patients with end-stage kidney disease, but little is known about dialysis access strategy in this context. We studied practice patterns of dialysis access and how they relate with outcomes in adults wait-listed early for KT according to the intended donor source. Methods This study from the REIN registry (2002–2014) included 9331 incident dialysis patients (age 18–69) wait-listed for KT before or by 6?months after starting dialysis: 8342 candidates for deceased-donor KT and 989 for living-donor KT. Subdistribution hazard ratios (SHR) of KT and death associated with hemodialysis by catheter or peritoneal dialysis compared with arteriovenous (AV) access were estimated with Fine and Gray models. Results Living-donor candidates used pretransplant peritoneal dialysis at rates similar to deceased-donor KT candidates, but had significantly more frequent catheter than AV access for hemodialysis (adjusted OR 1.25; 95%CI 1.09–1.43). Over a median follow-up of 43 (IQR: 23–67) months, 6063 patients received transplants and 305 died before KT. Median duration of pretransplant dialysis was 15 (7–27) months for deceased-donor recipients and 9 (5–15) for living-donor recipients. Catheter use in deceased-donor candidates was associated with a lower SHR for KT (0.88, 95%CI 0.82–0.94) and a higher SHR for death (1.53, 95%CI 1.14–2.04). Only five deaths occurred in living-donor candidates, three of them with catheter use. Conclusions Pretransplant dialysis duration may be quite long even when planned with a living donor. Advantages from protecting these patients from AV fistula creation must be carefully evaluated against catheter-related risks.
| S-EPMC7532567 | biostudies-literature
Project description:In the context of an aging end-stage renal disease population with multiple comorbid conditions, transplantation professionals face challenges in evaluating the global health of patients awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis.Retrospective cohort study of wait-listed patients using data for functional status from a national dialysis provider linked to United Network for Organ Sharing registry data.Adult kidney transplantation candidates added to the waiting list between 2000 and 2006.Physical Functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey, analyzed as a time-varying covariate.Kidney transplantation; survival benefit of transplantation versus remaining wait-listed.We used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplantation status was modeled as a time-varying covariate.The cohort comprised 19,242 kidney transplantation candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline Physical Functioning score quartile were more likely to be inactivated (adjusted HR vs highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse Physical Functioning score was associated with shorter 3-year survival (84% vs 92% for the lowest vs highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile.Functional status is self-reported.Even patients with low function appear to live longer with kidney transplantation versus dialysis. For wait-listed patients, global health measures such as functional status may be more useful in counseling patients about the probability of transplantation than in identifying who will derive a survival benefit from it.
| S-EPMC4624021 | biostudies-literature
Project description:BACKGROUND:PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. METHODS:Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. RESULTS:Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported 'being deferred' as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. CONCLUSION:The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and generally acceptable to most participants in this study.
| S-EPMC5398545 | biostudies-literature