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Browsing by Author "Segev, Dorry L."
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Item A Metabolomics Approach to Identify Metabolites Associated With Mortality in Patients Receiving Maintenance Hemodialysis(Elsevier, 2024-06-29) Al Awadhi, Solaf; Myint, Leslie; Guallar, Eliseo; Clish, Clary B.; Wulczyn, Kendra E.; Kalim, Sahir; Thadhani, Ravi; Segev, Dorry L.; McAdams DeMarco, Mara; Moe, Sharon M.; Moorthi, Ranjani N.; Hostetter, Thomas H.; Himmelfarb, Jonathan; Meyer, Timothy W.; Powe, Neil R.; Tonelli, Marcello; Rhee, Eugene P.; Shafi, Tariq; Medicine, School of MedicineIntroduction: Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis. Methods: We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models. Results: The mean age of the participants was 64 years, the mean dialysis duration was 35 days, and there were 44 deaths (8.4%) during a 1-year follow-up period. Two metabolites were significantly associated with 1-year mortality. Quinolinate levels (a kynurenine pathway metabolite) were 1.72-fold higher in patients who died within year 1 compared with those who did not (pFDR, 0.009), wheras mesaconate levels (an emerging immunometabolite) were 1.57-fold higher (pFDR, 0.002). An additional 42 metabolites had high importance as per LASSO, 46 per RF, and 9 per both ML models but were not significant per limma. Conclusion: Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.Item Barriers to access in pediatric living‐donor liver transplantation(Wiley, 2019-09) Mogul, Douglas B.; Lee, Joy; Purnell, Tanjala S.; Massie, Allan B.; Ishaque, Tanveen; Segev, Dorry L.; Bridges, John F. P.; Medicine, School of MedicineChildren receiving a LDLT have superior post‐transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well‐informed about LDLT but individuals with public insurance were significantly less likely to feel well‐informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT.Item Clarifying the HOPE Act landscape: The challenge of donors with false-positive HIV results(Wiley, 2020-02) Durand, Christine M.; Werbel, William; Doby, Brianna; Brown, Diane; Desai, Niraj M.; Malinis, Maricar; Price, Jennifer; Chin-Hong, Peter; Mehta, Shikha; Friedman-Moraco, Rachel; Turgeon, Nicole A.; Gilbert, Alexander; Morris, Michele I.; Stosor, Valentina; Elias, Nahel; Aslam, Saima; Santos, Carlos A.Q.; Hand, Jonathan M.; Husson, Jennifer; Pruett, Timothy L.; Agarwal, Avinash; Adebiyi, Oluwafisayo; Pereira, Marcus; Small, Catherine B.; Apewokin, Senu; Lee, Dong Heun; Haidar, Ghady; Blumberg, Emily; Mehta, Sapna A.; Huprikar, Shirish; Florman, Sander S.; Redd, Andrew D.; Tobian, Aaron A.R.; Segev, Dorry L.; Medicine, School of MedicineItem Decreasing deceased donor transplant rates among children (≤6 years) under the new kidney allocation system(Elsevier, 2018) Shelton, Brittany A.; Sawinski, Deirdre; Ray, Christopher; Reed, Rhiannon D.; MacLennan, Paul A.; Blackburn, Justin; Young, Carlton J.; Gray, Stephen; Yanik, Megan; Massie, Allan; Segev, Dorry L.; Locke, Jayme E.; Health Policy and Management, School of Public HealthThe Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time-to-event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014), Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.