Faculty Bibliography

BACKGROUND:Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS:A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS:Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION/CONCLUSIONS:Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

BACKGROUND:The association between exposure to air pollution and papillary thyroid carcinoma is unknown. We sought to estimate the relationship between long-term exposure to the fine (diameter ≤ 2.5 μm) particulate matter component of air pollution and the risk of papillary thyroid cancer. METHODS:Adult (age ≥18) patients with newly diagnosed papillary thyroid carcinoma between January 1, 2013 and December 31, 2016 across a single health system were identified using electronic medical records. Data from 1,990 patients with papillary thyroid carcinoma were compared with 3,980 age- and sex-matched control subjects without any evidence of thyroid disease. Cumulative fine (diameter <2.5 μm) particulate matter exposure was estimated by incorporating patients' residential zip codes into a deep learning neural networks model, which uses both meteorological and satellite-based measurements. Conditional logistic regression was performed to assess for association between papillary thyroid carcinoma and increasing fine (diameter ≤2.5 μm) particulate matter concentrations over 1, 2, and 3 years of cumulative exposure preceding papillary thyroid carcinoma diagnosis. RESULTS:n = 0.04). Among current smokers (n = 623), the risk of developing papillary thyroid carcinoma was highest (adjusted odds ratio = 1.35, 95% confidence interval: 1.12-1.63). CONCLUSION/CONCLUSIONS:Increasing concentration of fine (diameter ≤2.5 μm) particulate matter in air pollution is significantly associated with the incidence of papillary thyroid carcinoma with 2 and 3 years of exposure. Our novel findings provide additional insight into the potential associations between risk factors and papillary thyroid carcinoma and warrant further investigation, specifically in areas with high levels of air pollution both nationally and internationally.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Rationale & Objective/UNASSIGNED:Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. Study Design/UNASSIGNED:Retrospective database study. Setting & Participants/UNASSIGNED:Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures/UNASSIGNED:Various immunosuppression regimens in the first 3 months after transplant. Outcomes/UNASSIGNED:Development of DM >3 months-to-1 year posttransplant. Analytical Approach/UNASSIGNED:We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. Results/UNASSIGNED:(aHR, 0.63; 95% CI, 0.46-0.87). Limitations/UNASSIGNED:Retrospective study and lacked data on immunosuppression levels. Conclusions/UNASSIGNED:The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

INTRODUCTION:Loneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). METHODS:We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables. RESULTS:Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. CONCLUSION:Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.