Adrenal cysts less than 10 cm can be safely observed.

BACKGROUND: Adrenal cysts are rare and appropriate management is unclear due to a lack of data on their natural history. Understanding adrenal cyst growth patterns would assist in clinical management. METHODS: This single-institution study included all adult patients diagnosed with simple adrenal cysts between 2004 and 2021. Baseline characteristics and outcomes of those who underwent resection (ADX) or observation (OBS) were compared using the chi-squared test, student's t-test, and Wilcoxon rank-sum test. Growth curves and sensitivity analysis were plotted for all patients who had follow-up imaging. RESULTS: We identified 77 patients with imaging-confirmed adrenal cysts. The majority were female (75.3%) and more than half were white (55.8%). One-third of patients underwent ADX, and the remaining were observed. ADX patients were younger (median age [IQR]: 55.5 y [45.0-68.2 y] vs. 44.2 y [38.7-55.0 y], p = 0.01) and more likely to be Hispanic (12% vs. 0%, p = 0.05). ADX patients presented with larger cysts (5.6 vs. 2.6 cm, p = 0.002). The median time from diagnosis to last follow-up was 1.1 y for ADX and 4.1 y for OBS. Average growth for OBS was 0.3 cm/y, while average growth for ADX was 3.9 cm/y. In ADX patients, cysts >10 cm grew significantly faster than cysts <10 cm (median growth rate 13.2 cm/y vs. 0.3 cm/y, p < 0.05). There was no adrenal malignancy diagnosis, hyperfunctionality, or observation-related complications (e.g., rupture). CONCLUSION: While size >4-6 cm has guided surgical referral for solid adrenal masses, this study demonstrates a size threshold of 10 cm, below which asymptomatic, simple adrenal cysts can safely be observed.

Association between Pre-Kidney Transplant Elevated Parathyroid Hormone and Post-Transplant Graft Loss.

BACKGROUND: Prior to kidney transplantation (KT) most patients have an elevated parathyroid hormone (PTH). However, the impact of PTH on post-KT mortality and graft loss is unclear. We quantified the association between PTH levels measured at transplant and adverse post-KT outcomes. STUDY DESIGN: A prospective longitudinal cohort of 1,136 KT recipients from a single tertiary care center between 12/2008 and 2/2020. Pre-KT PTH levels were abstracted retrospectively. Adjusted multivariable Cox proportional hazards models were used to estimate the association between pre-KT PTH levels and mortality and death-censored graft loss (DCGL). RESULTS: Of 1,136 recipients, pre-KT PTH levels were ≤300pg/mL in 62.3% and >600pg/mL in 12.5%. Compared to those with a pre-KT PTH≤300pg/mL, patients with a pre-KT PTH>600pg/mL were more likely to be Black (51.4% vs. 34.6%) and have a longer dialysis vintage (4.8y vs. 1.7y) (p<0.001). Those with a pre-KT PTH>600pg/mL had a higher 10-year cumulative incidence of DCGL than those with PTH≤300pg/mL (31.7% vs. 15.4%, p<0.001). After adjusting for confounders, pre-KT PTH>600pg/mL was associated with a 1.76-fold increased risk of DCGL (95% CI: 1.16-2.65). The magnitude of this association differed by race (pinteraction=0.011) and by treatment (pinteraction=0.018). Among non-Black patients, a PTH>600pg/mL was associated with a 3.21-fold increased risk of DCGL compared to those with PTH≤300pg/mL (95%CI: 1.77-5.81). Among untreated patients, those with PTH>600pg/mL had a 2.54-fold increase in DCGL (95%CI: 1.44-4.47). There was no association between pre-KT PTH and mortality risk. CONCLUSIONS: PTH >600pg/mL prior to KT increased the risk of DCGL by 76%, demonstrating the importance of treating PTH prior to KT to prevent graft loss in a contemporary era with the introduction and widespread availability of medical therapy.

Making Choices: A Multi-institutional, Longitudinal Cohort Study Assessing Changes in Treatment Outcome Valuation for Low-Risk Thyroid Cancer.

OBJECTIVE: To evaluate the relative importance of treatment outcomes to patients with low-risk thyroid cancer (TC). SUMMARY BACKGROUND DATA: Overuse of total thyroidectomy (TT) for low-risk TC is common. Emotions from a cancer diagnosis may lead patients to choose TT resulting in outcomes that do not align with their preferences. METHODS: Adults with clinically low-risk TC enrolled in a prospective, multi-institutional, longitudinal cohort study from 11/2019-6/2021. Participants rated treatment outcomes at the time of their surgical decision and again 9 months later by allocating 100 points amongst 10 outcomes. T-tests and Hotelling's T 2 statistic compared outcome valuation within and between subjects based on chosen extent of surgery (TT vs. lobectomy). RESULTS: Of 177 eligible patients, 125 participated (70.6% response) and 114 completed the 9-month follow-up (91.2% retention). At the time of the treatment decision, patients choosing TT valued the risk of recurrence more than those choosing lobectomy and the need to take thyroid hormone less ( P <0.05). At repeat valuation, all patients assigned fewer points to cancer being removed and the impact of treatment on their voice, and more points to energy levels ( P <0.05). The importance of the risk of recurrence increased for those who chose lobectomy and decreased for those choosing TT ( P <0.05). CONCLUSION: The relative importance of treatment outcomes changes for patients with low-risk TC once the outcome has been experienced to favor quality of life over emotion-related outcomes. Surgeons can use this information to discuss the potential for asthenia or changes in energy levels associated with total thyroidectomy.

High-Performance Iridium-Molybdenum Oxide Electrocatalysts for Water Oxidation in Acid: Bayesian Optimization Discovery and Experimental Testing.

Ir oxides are costly and scarce catalysts for oxygen evolution reaction (OER) in acid. There has been extensive interest in developing alternatives that are either Ir-free or require smaller amounts of Ir to drive the reactions at acceptable rates. One design strategy is to identify Ir-based mixed oxides that achieve similar performance while requiring smaller amounts of Ir. The obstacle to this strategy has been a very large phase space of the Ir-based mixed metal oxides, in terms of the metals combined with Ir and the different crystallographic structures of the mixed oxides, which prevents a thorough exploration of possible materials. In this work, we developed a workflow that uses machine-learning-aided Bayesian optimization in combination with density functional theory to make the exploration of this phase space plausible. This screening identified Mo as a promising dopant for forming acid-tolerant Ir-based oxides for the OER. We synthesized and characterized the Ir-Mo mixed oxides in the form of thin-film electrocatalysts with a known surface area. We show that these mixed oxides exhibited overpotentials ∼30 mV lower than a pure Ir control while maintaining 24% lower Ir dissolution rates than the Ir control. These findings suggest that Mo is a promising dopant and highlight the promise of machine learning to guide the experimental exploration and optimization of catalytic materials.

Association of Postoperative Delirium With Incident Dementia and Graft Outcomes Among Kidney Transplant Recipients.

BACKGROUND: Kidney transplant (KT) recipients have numerous risk factors for delirium, including those shared with the general surgical population (eg, age and major surgery) and transplant-specific factors (eg, neurotoxic immunosuppression medications). Evidence has linked delirium to long-term dementia risk in older adults undergoing major surgery. We sought to characterize dementia risk associated with post-KT delirium. METHODS: Using the United States Renal Data System datasets, we identified 35 800 adult first-time KT recipients ≥55 y. We evaluated risk factors for delirium using logistic regression. We evaluated the association between delirium and incident dementia (overall and by subtype: Alzheimer's, vascular, and other/mixed-type), graft loss, and death using Fine and Gray's subhazards models and Cox regression. RESULTS: During the KT hospitalization, 0.9% of recipients were diagnosed with delirium. Delirium risk factors included age (OR = 1.40, 95% CI, 1.28-1.52) and diabetes (OR = 1.38, 95% CI, 1.10-1.73). Delirium was associated with higher risk of death-censored graft loss (aHR = 1.52, 95% CI, 1.12-2.05) and all-cause mortality (aHR = 1.53, 95% CI, 1.25-1.89) at 5 y post-KT. Delirium was also associated with higher risk of dementia (adjusted subhazard ratio [aSHR] = 4.59, 95% CI, 3.48-6.06), particularly vascular dementia (aSHR = 2.51, 95% CI, 1.01-6.25) and other/mixed-type dementia (aSHR = 5.58, 95% CI, 4.24-7.62) subtypes. The risk of all-type dementia associated with delirium was higher for younger recipients aged between 55 and 64 y ( Pinteraction = 0.01). CONCLUSIONS: Delirium is a strong risk factor for subsequent diagnosis of dementia among KT recipients, particularly those aged between 55 and 64 y at the time of transplant. Patients experiencing posttransplant delirium might benefit from early interventions to enhance cognitive health and surveillance for cognitive impairment to enable early referral for dementia care.

Prevalence and risk factors for dysphagia in older adults after thyroid and parathyroid surgery.

BACKGROUND: We aimed to determine the prevalence and risk factors for dysphagia in adults 65 years and older before and after thyroidectomy or parathyroidectomy. METHODS: We performed a longitudinal prospective cohort study of older adults undergoing initial thyroidectomy or parathyroidectomy. We administered the Dysphagia Handicap Index questionnaire preoperatively and 1, 3, and 6 months postoperatively. We compared preoperative and postoperative total and domain-specific scores using paired t tests and identified risk factors for worse postoperative scores using multivariable logistic regression. RESULTS: Of the 175 patients evaluated, the mean age was 71.1 years (range = 65-94), 73.7% were female, 40.6% underwent thyroidectomy, 57% underwent bilateral procedures, and 21.1% had malignant diagnoses. Preoperative swallowing dysfunction was reported by 77.7%, with the prevalence 22.4% greater in frail than robust patients (P = .013). Compared to preoperative scores, 43.4% and 49.1% had worse scores at 3 and 6 months postoperatively. Mean functional domain scores increased by 62.3% at 3 months postoperatively (P = .007). Preoperative swallowing dysfunction was associated with a 3.07-fold increased likelihood of worse functional scores at 3 months. Whereas frailty was associated with preoperative dysphagia, there was no association between worse postoperative score and age, sex, race, frailty, body mass index, smoking status, gastroesophageal reflux disease, comorbidity index, malignancy, surgical extent, or type of surgery. CONCLUSION: Adults 65 years and older commonly report swallowing impairment preoperatively, which is associated with a 3.07-fold increased likelihood of worsened dysphagia after thyroid and parathyroid surgery that may persist up to 6 months postoperatively.

Socioeconomic disparity in the association between fine particulate matter exposure and papillary thyroid cancer.

BACKGROUND: Limited data exists suggesting that cumulative exposure to air pollution in the form of fine particulate matter (aerodynamic diameter ≤ 2.5 µm [PM2.5]) may be associated with papillary thyroid carcinoma (PTC), although this relationship has not been widely established. This study aims to evaluate the association between PM2.5 and PTC and determine the subgroups of patients who are at the highest risk of PTC diagnosis. METHODS: Under IRB approval, we conducted a case-control study of adult patients (age ≥ 18) newly diagnosed with PTC between 1/2013-12/2016 across a single health care system were identified using electronic medical records. These patients were compared to a control group of patients without any evidence of thyroid disease. Cumulative PM2.5 exposure was calculated for each patient using a deep learning neural networks model, which incorporated meteorological and satellite-based measurements at the patients' residential zip code. Adjusted multivariate logistic regression was used to quantify the association between cumulative PM2.5 exposure and PTC diagnosis. We tested whether this association differed by gender, race, BMI, smoking history, current alcohol use, and median household income. RESULTS: A cohort of 1990 patients with PTC and a control group of 6919 patients without thyroid disease were identified. Compared to the control group, patients with PTC were more likely to be older (51.2 vs. 48.8 years), female (75.5% vs 46.8%), White (75.2% vs. 61.6%), and never smokers (71.1% vs. 58.4%) (p < 0.001). After adjusting for age, sex, race, BMI, current alcohol use, median household income, current smoking status, hypertension, diabetes, COPD, and asthma, 3-year cumulative PM2.5 exposure was associated with a 1.41-fold increased odds of PTC diagnosis (95%CI: 1.23-1.62). This association varied by median household income (p-interaction =0.03). Compared to those with a median annual household income <$50,000, patients with a median annual household income between $50,000 and < $100,000 had a 43% increased risk of PTC diagnosis (aOR = 1.43, 95%CI: 1.19-1.72), and patients with median household income ≥$100,000 had a 77% increased risk of PTC diagnosis (aOR = 1.77, 95%CI: 1.37-2.29). CONCLUSIONS: Cumulative exposure to PM2.5 over 3 years was significantly associated with the diagnosis of PTC. This association was most pronounced in those with a high median household income, suggesting a difference in access to care among socioeconomic groups.

Sleep duration and cognitive function among older adults with chronic kidney disease: results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (CKD) population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD. METHODS: This was a study of 3215 older adults (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011-14) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed and global cognition) and kidney function. We quantified the association between sleep duration and cognitive function using linear regression and tested whether the associations differed among those with CKD and without using a Wald test for interaction. RESULTS: Among 3215 participants, 13.3% reported 2-5 hours of sleep/day, 75.2% reported 6-8 hours, and 11.5% reported ≥9 hours. Persons with CKD were more likely to sleep ≥9 hours [odds ratio 1.73 (95% confidence interval 1.22-2.46)]. Among participants with CKD, those with a sleep duration ≥9 hours demonstrated worse global cognitive function (P for interaction = .01), immediate recall (P for interaction = .01) and verbal fluency (P for interaction = .004) than those with a sleep duration of 6-8 h; no differences were observed for participants with CKD who slept 2-5 hours. Among participants without CKD, sleep was not associated with any measures of cognitive function. CONCLUSIONS: Longer sleep duration is associated with worse cognitive function only among persons with CKD, and global cognition, delayed recall and verbal fluency are particularly affected. Studies should identify interventions to improve sleep patterns and quality in this population.

Hyperparathyroidism at 1 year after kidney transplantation is associated with graft loss.

BACKGROUND: Hyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes. METHODS: We identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race. RESULTS: Of 824 recipients, 60.9% had post-transplant hyperparathyroidism. Compared with non-hyperparathyroidism patients, those with post-transplant hyperparathyroidism were more likely to be Black (47.2% vs 32.6%), undergo dialysis before kidney transplantation (86.9% vs 76.6%), and have a parathyroid hormone level ≥300 pg/mL before kidney transplantation (26.8% vs 9.5%) (all P < .001). Patients with post-transplant hyperparathyroidism had a 1.6-fold higher risk of death-censored graft loss (adjusted hazard ratio = 1.60, 95% confidence interval: 1.02-2.49) compared with those without post-transplant hyperparathyroidism. This risk more than doubled in those with parathyroid hormone ≥300 pg/mL 1 year after kidney transplantation (adjusted hazard ratio = 4.19, 95% confidence interval: 1.95-9.03). The risk of death-censored graft loss did not differ by age, sex, or race (all Pinteraction > .05). There was no association between post-transplant hyperparathyroidism and mortality. CONCLUSION: The risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.

Black patients are more likely to undergo parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Prior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism. METHODS: We used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race. RESULTS: Of this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74-1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27-1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy. CONCLUSION: Black patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.

Secondary Hyperparathyroidism and Cognitive Decline.

Purpose of Review: Secondary hyperparathyroidism (SHPT) likely contributes to the high prevalence of cognitive decline found among individuals with end-stage kidney disease (ESKD). Our objective is to critically evaluate the recent literature regarding the association between SHPT and cognitive decline and identify potential mechanisms. Recent Findings: Nine studies assessing the relationship between SHPT and cognition have been published in the last two decades, each showing that elevated parathyroid hormone (PTH) levels were associated with cognitive decline. One also found structural changes within the brain related to SHPT. Additionally, two found that SHPT treatment decreases the risk of cognitive decline in ESKD patients. Summary: SHPT is associated with cognitive impairment. However, the severity of SHPT associated with these changes and the specific cognitive domains affected remain unclear. Future studies are needed to focus on specific cognitive domains, the trajectory of cognitive decline, and optimal treatment strategies including the impact of kidney transplant and tertiary hyperparathyroidism.

Key recommendations from the 2021 "inclusion of older adults in clinical research" workshop.

Older adults are often underrepresented in clinical research, even though older adults are major consumers of novel therapies. We present major themes and recommendations from the 2021 "Inclusion of Older Adults in Clinical Research" Workshop, convened by the Clinical and Translational Science Award (CTSA) Inclusion of Older Adults as a Model for Special Populations Workgroup and the Research Centers Collaborative Network (RCCN). The goal of this workshop was to develop strategies to assist the research community in increasing the inclusion of older adults in clinical research. Major identified barriers include historical lack of federal guidelines, ageist biases and stereotypes, and lack of recruitment and retention techniques or infrastructure focused on older adults. Three key recommendations emerged: 1) engaging with the policymaking process to further promote inclusion; 2) using the CTSA Workgroup Presentation Materials Library and other resources to overcome ageism, and 3) building institutional capacity to support age inclusion.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

The impact of patient age on practice patterns and outcomes for primary hyperparathyroidism.

BACKGROUND: Management of asymptomatic primary hyperparathyroidism (PHPT) in older patients (age >50) is controversial. The 4th International Workshop on the Management of Asymptomatic PHPT recommends surveillance for older patients who lack objective signs of disease, whereas The American Association of Endocrine Surgeons (AAES) guidelines recommend consideration of parathyroidectomy for patients of any age with subjective constitutional, neuropsychiatric, or cognitive symptoms. Therefore, the primary objective of this study was to evaluate the association between patient age and both practice patterns and outcomes in the management of patients with sporadic PHPT. METHODS: The Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) database was queried for all adults (age ≥18) who underwent an index parathyroidectomy for sporadic primary hyperparathyroidism between 2014 and 2020. Associations between patient age (≤50 years vs. >50 years) and both practice patterns and outcomes were evaluated separately using adjusted multivariable logistic and multinomial regression models. RESULTS: Of 9,938 patients who underwent parathyroidectomy, 8,080 (81.3%) were >50 years old and 1,858 (18.7%) were ≤50. Of this cohort, 17% of older patients and 26% of younger patients presented with only subjective symptoms. Compared to younger patients, older patients were more likely to have an objective indication for parathyroidectomy (aOR = 1.8, 95%CI: 1.6-2.0, p < 0.001). They were also more likely to undergo ≥2 imaging studies pre-operatively (aOR = 1.2, 95%CI: 1.1-1.3, p = 0.003), to undergo bilateral neck exploration (aOR = 1.4, 95%CI: 1.3-1.6, p < 0.001), and to have multi-gland disease (aOR = 1.6, 95%CI: 1.4-1.8, p < 0.001). There was no difference between age groups and parathyroidectomy-related complications including hypocalcemia, vocal cord dysfunction, hematoma requiring evacuation, or reintubation, however, older patients were less likely to have any peri-operative morbidity (aOR = 0.7, 95%CI: 0.6-0.9, p = 0.011). CONCLUSIONS: Older patients were more likely to meet objective criteria prior to undergoing parathyroidectomy by CESQIP participating high-volume endocrine surgeons, however they were less likely to have peri-operative complications compared to younger patients. Given the growing evidence demonstrating improvement of both objective and subjective symptoms after parathyroidectomy for PHPT, additional studies are still needed to fully understand the benefit of surgical referral in older adults for less objective indications.