Citations

Abstract Background: Flash glucose monitoring (FGM) can improve diabetes management, but no randomised controlled trials (RCTs) of FGM have been undertaken in Indigenous Australian populations. This study aimed to assess the feasibility of performing a RCT of FGM in Indigenous Australians with type 2 diabetes. Methods: In this open-labelled pilot RCT, Indigenous adults with type 2 diabetes were randomised to FGM or standard care for 6 months. Eligible participants were being treated with injectable diabetes medications and had a glycosylated haemoglobin (HbA1c) ≥ 7.0%. The feasibility outcome was the proportion of participants completing the trial. The preliminary effective outcome was the change in HbA1c. Secondary effectiveness outcomes included a change in time spent in target blood glucose; safety (hypoglycaemic episodes); and quality of life (EuroQol 5-Dimension 3-Level (EQ-5D-3L) score). Results: Of 126 screened individuals, 74 were eligible, 40 (31.7%) were randomised and 39 (97.5%) completed the study. Participants’ baseline characteristics were similar between the FGM and usual care groups, except for sex and body mass index. There were no between-group differences for: change in HbA1c; percentage of time spent in target blood glucose, low glucose and high glucose; or EQ-5D-3L scores. No severe hypoglycaemic episodes occurred. Conclusions: This is the first pilot RCT of FGM in Indigenous Australians with type 2 diabetes. The results support a larger RCT, which is currently in progress. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR12621000021875), retrospectively registered on 14 January 2021.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50–59, 60–69, and ≥ 70 years. RESULTS Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50–59 years, 85.0% in those 60–69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01–1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02–1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60–0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90–18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84–0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

Abstract Context Patients with adrenal hormone excess demonstrate increased cardiovascular (CV) risk and mortality. Objective We aimed to determine the effect of adrenal disorders on the inflammation marker glycoprotein acetylation (GlycA), total branched-chain amino acids (BCAAs), ketone bodies, and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. Methods We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFAs), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGLs), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n = 802). Referent individuals included participants in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study (n = 5241). GlycA, BCAAs, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, and statin therapy. Results In age- and sex-adjusted comparison to referent individuals, increased GlycA was noted in all patient categories, increased BCAAs in NFA, MACS, CS, PA, and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS, and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of participants with diabetes and CV disease. Conclusion Patients with functioning and nonfunctioning adrenal masses demonstrated increased GlycA and BCAAs, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

This survey study reports on use of renal replacement therapy, hemodynamic support, sedation, neuroimaging, and extracorporeal membrane oxygenation at Renal Anhydramnios Fetal Therapy trial sites for neonates with either bilateral renal agenesis or fetal kidney failure.

Abstract Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P < .001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy.

Abstract Aging, a major risk factor for delirium, is associated with accumulation of senescent cells in many tissues of the body. Senescent cells produce a host of proinflammatory and tissue remodeling factors collectively termed the senescence-associated secretory phenotype (SASP), which are secreted into circulation. The relationship between increased senescent cell burden and risk of delirium is not known. This study aimed to determine whether changes in circulating SASP proteins are associated with increased risk of postoperative delirium in cognitively intact older adults. Participants were recruited among patients scheduled for surgical or transcatheter aortic valve replacement, and blood was obtained at the presurgical visit. SASP factors were measured using commercially available multiplex magnetic bead immunoassays based on Luminex xMAP multianalyte profiling platform and analyzed on a MAGPIX system. Activin A concentration was determined by a Quantikine ELISA kit. Delirium cases were identified by manual chart abstraction, utilizing the problem list, ICD-10 codes, clinical notes, and nursing flowsheets. Eight of 62 (12.9%) of patients within the cohort developed postoperative delirium. Length of stay was significantly longer for patients who developed delirium (10.6 days) versus patients without delirium (6 days). Concentrations of SASP factors Activin A and PAPP-A were significantly higher in plasma of patients with delirium vs. those who did not develop delirium. IL-1 alpha concentration was significantly lower in patients with delirium vs without delirium. Other SASP factors measured were not statistically different between groups. More study is needed to determine whether these changes are directly related to increased senescent cell burden.