Sleep disruption in patients with active and treated endogenous Cushing's syndrome.

CONTEXT: The hypothalamic-pituitary-adrenal axis is a critical regulator of circadian rhythm in humans. Impaired sleep adversely affects metabolic, emotional, and cognitive health. OBJECTIVE: To characterize sleep disturbances in patients with active and treated Cushing's syndrome (CS), and identify factors associated with impaired sleep in treated patients. DESIGN: Single-center cross-sectional study. METHODS: Patients with pituitary or adrenal CS enrolled in an observational study completed Nottingham Health Profile (NHP), CushingQoL, and Hospital Anxiety and Depression assessments. Cross-sectional analysis was conducted including patients with active and treated disease. RESULTS: 113 (94 female) patients with CS were included, 104 pituitary and 9 adrenal, with mean age at diagnosis of 43.9 ± 13.4 years. Mean and maximum duration of follow up was 5.1 and 23 years. Mean NHP sleep score was lower (i.e., improved) in patients with treated vs. active disease (29.6 ± 30.2 vs. 51.9 ± 30.9, p = 0.0005), as was CushingQoL sleep score (p = 0.015), but 41.5% of patients with treated disease stated they often or always had trouble sleeping. The proportion of treated vs. active patients taking medication for sleep, mood, or pain was not different. Neither NHP nor CushingQoL pain scores were lower in treated vs. active patients (p = 0.39 and 0.53). In patients with treated CS, anxiety and depression correlated with worse sleep scores. CONCLUSIONS: Patients with treated CS report improved sleep quality compared to those with active disease, but almost half of treated patients still report sleep challenges. The need for sleep medications, reported by one third of patients, was not different after CS treatment. Ongoing mood disturbances may play a role in persistent sleep disruption. Further work should focus on determinants of sleep impairments in treated CS patients.

Suture Fixation to Reduce Graft Detachment in Descemet Stripping Endothelial Keratoplasty.

PURPOSE: The aim of this study was to report the outcomes of graft fixation using interrupted, full-thickness sutures on graft detachment after Descemet stripping endothelial keratoplasty (DSEK). METHODS: All DSEK procedures performed at Mayo Clinic, Rochester, MN, from 2015 through 2022 were retrospectively reviewed. Risk factors for graft detachment were defined as previous incisional glaucoma surgery, previous penetrating keratoplasty, or absence of the normal lens-capsule barrier. Cases were categorized into sutured, high-risk grafts; unsutured, high-risk grafts; and unsutured, low-risk grafts. The primary outcome was graft detachment, and secondary outcomes were early graft failure and graft clarity at 12 months after surgery. RESULTS: Demographics between the high-risk groups were similar for sex and age at the time of surgery. Graft detachment occurred in 4 of 97 sutured, high-risk eyes (4.1%) and 24 of 119 unsutured high-risk eyes (20.2%) ( P = 0.002). In comparison, graft detachment occurred in 18 of 181 unsutured low-risk eyes (9.9%). The incidence of early graft failure was 2.1%, 5.0%, and 3.3% and late graft failure by 12 months was 9.8%, 12.8%, and 4.2%, respectively. CONCLUSIONS: In eyes with high-risk factors for graft detachment, suture fixation of the graft in DSEK decreased graft detachment to a rate at least as low as that in low-risk eyes.

Voxelotor improves red blood cell functionality in children with sickle cell anaemia: An ancillary study of the HOPE-KIDS 1 trial.

INTRODUCTION: Sickle haemoglobin (HbS) polymerisation perturbs red blood cell (RBC) rheology and drives sickle cell disease (SCD) pathophysiology. Voxelotor is an HbS polymerisation inhibitor that increases haemoglobin (Hb)-oxygen affinity. METHODS/RESULTS: In this 48-week, prospective, single-centre translational study, 10 children aged 4-11 years with SCD were treated with voxelotor. Improvements in RBC deformability were observed using osmotic/oxygen gradient ektacytometry, with increases in minimal and maximal elongation index and reductions in point of sickling. Increased Hb and reduced markers of haemolysis were also observed. CONCLUSION: These findings suggest that voxelotor treatment is associated with reduced RBC sickling and haemolysis in children with SCD.