Brain structure and function in primary adrenal insufficiency

Individuals with primary adrenal insufficiency (PAI), i.e., congenital adrenal hyperplasia (CAH) and autoimmune Addison’s disease (AAD), suffer from impaired production of the adrenal gland hormones cortisol and aldosterone, and in the case of AAD, also androgens. Replacement medication for these hormones is sub-optimal due to the difficulties in replicating the natural rhythms of cortisol secretion. The hormones are known to affect brain function via many mechanisms, and both pre- and postnatal hormone dysregulation may affect cognitive functioning, brain structure and brain function. Therefore, studying brain health in PAI is of interest and is needed to optimise treatment and patient wellbeing. The present thesis investigated brain structure related to cognitive functioning in individuals with CAH, and cognitive functioning, brain structure and resting-state functional connectivity in individuals with AAD. We found that individuals with CAH have impairments in white matter microstructure, as well as cortical thinning of the frontoparietal network that was related to weaker performance on a visuospatial working memory task. On the other hand, individuals with AAD performed equally to control subjects on most measures of cognitive functions assessed with standardized tests during the lab-visit, but they self-reported executive function problems in daily life, which were related to experienced mental fatigue. As opposed to individuals with CAH, those with AAD did not have profound differences in the structure of the brain, apart from smaller total brain volumes. However, they displayed increased resting-state functional connectivity, particularly in primary visual regions and the orbitofrontal cortex. Our results suggest that the effects of adrenal hormone insufficiency affect individuals with CAH and AAD differently. This difference may be related to the onset of the disease, which is from conception for those with CAH and in adolescence or adulthood for those with AAD. Long-term follow-up studies are needed to assess whether the observed differences contribute to increased cognitive decline later in life and how to optimise replacement medication to sustain brain health

Overlapping Dialogue : On the Sound Editing in Nashville

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Prone vs. supine accelerated partial breast irradiation on an MR-Linac: A planning study

Background and purpose: Accelerated partial breast irradiation (APBI) may benefit from the MR-Linac for target definition, patient setup, and motion monitoring. In this planning study, we investigated whether prone or supine position is dosimetrically beneficial for APBI on an MR-Linac and we evaluated patient comfort. Materials and methods: Twenty-patients (9 postoperative, 11 preoperative) with a DCIS or breast tumor <3 cm underwent 1.5 T MRI in prone and supine position. The tumor or tumor bed was delineated as GTV and a 2 cm CTV-margin and 0.5 cm PTV-margin were added. 1.5 T MR-Linac treatment plans (5 × 5.2 Gy) with 11 beams were created for both positions in each patient. We evaluated the number of plans that achieved the planning constraints and performed a dosimetric comparison between prone and supine position using the Wilcoxon signed-rank test (p-value <0.01 for significance). Patient experience during scanning was evaluated with a questionnaire. Results: All 40 plans met the target coverage and OAR constraints, regardless of position. Heart Dmean was not significantly different (1.07 vs. 0.79 Gy, p-value: 0.027). V5Gy to the ipsilateral lung (4.4% vs. 9.8% median, p-value 0.009) and estimated delivery time (362 vs. 392 s, p-value: 0.003) were significantly lower for prone position. PTV coverage and dose to other OAR were comparable between positions. The majority of patients (13/20) preferred supine position. Conclusion: APBI on the MR-Linac is dosimetrically feasible in prone and supine position. Mean heart dose was similar in both positions. Ipsilateral lung V5Gy was lower in prone position

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

BACKGROUND There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 personyears in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.)

An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in g irls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up resear ch is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DE X may avoid unnecessary treatment and improve treatment safety