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Beyond the Odyssey’s Horizon: Investigating Healthcare Access and Its Associated Factors in Swiss Rare Disease Patients
No full textInfertility, Reproductive Decisions, and Stress: Psychological Backgrounds and Outcomes of Assisted Reproduction and Social Egg Freezing
No full textUnlocking Playfulness: The Role of Low Executive Functions and Parental Play Behaviour in Shaping the Developmental Trajectories of Children’s Playfulness
No full textFraming Artificial Intelligence: Understanding How AI Is Framed in EU Political and Media Discourse Using Large Language Models
No full textThe Power of Invisibility – Caretaker Governments in Advanced Parliamentary Democracies, 1945–2022
No full textMensch-Maschine-Interaktion an der Schnittstelle von Sprache, Technologie und Gesellschaft: Eine interdisziplinäre Analyse
No full textPrevalence and Outcome of Secondary Hypogonadism in Male Patients with Cushing's Syndrome and Mild Autonomous Cortisol Secretion
No full textBACKGROUND
Secondary hypogonadism (SH) is common in men with Cushing's syndrome (CS), but its impact on comorbidities is largely unknown and longitudinal data are scarce. If SH also affects men with mild autonomous cortisol secretion (MACS) is unknown.
METHODS
We included 30 treatment-naïve adult men with CS and 17 men with MACS diagnosed since 2012. Hypogonadism was diagnosed based on total testosterone (TT) concentrations < 10.4 nmol/L and age-specific cut-offs. Outcomes were compared to age- and BMI-matched controls. In 20 men in remission of CS, a longitudinal analysis was conducted at 6, 12, and 24 months.
RESULTS
Men with CS had significantly lower concentrations of TT, bioavailable T, and free T compared to controls (P < .0001) with lowest concentrations in ectopic CS. Likewise, TT was lower in men with MACS compared to controls. At baseline, 93% of men with CS and 59% of men with MACS had SH. Testosterone correlated negatively with late night salivary cortisol and serum cortisol pre- and post-1 mg dexamethasone suppression test. Following successful surgery, TT increased significantly (P = .001), normalising within 6 months. Despite normalisation, several RBC parameters remained lower in men with CS even 2 years after successful surgery.
CONCLUSIONS
Secondary hypogonadism is common in men with CS and MACS but usually reversible after successful surgery. The persisting changes observed in RBC parameters need to be further investigated in larger cohorts and longer follow-up durations
Drug-induced cholestasis (DIC) predictions based on in vitro inhibition of major bile acid clearance mechanisms
No full textMixed integer bilevel optimization with a k-optimal follower: a hierarchy of bounds
No full textWe consider mixed integer bilevel linear optimization problems in which the decision variables of the lower-level (follower’s) problem are all binary. We propose a general modeling and solution framework motivated by the practical reality that in a Stackelberg game, the follower does not always solve their optimization problem to optimality. They may instead implement a locally optimal solution with respect to a given upper-level decision. Such scenarios may occur when the follower’s computational capabilities are limited, or when the follower is not completely rational. Our framework relaxes the typical assumption of perfect rationality that underlies the standard modeling framework by defining a hierarchy of increasingly stringent assumptions about the behavior of the follower. Namely, at level k of this hierarchy, it is assumed that the follower produces a k-optimal solution. Associated with this hierarchy is a hierarchy of upper and lower bounds that are in fact valid for the classical case in which complete rationality of the follower is assumed. Two mixed integer linear programming (MILP) formulations are derived for the resulting optimization problems. Extensive computational results are provided to demonstrate the effectiveness of the proposed MILP formulations and the quality of the bounds produced. The latter are shown to dominate the standard approach based on a single-level relaxation at a reasonable computational cost. Finally, we also explore a class of bilevel problems for which 2-optimal lower-level solutions imply global optimality, and hence we can solve these bilevel problems exactly using the developed MILP formulations
Frequency of Clinical Signs in Patients with Cushing's Syndrome and Mild Autonomous Cortisol Secretion : Overlap is Common
No full textBACKGROUND
Cushing's syndrome (CS) can be difficult to diagnose. A timely diagnosis, however, is the cornerstone for targeted treatment, to reduce morbidity and mortality. One reason for the difficulties to identify early on patients with CS might be the presence of a mild phenotype. The aim of the study was to classify the phenotypic landscape of CS. We studied patients with overt CS and mild autonomous cortisol secretion (MACS).
METHOD
The study was part of the German Cushing's registry. Patients were prospectively included at time of diagnosis and the number of comorbidities and clinical signs and symptoms were assessed in a standardized fashion. One hundred twenty-nine patients with CS (pituitary CS, n = 85, adrenal CS, n = 32, ectopic CS, n = 12, respectively) and 48 patients with MACS were included. Patients with clinical signs and/or comorbidities typical for CS and at least 2 pathological screening tests were classified as having CS. Patients with a 1 mg low-dose-dexamethasone-suppression test above 1.8 µg/dL without being clinically overt CS were classified as having MACS.
RESULTS
On average, patients with CS had 2 comorbidities (range 1-3) at time of diagnosis (pituitary CS: 2 [1-3], adrenal CS: 3 [2-4], ectopic CS: 3 [2-4]). Patients with MACS, however, had 3 comorbidities (range 2-3). Hypertension was the most common comorbidity in all subtypes of CS (78%-92%) and in patients with MACS (87%). Of a total of 11 clinical signs, patients with CS had on average 5 with 28% of patients having between 0 and 3 clinical signs, 50% 4-7 signs, and 22% more than 7 clinical signs. Patients with MACS had on average 2 clinical signs (range 1-3) at time of diagnosis.
CONCLUSION
The phenotypic landscape of CS is quite variable. The frequency of comorbidities is similar between patients with CS and MACS. A relevant number of patients with overt CS have just a few clinical signs. There is also an overlap in frequency of symptoms and clinical signs between patients with CS and MACS. According to the current guidelines, 96% of our patients with MACS fall into the category "consideration of adrenalectomy". This should be kept in mind when making treatment decisions in the latter group of patients