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SummaryGiven the growing use of immune checkpoint inhibitor (ICI) therapy in oncology, the prevalence of endocrine side effects is rapidly increasing. As clinicians are nowadays frequently confronted with these side effects in routine clinical care, awareness, better knowledge of endocrine irAEs and their clinical presentation and diagnosis is crucial for an adequate management. In this short-review we give a compact overview of the recent recommendations for the management of endocrine irAE related to ICIs and highlight difficulties and uncertainties in current clinical practice.

Purpose Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. Materials and Methods The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). Results In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p p p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). Conclusion After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women. Graphical abstract

Objective Measurement of IGF-I is important in the management of patients with growth hormone disorders. Here we aim to establish normative data for two new IGF-I assay kits based on a large random sample of the French general adult population. Subjects and methods We measured IGF-I in 911 healthy adults (18–90 years) with two immunoassays (ROCHE Elecsys® and IMMULITE-2000 calibrated against the new IS 02/2547). We compared the data with those of the six immunoassays (iSYS, LIAISON XL, IMMULITE-2000 calibrated against the first IS 87/518, IGF-I RIACT, Mediagnost ELISA, and Mediagnost RIA) that we reported previously. The pairwise concordance among the eight assays was assessed with Bland–Altman plots for both the IGF-1 raw data and the standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorizing IGF-I SDS (ClinicalTrials.gov Identifier: NCT01831648). Results The normative data included the range of values (2.5–97.5 percentiles) given by the two new IGF-I assays according to age group and sex. A formula for the SDS calculation is provided. As for the previous six assays, the lower limits of the reference intervals of the two new assays were similar, but the upper limits varied markedly. The pairwise concordances were only moderate (kappa 0.57). Conclusions Data obtained for these two new IGF-I immunoassays confirm that despite being obtained in the same large healthy population, the reference intervals of the eight commercial IGF-1 assay kits showed noteworthy differences. The agreement among the various methods was moderate to good.

OBJECTIVES To identify variables independently associated with a meaningful improvement in QOL long after surgical treatment of drug-resistant MTLE-HS patients. MATERIAL & METHODS We prospectively evaluated 72 consecutive MTLE-HS surgically treated patients and analyzed pre and post-surgical variables independently associated with a meaningful improvement in QOL evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31) overall score, and its domain scores determined at follow-up after 36 to 131 months (mean 93 months) after surgery. RESULTS The mean overall QOLIE-31 score and its subdomain scores improved significantly after surgery (p

The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. The relation between synaptic plasticity in the human limbic system structures and autonomic regulation in humans is unknown. This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE, n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distribution of sociodemographic, clinical, neuroimaging, and neurosurgical variables. P-GluA1-Ser845 levels in AMY show a negative association (p

OBJECTIVE Recent studies indicate that sodium-glucose cotransporter 2 (SGLT-2) inhibition increases endogenous glucose production (EGP), potentially counteracting the glucose-lowering potency, and stimulates lipid oxidation and lipolysis. However, the acute effects of SGLT-2 inhibition on hepatic glycogen, lipid, and energy metabolism have not yet been analyzed. We therefore investigated the impact of a single dose of dapagliflozin (D) or placebo (P) on hepatic glycogenolysis, hepatocellular lipid (HCL) content and mitochondrial activity (kATP). RESEARCH DESIGN AND METHODS Ten healthy volunteers (control [CON]: age 30 ± 3 years, BMI 24 ± 1 kg/m2, HbA1c 5.2 ± 0.1%) and six patients with type 2 diabetes mellitus (T2DM: age 63 ± 4 years, BMI 28 ± 1.5 kg/m2, HbA1c 6.1 ± 0.5%) were investigated on two study days (CON-P vs. CON-D and T2DM-P vs. T2DM-D). 1H/13C/31P MRS was performed before, 90–180 min (MR1), and 300–390 min (MR2) after administration of 10 mg dapagliflozin or placebo. EGP was assessed by tracer dilution techniques. RESULTS Compared with CON-P, EGP was higher in CON-D (10.0 ± 0.3 vs. 12.4 ± 0.5 μmol kg−1 min−1; P < 0.05) and comparable in T2DM-D and T2DM-P (10.1 ± 0.7 vs. 10.4 ± 0.5 μmol kg−1 min−1; P = not significant [n.s.]). A strong correlation of EGP with glucosuria was observed (r = 0.732; P < 0.01). The insulin-to-glucagon ratio was lower after dapagliflozin in CON-D and T2DM-D compared with baseline (P < 0.05). Glycogenolysis did not differ between CON-P and CON-D (−3.28 ± 0.49 vs. −2.53 ± 0.56 μmol kg−1 min−1; P = n.s.) or T2DM-P and T2DM-D (−0.74 ± 0.23 vs. −1.21 ± 0.33 μmol kg−1 min−1; P = n.s.), whereas gluconeogenesis was higher after dapagliflozin in CON-P compared with CON-D (6.7 ± 0.6 vs. 9.9 ± 0.6 μmol kg−1 min−1; P < 0.01) but not in T2DM. No significant changes in HCL and kATP were observed. CONCLUSIONS The rise in EGP after SGLT-2 inhibition is due to increased gluconeogenesis, but not glycogenolysis. Changes in glucagon and the insulin-to-glucagon ratio are not associated with an increased hepatic glycogen breakdown. HCL and kATP are not significantly affected by a single dose of dapagliflozin.

Background Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. Objective To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. Methods This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. Results Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. Limitations Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. Conclusion Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

Die Nebenniereninsuffizienz (NNI) ist eine seltene, unbehandelt jedoch potenziell lebensbedrohlich verlaufende Erkrankung. Aufgrund der vor allem anfanglich unspezifischen klinischen Symptomatik ist es fur die behandelnden Arztinnen und Arzte wichtig, die Moglichkeit einer NNI als Differenzialdiagnose bei zunehmender Schwache, Gewichtsabnahme, Mudigkeit, aber auch Hyponatriamie und Hypoglykamie in Betracht zu ziehen. Die Therapie der NNI ist eine moglichst physiologische Glukokortikoidsubstitution, wobei hier Hydrocortison aufgrund seiner kurzen Halbwertszeit der Vorzug gegeben werden sollte. Auf eine adaquate Dosisadaptierung bei Sondersituationen ist zur Vermeidung von Nebennierenkrisen unbedingt zu achten. Bei der primaren NNI ist zusatzlich noch die Mineralokortikoidtherapie von Relevanz, wahrend bei der sekundaren und tertiaren NNI die anderen Hypophysenhormonachsen kontrolliert und bei Bedarf im Verlauf substituiert werden sollten.

OBJECTIVE Sudden unexpected death in epilepsy (SUDEP) is a tragic event. Cardiac models of sudden death state that, paradoxically, healthy individuals compose most of the victims of this event. Exploration of cardiac physiological variables related to outcome could help unveil risk markers for sudden death in epilepsy. We investigated left ventricle end-systolic elastance, arterial-effective elastance and ventricle-arterial coupling (VAC) in PWE compared with controls. MATERIAL & METHODS Adult patients with temporal lobe epilepsy without known cardiovascular diseases were submitted to treadmill test and transthoracic echocardiogram. Individuals without epilepsy matched by sex, age, and body mass index composed the control group. Cardiac risk factors, exercise performance, autonomic data from treadmill test, systolic and diastolic function, morphological cardiac data, and left ventricle pressure-volume loop were recorded. RESULTS Sixty subjects were consecutively enrolled (30 PWE and 30 controls). Epilepsy duration was 22.5 ± 10.7 years (age of onset 15.2 ± 10.1 years). Treadmill variables were significantly worse in TLE patients compared with controls. End-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling were similar between groups. Female sex, percentage of maximal predicted heart rate achieved in exercise, exercise time, and epilepsy duration explained 28,4% of VAC in PWE in multiple stepwise linear regression (P = .018). CONCLUSIONS Some aspects of the cardiac pressure-volume curves, mainly linked to left ventricle systolic performance, contractile function and their interaction with afterload appears normal in young PWE and cannot explain their increase risk to adverse outcomes or lower physical fitness.

Background In severe obesity, hypogonadism in men and androgen excess in women are frequently observed. Sex hormones play an important role in body composition and glucose and lipid metabolism. However, whether pre-operative gonadal dysfunction impacts weight loss after bariatric surgery is not fully known. Methods A total of 49 men and 104 women were included in a retrospective analysis. Anthropometric characteristics, glucose and lipid metabolism, and androgen concentrations were assessed pre-operatively and 17.9 ± 11 or 19.3 ± 12 months post-operatively in men and women. Men with (HYPOmale) and without (controls: CONmale) pre-operative hypogonadism, as well as women with (HYPERfemale) and without (controls: CONfemale) pre-operative hyperandrogenemia, were compared. Results In men, pre-operative hypogonadism was present in 55% and linked to a higher body mass index (BMI): HYPOmale 50 ± 6 kg/m2 vs. CONmale 44 ± 5 kg/m2, p = 0.001. Bariatric surgery results in comparable changes in BMI in HYPOmale and CONmale − 16 ± 6 kg/m2 vs. − 14 ± 5 kg/m2, p = 0.30. Weight loss reversed hypogonadism in 93%. In women, androgen excess was present in 22%, independent of pre-operative BMI: CONfemale 44 ± 7 kg/m2 vs. HYPERfemale 45 ± 7 kg/m2, p = 0.57. Changes in BMI were comparable in HYPERfemale and CONfemale after bariatric surgery − 15 ± 6 kg/m2 vs. − 15 ± 5 kg/m2, p = 0.88. Hyperandrogenemia was reversed in 61%. Conclusions Besides being frequently observed, hypogonadism in men and androgen excess in women have no impact on post-surgical improvements in body weight and glucose and lipid metabolism. Weight loss resulted in reversal of hypogonadism in almost all men and of hyperandrogenemia in the majority of women.

Background Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, patients suffering from primary adrenal insufficiency (AI) have an increased mortality, mainly due to cardiovascular diseases. Only little knowledge exists on the contribution of MC substitution to the cardiovascular risk. Therefore, this study investigates the impact of plasma renin concentration on parameters of micro- and macrovascular function. Methods 26 patients with primary AI [female = 18, age: 51 (28; 78) years; BMI: 24 (18; 40) kg/m2; disease duration: 18 (5; 36) years] were included in this cross-sectional analysis. Intima media thickness (IMT) and pulse wave velocity (PWV) were investigated to assess macrovascular remodeling and arterial stiffness. Microvascular function was estimated by post-occlusive reactive hyperemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded. Patients were grouped according to their median plasma renin concentration of previous visits (Reninhigh vs Reninlow) and were compared to a group of healthy women [age: 44 (43; 46) years; BMI: 24.2 (21.8; 27.5)]. Results PWV was significantly higher in AI patients compared to controls [9.9 (5; 18.5) vs 7.3 (6.8; 7.7) m/s; p low time to peak perfusion was significantly longer [6.0 (3; 15) vs 3.5 (1.5; 11) s; p high and Reninlow. No impact of GC dose was observed. Conclusions Microvascular function is not impaired in patients with primary AI under adequate replacement therapy, although higher renin concentrations are associated with subclinical improvements. No relation between RAAS activity and macrovascular function is observed, while arterial stiffness might be increased in primary AI.

Context A substantial number of patients undergoing bariatric surgery are prescribed psychopharmacological medication. However, the impact of concomitant psychopharmacological medication on the frequency of relevant vitamin deficiencies in postoperative follow-up is not known. Methods Five hundred twenty-four patients with obesity who underwent bariatric surgery (January 2004 to September 2018) with follow-up of at least 12 months, were included in retrospective analysis. Postoperative follow-up visits between January 2015 and September 2019 were analyzed. Anthropometric and laboratory data were analyzed at the first documented follow-up visit after on average 39.5 ± 37.3 months and at every following visit during the observation period. Patients with prescribed psychopharmacological drugs (PD) were compared with patients without (control group, CON). Results Psychopharmacological medication was documented in 25% (132) of patients. In 59 patients documented prescription of more than one psychiatric drug was found, whereas psychopharmacological monotherapy was found in 73 patients. Frequencies of vitamin deficiencies were comparable between PD and CON (vitamin A: p = 0.852; vitamin D: p = 0.622; vitamin E: p = 0.901; folic acid: p = 0.941). Prevalence of vitamin B12 deficiency was rare (6% CON, 1% PD) but was significantly higher in CON (p = 0.023). A comparison of CON and POLY also showed no significant differences between the groups concerning prevalence of vitamin deficiencies. Conclusions Intake of psychopharmacological medication is highly prevalent in patients after bariatric surgery. Patients with psychopharmacological medication, who participate in structured follow-up care after bariatric surgery, are not at higher risk for vitamin deficiencies compared with controls.

High-intensity training (HIT) is known to have deteriorating effects on performance which manifest in various physiological changes such as lowered force production and oxidative capacity. However, the effect of HIT in climbing on finger flexor performance has not been investigated yet. Twenty-one climbers partook in an intervention study with three assessment time points: pre-HIT, post-HIT, and 24-h post-HIT. The HIT involved four five-minute exhaustive climbing tasks. Eight climbers were assigned to a control group. Assessments consisted of three finger flexor tests: maximum voluntary contraction (MVC), sustained contraction (SCT), and intermittent contraction tests (ICT). During the SCT muscle oxygenation (SmO2) metrics were collected via NIRS sensors on the forearm. The HIT had significant deteriorating effects on all force production metrics (MVC − 18%, SCT − 55%, ICT − 59%). Post-24 h showed significant recovery, which was less pronounced for the endurance tests (MVC − 3%, SCT − 16%, ICT − 22%). SmO2 metrics provided similar results for the SCT with medium to large effect sizes. Minimally attainable SmO2 and resting SmO2 both showed moderate negative correlations with pre-HIT force production respectively; r = − 0.41, P = 0.102; r = − 0.361, P = 0.154. A strong association was found between a loss of force production and change in minimally attainable SmO2 (r = − 0.734, P = 0.016). This study presents novel findings on the deteriorating effects of HIT on finger flexor performance and their oxidative capacity. Specifically, the divergent results between strength and endurance tests should be of interest to coaches and athletes when assessing athlete readiness., Journal of Science in Sport and Exercise, 4 (2), ISSN:26621371

We present the case of a 66-year-old bisexual patient suffering from painful bloody defecation, linked to rectal thickening, rectovesical fistula and enlarged lymph nodes in the mesorectal area. The patient was misdiagnosed with rectal cancer (T3 N2) on MRI but the symptoms of the patient were due to lymphogranuloma venereum. After adequate treatment with doxycycline, symptoms faded within days; a control MRI showed complete regression of all pathologic alterations.

Context Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~98%) and hypothalamic obesity (~50%). Objective To determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction. Design Retrospective case control study. Setting Multicenter international study. Patients and participants Obese craniopharyngioma patients (N = 16; of which 12 women) with a history of bariatric surgery [12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age of 21 years (range 15-52), median follow-up 5.2 years (range 2.0-11.3)] and age/sex/surgery/BMI-matched obese controls (N = 155). Main outcome measures Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated. Results Mean weight loss at 5-year follow-up was 22.0% (95% CI 16.1, 27.8) in patients versus 29.5% (28.0, 30.9) in controls (P = 0.02), which was less after Roux-en-Y gastric bypass (22.7% [16.9, 28.5] vs. 32.0% [30.4, 33.6]; P = 0.003) but at a similar level after sleeve gastrectomy (21.7% [–1.8, 45.2] vs. 21.8% [18.2, 25.5]; P = 0.96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems. Conclusions Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears effective and relatively safe in the treatment of obese craniopharyngioma patients.

Clinically non functioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active. They are not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing's disease or hyperthyroidism (TSH-secreting adenomas) and are therefore usually diagnosed by signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy), but also incidentally. Biochemical work up often documents several pituitary insufficiencies. In histopathology, the majority of NFPAs is gonadotroph. In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is at distance to the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects.

Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Material and Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months, hyperthyroid, n = 50: 23.1 months, hypothyroid, n = 70: 47.9 months, p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months, with, n = 67: 51.3 months, p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months, p = 0.045). Conclusions: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

Background Acromegaly is associated with changes in body composition. Long-term changes following acromegaly treatment and the impact of different treatments have been less investigated. Methods We performed a retrospective study in 201 patients with acromegaly. Body composition was assessed by dual-energy X-ray absorptiometry. To investigate the specific effects of treatment vs aging, changes in body composition were compared in one group of patients evaluated both at the time of active and controlled disease (active-to-controlled (A>C); n = 31) and in another group of patients evaluated two times while the disease was controlled (controlled-to-controlled (C>C); n = 32). Results In the whole cohort, insulin-like growth factor I (IGF-I) was correlated with fat (r = −0.369; P < 0.001) and lean mass (r = 0.383; P < 0.001). Patients from A>C and C>C groups were comparable for age, sex, BMI and follow-up duration (P = n.s.). Reduction in IGF-I levels was associated with an increase in fat mass and a decrease in lean mass in the A>C group, which was four and eight times more pronounced compared to the C>C group (fat mass: +39 ± 34% vs +10 ± 15%, P < 0.001; lean mass: −8 ± 8% vs −0.2 ± 6%, P < 0.001, respectively). Changes in fat mass were negatively associated with IGF-I (r = −0.450; P = 0.011) and independent of the individual therapy. The daily dose of pegvisomant correlated with fat mass (r = 0.421; P = 0.002) and insulin sensitivity index (r = −0.466; P < 0.001). Conclusions Treatment of acromegaly strongly impacts body composition until biochemical disease remission, characterized by an increase in fat mass and a decrease in lean mass. These changes are closely associated with the normalization of IGF-I. Thereafter, body composition changes are similar to what is observed with aging.

Context Cardiovascular disease is the leading cause of death in patients with Cushing syndrome. Cortisol excess and adverse metabolic profile could increase cardiac fat, which can subsequently impair cardiac structure and function. Objective We aimed to evaluate cardiac fat mass and distribution in patients with Cushing syndrome. Methods In this prospective, cross-sectional study, 23 patients with Cushing syndrome and 27 control individuals of comparable age, sex, and body mass index were investigated by cardiac magnetic resonance imaging and proton spectroscopy. Patients were explored before and after biochemical disease remission. Myocardial fat measured by the Dixon method was the main outcome measure. The intramyocardial triglyceride/water ratio measured by spectroscopy and epicardial and pericardial fat volumes were secondary outcome measures. Results No difference was found between patients and controls in intramyocardial lipid content. Epicardial fat mass was increased in patients compared to controls (30.8 g/m2 [20.4-34.8] vs 17.2 g/m2 [13.1-23.5], P Conclusion Intramyocardial fat stores are not increased in patients with Cushing syndrome, despite highly prevalent metabolic syndrome, suggesting increased cortisol-mediated lipid consumption. Cushing syndrome is associated with marked accumulation of epicardial and pericardial fat. Epicardial adiposity may exert paracrine proinflammatory effects promoting cardiomyopathy.

Most wearable robots that assist the gait of workers, soldiers, athletes, and hobbyists are developed towards a vision of outdoor, overground walking. However, so far, these devices have predominantly been tested indoors on laboratory treadmills. It is unclear whether treadmill-based laboratory tests are an accurate representation of overground ambulation outdoors with respect to essential outcomes such as the metabolic benefits of robotic assistance. In this study, we investigated the metabolic benefits of the Myosuit, a wearable robot that assists hip and knee extension during the stance phase of gait, for eight unimpaired participants during uphill walking trials in three settings: outside, on a self-paced treadmill with a virtual reality display, and on a standard treadmill at a fixed gait speed. The relative metabolic reduction with Myosuit assistance was most pronounced in the outside setting at − 10.6% and significantly larger than in the two treadmill settings (− 6.9%, p = 0.015 and − 6.2%, p = 0.008). This indicates that treadmill tests likely result in systematically low estimate for the true metabolic benefits of wearable robots during outside, overground walking. Hence, wearable robots should preferably be tested in an outdoor environment to obtain more representative—and ultimately more favorable—results with respect to the metabolic benefit of robotic gait assistance., Scientific Reports, 11, ISSN:2045-2322

Soft robotic suits are good candidates both for supporting physical therapy in clinical environments and for improving mobility in outdoor settings. Here, we investigate both modes of use using the Myosuit, a lightweight robotic suit for the lower limbs: (1) we show that it can be safely used to support a supervised physical therapy program, and (2) present a single-case study on the immediate effects that Myosuit assistance can have in an outdoor setting. Eight participants with diverse walking impairments completed a five-sessions Myosuit-assisted training program, showing an average improvement in walking performance that is encouraging for the design of a future controlled study. When walking on a sloped mountain path, one participant with incomplete spinal cord injury showed a 30% increase in walking speed and 9% reduction in cost of transport when assisted by the Myosuit, compared to when not wearing the device.

Psoriasis is a chronic inflammatory skin disease that involves numerous types of immune cells and cytokines resulting in an inflammatory feedback loop and hyperproliferation of the epidermis. A more detailed understanding of the underlying pathophysiology has revolutionized anti-psoriatic treatment and led to the development of various new drugs targeting key inflammatory cytokines such as IL-17A and IL-23. Successfully treated psoriatic lesions often resolve completely, leaving nothing visible to the naked eye. However, such lesions tend to recur within months at the exact same body sites. What is left behind at the cellular and molecular levels that potentially reinitiates psoriasis? Here, we elucidate the cellular and molecular “scar” and its imprints left after clinical resolution of psoriasis treated with anti-TNFα, anti-IL-17, or anti-IL-23 antibodies or phototherapy. Hidden cytokine stores and remaining tissue-resident memory T cells (TRMs) might hold the clue for disease recurrence.

Fumaric acid esters are recommended in European guidelines for induction and maintenance treatment of patients with moderate to severe plaque psoriasis. A systemic medication with pure dimethyl fumarate without monoethyl fumarate salts was recently licensed in Europe. The efficacy and safety of pure dimethyl fumarate were assessed in patients with severe (physician global assessment) plaque psoriasis in Austria in the BRIDGE trial. In this double blind, randomized, placebo-controlled trial patients received 16-week treatment with pure dimethyl fumarate in a head to head comparison with dimethyl fumarate with monoethyl fumarate salts, which is licensed in Germany. In this post hoc analysis the efficacy and safety were assessed in patients with severe psoriasis in Austria. Efficacy measures significantly improved in both active treatment arms compared to placebo in 65 patients after 16 weeks of treatment. Physician global assessment of clear/almost clear in the dimethyl fumarate group was non-inferior to the dimethyl fumarate with monoethyl fumarate salts group 2 months after end of treatment. No serious adverse reaction occurred in patients with dimethyl fumarate in contrast to the second active treatment. Efficacy outcome was paralleled by quality of life improvements. This is the first report of dimethyl fumarate in a severely affected population with plaque psoriasis. Dimethyl fumarate is effective and safe in the systemic treatment of adults with severe psoriasis (physician global assessment).

In this article, we explore the interaction of brain and heart in patients with epilepsy (PWE), focusing on new insights into possible pathways from epilepsy, catecholaminergic toxicity, subtle cardiac changes and sudden death. Initial evidence and biological plausibility point to an interaction between autonomic dysfunction, higher sympathetic drive, myocardial catecholaminergic toxicity and cardiac fibrosis resulting in subtle myocardial changes in structure, function, arrhythmogenesis and/or a heart failure-like phenotype in PWE. Non invasive imaging and biomarkers of cardiac injury and fibrosis are emerging as possible diagnostic tools to better stratify the risk of such individuals. Translational lessons from cardiac models of disease and ultra-structural lesions are used to support these considerations.

Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT).Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/mIn the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*mAdult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism.AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

Background Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most prevalent type of surgically remediable epilepsy and highly associated with psychiatric comorbidities. This study aimed to evaluate Hospital anxiety and depression scale-anxiety subscale (HADS-A) and The State-Trait Anxiety Inventory – Trait subscale (STAI-T) accuracy for detection of anxiety disorders in patients with drug-resistant MTLE-HS. Methods One hundred three consecutive patients with drug-resistant MTLE-HS were enrolled. Diagnosis was based on the anamnesis, neurological examination, video-electroencephalogram (VEEG) analyses, and magnetic resonance imaging (MRI). Psychiatric interviews were based on DSM-IV-TR criteria and ILAE Commission of Psychobiology classification as a gold standard; HADS-A and STAI-T were used as psychometric diagnostic tests, and receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores. Results The areas under the curve (AUCs) were higher than 0.7 (0.6–0.8) for both scales. The STAI-T cutoff point of ˃53 and the HADS-A cutoff point of ˃7 showed both around of 80% (44.4–97.7) sensitivity and 80% (66.9–86.9) and 60% (46.5–68.6) of specificity, respectively. In this sample the prevalence of anxiety disorders was 11.7% and both scales showed a high negative predictive value such as 96% (87.1–99.0) but low positive predictive value such as 30% (22.1–45.2) and 20% (15.0–27.2) respectively. Limitations The small number of cases in the diagnostic population; the results are only applied to drug resistant MTLE-HS; the psychiatric diagnosis were not based on a structured psychiatric interview; possible observer bias in 7 illiterate patients; the antidepressant treatment was not controlled. Conclusions In MTLE-HS, STAI-T and HADS-A had a similar and low positive predictive value and high negative predictive value. The implications for the HADS-A and STAI-T usefulness for anxiety disorders screening in patients with other epilepsies types deserve further investigations. If replicated in other populations, these findings may have important relevance for the presurgical screening of anxiety disorders in MTLE-HS patients who are candidates to epilepsy surgery.

Diagnosis of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), can be challenging given the overlapping clinical and pathologic features with various other conditions. High-throughput TCR sequencing (HT-TCRseq) has an outstanding capacity to facilitate diagnosis of CTCL1 , identify aggressive forms of MF in early-stage2 , and associate burden of malignant cells with response to PUVA treatment3 .

Background: Migraine and epilepsy are both common episodic disorders, typically precipitated or inhibited by some modulatory factors (MFs).Objective: To assess the self-perception of MFs in patients with migraine (PWM) compared to patients with epilepsy (PWE) with a standardized protocol in different countries.Methods: Transcultural multicenter comparative cross-sectional study. All consecutive patients who fulfilled the ICHD-3 criteria for migraine and ILAE's criteria for epilepsy, with at least 1 year of follow-up were interviewed with a semi-structured questionnaire on clinical and epidemiological data and were asked to identify all experienced MFs from a provided list.Results: A total of 608 individuals were surveyed at five university referral centers in Brazil, Guatemala, Lithuania and Turkey. Two hundred and nineteen (91.6%) PWM and 305 (82.7%) PWE identified attack precipitating factors (PFs; p < 0.001). The most frequent three PFs reported by epilepsy patients were: “lack of sleep” (56.6%), “emotional stress” (55.3%), “negative feelings” (53.9%), while among migraine patients “emotional stress” (81.6%), “lack of sleep” (77.8%), “negative feelings” (75.7%) were cited. Inhibitory factors (IFs) for the episodes were reported by 68 (28.5%) PWM and 116 (31.4%) PWE. “Darkness” was the most common one, described by 35.6% of PWM whereas “positive feelings” reported by 10.6% of PWE. Most MFs are concordant across the countries but some transcultural differences were noted.Conclusion: The MFs of migraine and epilepsy attacks and their varying frequencies according to different countries were investigated with the same standardized questionnaire, for the first time. MFs were recognized very often in both migraine and epilepsy cohorts, but in distinct disease-specific prevalence, being more frequent in migraine. Recognition of self-perceived MFs may be helpful for the management of both illnesses.

Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing’s disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.

Objective: This study aimed to analyse the effect of neuropsychological activation methods on interictal epileptiform discharges, compared to standard activation methods, for both focal and generalized epilepsies. Methods: This was a multicentre, prospective study including 429 consecutive EEG recordings of individuals with confirmed or suspected diagnosis of epilepsy. Neuropsychological activation included reading aloud in foreign and native language, praxis and a letter cancelation task (each with a duration of three minutes). After counting interictal discharges in three-minute time windows, activation and inhibition were assessed for each procedure, accounting for spontaneous fluctuations (95% CI) and compared to the baseline condition with eyes closed. Differences between generalized and focal epilepsies were explored. Results: Interictal epileptiform discharges were present in 59.4% of the recordings. Activation was seen during hyperventilation in 31%, in at least one neuropsychological activation method in 15.4%), during intermittent photic simulation in 13.1% and in the resting condition with eyes open in 9.9%. The most frequent single cognitive task eliciting activation was praxis (10.3%). Lasting activation responses were found in 18–25%. Significant inhibition was found in 88/98 patients with baseline interictal epileptiform discharges, and was not task-specific. Significance: Adding a brief neuropsychological activation protocol to the standard EEG slightly increased its sensitivity in patients with either focal or generalized epilepsy. However, in unselected epilepsy patients, this effect seems only exceptionally to result in ultimate diagnostic gain, compared to standard procedures. From a diagnostic perspective, cognitive tasks should be reserved for patients with a suspicion of cognitive reflex epilepsy/seizures and probably require longer exposure times. Further research is needed to explore potential therapeutic applications of the observed inhibition of interictal epileptiform discharges by cognitive tasks in some patients.

Anxiety and depressive symptoms are prevalent in patients with refractory mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL).(1) To follow the levels of anxiety and depressive symptoms long-term after ATL among patients with refractory MTLE-HS; (2) To identify pre- and postsurgical variables associated with the levels of anxiety and depressive symptoms after surgery.We compared the levels of anxiety and depressive symptoms determined by the Hospital Anxiety and Depression Scale (HADS) before and long after ATL (mean 104 months, range 70-130) in 41 consecutive patients refractory MTLE-HS. The last follow-up was between September 2018 and March 2020. We also determined pre- and postsurgical variables independently associated with the HADS scores after surgery.The scores of HADS and its subdomains related to anxiety and depression decreased significantly (p 0.01) after ATL. After multiple linear regressions, the HADS-Anxiety scores before surgery (B = 0.47, CI 95% 0.20 to 0.75, p = 0.001) and at follow-up after surgery (B = 0.07, CI 0.00 to 0.14, p = 0.05) remain independently and positively associated with HADS-Anxiety scores after surgery. The HADS-Depression scores after surgery were independently positively associated with HADS-Depression scores before surgery (B = 0.39, CI 95% 0.10 to 0.76, p = 0.01) and worse seizure control after surgery (B = 1.55, CI 95% 0.23 to 2.87, p = 0.02).Anxiety and depressive symptoms in patients with MTLE-HS significantly improved after ATL. Presurgical levels of anxiety and depressive symptoms, respectively, were positively associated with the postsurgical levels of those symptoms. Length of follow-up is associated with anxiety, and worse seizure control is associated with depressive symptoms after ATL. The results have implications for the surgical management of MTLE-HS patients.

Introduction: Sclerostin, an inhibitor of bone formation, has emerged as a potential negative regulator of glucose homeostasis. We aimed to investigate if serum sclerostin associates with insulin sensitivity, beta cell function, prediabetes or metabolic syndrome in healthy men. Materials and methods: Serum sclerostin was measured in basal and insulin-stimulated samples from 526 men without diabetes from the RISC cohort study. An OGTT was performed at baseline and after 3 years. An IVGTT and a hyperinsulinaemic-euglycaemic clamp were performed at baseline. Insulin sensitivity was estimated by the oral glucose sensitivity index (OGIS) and the M-value relative to insulin levels. Beta cell function was assessed by the acute and total insulin secretion (ISRtot) and by beta cell glucose sensitivity. Results: Serum sclerostin levels correlated positively with age but were similar in individuals with (n = 69) and without (n = 457) prediabetes or the metabolic syndrome. Serum sclerostin was associated with measures of neither insulin sensitivity nor beta cell function at baseline in age-adjusted analyses including all participants. However, baseline serum sclerostin correlated inversely with OGIS at follow-up in men without prediabetes (B: −0.29 (−0.57, −0.01) p = 0.045), and inversely with beta cell glucose sensitivity in men with prediabetes (B: −13.3 (−26.3, −0.2) p = 0.046). Associations between serum sclerostin and 3-year changes in measures of glucose homeostasis were not observed. Acute hyperinsulinemia suppressed serum sclerostin (p = 0.02), and this reduction correlated with OGIS and ISRtot. Conclusions: Overall, serum sclerostin was not associated with prediabetes, insulin sensitivity or insulin secretion in healthy men. The inverse relationship between serum sclerostin and insulin sensitivity at follow-up was weak and likely not of clinical relevance. The ability of insulin to reduce sclerostin, possibly promoting bone formation, needs to be clarified.

Aim To assess predictors of in‐hospital mortality in people with prediabetes and diabetes hospitalized for COVID‐19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. Materials and Methods A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID‐19. The primary outcome was in‐hospital mortality and the predictor variables upon admission included clinical data, co‐morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in‐hospital mortality. Results The mean age of people hospitalized (n = 238) for COVID‐19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C‐reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in‐hospital mortality with a C‐statistic of 0.889 (95% CI: 0.837‐0.941) and calibration of 1.000 (P = .909). Conclusions The in‐hospital mortality for COVID‐19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in‐hospital mortality.

Sudden unexpected death in epilepsy (SUDEP) has been identified as one of the most prevalent causes of mortality in epilepsy, and SUDEP has consequently become an important topic of research. The causes appear multifactorial, including epilepsy-induced cardiac arrest. Current understanding of autopsy negative sudden unexplained death (SUD) in general population and its relation to sudden arrhythmic death syndrome (SADS) could shed some light in SUDEP. Mutual attention to the findings of sudden death in cardiology and epilepsy are discussed here. We performed a narrative review on SUDEP, epilepsy and molecular/genetic autopsy in this population. A proposal of an extended terminology for SUDEP classification is discussed in light of recent issues related to molecular autopsy and genetics. The extended classification might be a step forward in research protocols and a tool for better understanding SUDEP.

For many neuromuscular conditions including spinal cord injury, physical exercise training is a recommended part of treatment. High intensity exercise has been found to more effectively promote ambulatory function than moderate intensity exercise. To reach optimal intensity levels, fully ambulatory individuals can adjust their walking speed. In contrast, individuals with neuromuscular deficits may not be able to walk, or only at slow speeds that elicit an insufficient cardiovascular response.In our case study with one spinal cord injured patient, we investigated if assistance from a wearable robot, the Myosuit, can increase exercise intensity towards more effective training.During outside uphill-walking trials, assistance from the Myosuit allowed the patient to increase his walking speed by 30 % to 0.48 m/s and increased energy expenditure by 17 % compared to not wearing the suit. An analysis of gait kinematics suggests that the Myosuit facilitated faster walking by replacing missing hip extensor function and promoting a more upright posture. The metabolic equivalents (METS) during walking with the Myosuit of 7.15 indicate a consistently high exercise intensity. In contrast, one of two unassisted trials only reached a moderate intensity (METS < 6). The concurrent increase in speed and energy expenditure when wearing the Myosuit corresponds to a 9 % increase in the efficiency of walking.Our findings show that the Myosuit can increase the efficiency of walking for a user with incomplete spinal cord injury and suggest that the Myosuit can act as a tool to increase the efficacy of movement training., 2020 8th IEEE RAS/EMBS International Conference for Biomedical Robotics and Biomechatronics (BioRob), ISBN:978-1-7281-5907-2, ISBN:978-1-7281-5908-9

Interictal dysphoric disorder (IDD) is a poorly understood psychiatric disorder of epilepsy patients. Interictal dysphoric disorder is characterized by depressive, somatoform, and affective symptoms observed in up to 5.9% of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study aimed to evaluate the association between ictal fear (IF) and the psychiatric symptoms and diagnosis in MTLE-HS patients. We included 116 (54.3% male) consecutive adult patients (36 ± 11 years) with MTLE-HS. Anxiety and depression symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS) and the psychiatric diagnosis were according to Fourth Edition of the Diagnosis and Statistical Manual of Mental Disorders (DSM-IV). The independent association between the occurrence of IF aura and the psychiatric diagnosis was determined by binary regression. When compared to those with other auras or without aura, patients reporting IF have higher HADS anxiety, but not HADS depression, scores. Ictal fear was independently associated with the diagnosis of interictal dysphoric disorder (OR, IC 95% = 7.6, 1.3–43.2, p = 0.02), but not with the diagnosis of anxiety (OR, CI 95% = 0.72, 0.08–6.0, p = 0.73), depression (OR, CI 95% = 0.94, 0.19–4.8, p = 0.94) or psychotic disorders (p = 0.99). Only patients with drug-resistant MTLE-HS were included and the small number of cases with DD diagnosis in the sample. In MTLE-HS patients, the occurrence of IF is associated with higher levels of anxiety symptoms and IDD. The results provide insights about fear-related neural network connections with anxiety symptoms and the IDD in MTLE-HS.

ObjectiveTo test the hypothesis that neurophysiologic biomarkers of muscle activation during convulsive seizures reveal seizure severity and to determine whether automatically computed surface EMG parameters during seizures can predict postictal generalized EEG suppression (PGES), indicating increased risk for sudden unexpected death in epilepsy. Wearable EMG devices have been clinically validated for automated detection of generalized tonic-clonic seizures. Our goal was to use quantitative EMG measurements for seizure characterization and risk assessment.MethodsQuantitative parameters were computed from surface EMGs recorded during convulsive seizures from deltoid and brachial biceps muscles in patients admitted to long-term video-EEG monitoring. Parameters evaluated were the durations of the seizure phases (tonic, clonic), durations of the clonic bursts and silent periods, and the dynamics of their evolution (slope). We compared them with the duration of the PGES.ResultsWe found significant correlations between quantitative surface EMG parameters and the duration of PGES (p < 0.001). Stepwise multiple regression analysis identified as independent predictors in deltoid muscle the duration of the clonic phase and in biceps muscle the duration of the tonic-clonic phases, the average silent period, and the slopes of the silent period and clonic bursts. The surface EMG-based algorithm identified seizures at increased risk (PGES ≥20 seconds) with an accuracy of 85%.ConclusionsIctal quantitative surface EMG parameters correlate with PGES and may identify seizures at high risk.Classification of evidenceThis study provides Class II evidence that during convulsive seizures, surface EMG parameters are associated with prolonged postictal generalized EEG suppression.

Background Patients with active acromegaly exhibit low hepatocellular lipid content (HCL) despite pronounced insulin resistance. This contrasts the strong association of insulin resistance with non-alcoholic fatty liver disease in the general population. Acromegaly may therefore help to elucidate antisteatotic pathways. Since low HCL in acromegaly might be caused by changes in oxidative substrate metabolism and interorgan crosstalk we investigated mitochondrial activity and plasma metabolomics as well as lipidomics in active acromegaly. Approach & Results Patients In this cross-sectional study, 15 patients with active acromegaly (ACRO) and 17 healthy controls (CON) matched for age, BMI, gender and body composition were included. All participants were invited to undergo 31P/1H-7T-MR-spectroscopy of the liver and skeletal muscle, as well as plasma metabolomic profiling and an oral glucose tolerance test. In comparison to CON, ACRO were insulin resistant, and showed significant lower HCL but their hepatic ATP-synthesis rate adjusted to HCL was significantly increased (h_kATP:0.19[0.14;0.24]vs0.28[0.22;0.34]s-1);p=0.024). Furthermore, the HCL-adjusted ratio of unsaturated to saturated intracellular fatty acids was decreased in ACRO (8.4%vs25.5% of HCL,p Conclusions The dissociation of hepatic lipid content and peripheral insulin resistance in acromegaly is associated with high mitochondrial activity as indicated by liver specific upregulation of the ATP-synthesis rate. This is paralleled by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a change in circulating carnitine species, also reflecting an increased mitochondrial activity. Our findings hint at potential direct effects of growth hormone excess on hepatic lipid and energy metabolism.

The purpose of this study was to examine the relationship between subjectively perceived seizure provocative factors or inhibitors and objectively recorded changes in epileptiform activity (EA) during EEG activation procedures.Consenting epilepsy patients (≥18 years old) were asked to complete a questionnaire by indicating whether items on a list provoke, inhibit or have no effect on their seizures. A scalp EEG was recorded afterwards to evaluate baseline epileptiform activity and its change (increase/decrease in frequency) during a set of activation procedures. These included hyperventilation, intermittent photic stimulation (IPS), eye-closing/eye-opening, tasks of reading aloud in a native and a foreign language, solving a Rubik's cube and crossing-out letters. We used correlation and multiple regression analysis to search for associations between the sum of self-reported provocative/inhibiting items and changes in EA.Of the 90 patients recruited 75 (83.3%) indicated at least one seizure provocative factor. Sleep deprivation, emotional stress, negative emotions and alcohol use were most frequently selected as provoking seizures. Positive feelings, focused thinking, mental calculation and exercising were the most predominant seizure inhibitors. EEG data revealed a weak, but statistically significant correlation with the sum of items in distinct questionnaire groups (0.20 ≤ Spearman's ρ ≤ 0.39). Sensory stimuli (olfactory, gustatory, auditory and visual), cognitive phenomena (thoughts and feelings) and substance use were found to be significantly correlated with EEG results by being self-reported as both provoking and inhibiting seizures. A statistically significant relationship was also found between the increase in EA while reading aloud in a native language and the number of physiological states (sleep deprivation, stress etc.) indicated as provoking seizures (Spearman's ρ = 0.320, P = 0.005). A suitable stepwise multiple regression model was feasible for this finding (F(3, 71) = 7.396, P0.001, adjusted R squared = 0.206) with the additional inclusion of EA change during IPS and epilepsy type as explanatory variables.Our pilot study indicates that there is a previously non-explored association between patients' self-perception of seizure provocative/inhibiting factors and objectively recorded changes in epileptiform activity during activation EEGs. Distinct EEG tests might be useful in activating ictogenic networks that are sensitive to indirect influence by hormonal, emotional or diurnally variable factors.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent (31)P/(1)H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

To move a condition from its genetic definition to a comprehensive syndrome description is an important step forward, and Vlaskamp et al.1 can be thanked for having done this for SYNGAP1 . The inclusion of 57 patients in a multicenter study provided an excellent, detailed delineation of the seizure syndrome. Attention is drawn to some reflex epileptic traits, including seizures precipitated by eating. In a recent study,2 we have particularly addressed this feature and noted that, whereas eating-induced seizures commonly are related to various phases of food intake, the trigger in our cases seemed, more narrowly, to be biting and chewing. They seem, thus, to represent a pathomechanism different from other eating-induced seizures. In addition, we saw that these patients were also commonly eye-closure sensitive.

Background Medical phototherapy can lead to the manifestation of polymorphic light eruption (PLE), though little is known about the frequency of such events. Aims The aim of this Austrian single center study was to retrospectively investigate over a 4‐year time period the frequency of PLE in patients prone to the condition and patients with other diseases under phototherapy (mainly narrow‐band and broad‐band UVB). Materials and Methods The data for analysis were obtained from the electronic health and patient record database and patient files of the Photodermatology Unit, Department of Dermatology, Medical University of Graz, Austria. Results PLE occurred in 24.3% (18/74) of PLE patients but only 0.7% (3/421) of psoriasis patients under phototherapy (chi‐square; P

Aktuelle Leitlinien empfehlen, im Rahmen der Abklarung einer Hyponatriamie eine primare Hypothyreose auszuschliesen. Die Evidenz aus groseren Studien und damit die Bedeutung fur den klinischen Alltag sind hierfur jedoch nicht eindeutig und durchaus kritisch zu hinterfragen. Es gibt verschiedene Erklarungsmechanismen, wie die Schilddrusenunterfunktion eine Hyponatriamie auslosen konnte. Ein Ansatz geht davon aus, dass der bei hypothyreoten Patienten erhohte ADH-Spiegel uber eine Wasserretention zu einer Hyponatriamie fuhren konnte. Ein weiterer Ansatz beruft sich auf eine reduzierte Herzfunktion, welche durch eine Schilddrusenunterfunktion ausgelost werden kann. Dies sowie mogliche Veranderungen in der Niere, insbesondere eine reduzierte glomerulare Filtrationsrate, konnten eine Hyponatriamie erklaren. Ob diese Mechanismen jedoch auch fur den medizinischen Alltag von Relevanz sind bzw. eine Schilddrusenunterfunktion alleine ausreicht, um eine klinisch relevante Hyponatriamie zu induzieren, ist unklar. Eine kurzlich von uns publizierte Studie an einem grosen Patientenkollektiv mit Hyponatriamie konnte keinen wesentlichen Einfluss einer Hypothyreose zeigen. In Zusammenschau der vielen Studien zu dieser Thematik lasst sich folgern, dass eine Hypothyreose als alleiniges Krankheitsbild, wenn uberhaupt, sehr selten fur eine klinisch relevante Hyponatriamie verantwortlich sein durfte. Bei Patienten mit einem verminderten Natriumspiegel gibt es viele alternative Ursachen, welche nicht ubersehen werden sollten.