Potential role of skeletal muscle glycerophosphocholine in response to altered fluid balance in humans: an in vivo nuclear magnetic resonance study.

Many cells adapt to hyperosmolal conditions by upregulation of organic osmolytes to maintain cell function and integrity. Glycerophosphocholine (GPC), a recognized osmolyte in renal medullary cells, is the major phosphodiester (PDE) in human skeletal muscle, wherefore we hypothesized muscular GPC to be associated with surrogate parameters of fluid status and osmolality in healthy humans. The objective of this study was to investigate the relationship of muscular GPC with surrogate parameters of body fluid status and osmolality. We analyzed data of 30 healthy volunteers who underwent noninvasive 31P-magnetic resonance spectroscopy of either calf (n = 17) or thigh (n = 13) muscle. Therefore, we conducted correlation analyses between phosphor metabolites, and blood values depicting body fluid status and osmolality. Relevant parameters were further implemented in a multivariable regression model to evaluate if GPC concentrations can depict variations in fluid and electrolyte balance. Uric acid (0.437, P = 0.018) and urea (0.387, P = 0.035) were significantly correlated with GPC, which in case of uric acid was independent of sex. Considering sex, following multivariable regression reported GPC as suitable parameter to predict uric acid (R2 = 0.462, adjusted R2 = 0.421; P < 0.001). Our data indicate a connection between muscular GPC concentrations and uric acid, which is a marker of body fluid status, in healthy human subjects, suggesting that skeletal muscle might regulate GPC content in adaptation to changes in fluid status.NEW & NOTEWORTHY Using in vivo magnetic resonance spectroscopy, our study is the first one indicating fluid balance-dependent properties of glycerophosphocholine concentrations in human skeletal muscle. In vivo examination of GPC as organic osmolyte in human skeletal muscle marks a novel approach, which might give further insight on how water and electrolyte balance affect muscle tissue. Beside this main finding, glycerophosphocholine of both calf and thigh muscle correlated remarkably with blood laboratory parameters of lipid metabolism in our study population.

Prediction of individual graft for anterior cruciate ligament reconstruction using anthropometric data.

INTRODUCTION: Multiple options for individual anterior cruciate ligament (ACL) reconstruction exist; still, there are no guidelines for the preoperative preparation. The aim of this study was to assess the correlation between patients' anthropometric data (height, weight, and age) and measurements of potential tendons (quadriceps-, patella, hamstrings tendon) for an anterior cruciate ligament reconstruction. MATERIAL AND METHODS: MR images of 102 patients have been analyzed. Measurements of the ACL were performed with respect to its length and angle. The diameter and length as well as width of the quadriceps and patella tendon, the cross-sectional area (CSA) and diameter of the hamstring tendons have been assessed. Patients' height, weight, BMI, sex and age have been recorded. The correlations of these measurements with the patients' anthropometric data have been calculated. Inter-rater and intra-rater reliability based on intra-class correlation (ICC) was evaluated. RESULTS: The mean lengths of the ACL were 29.8 ± 3.5 mm, tibial insertion sites 15.8 ± 2.5 mm and femoral insertion sites 15.2 ± 3.0 mm. Thickness of the quadriceps tendons was 4.7 ± 1.1 mm and patella tendon 3.2 ± 0.7 mm. The patients' height showed significant positive correlations with the CSA of the hamstring tendon measurements, the length of the ACL, and the insertion sites of the ACL. Patients' weight showed significant positive correlations with patella tendon thickness, the CSA of the hamstring tendons, the length of the ACL, and the tibial and femoral insertion sites. Patients' age showed a significant positive correlation with patella tendon thickness. The ICCs for intra- and inter-rater reliability were 0.98 (95% CI 0.95-0.99, p < 0.001) and 0.94 (95% CI 0.88-0.99, p < 0.001). CONCLUSION: Anthropometric data with respect to height, weight, and sex can help to predict the dimension of tendons for ACL reconstruction and do correlate with ACL tendon. Patients at risk for small graft dimensions and failure are younger than 20 years and physically active. MRIs of patients at risk for small graft dimensions should be analyzed on tendon length and cross section areas preoperatively to determine the appropriate tendon harvest and fixation technique.

Repeatability assessment of sodium (23Na) MRI at 7.0 T in healthy human calf muscle and preliminary results on tissue sodium concentrations in subjects with Addison's disease.

OBJECTIVES: To determine the relaxation times of the sodium nucleus, and to investigate the repeatability of quantitative, in vivo TSC measurements using sodium magnetic resonance imaging (23Na-MRI) in human skeletal muscle and explore the discriminatory value of the method by comparing TSCs between healthy subjects and patients with Addison's disease. MATERIALS AND METHODS: In this prospective study, ten healthy subjects and five patients with Addison's disease were involved. 23Na-MRI data sets were acquired using a density-adapted, three-dimensional radial projection reconstruction pulse sequence (DA-3DPR) with a modification for the relaxation times measurements. Differences in TSC between muscle groups and between healthy participants were analysed using a nonparametric Friedman ANOVA test. An interclass correlation coefficient (ICC) was used as the repeatability index. Wilcoxon rank sum test was used for evaluation of differences in TSC between study participants. RESULTS: The mean T1 in the gastrocnemius medialis (GM), the tibialis anterior (TA), and the soleus (S) was 25.9 ± 2.0 ms, 27.6 ± 2.0 ms, and 28.2 ± 2.0 ms, respectively. The mean short component of T2*, T2*short were GM: 3.6 ± 2.0 ms; TA: 3.2 ± 0.5 ms; and S: 3.0 ± 1.0 ms, and the mean long component of T2*, T2*long, were GM: 12.9 ± 0.9 ms; TA: 12.8 ± 0.7 ms; and S: 12.9 ± 2.0 ms, respectively. In healthy volunteers, TSC values in the GM were 19.9 ±0.1  mmol/L, 13.8 ±0.2 mmol/L in TA, and 12.6 ± 0.2 mmol/L in S, and were significantly different (p = 0.0005). The ICCs for GM, TA and S were 0.784, 0.818, 0.807, respectively. In patients with Addison's disease, TSC in GC, TA, and S were 10.2 ± 1.0 mmol/L, 8.4 ± 0.6 mmol/L, and 7.2 ± 0.1 mmol/L, respectively. CONCLUSIONS: TSC quantification in a healthy subject's calf at 7.0 T is reliable; the technique is able to distinguish sodium level differences between muscles and between healthy subjects and Addison's disease patients.

The impact of the SARS-CoV2 pandemic on the prescription of thyroid medication in Austria - A nationwide population-based registry analysis.

BACKGROUND: Case reports indicate a clinical connection between SARS-CoV-2 and thyroid dysfunctions. However, evidence from large population-based registry analyses is sparse, especially in Europe, where iodine deficiency is common. This study aimed to analyze the impact of the COVID-19 pandemic on healthcare provision for thyroid diseases in Austria. METHODS: We performed a retrospective, population-based registry analysis of the Austrian health insurance fund database, covering more than 9 million inhabitants. Data from all patients with prescriptions of thyroid-specific drugs and/or inpatient thyroid-related diagnoses from 2017 to 2019 (pre-pandemic years) were compared to 2020 and 2021 (pandemic years; characterized by high numbers of SARS-CoV2 infections and population-wide vaccination strategy). The incidence rates of thyroid medication prescriptions for hypothyroidism and hyperthyroidism were calculated for every year to evaluate the impact of the pandemic. RESULTS: The incidence rate for total thyroid medication prescription was 539.07/100,000 individuals (534.23-543.93 95%CI) in 2018 and declined during the pandemic (2020: 387.19/100,000 (383.12-391.29 95%CI); 2021: 336.90/100,000 (333.11-340.73 95%CI)). Similarly, the incidence rate for levothyroxine prescription was higher pre-pandemic (2018: 465.46/100,000 (460.97-469.98 95%CI) and declined during the pandemic (2020: 348.14/100,000 (344.28-352.03 95%CI); 2021: 300.30/100,000 (296.7-303.91 95%CI). The incidence rates of thiamazole prescriptions (2018: 10.24/100,000 (9.58-10.93 95%CI); 2020: 8.62/100,000 (8.03-9.26 95%CI); 2021: 11.17/100,000 (10.49-11.89 95%CI) were stable. CONCLUSIONS: These findings suggest no clinically significant impact of SARS-CoV2 and/or vaccination on thyroid function at a population level.

The Timing of Pregnancies After Bariatric Surgery has No Impact on Children's Health-a Nationwide Population-based Registry Analysis.

PURPOSE: Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children's outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12-24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied. MATERIALS AND METHODS: A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring's data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months. RESULTS: Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval. CONCLUSION: Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children.

Increased GH/IGF-I Axis Activity Relates to Lower Hepatic Lipids and Phosphor Metabolism.

CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. OBJECTIVE: The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. METHODS: We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1H/31P magnetic resonance spectroscopy. RESULTS: In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = -0.31; P = .02), GH during oral glucose tolerance test (R = -0.51; P < .01), and IGF-I (R = -0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. CONCLUSION: GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism.

Intensive care in an older population: Influence of age, comorbidities and sex in 304 plastic and reconstructive surgical patients older than 75 years.

AIM: An aging population will lead to an increasing demand for critical care resources. Hence, we evaluated the potential influence of age, comorbidities and sex in plastic and reconstructive patients ≥75 years that were admitted to the intensive care unit (ICU). METHODS: We included 304 patients who required intensive care between 2000 and 2019. Besides patient demographics, medical case characteristics were statistically evaluated. RESULTS: In this study, 184 patients were female (61%) (120 male), the median age was 81.8 years (25th and 75th percentiles: 77.4-87.2) with a range of 75.0-98.9 years. The median length of stay in the ICU was 12 days (25th and 75th percentiles: 3-28) with a range of 0-382 days. The reasons for admission were burn injury (n = 230, 76%), necrotizing fasciitis (n = 34, 11%), non-combustion-related traumas (n = 22, 7%) and postoperative observation after plastic surgery procedures (n = 18, 6%). In total, 108 patients (36%), who were significantly older (P = 0.005) and had a significantly shorter stay (P < 0.001) compared with the surviving cohort, died during their stay in the ICU. Our multivariable logistic regression model revealed that age (odds ratio: 1.05 [1.01, 1.09]; P = 0.017) and number of operations (odds ratio: 0.75 [0.60, 0.96]; P = 0.023) were significant predictors for death in the ICU. DISCUSSION: Age plays a critical role in determining fatal outcome of old patients requiring intensive care. In contrast, sex and number of comorbidities shows no significant influence. Geriatr Gerontol Int 2022; 22: 597-602.

Sex-Specific Differences in Mortality of Patients with a History of Bariatric Surgery: a Nation-Wide Population-Based Study.

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 < 0.001(Chi-squared)). Moreover, the 30-day mortality was 0.19% and sixfold higher in men compared to women (0.48 vs. 0.08%; p < 0.001). CV (82%) and PSY (55%) were the most common comorbidities in deceased patients with no sex-specific differences. Diabetes (38%) was more common in men (43 vs. 33%; 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.

Feasibility of Hepatic Fat Quantification Using Proton Density Fat Fraction by Multi-Echo Chemical-Shift-Encoded MRI at 7T.

Fat fraction quantification and assessment of its distribution in the hepatic tissue become more important with the growing epidemic of obesity, and the increasing prevalence of diabetes mellitus type 2 and non-alcoholic fatty liver disease. At 3Tesla, the multi-echo, chemical-shift-encoded magnetic resonance imaging (CSE-MRI)-based acquisition allows the measurement of proton density fat-fraction (PDFF) even in clinical protocols. Further improvements in SNR can be achieved by the use of phased array coils and increased static magnetic field. The purpose of the study is to evaluate the feasibility of PDFF imaging using a multi-echo CSE-MRI technique at ultra-high magnetic field (7Tesla). Thirteen volunteers (M/F) with a broad range of age, body mass index, and hepatic PDFF were measured at 3 and 7T by multi-gradient-echo MRI and single-voxel spectroscopy MRS. All measurements were performed in breath-hold (exhalation); the MRI protocols were optimized for a short measurement time, thus minimizing motion-related problems. 7T data were processed off-line using Matlab® (MRI:multi-gradient-echo) and jMRUI (MRS), respectively. For quantitative validation of the PDFF results, a similar protocol was performed at 3T, including on-line data processing provided by the system manufacturer, and correlation analyses between 7 and 3T data were performed off-line. The multi-echo CSE-MRI measurements at 7T with a phased-array coil configuration and an optimal post-processing yielded liver volume coverage ranging from 30 to 90% for high- and low-BMI subjects, respectively. PDFFs ranged between 1 and 20%. We found significant correlations between 7T MRI and -MRS measurements (R2 ≅ 0.97; p < 0.005), and between MRI-PDFF at 7T and 3T fields (R2 ≅ 0.94; p < 0.005) in the evaluated volumes. Based on the measurements and analyses performed, the multi-echo CSE-MRI method using a 32-channel coil at 7T showed its aptitude for MRI-based quantitation of PDFF in the investigated volumes. The results are the first step toward qMRI of the whole liver at 7T with further improvements in hardware.

Gluconeogenesis, But Not Glycogenolysis, Contributes to the Increase in Endogenous Glucose Production by SGLT-2 Inhibition.

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.

Bariatric Surgery for Hypothalamic Obesity in Craniopharyngioma Patients: A Retrospective, Matched Case-Control Study.

CONTEXT: Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~ 98%) and hypothalamic obesity (~ 50%). OBJECTIVE: This work aims to determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction. METHODS: This retrospective, case-control, multicenter, international study included obese craniopharyngioma patients (N = 16; of whom 12 are women) with a history of bariatric surgery (12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age 21 years [range, 15-52 years], median follow-up 5.2 years [range, 2.0-11.3 years]) and age/sex/surgery/body mass index-matched obese controls (N = 155). 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 vs 29.5% (95% CI, 28.0%-30.9%) in controls (P = .02), which was less after Roux-en-Y gastric bypass (22.7% [16.9%-28.5%] vs 32.0% [30.4%-33.6%]; P = .003) but at a similar level after sleeve gastrectomy (21.7% [-1.8% to 45.2%] vs 21.8% [18.2%-25.5%]; P = .96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems. CONCLUSION: 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 to be effective and relatively safe in the treatment of obese craniopharyngioma patients.

Pre-operative Obesity-Associated Hyperandrogenemia in Women and Hypogonadism in Men Have No Impact on Weight Loss Following Bariatric Surgery.

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.

Effects of Thyroid Function on Phosphodiester Concentrations in Skeletal Muscle and Liver: An In Vivo NMRS Study.

CONTEXT: Thyroid function is clinically evaluated by determination of circulating concentrations of thyrotropin (thyroid-stimulating hormone; TSH) and free thyroxine (fT4). However, a tissue-specific effector substrate of thyroid function is lacking. Energy-rich phosphorus-containing metabolites (PM) and phospholipids (PL) might be affected by thyroid hormone action and can be noninvasively measured by 31P nuclear magnetic resonance spectroscopy (NMRS). OBJECTIVES: To measure the actions of peripheral thyroid hormones on PM and PL tissue concentrations. DESIGN AND SETTING: A longitudinal, prospective pilot study was performed. PARTICIPANTS: Nine patients with hyperthyroidism (HYPER) and 4 patients with hypothyroidism (HYPO) were studied at baseline and 3 months after treatment. MAIN OUTCOME MEASURES: High-field 1H/31P NMRS was used to assess profiles of PM, PL, and flux through oxidative phosphorylase in liver and skeletal muscle, as well as ectopic tissue lipid content. RESULTS: The concentrations of total skeletal muscle (m-) and hepatic (h-) phosphodiesters (PDE) and one of the PDE constituents, glycerophosphocholine (GPC), were lower in HYPER compared with HYPO (m-PDE: 1.4 ±â€…0.4 mM vs 7.4 ±â€…3.5 mM, P = 0.003; m-GPC: 0.9 ±â€…0.3 mM vs 6.7 ±â€…3.5 mM, P = 0.003; h-PDE: 4.4 ±â€…1.4 mM vs 9.9 ±â€…3.9 mM, P = 0.012; h-GPC: 2.2 ±â€…1.0 mM vs 5.1 ±â€…2.4 mM, P = 0.024). Both h-GPC (rho = -0.692, P = 0.018) and h-GPE (rho = -0.633, P = 0.036) correlated negatively with fT4. In muscle tissue, a strong negative association between m-GPC and fT4 (rho = -0.754, P = 0.003) was observed. CONCLUSIONS: Thyroxine is closely negatively associated with the PDE concentrations in liver and skeletal muscle. Normalization of thyroid dysfunction resulted in a decline of PDE in hypothyroidism and an increase in hyperthyroidism. Thus, PDE might be a sensitive tool to estimate tissue-specific peripheral thyroid hormone action.

Psychopharmacological Medication Has No Influence on Vitamin Status After Bariatric Surgery in Long-term Follow-up.

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.

Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects.

BACKGROUND: Increased fructose intake has been associated with metabolic consequences such as impaired hepatic lipid metabolism and development of nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: The aim of this study was to investigate the role of fructose in glucose and lipid metabolism in the liver, heart, skeletal muscle, and adipose tissue. METHODS: Ten healthy subjects (age: 28 ± 19 y; BMI: 22.2 ± 0.7 kg/m2) underwent comprehensive metabolic phenotyping prior to and 8 wk following a high-fructose diet (150 g daily). Eleven patients with NAFLD (age: 39.4 ± 3.95 y; BMI: 28.4 ± 1.25) were characterized as "positive controls." Insulin sensitivity was analyzed by a 2-step hyperinsulinemic euglycemic clamp, and postprandial interorgan crosstalk of lipid and glucose metabolism was evaluated, by determining postprandial hepatic and intra-myocellular lipid and glycogen accumulation, employing magnetic resonance spectroscopy (MRS) at 7 T. Myocardial lipid content and myocardial function were assessed by 1H MRS imaging and MRI at 3 T. RESULTS: High fructose intake resulted in lower intake of other dietary sugars and did not increase total daily energy intake. Ectopic lipid deposition and postprandial glycogen storage in the liver and skeletal muscle were not altered. Postprandial changes in hepatic lipids were measured [Δhepatocellular lipid (HCL)_healthy_baseline: -15.9 ± 10.7 compared with ± ΔHCL_healthy_follow-up: -6.9 ± 4.6; P = 0.17] and hepatic glycogen (Δglycogen_baseline: 64.4 ± 14.1 compared with Δglycogen_follow-up: 51.1 ± 9.8; P = 0.42). Myocardial function and myocardial mass remained stable. As expected, impaired hepatic glycogen storage and increased ectopic lipid storage in the liver and skeletal muscle were observed in insulin-resistant patients with NAFLD. CONCLUSIONS: Ingestion of a high dose of fructose for 8 wk was not associated with relevant metabolic consequences in the presence of a stable energy intake, slightly lower body weight, and potentially incomplete absorption of the orally administered fructose load. This indicated that young, metabolically healthy subjects can at least temporarily compensate for increased fructose intake. This trial was registered at www.clinicaltrials.gov as NCT02075164.

A Comparison of Dynamic Hip Screw and Two Cannulated Screws in the Treatment of Undisplaced Intracapsular Neck Fractures-Two-Year Follow-Up of 453 Patients.

One of the most common fractures is that of the intracapsular femoral neck; however, the optimal implant for head-preserving treatment remains controversial. The aim of the study was to compare the outcomes of treating undisplaced intracapsular femoral neck fractures with either the dynamic hip screw (DHS) or the double cannulated screw fixation (CSFN). This retrospective cohort study analysed the data of 453 patients, with a mean age of 76.9 years, whose intracapsular fractures were treated with the DHS or CSFN between 2005 and 2013. The analysis focused on the rates of revision surgeries and complications; however, the impact of confounding exogenous factors, such as smoking and alcohol, were also considered. No significant difference was observed between the revision rates of DHS and CSFN (15.0% vs. 13.1%; p = 0.565). According to the complication rate, the advantage in favour of the CSFN was not significant (20.5% vs. 13.1%, p = 0.038). The use of the DHS was associated with a 13 min longer surgery (p < 0.0001) and a one day longer hospitalization (p = 0.242). Excessive consumption of alcohol was associated with an increased incidence of avascular necrosis (18.6% vs. 8.7%, p = 0.035). The choice of implant showed no significant impact on rates of revision surgery and complications. In terms of socioeconomic factors, the fixation with two cannulated screws was more favourable, making it the more cost-effective and less stressful method.

Reduced hepatocellular lipid accumulation and energy metabolism in patients with long standing type 1 diabetes mellitus.

The prevalence of obesity and metabolic syndrome increases in patients with type 1 diabetes mellitus (T1DM). In the general population this is linked with ectopic lipid accumulation in liver (HCL) and skeletal muscle (IMCL), representing hallmarks in the development of insulin resistance. Moreover, hepatic mitochondrial activity is lower in newly diagnosed patients with T1DM. If this precedes later development of diabetes related fatty liver disease is currently not known. This study aims to investigate energy metabolism in liver (kATP) and skeletal muscle (kCK) and its impact on HCL, IMCL, cardiac fat depots and heart function in 10 patients with long standing T1DM compared to 11 well-matched controls by 31P/1H magnetic resonance spectroscopy. HCL was almost 70% lower in T1DM compared to controls (6.9 ± 5% vs 2.1 ± 1.3%; p = 0.030). Also kATP was significantly reduced (0.33 ± 0.1 s-1 vs 0.17 ± 0.1 s-1; p = 0.018). In T1DM, dose of basal insulin strongly correlated with BMI (r = 0.676, p = 0.032) and HCL (r = 0.643, p = 0.045), but not with kATP. In the whole cohort, HCL was significantly associated with BMI (r = 0.615, p = 0.005). In skeletal muscle kCK was lower in patients with T1DM (0.25 ± 0.05 s-1 vs 0.31 ± 0-04 s-1; p = 0.039). No significant differences were found in IMCL. Cardiac fat depots as well as heart function were not different. Our results in patients with long standing T1DM show that HCL is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle.

Plasma renin levels are associated with cardiac function in primary adrenal insufficiency.

BACKGROUND: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease. The role of MC replacement is not known. Therefore, we assessed whether renin concentrations during routine GC and MC substitution therapy are associated with heart function and morphology. METHODS: Thirty two patients with primary AI were included in a cross-sectional case-control study. In total, 17 patients and 34 healthy controls (age: 48 ± 12 vs. 46 ± 18 years; BMI: 23 ± 3 vs. 24 ± 3 kg/m2) underwent magnetic resonance spectroscopy and imaging measurements to assess cardiac function, morphology, ectopic lipids, and visceral/subcutaneous fat mass. Patients were divided according to their actual plasma renin concentration at the study visit (Actual-Reninlow vs. Actual-Reninhigh) and their median plasma renin concentration of previous visits (Median-Reninlow vs. Median-Reninhigh). RESULTS: Ejection fraction was higher (67 ± 5 vs. 55 ± 3%; p = 0.001) and left ventricular mass was lower (60 ± 9 vs. 73 ± 10 g/m2; p = 0.025) in Actual-Reninhigh. Median-Reninhigh was associated with lower cardiac mass (64 ± 9 vs. 76 ± 11 g/m2; p = 0.029). Blood pressure, glucose, and lipid metabolism, as well as ectopic lipid content, pericardial fat mass, and visceral/subcutaneous fat were not different between the groups. Compared with controls, ejection fraction was significantly lower in patients with AI (56 ± 4 vs. 63 ± 8%; p = 0.019). No differences were found in patients with ≤20 mg compared with >20 mg of hydrocortisone per day. CONCLUSIONS: Higher renin concentrations are associated with more favorable cardiac function and morphology in patients with primary AI.

Identifying a disease-specific renin-angiotensin-aldosterone system fingerprint in patients with primary adrenal insufficiency.

BACKGROUND: In patients suffering from primary adrenal insufficiency (AI) mortality is increased despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, mainly due to an increased cardiovascular risk. Since activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the modulation of cardiovascular risk factors, we performed in-depth characterization of the RAAS activity. METHODS: Eight patients with primary AI (female = 5; age: 56 ± 21 years; BMI: 22.8 ± 2 kg/m2; mean blood pressure: 140/83 mmHg; hydrocortisone dose: 21.9 ± 5 mg/day; fludrocortisone dose: 0.061 ± 0.03 mg/day) and eight matched healthy volunteers (female = 5; age: 52 ± 21 years; BMI: 25.2 ± 4 kg/m2; mean blood pressure:135/84 mmHg) were included in a cross-sectional case-control study. Angiotensin metabolite profiles (RAS-fingerprints) were performed by liquid chromatography mass spectrometry. RESULTS: In patients suffering from primary AI, RAAS activity was highly increased with elevated concentrations of renin concentration (P = 0.027), angiotensin (Ang) I (P = 0.022), Ang II (P = 0.032), Ang 1-7 and Ang 1-5. As expected, aldosterone was not detectable in the majority of AI patients, resulting in a profoundly suppressed aldosterone-to-AngII ratio (AA2 ratio, P = 0.003) compared to controls. PRA-S, the angiotensin-based marker for plasma renin activity, correlated with plasma renin activity (r = 0.983; P < 0.01) and plasma renin concentration (r = 0.985; P < 0.001) and was significantly increased in AI patients. CONCLUSIONS: AI is associated with a unique RAAS profile characterized by the absence of aldosterone despite strongly elevated levels of angiotensin metabolites, including the potent vasoconstrictor AngII. Despite state-of-the-art hormone replacement therapy, the RAAS remains hyperactivated. The contribution of Ang II in cardiovascular diseases in AI patients as well as a potential role for providing useful complementary information at diagnosis and follow up of AI should be investigated in future trials.