Prolactin levels in functional hypothalamic amenorrhea: a retrospective case-control study.

PURPOSE: Functional hypothalamic amenorrhea (FHA) is due to hypothalamic dysregulation. Literature lacks data about prolactin in FHA women, although both prolactin levels and FHA are associated with stress. Moreover, polycystic ovarian morphology is common in FHA and there is an association between FHA and polycystic ovary syndrome. Thus, the aim of this study was to assess prolactin levels in FHA patients and controls with a special focus on factors influencing prolactin levels, that could be considered as "sensors" of the hypothalamic-pituitary dysregulation. METHODS: In a retrospective cohort study, 140 women with clearly defined FHA were compared to 70 healthy, normally ovulating women matched for age. The main outcome parameter was prolactin. Factors associated with prolactin levels > 12 µg/L were tested using a multivariable binary logistic regression model. RESULTS: The median prolactin level was 11.5 µg/L (interquartile range, IQR 7.5-14.4), which was similar to the control group (median 10.7, IQR 8.3-14.5; p = 0.065). Only two women had hyperprolactinemia (prolactin > 25 µg/L; 1.4%). In a multivariable binary logistic regression model eating disorder (odds ratio, OR 0.206; p = 0.040), excessive exercise (OR 0.280; p = 0.031) and TSH (OR 1.923; p = 0.020) were significantly associated with prolactin levels > 12 µg/L. CONCLUSION: Women with FHA have similar prolactin levels to healthy age-matched individuals. Eating disorders and excessive exercise where associated with prolactin levels < 12 µg/L, in contrast to TSH.

Prevalence of functional hypothalamic amenorrhea in a cohort of women referred because of polycystic ovary syndrome.

In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients of about 2% was found. It is necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long-term effects in women with undiagnosed FHA.

Stress and polycystic ovarian morphology in functional hypothalamic amenorrhea: a retrospective cohort study.

BACKGROUND: Women with functional hypothalamic amenorrhea (FHA) reveal polycystic ovarian morphology (PCOM) in up to 50%. If stress sensitivity in women with polycystic ovary syndrome (PCOS) is the reason why PCOS women are prone to develop FHA, patients with FHA caused by stress should reveal PCOM more often. METHODS: In a retrospective cohort study, 38 stress-associated and 38 excessive exercise-induced FHA women were included. The main outcome parameter was PCOM. In addition, the focus was on general patient characteristics as well as on prolactin, dehydroepiandrosterone-sulphate (DHEAS), and anti-Mullerian hormone (AMH). RESULTS: PCOM was found in 34/76 patients (44.7%). The stress group showed a higher prevalence of PCOM than the excessive exercise group (57.9% versus 31.6%, p = 0.019) as well as higher prolactin levels (median 13.2ng/mL versus 11.7ng/mL, p = 0.008) and a trend towards higher DHEAS levels (p = 0.058). CONCLUSIONS: In FHA women, the PCOM prevalence was significantly higher in the stress-group than in the excessive exercise-group. The well-known stress sensitivity in women with PCOS might explain why PCOS women are prone to develop FHA as well as the high PCOM prevalence in FHA women.

Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis.

[Figure: see text].

N-terminal pro-brain natriuretic peptide is a prognostic marker for response to intensive chemotherapy, early death, and overall survival in acute myeloid leukemia.

Patient-related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed NT-proBNP levels at diagnosis in 312 AML patients (median age: 61 years; range 17-89 years) treated with 3 + 7-based induction-chemotherapy and consolidation with up to four cycles of intermediate or high-dose ARA-C. NT-proBNP levels were elevated in 199 patients (63.8%), normal (0-125 pg/ml) in 113 (36.2%), and highly elevated (>2000 pg/ml) in 20 patients (6.4%). Median NT-proBNP levels differed significantly among patients with complete remission (153.3 pg/ml), no remission (225.9 pg/ml), or early death (735.5 pg/ml) (p = .002). In multivariate analysis, NT-proBNP, age, and the 2009 European LeukemiaNet (ELN-2009) classification were independent predictors of outcome after induction chemotherapy. Overall survival (OS) differed significantly between patients with normal, moderately elevated, and highly elevated NT-proBNP (p < .001). These differences were observed in all patients and in patients <60 years but not in those ≥60 years. In multivariate analysis, NT-proBNP, age, and ELN-2009 remained independent prognostic variables for OS (p < .01). Together, NT-proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML.

Effect of etelcalcetide versus alfacalcidol on left ventricular function and feature-tracking cardiac magnetic resonance imaging in hemodialysis-a post-hoc analysis of a randomized, controlled trial.

BACKGROUND: Calcimimetic therapy with etelcalcetide (ETEL) has been shown to attenuate the advancement of left ventricular (LV) hypertrophy in hemodialysis patients measured by cardiac magnetic resonance (CMR). The aim of the study was to evaluate whether this effect is accompanied by alterations in LV function and myocardial composition. METHODS: This was a post-hoc analysis of a randomized-controlled trial of ETEL versus Alfacalcidol (ALFA) in 62 hemodialysis patients. LV function was assessed using LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) on feature-tracking (FT) CMR. Myocardial tissue characteristics were analyzed using parametric T1 and T2 mapping. RESULTS: Of the total study cohort (n = 62), 48 subjects completed both CMR scans with sufficient quality for FT analysis. In the one-year follow-up, LV GLS deteriorated in the ALFA group, whereas the ETEL group remained stable (LV GLS change: + 2.6 ± 4.6 versus + 0.3 ± 3.8; p = 0.045 when adjusting for randomization factors and baseline LV GLS). We did not observe a difference in the change of LVEF between the two groups (p = 0.513). The impact of ETEL treatment on LV GLS over time remained significant after additional adjustment for the change in LV mass during the study period. ETEL treatment did not significantly affect other CMR parameters. There were no changes in myocardial composition between treatment groups (T1 time change: + 15 ± 42 versus + 10 ± 50; p = 0.411; T2 time change: - 0.13 ± 2.45 versus - 0.70 ± 2.43; p = 0.652). CONCLUSIONS: In patients undergoing hemodialysis, treatment with ETEL was protective against deterioration of LV longitudinal function, as evaluated through FT CMR, when compared to the control therapy of ALFA. This effect was not mediated by the change in LV mass. Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03182699 . Unique identifier: NCT03182699.

Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

Can thiamine substitution restore cognitive function in alcohol use disorder?

AIMS: While clinical consequences of thiamine deficiency in alcohol use disorder (AUD) are severe, evidence-based recommendations on dosage, type of administration and duration of thiamine substitution (TS), and its' target levels remain sparse. This study aimed to compare the effect of two best practice TS regimens on thiamine blood levels (i.e. thiamine pyrophosphate, TPP) and cognitive function. METHODS: In 50 patients undergoing in-patient alcohol-withdrawal treatment, TPP levels were determined at baseline and end of weeks 1, 2 and 8 following administration of oral TS (3 × 100 mg/day for 7 days followed by 1 × 100 mg/day thereafter) either with or without preceding intravenous TS (3 × 100 mg/day for 5 days). An extensive psychiatric assessment was conducted at baseline, including an evaluation of AUD severity and depressive symptoms. Additionally, cognitive function and depressive symptoms were repeatedly evaluated. RESULTS: Relevant increases (mean increase by 100.2 nmol/l [CI 76.5-123.8], P < 0.001) in peripheral blood TPP levels were observed in all patients at the end of weeks 1 and 2. Furthermore, no relevant difference between the intravenous and the oral group was found (average difference between increases: 2.3 nmol/l, P = 0.912). Importantly, an association between the 'extent of the response' to TS and the performance in a memory task was revealed in secondary analyses. CONCLUSION: TS was associated with improving cognitive function in patients with AUD, independently of the substitution regime. Thus, in clinical practice, oral TS might be a sufficient but obligatory medication to prevent cognitive decline in AUD in the absence of Wernicke-Korsakoff Syndrome.

Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology.

BACKGROUND: To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment. METHODS: In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these. RESULTS: Serum levels of gonadotropins and estradiol were lower in FHA women than in controls (p < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40-2.50, versus 3.08 ng/mL, IQR 2.24-4.10, respectively, p < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4-370.0, versus 604.9%, IQR 360.0-1122.0; p < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment; p = 0.002). CONCLUSIONS: In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.

Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD). METHODS: Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed in 215 prospectively recruited patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein catheterization. Patients with non-elective hospitalization or bacterial infection were excluded. Histological alpha-smooth muscle actin (α-SMA) area was quantified on full biopsy scans by automated morphometric quantification in a subset of 34 patients who underwent concomitant transjugular liver biopsy. RESULTS: Histological α-SMA proportionate area correlated with enhanced liver fibrosis (ELF) score (Spearman's ρ = 0.660, p < .001), markers of collagen formation (PRO-C3, ρ = 0.717, p < .001; PRO-C6, ρ = 0.526, p = .002) and tissue inhibitor of metalloproteinases-1 (TIMP1; ρ = 0.547, p < .001), indicating that these blood biomarkers are capable of reflecting the dynamic process of ECM turnover. CRP, IL-6 and PCT levels correlated with ELF, biomarkers of collagen synthesis/degradation and TIMP1, both in compensated and decompensated patients. Multivariate linear regression models (adjusted for HVPG) confirmed that CRP, IL-6 and PCT were independently linked to markers of liver fibrogenesis and ECM turnover. CONCLUSION: Systemic inflammation is linked to both liver fibrogenesis and ECM turnover in ACLD and this association is not confounded by the severity of liver disease, as evaluated by HVPG. Our study confirms experimental data on the detrimental impact of SI on ECM deposition and fibrosis progression in a thoroughly characterized cohort of patients with ACLD.

Thyroid and androgen receptor signaling are antagonized by µ-Crystallin in prostate cancer.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein µ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRß) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

Oral Contraceptive Intake and Iodine Status in Young Women.

OBJECTIVE: Similar to pregnant women, women taking an oral contraceptive (OC) might have elevated iodine requirements due to the altered hormonal state. This is the first study aimed at investigating the prevalence of iodine deficiency and possible influences of OC intake on urine creatinine and iodine levels in young women. METHODS: One hundred fifty-five women between the age of 18 and 35 years (62 taking an OC and 93 controls) participated in a cross-sectional pilot study at the Medical University of Vienna, which included a 1-spot urine sample and a questionnaire on OC intake as well as a food questionnaire. RESULTS: The median urinary iodine concentration (UIC) in this study was 68 µg/L (41, 111 µg/L) suggesting an inadequate iodine status in the women according to the WHO guidelines. Median UIC (OC: 89 µg/L, IQR 55-120; control: 59 µg/L, IQR 39-91, p = 0.010) and urine creatinine (OC: median = 99.0 µg/L, IQR 74.9-175.5; control: 77.0 µg/L, IQR 49.6-147.2, p = 0.030) levels were significantly higher in OC women than in the control group. UIC corrected for urine creatinine was comparable between both groups. CONCLUSION: With similar creatinine-corrected UICs in both groups, OC intake might not have a significant impact on iodine status. However, the low median UIC in a vulnerable group of young women potentially conceiving in the following years points at the necessity of optimizing the iodine intake in the Austrian population and reiterates the insufficiency of the current iodine supplementation measures.

Autoimmunological serum parameters and bone mass density in premature ovarian insufficiency: a retrospective cohort study.

PURPOSE: It is still not clear whether to screen women with primary premature ovarian insufficiency for autoimmunity. Moreover, a possible association of autoimmunity with decreased bone mass density in premature ovarian insufficiency patients has not been evaluated. Thus, the objectives of this study were to review our experience with the use of an autoimmune screening panel in premature ovarian insufficiency women and to focus on bone mass density. METHODS: In a retrospective cohort study, 76 chromosomally normal women with primary premature ovarian insufficiency were included. The main outcome parameters were the results of an autoimmune screening panel and of dual-energy X-ray absorptiometry. RESULTS: Median age was 33 years. Sixty percent of premature ovarian insufficiency patients revealed abnormal dual-energy X-ray absorptiometry results (minimal T-score < -1.0). Any signs of autoimmunity were found in 21 women (36.2%). The most frequent abnormal results were increased thyroperoxidase antibodies (24.1%) and thyroglobulin antibodies (20.7%). A longer duration of amenorrhea (ß = -0.015; p = 0.007), any abnormality during autoimmune screening (ß = -0.940; p = 0.010), and a lower body mass index (ß = -0.057; p = 0.036) were associated with a lower minimal T-score. CONCLUSION: In chromosomally normal women with primary premature ovarian insufficiency, the prevalence of autoimmunity and decreased bone mass density seem high. Our data highlight the association between autoimmune abnormalities and decreased dual-energy X-ray absorptiometry results.

Side-by-Side Comparison of Three Fully Automated SARS-CoV-2 Antibody Assays with a Focus on Specificity.

BACKGROUND: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. METHODS: We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. RESULTS: All 3 assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. CONCLUSION: We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

Non-invasive detection of portal hypertension by enhanced liver fibrosis score in patients with different aetiologies of advanced chronic liver disease.

BACKGROUND AND AIMS: The enhanced liver fibrosis (ELF) score comprises serum markers of fibrogenesis and matrix remodelling and was developed to detect liver fibrosis, however, it may also be useful for the non-invasive detection of portal hypertension (PHT). METHODS: ELF score and its single components (TIMP1/PIIINP/HA) were analysed in 201 patients with advanced chronic liver disease (ACLD; ie hepatic venous pressure gradient (HVPG) ≥6 mm Hg). Patients with pre-/post-hepatic PHT, hepatocellular carcinoma beyond Milan criteria, and history of TIPS implantation or liver transplantation were excluded. RESULTS: ELF and its single components correlated with HVPG in the overall cohort: ELF: r = .443, TIMP1: r = .368, PIIINP:r = .332, and HA:r = .419 (all P < .001). The strength of the correlation between ELF and HVPG decreased in higher HVPG strata: 6-9 mm Hg:r = .569(P = .004), 10-19 mm Hg:r = .304 (P = .001) and ≥20 mm Hg:r = -.023(P = .853). Area under the receiver operating characteristics (AUROC) of ELF score to detect clinically significant PHT (CSPH; HVPG ≥ 10 mm Hg) was 0.833. Importantly, HA alone yielded an AUROC of 0.828. Detection of CSPH in strictly compensated ACLD (cACLD) patients was less accurate: AUROC: 0.759 (P < .001). CSPH was ruled-in by ELF ≥ 11.1 with a PPV of 98% (sensitivity: 61%/specificity: 92%/NPV:24%), but CSPH could not be ruled-out. ELF score had a low AUROC of 0.677 (0.60-0.75; P < .001) for the diagnosis of high-risk PHT (HRPH; HVPG ≥ 20mm Hg) and, thus, HRPH could not be ruled-in by ELF. However, ELF < 10.1 ruled-out HRPH with a NPV of 95% (sensitivity: 97%/specificity: 26%/PPV: 39%). CONCLUSION: The ELF score correlates with HVPG at values <20 mm Hg. An ELF ≥ 11.1 identifies patients with a high probability of CSPH, while an ELF < 10.1 may be used to rule-out HRPH.

Impact of HSD17B13 rs72613567 genotype on hepatic decompensation and mortality in patients with portal hypertension.

BACKGROUND & AIMS: The loss-of-function rs72613567 T > TA-variant in the 17ß-hydroxysteroid dehydrogenase 13 (HSD17B13) gene might protect from alcoholic and non-alcoholic fatty liver disease (ALD/NAFLD) and associated fibrosis/cirrhosis. We investigated the impact of the T > TA-variant on hepatic decompensation and mortality and investigated its implications on retinol and sex steroid metabolism in patients who had already developed advanced chronic liver disease (ACLD). METHODS: Retrospective analysis in prospectively characterized patients with viral hepatitis- and ALD/NAFLD-induced portal hypertension (hepatic venous pressure gradient (HVPG) ≥ 6 mmHg) diagnosed at the Medical University of Vienna. RESULTS: Among 487 patients who were followed longitudinally, 166 (34%) were heterozygous and 24 (5%) were homozygous for the 'protective' TA-allele. Patients harbouring at least one TA-allele had a lower MELD (9 (8-12) vs 10 (8-13) points; P = .003) and showed a trend towards lower HVPG (16 ± 6 vs 17 ± 7 mmHg; P = .067). Interestingly, in competing risk analyses adjusted for age, HVPG and MELD, harbouring the TA-allele was associated with numerically increased risks for mortality (adjusted subdistribution hazard ratio (aSHR): 1.3 (95% confidence interval (95% CI): 0.888-1.91); P = .18), liver-related death (aSHR: 1.34 (95% CI: 0.9-1.98); P = .15) and hepatic decompensation (aSHR: 1.29 (95% CI: 0.945-1.77); P = .11). This might be explained by trends towards worse outcomes (eg liver-related death: aSHR: 1.64 (95% CI: 0.95-2.84); P = .076) in patients with viral hepatitis-induced ACLD. In a cross-sectional analysis of 211 additional patients, serum retinol levels were comparable between HSD17B13 genotypes, but in males, serum testosterone levels numerically decreased with an increasing number of TA-alleles. CONCLUSION: In patients with viral hepatitis- and ALD-induced portal hypertension, the T > TA-variant was not protective of hepatic decompensation and mortality. Further studies should investigate the pathophysiological mechanisms underlying the effects of HSD17B13 genotype at different stages of liver disease.

Effect of one-anastomosis gastric bypass on cardiovascular risk factors in patients with vitamin D deficiency and morbid obesity: A secondary analysis.

BACKGROUND AND AIMS: Bariatric patients often suffer from vitamin D (VD) deficiency, and both, morbid obesity and VD deficiency, are related to an adverse effect on cardiovascular disease (CVD) risk. Therefore, we assessed the change of known CVD risk factors and its associations during the first 12 months following one-anastomosis gastric bypass (OAGB). METHODS AND RESULTS: In this secondary analysis, CVD risk factors, medical history and anthropometric data were assessed in fifty VD deficient (25-hydroxy-vitamin D (25(OH)D) <75 nmol/l) patients, recruited for a randomized controlled trial of VD supplementation. Based on previous results regarding bone-mass loss and the association between VD and CVD risk, the study population was divided into patients with 25(OH)D ≥50 nmol/l (adequate VD group; AVD) and into those <50 nmol/l (inadequate VD group; IVD) at 6 and 12 months (T6/12) postoperatively. In the whole cohort, substantial remission rates for hypertension (38%), diabetes (30%), and dyslipidaemia (41%) and a significant reduction in CVD risk factors were observed at T12. Changes of insulin resistance markers were associated with changes of total body fat mass (TBF%), 25(OH)D, and ferritin. Moreover, significant differences in insulin resistance markers between AVD and IVD became evident at T12. CONCLUSION: These findings show that OAGB leads to a significant reduction in CVD risk factors and amelioration of insulin resistance markers, which might be connected to reduced TBF%, change in 25(OH)D and ferritin levels, as an indicator for subclinical inflammation, and an adequate VD status. REGISTERED AT CLINICALTRIALS.GOV: (Identifier: NCT02092376) and EudraCT (Identifier: 2013-003546-16).

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty.

INTRODUCTION: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. METHODS: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. RESULTS: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. CONCLUSIONS: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin.

BACKGROUND: A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy. METHODS: Human chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression. RESULTS: Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin. CONCLUSION: Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Glycated hemoglobin concentrations of red blood cells minimally increase during storage under standard blood banking conditions.

BACKGROUND: Few and inconsistent data exist describing the effect of storage duration on glycated hemoglobin (HbA1c) concentrations of red blood cells (RBCs), impeding interpretation of HbA1c values in transfused diabetic patients. Hence the aim of this study was to evaluate to what extent HbA1c concentrations of RBCs change during the maximum allowed storage period of 42 days. STUDY DESIGN AND METHODS: Blood was drawn from 16 volunteers, leukofiltered, and stored under standard blood banking conditions. HbA1c concentrations of RBCs were measured on Days 1 and 42 of storage using three different validated devices (ion-exchange high-performance liquid chromatography Method A1 and A2, turbidimetric immunoassay Method B). RESULTS: Mean HbA1c concentrations of RBCs on Day 1 were 5.3 ± 0.3% (Method A1), 5.4 ± 0.4% (Method A2), and 5.1 ± 0.4% (Method B). HbA1c concentrations increased to 5.6 ± 0.3% (A1, p < 0.0001), 5.7 ± 0.3% (A2, p = 0.004), and 5.5 ± 0.4% (B, p < 0.0001) on Day 42, respectively, corresponding to a 1.06-fold increase across all methods. Glucose concentrations in the storage solution of RBCs decreased from 495 ± 27 to 225 ± 55 mg/dL (p < 0.0001), confirming that stored RBCs were metabolically active. CONCLUSION: These results suggest a significant, albeit minor, and most likely clinically insignificant increase in HbA1c concentrations during storage of RBCs for 42 days.