The role of serum sphingolipids as potential biomarkers of non-response to direct acting antiviral therapy in chronic hepatitis C virus infection

Elimination strategies of chronic hepatitis C virus (HCV) infection aim to optimize the high antiviral potency of direct-acting antivirals (DAAs). Sphingolipids (SLs) constitute bioactive lipid compounds with a remarkable second messenger potential. SL levels associate with responsiveness to interferon treatment in HCV-patients, thus prompting the question whether failure to DAAs can be predicted by the serologic sphingolipidomic profile. Liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) was used to retrospectively quantify various sphingolipid metabolites in baseline serum samples of 97 chronic HCV patients with DAA failure compared with an age-matched cohort of 95 HCV-patients with sustained virological response (SVR). Sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SA1P) serum concentrations were significantly upregulated at baseline in patients with DAA failure compared to patients with SVR. Similarly, GluC24:1Cer baseline levels were significantly upregulated in patients with DAA failure compared to the patients with SVR. However, GluC18Cer serum levels showed decreased baseline levels for patients with DAA failure compared to patients with SVR. In multivariate analysis sphinganine (OR 0.08494, CI 0.07393–0.9759, p = .021223), SA1P (OR 0.9818, CI 0.9653–0.9987, p = .034801), GluCerC18 (OR 1.0683, CI 1.0297–1.1104, p = .000786) and GluCer24:1 (OR 0.9961, CI 0.994–0.998, p = .000294) constituted independent predictors of treatment response. In conclusion, serum sphingolipid concentrations, in particular sphingosine, sphinganine and their derivatives S1P and SA1P as well as glucosylceramides may identify at baseline the minority of HCV patients with DAA failure. Serum sphingolipids could constitute additional biomarkers for national treatment strategies aiming to eliminate HCV infection.     

Impact of estrogens on resting energy expenditure: A systematic review

The fear of weight gain is one of the main reasons for women not to initiate or to early discontinue hormonal contraception or menopausal hormone therapy. Resting energy expenditure is by far the largest component and the most important determinant of total energy expenditure. Given that low resting energy expenditure is a confirmed predictive factor for weight gain and consecutively for the development of obesity, research into the influence of sex steroids on resting energy expenditure is a particularly exciting area. The objective of this systematic review was to evaluate the effects of medication with natural and synthetic estrogens on resting energy expenditure in healthy normal weight and overweight women. Through complex systematic literature searches, a total of 10 studies were identified that investigated the effects of medication with estrogens on resting energy expenditure. Our results demonstrate that estrogen administration increases resting energy expenditure by up to +208 kcal per day in the context of contraception and by up to +222 kcal per day in the context of menopausal hormone therapy, suggesting a preventive effect of circulating estrogen levels and estrogen administration on weight gain and obesity development.     

Basic therapy for rheumatoid arthritis: Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often the initial treatment for rheumatoid arthritis. NSAID-induced inhibition of cyclooxygenase-2 (COX2) and cyclooxygenase-1 appears to correlate with clinical efficacy and toxicity, respectively. Newer NSAIDs with greater COX2 selectivity offer the promise of less toxic therapy.     

Patterns of care in radiotherapy of breast cancer in Austria 1985: data acquisition and comparison with data of US-PCS 1983.

PURPOSE: In Austria, a Patterns of Care Study (PCS) has been conducted to evaluate the standards of practice for breast cancer patients. The year 1985 was selected in order to establish a base data set. MATERIALS AND METHODS: At all nine radiation therapy facilities active in patient treatment in 1985, ten patients charts were randomly selected and reviewed. Evaluation of the radiotherapeutic standards was the principal purpose, however, surgical and histopathological parameters were also considered. RESULTS: Results of the Austrian PCS (including 90 patients) were compared with the "1983 Patterns of Care Process Survey for Definitive Breast Irradiation" performed in 1983 in the U.S. (including 191 patients). Documentation of pathologic tumour size (83% vs. 73%), histologic tumour subtype (99% vs. 97%) and microscopic margin analysis (60% vs. 51%) showed comparable results. Technical equipment was obviously quite different in the two countries, cobalt therapy was used in 25% in the US-PCS compared to 71% in the Austrian PCS. A clear difference also was obtained concerning the use of wedges for tangential breast/thoracic wall fields (64% vs. 21%) and the frequency of portal films (93% vs. 26%). CONCLUSIONS: Comparing both PCS studies, we found overall many similarities. Differences could be obtained in the quality level of radiation treatment, as for example use of wedges for tangential fields and the number of portal films. In a next step, a further Austrian PCS is planned to compare the Austrian base data from 1985 with quality standards from 1993 and 2001.