Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on β-cell function at one year after surgery: a systematic review.

Bariatric surgery is a highly effective obesity treatment resulting in substantial weight loss and improved glucose metabolism. We hereby aimed to summarize available evidence of the effect of the two most common bariatric surgery procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), on dynamic measures of β-cell function (BCF). A systematic search of the literature was conducted in 3 bibliographic databases for studies reporting effects of RYGB and/or SG on BCF assessed using dynamic metabolic perturbation (oral or intravenous bolus stimulation), performed before and 1 year (± 3 months) after surgery. Twenty-seven unique studies (6 randomized controlled trials and 21 observational studies), involving a total of 1,856 obese adults were included for final analysis. 25 and 9 studies report effects of RYGB and SG on BCF respectively (7 studies compared the two procedures). 7 studies report results according to pre-surgical diabetic status. Owing to variable testing procedures and BCF indices reported, no meta-analysis was feasible, and data were summarized qualitatively. For both surgical procedures, most studies suggest an increase in BCF and disposition index, particularly when using oral stimulation, with a more pronounced increase in diabetic than non-diabetic individuals. Additionally, limited indications for greater effects after RYGB and SG was found. The quality of the included studies was in general satisfactory. The considerable heterogeneity of test protocols and outcome measures underscores the need for a harmonization of BCF testing in future research

Study of Early Elevated Gas6 Plasma Level as a Predictor of Mortality in a Prospective Cohort of Patients with Sepsis.

Growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein interacting with anionic phospholipids and TAM tyrosine kinase receptors, is elevated in plasma of septic patients. Previous studies did not find different levels between survivors and non-survivors at admission because either they included a low number of patients (<50) or a low number of non-survivors (5%). To determine, in a larger cohort of septic patients comprising an expected number of non-survivors, the performance of the plasma level of Gas6 and its soluble receptor Axl (sAxl) within 24 hours of admission to predict in-ICU mortality. Septic adults with or without shock. Gas6 and sAxl were prospectively measured by ELISA at day 0, 3, 7, and then weekly until discharge or death. We evaluated 129 septic patients, including 82 with and 47 without shock, with in-ICU mortality rate of 19.4% and in-hospital mortality rate of 26%. Gas6 level was higher in non-survivors than in survivors (238 vs. 167%, P = 0.003); this difference remained constant during the ICU stay. The area under the ROC curve for Gas6 (0.695 [95% CI: 0.58-0.81]) was higher than for sAxl, procalcitonin, CRP, IL-1beta, IL-6 and-alpha, and slightly higher than for IL-8, IL-10, SOFA and APACHEII scores in predicting in-ICU mortality. Considering 249% as a cut-off value, Gas6 measurement had a negative predictive value for mortality of 87%. It seems that Gas6 plasma level within 24 hours of ICU admission may predicts in-ICU mortality in patients with sepsis. If our result are confirmed in external validation, Gas6 plasma level measurement could contribute to the identification of patients who may benefit most from more aggressive management

Mitapivat, a pyruvate kinase activator, improves transfusion burden and reduces iron overload in M-thalassemic mice

Not available

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Adverse metabolic outcomes in the early and Iate postpartum after gestational diabetes are broader than glucose control

En tant que sujet de ma thèse de doctorat à l'Université de Lausanne, nous avons récemment finalisé une analyse rétrospective évaluant les résultats du post-partum dans une cohorte de 622 femmes suivies à la clinique du diabète gestationnel du CHUV, qui a récemment été accepté dans BMJ Open Diabetes Research and Care {Impact Factor 3.4). Le but de cette analyse était d'identifier les résultats métaboliques chez les femmes atteintes de diabète gestationnel. Nous avons décrit une prévalence importante de l'obésité et du prédiabète, ainsi que du syndrome métabolique, déjà à 2 mois postpartum. Il y avait également plus de femmes désormais dans des catégories de supoids et d'obéstié en comparant à leur BMI d'avant la grossesse. Nous avons ensuite effectué une analyse d'un sous-groupe de 162 femmes ayant un suivi à 1 an postpartum, et démontré une nouvelle augmentation de l'obésité, du prédiabète et du syndrome métabolique au cours de la période post-partum d'un an. Enfin, nous avons identifié certains prédicteurs du développement de prédiabète, obesité et syndrome métabolique Ces résultats sont très importants cliniquement, car ils permettent d'optimiser l'intervention en pré- et péripartum, en plus du postpartum, afin d'éviter à ces femmes de développer des complications métaboliques à long terme

Diètes cétogènes : la solution miracle ?

The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered and aimed at improving some of the components of the metabolic syndrome. Among various diets, carbohydrate restriction is popular, specifically ketogenic diets, which are very low in carbohydrates and usually high in fats and /or proteins. Results are controversial, but some benefits such as weight loss and improved glycemic control have been described. Nevertheless, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events such as the development of nonalcoholic fatty liver disease. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors based on available evidence

Pied diabétique : une prise en charge complexe et multidisciplinaire

Le syndrome du pied diabétique est une complication fréquente chez les personnes ayant un diabète et une atteinte de la sensibilité périphérique. Cette situation complexe nécessite une détection clinique précoce, par les divers professionnels de la santé mais aussi par les patients et leurs proches. L’évolution clinique, la gravité du pronostic et la prise en charge seront déterminées par la rapidité du diagnostic. En cas d’atteinte confirmée, une prise en charge multidisciplinaire est nécessaire. L’intervention la plus importante, tant pour la prévention que le traitement, est la décharge du pied atteint

Symptômes musculaires associés aux statines : quelle prise en charge en 2018 ?

Statins are the first line treatment in hyperlipidemia, either in primary or secondary prevention of cardiovascular diseases. One of the most prescribed drug class worldwide, this drug class is often the focus of highly publicized drug controversies. Various adverse effects have been attributed to statins, in particular statin-associated muscle symptoms (SAMS). This condition varies in severity (from frequent isolated myalgia to rare severe myositis, even rhabdomyolysis) and often leads to treatment termination. Because SAMS are a daily challenge in clinical practice, we review here the recent medical literature on this topic and suggest a management strategy to be shared with the patient as an active partner.Les statines représentent la première ligne de traitement en cas d’hypercholestérolémie, que ce soit en prévention primaire ou secondaire des maladies cardiovasculaires. C’est l’une des classes médicamenteuses les plus prescrites au monde, mais qui fait l’objet de controverses médiatisées. De nombreux effets indésirables ont été attribués à la prise de statines, notamment les symptômes musculaires associés aux statines (SMAS). On relève différents types d’atteinte, d’intensité croissante (de myalgies fréquentes à une myosite sévère mais rare, voire une rhabdomyolyse), pouvant mener à l’arrêt du traitement. Au vu du défi que représentent les SMAS dans la pratique courante ambulatoire, cet article donne au praticien un aperçu de la littérature récente, ainsi qu’une proposition de prise en charge à partager avec le patient