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La mastocytose systémique indolente (MSI), maladie clonale des mastocytes principalement induite par la mutation D816V du gène KIT, s’accompagne de symptômes invalidants à long terme, dont une anaphylaxie pouvant mettre la vie en danger, mais aussi une mauvaise qualité de vie (QdV) et une morbidité significative. La plupart des patients reçoivent des traitements axés sur les symptômes qui s’avèrent souvent inefficaces. L’avapritinib, un inhibiteur oral, puissant et sélectif de la mutation D816V de KIT, est le premier et le seul traitement approuvé pour les patients adultes atteints de MSI dans l’UE et aux États-Unis.

La MSI, principalement induite par la mutation D816V du gène KIT, est le sous-type de mastocytose systémique le plus fréquent et peut causer des symptômes invalidants. L’étude PIONEER (NCT03731260) a évalué la sécurité d’emploi et l’efficacité de l’avapritinib, un inhibiteur sélectif expérimental de KIT D816V, versus placebo, chez les patients qui poursuivaient dans les deux bras leurs traitements symptomatiques (BSC).

Non-alcoholic fatty liver disease is a common finding in obese subjects, and increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. The aim of this study was to evaluate whether the extent of liver enlargement is related to the severity of the metabolic syndrome in obese women. The relationship between ultrasound-measured hepatic left lobe volume (HLLV) and various features of the metabolic syndrome was evaluated in 85 obese women. The mean±SD value of HLLV in obese women was 431±214 ml (range 46–1019 ml) while it was 187±31 ml (range 143–258 ml) in lean subjects. In a multiple logistic regression analysis, ultrasound-measured intra-abdominal fat was the only anthropometric measure independently associated with HLLV. A strong positive association was found between HLLV and serum liver enzymes, triglycerides, glucose, insulin, uric acid, C reactive protein, systolic and diastolic blood pressure, while a negative correlation was observed between HLLV and HDL cholesterol. The values of HLLV corresponding to the cut-off values of various risk factors for the diagnosis of the metabolic syndrome were calculated, yielding a mean value of 465 ml. In conclusion, ultrasound measurement of HLLV represents a simple, reliable and low-cost tool for the evaluation of liver involvement in the metabolic syndrome. The strong association between liver enlargement and various cardiovascular risk factors associated with insulin resistance supports the role of liver steatosis as an important link among the many facets of the metabolic syndrome in human obesity.

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m^2^.^7) than did control subjects (37 +/- 8 g/m^2^.^7, P@?< .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P@?< .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1@?+/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.

Thyroid dysfunction is associated with metabolic changes that affect mass and adipocyte function, as well as lipid and carbohydrate metabolism. Adipose tissue performs complex metabolic and endocrine functions. Leptin and adiponectin are two of the most important adipocytokines, both involved in the regulation of intermediate metabolism. The aim of this study was to evaluate the relationships between thyroid status and circulating levels of the two adipose tissue hormones. We studied 15 patients with hyperthyroidism, 15 patients with hypothyroidism and 15 euthyroid subjects, all matched by sex, age and body mass index (BMI). Serum concentrations of free thyroxine, free triiodothyronine, thyrotropin, leptin and adiponectin and anthropometric parameters (weight, height, BMI) were assessed. No significant difference was found among the 3 groups, as assessed by Student’s t-test, both for adiponectin and leptin. We conclude that metabolic changes associated with thyroid dysfunction are not related to variations in serum levels of adiponectin or leptin.

Tsetse are able to absorb undigested proteins such as albumin or fragments of globulins from the midgut into the hemolymph.