[Antiplatelet agents and transfusion]. / Antiplaquettaires et transfusion.

Antiplatelet agents are at risk for bleeding complications, the management of which differs depending on the clinical situation and on the antiplatelet agent itself. Neutralization of antiplatelets is sometimes necessary, most often leading to platelet transfusion, although the benefit of this strategy is poorly documented. In addition, if platelet transfusion corrects the platelet inhibition induced by aspirin and probably by clopidogrel and prasugrel, it does not neutralize ticagrelor, as a consequence of its pharmacological properties. The clinical benefit of platelet transfusion is limited, and the most recent studies are challenging it. However, it is indicated on a perioperative basis for surgeries with high hemorrhagic risk and is discussed in severe hemorrhages. The neutralization of ticagrelor is a concern and the antidote currently under development may be a solution. In all cases, other therapeutic solutions may be considered, such as administration of desmopressin, tranexamic acid or activated factor VII.

CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.

Poor trabecular microarchitecture at the distal radius in older men with increased concentration of high-sensitivity C-reactive protein--the STRAMBO study.

Low-grade inflammation, assessed by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with higher fracture risk irrespective of areal bone mineral density (aBMD). We assessed the association of hsCRP with bone microarchitecture (measured by high-resolution pQCT) at the distal radius and tibia in 1,149 men, aged 19-87 years. hsCRP concentration increased with age until the age of 72, then remained stable. aBMD was not correlated with hsCRP level. After adjustment for confounders, bone microarchitecture was not associated with hsCRP level in men aged <72. After the age of 72, hsCRP >5 mg/L was associated with lower trabecular density, lower trabecular number, higher trabecular spacing, and more heterogeneous trabecular distribution (p < 0.05-0.005) at the distal radius versus hsCRP ≤ 5 mg/L. Similar differences were found for the fourth hsCRP quartile (>3.69 mg/L) versus the three lower quartiles combined. Cortical parameters of distal radius and microarchitectural parameters of distal tibia did not vary according to hsCRP concentration in men aged ≥ 72. Fracture prevalence increased with increasing hsCRP level. After adjustment for confounders (including aBMD), odds for fracture were higher in men with hsCRP >5 mg/L compared to hsCRP <1 mg/L (OR = 2.22, 95 % CI 1.29-3.82) and did not change after additional adjustment for microarchitectural parameters. The association between hsCRP level and bone microarchitecture was observed only for trabecular parameters at the radius in men aged ≥72. Impaired bone microarchitecture does not seem to explain the association between elevated CRP level and higher risk of fracture.