Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

Orange juice and its major polyphenol hesperidin consumption do not induce immunomodulation in healthy well-nourished humans

International audienceBACKGROUND & AIMS: Polyphenols exert a variety of biological properties, including antioxidant, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men, we investigated the effects of orange juice and its major polyphenolic compound hesperidin on a panel of immune cell functions, including cytokine secretion by leukocytes, lytic activity of NK cells, and the Reactive Oxygen Species (ROS) burst by polymorphonuclear neutrophil cells (PMN). METHODS: The protocol design was divided into three 4-week treatment periods separated by 3-week wash-out intervals, for total study duration of 18 weeks. During treatment periods, volunteers (n = 24) consumed daily 500 mL of orange juice, or an isocaloric control beverage with hesperidin (292 mg in a capsule), or of the same control beverage with a placebo. RESULTS: Whatever the intake was, no variations were recorded on leukocyte subset distributions (PMN, B and T lymphocytes, NK cells and monocytes), ROS production by stimulated PMNs, lytic activity of NK cells or cytokine production capacity of leukocytes in well-nourished healthy volunteers. CONCLUSIONS: We show that consumption within the usual daily intake range of orange juice and its major polyphenol hesperidin do not induce immunomodulation of cell immune function in healthy well-nourished humans

Case Report about Fatal or Near-Fatal Hypersensitivity Reactions to Cetuximab: Anticetuximab IgE as a Valuable Screening Test

Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anti-cetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae strains isolated from adults in France: evolution between 2001 and 2003.

International audienceAntibiotic-resistant Streptococcus pneumoniae (Sp) are described around the world. The present national surveillance study report analyzes more than 6000 Sp strains, isolated from adults across France in 2001 and 2003, from blood cultures (3086 in 2001 and 3164 in 2003), cerebrospinal fluid (respectively, 238 and 240), or middle ear fluid (respectively, 110 and 100). The proportion of isolates with reduced susceptibility to penicillin fell significantly between 2001 and 2003 from 46.5% to 43.9%. The proportion of high-level resistant strains to penicillin minimal inhibitory concentrations (MIC > 1 mg/L), amoxicillin, and cefotaxime (MIC > 2 mg/L) slightly decreased but remained low: 10.6%, 1.2%, and 0.2% in 2003. Resistance to other antibiotics (erythromycin, cotrimoxazole, tetracycline, and chloramphenicol) also decreased. Decrease in prevalence of penicillin-resistant Sp varied according to specimen source. The proportion of penicillin nonsusceptible pneumococci decreased in blood cultures and middle ear fluids between 2001 and 2003 but increased in cerebrospinal fluid (43.4% and 46.5%, respectively). Serotypes covered by the heptavalent vaccine accounted for 42.4% of all isolates recovered in 2001 and 46.1% in 2003. Prevalence of antibiotic-resistant Sp decreased in 2003 in France

Observatoires régionaux du pneumocoque : épidémiologie et résistance aux antibiotiques des souches de Streptococcus pneumoniae isolées en France en 2007

International audienceRésuméLes observatoires régionaux du pneumocoque (ORP), créés à partir de 1995, participent aux côtés du Centre national de référence des pneumocoques et de l’Institut de veille sanitaire à la surveillance étroite de l’évolution de la résistance du pneumocoque aux antibiotiques. En 2007, les 23 ORP français ont étudié la sensibilité aux antibiotiques et le sérogroupe de 5 302 souches de pneumocoque isolées de liquides céphalo-rachidiens (LCR), d’hémocultures, de pus d’otite moyenne aiguë, de liquides pleuraux de l’enfant et de l’adulte (≥ 16 ans) ainsi que de certains échantillons pulmonaires de l’adulte (≥ 16 ans). L’étude a montré que 38,2 % des souches étaient de sensibilité diminuée à la pénicilline (PSDP), 19,3 % à l’amoxicilline et 10,5 % au céfotaxime. Le pourcentage de PSDP différait selon les régions, allant de 29 % en Alsace à 50 % à Paris Ile-de-France Ouest. Il était plus élevé chez l’enfant (50,2 %) que chez l’adulte (33,7 %) et variait selon le prélèvement (enfant/adulte) : hémocultures (27,8 %/32,5 %), LCR (33,7 %/34,6 %), pus d’otite moyenne aiguë (60,2 %/27,5 %), liquides pleuraux (50 %/31 %). Les PSDP étaient souvent multirésistants avec en particulier un pourcentage élevé de résistance à l’érythromycine (84,2 % contre 12,7 % pour les pneumocoques sensibles à la pénicilline). Enfin, le sérogroupe majoritairement rencontré était le sérogroupe 19 (25,2 % des isolats).</p

Epidemiology and antimicrobial resistance of Streptococcus pneumoniae in France in 2007: data from the pneumococcus surveillance network.

International audienceAntimicrobial resistance of Streptococcus pneumoniae in France is closely monitored by the pneumococcus surveillance network, founded in 1995, which collects data from regional observatories (Observatoire Régionaux du Pneumocoque [ORP]). In 2007, 23 ORPs analyzed the antibiotic susceptibility of 5,302 isolates of S. pneumoniae recovered in France from cerebrospinal fluid, blood, middle ear fluid, and pleural fluid, as well as from adult respiratory samples. The study showed that 38.2% of the strains were nonsusceptible to penicillin, 19.3% nonsusceptible to amoxicillin, and 10.5% nonsusceptible to cefotaxime. The percentage of pneumococcus nonsusceptible to penicillin varied according to both the sample and the age of the patient (child/adult): blood (27.8%/32.5%), cerebrospinal fluid (33.7%/34.6%), middle ear fluid (60.2%/27.5%), and pleural fluid (50.0%/31.0%). Between 2003 and 2007, the frequency of penicillin resistance in invasive pneumococcal disease gradually decreased from 46.4% to 29.0% in children and from 43.8% to 32.7% in adults. This decrease coincided with the introduction of a seven-valent pneumococcal conjugate vaccine into immunization programs and with a general reduction in levels of antibiotic consumption in France

Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study

International audienceBackground:Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors.Methods:Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT.Findings:Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p  50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria