Strong incidence of Pseudomonas aeruginosa on bacterial rrs and ITS genetic structures of cystic fibrosis sputa.

Cystic fibrosis (CF) lungs harbor a complex community of interacting microbes, including pathogens like Pseudomonas aeruginosa. Meta-taxogenomic analysis based on V5-V6 rrs PCR products of 52 P. aeruginosa-positive (Pp) and 52 P. aeruginosa-negative (Pn) pooled DNA extracts from CF sputa suggested positive associations between P. aeruginosa and Stenotrophomonas and Prevotella, but negative ones with Haemophilus, Neisseria and Burkholderia. Internal Transcribed Spacer analyses (RISA) from individual DNA extracts identified three significant genetic structures within the CF cohorts, and indicated an impact of P. aeruginosa. RISA clusters Ip and IIIp contained CF sputa with a P. aeruginosa prevalence above 93%, and of 24.2% in cluster IIp. Clusters Ip and IIIp showed lower RISA genetic diversity and richness than IIp. Highly similar cluster IIp RISA profiles were obtained from two patients harboring isolates of a same P. aeruginosa clone, suggesting convergent evolution in the structure of their microbiota. CF patients of cluster IIp had received significantly less antibiotics than patients of clusters Ip and IIIp but harbored the most resistant P. aeruginosa strains. Patients of cluster IIIp were older than those of Ip. The effects of P. aeruginosa on the RISA structures could not be fully dissociated from the above two confounding factors but several trends in these datasets support the conclusion of a strong incidence of P. aeruginosa on the genetic structure of CF lung microbiota

A French National Survey on Clotting Disorders in Mastocytosis.

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids

Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor

International audienc

Off-Label Use Of Biological Therapies In Relapsing And/Or Refractory Polyarteritis Nodosa

Wo

A simple clinical and biological score to promote and enhance Ferroportine disease screening.

International audienc

Proportion of V5-V6 <i>rrs</i> sequences per genera over the full dataset but without considering reads classified in the <i>Pseudomonas</i>.

<p>Pp: sputa DNA extracts from CF patients colonized by <i>P</i>. <i>aeruginosa</i>. Pn: sputa DNA extracts from CF patients not colonized by <i>P</i>. <i>aeruginosa</i>. Only genera representing more than 0.1% of the full library were considered. * Significant differences (p<0.05) between the Pp and Pn groups were detected by univariate Wilcoxon Mann-Whitney statistical tests while considering reads of each OTU identified per genera (with n OTU > 5 per genera); see materials and methods for the computing, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173022#pone.0173022.s003" target="_blank">S3 Table</a> for the number of reads per genera and variance analyses of read numbers per OTU among a genus.</p

Multiple correspondence analysis of antibiotic susceptibilities among (A) <i>Pseudomonas aeruginosa</i> isolates recovered from the sputa, and (B) their matching RISA clusters (Ip, IIp and IIIp).

<p>Resistances are in red (antibiotic_R) and susceptibilities in green (antibiotic_S). Percentage of inertia are shown in the corner (A). Confidential ellipses on the panel B represent the statistical distinction of the cluster Ip (black), IIp (red) and IIIp (green) and the 4 resistance patterns (R1, R2 R3 and R4 in grey) observed among the <i>P</i>. <i>aeruginosa</i> strains (with 5% threshold). Antibiotics: (i) beta-lactams: TIC, ticarcillin; TCC, ticarcillin-clavulanic acid; PIP, piperacillin; PPT, piperacillin-tazobactam; CAZ, ceftazidime; FEP, cefepime; ATM, aztreonam; IPM, imipenem and MEM, meropenem, (ii) aminoglycosids: GMI, gentamicin; AKN, amikacin, TMN, tobramycin (iii) fluoroquinolones: CIP, ciprofloxacin and (iv) FF, fosfomycin.</p

Hierarchical clustering of RISA profiles obtained from 104 independent CF sputa DNA extracts.

<p>Pp (highlighted in pale grey): sputa DNA extracts from CF patients colonized by <i>P</i>. <i>aeruginosa</i>. Pn: sputa DNA extracts from CF patients not colonized by <i>P</i>. <i>aeruginosa</i>. Three main clusters of RISA profiles were detected. These were supported by significant bootstrap values shown in ovale. PFGE <i>Spe</i>I <i>P</i>. <i>aeruginosa</i> clonal lineages recovered among several CF sputa are indicated. CC: clonal complexes.</p

Confounding factors associated with RISA clusters Ip, IIp and IIIp.

<p>A significant difference between the proportion or median of age of patients was indicated with * (Fischer exact test, Kruskall Wallis test, p<0,05). F = Female, Fcol = age of the first onset of <i>P</i>. <i>aeruginosa</i> colonization; Exacerb. = clinical exacerbation. Aero = aerosol, IV = intraveneous. AMC, amoxicillin-clavulanic acid; CAZ, ceftazidime; TAZ, Tazocillin; CIP ciprofloxacin; CS, colistin; TMN, tobramycin; AZI, azithromycin; SXT, sulfamethoxazole-trimethoprim.</p

Clinical spectrum and therapeutic management of auto-immune myelofibrosis: a nation-wide study of 30 cases

International audienceNo abstract availabl