CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome.

High-sensitivity cardiac troponin assays: answers to frequently asked questions.

Cardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed 'high-sensitivity cardiac troponin' (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions.

Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide.

Objective: To measure plasma concentrations of high-sensitivity cardiac troponin T (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with systemic sclerosis (SSc; scleroderma) and age- and sex-matched healthy control subjects, and to examine the contribution of traditional cardiovascular risk factors and SSc features to the concentrations of these 2 cardiac biomarkers.

Methods: Plasma HS-cTnT and NT-proBNP concentrations were measured using the electrochemiluminescence method and sandwich immunoassay, respectively.

Results: The study group comprised 161 unrelated patients with SSc and 213 matched control subjects.

Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies.

We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin.

The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3-CD4+ aberrant T-cell phenotype.

The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network.

Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion.

We used circular chromatin conformation capture (4C) to identify a physical contact in human pancreatic islets between the region near the insulin (INS) promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, which encodes a Ca(2+)-dependent chloride ion channel. In response to glucose, this contact was strengthened and ANO1 expression increased, whereas inhibition of INS gene transcription by INS promoter targeting siRNA decreased ANO1 expression, revealing a regulatory effect of INS promoter on ANO1 expression. Knockdown of ANO1 expression caused decreased insulin secretion in human islets, establishing a physical proximity-dependent feedback loop involving INS transcription, ANO1 expression, and insulin secretion.

Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients.

Objective: The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis.

Methods: First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients.

Catalytic methylation of aromatic amines with formic acid as the unique carbon and hydrogen source.

A novel methodology is presented for the direct methylation of amines, using formic acid as a unique source of carbon and hydrogen. Based on ruthenium(II) catalysts, the formation of the N-CH3 group proceeds via an efficient formylation/transfer hydrogenation pathway.

B-type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy.

Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema.

A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel antimalarial Spiroindolone KAE609 (Cipargamin) to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers.

This first-in-human randomized, double-blind, placebo-controlled, ascending-single and -multiple oral dose study was designed to evaluate the safety, tolerability, and pharmacokinetics in healthy volunteers of KAE609 (cipargamin; formerly NITD609), a spiroindolone now in trials for malaria treatment. It was studied in single-dose cohorts (1 to 300 mg, including one 30-mg food effect cohort) with 4 to 10 subjects in each cohort and in multiple-dose cohorts (10 to 150 mg once daily for 3 days) with 8 subjects in each cohort. The follow-up period was 6 to 8 days post-last dose.

Efficient disproportionation of formic acid to methanol using molecular ruthenium catalysts.

The disproportionation of formic acid to methanol was unveiled in 2013 using iridium catalysts. Although attractive, this transformation suffers from very low yields; methanol was produced in less than 2% yield, because the competitive dehydrogenation of formic acid (to CO2 and H2) is favored. We report herein the efficient and selective conversion of HCOOH to methanol in 50% yield, utilizing ruthenium(II) phosphine complexes under mild conditions.

Spiroindolone KAE609 for falciparum and vivax malaria.

Background: KAE609 (cipargamin; formerly NITD609, Novartis Institute for Tropical Diseases) is a new synthetic antimalarial spiroindolone analogue with potent, dose-dependent antimalarial activity against asexual and sexual stages of Plasmodium falciparum.

Methods: We conducted a phase 2, open-label study at three centers in Thailand to assess the antimalarial efficacy, safety, and adverse-event profile of KAE609, at a dose of 30 mg per day for 3 days, in two sequential cohorts of adults with uncomplicated P. vivax malaria (10 patients) or P.

Serum free light chains of immunoglobulins as biomarkers for systemic sclerosis characteristics, activity and severity.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Humoral immunity and B cells are thought to play an important role in the pathophysiology of the disease. B cells are activated, produce specific autoantibodies and profibrotic cytokines.

Potentiometry up to 275°C: example of pH titrations of cobalt ferrite particles.

Hypothesis: High temperature potentiometry (or pH-metry) is needed for specific hydrothermal applications such as acid-base titration of metallic oxides particles to predict their reactivity toward dissolved species, or to describe the surface charge mechanisms. We present here a specific set-up, operational up to 300°C, H2-free and compatible with oxidizing conditions.

Experiments: An autoclave in Hastelloy with a zirconia pH probe has been used to titrate a suspension of cobalt ferrite (CoFe2O4), a typical corrosion product found in cooling circuit, up to 275°C.

A randomised controlled trial of kinematically and mechanically aligned total knee replacements: two-year clinical results.

We have previously reported the short-term radiological results of a randomised controlled trial comparing kinematically aligned total knee replacement (TKR) and mechanically aligned TKR, along with early pain and function scores. In this study we report the two-year clinical results from this trial. A total of 88 patients (88 knees) were randomly allocated to undergo either kinematically aligned TKR using patient-specific guides, or mechanically aligned TKR using conventional instruments.

European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay.

Background: International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a new high sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper reference limit (URL).

Methods: Laboratories from nine European countries evaluated the ARCHITECT STAT high sensitive troponin I (hs-TnI) immunoassay on the ARCHITECT i2000SR/i1000SR immunoanalyzers.

Alopecia induced by tumour necrosis factor-alpha antagonists: description of 52 cases and disproportionality analysis in a nationwide pharmacovigilance database.

Objectives: The aim of this research was to describe the cases of TNF-α antagonist-related alopecia reported in the French Pharmacovigilance Database (FPVD) and to investigate the association between exposure to TNF-α antagonists and occurrence of alopecia.

Methods: All spontaneous reports of TNF-α antagonist-related alopecia recorded in the FPVD between January 2000 and April 2012 were colligated and described. We conducted disproportionality analyses (case/non-case method) to assess the link between the occurrence of alopecia and exposure to TNF-α antagonists.

Activation of aryl and heteroaryl halides by an iron(I) complex generated in the reduction of [Fe(acac)₃] by PhMgBr: electron transfer versus oxidative addition.

The mechanism of the reactions of aryl/heteroaryl halides with aryl Grignard reagents catalyzed by [Fe(III)(acac)3] (acac=acetylacetonate) has been investigated. It is shown that in the presence of excess PhMgBr, [Fe(III)(acac)3] affords two reduced complexes: [PhFe(II)(acac)(thf)n] (n=1 or 2) (characterized by (1)H NMR and cyclic voltammetry) and [PhFe(I)(acac)(thf)](-) (characterized by cyclic voltammetry, (1)H NMR, EPR and DFT). Whereas [PhFe(II)(acac)(thf)n] does not react with any of the investigated aryl or heteroaryl halides, the Fe(I) complex [PhFe(I)(acac)(thf)](-) reacts with ArX (Ar=Ph, 4-tolyl; X=I, Br) through an inner-sphere monoelectronic reduction (promoted by halogen bonding) to afford the corresponding arene ArH together with the Grignard homocoupling product PhPh.

Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: New data from a French cohort and a systematic review and meta-analysis.

Objective: Studies assessing the prevalence of anti-RNA polymerase III (anti-RNAP III) antibodies in systemic sclerosis (SSc) have yielded a wide range of results. The aim of the present study was to describe a new SSc cohort tested for presence of anti-RNAP III and perform a systematic review and meta-analysis to assess the prevalence of anti-RNAP III in patients worldwide and the potential factors of variability.

Methods: Seropositivity for anti-RNAP III was evaluated in a French cohort of SSc patients.

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab.

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case-control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded).

Differential interferences of hemoglobin and hemolysis on insulin assay with the Abbott Architect-Ci8200 immunoassay.

Objectives: This paper evaluates the effect of hemoglobin (Hb) and hemolysis on insulin measurements with the Architect-Ci8200 analyzer.

Design And Methods: Insulin concentrations were measured using the Architect-Ci8200. Interference studies were performed by spiking serum pools of defined insulin concentrations with increasing concentrations of either free Hb or hemolysate.

Inflammation and disease activity are associated with high circulating cardiac markers in rheumatoid arthritis independently of traditional cardiovascular risk factors.

Objective: To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates.

Methods: The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls.

Results: We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs).

In situ real time infrared spectroscopy of sorption of (poly)molybdate ions into layered double hydroxides.

The sorption of (poly)molybdate ions into layered double hydroxides (LDHs), with Zn(2+) and Al(3+) cations, has been followed by in situ infrared spectroscopy using the attenuated total reflection technique. The exchange between solution molybdate species and interlayer anions has been followed in real time, illustrating the different behavior of molybdate ions and polymolybdate species. In a first part, the Mo(VI) speciation in solution was performed by comparison of thermodynamical calculations and infrared spectroscopy of solutions with different pH.

Relevance of partitioning DLCO to detect pulmonary hypertension in systemic sclerosis.

We investigated whether partitioning DLCO into membrane conductance for CO (DmCO) and pulmonary capillary blood volume (Vcap) was helpful in suspecting precapillary pulmonary (arterial) hypertension (P(A)H) in systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD). We included 63 SSc patients with isolated PAH (n=6), isolated ILD (n=19), association of both (n=12) or without PAH and ILD (n=26). Partitioning of DLCO was performed by the combined DLNO/DLCO method.

A new stochastic approach for the simulation of agglomeration between colloidal particles.

This paper presents a stochastic approach for the simulation of particle agglomeration, which is addressed as a two-step process: first, particles are transported by the flow toward each other (collision step) and, second, short-ranged particle-particle interactions lead either to the formation of an agglomerate or prevent it (adhesion step). Particle collisions are treated in the framework of Lagrangian approaches where the motions of a large number of particles are explicitly tracked. The key idea to detect collisions is to account for the whole continuous relative trajectory of particle pairs within each time step and not only the initial and final relative distances between two possible colliding partners at the beginning and at the end of the time steps.