Etude d'une cohorte de 33 patients traités par anticorps monoclonal (inolimomab) pour une maladie du greffon contre l'hôte réfractaire à la corticothérapie après allogreffe de cellules souches hématopoïétiques

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Dinuclear iron(III) complexes as models for active site of methane monooxygenase

Affich

Right isovolumic contraction velocity predicts survival in pulmonary hypertension.

Right ventricular function is a strong determinant of prognosis in severe pulmonary hypertension.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identifying patients with cerebral infarction within the time window compatible with reperfusion therapy, diagnostic performance of glutathione S-transferase-π (GST-π) and peroxiredoxin 1 (PRDX1): exploratory prospective multicentre study FLAG-1 protocol

Introduction Plasma biomarkers may be useful in diagnosing acute cerebral infarction requiring urgent reperfusion, but their performance remains to be confirmed. If confirmed, these molecules could be used to develop rapid and reliable decentralised measurement methods, making it possible to initiate reperfusion therapy before hospital admission. The FLAG-1 large prospective study will constitute a plasma bank to assess the diagnostic performance of two biomarkers: glutathione S-transferase-π and peroxiredoxin 1. These molecules are involved in the oxidative stress response and could identify cerebral infarction within a therapeutic window of less than 4.5 hours following the onset of symptoms. Secondary objectives include assessing performance of these biomarkers within 3-hour and 6-hour windows; identifying additional biomarkers diagnosing cerebral infarction and significant criteria guiding therapeutic decisions: ischaemic features of stroke, presence of diffusion/fluid-attenuated inversion recovery mismatch, volume of cerebral infarction and penumbra on cerebral MRI.Methods and analysis The exploratory, prospective, multicentre FLAG-1 Study will include 945 patients with acute stroke symptoms (onset ≤12 hours, National Institute of Health Stroke Scale score ≥3). Each patient’s 25 mL blood sample will be associated with cerebral MRI data. Two patient groups will be defined based on the time of blood collection (before and after 4.5 hours following onset). Receiver operating characteristic analysis will determine the diagnostic performance of each biomarker, alone or in combination, for the identification of cerebral infarction <4.5 hours.Ethics and dissemination The protocol has been approved by an independent ethics committee. Biological samples are retained in line with best practices and procedures, in accordance with French legislation. Anonymised data and cerebral imaging records are stored using electronic case report forms and a secure server, respectively, registered with the French Data Protection Authority (Commission Nationale de l'Informatique et des Libertés (CNIL)). Results will be disseminated through scientific meetings and publication in peer-reviewed medical journals.Trial registration number ClinicalTrials.gov Registry (NCT03364296)

Anti-donor HLA antibody response after pancreatic islet grafting: characteristics, risk factors and impact on graft function

International audienc

Superoxide dismutase 2 (SOD2) contributes to genetic stability of native and T315I-mutated BCR-ABL expressing leukemic cells

International audienceManganese Superoxide dismutase 2 (SOD2) plays a crucial role in antioxidant defense but there are no data suggesting its role in genetic instability in CML. We evaluated the effects of SOD2 silencing in human UT7 cell line expressing either non-mutated or T315I-mutated BCR-ABL. Array-CGH experiments detected in BCR-ABL-expressing cells silenced for SOD2 a major genetic instability within several chromosomal loci, especially in regions carrying the glypican family (duplicated) and β-defensin genes (deleted). In a large cohort of patients with chronic myeloid leukemia (CML), a significant decrease of SOD2 mRNA was observed. This reduction appeared inversely correlated with leukocytosis and Sokal score, high-risk patients showing lower SOD2 levels. The analysis of anti-oxidant gene expression analysis revealed a specific down-regulation of the expression of PRDX2 in UT7-BCR-ABL and UT7-T315I cells silenced for SOD2 expression. Gene set enrichment analysis performed between the two SOD2-dependent classes of CML patients revealed a significant enrichment of Reactive Oxygen Species (ROS) Pathway. Our data provide the first evidence for a link between SOD2 expression and genetic instability in CML. Consequently, SOD2 mRNA levels should be analyzed in prospective studies as patients with low SOD2 expression could be more prone to develop a mutator phenotype under TKI therapies

Association of Dietary Patterns Derived Using Reduced‐Rank Regression With Subclinical Cardiovascular Damage According to Generation and Sex in the STANISLAS Cohort

International audienceBackgroundThe diet impact on cardiovascular(CV) diseases has been investigated widely, but the association between dietary patterns(DPs) and subclinical CV damage remains unclear. More informative DPs could be provided by considering metabolic syndrome(MetS) components as intermediate markersThis study aimed to identify DPs according to generation and sex using reduced-rank regression(RRR) with MetS components as intermediate markers, and assess their associations with intima-media thickness, left-ventricular mass (LV mass), and pulse-wave velocity (cfPWV) in an initially healthy population based family study. Methods and ResultsThis study included 1527 participants from the STANISLAS cohort fourth examination. DPs were derived using RRR according to generation (G1:age≥50years; G2:age<50years) and sex. Associations between DPs and CV damage were analyzed using multivariable linear regression models.Although identified DP were correlated between generations and sex, qualitative differences were observed: whereas only unhealthy DPs were found for both men generations, healthy DP were identified in G2(“fruity desserts”) and G1(“fiber and w3 oil”) women. The “alcohol”, “Fast food and Alcohol”, “Fried, processed and dairy products”, “meat, starch, sodas, and fat” DPs in G1, G2 men, and in G1, G2 women respectively, were associated with high LV mass[β (95% confidence interval): 0.23(0.10; 0.36); 0.76(0.00; 1.52); 1.71(0.16; 3.26) and 1.80(0.45; 3.14)]. The “alcohol” DP in G1 men was positively associated with cfPWV[0.22(0.09; 0.34)]. Conclusions The DPs that explain the maximum variation in MetS components had different associations with subclinical CV damage across generation and sex. Our results indicate that dietary recommendations should be tailored according to age and sex

Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation

International audienceAims The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P 0.05). Conclusions A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients