Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity.

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs).

Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients.

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers.

Correlates of pre-hospital morphine use in ST-elevation myocardial infarction patients and its association with in-hospital outcomes and long-term mortality: the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) programme.

Aims: The use of opioids is recommended for pain relief in patients with myocardial infarction (MI) but may delay antiplatelet agent absorption, potentially leading to decreased treatment efficacy.

Methods And Results: In-hospital complications (death, non-fatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to pre-hospital morphine use were assessed in 2438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010. The analyses were replicated in the 1726 STEMI patients of the FAST-MI 2005 cohort, in which polymorphisms of CYP2C19 and ABCB1 had been assessed.

Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency.

Objective: On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets.

Methods: We performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7-47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events.

Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report.

Aims: Comparative studies suggest that stem cells committed to a cardiac lineage are more effective for improving heart function than those featuring an extra-cardiac phenotype. We have therefore developed a population of human embryonic stem cell (ESC)-derived cardiac progenitor cells.

Methods And Results: Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor inhibitor.

Exploring the Early Organization and Maturation of Linguistic Pathways in the Human Infant Brain.

Linguistic processing is based on a close collaboration between temporal and frontal regions connected by two pathways: the "dorsal" and "ventral pathways" (assumed to support phonological and semantic processing, respectively, in adults). We investigated here the development of these pathways at the onset of language acquisition, during the first post-natal weeks, using cross-sectional diffusion imaging in 21 healthy infants (6-22 weeks of age) and 17 young adults. We compared the bundle organization and microstructure at these two ages using tractography and original clustering analyses of diffusion tensor imaging parameters.

Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency.

Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs).

Impact of common risk factors of fibrosis progression in chronic hepatitis C.

Objective: The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C.

Design: We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy.

Characterization and multicentric validation of a common standard for Toxoplasma gondii detection using nucleic acid amplification assays.

The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community.

Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience.

Aim: There is now compelling evidence that cells committed to a cardiac lineage are most effective for improving the function of infarcted hearts. This has been confirmed by our pre-clinical studies entailing transplantation of human embryonic stem cell (hESC)-derived cardiac progenitors in rat and non-human primate models of myocardial infarction. These data have paved the way for a translational programme aimed at a phase I clinical trial.

Metabolic syndrome across Europe: different clusters of risk factors.

Background: Metabolic syndrome (MetS) remains a controversial entity. Specific clusters of MetS components - rather than MetS per se - are associated with accelerated arterial ageing and with cardiovascular (CV) events. To investigate whether the distribution of clusters of MetS components differed cross-culturally, we studied 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA in the MARE (Metabolic syndrome and Arteries REsearch) Consortium.

Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man.

The kallikrein-kinin system has been suggested to participate in the control of glucose metabolism. Its role and the role of angiotensin-I-converting enzyme, a major kinin-inactivating enzyme, are however the subject of debate. We have evaluated the consequence of deficiency in tissue kallikrein (TK), the main kinin-forming enzyme, on the development of insulin resistance and diabetes in mice and man.

Association between eprosartan-based hypertension therapy and improvement in cognitive function score: long-term follow-up from the OSCAR observational study.

Objective: The Observational Study on Cognitive function And systolic blood pressure Reduction (OSCAR) was designed to evaluate the impact of eprosartan-based therapy on cognitive function in a cohort of 25,745 hypertensive subjects followed for six months.

Methods: In this supplementary analysis, we studied the relationship between eprosartan-based therapy and cognitive function (assessed using the Mini-Mental State Examination (MMSE)) after 12-month follow-up of 3600 patients (the long-term follow-up on-treatment population).

Results: Reduction in blood pressure was sustained over 12 months, with mean systolic blood pressure/diastolic blood pressure 130.