Severe traumatic brain injury, frontal lesions, and social aspects of language use: A study of French-speaking adults

International audienceThe purpose of this study was to gain insight into the social (pragmatic) aspects of language use by French-speaking individuals with frontal lesions following a severe traumatic brain injury. Eleven participants with traumatic brain injury performed tasks in three areas of communication: production (interview situation), comprehension (direct requests, conventional indirect requests, and hints), and metapragmatic knowledge. The results of the patients pointed out some strengths (turn-taking in production, and request comprehension, including hints and the speaker's intention) and some weaknesses (topic maintenance in production and metapragmatic knowledge). The patients' good comprehension of requests and their difficulty expressing metapragmatic knowledge suggest that they differ from controls in how they "explain the world": their knowledge of the event sequence was not based on verbally expressible knowledge about the relationship between the structural characteristics of a request utterance and those of its social production context. The pragmatic skills of persons with traumatic brain injury seem to vary across tasks: these individuals have specific strengths and weaknesses in different domains. In addition, marked interindividual differences were noted among the patients: three of them had only one weak point, topic maintenance. These interindividual differences were not systematically linked to performance on executive function tests, but lesion unilaterality (right or left) seems to help preserve patients' pragmatic and metapragmatic skills. The discussion stresses the need to take each patient's strengths and weaknesses into account in designing remediation programs

Improving Chemotherapy-Induced Peripheral Neuropathy in Patients with Breast or Colon Cancer after End of (Neo)adjuvant Therapy: Results from the Observational Study STEFANO

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect persisting after completion of neurotoxic chemotherapies. This observational study was designed to evaluate the effectiveness of the dietary supplement OnLife (R) (patented mixture of specific fatty acids and palmitoylethanolamide) in improving symptoms of CIPN in breast and colon cancer patients. Methods: Improvement of CIPN was evaluated in adult patients, previously treated with (neo)adjuvant paclitaxel- (breast cancer) or oxaliplatin-based (colon cancer) therapies, receiving OnLife (R) for 3 months after completion of chemotherapy. The primary endpoint was to compare the severity of peripheral sensory neuropathy (PSN) and peripheral motor neuropathy (PMN) before and at the end of OnLife (R) treatment. Secondary endpoints included the assessment of patient-reported quality of life and CIPN symptoms as assessed by questionnaires. Results: 146 patients (n = 75 breast cancer patients and n = 71 colon cancer patients) qualified for analysis; 31.1% and 37.5% of breast cancer patients had an improvement of PSN and PMN, respectively. In colon cancer patients, PSN and PMN improved in 16.9% and 20.0% of patients, respectively. According to patient-reported outcomes, 45.9% and 37.5% of patients with paclitaxel-induced PSN and PMN, and 23.9% and 22.0% of patients with oxaliplatin-induced PSN and PMN experienced a reduction of CIPN symptoms, respectively. Conclusion: OnLife (R) treatment confirmed to be beneficial in reducing CIPN severity and in limiting the progression of neuropathy, more markedly in paclitaxel-treated patients and also in patients with oxaliplatin-induced CIPN

CCM2 deficient endothelial cells undergo a ROCK dependent reprogramming into senescence associated secretory phenotype

International audienc

First‐line pazopanib in intermediate‐ and poor‐risk patients with metastatic renal cell carcinoma: Final results of the FLIPPER

Temsirolimus has long been the only approved first-line standard of care (SOC) with overall survival (OS) benefit in poor-risk patients with advanced or metastatic renal cell cancer (mRCC). However, tyrosine kinase inhibitors are also commonly used in clinical practice. Pazopanib is an SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER (First-Line Pazopanib in Poor-Risk Patients with Metastatic Renal Cell Carcinoma) study aimed to assess efficacy and safety of first-line pazopanib in poor-risk mRCC patients. FLIPPER was a single-arm, multicenter, Phase IV trial. Key inclusion criteria were treatment-naive clear cell, inoperable advanced or mRCC, poor-risk according to MSKCC with slight modification, Karnofsky performance status (KPS) >= 60% and adequate organ function. Oral pazopanib 800 mg was given daily. Primary endpoint was the 6-month progression-free survival rate (PFS6). Secondary endpoints included PFS, OS, overall response rate (ORR), duration of response (DOR) and safety. For analysis, descriptive statistics were used. Between 2012 and 2016, 60 patients had been included. Forty-three patients qualified for safety analyses, 34 for efficacy. Median age was 66 years, 64.7% of patients were poor-risk, 82.4% had a KPS <= 70%. PFS6 was 35.3% (95% CI, 19.7-53.5). Median PFS and OS were 4.5 months (95% CI, 3.6-7.8) and 9.3 months (95% CI, 6.6-22.2), respectively. ORR was 32.4% (95% CI, 17.4-50.5), median DOR 9.7 months (95% CI, 1.8-12.4). The most common treatment-related grade 3/4 adverse event reported in 4.7% of patients was hypertension. No treatment-related death occurred. Since pazopanib is active and well tolerated in poor-risk patients with clear cell mRCC, our results support its use as first-line treatment in this setting

A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity

This work concerns the isolation and structure elucidation of compounds obtained from the extract of leaves and stem bark of Combretum fragrans F. Hoffm. Both extracts and some isolated compounds were tested for antiproliferative activity on glioblastoma (U87MG and C6 cells) and prostate (PC-3 cells) cancer cell lines using XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay. The dichloromethane/methanol (1:1) extract of the leaves led to the isolation of two new compounds such as fragransinate (1) and combretin C (2), alongside five known compounds such as combretin A (3), belamcanidin (4), cirsilineol (5), velutin (6), and a mixture of β-sitosterol-3-O-β-d-glucopyranoside (10a) and stigmasterol-3-O-β-d-glucopyranoside (10b), whereas the methanol extract of the stem bark led to the isolation of three known compounds betulinic acid (7), bellericagenin B (8), and a mixture of β-sitosterol (9a) and stigmasterol (9b). The structure of compounds was elucidated by nuclear magnetic resonance and mass spectrometry data. The methanol extract of the stem bark showed a powerful antiproliferative activity on all tested cells, as well as the extract of leaves which also showed important cytotoxicity effect. Compound (3) showed good antiproliferative activity particularly on U87MG and PC-3 cells, whereas compound (5) exhibits moderated activity. Compounds (2) and (8) were not active on all tested cells

Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients

Bi-allelic loss-of-function variants of OTOA are a well-known cause of moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions of the gene are well known, gene conversions to pseudogene OTOAP1 have been reported in the literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for a converted allele and a deletion of OTOA. The conversions were initially detected through sequencing depths anomalies at the OTOA locus after exome sequencing, then confirmed with long range PCRs. Both conversions lead to loss-of-function by introducing a premature stop codon in exon 22 (p.Glu787*). Using genomic alignments and long read nanopore sequencing, we found that the two probands carry stretches of converted DNA of widely different lengths (at least 9kbp and around 900bp respectively). This article is protected by copyright. All rights reserved

Familial history of cancer and childhood acute leukemia: a French population-based case-control study.

International audienceA case-control study was conducted to investigate the role of a familial history of cancer in the etiology of childhood acute leukemia. The history of cancer in the relatives of 472 cases was compared with that of 567 population-based controls. Recruitment was frequency matched on age, sex and region. The familial history of cancer in each child's relatives was reported by the mother in response to a standardized self-administered questionnaire. A familial history of solid tumor in first or second-degree relatives was associated with an increased risk of acute lymphoblastic leukemia (odds ratio (OR)=1.6 [95% confidence interval, 1.2-2.1]), while a familial history of hematopoietic malignancies in first or second-degree relatives was associated with an increased risk of acute myeloid leukemia (OR=4.3 [1.4-13]). The ORs for the histories of cancer increased with the number of relatives with cancer (OR=1.5 [1.1-2.0] for one relative and OR=2.3 [1.3-3.8] for two relatives or more; Ptrend<0.0001). Significant associations between childhood acute leukemia and familial history of genital cancers and brain tumor were also observed (OR=2.7 [1.2-5.8] and OR=10.7 [1.3-86], respectively). This study supports the hypothesis that a familial history of cancer may play a role in the etiology of childhood acute leukemia. It also evidences some specific associations that require further investigation

Recommandations pour la pratique clinique : « Interventions pendant la période périnatale ». Synthèse

Ces recommandations de pratique clinique (RPC) ont pour but de définir les messages et les interventions de prévention à délivrer aux femmes et aux co-parents par les différents professionnels de la périnatalité. Les recommandations sont divisées en dix chapitres, réparties sur quatre axes : 1/ l’adaptation des comportements maternels (activité physique, substances psychoactives) ; 2/ les comportements alimentaires ; 3/ l’exposition domestique aux agents toxiques (usages domestiques, cosmétiques) ; 4/ la promotion de la santé de l’enfant (allaitement maternel, liens d’attachement, écrans, mort inattendue du nourrisson, syndrome du bébé secoué). Une hiérarchie des différents messages de prévention a été proposée selon les périodes afin de tenir compte des contraintes de temps rencontrées par les professionnels