Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

International audienc

Maintien de la remission sous infliximab au long cours dans la recto-colite hémorragique

Evaluer si l efficacité de l infliximab (IFX) chez les patients ayant une RCH réfractaire qui ont initialement répondu au traitement d induction se maintient au cours des mois suivants et permet d éviter la colectomie. Nous avons par ailleurs recherché des facteurs prédictifs de colectomie et d échappement au traitement d entretien. Soixante douze patients ayant une recto-colite hémorragique ou une colite indéterminée réfractaires au traitement conventionnel et traités par IFX dans 4 centres experts français étaient étudiés. Tous ces patients avaient bénéficié d un traitement d induction selon le schéma standard et d au moins une perfusion d IFX à la dose de 5mg/kg en traitement d entretien. Au cours de l évolution, les modifications (augmentation des doses, rapprochement des perfusions) ou arrêt du traitement, changement de traitement ou chirurgie étaient notés. Huit patients ont été colectomisés au cours du suivi, donnant un taux actuariel de colectomie de 13% à 3 ans. Trois variables apparaissaient prédictives du risque de colectomie : avoir une maladie récente (p=0.048 ;HR=6 ; IC :[0,98-38,9]), avoir des signes endoscopiques de gravité (p=0,016 ; HR=6,07 ; IC :[1,36-27,22]) et avoir une hyperplaquettose à la 4ème perfusion d IFX (p=0,03 ; HR=6,13 ; IC :[1,16-32,47]). Au cours du suivi, des modifications du traitement ont été necessaires chez 47 patients (71% à 3 ans). Cinq patients ont été placés sous adalimumab en conservant leur réponse. Notre travail confirme l efficacité de l IFX en traitement d entretien au cours de la RCH réfractaire au traitement conventionnel. La plupart des patients répondeurs au traitement d induction par IFX maintiennent cette réponse, même s il est souvent nécessaire d adapter le traitement anti-TNF, et échappent au traitement chirurgical. Le risque de colectomie existe essentiellement lorsque la coloscopie initiale avait montré des signes de gravité, et paraît faible dans le cas contraire.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

La compréhension des énoncés de problèmes arithmétiques (rôle du modèle de situation)

POITIERS-BU Droit Lettres (861942101) / SudocSudocFranceF

Gastrointestinal bleeding of undetermined origin: What diagnostic strategy to propose?

CERVOXY CLINInternational audienceGastrointestinal bleeding of undetermined origin (GBUO) is defined as gastrointestinal bleeding without an identified cause or location despite an endoscopic assessmentincluding an esogastroduodenal endoscopy (EOGD) and a total colonoscopy. A distinction is madebetween exteriorized GBUO and non-exteriorized occult GBUO. The causes in the majority ofcases (vascular, inflammatory and tumoral) are located in the small intestine. The diagnosticstrategy aiming to locate the origin of the GBUO is a real challenge. Innovation in endoscopicand imaging techniques has enabled minimally invasive exploration of the small intestine. InEurope, there is a strong consensus to recommend a video-capsule endoscopy (VCE) as the firstintention study. If there is reason to suspect intestinal obstruction, VCE is contraindicated and aCT-enteroscopy is then performed as first intention. Enteroscopy is performed as a second-linetreatment, either for therapeutic purposes after a positive VCE or CT-enteroclysis, or for diagnostic purposes after a negative VCE. Finally, intraoperative enteroscopy (IOE) coupled withsurgical exploration should be reserved either for therapeutic purposes in the event of impossibility or failure of preoperative enteroscopy, or for diagnostic purposes in the event of recurrentGBUO after failure of all other studies and explorations of the small intestine

Circulating microparticles from Crohn's disease patients cause endothelial and vascular dysfunctions.

BACKGROUND: Microparticles (MPs) are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD) patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice. METHODS: Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS) and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed. RESULTS: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites. CONCLUSIONS: We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage

Le harcèlement sexuel : une dépénalisation qui fait mauvais genre

Commentaire collectif de la décision du Conseil constitutionnel QPC n° 2012-240 du 4 mai 2012, publié sur le blog du programme de Recherche et d’Études sur le Genre et les Inégalités dans les Normes en Europe (REGINE), http://regine-droit.blogspot.fr/2012/05/le-harcelement-sexuel-une.htm

Disequilibrium between <i>BRCA1</i> and <i>BRCA2</i> Circular and Messenger RNAs Plays a Role in Breast Cancer

Breast cancer is a frequent disease for which the discovery of markers that enable early detection or prognostic assessment remains challenging. Circular RNAs (circRNAs) are single-stranded structures in closed loops that are produced by backsplicing. CircRNA and messenger RNA (mRNA) are generated co-transcriptionally, and backsplicing and linear splicing compete against each other. As mRNAs are key players in tumorigenesis, we hypothesize that a disruption of the balance between circRNAs and mRNAs could promote breast cancer. Hence, we developed an assay for a simultaneous study of circRNAs and mRNAs, which we have called splice and expression analyses by exon ligation and high-throughput sequencing (SEALigHTS). Following SEALigHTS validation for BRCA1 and BRCA2, our hypothesis was tested using an independent research set of 95 pairs from tumor and adjacent normal breast tissues. In this research set, ratios of BRCA1 and BRCA2 circRNAs/mRNAs were significantly lower in the tumor breast tissue compared to normal tissue (p = 1.6 × 10−9 and p = 4.4 × 10−5 for BRCA1 and BRCA2, respectively). Overall, we developed an innovative method to study linear splicing and backsplicing, described the repertoire of BRCA1 and BRCA2 circRNAs, including 15 novel ones, and showed for the first time that a disequilibrium between BRCA1 and BRCA2 circRNAs and mRNAs plays a role in breast cancer

Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease

International audienceBackground & aims - Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. Methods - We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. Results - After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. Conclusions - In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies

Correlations between baseline 18F-FDG PET tumour parameters and circulating DNA in diffuse large B cell lymphoma and Hodgkin lymphoma

International audienceBackground: 18F-FDG PET/CT is a standard for many B cell malignancies, while blood DNA measurements are emerging tools. Our objective was to evaluate the correlations between baseline PET parameters and circulating DNA in diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL).Methods: Twenty-seven DLBCL and forty-eight cHL were prospectively included. Twelve PET parameters were analysed. Spearman’s correlations were used to compare PET parameters each other and to circulating cell-free DNA ([cfDNA]) and circulating tumour DNA ([ctDNA]). p values were controlled by Benjamini–Hochberg correction.Results: Among the PET parameters, three different clusters for tumour burden, fragmentation/massiveness and dispersion parameters were observed. Some PET parameters were significantly correlated with blood DNA parameters, including the total metabolic tumour surface (TMTS) describing the tumour–host interface (e.g. ρ = 0.81 p < 0.001 for [ctDNA] of DLBLC), the tumour median distance between the periphery and the centroid (medPCD) describing the tumour’s massiveness (e.g. ρ = 0.81 p < 0.001 for [ctDNA] of DLBLC) and the volume of the bounding box including tumours (TumBB) describing the disease’s dispersion (e.g. ρ = 0.83 p < 0.001 for [ctDNA] of DLBLC).Conclusions: Some PET parameters describing tumour burden, fragmentation/massiveness and dispersion are significantly correlated with circulating DNA parameters of DLBCL and cHL patients. These results could help to understand the pathophysiology of B cell malignancies

Correlations between circulating MPs level and biological parameters of CD patients.

<p>Correlations between circulating MPs level and biological parameters of CD patients.</p