Étude de l évolution lésionnelle en IRM de la maladie de Crohn anopérinéale chez 49 patients traités par anti-TNF alpha

Introduction : le traitement de la maladie de Crohn avec lésions anopérinéales (LAP) repose sur une approche médico-chirurgicale combinant antibiothérapie, drainage, immunosuppresseurs et anti-TNF a. L évaluation de la réponse au traitement demeure un problème de nos jours. Objectif : décrire l évolution clinique et à l IRM des LAP sous traitement, évaluer la concordance entre l évolution clinique et l évolution IRM et définir des facteurs prédictifs de rémission clinique et de cicatrisation lésionnelle à l IRM. Patients et méthodes : tous les patients avec une maladie de Crohn avec LAP suivis dans notre centre tertiaire de 2000 à 2012 ayant bénéficié d un traitement par anti-TNF a et d une IRM pelvienne au moment du diagnostic et à la fin de l étude ont été inclus dans l étude. L analyse des données était rétrospective. L évaluation clinique reposait sur les critères de Present et l évaluation IRM sur le score de Van Assche et la prise de contraste après injection de gadolinium. Résultats : 49 patients ont été inclus dans notre étude avec une médiane de suivi de 40 mois. La rémission clinique, la réponse et la non-réponse étaient retrouvées chez respectivement 53,1%, 20,4% et 26,5% des patients. La rémission clinique associée à une cicatrisation lésionnelle à l IRM était retrouvée chez 32,7% des patients. Une amélioration, une stabilisation et une aggravation des lésions à l IRM étaient retrouvées chez respectivement 61,2%, 16,3% et 22,4% des patients. Le facteur prédictif de rémission clinique en analyse multivariée est l absence d atteinte rectale endoscopique au diagnostic. Les facteurs prédictifs de rémission clinique associée à une cicatrisation IRM sont l absence d atteinte rectale endoscopique et la présence d une fistule ano ou rectovaginale au diagnostic. Conclusion : Une cicatrisation lésionnelle associée à une rémission clinique est obtenue chez près d un malade sur trois. L atteinte rectale est le facteur prédictif majeur de réponse au traitement. La place de la cicatrisation lésionnelle doit faire l objet de travaux prospectifs pour évaluer son intérêt et celui de l IRM dans le suivi et la prise en charge des patients.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

A Bayesian implementation of quality-by-design for the development of cationic nano-lipid for siRNA transfection

International audienceUnlike Quality by Testing approach, where products were tested only after drug manufacturing, Quality by Design (QbD) is a proactive control quality paradigm, which handles risks from the early development steps. In QbD, regression models built from experimental data are used to predict a risk mapping called Design Space in which the developers can identify values of critical input factors leading to acceptable probabilities to meet the efficacy and safety specifications for the expected product. These empirical models are often limited to quantitative responses. Moreover, in practice the smallness and incompleteness of datasets degrade the quality of predictions. In this study, a Bayesian approach including variable selection, parameter estimation and model quality assessment is proposed and assessed using a real case study devoted to the development of a Cationic Nano-Lipid Structures for siRNA Transfection. Two original model structures are also included to describe both binary and percentage response variables. The results confirm the practical relevance and applicability of the Bayesian implementation of the QbD analysis

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease

International audienc

Deep remission on magnetic resonance imaging impacts outcomes of perianal fistulizing Crohn’s disease

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Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF – Texte court

International audienceThis work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C)

Pratiques innovantes auprès des jeunes en difficulté

L'étendue des expérimentations locales dans le domaine de l'intervention psychosociale auprès des jeunes et de leur famille est largement méconnue. Pourtant, si l'on innove, c'est pour répondre à la nécessité souvent criante de s'adapter à l'environnement de travail et à la clientèle. Or, lorsque les pratiques originales restent dans l'ombre, les intervenants courent le risque de passer à côté de trouvailles utiles et de reproduire les erreurs du passé. Ce livre décrit une trentaine d'initiatives en cours dans le réseau des centres jeunesse du Québec. Les auteurs sont des praticiens et des universitaires dont la collaboration a permis de trouver des solutions prometteuses pour offrir aux jeunes en difficulté un soutien individuel et familial adéquat

The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis

Background PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. Methods We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. Results We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52–0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77–0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. Conclusions The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection

Pancreatology

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection