USF-1 Is Critical for Maintaining Genome Integrity in Response to UV-Induced DNA Photolesions

An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations. This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents. To protect against this, cells have evolved effective mechanisms to recognize DNA damage, signal its presence, and mediate its repair. While these responses are expected to be highly regulated because they are critical to avoid human diseases, very little is known about the regulation of the expression of genes involved in mediating their effects. The Nucleotide Excision Repair (NER) is the major DNA–repair process involved in the recognition and removal of UV-mediated DNA damage. Here we use a combination of in vitro and in vivo assays with an intermittent UV-irradiation protocol to investigate the regulation of key players in the DNA–damage recognition step of NER sub-pathways (TCR and GGR). We show an up-regulation in gene expression of CSA and HR23A, which are involved in TCR and GGR, respectively. Importantly, we show that this occurs through a p53 independent mechanism and that it is coordinated by the stress-responsive transcription factor USF-1. Furthermore, using a mouse model we show that the loss of USF-1 compromises DNA repair, which suggests that USF-1 plays an important role in maintaining genomic stability

Etude de la fonction myocardique ventriculaire gauche par Doppler tissulaire en pré et post-opératoire chez les patients porteurs d'une valvulopathie unique chirurgicale

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease.

International audienceBACKGROUND: Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS). AIM: To assess the correlation between LS and HVPG and to investigate the performance of transient elastography for the diagnosis of significant portal hypertension (PHT). METHODS: Liver stiffness was measured by Fibroscan in 150 consecutive patients who underwent a liver biopsy with haemodynamic measurements. Usual clinical and biological data were collected. Significant PHT was defined as a HVPG > or = 10 mmHg. RESULTS: Hepatic venous pressure gradient was found to be > or = 10 mmHg in 76 patients. Cirrhosis was diagnosed in 89 patients. HVPG was found to be correlated with: LS (rho = 0.858; P < 0.001) and inversely correlated with prothrombin index (rho = -0.718; P < 0.001). Regarding significant PHT, AUROC for LS and prothrombin index were 0.945 [0.904-0.987] and 0.892 [0.837-0.947] respectively. The cut-off value of 21 kPa accurately predicted significant PHT in 92% of the 144 patients for whom LS was successful. CONCLUSION: Liver stiffness measurement is correlated with HVPG and transient elastography identifies patients with significant PHT

Recommandations pour la mise en place de staffs pluriprofessionnels (SPP) dans les services de soins

International audienceThe context and constraints of modern medicine (hospital beds and caregivers’ reductions, ambulatory shift, new therapeutic approaches, integration of supportive care…) combined with new societal and Health system changes (ageing population, chronic diseases, new requirements of the patients…) redefine the orientations of care and question professional practices. The participative approach (PA) as a model of team organization proposes solutions involving the skills of the various interacting caregivers and experimental knowledge and consideration of patient needs. The multi-professional staff (MPS) is a collaborative tool of this participative approach that federates a team around a health or care project personalized from the crosschecked eyes of care professionals and from a shared decision-making process. Its objective is to combine the improvement of quality of care with quality of life at work. It requires a transversal mindset of teams, intrinsic values and specific characteristics. Its organization is simple but requires some rules and we will develop the main steps to success. This article, which is the result of a joint reflection and experience of health professionals, shows the principles and wants to demonstrate the weakness of MPS. The interest of the French National Cancer Institute for this collaborative tool is an asset for further work in the perspective of generalization of MPS for all patients with chronic disease and not only for patients at palliative phase.Le contexte et les contraintes de la médecine moderne (réduction des lits d’hospitalisation, virage ambulatoire, diminution du nombre de soignants, nouvelles thérapies, intégration des soins de support…) conjointement aux nouvelles données sociétales et des systèmes de santé (vieillissement de la population, maladies chroniques, exigences nouvelles des personnes malades…) redéfinissent les champs du soin et interrogent les pratiques professionnelles. La démarche participative en tant que modèle d’organisation du travail en équipe propose des solutions faisant intervenir aussi bien les compétences des divers professionnels de santé en interaction, que les savoirs expérientiels et la prise en compte des préférences des personnes malades. Le staff pluriprofessionnel est un outil de la démarche participative, qui fédère une équipe autour d’un projet de soin ou de santé individualisé à partir des regards croisés des professionnels du soin et des prises de décision partagées. Son objectif est d’allier l’amélioration de la qualité du soin à celle de la qualité de vie au travail. Il requiert un état d’esprit transversal, des valeurs intrinsèques et des caractéristiques spécifiques . Son organisation est simple mais obéit à quelques règles. Nous en développerons les principales étapes. Cet article, issu d’une réflexion commune de professionnels de santé, vient démontrer ses principes et sa faisabilité. L’intérêt manifesté par l’INCa pour cet outil est un atout de poids pour la suite de ce travail dans l’optique d’une généralisation des staffs pluriprofessionnel pour tous les patients atteints d’une pathologie chronique et pas seulement pour les patients en situation palliative

Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUND The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. AIMS To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. METHODS 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. RESULTS The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone. CONCLUSIONS Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone

Patency of stents covered with polytetrafluoroethylene in patients treated by transjugular intrahepatic portosystemic shunts: long-term results of a randomized multicentre study.

International audienceAn 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P=0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P<0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P<0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1+/-1.6 to 7+/-2.2 at 2 years -P<0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased

The Authors

Abstract An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P = 0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P o 0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P o 0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1 AE 1.6 to 7 AE 2.2 at 2 years -P o 0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased. Transjugular intrahepatic portosystemic shunts (TIPS) have been increasingly used for the treatment of complications of portal hypertension in patients with cirrhosis (1, 2). However, the main limitation of this procedure is the high rate of shunt dysfunction. This dysfunction is mainly owing to pseudointimal hyperplasia growing inside the stent, so that the diameter of the shunt progressively decreases, leading to recurrence of portal hypertension and its complications. Accordingly, close monitoring of shunt patency is needed and more than 80% of the patients will require shunt revision within the first 2 years (3, 4). Experimental (5, 6) and preliminary clinical studies (7-11) have suggested that the use of stents covered with polytetrafluoroethylene (e-PTFE) could improve shunt patency by avoiding the pseudointimal hyperplasia. One retrospective study had shown that survival was improved by using a covered stent in patients treated by TIPS (12). In our randomizedcontrolled trial comparing covered and uncovered stents for TIPS (13), no difference regarding survival was observed between the two groups. Primary patency and clinical outcome of patients treated by covered stents were improved. However, the mean follow-up was only 1 year, raising the question of the long-term patency and safety of covered stents. We report hereby the results of our randomized study, 2 years after the last patient had been included. The main result was that improvement Liver Internationa

Sofosbuvir-Daclatasvir Is Suboptimal in Patients with Genotype 2 Chronic Hepatitis C Infection: Real-life Experience from the HEPATHER ANRS CO22 Cohort

International audienc

Retreatment with sofosbuvir plus grazoprevir plus elbasvir plus ribavirin of patients with Hepatitis C virus Genotype 1 or 4 with RASs at failure of a sofosbuvir plus ledipasvir or plus daclatasvir or plus simeprevir regimen (ANRS HC34 REVENGE study)

International audience67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) - Boston, MA - 2016-11-1