257 A novel polysaccharide-based porous scaffold for cell delivery into the infarcted heart

BackgroundCellular cardiomyoplasty has been proposed as an attractive strategy to repair myocardial damage. One of the crucial point is the optimal delivery strategy. In the present study, we examined the use of an implantable porous scaffold for promoting bone marrow-derived mesenchymal stem cells (MSCs) survival and functions in a rat model of acute myocardial infarction.Methods and ResultsCardiac patch was based on biodegradable polysaccharides porous scaffold. After ligation of the left anterior coronary artery, the fate of 1x106 GFP+ MSC administered either using cellularized scaffold implantation or direct injection was examined at 1 and 2 months. The number of residual GFP+ cells in the sample studied was estimated on the basis of the fluorescence emitted by a defined number of GFP+ cells used for calibration. Cellularized scaffold allowed a more efficient delivery and the difference with direct injection was significant at 2 months, with respectively 2100±1300×103 and 215±85x103 residual GFP+ cells (p<0.03). Cardiac tissue levels of matrix metalloproteinase-2 and -9 mRNA were similar whatever the administration conditions but a slight increase in the local production of vascular endothelial growth factor was observed at 2 months after patch implantation in comparison to direct injection (p<0.05). In animals having received MSC implemented on scaffold, clusters of GFP+ cells, mainly phenotypically consistent with immature MSC cells, were detected in the peri-infarct area. The increased survival using scaffold was not translated in an improved myocardial remodelling and functions with no significant difference in the LVEDD, LVESD, and FS between the 2 groups as in comparison with animals implanted with non cellularized scaffold.ConclusionsThese findings demonstrate that the implantation of cellularized grafts is safe and effective for delivering mesenchymal stem cells into damaged myocardium, and results in a better cellular engraftment compared to direct injection

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Naissance anormale isolée du tronc commun de l'artère coronaire gauche à partir du sinus de Valsalva droit (à propos d'un cas et revue de la littérature)

Anomalie rare la naissance du tronc commun de l'artère coronaire gauche à partir du sinus de Valsalva droit comporte un risque d'accident ischémique aigu de mort subite, en particulier lorsque le vaisseau chemine entre l'aorte et l'artère pulmonaire. Les patients qui décèdent subitement ont presque toujours moins de 35 ans, le plus souvent moins de 20 ans. La mort subite est associée à l'effort dans la majorité des cas. Elle est souvent précédée d'une symptomatologie d'appel.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

Facteurs prédictifs de l augmentation du Brain Natriuretic Peptid dans la cardiomyopathie hypertrophique

Nous avons voulu déterminer quels sont les facteurs cliniques et échographiques responsables de l'augmentation du taux de Brain natriuretic Peptid (BNP) chez les patients atteints de cardiomyopathie hypertrophique (CMH). Dans cette étude rétrospective, nous avons mesuré chez 62 patients des données cliniques, échographiques et le taux de BNP. Une analyse multivariée montre que les paramètres indépendamment corrélés à une augmentation du taux de BNP chez les patients atteints de CMH sont le stade NYHA, la diminution de la vélocité de l'onde Ea et la clairance de la créatinine. Ainsi, le taux de BNP est indépendamment relié à la présence et à la sévérité des symptômes d'insuffisance cardiaque ainsi qu à la vélocité de la paroi myocardique.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Disruption of the SEMA3D gene in a patient with congenital heart defects

International audienceCongenital heart defect (CHD) is the leading malformation among newborns. However, its genetic basis remains mostly unknown. We report a child with transposition of the great arteries, ventricular septal defect, and coarctation of the aorta. By array comparative genomic hybridization, we identified a duplication of the 5' half of semaphorin3D (SEMA3D). Breakpoint sequencing and fiber fluorescent in situ hybridization showed tandem duplication. Expression studies showed a higher level of SEMA3D mRNA in patient's lymphoblasts versus controls. Moreover, we demonstrated the presence of a truncated SEMA3D poly-A tailed mRNA, resulting from an abnormal transcription of SEMA3D partial duplication. Sema3D is an axon guidance protein essential for the correct migration of cardiac neural crest cells (CNCC) into the outflow tract. Sema3D(-/-) mice present with CHD but its role in humans remains unclear. Our results suggest that truncated SEMA3D may have hampered the migration of CNCC during heart development, contributing to patient's CHD

Le parcours

Les articles de ce numéro ont été sélectionnés parmi les interventions de la journée d'étude "Le parcours" organisée à l'Institut d'Anglais Charles V, Université de Paris VII

CorticalFlow: A Diffeomorphic Mesh Deformation Module for Cortical Surface Reconstruction

In this paper we introduce CorticalFlow, a new geometric deep-learning model that, given a 3-dimensional image, learns to deform a reference template towards a targeted object. To conserve the template mesh’s topological properties, we train our model over a set of diffeomorphic transformations. This new implementation of a flow Ordinary Differential Equation (ODE) framework benefits from a small GPU memory footprint, allowing the generation of surfaces with several hundred thousand vertices. To reduce topological errors introduced by its discrete resolution, we derive numeric conditions which improve the manifoldness of the predicted triangle mesh. To exhibit the utility of CorticalFlow, we demonstrate its performance for the challenging task of brain cortical surface reconstruction. In contrast to current state-of-the-art, CorticalFlow produces superior surfaces while reducing the computation time from nine and a half minutes to one second. More significantly, CorticalFlow enforces the generation of anatomically plausible surfaces; the absence of which has been a major impediment restricting the clinical relevance of such surface reconstruction methods.</p