Transplantation thoracique et grossesse (l'expérience nantaise)

La transplantation thoracique a pour but de sauver la vie des patients mais aussi de leur assurer une qualité de vie normale avec souvent, un désir de grossesse pour les jeunes greffées. Notre travail a étudié rétrospectivement les dossiers de douze patientes ayant mené à terme quatorze grossesses. Il s'agit d une situation à risque materno-foetal nécessitant une information éclairée des jeunes couples et une planification attentive, notamment en ce qui concerne la gestion du traitement médicamenteux. Les risques d hypertension artérielle et de préeclampsie obligent souvent à un accouchement prématuré par césarienne. Les enfants sont exposés à un risque tératogène, génétique et naissent hypotrophes. La grossesse chez ces patientes peut être autorisée sous couvert d une surveillance médico-obstétricale stricte. La principale réserve à ce projet familial reste la surmortalité maternelle.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge multidisciplinaire de l'insuffisance cardiaque (l'expérience du réseau de suivi et de traitement de l'insuffisance cardiaque de la région nantaise, Respecti-cœur)

L'insuffisance cardiaque (IC) est une pathologie chronique invalidante dont la prévalence ne cesse de croître dans les pays industrialisés, parallèlement au vieillissement de la population et aux progrès réalisés dans les autres domaines de la cardiologie comme la maladie coronaire ou l'HTA. Le réseau de suivi et de traitement de l'IC Respecti-cœur organise la prise en charge multidisciplinaire de cette pathologie, autour de la promotion de l'éducation thérapeutique et de la mise en place d'un suivi régulier du patient insuffisant cardiaque par des infirmières spécialisées, en collaboration avec le médecin traitant. L'évaluation des objectifs médicaux a montré que le réseau permet de diminuer le nombre et la durée des réhospitalisations pour IC à un an, alors qu'il n'influence que de manière modeste l'optimisation des traitements médicaux recommandés dans l'IC.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

DLL4 conveys Notch-dependent signals achieving selective macrophage differentiation or death

International audienceMolecular mechanisms underlying vascular and inflammatory cell network at endothelial and macrophage levels are still unclear. Here we found that microvascular inflammation associates with changes in Notch signaling at endothelium/monocyte interface including loss of endothelial Notch4 and the acquisition of the Notch ligand Dll4 in both cell types. We showed that endothelial DLL4 induces circulating monocytes to polarize into a M1-type pro-inflammatory macrophages (CD40highCD64highCD200Rlow HLADRlowCD11blow) eliciting the production of IL-6. Dll4 and IL-6 are both Notch-dependent and are required for macrophage polarization through selective down and upregulation of M2and M1-type markers, respectively. Subsequently, we investigated the ability of DLL4 to interfere with M2 polarization. We found that DLL4 triggers a specific alteration of the IL-4 induced M2 phenotype through a significant inhibition of M2 markers (CD11b, CD206, CD200R). DLL4 also induces caspase3/7-dependent apoptosis specifically in M2 differentiating macrophages while DLL1 had no effect. DLL4 signals via Notch1 and DLL4mediated apoptosis is Notch-dependent. Fully differentiated M2 macrophages became resistant to DLL4 action. DLL4 upregulates gene expression, upon M2 upon differentiation, affecting the Notch pattern (Notch1, 3, Jag1) and activity (Hes1), transcription (IRF5, STAT1) that associates with decrease in Akt but not STAT6 phosphorylation. In conclusion, our findings reveal an interplay between DLL4/Notch and IL-6/IL-6R or IL-4/IL-4R signaling pathways supporting M1 differentiation and impairing M2 differentiation via apoptosis

Notch signaling mediates crosstalk between endothelial cells and macrophages via Dll4 and IL6 in cardiac microvascular inflammation

International audienceAlthough short-term outcomes have improved with modern era immunosuppression, little progress has been made in long-term graft survival in cardiac transplantation. Antibody-mediated rejection (AMR) is one of the leading causes of graft failure and contributes significantly to poor long-term outcomes. Endothelial cell (EC) injury, intravascular macrophage infiltrate and microvascular inflammation are the histological features of AMR. Nevertheless, mechanisms of AMR remain unclear and treatment is still limited. Here, we investigated the mechanisms underlying vascular and inflammatory cell network involved in AMR at endothelial and macrophage levels, using endomyocardial transplant biopsies and EC/monocyte cocultures. First, we found that AMR associates with changes in Notch signaling at endothelium/monocyte interface including loss of endothelial Notch4 and the acquisition of the Notch ligand Dll4 in both cell types. We showed that endothelial Dll4 induces macrophage polarization into a pro-inflammatory fate (CD40 high CD64 high CD200R low HLA-DR low CD11b low) eliciting the production of IL-6. Dll4 and IL-6 are both Notch-dependent and are required for macrophage polarization through selective down and upregulation of M2-and M1-type markers, respectively. Overall, these findings highlight the impact of the graft's endothelium on macrophage recruitment and differentiation upon AMR via Notch signaling. We identified Dll4 and IL-6 as coregulators of vascular inflammation in cardiac transplantation and as potential targets for immunotherapy

Romiplostim as a Transfusion Saving Strategy in 20 Patients after Heart or Lung Transplantation: A Single Centre before-after Pilot Study

International audienceBACKGROUND: Thrombocytopenia is a common disorder after heart or lung transplantation. Platelet transfusion is often required to maintain haemostasis but represents a specific cause of morbidity and mortality in this setting including alloimmunisation and graft rejection. STUDY DESIGN AND METHODS: As part of a health-care quality improvement project, in a single-centre before-after pilot study, the relevance of a platelet transfusion saving strategy based on romiplostim administration after transplantation was assessed in patients with platelet count <100\,\texttimes\,109/L. Transfusions on days 28 and 90 were compared using propensity matched score for adjustment of demographic characteristics at baseline. The primary outcome was platelet transfusion until day 28 after transplantation. RESULTS: Ninety-three patients were analysed (73 before vs. 20 after). The median [interquartile range] number of platelet concentrate was 1 [0;4.0] before versus 0.5 [0;2.0] in the after period, mean difference 0.5 confidence interval 95% [-0.7 to 1.7], p\,=\,0.39. On day 28, median [interquartile range] red blood cell transfusion was significantly higher in the before versus the after period, 7 [2.0;13.5] versus 6 [1.5;8.5], mean difference 3.2 CI 95% [0.4-6.0], p\,=\,0.02. At 6\,months, the rate of patients with de novo anti-human leukocyte antigen alloimmunisation was 45% before versus 53% in the after period (p\,=\,0.56). Deep venous thrombosis was detected in nine patients (12%) before versus seven patients (35%) in the after period (p\,=\,0.04). CONCLUSION: Romiplostim did not significantly reduce platelet transfusion after heart or lung transplantation. Its relevance and safety in a global transfusion strategy remains to be studied in this setting in a large randomised study

Heart Transplantation in 8 Patients with Systemic Sclerosis: Results of a French National Registry

International audienceMeeting Abstract: BO41

Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation.

International audienceINTRODUCTION: Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease). In an attempt to clarify the frontier between these two entities, we have characterized cardiac conduction defect and its evolution with aging in a cohort of 78 patients carrying a SCN5A mutation linked to Brugada syndrome. METHODS AND RESULTS: Families were included in the study if a SCN5A mutation was identified in a BS proband and if at least two family members were mutation carriers. Sixteen families met the study criteria, representing 78 carriers. Resting ECG showed a spontaneous BS ECG pattern in 28 of 78 (36%) gene carriers. Intraventricular conduction anomalies were identified in 59 of 78 gene carriers including complete (17) or incomplete (24) right bundle branch block, right bundle branch block plus hemiblock (6), left bundle branch block (1), hemiblock (1), and parietal block (10). PR and QRS duration were longer in the gene carrier cohort in comparison with their relatives carrying no mutation. Finally, in the gene carrier cohort conduction defect progressively aggravated with aging leading in five occasions to pacemaker implantations. CONCLUSION: The present study shows that the most common phenotype of gene carriers of a BS-type SCN5A mutation is progressive cardiac conduction defects similar to the Lenègre disease phenotype. In consequence, we propose that carriers of a SCN5A mutation need a clinical and ECG follow-up because of the risk associated with severe conduction defects

Heart transplantation in selected patients aged 60 years and older: a two-decade retrospective and multicentre analysis

International audienceOBJECTIVES: This study analysed survival and long-term outcomes of heart transplantation in patients aged 60 years and older. We also analysed the impact of a national graft allocation priority [Super Emergency (SE)] and compared survival with younger patients in our centres and in France. METHODS: We performed a multicentre (University Hospitals in Nantes, Rennes and Tours), 2-decade retrospective study between 1 January 1994 and 31 December 2013. Elderly recipients were placed on the same list as younger patients; the use of marginal donors remained occasional. RESULTS: A total of 212 patients aged between 60 and 68 years were included. The 1-, 5-, and 10-year survival rates were 83.2%, 77.4% and 63.8%, respectively, which were significantly worse than those of recipients aged <60 years (1-, 5-, and 10-year survival rates of 87.3%, 80.4% and 68.0%, respectively). The postoperative course was acceptable. The main cause of death was malignancy (29.8% in our cohort). Survival was similar between the first and second decades and among the SE group. Our population exhibited better survival than patients <60 years transplanted in France during the same period with 1-, 5-, and 10-year survival rates of 76.8%, 68.0% and 56.3%, respectively. Predictors of survival in the multivariate analysis included ischaemic cardiomyopathy [hazard ratio (HR) 4.1] and postoperative complications, such as dialysis (HR 9.5) and mechanical circulatory support (HR 4.2). CONCLUSIONS: We report positive postoperative course and long-term outcomes after heart transplantation in older recipients using conventional donors. Our satisfactory outcomes may be explained by the stringent selection of recipients combined with regular follow-up

Long-term outcome of patients with non-operated prosthetic valve infective endocarditis is relapse the main issue?

International audienceIn non-operated prosthetic valve endocarditis (PVE), long term outcome is largely unknown. We report the follow-up of 129 non-operated patients with PVE alive at discharge. At one year, the mortality rate was 24%, relapses and reinfection were rare (5% each). Enterococcal PVE was associated with a higher risk of relapse