L'analyse échographique bidimensionnelle du strain, un nouvel outil en réanimation des cardiopathies congénitales?

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Intérêt de la procalcitonine comme marqueur de l'infection bactérienne après chirurgie cardiaque sous circulation extra-corporelle chez l'enfant

La période post-opératoire est souvent marquée par la présence d'un syndrome de réponse inflammatoire systémique (SIRS) après une circulation extra-corporelle (CEC) chez l'enfant. Le diagnostic d infection post-opératoire est de ce fait difficile à poser avec les éléments cliniques et biologiques classiques. La procalcitonine (PCT), marqueur spécifique de l infection bactérienne, pourrait constituer une aide diagnostique. Objectif Evaluer l intérêt du dosage de la PCT dans le diagnostic de l infection bactérienne après une CEC chez l enfant. Méthodes Un dosage de PCT a été réalisé chez tous les enfants suspects d infection post-opératoire. Ce dosage était répété à 24 heures d intervalle. Le diagnostic d infection a été établi rétrospectivement grâce à des critères référencés. Résultats Sur les 95 enfants inclus sur une période d un an et demi, 14 ont été infectés. Dans les 72 premières heures post-opératoires, le taux de PCT est significativement plus élevé chez les infectés que chez les non infectés (20,24 ng/mL versus 0,72 ng/mL). Une valeur seuil de 13 ng/mL permet d obtenir une sensibilité de 100% pour une spécificité de 85%. Les faux positifs sont dus au SIRS. Après 72 heures post-opératoires, le test est moins sensible et moins spécifique. Le fait de réaliser un deuxième dosage à 24 heures d intervalle permet, pour une valeur seuil de 0,38 ng/mL, d'obtenir une sensibilité de 100% pour une spécificité de 50%. Conclusion La PCT est un marqueur discriminant de l infection dans la période post-opératoire précoce mais est beaucoup moins performant après 72 heures post-opératoires. Un deuxième dosage permet alors, du fait d une cinétique de la PCT différente chez les patients infectés, d'en améliorer la sensibilité.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

First Case of Q Fever Endocarditis Involving the Melody(A (R)) Transcatheter Pulmonary Valve in an Afebrile Child

International audienceIn this article we report the first case of Q fever endocarditis in a 13 years old child with a percutaneous pulmonary Melody(A (R)) valve. The patient had a new onset of Melody valve dysfunction associated with the combination of hepatosplenomegaly and pancytopenia but was afebrile. Although blood cultures were negative, we have further investigated in the direction of infective endocarditis by performing PCR detection and the serology of C. burnetii which were positive. A combination antibiotic therapy with doxycycline and hydroxychloroquine was started with good clinical evolution. Our case emphasizes the fact that any Melody valvular dysfuntion should be considered as a potential infective endocarditis despite the absence of typical bacterial features

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model

Aims. To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model. Background. Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release. Methods. After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion (n = 6) and 15 mm ASO (n = 6) devices. After 1 month (n = 3 for each device) and 3 months (n = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed. Results. Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration. Conclusions. In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes

Exonic Deletions of FXN and Early-Onset Friedreich Ataxia.

International audienceBACKGROUND: Friedreich ataxia (FA) is the most frequent type of autosomal recessive cerebellar ataxia, occurring at a mean age of 16 years. Nearly 98% of patients with FA present with homozygous GAA expansions in the FXN gene. The remaining patients are compound heterozygous for an expansion and a point mutation. Patients who are compound heterozygous for an exonic deletion and an expansion are exquisitely rare. OBJECTIVES: To describe 6 patients affected with FA due to an exonic deletion mutation (FAexdel) and to compare these 6 patients with FAexdel with 46 patients consecutively diagnosed with typical FA due to homozygous GAA expansion and whose small expansions were within the same range as that of the expansions of the patients with FAexdel. DESIGN: Description of a series. SETTING: Academic research. Patients Six patients with FAexdel and 46 patients with typical FA. Intervention FXN gene analysis, including assessments of GAA expansion and exon sequencing and determination of exonic copy numbers using multiplex ligation-dependent probe amplification. RESULTS: We identified 6 patients with FA who presented with the combination of 1 GAA expansion and 1 FXN exonic deletion. The mean (SD) age at onset of the disease was earlier for patients with FAexdel (7 [4] years [range, 3-12 years]) than for patients with typical FA (15 [5] years [range, 6-30 years]) (P = .001), and the median time to confinement to wheelchair was shorter for patients with FAexdel (20 years) than for patients with typical FA (28 years) (P = .002). There was no difference between the mean (SD) size of the expansion for the patients with FAexdel (780 [256] GAA triplet repeat sequences [range, 340-1070 GAA triplet repeat sequences]) and the mean (SD) size of the short expansion for the patients with typical FA (634 [163] GAA triplet repeat sequences [range, 367-1000 GAA triplet repeat sequences]) (P = .10). The mean disease duration before becoming wheelchair bound was shorter for patients with FAexdel (9 years) than for patients with typical FA (13 years), and the incidence of cardiomyopathy was higher for patients with FAexdel (84%) than for patients with typical FA (68%). However, these differences were not significant, probably owing to the small size of the FAexdel group. The other extraneurological signs, such as scoliosis or diabetes mellitus, were particularly frequently observed in the FAexdel group. One patient presented at 9 years of age with severe angina and marked cardiomyopathy that confined her to a wheelchair. Three patients had disabling autonomic disturbances. It appears that exonic deletion significantly contributes to the clinical picture of patients with FA. CONCLUSIONS: Friedreich ataxia due to an exonic deletion mutation corresponds to an early onset and severe variant of FA. FXN should be investigated for exonic deletion in patients with early-onset FA in which only 1 GAA expansion without a point mutation is found. Patients with FAexdel have to be carefully observed using cardiological, orthopaedic, endocrinological, gastroenterological, and ophthalmological data. Friedreich ataxia due to an exonic deletion mutation should be suspected in young patients presenting with severe scoliosis

HRAS germline mutations impair LKB1/AMPK signaling and mitochondrial homeostasis in Costello syndrome models

Germline mutations that activate genes in the canonical RAS/MAPK signaling pathway are responsible for rare human developmental disorders known as RASopathies. Here, we analyzed the molecular determinants of Costello syndrome (CS) using a mouse model expressing HRAS p.G12S, patient skin fibroblasts, hiPSC-derived human cardiomyocytes, a HRAS p.G12V zebrafish model, and human fibroblasts expressing lentiviral constructs carrying HRAS p.G12S or HRAS p.G12A mutations. The findings revealed alteration of mitochondrial proteostasis and defective oxidative phosphorylation in the heart and skeletal muscle of CS mice that were also found in the cell models of the disease. The underpinning mechanisms involved the inhibition of the AMPK signaling pathway by mutant forms of HRAS, leading to alteration of mitochondrial proteostasis and bioenergetics. Pharmacological activation of mitochondrial bioenergetics and quality control restored organelle function in HRAS p.G12A and p.G12S cell models, reduced left ventricle hypertrophy in CS mice, and diminished the occurrence of developmental defects in the CS zebrafish model. Collectively, these findings highlight the importance of mitochondrial proteostasis and bioenergetics in the pathophysiology of RASopathies and suggest that patients with CS may benefit from treatment with mitochondrial modulators

Impact of Sophrology on cardiopulmonary fitness in teenagers and young adults with a congenital heart disease: The SOPHROCARE study rationale, design and methods

International audienceBackground: Recent advances in the field of congenital heart disease (CHD) have significantly improved the overall prognosis. Now more attention is being given to health-related quality of life (HRQoL) and promotion of physical activity. Non-invasive relaxation therapy may be effective in cardiac patients concerned with exercise-induced dyspnoea. The SOPHROCARE randomised trial aims to assess the impact of Caycedian Sophrology on cardiopulmonary fitness in adolescents and young adults with CHD.Methods: The SOPHROCARE trial is a nationwide, multicentre, randomised, controlled study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (8 Sophrology group sessions vs. no intervention). The primary outcome is the change in percent predicted maximum oxygen uptake (VO2max) between baseline and 12-month follow-up. A total of 94 patients in each group is required to observe a significant increase of 10% in VO2max with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VE/VCO2 slope, ventilatory anaerobic threshold, oxygen pulse, respiratory response to hypercapnia), health-related quality of life score (PedsQL), physical and psychological status.Conclusion: After focusing on the survival in CHD, current research is opening on secondary prevention and patient-related outcomes. We sought to assess in the SOPHROCARE trial, if a Sophrology program, could improve exercise capacity and quality of life in youth with CHD.Trial registration: Clinicaltrials.gov (NCT03999320)