Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome

A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneuploidy (DS + KS) associated with congenital heart defects have been published of which none had a double aortic arch. Our case report should draw attention to the possibility of a double aortic arch in patients with severe feeding and respiratory problems and a double aneuploidy

Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

OBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS

Liver X receptors are required for thymic resilience and T cell output

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)-a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity-critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire. LXRαβ's functions are cell specific, and the resulting phenotypes are mutually independent. Although thymic macrophages require LXRαβ for cholesterol efflux, thymic epithelial cells (TECs) use LXRαβ for self-renewal and thymocytes for negative selection. Consequently, TEC-derived LXRαβ protects against homeostatic premature involution and orchestrates thymic regeneration following stress, while thymocyte-derived LXRαβ limits cell disposal during negative selection and confers heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXRαβ governs T lymphocyte education and illuminate LXRαβ's indispensable roles in adaptive immunity

Down-sizing of cryopreserved homografts is a valuable technique, but do not make them too small

Cardiolog

Surgical treatment of Marfan syndrome and related disorders is all about dealing with uncertainties

Thoracic Surger

Valve-sparing root replacement in children

In children, words of caution have been raised about valve-sparing procedures especially regarding the valve-remodelling technique. This study reviewed our experience with the valve-sparing reimplantation technique in children. All consecutive paediatric ( <18 years) patients who underwent valve-sparing root replacement in our centre in the past 12.5 years were retrospectively analysed. Nineteen patients (median age 13.2 years, 10 months to 17.9 years) underwent valve-sparing root replacement using the reimplantation technique. Seventeen had connective tissue disease. An adult-sized vascular prosthesis could be implanted in all cases. Additional cusp repair was required in 3 patients. Follow-up was 4.4 ± 3.8 years. There was no perioperative mortality and one late death. Of the 3 patients that needed cusp repair, 1 developed Grade 3 aortic valve regurgitation (AR) and required aortic valve replacement and 2 had Grade 1 AR. Ninety-four percent of the other patients had Grade 0 AR at latest follow-up, 1 patient (6%) had Grade 1 AR. Our data show that valve-sparing root surgery using the reimplantation technique can be performed safely in children. Mid-term follow-up yields stable and favourable results. When leaflet reconstruction is necessary on top of the reimplantation procedure, rate of recurrent AR seems to be highe

Fifteen years' experience with the use of artificial chords for valve reconstruction in children

OBJECTIVES: To retrospectively review our experience with artificial chords in mitral and tricuspid reconstructive surgery in children. METHODS: All consecutive paediatric ( <18 years) patients who underwent mitral or tricuspid valve reconstruction with the use of artificial chords in our centre in the past 15 years were retrospectively analysed. RESULTS: Thirty-nine patients (age 3 days to 17 years) underwent reconstruction of the mitral (n = 27) or tricuspid (n = 12) valve using artificial chords. Mean number of chords was 3.5 +/- 1.7. In 26 of 27 mitral valve patients, chords were placed on the anterior leaflet, in one on the posterior leaflet. In 10 of the 12 tricupid valve, patients chords were placed on the anterior leaflet and in 2 on the septal leaflet. All mitral patients underwent annuloplasty (10 bilateral Wooler-Kay and 17 rigid ring annuloplasty). Ten of the 12 tricuspid patients underwent annuloplasty (1 rigid ring and 9 commissural plication). Follow-up was after 8.7 +/- 5.5 years. There was no early or late mortality. The actuarial freedom from reoperation rates at 1, 5 and 10 years were 95%, 91% and 81%, respectively. No reoperations occurred in the tricuspid group. In the mitral group, there were 2 early failures and 3 late reoperations due to mitral stenosis. Restricted leaflet motion probably caused by the artificial chords was seen in only 1 patient. CONCLUSIONS: Our data show that long-term durability of mitral and tricuspid valve reconstruction using artificial chords in children is good. Despite patient growth, restricted leaflet motion by the artificial chords does not seem to form a major proble

Hybrid branch pulmonary artery stent placement in adults with congenital heart disease

Valuable treatment modalities for branch pulmonary artery (BPA) stenoses are surgical patch angioplasty, percutaneous BPA stenting and hybrid stent placement. The purpose of this study was to report our institutional experience with hybrid stent placement to relieve BPA stenoses. Between August 2007 and May 2014, 7 adults (5 females) with congenital heart disease (CHD) had elective intraoperative BPA stent placement. All 7 patients had undergone previous surgery [6 tetralogy of Fallot repairs and 1 arterial switch operation for transposition of the great arteries (TGAs)]. A total of 7 stents (4 right pulmonary artery, 3 left pulmonary artery) were implanted under direct vision, concomitant with a pulmonary homograft implantation (tetralogy of Fallot patients), or because percutaneous stenting was not feasible (TGA patient). Retrospective analysis of clinical data, procedural details and outcomes was performed. Overall, the mean age was 35 ± 7.2 years. Stent implantation was successful in all procedures. The mean postinflation stent diameter was 13.3 ± 2.0 mm. No stent migration, fracture, stent thrombosis, reintervention or deaths occurred. In 1 case the procedure was complicated by a right pulmonary artery tear just distal to the stent which was repaired by surgical patch angioplasty. At a mean follow-up of 55.6 ± 26 months no patient required catheter reintervention or surgery. Echocardiography (mean follow-up 47.1 ± 22 months), MRI (mean follow-up 43.8 ± 37 months) and CT data (mean follow-up 14.8 ± 10 months) demonstrate a BPA diameter increment from a mean 5.57 ± 2.29 to 10.71 ± 2.56 mm. Hybrid intraoperative BPA stent placement is safe and effective and can be used as an alternative for surgical patch angioplasty or if percutaneous BPA stenting is not feasible. Short- to mid-term results are goo