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