Exaggerated elastin turnover in young individuals with Marfan syndrome: new insights from the AIMS trial.

Aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta are pathological hallmarks of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood.

Methods And Results: In this analysis of the AIMS randomized controlled trial, the association of plasma desmosine (pDES)-a specific biomarker of mature elastin degradation-with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls. There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults.

A phenotypic screen of Marfan syndrome iPSC-derived vascular smooth muscle cells uncovers GSK3β as a new target.

Marfan syndrome (MFS) is a rare connective tissue disorder caused by mutations in FBN1. Patients with MFS notably suffer from aortic aneurysm and dissection. Despite considerable effort, animal models have proven to be poorly predictive for therapeutic intervention in human aortic disease.

Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

Background: Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.

Methods: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021.

Determining the genetic contribution in patients with non-syndromic ascending thoracic aortic aneurysms: Correlation with findings from computational pathology.

Objectives: This study aims to identify the clinical utility of targeted-genetic sequencing in a cohort of patients with TAA and establish a new method for regional histological characterisation of TAA disease.

Methods: Fifty-four patients undergoing surgery for proximal TAA were recruited.

Exclusions: connective tissue disease, bicuspid aortic valves, redo surgery.

Prevalence of Coding Variants in French-Canadian and British AIS Cohort.

Adolescent idiopathic scoliosis (AIS) is a complex common disorder of multifactorial etiology defined by a deviation of the spine in three dimensions that affects approximately 2% to 4% of adolescents. Risk factors include other affected family members, suggesting a genetic component to the disease. The gene was identified as one of the first ciliary candidate genes for AIS, as three variants were identified in large families with multiple members affected with idiopathic scoliosis.

Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family.

Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial.

Background: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.

Methods: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK.

Prevalence and progression of aortic root dilatation in highly trained young athletes.

Objectives: Aortic root dilatation is reported in young athletes; however, it is unclear whether such remodelling is physiological or, whether it represents a potential aortopathy. This observational study investigated the prevalence and progression of aortic root dilatation in young athletes competing at regional or national level.

Methods: Between 2003 and 2015, 3781 athletes aged 19±5.

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

Purpose: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management.

Methods: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed.

Non-cardiac manifestations of Marfan syndrome.

Because of the widespread distribution of fibrillin 1 in the body, Marfan syndrome (MFS) affects virtually every system. The expression of this single dominantly inherited gene is variable within a family, and between families. There is some genotype-phenotype correlation which is helpful in guiding long-term prognosis, and management.

The role of advanced echocardiography and cardiovascular magnetic resonance in the assessment of myocardial function in Marfan syndrome-An update.

Cardiovascular assessment of patients with Marfan syndrome has normally focused on the aortic root and vascular manifestations of the disease due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected in these patients, the evidence has been controversial. Advanced echocardiography and cardiovascular magnetic resonance imaging have proven to be effective, accurate, and more sensitive in the detection of subtle cardiac dysfunction.

Aortic Root Surgery: Does High Surgical Volume and a Consistent Perioperative Approach Improve Outcome?

There is evidence that high surgical volume and team consistency improve outcomes. Mortality of 4%-12% for aortic root surgery has been reported in the United States and UK. We aim to assess outcomes of patients undergoing aortic root surgery by a consistent, high-volume team.

Cardiovascular Management of Adults with Marfan Syndrome.

Marfan syndrome (MFS) is a disease in which connective tissue becomes weak secondary to fibrillin-1 mutations, resulting in aortic dilatation, aneurysm formation, aortic dissection, aortic regurgitation and mitral valve prolapse. This autosomal dominantly inherited condition, which was first reported in 1895 and was more fully described in 1931, is characterised by abnormal Fibrillin-1 protein (FBN1) (discovered in 1990), which is encoded by the gene (reported in 1991). In the 1970s, the life expectancy of people with MFS was 40-50 years, mainly due to increased risk of aortic dissection or heart failure from aortic or mitral regurgitation.

Role of community pharmacists in the use of antipsychotics for behavioural and psychological symptoms of dementia (BPSD): a qualitative study.

Objective: This study aimed to use qualitative methodology to understand the current role of community pharmacists in limiting the use of antipsychotics prescribed inappropriately for behavioural and psychological symptoms of dementia.

Design: A qualitative study employing focus groups was conducted. Data were analysed using thematic analysis.

Genetic testing in Marfan syndrome.

Genetic testing is aiding rapid diagnosis of Marfan syndrome as a basis for management of eye, heart and skeletal disease. The affected patient's mutation can be used as a basis for prenatal or postnatal diagnosis of offspring. Preimplantation genetic diagnosis, the technique of choice, can ensure an unaffected pregnancy.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

Rationale: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial.

Aortic Disease Presentation and Outcome Associated With ACTA2 Mutations.

Background: ACTA2 mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with ACTA2 mutations.

Methods And Results: Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various ACTA2 mutations.

A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol.

Background: Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS.

Bone-anchored hearing devices in children with unilateral conductive hearing loss: a patient-carer perspective.

Objectives: We sought to determine the outcome of implantation of a bone-anchored hearing device in children with unilateral conductive hearing loss.

Methods: A retrospective case note analysis was used in a tertiary referral pediatric hospital to study 17 consecutive cases of pediatric patients with unilateral conductive hearing loss who were fitted with a bone-anchored hearing device between 2005 and 2010.

Results: The average age of the patients at the time of bone-anchored hearing device fitting was 10 years 6 months (range, 6 years 3 months to 16 years).

A variant in LDLR is associated with abdominal aortic aneurysm.

Background: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance.