Cardiovascular magnetic resonance of pulmonary artery growth and ventricular function after Norwood procedure with Sano modification

For hypoplastic left heart syndrome (HLHS), there have been concerns regarding pulmonary artery growth and ventricular dysfunction after first stage surgery consisting of the Norwood procedure modified with a right ventricle-to-pulmonary artery conduit. We report our experience using cardiovascular magnetic resonance (CMR) to determine and follow pulmonary arterial growth and ventricular function in this cohort

Reference intervals for the echocardiographic measurements of the right heart in children and adolescents: a systematic review

BACKGROUND: Transthoracic echocardiography is the primary imaging modality for the diagnosis of right ventricular (RV) involvement in congenital and acquired heart diseases. There is increasing recognition of the contribution of RV dysfunction in heart diseases affecting children and adolescents, but there is insufficient information on reference intervals for the echocardiographic measurements of the right heart in children and adolescents that represent all the continental populations of the world.OBJECTIVE:The aim of this systematic review was to collate, from published studies, normative data for echocardiographic evaluation of the right heart in children and adolescents, and to identify gaps in knowledge in this field especially with respect to sub-Saharan Africans. METHODS: We performed a systematic literature search to identify studies of reference intervals for right heart measurements as determined by transthoracic echocardiography in healthy children and adolescents of school-going age. Articles were retrieved from electronic databases with a combination of search terms from the earliest date available until May 2013. RESULTS: Reference data were available for a broad range of variables. Fifty one studies out of 3096 publications were included. The sample sizes of the reference populations ranged from 13 to 2036 with ages varying from 5 to 21 years. We identified areas lacking sufficient reference data. These included reference data for determining right atrial size, tricuspid valve area, RV dimensions and areas, the RV % fractional area change, pulmonary artery pressure gradients and the right-sided haemodynamics, including the inferior vena cava dimensions and collapsibility. There were no data for sub-Saharan African children and adolescents. CONCLUSION: Reliable reference data are lacking for important echocardiographic measurements of the RV in children and adolescents, especially for sub-Saharan Africans

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

Examining the Estrogen Receptor as a Targetable Vulnerability at All Stages of ER+ Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women, second in lethality to lung cancer. Approximately 70% of breast cancer tumors express estrogen receptor (ER), and therefore are considered ER positive (ER+). These cases are treated with endocrine therapy, targeted therapy specific to ER through inhibition of estrogen synthesis or direct interaction with ER, halting proliferative signaling. While effective at reducing breast cancer tumors and preventing progression, up to 50% of patients develop resistance to this treatment. A majority of returning tumors maintain ER expression, thereby responding to other classes of endocrine therapy. This thesis focuses on the development of novel endocrine therapies and their efficacy in a variety of endocrine therapy-resistant breast cancer cell models alone or in combination. The novel therapies include orally bioavailable selective ER degraders (SERDs) and selective human ER partial agonists (ShERPAs), both effective in resistance to selective ER modulator (SERM)-resistant breast cancer cell lines. ShERPAs also reduce viability of a SERD-resistant cell line. In addition to novel therapies, resistance within the breast cancer cell models was characterized, probing for vulnerabilities to be targeted with combination therapy. Enriched survival and proliferative pathways were investigated in an ER+ cell line resistant to all clinical endocrine therapies but sensitive to ShERPAs. Combination therapy to target these pathways was then explored with the ShERPA for improved antiproliferative activity. Combinations with the orally bioavailable SERD were also investigated for antiproliferative activity in the SERM-resistant cell lines. This thesis demonstrates the vulnerabilities of ER within endocrine therapy-resistant breast cancer and optimization of targeting these vulnerabilities

New insights in glaciers characterization by differential diagnosis integrating GPR and remote sensing techniques: A case study for the Eastern Gran Zebr\uf9 glacier (Central Alps)

In GPR profiles, ice is usually imaged as a mostly electromagnetic transparent facies. However, diffraction events, as well as internal layering, can be also observed. In some cases, the bedrock below glaciers is masked by dense diffractions usually interpreted as the effect of liquid water pockets inside the so-called warm ice. However, the actual physical meaning of such GPR facies is not always obvious, because it can be related also to mixed debris and ice deposits. We adopted a strategy well known in medical sciences and referred as \u201cdifferential diagnosis\u201d in order to infer which is the actual meaning of a high scattering facies imaged within the Eastern Gran Zebr\uf9 glacier (Central Italian Alps) and, more generally, of all the internal glacier features. In fact, in many cases, there is no direct information to limit the subjectivity of geophysical interpretation; therefore, we provide all the discriminative hypotheses based on both independent and integrated criteria including GPR attribute analysis, imaging effects, reflection analysis, GPR frequency evaluations combined with geomorphological and remote sensing data obtained by two photogrammetric UAV and thermal infrared surveys. On the basis of the differential diagnosis, we concluded that the high scattering zone embedded within the studied glacier is most likely related to a mixture of ice and debris probably formed during a past shrinking phase. Beside this case study, this approach could be helpful in other GPR glaciological surveys, in which the target is related not only to the bedrock detection, but also to a detailed analysis of the internal facies of a glacier