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Aim To determine the variability in CT measurements of proximal thoracic aortic diameters obtained using double-oblique short axis and semiautomatic centerline analysis techniques. Institutional review board approval, with waiver of informed consent, was obtained for this HIPAA-compliant, retrospective study. Cardiac gated thoracic aortic CT scans were evaluated in 25 patients. Maximum aortic diameter measurements at the annulus, sinuses, sinotubular junction and ascending aorta were generated using double-oblique short axis and semiautomatic centerline analysis techniques. Intraobserver and interobserver variability and variability between techniques were assessed using the Wilcoxon signed rank test, Spearman’s correlation coefficients and Bland-Altman plots. Mean intraobserver diameter differences using double oblique views ranged from −0.3 to 0.6 mm. The 95 % confidence interval for difference in diameters was ±2.4 to ±5.1 mm for radiologist #1 and ±2.6 to ±5.2 mm for radiologist #2, depending on location. Mean intraobserver diameter differences using centerline analysis ranged from 0.2 to 2.3 mm, and the 95 % confidence interval for difference in diameters was ±2.0 to ±4.6 mm, depending on location. Significant interobserver differences were seen for both double oblique views and centerline analysis. Measurements obtained using the two methods were strongly correlated (r = 0.81–0.99), although they were consistently larger using centerline analysis (95 % confidence interval, ±1.8 to ±3.2 mm). Although measurement variability of the proximal thoracic aorta was generally low using double oblique and centerline analysis techniques, differences of up to approximately 5 mm in diameter occurred within the 95 % confidence interval. Neither technique was clearly more reliable than the other.

Thoracic aortic enlargement is an increasingly recognized condition that is often diagnosed on imaging studies performed for unrelated indications. The risk of unrecognized and untreated aortic enlargement and aneurysm includes aortic rupture and dissection which carry a high burden of morbidity and mortality. The etiologies underlying thoracic aortic enlargement are diverse and can range from degenerative or hypertension associated aortic enlargement to more rare genetic disorders. Therefore, the evaluation and management of these patients can be complex and requires knowledge of the pathophysiology associated with thoracic aortic dilation and aneurysm. Additionally, there have been important advances in the treatment available to patients with thoracic aortic disease, including an increased role of endovascular therapy. Given the risk of mortality, increased clinical recognition and advances in therapeutics, the American College of Cardiology, American Heart Association and related professional societies have recently published guidelines on the management of thoracic aortic disease. This review focuses on the pathophysiology and various etiologies that lead to thoracic aortic aneurysm along with the diagnostic modalities and management of asymptomatic patients with thoracic aortic disease.

Gastroesophageal reflux disease (GERD) is frequently managed by primary-care physicians (PCPs) although little is known about their current practices and management patterns. We administered a questionnaire-based survey to PCPs attending sponsored educational conferences on GERD. Questionnaires were completed anonymously before the conferences and asked about prescribing patterns, indications for surgical referral, and issues concerning Barrett's esophagus and H. pylori infection. A total of 1046 completed questionnaires (97% acceptance rate) were received. Most PCPs prescribed a proton pump inhibitor (PPI) for GERD without prior authorization and without first using an H2-receptor antagonist (H2RA). Many gave an H2RA with once-daily PPI treatment for patients with nocturnal heartburn. Most referrals for anti-reflux surgery were for inadequate response to medical treatment, although PCPs usually first sought gastroenterological consultation. There was a widespread acceptance of screening GERD patients for Barrett's esophagus. There was general confusion about any relationship between H. pylori infection and GERD; 80% of PCPs tested for the infection in at least some patients who only had symptoms of GERD. Our survey has identified a number of areas of controversy and confusion related to the management of GERD. We hope that our findings can assist in the development of educational materials on GERD for PCPs.

Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4 . GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development. Bicuspid aortic valve (BAV) is the most common human congenital cardiovascular malformation. Here, the authors perform a genome-wide association study for BAV and identify risk variants in the gene region of cardiac-specific transcription factor GATA4 and implicate GATA4 in heart valve development.

Dinaciclib is a potent CDK1, 2, 5 and 9 inhibitor being developed for the treatment of cancer. Additional understanding of antitumor mechanisms and identification of predictive biomarkers are important for its clinical development. Here we demonstrate that while dinaciclib can effectively block cell cycle progression, in vitro and in vivo studies, coupled with mouse and human pharmacokinetics, support a model whereby induction of apoptosis is a main mechanism of dinaciclib's antitumor effect and relevant to the clinical duration of exposure. This was further underscored by kinetics of dinaciclib-induced downregulation of the antiapoptotic BCL2 family member MCL1 and correlation of sensitivity with the MCL1-to-BCL-xL mRNA ratio or MCL1 amplification in solid tumor models in vitro and in vivo. This MCL1-dependent apoptotic mechanism was additionally supported by synergy with the BCL2, BCL-xL and BCL-w inhibitor navitoclax (ABT-263). These results provide the rationale for investigating MCL1 and BCL-xL as predictive biomarkers for dinaciclib antitumor response and testing combinations with BCL2 family member inhibitors.