Angiopoietin-1 Knockout Mice as a Genetic Model of Open-Angle Glaucoma.

Purpose: A leading cause of blindness worldwide, glaucoma is often caused by elevated intraocular pressure (IOP) due to impaired aqueous humor outflow from the anterior chamber through Schlemm's canal (SC) and the trabecular meshwork. Despite the large clinical burden, glaucoma research and drug development are hindered by a limited selection of preclinical models that accurately recapitulate human disease. Here, we propose that Angpt1 conditional knockout mice may provide one such model. Angiopoietin/TEK (ANGPT/TEK) signaling is crucial for SC formation and integrity in mice and humans, and mice lacking TEK or its ligand ANGPT1 develop a hypomorphic SC insufficient for normal aqueous humor outflow. Methods: We used a comprehensive histology and physiology approach to characterize the glaucoma phenotype of Angpt1 inducible knockout mice, especially focusing on retina morphology and function. Results: Angpt1 deletion resulted in persistent ocular hypertension beginning in the first month after birth and leading to decreased visual acuity with age due to glaucomatous neuropathy. In the neural retina, we identified marked and specific loss of the retinal ganglion cells, whereas other retinal neurons exhibited largely normal morphology and patterning. Electroretinogram recordings demonstrated reduced scotopic threshold response, further indicating loss of retinal ganglion cell function. Conclusions: These findings highlight the potential of Angpt1 conditional knockout mice as a valuable new glaucoma model. Translational Relevance: Currently, few reliable, rapid-onset genetic glaucoma models are available, and Angpt1 knockout mice will provide an additional tool for studies of IOP-induced neural damage, mechanisms of disease progression, and novel treatment strategies.

Treatment Gap in Primary Prevention Patients Presenting With Acute Coronary Syndrome.

Previous studies assessing healthcare provider compliance to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines indicate a significant underuse of statin therapy at appropriate intensity. However, data are limited in primary prevention patients. Our study aimed to evaluate the impact of the 2013 ACC/AHA guidelines through a retrospective analysis of primary prevention patients presenting with first time acute coronary syndrome (ACS). We retrospectively calculated the 10-year predicted Atherosclerotic Cardiovascular Disease (10yASCVD) risk in 1,265 patients ages 40 to 75 who presented with ACS and no previous ASCVD. In patients without known ambulatory systolic blood pressure, a multivariable linear regression model was used to predict outpatient systolic blood pressure. Outcomes analyzed in each 10yASCVD category included statin status and statin intensity (high/medium/low) with further categorization by type of ACS event and date of left heart catheterization. In both primary analysis and sensitivity analysis (patients with predicted systolic blood pressure), statistical significance was shown with respect to overall statin status, ST Elevation Myocardial Infarction, and date of left heart catheterization. In summary, retrospective calculation of 10yASCVD in patients with a first ACS event showed a significant number of ACS patients would have qualified for statin therapy per 2013 ACC/AHA guidelines before their event but had not been initiated on one.

Prospective respiratory triggering improves high-resolution brachial plexus MRI quality.

BACKGROUND: Oblique sagittal MRI sequences, orthogonal to the longitudinal axis of the brachial plexus, can reliably depict morphologic and signal abnormalities. However, nerve visualization may be obscured by ghosting artifact from periodic respiratory motion. Respiratory triggering (RT) with a thoracoabdominal bellows can reduce ghosting artifact, but it is not routinely used for brachial plexus MRI. Furthermore, the efficacy of prospective RT for brachial plexus imaging has not yet been reported. PURPOSE: To compare brachial plexus MRI sequences acquired with and without respiratory triggering. STUDY TYPE: Prospective. SUBJECTS: Five volunteers and 20 patients were included. Each subject was imaged with and without RT during the same session. FIELD STRENGTH/SEQUENCE: Proton density or T2 -weighted Dixon fat suppressed sequences were obtained at 3.0T using receive-only 16-channel flexible array coils. ASSESSMENT: Three musculoskeletal radiologists blindly evaluated each sequence using subjective scoring criteria for ghosting artifact, nerve conspicuity, and diagnostic confidence. Nerve conspicuity scores at three distinct plexus levels were summed to calculate an overall image quality score. STATISTICAL TESTS: Marginal proportional odds logistic regression models were used to compare all scores between RT and non-RT. Gwet's agreement coefficient was used to assess interobserver and intraobserver reliability. RESULTS: Mean scan time per sequence increased from 4:25 minutes (95% confidence interval [CI], 4:02-4:49 min) with non-RT to 6:09 minutes (95% CI, 5:42-6:35 min) with RT. RT reduced ghosting artifact (odds ratio [OR] = 0.21, 95% CI: 0.09-0.46, P < 0.001), improved overall image quality (OR = 4.88, 95% CI: 2.18-10.95, P < 0.001), and increased diagnostic confidence (OR = 3.72, 95% CI: 1.61-8.63, P = 0.002) for all readers. Interobserver agreement for ghosting artifact and image quality was substantial to almost perfect (AC2 = 0.74-0.85). Interobserver agreement for all other scores was moderate to almost perfect (AC2 = 0.61-0.82). Intraobserver agreement was substantial to almost perfect for all parameters (AC2 = 0.76-1.0). DATA CONCLUSION: Prospective RT with bellows can effectively minimize ghosting artifact and improve image quality for brachial plexus MRI within clinically optimal acquisition times. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2.