Faculty Bibliography

PURPOSE/OBJECTIVE:To characterize the in vivo effect of cyclopentolate on the microstructure of Schlemm canal (SC) in healthy eyes. METHODS:For healthy subjects, 81 serial horizontal enhanced depth imaging optical coherence tomography B-scans (interval between scans, ∼35 μm) of the nasal corneoscleral limbal area were obtained before and 1 hour after cyclopentolate 1% administration in 1 eye. The structures of aqueous and blood vessels in each scan were used as landmarks to select 50 overlapping scans between the 2 sets of 81 serial scans (before and after cyclopentolate administration). The SC cross-sectional area was measured in each of the 50 selected scans. After 3-dimensional reconstruction, SC volume was determined. RESULTS:Twelve eyes (12 healthy subjects) were imaged successfully before and after cyclopentolate administration. Mean age was 27.8±4.9 years (range, 25 to 38 y). Following cyclopentolate administration, mean intraocular pressure did not change significantly (13.9±1.5 to 14.2±1.5 mm Hg; P=0.19). Mean SC cross-sectional area decreased by 17%, from 3563±706 to 2959±460 μm (P<0.001). Mean SC volume in the overlapping area (approximately 1.7 mm of circumferential length of SC) decreased from 6,164,061±1,220,787 to 5,119,462±794,763 μm (P<0.001). The decrease in the mean SC cross-sectional area after cyclopentolate administration was greater in eyes with larger baseline SC cross-sectional area (P<0.001, R=0.873). CONCLUSIONS:Cyclopentolate causes a reduction in SC dimensions in healthy eyes. Future studies are warranted to determine the exact mechanism(s) of this change.

A deluge of whole-genome sequencing has begun to give insights into the patterns and processes of microbial evolution, but genome sequences have accrued in a haphazard manner, with biased sampling of natural variation that is driven largely by medical and epidemiological priorities. For instance, there is a strong bias for sequencing epidemic lineages of methicillin-resistant Staphylococcus aureus (MRSA) over sensitive isolates (methicillin-sensitive S. aureus: MSSA). As more diverse genomes are sequenced the emerging picture is of a highly subdivided species with a handful of relatively clonal groups (complexes) that, at any given moment, dominate in particular geographical regions. The establishment of hegemony of particular clones appears to be a dynamic process of successive waves of replacement of the previously dominant clone. Here we review the phylogenomic structure of a diverse range of S. aureus, including both MRSA and MSSA. We consider the utility of the concept of the 'core' genome and the impact of recombination and horizontal transfer. We argue that whole-genome surveillance of S. aureus populations could lead to better forecasting of antibiotic resistance and virulence of emerging clones, and a better understanding of the elusive biological factors that determine repeated strain replacement.

BACKGROUND: An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. METHODS: We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. RESULTS: Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and non-aortic stenosis controls (n=224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n=24) of aortic stenosis subjects compared with 12.5% (n=28) of controls (unadjusted OR 1.90, 95% CI 1.05-3.48, p=0.038). Multivariate analysis retained significance only for gout (adjusted OR 2.08, 95% CI 1.00-4.32, p=0.049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 +/- 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 +/- 1.8 vs. 75.8 +/- 1.0 years old, p=0.16). CONCLUSIONS: Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications.

OBJECTIVE: To critically evaluate the efficacy of renin angiotensin system inhibitors (RASi) in patients with coronary artery disease without heart failure, compared with active controls or placebo. DESIGN: Meta-analysis of randomized trials. DATA SOURCES: PubMed, EMBASE, and CENTRAL databases until 1 May 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized trials of RASi versus placebo or active controls in patients with stable coronary artery disease without heart failure (defined as left ventricular ejection fraction >/=40% or without clinical heart failure). Each trial had to enroll at least 100 patients with coronary artery disease without heart failure, with at least one year's follow-up. Studies were excluded if they were redacted or compared use of angiotensin converting enzyme inhibitors with angiotensin receptor blockers. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, incident diabetes, and drug withdrawal due to adverse effects. RESULTS: 24 trials with 198 275 patient years of follow-up were included. RASi reduced the risk of all cause mortality (rate ratio 0.84, 95% confidence interval 0.72 to 0.98), cardiovascular mortality (0.74, 0.59 to 0.94), myocardial infarction (0.82, 0.76 to 0.88), stroke (0.79, 0.70 to 0.89), angina, heart failure, and revascularization when compared with placebo but not when compared with active controls (all cause mortality, 1.05, 0.94 to 1.17; Pinteraction=0.006; cardiovascular mortality, 1.08, 0.93 to 1.25, Pinteraction<0.001; myocardial infarction, 0.99, 0.87 to 1.12, Pinteraction=0.01; stroke, 1.10, 0.93 to 1.31; Pinteraction=0.002). Bayesian meta-regression analysis showed that the effect of RASi when compared with placebo on all cause mortality and cardiovascular mortality was dependent on the control event rate, such that RASi was only beneficial in trials with high control event rates (>14.10 deaths and >7.65 cardiovascular deaths per 1000 patient years) but not in those with low control event rates. CONCLUSIONS: In patients with stable coronary artery disease without heart failure, RASi reduced cardiovascular events and death only when compared with placebo but not when compared with active controls. Even among placebo controlled trials in this study, the benefit of RASi was mainly seen in trials with higher control event rates but not in those with lower control event rates. Evidence does not support a preferred status of RASi over other active controls.