Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigated whether select urine kidney injury biomarkers were associated with higher risk of heart failure (HF), CVD, and death in persons with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:) all-cause death. RESULTS:d-glucosaminidase/Cr was associated with HF in continuous analyses (aHR per log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atherosclerotic CVD events (aHR per log SD higher 1.21 [95% confidence interval, 1.02 to 1.41]), whereas both KIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinase-associated lipocalin/Cr (quintile 5 versus quintile 1 aHR of 1.82 [95% confidence interval, 1.19 to 2.8]) were associated with all-cause death. CONCLUSIONS:Selected urine kidney injury biomarkers were independently associated with higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Cr was associated with each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.

: Research suggests that language predicts executive function (EF) in the preschool period; however, the relation between language and EF in the transition to formal schooling has not been previously examined. Given that language and EF are both important for school readiness, it is valuable to examine the ways in which they may be interrelated during the start of formal schooling. Research and theory suggest that expressive language in particular may be bidirectionally related to EF. To test this hypothesis, we analysed data from five- and six-year-old children (N = 347) who completed measures of expressive vocabulary and EF in the fall and spring of kindergarten and the fall of first grade. Path analysis revealed significant cross-lagged paths between EF and expressive vocabulary in kindergarten and from kindergarten into first grade, above and beyond stability in these constructs. The findings are discussed in relation to the current understanding of the relation between language and EF and the best ways in which to support and promote school readiness and early school achievement.

Importance: A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. Objective: To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. Design, Setting, and Participants: The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). Main Outcomes and Measures: Association of pupillary response characteristics with alterations in retinal architecture. Results: Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). Conclusions and Relevance: In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

Purpose of Review Advances in medical therapy have resulted in a growing population of older adults with advanced heart failure. Frailty is a clinical syndrome that increases in prevalence with age and is highly prevalent in patients with heart failure. This paper reviews the complex relationship between frailty and advanced systolic heart failure in older adults, including the potential for reversal of frailty following advanced cardiac interventions. Recent Findings Frailty is predictive of adverse outcomes, including rehospitalization and mortality, in heart failure patients. Several small studies have shown that mechanical circulatory support can modify, and possibly reverse, functional impairments and the pathophysiologic changes associated with heart failure-related frailty. Summary Frailty is highly prevalent in patients with advanced heart failure and is a powerful prognostic marker. Routine frailty assessment could allow clinicians to define optimal patient-centered care strategies for older adult patients with advanced heart failure.