Faculty Bibliography

Creatinine-based glomerular filtration rate estimation (eGFR_cr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFR_cr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFR_cr or eGFR_cys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFR_BTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches.

OBJECTIVE:Severe hypoglycemia is a rare but important complication of type 2 diabetes. Few studies have examined the epidemiology of hypoglycemia in a community-based population. RESEARCH DESIGN AND METHODS:We included 1,206 Atherosclerosis Risk in Communities (ARIC) Study participants with diagnosed diabetes (baseline: 1996-1998). Severe hypoglycemic events were identified through 2013 by ICD-9 codes from claims for hospitalizations, emergency department visits, and ambulance use. We used Cox regression to evaluate risk factors for severe hypoglycemia. RESULTS:score: HR 1.57; 95% CI 1.33-1.84). In an analysis of nontraditional risk factors, low 1,5-anhydroglucitol, difficulty with activities of daily living, Medicaid insurance, and antidepressant use were positively associated with severe hypoglycemia after multivariate adjustment. CONCLUSIONS:Poor glycemic control, glycemic variability as captured by 1,5-anhydroglucitol, kidney damage, and measures of cognitive and functional impairments were strongly associated with increased risk of severe hypoglycemia. These factors should be considered in hypoglycemia risk assessments when individualizing diabetes care for older adults.

Little is known about oncology provider recommendations regarding best practices in contraception use during cancer treatment and through survivorship for adolescent and young adult (AYA) cancer patients. This review examined the literature to identify related studies on contraception recommendations, counseling discussions, and methods of contraception in the AYA oncology population. A literature review was conducted using PubMed, including all peer-reviewed journals with no publication date exclusions. A systematic review of the literature was conducted using combinations of the following phrases or keywords: "oncology OR cancer" AND "contraception, family planning, contraceptive devices, contraceptive agents, intrauterine devices OR IUD, vaccines, spermatocidal agents, postcoital, immunologic, family planning, vasectomy, tubal ligation, sterilization" AND "young adult OR adolescent" AND "young adult AND adolescent". Reviewers assessed articles using the "Quality Assessment Tool for Quantitative Studies" which considers: (1) selection bias; (2) study design; (3) confounders; (4) blinding; (5) data collection methods; and (6) withdrawals and dropouts. A total of five articles were included and all studies were quantitative. Results showed no consistent recommendations among providers, references to guidelines, or methods of contraceptive types. Provider guidelines for discussions with AYA patients should be expanded to provide comprehensive, consistent, and quality cancer care in the AYA population.

Optimism and cynical hostility are associated with health behaviors and health outcomes, including morbidity and mortality. This analysis assesses their association with longitudinal vigorous physical activity (PA) in postmenopausal women of the Women's Health Initiative (WHI). Subjects include 73,485 women nationwide without history of cancer or cardiovascular disease (CVD), and no missing baseline optimism, cynical hostility, or PA data. The Life Orientation Test-Revised Scale measured optimism. A Cook Medley questionnaire subscale measured cynical hostility. Scale scores were divided into quartiles. Vigorous PA three times or more per week was assessed via self-report at study baseline (1994-1998) and through follow-up year 6. Descriptive analysis mapped lifetime trajectories of vigorous PA (recalled at ages 18, 25, 50; prospectively assessed at baseline, and 3 and 6 years later). Hierarchical generalized linear mixed models examined the prospective association between optimism, cynical hostility, and vigorous PA over 6 years. Models adjusted for baseline sociodemographic variables, psychosocial characteristics, and health conditions and behaviors. Vigorous PA rates were highest for most optimistic women, but fell for all women by approximately 60% between age 50 and study baseline. In adjusted models from baseline through year 6, most vs. least optimistic women were 15% more likely to exercise vigorously (p < 0.001). Cynical hostility was not associated with lower odds of longitudinal vigorous PA after adjustment. Results did not differ by race/ethnicity or socioeconomic status. Higher optimism is associated with maintaining vigorous PA over time in post-menopausal women, and may protect women's health over the lifespan.

Research investigating facilitators of survivorship care among underserved breast cancer survivors (BCS) is sparse. This study aimed to explore facilitators of survivorship care among underserved BCS within the first 5 years following chemotherapy, radiation, or surgery for breast cancer. In-depth interviews were conducted, using a semi-structured interview guide, with underserved BCS exploring survivorship care experiences. Content analysis of the verbatim transcripts was applied, and results were summarized according to themes related to facilitators of breast cancer survivorship care. Interviews were conducted with 25 BCS. Eight main themes were identified: coordination of care; positive perceptions of health care providers; communication between patient and health care providers; financial and insurance facilitators; information, classes, and programs provided; assistance provided by organizations and health care professionals; transportation facilitators; and job flexibility. This study provides a comprehensive look at facilitators of survivorship care among underserved BCS. BCS endorsed several facilitators of their survivorship care, mainly at the interpersonal, organizational, and societal level. This study adds to the research literature on catalysts of care among underserved BCS. Results from this study are currently being used to inform a patient navigation intervention to facilitate care among this population.

Inhalation of ozone (O₃), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O₃ Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O₃-induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O₃, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O₃ To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl-β-methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O₃ In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O₃ increased BALF chemerin in mice of both genotypes, yet following O₃ exposure, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O₃ increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O₃ exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O₃-induced lung pathology.

BACKGROUND: Animals exposed to anesthetics during specific age periods of brain development experience neurotoxicity, with neurodevelopmental changes subsequently observed during adulthood. The corresponding vulnerable age in children, however, is unknown. METHODS: An observational cohort study was performed using a longitudinal dataset constructed by linking individual-level Medicaid claims from Texas and New York from 1999 to 2010. This dataset was evaluated to determine whether the timing of exposure to anesthesia 28 days and 6 months and 1 year old and