Faculty Bibliography

Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures.

BACKGROUND:Language barriers can influence the quality of health care and health outcomes of limited English proficient patients with cancer. The use of medical interpretation services can be a valuable asset for improving communications in emergency care settings. OBJECTIVE:To evaluate whether a mobile translation application increased call frequency to interpreter services among providers in an Urgent Care Center at a comprehensive cancer center and to assess provider satisfaction of the mobile application. RESEARCH DESIGN/METHODS:Prospective pre-post nonrandomized intervention of a mobile translation application with access to an over the phone interpreter (OPI) service at the push of a button and poststudy satisfaction survey. SUBJECTS/METHODS:Sixty-five clinicians working at the Urgent Care Center in a cancer center in New York City. MEASURES/METHODS:Mean call frequency to OPI services, tested by the nonparametric Wilcoxon Mann Whitney test, and self-reported provider satisfaction descriptives. RESULTS:The mobile application contributed to increasing the frequency of phone calls to OPI services during the intervention period (mean=12.8; P=0.001) as compared with the preintervention period (mean=4.3), and showed continued use during the postintervention period (mean=5.7). Most clinicians were satisfied with the use of the mobile application and access to the OPI services. CONCLUSIONS:The results suggest that mobile application tools contribute to increasing the use and ease of access to language services. This has the potential to improve the quality of communication between medical providers and limited English proficient patients in the delivery of cancer care in urgent care settings.

RATIONALE, AIMS, AND OBJECTIVES/UNASSIGNED:There are well-documented barriers that have limited widespread, sustained adoption of screening and brief intervention for risky substance use in health care settings. In order to better inform implementation efforts, this study evaluates whether patient characteristics, screening results, and implementation success indicators differed between two clinical setting types: primary care and emergency. METHODS:Patients presenting to an emergency or primary care setting were screened for risky substance use (n = 41 567). Patients with a positive screen were further assessed for psychosocial, health, and substance use problems (n = 1604). Differences in patient characteristics between primary care and emergency settings were examined using chi-square and t tests. Multilevel logistic regression was used to examine whether setting type predicted screening results. Site-level indicators of implementation success were calculated (percentage prescreens completed, percentage full screens completed, and percentage refused services) for all patient visits (n = 78 656). RESULTS:As compared with primary care patients, emergency patients had more severe substance use patterns and screening scores, were more likely to use a variety of illicit drugs, and reported more psychosocial issues. In logistic regression models, setting type did not predict whether patients screened positive; however, it did predict screening into a higher vs lower risk category such that emergency patients were more likely to be in a higher risk category. Emergency settings had lower indicators of implementation success (eg, 14% lower prescreen completion rate) as compared with primary care settings on some implementation measures. CONCLUSIONS:This evaluation found important differences in patient characteristics and screening and implementation results between primary care and emergency settings. Health care organizations and administrators implementing screening and brief intervention should attend to setting differences that could affect implementation and clinical care.

Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.

In the original paper, we used the variable "URBRUR08," from the 2008 survey wave as a measure of childhood urbanicity. Upon further investigation we realized that this variable actually measured Beale urban-rural code during the respondent's adulthood.  Thus, we reran our analysis of the pseudo-heritability of childhood urbanicity using the variable. The original results hold such that even with the first 20 principal components held constant, childhood urban-rural status appears to be ~20% "heritable" in GREML models-a figure that is actually higher than the original estimate reported in the paper (14% controlling for 25 PCs, 15% controlling for 10 PCs, and 29% controlling for two PCs). Meanwhile, the heritabilities of the other phenotypes-height, BMI and education-still do not change when they are residualized on childhood urbanicity. In other words, the original results of the paper do not change.

BACKGROUND:Coding of systolic function in heart failure is important but the accuracy is uncertain. METHODS:We used data from chart review of VA heart failure hospitalizations between 2006 and 2013. Trained abstractors determined the documented diagnosis of heart failure and the left ventricular ejection fraction (LVEF). We compared this LVEF to the primary and secondary International Classification of Disease (ICD)-9 codes for heart failure for the same hospitalization. RESULTS:Among 43,044 hospitalizations for heart failure, the primary discharge diagnosis was coded as systolic heart failure in 18%, diastolic heart failure in 17% and other heart failure codes in 65%. For an LVEF less than 40%, a systolic heart failure code had a sensitivity of 29% and a positive predictive value of 76%. The code for systolic heart failure was used more frequently over time with sensitivity increasing from 16% to 37% but at the expense of the positive predictive value which decreased from 80% to 74%. The overall area under the receiver operating curve for the relationship between LVEF and the systolic heart failure code was 0.71. Using a LVEF > 50% to define diastolic heart failure, led to a sensitivity of 29% for a diastolic heart failure code with a positive predictive value of 78%. In multivariate analysis, a systolic heart failure code had an odds ratio for 1-year mortality of 1.1 (95% CI 1.03-1.17) compared to not having a systolic heart failure code. CONCLUSION/CONCLUSIONS:Coding for systolic and diastolic heart failure is associated with LVEF but the accuracy is too poor to substitute for the documented LVEF in performance measurement.

BACKGROUND AND PURPOSE/OBJECTIVE:Cardiac biomarkers may help identify stroke mechanisms and may aid in improving stroke prevention strategies. There is limited data on the association between these biomarkers and acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We hypothesized that cardiac biomarkers (cardiac troponin and left atrial diameter [LAD]) would be associated with the presence of LVO. METHODS:Data were abstracted from a single center prospective AIS database over 18 months and included all patients with AIS with CT angiography of the head and neck. The presence of LVO was defined as proximal LVO of the internal carotid artery terminus, middle cerebral artery (M1 or proximal M2), or basilar artery. Univariate analyses and predefined multivariable models were performed to determine the association between cardiac biomarkers (positive troponin [troponin ≥0.1 ng/mL] and LAD on transthoracic echocardiogram) and LVO adjusting for demographic factors (age and sex), risk factors (hypertension, diabetes, hyperlipidemia, history of stroke, congestive heart failure, coronary heart disease, and smoking), and atrial fibrillation (AF). RESULTS:We identified 1234 patients admitted with AIS; 886 patients (71.8%) had vascular imaging to detect LVO. Of those with imaging available, 374 patients (42.2%) had LVO and 207 patients (23.4%) underwent thrombectomy. There was an association between positive troponin and LVO after adjusting for age, sex and other risk factors (adjusted OR 1.69 [1.08-2.63], P = .022) and this association persisted after including AF in the model (adjusted OR 1.60 [1.02-2.53], P = 0.043). There was an association between LAD and LVO after adjusting for age, sex, and risk factors (adjusted OR per mm 1.03 [1.01-1.05], P = 0.013) but this association was not present when AF was added to the model (adjusted OR 1.01 [0.99-1.04], P = .346). Sensitivity analyses using thrombectomy as an outcome yielded similar findings. CONCLUSIONS:Cardiac biomarkers, particularly serum troponin levels, are associated with acute LVO in patients with ischemic stroke. Prospective studies are ongoing to confirm this association and to test whether anticoagulation reduces the risk of recurrent embolism in this patient population.