Faculty Bibliography

Introduction The NYU Lung Cancer Biomarker Center recruited 1054 smokers (<=20 pack-years) between 03/2000 and 06/2010 and screened them with CT-scans and respiratory questionnaires. Questionnaires contained demographic characteristics, occupational exposures, lifestyle information including smoking history and alcohol use, personal and family medical history, and pulmonary symptoms. CT-scans showed the disease status and emphysema. We hypothesized that information collected in the questionnaires would be associated with the subject's disease status. Methods The 1054 Subjects were classified into 4 groups based on the results of enrollment CT-scans. This categorization showed 331 subjects with solid nodule(s) only, 95 with ground glass opacity (GGO) only, 126 with both solid nodule(s) and GGO(s), and the remaining 502 subjects with no nodules. Chi-squared tests were used to assess the relationship between disease category and each single predictor. Polytomous logistic regression was used to assess the association between disease category and multiple predictors. Forward/backward stepwise regression was used in model selection. Results Univariate analysis showed that gender (CMH =8.7092, p-value=0.0032), age (CMH=29.2219, p-value<0.0001), marijuana smoking (CMH=10.9024, p-value=0.0010), emphysema (CMH=9.0929, p-value=0.0026) and years of smoking (CMH=15.4712, p-value<0.0001) were significantly associated with disease categories. Further tests showed that years of smoking was highly associated with age, and did not contribute to prediction of disease category when age was included in the model, as shown by our multivariate analysis. In multivariate analysis, increasing age, gender (male) and history of emphysema were significant predictors of worsening disease class. Moreover, when we stratified by gender, the analysis indicated that in males, older men were more likely to develop solid nodules (OR=1.275, 95% CI [1.0063, 1.0490]) and more likely to have mixed nodules (OR= 1.0664, 95% CI= [1.0331, 1.1008]) than younger men. Males with emphysema were far more likely to have solid nodules compared with those without emphysema (OR= 1.9678, 95% CI= [1.3128, 2.9495]). Our analysis also revealed that in females, age was the only significant risk factor: older women were more likely to have mixed nodules than younger women (OR= 1.0593, 95% CI= [1.0274, 1.0922]). It is notable that all smoking related variables were not significantly associated with nodule class in our multivariable analysis. Conclusion Our analysis suggests that age, gender and emphysema play a critical role in the development of disease (solid nodule or GGO). Also, our analysis has shown that smoking is not likely to play a major role in the development of the disease in this high risk cohort

Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t) ), perfusion fraction (f(p) ), and pseudodiffusivity (D(p) ). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (+/-standard deviation) values (2.44 +/- 0.30 vs. 1.34 +/- 0.39 mum(2) /msec, P < 0.01) and D(t) (2.36 +/- 0.38 vs. 1.15 +/- 0.35 mum(2) /msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 +/- 5.0% vs. 6.9 +/- 2.9%, P = 0.06), but less so with D(t) (1.14 +/- 0.32 mum(2) /msec vs. 1.18 +/- 0.52 mum(2) /msec, P = 0.88) and D(p) (14.9 +/- 11.4 mum(2) /msec vs. 16.1 +/- 5.7 mum(2) /msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc

Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme degrading the extracellular matrix and overexpressed by many tumors. Here, we documented the presence of MMP-2-specific CD4(+) T cells in tumor-infiltrating lymphocytes (TILs) from melanoma patients. Strikingly, MMP-2-specific CD4(+) T cells displayed an inflammatory T(H)2 profile, i.e., mainly secreting TNF-alpha, IL-4, and IL-13 and expressing GATA-3. Furthermore, MMP-2-conditioned dendritic cells (DCs) primed naive CD4(+) T cells to differentiate into an inflammatory T(H)2 phenotype through OX40L expression and inhibition of IL-12p70 production. MMP-2 degrades the type I IFN receptor, thereby preventing STAT1 phosphorylation, which is necessary for IL-12p35 production. Active MMP-2, therefore, acts as an endogenous type 2 'conditioner' and may play a role in the observed prevalence of detrimental type 2 responses in melanoma

BACKGROUND: There are little data on the appropriate endpoint for slow pathway ablation that balances acceptable procedural times, recurrence rates, and complication rates. This study compared recurrence rates of three commonly utilized endpoints of slow pathway ablation for atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: We performed a meta-analysis of AVNRT slow pathway ablation cohorts by searching electronic databases, the Internet, and conference proceedings. Inclusion criteria were age >18 years, >20 human subjects per study, primary AVNRT ablation, English language publication, and >1 month of follow-up. Data were analyzed with a fixed-effects model using Comprehensive Meta-Analysis software version 2.2.046 (Biostat, Englewood, NJ, USA). RESULTS: We included 10 studies encompassing 1,204 patients with a mean age of 41-53 years. Endpoints were complete slow pathway ablation, residual jump only, and single remaining echo beat. Pooled estimates revealed 28 of 641 patients (4.4%) with complete slow pathway ablation, 13 of 192 patients (6.8%) with a residual jump only, and 24 of 371 patients (6.5%) with one echo had recurrences. With uniform isoproterenol use after ablation, there was no significant difference in recurrence rates among the endpoints. However, when isoproterenol was utilized after ablation only if needed to induce AVNRT before ablation, a significantly higher recurrence rate occurred in patients with a residual jump (P = 0.002), a single echo (P = 0.003), or the combined group of a residual jump and/or one echo (P = 0.001). CONCLUSIONS: Isoproterenol should be used routinely after slow pathway modification, when a residual jump and/or single echo remain

OBJECTIVE: Functional ischemic mitral regurgitation is a complication of ventricular remodeling; standard therapy is reduction annuloplasty and coronary artery bypass grafting. Unfortunately, outcomes are retrospective and contradictory. We report a multicenter study that documents the outcomes of reduction annuloplasty for functional ischemic mitral regurgitation. METHODS: Twenty-one centers randomized 75 patients to the coronary artery bypass grafting + reduction annuloplasty subgroup that was the control arm of the Randomized Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve trial. Entry criteria included patients requiring revascularization, patients with severe or symptomatic moderate functional ischemic mitral regurgitation, an ejection fraction 25% or greater, a left ventricular end-diastolic dimension 7.0 cm or less, and more than 30 days since acute myocardial infarction. All echocardiograms were independently scored by a core laboratory. Reduction annuloplasty was achieved by device annuloplasty. Two patients underwent immediate intraoperative conversion to a valve replacement because reduction annuloplasty was unable to correct mitral regurgitation; as-treated results are presented. RESULTS: Thirty-day mortality was 4.1% (3/73). Patients received an average of 2.8 bypass grafts. Mean follow-up was 24.6 months. Mitral regurgitation was reduced from 2.6 +/- 0.8 preoperatively to 0.3 +/- 0.6 at 2 years. Freedom from death or valve reoperation was 78% +/- 5% at 2 years. There was significant improvement in ejection fraction and New York Heart Association class with reduction of left ventricular end-diastolic dimension. Cox regression analyses suggested that increasing age (P = .001; hazard ratio, 1.16 per year; 95% confidence interval, 1.06-1.26) and renal disease (P = .018; hazard ratio, 3.48; 95% confidence interval, 1.25-9.72) were associated with decreased survival. CONCLUSIONS: Coronary artery bypass grafting + reduction annuloplasty for functional ischemic mitral regurgitation predictably reduces mitral regurgitation and relieves symptoms. This treatment of moderate to severe mitral regurgitation is associated with improved indices of ventricular function, improved New York Heart Association class, and excellent freedom from recurrent mitral insufficiency. Although long-term prognosis remains guarded, this multicenter study delineates the intermediate-term benefits of such an approach

OBJECTIVES: We sought to determine whether patients with functional mitral regurgitation (FMR) would benefit from ventricular reshaping by the Coapsys device (Myocor, Inc., Maple Grove, Minnesota). BACKGROUND: FMR occurs when ventricular remodeling impairs valve function. Coapsys is a ventricular shape change device placed without cardiopulmonary bypass to reduce FMR. It compresses the mitral annulus and reshapes the ventricle. We hypothesized that Coapsys for FMR would improve clinical outcomes compared with standard therapies. METHODS: RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) was a randomized, prospective, multicenter study of patients with FMR and coronary disease with core laboratory analysis. After enrollment, patients were stratified to the standard indicated surgery: either coronary artery bypass graft alone or coronary artery bypass graft with mitral valve repair. In each stratum, randomization was to either control (indicated surgery) or treatment (coronary artery bypass graft with Coapsys ventricular reshaping). RESULTS: The study was terminated when the sponsor failed to secure ongoing funding; 165 patients were randomized. Control and Coapsys both produced decreases in left ventricular (LV) end-diastolic dimension and MR at 2 years (p < 0.001); Coapsys provided a greater decrease in LV end-diastolic dimension (p = 0.021). Control had lower MR grades during follow-up (p = 0.01). Coapsys showed a survival advantage compared with control at 2 years (87% vs. 77%) (hazard ratio: 0.421; 95% confidence interval: 0.200 to 0.886; stratified log-rank test; p = 0.038). Complication-free survival (including death, stroke, myocardial infarction, and valve reoperation) was significantly greater with Coapsys at 2 years (85% vs. 71%) (hazard ratio: 0.372; 95% confidence interval: 0.185 to 0.749; adjusted log-rank test; p = 0.019). CONCLUSIONS: Analysis of RESTOR-MV indicates that patients with FMR requiring revascularization treated with ventricular reshaping rather than standard surgery had improved survival and a significant decrease in major adverse outcomes. This trial validates the concept of the ventricular reshaping strategy in this subset of patients with heart failure. (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve [RESTOR-MV]; NCT00120276)

Agents of opportunity (AO) in academic medical centers (AMC) are defined as unregulated or lightly regulated substances used for medical research or patient care that can be used as 'dual purpose' substances by terrorists to inflict damage upon populations. Most of these agents are used routinely throughout AMC either during research or for general clinical practice. To date, the lack of careful regulations for AOs creates uncertain security conditions and increased malicious potential. Using a consensus-based approach, we collected information and opinions from staff working in an AMC and 4 AMC-affiliated hospitals concerning identification of AO, AO attributes, and AMC risk and preparedness, focusing on AO security and dissemination mechanisms and likely hospital response. The goal was to develop a risk profile and framework for AO in the institution. Agents of opportunity in 4 classes were identified and an AO profile was developed, comprising 16 attributes denoting information critical to preparedness for AO misuse. Agents of opportunity found in AMC present a unique and vital gap in public health preparedness. Findings of this project may provide a foundation for a discussion and consensus efforts to determine a nationally accepted risk profile framework for AO. This foundation may further lead to the implementation of appropriate regulatory policies to improve public health preparedness. Agents of opportunity modeling of dissemination properties should be developed to better predict AO risk