Internal Medicine Donald W. Seldin, M.D. Research Symposium 2016

1 Presenter: Donghai Wen Authors: Donghai Wen, Bangchen Wang, Ryan Cornelius, Yang Yuan, Huaqing Li2 Jun Wang-France, and Steven Sansom Title: A Micropuncture Study of the Net K Secretion in the Thick Ascending Limb of Mice on a Low Na High K Diet Abstract: Understanding the effect of a cardioand reno-protective low Na high K diet (LNaHK) on renal K handling is crucial to choosing diuretics and anti-hypertensives for patients on such diets. We previously showed that furosemide, an inhibitor of the Na-K-Cl cotransporter (NKCC2) in the thick ascending limb (TAL), increased urinary K excretion (UKV) in mice on a control diet but decreased UKV in mice on LNaHK. We hypothesized that there is a net K secretion in the TAL of mice on LNaHK. Male C57BL/6 mice were given either a control diet or LNaHK for 7–14 days. Mice were anesthetized and received modified saline (140mM NaCl, 5mM KHCO3, 2% mannitol) intravenously. Free-flow micropuncture was performed using K-selective micro-electrodes to measure the K concentration in the early distal tubule (EDT) before and after intravenous administration of vehicle (60μL 0.9% NaCl) or furosemide (60μL, 2mg/mL). Urine was collected via a bladder catheter. Urine Na concentration was measured by a flame photometer. Within 10 minutes of administration, furosemide increased [K] in the EDT of mice on a control diet (Δ = 1.88 ± 0.45 mM; N = 3) but decreased that of mice on LNaHK (Δ = -3.52 ± 0.85 mM; N = 4). Vehicle did not affect [K] in the EDT of mice on either diet. The increase in urinary Na excretion after furosemide was much greater in mice on LNaHK. These results indicate that there is a net K secretion in TAL of mice on LNaHK, and it is associated with increased NKCC2 activity. Understanding the effect of a cardioand reno-protective low Na high K diet (LNaHK) on renal K handling is crucial to choosing diuretics and anti-hypertensives for patients on such diets. We previously showed that furosemide, an inhibitor of the Na-K-Cl cotransporter (NKCC2) in the thick ascending limb (TAL), increased urinary K excretion (UKV) in mice on a control diet but decreased UKV in mice on LNaHK. We hypothesized that there is a net K secretion in the TAL of mice on LNaHK. Male C57BL/6 mice were given either a control diet or LNaHK for 7–14 days. Mice were anesthetized and received modified saline (140mM NaCl, 5mM KHCO3, 2% mannitol) intravenously. Free-flow micropuncture was performed using K-selective micro-electrodes to measure the K concentration in the early distal tubule (EDT) before and after intravenous administration of vehicle (60μL 0.9% NaCl) or furosemide (60μL, 2mg/mL). Urine was collected via a bladder catheter. Urine Na concentration was measured by a flame photometer. Within 10 minutes of administration, furosemide increased [K] in the EDT of mice on a control diet (Δ = 1.88 ± 0.45 mM; N = 3) but decreased that of mice on LNaHK (Δ = -3.52 ± 0.85 mM; N = 4). Vehicle did not affect [K] in the EDT of mice on either diet. The increase in urinary Na excretion after furosemide was much greater in mice on LNaHK. These results indicate that there is a net K secretion in TAL of mice on LNaHK, and it is associated with increased NKCC2 activity. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 12 Basic Science Research Abstract #2 Presenter: Danniel Zamora Authors: Danniel Zamora MD, David Greenberg MD Title: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) and their potential use against Pseudomonas aeruginosa biofilms Abstract: Pseudomonas aeruginosa (Pa) is a major human pathogen responsible for a variety of clinical infections. It has become increasingly antibiotic resistant and in addition has the ability to form biofilm further complicating treatment. Novel therapeutic approaches include the use of antisense technologies (peptideconjugated phosphorodiamidate morpholino oligomers (PPMOs)) that are designed to target pathogens in a sequence-specific way. We tested whether PPMOs could be effective against Pa biofilms. A PPMO directed against the essential gene AcpP, was compared to piperacillin-tazobactam (TZP) and a scrambledsequence control PPMO. Biofilms were exposed to multiple concentrations of each at 24, 32 and 40 hours and the amount of residual biofilm was assessed using crystal violet staining. TZP at concentrations ranging from 0.5 to 10 ug/mL were used while AcpP and Scr PPMOs were at concentrations from 0.5 to 20 uM were used. Analysis of the data was performed using Tukey comparison of means. AcpP showed extremely significant decrease in biofilm up to 10 uM compared to negative control (p < 0.0001). TZP showed decreased biofilm up to 4 ug/mL (p 0.010.05). Scramble showed no significant decrease in biofilm. Combination of AcpP and TZP showed decrease biofilm but unclear whether a synergistic response exists. The results illustrate the potential of PPMOs in biofilm inhibition and their potential use in conjunction with traditional antibiotics in combating drug resistant organisms. Pseudomonas aeruginosa (Pa) is a major human pathogen responsible for a variety of clinical infections. It has become increasingly antibiotic resistant and in addition has the ability to form biofilm further complicating treatment. Novel therapeutic approaches include the use of antisense technologies (peptideconjugated phosphorodiamidate morpholino oligomers (PPMOs)) that are designed to target pathogens in a sequence-specific way. We tested whether PPMOs could be effective against Pa biofilms. A PPMO directed against the essential gene AcpP, was compared to piperacillin-tazobactam (TZP) and a scrambledsequence control PPMO. Biofilms were exposed to multiple concentrations of each at 24, 32 and 40 hours and the amount of residual biofilm was assessed using crystal violet staining. TZP at concentrations ranging from 0.5 to 10 ug/mL were used while AcpP and Scr PPMOs were at concentrations from 0.5 to 20 uM were used. Analysis of the data was performed using Tukey comparison of means. AcpP showed extremely significant decrease in biofilm up to 10 uM compared to negative control (p < 0.0001). TZP showed decreased biofilm up to 4 ug/mL (p 0.010.05). Scramble showed no significant decrease in biofilm. Combination of AcpP and TZP showed decrease biofilm but unclear whether a synergistic response exists. The results illustrate the potential of PPMOs in biofilm inhibition and their potential use in conjunction with traditional antibiotics in combating drug resistant organisms. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 13 Basic Science Research Abstract #3 Presenter: Richard C Wu Authors: Richard Wu MD PhD, Cara Haymaker PhD, Hiu Liu, Ena Wang MD, Patrick Hwu MD, Laszlo Radvanyi PhD Title: Identification of a Novel T-cell Biomarker (BTLA, Band TLymphocyte Attenuator) and the Mechanism of Its Association with Positive Clinical Responses in a Phase II Adoptive T-cell Therapy (ACT) Trial for Metastatic Melanoma Abstract: Melanoma is difficult to treat once metastases occur. Adoptive Tcell therapy (ACT), which uses autologous tumor-infiltrating lymphocytes (TIL) expanded ex vivo with high-dose IL-2 with infusion into lymphodepleted patients, has emerged as a powerful treatmet approach. However, it is not known which Tcell biomarkers are associated with positive clinical responses to ACT. In a phase II clinical trial, 31 patients of both genders with Stage IIIc/IV melanoma over the age of 18 were treated with ACT. Expanded TIL from these patients were analyzed using flow cytometry with a comprehensive panel distinguishing the main Tcell subsets. Overall 15/31 patients (48.4%) responded (PR/CR) to TIL therapy with objective tumor regression. The clinical responses were quite durable, with many responders having a >12 month progression-free survival. By comparing the TIL biomarkers, we observed that responders received significantly higher numbers of CD8+ T cells (p = 0.0007). Unexpectedly, PD-1 expression on CD8+ TIL did not impact clinical response (p = 0.995), whereas higher BTLA expression on CD8+ TIL was significantly associated with positive clinical response (p = 0.002). Microarray analysis revealed CD8+BTLA+ TIL were less-differentiated than BTLATIL, and exhibited superior proliferation in response to IL-2. We also found that unique T-cell clones from CD8+BTLA+ TIL persisted longer in vivo. Moreover, BTLA could mediate a strong pro-survival signal via Akt by binding to HVEM. Melanoma is difficult to treat once metastases occur. Adoptive Tcell therapy (ACT), which uses autologous tumor-infiltrating lymphocytes (TIL) expanded ex vivo with high-dose IL-2 with infusion into lymphodepleted patients, has emerged as a powerful treatmet approach. However, it is not known which Tcell biomarkers are associated with positive clinical responses to ACT. In a phase II clinical trial, 31 patients of both genders with Stage IIIc/IV melanoma over the age of 18 were treated with ACT. Expanded TIL from these patients were analyzed using flow cytometry with a comprehensive panel distinguishing the main Tcell subsets. Overall 15/31 patients (48.4%) responded (PR/CR) to TIL therapy with objective tumor regression. The clinical responses were quite durable, with many responders having a >12 month progression-free survival. By comparing the TIL biomarkers, we observed that responders received significantly higher numbers of CD8+ T cells (p = 0.0007). Unexpectedly, PD-1 expression on CD8+ TIL did not impact clinical response (p = 0.995), whereas higher BTLA expression on CD8+ TIL was significantly associated with positive clinical response (p = 0.002). Microarray analysis revealed CD8+BTLA+ TIL were less-differentiated than BTLATIL, and exhibited superior proliferation in response to IL-2. We also found that unique T-cell clones from CD8+BTLA+ TIL persisted longer in vivo. Moreover, BTLA could mediate a strong pro-survival signal via Akt by binding to HVEM. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 14 Clinical Research Abstract #4 Presenter: Ami DeWaters Authors: Ami DeWaters MD, Eric Mortensen MD MSc Title: Sad white blood cells? The association of major depressive disorder and mortality in older veterans hospitalized for pneumonia Abstract: Major depressive disorder has been identified as an independent risk factor for mortality for many comorbid conditions. However, the association between major depression and a common global fatal infection, pneumonia, has not been examined. The aim of this study was to examine the association between major depressive disorder and mortality in patients hospitalized with pneumonia. Major depressive disorder has been identified as an independent risk factor for mortality for many comorbid conditions. However, the association between major depression and a common global fatal infection, pneumonia, has not been examined. The aim of this study was to examine the association between major depressive disorder and mortality in patients hospitalized with pneumonia. We conducted a retrospective study using administrative data of patients hospitalized at any VA hospital. We included patients greater than 65 years old hospitalized with pneumonia in 20022012. Major depressive disorder was defined with ICD-9 codes filed in the 12 months prior to admission. We used generalized linear mixed effect models to examine the association of major depressive disorder with mortality after controlling for confounders, including sociodemographics, Charlson comorbidity scores, and severity of illness. Of 103,997 patients who met the inclusion criteria, 9,247 had major depressive disorder. In the multilevel models, patients with depression had a significantly higher 30-day (odds ratio, 1.22; 95% confidence interval 1.15-1.29) and 90-day (odds ratio, 1.20; 95% confidence interval 1.12-1.29) mortality. For older veterans hospitalized with pneumonia, a diagnosis of major depressive disorder was associated with high mortality. This study highlights that major depressive disorder is potentially an independent risk factor for mortality for older adults hospitalized with pneumonia. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 15 Clinical Research Abstract #5 Presenter: Julie Kim Authors: Julie K. Kim, MD; David A. Khan, MD Title: Recurrence of Chronic Urticaria: Incidence and Associated Factors Abstract: Background: Chronic urticaria (CU) is urticaria that has been present for at least 6 weeks. CU affects both children and adults, and the characteristics of recurrent CU are not well established. Knowledge about factors that may help predict recurrence would be useful. Background: Chronic urticaria (CU) is urticaria that has been present for at least 6 weeks. CU affects both children and adults, and the characteristics of recurrent CU are not well established. Knowledge about factors that may help predict recurrence would be useful. Objective: We hypothesize that in recurrent CU, the use of alternative (non-antihistamine and non-antileukotriene) agents is more prevalent. Methods: A retrospective review was performed of the electronic medical charts of 167 adult patients diagnosed with CU in the allergy/immunology clinic at UTSW Medical Center for subtypes of CU and medication usage. Recurrence was defined as urticaria occurring at or greater than 6 months after cessation of therapy and resolution of symptoms. Descriptive statistics were used. Results: Of the 167 patients, 31 (19%) met criteria for recurrent CU. Fifteen (48%) of recurrent CU patients had a history of treatment with alternative agents compared to 46 (34%) of 136 CU patients without recurrence. The prevalence of steroid dependency was similar in both groups (16% in the recurrent CU group vs. 17%). Chronic idiopathic urticaria (CIU) was the most common diagnosis in both groups, while physical urticarias were more prevalent in CU patients without recurrence (15% vs. 0%). Conclusions: Chronic urticaria may recur in 1 in 5 patients. There appears to be a higher rate of alternative agent use in recurrent urticaria. Physical urticaria appears to recur less frequently than CIU. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 16 Clinical Research Abstract #6 Presenter: Javier Neyra Authors: Javier A. Neyra, MD, Xilong Li, PhD, MS, Beverley AdamsHuet, MS, Orson W. Moe, MD, Robert D. Toto Title: Acute kidney injury recovery at 90 days and subsequent CKD in critically ill sepsis survivors Abstract: Background: Acute kidney injury (AKI) is a frequent complication of sepsis and is associated with an increased risk for subsequent chronic kidney disease (CKD). The purpose of this study was to investigate whether incomplete 90-day AKI recovery increases the risk of CKD in sepsis survivors. Background: Acute kidney injury (AKI) is a frequent complication of sepsis and is associated with an increased risk for subsequent chronic kidney disease (CKD). The purpose of this study was to investigate whether incomplete 90-day AKI recovery increases the risk of CKD in sepsis survivors. Methods: We conducted a retrospective cohort study of patients admitted to the ICU with a diagnosis of severe sepsis or septic shock from May 2007 to December 2011. We excluded patients with eGFR <15 ml/min/1.73 m2 or receiving chronic renal replacement therapy (RRT) prior to ICU admission. Baseline serum creatinine (SCr) was defined as the most recent SCr within the 3month period before ICU admission. The highest SCr during ICU admission was used to diagnose AKI (KDIGO criteria). The independent variable, AKI recovery, was determined by the ratio of 90-day post-discharge SCr / baseline SCr in RRT-free survivors: <1.1 indicated complete AKI recovery; ≥1.1 to <1.5 incomplete (mild) AKI recovery; and ≥1.5 incomplete (severe) AKI recovery. The primary outcome measure was incident or progressive CKD based on relative or absolute glomerular filtration rate (eGFR) changes during the follow-up period. A Cox proportional hazard regression analysis adjusting for age, sex, race, baseline eGFR, diabetes, AKI severity, and the ICU admission Sequential Organ Failure Assessment (SOFA) score was performed. Results: Of 6290 ICU patients included in the study, 3642 (58%) suffered from AKI and 741 (12%) required acute RRT. The 90-day mortality rate was 26%. Among survivors, we identified 1249 patients that suffered from AKI, were RRT-free at 90 days following hospital discharge, and had available follow-up data. Incident or progressive CKD occurred in 319 of these 1249 patients: 54% of those with incomplete (severe) AKI recovery; 29% of those with incomplete (mild) AKI recovery; and 13% of those with complete AKI recovery, median follow-up 2.5 years. 90-day AKI recovery 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 17 status was an independent predictor of CKD (adjusted HR 4.73, 95% CI 3.54 – 6.32 for incomplete (severe) vs complete AKI recovery; 2.26, 1.65 – 3.10 for incomplete (mild) vs complete AKI recovery; and 2.09, 1.58 – 2.77 for incomplete (severe) vs incomplete (mild) AKI recovery. Other independent predictors of CKD post-AKI were older age, black race, anemia, and higher ICU admission SOFA score. Conclusions: Incomplete AKI recovery within 90 days following hospital discharge is a strong and independent predictor of CKD in sepsis survivors. The timely evaluation of AKI recovery may serve to risk-stratify sepsis survivors and implement more vigilant surveillance for CKD in this susceptible population. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 18 Clinical Research Abstract #7 Presenter: Sheenal Patel Authors: Sheenal V. Patel MD, David A. Khan, MD Title: Success of Alternative Therapies in Chronic Urticaria Patients Failing Omalizumab Abstract: Introduction: Since omalizumab’s approval in 2014 for refractory chronic urticaria (CU), more patients are being treated for this indication. However, studies looking at therapeutic failures with omalizumab are lacking. Introduction: Since omalizumab’s approval in 2014 for refractory chronic urticaria (CU), more patients are being treated for this indication. However, studies looking at therapeutic failures with omalizumab are lacking. Objective: To describe omalizumab treatment failures in refractory CU patients and report alternative therapies that may be considered in these patients. Methods: A retrospective chart review was conducted in the authors’ clinic from October 2005 to July 2015 to identify adults with refractory CU who had either partial or lack of response to at least three doses of omalizumab. Baseline characteristics, treatment course, duration of treatment, and alternative therapies used and their response were evaluated. Results: A total of forty patients were treated with omalizumab for refractory CU. Sixteen patients were identified who had partial or lack of response to at least three doses of omalizumab. Three patients improved on tacrolimus (2/3 with complete response), 1 had complete response on sirolimus, 1 had complete response on cyclosporine, and 1 had partial response on mycophenolate mofetil. Two have continued need for oral corticosteroids. Summary: This case series describes a group of patients who had partial or lack of response to omalizumab therapy. Other alternative therapies should be considered in these patients. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 19 Clinical Research Abstract #8 Presenter: Steve Dorman Authors: Steve Dorman, MD; April Clark, RD, CSP, LD; J. Andrew Bird, MD Title: Baked Egg Oral Immunotherapy (OIT) Accelerates Desensitization to Unbaked Egg (UBE) in Severely Egg Allergic Children Abstract: BACKGROUND: Regular ingestion of baked egg (BE) may accelerate desensitization to UBE for egg-allergic individuals. Treatment lacks for severely egg allergic children reacting to both BE and UBE. BACKGROUND: Regular ingestion of baked egg (BE) may accelerate desensitization to UBE for egg-allergic individuals. Treatment lacks for severely egg allergic children reacting to both BE and UBE. HYPOTHESIS: We hypothesized that BE OIT desensitizes severely egg allergic children to UBE. METHODS: Subjects reacting to a BE product containing 3.8g of egg protein per serving or with ovomucoid IgE>50kU/L were included. OIT dosing started with ingestion of a 125mg BE product, then home up-dosing at 2 and 4 weeks and 3, 6, and 9 months to a daily dose of 3.8g BE. Egg white (EW)-, ovomucoid-, and ovalbumin-specific IgE, and EW SPT were obtained at 0, 6, 12, 18 and 24 months. At 12 months subjects were challenged to 3.8g of BE and after at least 24 months were challenged to UBE. Matched data was compared using Wilcoxon rank-sum test. RESULTS: Four of 12 subjects have completed therapy. Six subjects withdrew secondary to non-compliance with BE ingestion, 1 subject began eating UBE at home and was removed from the study, and 1 is awaiting UBE challenge. Reaction rate was 1.3%. All adverse events were mild. Six of 7 subjects passed BE challenge at 12 months. At 24 months, all subjects (4) challenged to UBE passed. Mean EW IgE significantly decreased by 20.47 kU/L (p=0.0313). Ovomucoidand ovalbumin-specific IgE, and EW-SPT did not change significantly. CONCLUSIONS: BE OIT desensitizes severely egg allergic children to UBE. In our cohort, after one year of BE OIT 6/7 children passed a BE challenge. After two years of BE OIT all challenged to UBE passed, and EW–specific IgE significantly decreased. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 20 Clinical Research Abstract #9 Presenter: Yu (Ray) Zuo Authors: Yu Zuo MD, Rohan Willis, EB. Gonzalez, Allan R Brasier , Elizabeth Papalardo, Michelle Petri, Hong Fang2, E. Nigel Harris, Karel De Ceulaer, Monica Smikle, Luis M Vilá, John D Reveille, Graciela S Alarcón, Silvia S. Pierangeli Title: Comparative Analysis of a Novel Antiphospholipid Assay Utilizing a Mixture of Negatively Charged Phospholipid Antigens and Criteria Antiphospholipid Immunoassays in Lupus Patients Abstract: Background: While essential for the classification of antiphospholipid Syndrome (APS), aCL assays lack specificity and anti-β2GPI assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APHL assay and criteria antiphospholipid immunoassays in identifying APS related clinical manifestations in a large group of SLE patients. Background: While essential for the classification of antiphospholipid Syndrome (APS), aCL assays lack specificity and anti-β2GPI assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APHL assay and criteria antiphospholipid immunoassays in identifying APS related clinical manifestations in a large group of SLE patients. Methods: Serum samples from 1178 patients from the Hopkins (n=543), LUMINA (n=588) and Jamaican SLE cohorts (n=47) were examined for criteria abs assays and APhL assays. Correlation of assay positivity with clinical manifestations and sensitivity, specificity, positive and negative predictive values and likelihood ratios were evaluated. A case series analysis was also performed in patients for whom there was isolated positivity in one of the more specific assays. Results: Both IgG APHL and IgM APHL were significantly correlated with thrombosis, while only IgG APHL was significantly correlated with pregnancy morbidity. The IgG APHL assay had the greatest performance value as measured by positive likelihood ratio, increased sensitivity as compared to anti-β2GPI, and improved specificity compared to aCL assays. Approximately 2% (23/1178) of our patients tested positive for APHL and negative to criteria assays. Of these, 47.8% (11/23) had APS clinical manifestations, including thrombotic and pregnancy related morbidity. Conclusions: APhL antibodies represent a promising biomarker for the classification of APS patients. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 21 Clinical Research Abstract #10 Presenter: Anurag Mehta Authors: Anurag Mehta, MD; Nilay Kumar, MD; Ambarish Pandey, MD Title: Regional Differences in Outcomes of Heart Failure Hospitalization in the United States: A Contemporary Nationwide Analysis Abstract: Background and Objectives: Regional differences in outcomes of HF hospitalization have important health policy implications. There is a paucity of contemporary data on regional differences in HF hospitalization outcomes in a nationally representative sample in the US. Background and Objectives: Regional differences in outcomes of HF hospitalization have important health policy implications. There is a paucity of contemporary data on regional differences in HF hospitalization outcomes in a nationally representative sample in the US. Methods: We used the 2011 2012 National Inpatient Sample to include HF hospitalizations (primary diagnosis code ICD9 428.xx). Outcomes included in-hospital mortality, length of stay (LOS) and cost. Logistic models adjusted for patient characteristics and illness severity were used to test differences in outcomes. Results: There were 1.8 million hospitalizations with a primary diagnosis of HF in 2011 2012. Mean age was 72.6 years and 50.1% were women. Patients in the NE were older (mean 74.6 y, p<0.05 for NE vs. MW, S or W) and more likely to receive intensive lifesustaining therapies compared to other regions. Case fatality was 3.8% in NE vs. 3% MW, 3% S and 2.9% W (p<0.05 in pairwise comparison). This difference became non-significant for NE vs. MW and NE vs. S after adjusting for patient characteristic and illness severity. LOS was highest in the NE while costs were highest in the West after adjusting for confounders. Conclusions: Significant regional differences exist in outcomes of HF hospitalization in the US. These differences are partially explained by differences in patient characteristics and illness severity. Further investigation is warranted to understand the reasons for these differences. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 22 Clinical Research Abstract #11 Presenter: Bryan R Wilner Authors: Bryan R Wilner MD, Sonia Garg MD, Colby R Ayers MS, Satyam Sarma MD, Anand Rohatgi MD, Sandeep R. Das MD MPH, Darren K. McGuire MD, James A. de Lemos MD, Mark H. Drazner MD, Ian J. Neeland MD Title: Changes in generalized and central adiposity are dynamically associated with left ventricular remodeling Abstract: Introduction: Obesity is linked to an adverse cardiac structural phenotype. However, the effects of longitudinal changes in generalized and central adiposity on left ventricular (LV) remodeling are unknown. Introduction: Obesity is linked to an adverse cardiac structural phenotype. However, the effects of longitudinal changes in generalized and central adiposity on left ventricular (LV) remodeling are unknown. Methods: Dallas Heart Study participants without baseline cardiovascular disease or LV dysfunction underwent assessment of anthropometry and cardiac structure by MRI at baseline and 8 years later. Associations between change in weight and waist circumference (WC) with alterations in LV structure and function were assessed using multivariable linear regression. Results: The study cohort (n=1262) had a mean age of 44 years with 43% male, 44% black, and 36% obese at baseline. Those who gained >10% weight were younger, had lower BMI and LV mass at baseline, and had greater increases in blood pressure, glucose, and triglycerides at follow-up (p<0.05). In multivariable models, adjusted for age, sex, race, baseline adiposity and cardiac variables, and baseline and interim development of comorbidities, increases in weight and WC were associated with higher LV mass (β=0.09 and 0.07, p<0.0001), LV wall thickness (β=0.12 and 0.09, p<0.0001) and concentricity (β=0.06 for both, p=0.002); but not associated with LV end-diastolic volume or ejection fraction. Conclusion: Increasing weight and WC over time are associated with pathologic cardiac remodeling, characterized by concentric remodeling. Our findings have potential implications for the prevention and treatment of heart failure. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 23 Clinical Research Abstract #12 Presenter: Carolina De La Flor Authors: De La Flor C, Yek C, Chen TY, Singal AG, Adams-Huet B, Zoellner C, Casey L, Mayorga C, Jain MK Title: Direct-Acting Antiviral Therapy for Hepatitis C Improves FIB4 and APRI Scores in Both Cirrhotic and Non-Cirrhotic Patients Abstract: Background: The AST to Platelet Ratio Index (APRI) and Fibrosis 4 score (FIB4) are non-invasive measures of liver fibrosis in chronic hepatitis C (HCV). Here we examined the changes in both scores in cirrhotic and non-cirrhotic patients with HCV after direct acting antiviral therapy. Background: The AST to Platelet Ratio Index (APRI) and Fibrosis 4 score (FIB4) are non-invasive measures of liver fibrosis in chronic hepatitis C (HCV). Here we examined the changes in both scores in cirrhotic and non-cirrhotic patients with HCV after direct acting antiviral therapy. Methods: We analyzed a cohort of patients (n=81) with chronic HCV who completed treatment and achieved sustained viral response (SVR) at Parkland Memorial Hospital. Samples were obtained at baseline, week 4, end of treatment (EOT) and 12weeks post (SVR). Results: Of 81 patients, 60 had cirrhosis and 21 did not. At baseline, cirrhotics had higher ALT (p=0.03), AST (p<0.001), APRI (p<0.001), and FIB4 (p<0.001) and lower platelet counts (p<0.001) and viral loads (p=0.03) compared to non-cirrhotics. APRI and FIB4 declined in both groups, with the greatest decrease between baseline and week 4 (cirrhotics APRI p<0.001, FIB4 p<0.001 and non-cirrhotics APRI p<0.001, FIB4 p<0.001). Finally, FIB4 and APRI were not different in cirrhotics versus non-cirrhotics after SVR (FIB4 p=0.27, APRI p=0.72). Conclusion: We found that both scores decreased in cirrhotics and non-cirrhotics, suggesting that they may indicate a reduction in liver inflammation rather than a true decrease in fibrosis. Morever, APRI and FIB4 were not significantly different in cirrhotics as compared to non-cirrhotics after treatment, implying that these markers may no longer have a role in predicting cirrhosis after viral clearance. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 24 Clinical Research Abstract #13 Presenter: Christina Yek Authors: Christina Yek, Carolina De La Flor, Ting-Yi Chen, Amit Singal, Cindy Zoellner, Lisa Casey, Christian Mayorga, Mamta Jain Title: Success of Direct-Acting Antivirals for Hepatitis C in an Indigent Population Abstract: Direct-acting antivirals (DAAs) have revolutionized the management of chronic hepatitis C (HCV). The aim of our study was to examine the impact of coordinating limited resources to treat HCV-infected patients at a large urban safety-net hospital. Direct-acting antivirals (DAAs) have revolutionized the management of chronic hepatitis C (HCV). The aim of our study was to examine the impact of coordinating limited resources to treat HCV-infected patients at a large urban safety-net hospital. Our cohort included all patients who started interferon-free DAAbased HCV therapy at Parkland Memorial Hospital. Available clinic resources and staff included 0.4 FTE infectious disease/hepatology physician champions, 0.5 FTE nurse navigator, and 0.25 FTE mid-level provider that met once weekly for liver clinic. During a 20-month period, 280 patients were started on DAAs, representing a 350% increase in the rate of HCV treatment initiation from historical rates achieved with interferon-based regimens. Sustained viral response was achieved in 76% (n=135), an improvement from outcomes with interferon-based regimens (viral response in only 34%). A further 6% (n=11) had viral relapse, 2% (n=4) stopped treatment due to serious adverse events and 16% (n=28) were lost to follow-up. Risk factors for viral relapse were: infection with genotypes 1a or 2 (9% relapse in genotype 1a, 10% in genotype 2, vs 0% in infection with other genotypes), presence of cirrhosis (8% relapse vs 3% in non-cirrhotics) and prior treatment failure (9% relapse vs 5% in treatment-naïve patients). Our model of care increased treatment initiation and achieved exceptional effectiveness, suggesting that favorable outcomes can be achieved in limited resource settings. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 25 Clinical Research Abstract #14 Presenter: Sarah Kiani Authors: Sarah Kiani, Usman Salahuddin, Haekyung Jeon Slaughter, Atif Mohammad, Emmanouil S. Brilakis, Subhash Banerjee Title: Adverse Cardiovascular Outcomes in Individuals with Diabetes Mellitus after Stenting for Lower Extremity Peripheral Arterial Disease Abstract: There is equivocal data on outcomes of percutaneous Endovascular Intervention (EVI) for lower extremity Peripheral Artery Disease (PAD) in patients with diabetes mellitus (DM). There is equivocal data on outcomes of percutaneous Endovascular Intervention (EVI) for lower extremity Peripheral Artery Disease (PAD) in patients with diabetes mellitus (DM). 1,006 patients with primary stent implant procedures between 01/2005 and 10/2015 enrolled in the observational XLPAD registry (NCT01904851) were analyzed for 12 month major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE; target limb repeated endovascular intervention, surgical revascularization, and major amputation). Cochran-MantelHaenszel statistics and Cox proportional regressions and KaplanMeier curves were used for analysis. At baseline, patients with DM had higher prevalence (p<0.05) of underlying Cardiovascular Disease and advanced disease at presentation (Rutherford catgory and CLI) in comparison to patients without DM. Adjusted Cox models for baseline characteristics and medical therapy of interest showed that risk of mortality and MACE in 12 months increased by 390% and 215% in patients with DM compared to those without DM, respectively (Mortality: HR= 3.92, 95% CI 1.70-9.04, p<0.0001; MACE: HR=2.15, 95% CI 1.21-3.82, p<0.0001), while there was no significant DM group difference found in 12-month MALE (HR=0.96, 95% CI 0.761.21, p=0.7281). Conclusion: Lower extremity PAD EVI in individuals with DM is associated with significantly higher mortality and major adverse cardiovascular events. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 26 Clinical Research Abstract #15 Presenter: Timothy J Brown Authors: Timothy J. Brown MD, Matthew C Brennan MD, Michael Li MD, Ephraim W Church MD, Nicholas J. Brandmeir MD, Kevin Rakszawski MD, Akshal S. Patel MD, Elias B. Rizk MD, Dima Suki Ph.D, Raymond Sawaya MD, Michael Glantz MD. Title: Examining extent of resection and progression-free survival in glioblastoma: a systematic review and meta-analysis Abstract: background: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The relationship between extent of tumor resection (EOR) and progression-free survival (PFS) is ill-defined notwithstanding many relevant studies. We present the results of a quantitative systematic review addressing the effect EOR on PFS in patients with GBM. background: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The relationship between extent of tumor resection (EOR) and progression-free survival (PFS) is ill-defined notwithstanding many relevant studies. We present the results of a quantitative systematic review addressing the effect EOR on PFS in patients with GBM. Methods: Search engines were systematically reviewed with the guidance of an expert librarian. Additional articles were included after consultation with experts and evaluation of bibliographies. Data were analyzed to assess PFS following gross total resection (GTR), subtotal resection (STR), and biopsy (Bx). The body of evidence was evaluated according to GRADE criteria and PRISMA guidelines. Results: Our search yielded 1055 articles, of which 9 articles were included. The meta-analysis revealed decreased likelihood of one-year progression for GTR compared to STR (RR=0.66, 95% CI=0.43-0.99) decreased likelihood of six-month progression for STR compared to biopsy (RR=0.72, CI=0.51-1.00 p=0.05), and decreased likelihood of progression at 6 months with any EOR compared to Bx (RR=0.61, CI=0.44-0.84 p=0.003). The quality of the body of evidence was moderate to low. Conclusion: This is the largest quantitative systematic review performed on this subject. In GBM, PFS appears to be improved in a dose-dependent manner with increasing EOR. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 27 Clinical Research Abstract #16 Presenter: Timothy J Brown Authors: Timothy J. Brown MD, Matthew C Brennan MD, Michael Li MD PhD, Ephraim W Church MD, Nicholas J. Brandmeir MD, Kevin Rakszawski MD, Akshal S. Patel MD, Elias B. Rizk MD, Dima Suki PhD, Raymond Sawaya MD, Michael Glantz MD. Title: Extensive resection improves survival in glioblastoma: a systematic review and meta-analysis Abstract: Introduction: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The relationship between extent of tumor resection (EOR) and outcome remains undefined notwithstanding many relevant studies. Introduction: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The relationship between extent of tumor resection (EOR) and outcome remains undefined notwithstanding many relevant studies. Methods: Pubmed, CINAHL, and Web of Science were systematically reviewed with librarian guidance. Data were extracted from the text or Kaplan-Meier curves and analyzed to assess mortality following gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to GRADE criteria and PRISMA guidelines. Results: Our search yielded 37 articles suitable for inclusion. The meta-analysis revealed decreased oneand two-year mortality, for GTR compared to STR (RR=0.62, 95% CI=0.56-0.69 p<0.001, NNT=9; RR=0.84, CI=0.79-0.89 p<0.001 NNT=17) and one-year risk of mortality for STR compared to biopsy (RR=0.85, CI=0.80-0.91 p<0.001). Oneand two-year risk of mortality was similarly decreased for any resection compared to biopsy (RR=0.77, CI=0.71-0.84 p<0.001; RR=0.94, CI=0.89-1.00, p<0.001). The quality of the body of evidence by GRADE criteria was moderate to low. Conclusion: Our analysis represents the largest and only quantitative systematic review to date performed on this subject. GTR substantially improves the overall survival survival compared to STR, but the quality of the supporting studies is only moderate to low. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 28 Clinical Research Abstract #17 Presenter: Usman Akhtar and Nitin Kondamudi Authors: Usman Akhtar, Nitin Kondamudi, Colby Ayers, Ian Neeland Title: Visceral Adiposity Calculator from Dallas Heart Study: Population based risk estimator for visceral adipose tissue and associated cardiovascular risk Abstract: Introduction: Current research has linked visceral adipose tissue (VAT) to increased morbidity and mortality for overall cardiovascular disease. Our objective was to create a predictive model of VAT utilizing the extensive phenotyping data available from the Dallas Heart Study (DHS). Introduction: Current research has linked visceral adipose tissue (VAT) to increased morbidity and mortality for overall cardiovascular disease. Our objective was to create a predictive model of VAT utilizing the extensive phenotyping data available from the Dallas Heart Study (DHS). Methods/Results: A cross-sectional study was performed, measuring the associations between demographic and biomarker data and the outcome dependent variable: VAT measured with abdominal MR. Exposure variables were initially filtered based on their utility in daily clinical practice. The analysis was performed separately for males and females in order to create sex-specific indices. A backwards, step-wise selection model found ten variables with the strongest associations with visceral adiposity that further underwent an R2 selection model. The adjusted R-square was 0.6386 for women, and 0.6864 for men (P< .001). The variables included in the final model were waist circumference, age, TG/HDL ratio, and black race. For women, the fifth variable was plasma glucose, and for men, uric acid. Conclusion: Our study suggests that the above variables serve as a robust predictor of visceral adiposity based on the DHS data. This provides a practical tool to estimate visceral adiposity in the clinical setting, and can be invaluable in assessing and modifying associated cardiovascular risk. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 29 Clinical Research Abstract #18 Presenter: Arjun Gupta Authors: Arjun Gupta, Ambarish Pandey, Colby Ayers, Muhammad S. Beg, Susan G. Lakoski, Gloria L. Vega, Scott M. Grundy, David H. Johnson, Ian J. Neeland Title: A Prospective Analysis of Individual Body Fat Depots and Risk of Developing Cancer: Insights from the Dallas Heart Study Abstract: Background: Adiposity is associated with increased cancer risk; however BMI is an imprecise measure of adiposity. We examined the association of adipose tissue depots with the incident cancer in the Dallas Heart Study (DHS). Background: Adiposity is associated with increased cancer risk; however BMI is an imprecise measure of adiposity. We examined the association of adipose tissue depots with the incident cancer in the Dallas Heart Study (DHS). Methods: Individuals without prevalent cancer underwent quantification of adipose tissue depots: visceral (VAT), abdominal subcutaneous adipose tissue (SAT), liver fat and lower body subcutaneous fat (LBF), and were followed for the development of cancer using the Texas Cancer Registry. Multivariable Cox proportional hazards modeling was performed to examine the association between fat depots and incident cancer. Results: Among 2,627 participants, 167 (6.4%) developed incident cancer during a 12 year follow up period. Each standard deviation increase in VAT was associated with 25% increased risk of cancer: HR 1.25 (95% CI 1.061.47). The association was attenuated with the addition of age to the model. Each 1standard deviation increase in LBF was associated with a reduced incidence of cancer; HR 0.93 (95% CI 0.870.98) in the multivariable model. Conclusions: In this study, adiposity-associated cancer risk was heterogeneous and varied by fat depot: VAT was associated with incident cancer but not independent of age and LBF appeared to protect against cancer development. Further studies of the adiposity-cancer relationship are needed to elucidate this relationship and to examine the association with prognosis and response to therapy. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 30 Clinical Research Abstract #19 Presenter: Arjun Gupta Authors: Arjun Gupta, Kaustav Majumder, Nivedita Arora, Preet Paul Singh, Siddharth Singh Title: Obesity and mortality in patients with esophageal cancer: A systematic review and meta-analysis Abstract: Background: Obesity influences incidence of esophageal cancer (EC) with contrasting impact on esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESC). However its influence on EC mortality remains unclear. Background: Obesity influences incidence of esophageal cancer (EC) with contrasting impact on esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESC). However its influence on EC mortality remains unclear. Methods: We searched major databases and conference proceedings, up to June 2015, and identified observational studies reporting the association between obesity (premorbid BMI ≥ 30 kg/m2) and EC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing highest BMI category with reference category in each study using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: We identified 8 studies with 2,784,027 people, of whom 18% were obese. On meta-analysis, compared with EC patients with reference BMI, obese EC patients had aHR for mortality of 0.97 (95% CI, 0.661.43), with high heterogeneity (I2 = 88%). On analyzing patients with EAC alone (3 studies), aHR was 1.10 (95% CI, 0.432.82), with high heterogeneity (I2 = 95%). Data to separately analyze ESC or to perform subgroup analysis by gender, smoking status or geographic location. Conclusions: Obesity does not appear to be associated with mortality in patients with EC. However, high heterogeneity and limited data for subgroup analysis limits the interpretation of this analysis. Further prospective studies evaluating mortality in patients with established EC are needed to answer this question. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 31 Clinical Research Abstract #20 Presenter: Arjun Gupta Authors: Arjun Gupta, Hong Zhu, Alana Christie, Jeffrey Meyer, Saad Khan, Muhammad Beg Title: Racial and sex disparities in changing trends of squamous cell cancer of the anus (SSCA) Abstract: Background: Squamous cell carcinoma of the anus (SSCA) is one of few cancers with rising incidence. This is believed to represent changing epidemiology of HIV and HPV. We explored the racial and sex disparities in the incidence of SSCA. Background: Squamous cell carcinoma of the anus (SSCA) is one of few cancers with rising incidence. This is believed to represent changing epidemiology of HIV and HPV. We explored the racial and sex disparities in the incidence of SSCA. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify subjects with SCCA from 20002012. Age standardized incidence rates (IR) per 100,000 were generated for white males (WM), white females (WF), black males (BM) and black females (BF). The 2000 US standard population was used for age standardization. The trend of change of IR between groups was compared by testing the interaction between time and group in the linear regression model. SAS 9.4 was used for analysis Results: Among11,739 new cases of SSCA racial and sex distribution of cases was WM:32%, WF:54%, BM:5.4%, BF:5.4%. Median overall survival (OS) was WM:101 months (m), WF:139 m, BM: 71 m, BF 103 m (p < 0.005). The IR had the highest rate of increase for WF and BM (0.06/100,000 cases annually) while rates for BF and WM increased by 0.04 and 0.02/100,000 cases annually respectively. The overall test for difference in trend among WF, WM, BF and BM groups had a p value of 0.0099. Conclusions: The rate of increase of SSCA IR is highest for WF and BM. Additionally WF have the highest age standardized incidence of SCCA as well as the highest OS compared to other groups. These data support disparities in epidemiology and survival of anal cancer. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 32 Clinical Research Abstract #21 Presenter: Arjun Gupta Authors: Arjun Gupta, Kaustav Majumder, Nivedita Arora, Preet Paul Singh, Siddharth Singh, Ethan Halm, David H Johnson Title: Effect of premorbid body mass index on mortality in patients with lung cancer: A systematic review and meta-analysis Abstract: Background: Obesity is associated with reduced risk of developing lung cancer (LC), but its effect on LC mortality remains unclear. We performed a systematic review and metaanalysis to assess the association between premorbid body mass index (BMI) and LC mortality. Background: Obesity is associated with reduced risk of developing lung cancer (LC), but its effect on LC mortality remains unclear. We performed a systematic review and metaanalysis to assess the association between premorbid body mass index (BMI) and LC mortality. Methods: Conducting a systematic search of MEDLINE and the Cochrane library through December 2015, we identified observational studies reporting the association between premorbid BMI, and LCrelated mortality. We estimated summary adjusted hazard ratio (aHR) comparing obese (BMI > 30 kg/m2) and overweight (BMI 25-29.9 kg/m2) categories with reference category in each study, using random effects model. Results: 11 studies (including 1 pooled cohort study) comprising 2,953,278 individuals at inception, in whom 27,282 LC deaths occurred were analysed. Compared with LC patients with normal BMI, a reduction in mortality in both overweight [aHR, 0.83; 95% CI, 0.78-0.89] and obese [aHR 0.80, 95% CI; 0.74-0.87] individuals was seen, p-value between obese and overweight vs normal, 0.30). On subgroup analysis by sex and smoking status, no difference was noted between men vs women, and never smokers vs ever-smokers. Conclusions: Based on meta-analysis, obese and overweight LC patients have reduced mortality compared to leaner individuals. The protective effect was seen across sexes and smoking status. Ideal body weight in LC patients should be reconsidered. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 33 Clinical Research Abstract #22 Presenter: Daniel I Sullivan Authors: Daniel I. Sullivan, Fernando Torres, Amit Banga , Manish R. Mohanka, Srinivas Bollineni, Jessica Mullins, Usha Rao, Chantale Lacelle, Pavan Duddupudi, Dhiraj Surapaneni, Vaidehi Kaza Title: Associations between Donor Specific Antibody Treatment and Lung Transplant Outcomes Abstract: Purpose: Development of donor specific antibodies (DSA) is common after lung transplantation (LT), and is a risk factor for bronchiolitis obliterans syndrome (BOS). The aim of our study was to evaluate the association of prevalence and strength of DSA on survival and time to BOS. Purpose: Development of donor specific antibodies (DSA) is common after lung transplantation (LT), and is a risk factor for bronchiolitis obliterans syndrome (BOS). The aim of our study was to evaluate the association of prevalence and strength of DSA on survival and time to BOS. Methods: Records of patients receiving LT between 01/01/2010 and 6/30/2014 were examined to determine prevalence of DSA. Patients with cumulative mean fluorescence intensity (cMFI) greater than or equal to 4000 units at highest strength were defined as having DSA. This group was compared to those without DSA. Primary end points were survival and time to BOS grades 1, 2, and 3. Results: In our cohort, 48% of patients developed DSA. Mortality was 35% in the DSA positive group and 26% in the DSA negative group. A statistically insignificant trend toward reduced survival was seen in the DSA positive group (p = 0.14). Mean time to onset of BOS was 2.6 years in the DSA positive group and 2.9 years in the DSA negative group (p = 0.09). A strong correlation was seen for time to BOS grade 3 among DSA positive patients with cMFI greater than 10000 units (HR = 2.735, p = 0.001). Conclusions: The presence of DSA does not portend worse survival during our period of study. No statistical difference in time to BOS existed between groups with and without DSA. These preliminary findings need to be confirmed in larger multi-center, randomized, controlled trial with longer time to follow up. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 34 Clinical Research Abstract #23 Presenter: Daniel I Sullivan Authors: Daniel I. Sullivan, Fernando Torres, Amit Banga, Manish R. Mohanka, Srinivas Bollineni, Jessica Mullins, Usha Rao, Chantale Lacelle, Pavan Duddupudi, Dhiraj Surapaneni, Vaidehi Kaza Title: Associations between Donor Specific Antibody Treatment and Lung Transplant Outcomes Abstract: Purpose: Development of donor specific antibodies (DSA) is common after lung transplantation (LT), and is a risk factor for bronchiolitis obliterans syndrome (BOS). The aim of our study was to evaluate the association of DSA treatment on survival and time to BOS. Purpose: Development of donor specific antibodies (DSA) is common after lung transplantation (LT), and is a risk factor for bronchiolitis obliterans syndrome (BOS). The aim of our study was to evaluate the association of DSA treatment on survival and time to BOS. Methods: Records of patients receiving LT between 01/01/2010 and 6/30/2014 were examined to determine prevalence of DSA. Patients with cumulative mean fluorescence intensity (cMFI) greater than or equal to 4000 units at highest strength were defined as having DSA. Those who were treated for DSA were compared to those who were not. Primary end points were survival and time to BOS grades 1, 2, and 3. Results: In our cohort, 48% of patients developed DSA. Within this group, 51% were treated for DSA and 49% were not. Mean time to BOS onset in the treatment group was 2.3 years compared to 3.0 years in the control group (p = 0.003). Overall mortality was 43% and 28%, respectively for treatment and control groups (p = 0.18). Conclusions: No improvement in mortality was seen for patients who were treated for DSA during our period of study. Those who were treated had earlier onset of BOS. Despite the use of several available treatment options among patients with DSA, it remains unclear when to treat and how patients will respond to treatment. These preliminary findings need to be confirmed in larger multicenter, randomized, controlled trial with longer time to follow up. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 35 Clinical Research Abstract #24 Presenter: Fernando Woll Authors: Chinemerem J. Okwara, MD; Fernando Woll, MD; Aurelia Schmalstieg, MD; Kavita Bhavan, MD, MHS Title: A Retrospective Evaluation of Clinical Outcomes of Patients Treated with Outpatient Parenteral Antimicrobial Therapy (OPAT) for Liver abscess in a Resource Limited Setting Abstract: The aim of this study is to evaluate the clinical outcomes of patients with liver abscess who were treated in the PHHS OPAT clinic by retrospectively reviewing data on readmissions, mortality and duration of outpatient IV antibiotics. The aim of this study is to evaluate the clinical outcomes of patients with liver abscess who were treated in the PHHS OPAT clinic by retrospectively reviewing data on readmissions, mortality and duration of outpatient IV antibiotics. This is a retrospective review of our OPAT database from 2010 – 2013. Ten patients were identified from this database using the ICD-9 code for liver abscess who met our inclusion criteria. Demographics of the patient: Race: 5 Hispanic, 2 Caucasian, 2 African American and 1 Asian Diagnostic modality: Ct abdomen: 6, MR abdomen: 2 and ultrasound: 2 Microbiology: Polymicrobial: 5, single agent: 4 Antibiotic regimen: Ertapenem: 6, Ceftriaxone: 5, Daptomycin: 1, Vancomycin: 1 Mean length of stay: 13 days. Range 9-18 days Mean duration of intravenous antibiotics: 5.2 weeks. Range 2 – 6 weeks Percutaneous drainage of the abscess: Performed in 6/10 (60%) Mortality: 2/10 in 1 year Conclusions: OPAT is a safe option for the management of liver abscesses that require long-term IV antimicrobial therapy. There were not any mortality or readmission events during our study period that were due to complications of selfadministration of IV antimicrobials in our OPAT program or failure of antimicrobial therapy 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 36 Clinical Research Abstract #25 Presenter: Htet Khine Authors: Htet Khine, MD; Wei Cheng Yuet, PharmD; Beverley Huet, MS; Zahid Ahmad, MD Title: Familial Hypercholesterolemia, Statin-Induced Myopathy, and SLCO1B1 rs4149056 Abstract: Introduction: Patients with familial hypercholesterolemia (FH) may be at increased risk of statin-induced myopathy since they require long-term treatment with high-intensity statin therapy. We sought to determine 1) whether other predisposing factors, including the well-known genetic variant associated with statin-induced myopathy – solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056 – also increase the risk of myopathy in FH patients, and 2) the natural history and management for FH patients with statin-induced myopathy. Introduction: Patients with familial hypercholesterolemia (FH) may be at increased risk of statin-induced myopathy since they require long-term treatment with high-intensity statin therapy. We sought to determine 1) whether other predisposing factors, including the well-known genetic variant associated with statin-induced myopathy – solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056 – also increase the risk of myopathy in FH patients, and 2) the natural history and management for FH patients with statin-induced myopathy. Methods: We queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women) recruited from lipid clinics in the Dallas, TX area. Statin-induced myopathy was defined as muscle complaints (pain, weakness, or cramps) arising while taking a statin and resulting in an interruption in therapy. Genotyping of rs4149056 was performed by allelic discrimination using real-time polymerase chain reaction TaqMan assays. Results: Statin-induced myopathy occurred in 36% (n=97). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT), 48 heterozygotes (TC) and one homozygote (CC). The variant C allele was not associated with the risk of statin-induced myopathy (OR 0.70, [95% CI 0.37, 1.33]). The risk of myopathy was associated with age (OR 1.6, [95% CI 1.2, 2.2]), BMI in non-AfricanAmericans (0.90 [0.83, 0.97], and hypertension (0.4, [0.2, 0.9]). 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 37 Clinical Research Abstract #26 Presenter: Htet Khine Authors: Htet W. Khine, Katarina Steding-Ehrenborg, Jeffery L. Hastings, Michael W. Bungo, Jamie Kowal, James Daniels, Rick Page, Jeff Goldberger, Benjamin D. Levine Title: Effects of Prolonged Space Flight on Left Atrium Size and Risk of Atrial Fibrillation Abstract: Introduction: Atrial fibrillation (AF) is the most common arrhythmia in the United States, and its prevalence increases with age. With the aging of current astronauts, AF is an increased concern. The prevalence of AF in astronauts is about 5%, similar to that of the general population but with younger age of presentation. A few documented risk factors for AF include left atrial size enlargement (in the elderly population and competitive athletes), and increased number of premature atrial complexes (in those with acute stroke). The aim of this study is to evaluate changes in atrial structure and the supraventricular beats to determine whether space flight increases risk for AF. Introduction: Atrial fibrillation (AF) is the most common arrhythmia in the United States, and its prevalence increases with age. With the aging of current astronauts, AF is an increased concern. The prevalence of AF in astronauts is about 5%, similar to that of the general population but with younger age of presentation. A few documented risk factors for AF include left atrial size enlargement (in the elderly population and competitive athletes), and increased number of premature atrial complexes (in those with acute stroke). The aim of this study is to evaluate changes in atrial structure and the supraventricular beats to determine whether space flight increases risk for AF. Methods: We studied 12 astronauts (8 men, 4 women) who underwent cardiac MRI with gadolinium contrast before and after 6 months in space and Holter monitoring for multiple 48-hour time periods before flight, during flight, and on landing day. Long-axis images in the 2chamber, 3chamber and 4chamber view were used to obtain left atrium volumes. The Holter data were analyzed blindly by two experienced electrophysiologists. Results: Left atrium volume increased after 6 months (mean±SD 14±18ml, p=0.03). Five out of 12 astronauts displayed an increase larger than the coefficient of variation, 12.1%. Intraobserver variability for LA volume was -5±23ml, SEE 12.4. When compared to baseline data of supraventricular beats before flight, no changes were noted over time. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 38 Clinical Research Abstract #27 Presenter: Htet Khine Authors: Htet Khine, MD, John F. Teiber, PhD, Robert W. Haley, MD, Amit Khera, MD, Colby Ayers, MS, Anand Rohatgi, MD Title: Association of the Serum Myeloperoxidase/High-Density Lipoprotein Particle Ratio and Incident Cardiovascular Events in a Multi-Ethnic Population: Observations from the Dallas Heart Study Abstract: Introduction: Myeloperoxidase (MPO) promotes oxidation of lipoproteins whereas high-density lipoprotein (HDL) exerts antioxidative effects in part via paraoxonase-1 (PON1). MPO can induce dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We hypothesized that increased serum levels of MPO indexed to HDL particle concentration would be associated with an adverse phenotype with increased CVD risk and tested this hypothesis in a large multiethnic population free of CVD at baseline. Introduction: Myeloperoxidase (MPO) promotes oxidation of lipoproteins whereas high-density lipoprotein (HDL) exerts antioxidative effects in part via paraoxonase-1 (PON1). MPO can induce dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We hypothesized that increased serum levels of MPO indexed to HDL particle concentration would be associated with an adverse phenotype with increased CVD risk and tested this hypothesis in a large multiethnic population free of CVD at baseline. Methods: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD (57% women, 49% black). The associations of the MPO/HDLp ratio with incident ASCVD (first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results: MPO/HDLp was associated directly with total cholesterol, C-reactive protein, interleukin 18, and body mass index, and inversely with PON1 arylesterase activity, HDL-C, and HDL size. In adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total CVD (aHR, 1.91, 95% CI 1.27-2.85). 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 39 Clinical Research Abstract #28 Presenter: Jeanney Lew Authors: Jeanney Lew MD, Monika Sanghavi MD, MSCS, Colby R Ayers MS, Darren K McGuire MD, MHSc, Maria O Gore MD, Jarett D Berry MD, MS, Amit Khera MD, MSC, Anand Rohatgi MD, James A de Lemos MD Title: Understanding the Venus and Mars Effect: Sex-Based Differences Across a Spectrum of Cardiovascular Biomarkers Abstract: It is unknown whether sex-based differences in the prevalence and pathobiology of cardiovascular disease (CVD) can be informed by cardiovascular biomarker profiles. It is unknown whether sex-based differences in the prevalence and pathobiology of cardiovascular disease (CVD) can be informed by cardiovascular biomarker profiles. Methods: A cross-sectional analysis was performed using data from the Dallas Heart Study, a multi-ethnic probability based cohort study. Associations between sex and 26 distinct biomarkers were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, MRI and DEXA measures of body composition and fat distribution, kidney function, insulin resistance, LV mass by MRI, and menopausal status. Results: The study included 3429 individuals, mean age 43, 56% women and 52% African American. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney dysfunction. In fully adjusted models, women had higher levels of HDL-C and HDL-p, leptin, d-dimer, osteoprotegerin, and NTproBNP, and lower levels of lipoprotein-associated phospholipase A2, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetric dimethylarginine, hs-cTnT, and cystatin C. Conclusion: Even after accounting for sex-based differences in traditional CVD risk factors, body composition and LV mass, important differences in biomarkers exist between women and men in the population. Future studies are needed to investigate causality. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 40 Clinical Research Abstract #29 Presenter: Mark Weinreich Authors: Mark A. Weinreich, MD; Oanh K. Nguyen, MD, MAS; David Wang, MD; Helen G. Mayo, MLS; Eric M. Mortensen, MD, MSc; Ethan A. Halm, MD, MPH; and Anil N. Makam, MD, MAS Title: PNEUMONIA READMISSION RISK PREDICTION MODELS: A SYSTEMATIC REVIEW OF MODEL PERFORMANCE Abstract: Rationale: Hospitals are financially penalized for higher than expected 30-day readmission rates among patients discharged with pneumonia. Predicting which patients are at highest risk for readmission could enable hospitals to proactively reallocate scarce resources to reduce 30-day readmissions. The objective of this review is to synthesize the available literature on pneumonia readmission risk prediction models and describe their performance. Rationale: Hospitals are financially penalized for higher than expected 30-day readmission rates among patients discharged with pneumonia. Predicting which patients are at highest risk for readmission could enable hospitals to proactively reallocate scarce resources to reduce 30-day readmissions. The objective of this review is to synthesize the available literature on pneumonia readmission risk prediction models and describe their performance. Methods: We systematically searched Ovid MEDLINE, Embase, The Cochrane Library, and CINAHL databases from inception through July 2015. Results: Of the 992 citations reviewed, 7 studies met inclusion criteria, which included 8 unique risk prediction models. Model discrimination (c-statistic) ranged from 0.59 to 0.77. The best performing model had a c-statistic of 0.77, but was from a single site so may be less generalizable and was not internally validated. Models derived from electronic health record data outperformed those derived from administrative data. Conclusions: We found a limited number of validated pneumonia-specific readmission models and their predictive ability was modest. Future models should seek to include more detailed information from the EHR on clinical severity, course throughout the index hospitalization, and social factors that influence readmission risk. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 41 Clinical Research Abstract #30 Presenter: Mark Weinreich Authors: Kim Styrvoky, Mark Weinreich, Carlos E. Girod, Rosechelle Ruggiero Title: Risk Factors for Thirty-day Readmissions Among Sepsis Survivors at a Safety Net Hospital Abstract: Rationale: Sepsis is associated with increased morbidity, mortality and healthcare utilization. Thirty-day readmission rates are increasingly being used as a quality metric. The aim of this study was to identify factors associated with 30-day readmission rates of patients admitted with sepsis at a safety net hospital. Rationale: Sepsis is associated with increased morbidity, mortality and healthcare utilization. Thirty-day readmission rates are increasingly being used as a quality metric. The aim of this study was to identify factors associated with 30-day readmission rates of patients admitted with sepsis at a safety net hospital. Methods: Retrospective chart review of all patients admitted with sepsis during fiscal year 2013 was performed to determine 30-day readmission rates and describe patient characteristics during the initial hospitalization for sepsis. Multivariate logistic regression was used to identify characteristics associated with 30-day readmission. Results: At Parkland Hospital during fiscal year 2013 there were 1533 admissions for sepsis. Among the 1049 survivors, there were 306 readmissions within 30 days. Comorbid conditions associated with greater odds of 30-day readmissions included end-stage renal disease (OR, 1.26; 95% CI 1.17-1.36), malignancy (OR, 1.14; 95% CI 1.08-1.21), and cirrhosis (OR 1.11; 95% CI 1.02-1.20). Bacteremia during the initial hospitalization (OR 1.07; 95% CI 1.011.15) was associated with increased odds for 30-day readmission. Conclusions: Among sepsis survivors at Parkland Hospital, 29.1% were readmitted within 30 days. Factors associated with increased odds of 30-day readmission included the presence of a comorbid condition (ESRD, malignancy, cirrhosis), bacteremia during the initial hospitalization or being discharged with a catheter. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 42 Clinical Research Abstract #31 Presenter: Mark Weinreich Authors: Kim Styrvoky, Mark Weinreich, Carlos E. Girod, Rosechelle Ruggiero Title: Beyond Surviving Sepsis: Thirty-day Readmission Rates and Patient Characteristics at a Safety Net Hospital Abstract: Introduction: Patients admitted with sepsis have increased morbidity, mortality and healthcare utilization. Little is known about patient’s short-term morbidity following discharge. The aim of this study is to describe patients with sepsis who are readmitted within 30 days at a safety net hospital. Introduction: Patients admitted with sepsis have increased morbidity, mortality and healthcare utilization. Little is known about patient’s short-term morbidity following discharge. The aim of this study is to describe patients with sepsis who are readmitted within 30 days at a safety net hospital. Methods: During fiscal year (FY) 2013, a retrospective chart review was performed of all patients with an index admission of sepsis who were readmitted to Parkland Hospital within 30 days. Primary outcome was the sepsis readmission rate. Results: There were 1445 admissions for sepsis in FY 2013 at Parkland Hospital; 230 discrete patients accounting for 306 admissions were readmitted within 30 days. The mean age was 50.4 ±14.4 years. Comorbid conditions included diabetes mellitus (35.0%), malignancy (25.8%), ESRD (20.9%), cirrhosis (11.4%), CHF (10.4%), and HIV (6.2%). A quarter of the readmissions occurred within 7 days, 47.0% were secondary to infection and 27.8% were readmitted with sepsis. Thirty-seven percent required ICU care during their initial hospitalization as compared to 25.1% during the readmission; mortality was 2.9%. Conclusions: During FY 2013, 21.2% of patients admitted with sepsis were readmitted within 30 days at Parkland Hospital. Nearly half of the readmissions were secondary to infection. Morbidity was less than during the initial hospitalization but still notable, as 25.1% required an ICU stay during the readmission. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 43 Clinical Research Abstract #32 Presenter: Mark Weinreich Authors: Mark Weinreich, MD; Ling Han, PhD; TM Gill, MD; Una Makris, MD Title: Restricting Back Pain and Subsequent Disability Among Community-Living Older Adults Abstract: Introduction: Although back pain is common and costly, few longitudinal studies evaluate the association between back pain severe enough to restrict activity (restricting back pain) and the development of disability. The objective of this study was to evaluate the association between restricting back pain and subsequent essential(e) and instrumental(i) activities of daily living(ADL). Introduction: Although back pain is common and costly, few longitudinal studies evaluate the association between back pain severe enough to restrict activity (restricting back pain) and the development of disability. The objective of this study was to evaluate the association between restricting back pain and subsequent essential(e) and instrumental(i) activities of daily living(ADL). Methods: We evaluated the 754 participants (mean age 78 years, 64% women) of the Precipitating Events Project, a prospective study of community-living persons, all ADL independent at baseline, who completed monthly telephone assessments of restricting back pain and disability for 13 years. A recurrent events Cox model was used to evaluate the association between restricting back pain and subsequent disability. The model was adjusted for fixed-in-time (i.e., sex, ethnicity) and time-varying covariates (i.e., age, BMI, depressive symptoms, cognitive impairment, physical frailty) that were updated every 18 months. Results: Over a median follow-up of 113 months the rate (95% CI) of eADL and iADL disability was 3.62 (3.37,3.89) and 8.5 (8.05,8.98) per 100-person months respectively. After adjusting for covariates, restricting back pain was strongly associated with subsequent eADL and iADL disability, with a HR (95% CI)=3.47 (3.01,3.99) and 2.33 (2.08,2.61) respectively. Conclusions: In this longitudinal study, restricting back pain was independently associated with disability among older adults. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 44 Clinical Research Abstract #33 Presenter: Micah Eades Authors: Micah T. Eades, Colby R. Ayers, Amit Khera Title: Coronary artery calcium percentile stability in the Dallas Heart Study Abstract: Background: The 2013 ACC/AHA guidelines recommend upgrading risk classification for a coronary artery calcium (CAC) score ≥75th percentile when risk-based decisions are unclear. We sought to characterize and understand the long-term stability of CAC ≥75th percentile. Background: The 2013 ACC/AHA guidelines recommend upgrading risk classification for a coronary artery calcium (CAC) score ≥75th percentile when risk-based decisions are unclear. We sought to characterize and understand the long-term stability of CAC ≥75th percentile. Methods and Results: We used quantile regression with CAC scores from a reference population of 968 Dallas Heart Study (DHS) participants to define the 75th percentile for age and sex. We then stratified CAC scores from 699 DHS participants with paired CAC scans 6.7 [6.2, 7.3] years apart according to the defined 75th percentile. Of those with CAC ≥75th percentile, we found 60% had a pooled cohort risk less than the 7.5% treatment threshold and 76% had an absolute CAC score less than the 300 Agatston units (AU) guideline threshold. With reference to the benchmark 75th percentile, 76% remained above, and 91% remained below over the 6.7-year interval. A graded relationship was observed with 74% and 93% remaining above the 50th and 90th percentiles respectively. Those who moved from below to above the 75th percentile were more likely to have higher baseline CAC, diabetes, hypertension, smoking status, and antihypertensive medication use. Conclusion: Because CAC scores ≥75th percentile are a unique marker of cardiovascular risk that remain stable over time, they represent a reliable tool to guide long-term risk assessment. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 45 Clinical Research Abstract #34 Presenter: Stephen Dickson Authors: Stephen Dickson, Internal Medicine; Sharon Reimold, Cardiology Title: Changes In Valvuloarterital Impedance One Month After Transcatheter Aortic Valve Replacement In Patients With Severe Aortic Stenosis Abstract: Purpose: To noninvasively track the functionality of transcatheter aortic valve replacement (TAVR) and assess valvular disease burden by investigating the change in echocardiographic variables related to left ventricular (LV) strain including valvuloarterial impedance before and after TAVR. Purpose: To noninvasively track the functionality of transcatheter aortic valve replacement (TAVR) and assess valvular disease burden by investigating the change in echocardiographic variables related to left ventricular (LV) strain including valvuloarterial impedance before and after TAVR. Methods: Twenty patients with severe AS were retrospectively identified who 1) received a TAVR between 3/20/13 and 8/6/14, 2) had a complete transthoracic echocardiogram (TTE) within 10 weeks prior to TAVR and within 6 weeks after TAVR, and 3) had a pre-TAVR ejection fraction (EF) greater than 40%. All echocardiograms were re-analyzed without knowledge of the original published report by one trained researcher. Valvuloarterial impedance was calculated as (SAP + MG)/SVi, where systolic arterial pressure (SAP) was measured with a cuff sphygmomanometer and mean aortic gradient (MG) taken directly from the echocardiogram. Stroke volume index (SVi) was calculated as a function of stroke volume and body surface area. Results: One month after TAVR, non-indexed stroke volume showed a non-significant trend towards increasing (p=0.07) while a significant increase in indexed flow was noted (p=0.05). More impressively, a significant decrease in valvuloarterial impedance was observed (p<0.001). Conclusion: This study demonstrates a significant decrease in valvuloarterial impedance one month after successful TAVR, suggesting a potentially effective parameter for noninvasive assessment of TAVR functionality. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 46 Clinical Research Abstract #35 Presenter: Stephen Dickson Authors: Stephen Dickson, MD; Barbara Danek, Emmanouli Brilakis, MD Title: Using intracoronary Near-Infrared Spectroscopy (NIRS) to show differences in lipid core burden of plaques in uncontrolled diabetics Abstract: Purpose: To assess the lipid composition of coronary atherosclerotic plaques using intracoronary near-infrared spectroscopy (NIRS) in both diabetic and non-diabetic patients to allow a better understanding of diabetic coronary artery disease and improve outcomes in these patients. Purpose: To assess the lipid composition of coronary atherosclerotic plaques using intracoronary near-infrared spectroscopy (NIRS) in both diabetic and non-diabetic patients to allow a better understanding of diabetic coronary artery disease and improve outcomes in these patients. Methods: Three hundred and fifty four patients received an intracoronary angiogram with NIRS at the North Texas Veterans Affairs Medical Center between 2009 and 2015. Of those 354 patients, 203 patients that had 1) NIRS completed prior to coronary stent placement; 2) did not have a history of coronary artery bypass grafting; and 3) had a hemoglobin A1c within three months of the NIRS angiogram. Plaque lipid content was estimated by NIRS lipid core burden index (LCBI) and associated with corresponding patient hemoglobin A1c, serum lipid, and serum creatinine values. Patients were then grouped together based on A1c values and compared. Results: While there was no significant difference in LCBI scores between patients with a hemoglobin A1c greater than 7.0 and patients with a hemoglobin A1c less than 7.0, a meaningful but not significant (p=0.07) increase in LCBI was noted for patients with a hemoglobin A1c greater than 8.0. Conclusion: This study demonstrates an increase in lipid core burden of coronary artery plaques in uncontrolled diabetics, an important difference that may change interventional strategies in these patients in the future. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 47 Clinical Research Abstract #36 Presenter: Usman Akhtar Authors: Usman Akhtar, Emmanouil S. Brilakis Title: Meta-Analysis of Radial and Femoral Catheterization: Patient and Procedural Characteristics Contributing to The Radiation Exposure Difference Abstract: Background: This meta-analysis serves to provide a comprehensive analysis to better understand the variables that interact with radial artery catheterization to increase patient radiation exposure. Background: This meta-analysis serves to provide a comprehensive analysis to better understand the variables that interact with radial artery catheterization to increase patient radiation exposure. Methods: A comprehensive search algorithm was applied to the PubMed Database to find greater than 65 trials, encompassing over 80000 procedures. Effect size was utilized to provide differences between radial and femoral catheterization with regards to fluoroscopy time, dose area product, air kerma, and to determine whether certain patient and procedural characteristics increase the risk of radial radiation exposure. Results: The results showed that the small effect of increased radial radiation exposure for fluoroscopy time (d+ = .0.10) is amplified in certain subgroups studied including the DCA-only subgroup (d+ = .38), and in those subgroups of studies with increased women, and in those with patients that fit a metabolic syndrome phenotype with higher mean BMI, HLD, HTN, and Diabetes. The analysis of dose area product revealed a medium difference between radial and femoral catheterization (d+ = .25). Conclusions: Overall, the analysis shows that there is a small difference between mean radial and femoral catheterization times, and this difference is highly sensitive to the type of procedure performed and the phenotype of the patient. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 48 Clinical Research Abstract #37 Presenter: Wally Omar Authors: Wally Omar MD, Satyam Sarma MD, Erin Howden PhD, Justin Lawley PhD, Dean Palmer Title: The Effects of High Intensity Aerobic Exercise on Aortic Age Abstract: Background: Physical activity during middle age decreases the risk for developing heart failure. Aortic age, a measure of the intrinsic stiffening of the central arteries, is one means by which heart health can be measured. Past studies have postulated that the mechanism by which aerobic exercise confers cardiovascular benefit is through a decrease in afterload. The objective of this study, therefore, is to determine the changes in aortic age that occur after a high aerobic training program (HAT) in previously sedentary middle age adults. Background: Physical activity during middle age decreases the risk for developing heart failure. Aortic age, a measure of the intrinsic stiffening of the central arteries, is one means by which heart health can be measured. Past studies have postulated that the mechanism by which aerobic exercise confers cardiovascular benefit is through a decrease in afterload. The objective of this study, therefore, is to determine the changes in aortic age that occur after a high aerobic training program (HAT) in previously sedentary middle age adults. Methods: 61 healthy, middle-aged subjects were randomized to either yoga or HAT (2 moderate aerobic exercise sessions/week and 2 “4x4” aerobic interval sessions/week) for 6 months. Baseline and post-intervention aortic age was determined in the following manner: cardiac output (CO) was measured via the foreign-gas (C2H2) rebreathing method and stroke volume (SV) was determined from this measurement; a continuous finger arterial waveform was recorded, and normalized stroke volumes were generated from this waveform for ages 30 to 80; finally a linear regression analysis between the patient age and SV was constructed, the inverse function of which was used to determine aortic age. Results: After 6 months, adherence to training sessions was >90%. Baseline aortic age was a mean of 55 years in both groups. Aortic age increased with a mean of 8.5 years in the yoga group, but only 0.7 years in the HIAT group (p =0.026). 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 49 Clinical Research Abstract #38 Presenter: Wally Omar Authors: Wally Omar, MD, James De Lemos MD, Colby Ayers Title: Association of Leukocyte Telomere Length With High Sensitivity Troponin T in the General Population Abstract: Background: High-sensitivity troponin (hs-cTnT) assays have revealed that cardiac injury is indeed more prevalent than once thought. Approximately 15% of healthy individuals — i.e. those without cardiovascular disease, HTN, CKD or DM, will have elevated circulating troponins. We propose that the apparent gap between cardiac injury and its etiologies can be explained by telomere shortening, a process that is accelerated by oxidative injury and mutation. Telomere shortening has been shown to play a role in several fibrosing disease processes, but its role in cardiac injury is yet to be explored. Background: High-sensitivity troponin (hs-cTnT) assays have revealed that cardiac injury is indeed more prevalent than once thought. Approximately 15% of healthy individuals — i.e. those without cardiovascular disease, HTN, CKD or DM, will have elevated circulating troponins. We propose that the apparent gap between cardiac injury and its etiologies can be explained by telomere shortening, a process that is accelerated by oxidative injury and mutation. Telomere shortening has been shown to play a role in several fibrosing disease processes, but its role in cardiac injury is yet to be explored. Methods: A retrospective analysis of the Dallas Heart Study 2 (DHS2) cohort identified 3302 patients between the ages of 18 and 85 with data for both cTnT and leukocyte telomere length (LTL). LTL was obtained via quantitative PCR on circulating leukocytes and subsequently log transformed to achieve normalization. Logistic regression was employed to analyze the relationship between LTL and cTnT while adjusting for age, sex, and race. A multivariable regression was then utilized to assess the same relationship in the presence of the above factors. Results: We found a significant inverse correlation between age and LTL (r = -0.15, p<0.0001). LTL and hs-cTnT were also inversely correlated (r = -0.10, p<0.0001 unadjusted; r = -0.07, p= 0.03 when adjusted for age, sex and race), suggesting that telomere shortening may play a role in cardiac injury. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 50 Clinical Research Abstract #39 Presenter: Ariel Vinas Authors: Subhash Banerjee, MD, Ariel Vinas, MD, Atif Mohammad, MD, Omar Hadidi, MD, Rahul Thomas, MD, Karan Sarode, MA, Avantika Banerjee, BS, Puja Garg, PhD, Rick Weideman, PharmD, Bertis Little, PhD, Emmanouil Brilakis, MD, PhD Title: Significance of an Abnormal Ankle-Brachial Index in Patients With Established Coronary Artery Disease With and Without Associated Diabetes Mellitus Abstract: An abnormal ankle-brachial index (ABI) is associated with higher risk for future cardiovascular (CV) events; however, it is unknown whether this association is true in patients with established coronary artery disease (CAD) and associated diabetes mellitus (DM). We evaluated 679 patients with stable CAD enrolled in the Excellence in Peripheral Arterial Disease and Veterans Affairs North Texas Healthcare System peripheral arterial disease databases. ABI and 12-month major adverse CV events (MACEs, a composite of all-cause death, nonfatal myocardial infarction, need for repeat coronary revascularization, and ischemic stroke) were assessed. Cox proportional hazard models were used to assess the association of ABI and DM with subsequent CV events. An abnormal ABI (<0.9 or >1.4) was present in 72% of patients with stable CAD and 68% had DM. Using patients without DM and normal ABI as reference, the adjusted hazard ratio for 12-month MACE was 1.7 (95% confidence interval [CI] 0.71 to 4.06) for patients with DM and normal ABI; 2.03 (95% CI 0.83 to 4.9) for patients without DM with abnormal ABI; and 4.85 (95% CI 2.22 to 10.61) for patients with DM and abnormal ABI. In conclusion, in patients with stable CAD, an abnormal ABI confers an incremental risk of MACE in addition to DM and traditional CV risk factors. An abnormal ankle-brachial index (ABI) is associated with higher risk for future cardiovascular (CV) events; however, it is unknown whether this association is true in patients with established coronary artery disease (CAD) and associated diabetes mellitus (DM). We evaluated 679 patients with stable CAD enrolled in the Excellence in Peripheral Arterial Disease and Veterans Affairs North Texas Healthcare System peripheral arterial disease databases. ABI and 12-month major adverse CV events (MACEs, a composite of all-cause death, nonfatal myocardial infarction, need for repeat coronary revascularization, and ischemic stroke) were assessed. Cox proportional hazard models were used to assess the association of ABI and DM with subsequent CV events. An abnormal ABI (<0.9 or >1.4) was present in 72% of patients with stable CAD and 68% had DM. Using patients without DM and normal ABI as reference, the adjusted hazard ratio for 12-month MACE was 1.7 (95% confidence interval [CI] 0.71 to 4.06) for patients with DM and normal ABI; 2.03 (95% CI 0.83 to 4.9) for patients without DM with abnormal ABI; and 4.85 (95% CI 2.22 to 10.61) for patients with DM and abnormal ABI. In conclusion, in patients with stable CAD, an abnormal ABI confers an incremental risk of MACE in addition to DM and traditional CV risk factors. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 51 Clinical Research Abstract #40 Presenter: Jedrek Wosik Authors: Jedrek Wosik, MD; Thao Duong, MD; Jose R. Martinez Parachini, MD; Erica Resendes, BS; Bavana V. Rangan, BDS, MPH; Michele Roesle, RN, BSN; Nicole Minniefield, MD; Laura Collins, MD; Jerrold Grodin, MD; Shuaib M. Abdullah, MD; Subhash Banerjee, MD; Emmanouil S. Brilakis, MD, PhD Title: Echocardiogram Interpretation via Google Glass Abstract: Background: We evaluated the use of Google Glass for remote transthoracic echocardiography (TTE) video capture and interpretation. Background: We evaluated the use of Google Glass for remote transthoracic echocardiography (TTE) video capture and interpretation. Methods: Google Glass was used to record 17 TTE studies with 25 key findings. Ten physicians (3 faculty and 7 fellow cardiologists) interpreted recordings on a) desktop, b) iPhone, c) iPad, and d) Google Glass. Those interpretations were compared with those obtained by viewing the original studies on a desktop. One point was given for correct finding identification. Subjective rating of the user experience was also recorded. Results: The mean TTE interpretation score (maximum: 25 points) for the original TTE study viewed on a desktop was 24.3 ± 0.7. The scores for Google Glass recorded TTE images viewed on a desktop, an iPad, an iPhone and Google Glass were 21.3 ± 1.6, 18.3 ± 1.6, 18.8 ± 1.3, and 17.1 ± 2.1, respectively (p<0.001). Significant differences (p<0.05) were found between the original studies and all recordings for three findings: McConnell’s sign, bicuspid aortic valve and apical aneurysm. Most (70%) of the physicians were satisfied with the video quality acquired by Google Glass, but 80% were neutral regarding giving recommendations based on the captured images. Conclusion: Google Glass is able to capture hands-free videos of TTE studies, which can be viewed by specialists on a variety of devices; however, interpretation is less accurate than that of the original TTE viewed on a desktop computer. 1 ANNUAL DONALD W. SELDIN, M.D. RESEARCH SYMPOSIUM May 27, 2016 52 Clinical Research Abstract #41 Presenter: Ragisha Gopalakrishnan