Adjustment For Other Clinical Factors Research Articles

Femoral Neck Osteoporosis Is Associated with a Higher Odds of Coronary Artery Disease in Indian Postmenopausal Women: A Cross-sectional Study from a Teaching Hospital in Southern India.

Purpose: Epidemiological studies have shown an association between coronary artery disease (CAD) and osteoporosis. We studied the prevalence of CAD among postmenopausal women with osteoporosis. Factors that were significantly associated with CAD were also assessed. Methods: This was a cross-sectional study conducted over a period of 2 years. Consecutive postmenopausal women aged ≥50 years were recruited. The details of an underlying CAD were obtained. Bone biochemical parameters, bone mineral density and body composition were assessed. Results: A total of 370 postmenopausal women with mean (standard deviation [SD]) ages of 61.6 (6.2) and 60.1 (6.0) years and a body mass index of 25.3 (14.1) kg/m2 were recruited. Among them, 110 of 370 patients (29.7%) had an underlying CAD and 222 of 370 (60%) had osteoporosis at either the femoral neck or lumbar spine (LS). The odds of CAD among those with osteoporosis were 3.5 (95% confidence interval [CI]: 2.1-5.9). An LS T-score of ≤-2.2 had a sensitivity of 80% and a specificity of 45% in predicting CAD (area under the curve, AUC: 0.736; 95% CI: 0.677-0.795; p<0.001). A femoral neck T-score of ≤-1.9 had a sensitivity of 80% and a specificity of 60% in predicting CAD (AUC: 0.748; 95% CI: 0.696-0.800; p<0.001). On a logistic regression analysis after adjusting for various clinical parameters, femoral neck osteoporosis had the highest odds of CAD. Conclusion: The prevalence of CAD was higher among postmenopausal women with osteoporosis. Femoral neck osteoporosis conferred the highest odds of CAD after adjustment for other clinical factors.

Abstract 14792: Predisposing Risk Factors Affecting Reversibility of Left Ventricular Diastolic Dysfunction in Patients With Moderate Diastolic Dysfunction and Preserved Ejection Fraction

Introduction: Few data exist on factors affecting the reversibility of diastolic dysfunction (DD) especially in patients with preserved left ventricular ejection fraction (LVEF). Hypothesis: In the present study, we investigated the predisposing risk factors affecting the reversibility of DD in patients with moderate DD and preserved LVEF. Methods: A total of 600 patients with moderate DD and preserved LVEF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing factor affecting the reversibility of DD. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or mild DD (improved group) and 221 (37%) patients had maintained or worsened DD (unimproved group). Among the clinical risk factors, the incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (11 vs. 18, p=0.007). After adjustment for other clinical factors, PAF was determined to be an independent predisposing risk factor for the unimproved group (odds ratio, 2.76; 95% CI: 1.28-6.21, p=0.01). At follow-up echocardiography, the mean E/A ratio and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusions: We identified that PAF was an independent predisposing risk factor for the unimproved group in patients with moderate DD and preserved LVEF. Therefore, further management of PAF might be required in patients with moderate DD and preserved LVEF to prevent adverse cardiovascular events.

Effect of Metabolic Dysfunction-Associated Fatty Liver Disease on Left Ventricular Deformation and Atrioventricular Coupling in Patients With Metabolic Syndrome Assessed by MRI.

Metabolic dysfunction-associated fatty liver disease (MAFLD) was recently recognized as an important risk factor for cardiovascular diseases. To examine the effect of MAFLD on cardiac function in metabolic syndrome by MRI. Retrospective. One hundred seventy-nine patients with metabolic syndrome (MetS), 101 with MAFLD (MAFLD [+]) and 78 without (MAFLD [-]). Eighty-one adults without any of the components of MetS or cardiac abnormalities were included as control group. 3.0 T; balanced steady-state free precession sequence. Left atrial (LA) strain was assessed during three phases: reservoir strain (LA-RS), conduit strain (LA-CS), and booster strain (LA-BS). Left ventricular (LV) global longitudinal (LV-GLS) strain was also derived. The left atrioventricular coupling index (LACI) was calculated as the ratio of LA end-diastolic volume (LA-EDV) and LV-EDV. Student's t test or Mann-Whitney U test; One-way analysis of variance. A P value <0.05 was considered statistically significant. Among MetS patients, individuals with MAFLD had significantly lower magnitude LV-GLS (-11.6% ± 3.3% vs. -13.8% ± 2.7%) than those without MAFLD. For LA strains, LA-RS (36.9% ± 13.7% vs. 42.9% ± 13.5%) and LA-CS (20.0% ± 10.6% vs. 24.1% ± 9.2%) were also significantly reduced in MAFLD (+) compared to MAFLD (-). The LACIs (17.2% [12.9-21.2] % vs. 15.8% [12.2-19.7] %) were significantly higher in patients with MAFLD compared to those without MAFLD. After adjustment for other clinical factors, MAFLD was found to be independently correlated with LV-GLS (β=-0.270) and LACI (β=0.260). MAFLD had an unfavorable effect on LV myocardial strain in MetS. Moreover, LA strain and atrioventricular coupling were further impaired in patients with concomitant MAFLD compared to those without MAFLD. Last, MAFLD was independently associated with subclinical LV dysfunction and atrioventricular coupling after adjustment for other clinical factors. 3 TECHNICAL EFFICACY: 3.

Abstract 15083: Chronicity of Heart Failure, In-Hospital Clinical Trajectory, and Post-Discharge Outcomes Among Patients Hospitalized for Heart Failure

Introduction: Among patients hospitalized for HF, patients hospitalized with worsening chronic heart failure (WCHF) are at increased risk for morbidity and mortality compared with those who are recently diagnosed with HF. Whether there are differences in clinical course during hospitalization for HF is unclear. Methods: We pooled 735 participants hospitalized for HF in the DOSE, CARRESS, and ROSE trials. We grouped participants by whether HF was recently diagnosed (≤12 months) or WHCF (&gt;12 months). We compared changes in congestion, kidney function, and symptoms during hospitalization, as well as early post-discharge kidney and mortality outcomes. Results: Overall, 132 (18%) had recently diagnosed HF and 603 (82%) had WCHF. Compared with WCHF, patients with recently diagnosed HF tended to have lower serum creatinine and higher systolic blood pressure, ejection fraction, and serum NT-proBNP (all p&lt;0.05). In the first 72 hours, changes in body weight, global well-being visual analog scale, serum creatinine, and serum NT-proBNP, as well as net fluid loss were similar between patients with recently diagnosed versus WCHF (all p&gt;0.15) ( Figure ). Recently diagnosed HF showed improved dyspnea at 72 hours (p=0.03). There was no difference in change in serum creatinine from baseline to 60 days (p=0.75). There was a trend toward significantly increased odds of mortality during study follow-up (adjusted odds ratio 1.96 [95% confidence interval 0.97-3.94], p=0.06). Conclusion: Patients hospitalized for recently diagnosed and WCHF have generally similar in-hospital clinical trajectories, and similar changes in kidney function early post-discharge. Despite these similarities and adjustment for other clinical factors, patients with WCHF remain at increased risk for post-discharge mortality as compared with patients who are more recently diagnosed.

Abstract 10697: Both ST2 and BNP Predicts Atrial Fibrillation Independently of Heart Failure but BNP is Stronger When Used in Combination

Background: ST2, a novel marker of fibrosis in heart failure, may be a marker in Atrial fibrillation (AF) due to the role of fibrosis in AF. There is paucity of data suggesting the association of ST2 with AF. Hypothesis: To examine the association of ST2 with AF and its incremental value over traditional biomarkers. Methods: 619 unselected patients presenting to a Cardiology service had BNP and ST2 sent. They included patients with heart failure, acute coronary syndromes, elective cardioversion for AF and cardiac catheterisation. Results: Their characteristics are shown in Table1. Both ST2 and BNP levels were significantly higher in patients with heart failure, chronic kidney disease (CKD) and AF. The AF group (30%) were older and had higher prevalence of heart failure and CKD. Both ST2 and BNP were associated with AF in both univariable (Table 2) and multi-variable models, and remained independent predictors when adjusted for risk factors (Table 3 Model 2). However, ST2 loses significance when BNP is added to the model (Table 2 Model 3). While ST2 levels were significantly higher in males, there was no significant interaction when stratified by sex (interaction p=0.31). Conclusions: Both ST2 and BNP are independent predictors of AF even after adjustment for other clinical factors. When ST2 is used in combination with BNP, raised BNP appears to be a stronger predictor of AF than ST2.

Impact of major infections on 10-year mortality after revascularization in patients with complex coronary artery disease

BackgroundThe significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear. Methods and resultsThis is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62–1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057). ConclusionsDespite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years.Trial registration:SYNTAXES ClinicalTrials.gov reference: NCT03417050SYNTAX ClinicalTrials.gov reference: NCT00114972

Proton pump inhibitor usage reduces sustained viral response rates for veterans with HIV/HCV coinfection on ledipasvir/sofosbuvir: a real-world study from a multicentre VA cohort.

Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H2 -receptor antagonist [H2 B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H2 B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74-0.99, p=.03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26-0.85, p=.01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.

Association of Brain Atrophy and Masseter Sarcopenia With 1-Year Mortality in Older Trauma Patients

Older adults are disproportionately affected by trauma and accounted for 47% of trauma fatalities in 2016. In many populations and disease processes, described risk factors for poor clinical outcomes include sarcopenia and brain atrophy, but these remain to be fully characterized in older trauma patients. Sarcopenia and brain atrophy may be opportunistically evaluated via head computed tomography, which is often performed during the initial trauma evaluation. To investigate the association of masseter sarcopenia and brain atrophy with 1-year mortality among trauma patients older than 65 years by using opportunistic computed tomography imaging. This retrospective cohort study was conducted in a level 1 trauma center from January 1, 2011, to December 31, 2014, with a 1-year follow-up to assess mortality. Washington state residents 65 years or older who were admitted to the trauma intensive care unit with a head Abbreviated Injury Scale score of less than 3 were eligible. Patients with incomplete data and death within 1 day of admission were excluded. Data analysis was completed from June 2017 to October 2018. Masseter muscle cross-sectional area and brain atrophy index were measured using a standard clinical Picture Archiving and Communication System application to assess for sarcopenia and brain atrophy, respectively. Primary outcome was 1-year mortality. Secondary outcomes were discharge disposition and 30-day mortality. The study cohort included 327 patients; 72 (22.0%) had sarcopenia only, 71 (21.7%) had brain atrophy only, 92 (28.1%) had both, and 92 (28.1%) had neither. The mean (SD) age was 77.8 (8.6) years, and 159 patients (48.6%) were women. After adjustment for age, comorbidity, complications, and injury characteristics, masseter sarcopenia and brain atrophy were both independently and cumulatively associated with mortality (masseter muscle cross-sectional area per SD less than the mean: hazard ratio, 2.0 [95% CI, 1.2-3.1]; P = .005; brain atrophy index per SD greater than the mean: hazard ratio, 2.0 [95% CI, 1.1-3.5]; P = .02). Masseter muscle sarcopenia and brain atrophy were independently and cumulatively associated with 1-year mortality in older trauma patients after adjustment for other clinical factors. These radiologic indicators are easily measured opportunistically through standard imaging software. The results can potentially guide conversations regarding prognosis and interventions with patients and their families.

Serum biomarkers for predicting overall survival and early mortality in older patients with metastatic solid tumors.

We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy. Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined. Serum samples from 138 patients (median age: 75 years, range: 70-92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model. In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation.

Serum frailty biomarkers to predict overall survival in older patients with metastatic solid tumors: A substudy of prospective multi-center cohort study (KCSG PC13-09).

10041 Background: To determine individualized cancer treatment for older patients, easily measurable markers that predict functional decline and mortality are needed. The purpose of this study was to confirm prognostic value of potential biomarkers of frailty in older patients with metastatic solid tumors. Methods: Serum samples were prospectively collected before first line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors (KCSG PC13-09, WHO ICTRP number: KCT0001071). Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, Activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D (vitD) were measured by ELISA and IL-6, Myostatin, Irisin, FGF-19, FGF-21, FGF-23 by luminex mutiplex assay. Overall survival (OS) was studied by means of Kaplan-Meier, Log Rank and Cox methods. Results: Serum samples from 138 patients (median age: 75, range: 70-92) were collected from Feb 2014 to Dec 2016. During a median follow up time of 13.8 months, 72 (52.6%) patients had died. Among 13 serum markers, CRP (log-rank, P=0.006), Activin A (P=0.003), and Myostatin (P=0.043) were significantly correlated with OS in univariate analyses. In a Cox regression analysis, Activin A (HR 2.36, 95% CI 1.41-3.96; P=0.001) and Myostatin (HR 2.70, 95% CI 1.24-5.84; P=0.012) were significantly associated with OS after adjustment of other clinical factors (Age, Gender, ECOG PS, BMI, Geriatric assessment, Chemotherapy response, WBC, Albumin). Conclusions: In older cancer patients, high serum concentration of Activin A and Myostatin are predictive of poor OS. [Table: see text]

Impact of Ejection Fraction and Aortic Valve Gradient on Outcomes of Transcatheter Aortic Valve Replacement

BackgroundIn patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), studies have suggested that reduced left ventricular (LV) ejection fraction (LVEF) and low aortic valve gradient (AVG) are associated with worse long-term outcomes. Because these conditions commonly coexist, the extent to which they are independently associated with outcomes after TAVR is unknown. ObjectivesThe purpose of this study was to evaluate the impact of LVEF and AVG on clinical outcomes after TAVR and to determine whether the effect of AVG on outcomes is modified by LVEF. MethodsUsing data from 11,292 patients who underwent TAVR as part of the Transcatheter Valve Therapies Registry, we examined rates of 1-year mortality and recurrent heart failure in patients with varying levels of LV dysfunction (LVEF <30% vs. 30% to 50% vs. >50%) and AVG (<40 mm Hg vs. ≥40 mm Hg). Multivariable models were used to estimate the independent effect of AVG and LVEF on outcomes. ResultsDuring the first year of follow-up after TAVR, patients with LV dysfunction and low AVG had higher rates of death and recurrent heart failure. After adjustment for other clinical factors, only low AVG was associated with higher mortality (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32; p < 0.001) and higher rates of heart failure (hazard ratio: 1.52; 95% confidence interval: 1.36 to 1.69; p <0.001), whereas the effect of LVEF was no longer significant. There was no evidence of effect modification between AVG and LVEF with respect to either endpoint. ConclusionsIn this series of real-world patients undergoing TAVR, low AVG, but not LV dysfunction, was associated with higher rates of mortality and recurrent heart failure. Although these findings suggest that AVG should be considered when evaluating the risks and benefits of TAVR for individual patients, neither severe LV dysfunction nor low AVG alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR.

Prognostic Value of Preradiotherapy 18F-FDG PET/CT Volumetrics in Limited-Stage Small-Cell Lung Cancer

BackgroundWhether 18F-fludeoxyglucose positron emission tomography (PET)/computed tomography (CT) metrics predict outcome in limited-stage (LS) small-cell lung cancer (SCLC) has not been well established; most previous reports have only analyzed maximal standardized uptake values (SUVmax). We investigated multiple pretreatment PET metrics, including SUVmax, mean SUV (SUVmean), total lesion glycolysis, and metabolic tumor volume (MTV) in LS-SCLC patients undergoing chemoradiotherapy (CRT) and correlated them with survival and disease control outcomes. Patients and MethodsAll patients received platinum-based chemotherapy and a median radiation dose of 45 Gy. Kaplan-Meier and competing-risks analyses were performed to assess the prognostic value of PET metrics with respect to overall survival (OS), distant failure (DF), disease-free survival (DFS), and locoregional failure (LRF). Univariate and multivariate analyses were performed to account for the effect of other clinical factors on outcomes. ResultsA total of 120 patients with LS-SCLC had analyzable pre-CRT PET/CTs. The median follow up was 34 months. Median OS was 26.9 months. OS was 53.2% at 2 years and 33.1% at 5 years. SUVmax, SUVmean, MTV, and total lesion glycolysis of the primary tumor were not significantly associated with OS, LRF, and DFS on univariate analysis. MTV was significantly associated with DF (P = .024) on univariate but not multivariate analysis. ConclusionThis is the largest reported series to date evaluating the prognostic value of baseline PET metrics in LS-SCLC. Neither SUVmax nor other analyzed PET metrics demonstrated significant correlation with OS or LRF. MTV was correlated with DF and DFS, but this association was no longer significant after adjustment for other clinical factors. This analysis suggests that pretreatment PET scans, even with the use of advanced metrics, do not have independent prognostic value for outcomes in LS-SCLC patients after CRT.

Abstract P6-08-33: Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of AC followed by docetaxel: A multicenter retrospective cohort study

Abstract Background: The ratio of involved to retrieved lymph nodes (LNR) is suggested as a prognostic factor in operable breast cancer. However, there are conflicting results regarding its clinical significance after neoadjuvant chemotherapy. We investigated the prognostic value of LNR with a thorough evaluation of potential prognostic factors in a large cohort constructed from Health Insurance Review and Assessment Service database of Korea. Patients and method: This retrospective analysis is based on the data of 814 patients with clinical stage II/III breast cancer treated with four cycles of adriamycin/cyclophosphamide (AC) followed by four cycles of docetaxel (DOC) before surgery. We evaluated the clinical significance of the LNR (3 categories: Low, 0-0.20 vs. Intermediate, 0.21-0.65 vs. High, 0.66 -1.00) using Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Result: A total of 799 patients underwent breast surgery (Median age 45, range 16-74; Mastectomy 369, Lumpectomy 380, and Others 50). Axillary lymph node dissection was performed in 704 (88.1%) patients. Pathologic complete response (pCR, pT0/isN0) was achieved in 129 (16.1%) of 799 patients (HR+/HER2-, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; TNBC 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range 0-42) and 13.98 (range 1-64), respectively. The mean LNR was 0.17 (Low, 574 [71.8%]; Intermediate, 170 [21.3%]; High, 55 [6.9%]). In univariate analysis, LNR was significantly associated with worse relapse-free survival (3-yr RFS rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; P &amp;lt;0.0001, log-rank test). In multivariate analysis, LNR was not significantly associated with recurrence after adjustment of other clinical factors (Age, histologic grade, intrinsic subtype, ypT-stage, ypN-stage, lymphatic or vascular invasion, and pCR). Multivariate analysis for relapse-free survival P-valueHR95%CIAGE (&amp;lt;50, ≥50)0.157--ypT-stage&amp;lt;0.0001--ypN-stage0.035--pCR (T0/isN0)0.027--Lymphovascular invasion0.040--Subtype&amp;lt;0.0001--Histologic grade0.001--LNR Low (0-0.20)0.9541.00-LNR Intermediate (0.21-0.65)0.9731.010.55-1.86LNR High (0.66-1.00)0.7971.120.48-2.59 Conclusion: LNR is not superior to ypN-stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. Citation Format: Se Hyun Kim, Jee Hyun Kim, Tae-Yong Kim, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, In Hae Park, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Kyung Hae Jung. Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of AC followed by docetaxel: A multicenter retrospective cohort study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-33.

Soluble receptor for advanced glycation end products in critically ill patients and its associations with other clinical markers and 28-day mortality.

PurposeTo investigate the possible associations between serum levels of soluble receptor for advanced glycation end products (sRAGE) and specific clinical markers and prognosis in critically ill patients diagnosed with stress hyperglycemia.Patients and methodsA total of 70 critically ill patients and 25 normal controls were recruited for this study. Serum levels of sRAGE and advanced glycation end products (AGEs) were determined using enzyme-linked immunosorbent assay. Additional data on other clinical markers were obtained from patient records in the intensive care unit. Comparisons of sRAGE and AGEs levels between groups were assessed by t-test. The relationships between sRAGE and other clinical markers were assessed by Pearson’s correlation analyses and multiple linear regression analyses. Risk factors for prognosis, such as 28-day mortality were analyzed using logistic regression analysis.ResultsSerum sRAGE and AGEs levels were significantly higher in critically ill patients, compared to normal controls (P<0.05). The increase in serum sRAGE levels was significantly correlated with AGEs levels, interleukin-6 levels, and the sequential organ failure assessment score (P<0.01). Using multiple linear regression analysis, the association between AGEs and sRAGE remained significant after adjustment of other clinical factors. However, there were no significant correlations between sRAGE levels and patient outcome in these critically ill patients.ConclusionSerum sRAGE levels were significantly elevated in critically ill patients and positively correlated with higher AGEs levels, but sRAGE levels were not associated with increased mortality, suggesting sRAGE levels are not a predictor of prognosis in critically ill patients.

Up-Front Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Arising from the Myelodysplastic Syndrome

In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available. © 2014 S. Karger AG, Basel

Relation of coronary atherosclerosis and metabolic syndrome in asymptomatic subjects: evaluation with coronary CT angiography

To assess the relationship between metabolic syndrome (MetS) and coronary atherosclerosis using coronary CT angiography (CCTA) as the evaluation tool in asymptomatic cardiovascular disease (CVD) free subjects. The presence and extent of coronary atherosclerosis in 755 asymptomatic self-referred subjects were measured using CCTA. The relationships between coronary atherosclerosis, MetS, and other clinical factors were assessed. To further investigate the relationship between MetS and the presence and extent of coronary plaque, subjects were divided into 3 subgroups according to the number of metabolic factors (MF0, 1-2 or ≥ 3) and the number of coronary segments with plaque (segment involvement score: SIS0, 1, ≥ 2). MetS showed significant association with the presence of coronary plaque after adjustment for other clinical factors [odds radio (OR) 1.791 (1.159-2.775), P = 0.009]. Among metabolic components, abdominal obesity and high blood pressure were significantly associated with the presence of coronary plaque [OR 1.708 (1.189-2.455), P = 0.004; OR 1.677 (1.165-2.415), P = 0.005]. Coronary plaque was more frequently found in subgroups with a higher number of metabolic factors (32.4, 36.7 and 52.1 %). Higher SISs were also found in subjects with more MetS components (SIS1: 14.6, 16.2 and 27.2 %; SIS ≥ 2: 17, 19.7 and 23.7 %). In asymptomatic CVD free subjects, MetS and number of metabolic factors were related with an increased risk of the presence and the extent of coronary plaque. Abdominal obesity and high blood pressure were significantly associated with the presence of coronary plaque.

Relationship between cardiovascular autonomic (dys)function and microalbuminuria in type 2 Diabetes Mellitus

Background: Diabetic autonomic neuropathy is a serious and common complication of diabetes mellitus and in fact it is one of the most overlooked complications, thus very limited clinical and research data are available on early renal and cardiovascular autonomic complications in type 2 diabetes mellitus. Aims & Objective: To determine the possible association of elevated albumin excretion rate with cardiovascular autonomic activity in type 2 diabetes mellitus. Materials and methods: A cross-sectional study was conducted with one hundred and fifteen patients of type 2 diabetes mellitus. Microalbuminuria was defined as Albumin Excretion Rate (AER) > 30 mg/24 hr in an early morning urine sample. Nine parameters reflecting different aspects of cardiovascular autonomic function were measured and were summarized in a single cardiovascular autonomic function score (CAFS).The association between cardiovascular autonomic dysfunction and microalbuminuria was estimated by multiple linear regressions. Results: Patients with microalbuminuria had low levels of the autonomic function parameters i.e. mean CAFS, indicating impaired autonomic function. This association was consistent with increasing AER, and remained significant after multivariate adjustment for other clinical factors predictive of microalbuminuria. In additional analysis, we examined the autonomic function tests combined on the part of autonomic nervous system they predominantly represent. The results of these alternative combinations were comparable to those of the CAFS score. Conclusion: Cardiovascular autonomic dysfunction was independently associated with microalbuminuria in patients with type 2 diabetes mellitus, and that this association is independent of other previously identified determinants of albuminuria in type 2 diabetes mellitus. Therefore cardiovascular autonomic function tests should be monitored to pay attention to major potential cardiovascular complications even in asymptomatic patients, but especially among those with microalbuminuria.

Elevated Systemic Neutrophil Count in Diabetic Retinopathy and Diabetes: A Hospital-Based Cross-sectional Study of 30,793 Korean Subjects

To evaluate the association between systemic parameters including inflammatory markers and diabetic retinopathy (DR). This was a cross-sectional study enrolling 30,793 persons who visited a health care center for a medical checkup. Diabetic patients were classified into five DR groups: no DR; mild, moderate, or severe nonproliferative DR, and proliferative DR. A full laboratory workup and comprehensive medical data on the subjects were obtained and used for analysis. The mean (SD) age of the participants was 47.4 (11.9) years (range, 18-90) and the male-to-female ratio was 55.7:44.3. The prevalence of diabetes and DR were 6.6% (2,020/30,793) and 5.3% (108/2,020), respectively. Among inflammatory markers, the mean absolute neutrophil count (ANC; per microliter) was significantly higher in the DR than in the non-DR group (3900 vs. 3566; P = 0.0143) and in diabetic than in nondiabetic subjects (3583 vs. 3262; P < 0.0001). Subjects in the fourth quintiles of ANC showed 2.7 odds of having DR by multivariate analysis, and there was a linear trend in the odds ratios according to increasing ANC levels. The level of ANC and the ANC/leukocyte ratio also demonstrated a linearly increasing trend with the severity of DR, even after adjustment for other clinical factors, including HbA1c. Among significant risk factors of DR, ANC showed the second strongest predictive power for DR (AUROC = 0.590) after HbA1C (0.624). Elevated systemic neutrophil count is associated with the presence and severity of DR as well as diabetes. This result indicates that systemic subclinical inflammation is related with DR, and neutrophil-mediated inflammation may play an important role in the pathogenesis of DR.

Low handgrip strength is a predictor of osteoporotic fractures: cross-sectional and prospective evidence from the Hong Kong Osteoporosis Study

Handgrip strength (HGS) is a potentially useful objective parameter to predict fracture since it is an indicator of general muscle strength and is associated with fragility and propensity to fall. Our objective was to examine the association of HGS with fracture, to evaluate the accuracy of HGS in predicting incident fracture, and to identify subjects at risk of fracture. We analyzed a cross-sectional cohort with 2,793 subjects (1,217 men and 1,576 women aged 50–101 years) and a subset of 1,702 subjects which were followed for a total of 4,855 person-years. The primary outcome measures were prevalent fractures and incident major fragility fractures. Each standard deviation (SD) reduction in HGS was associated with a 1.24-fold increased odds for major clinical fractures even after adjustment for other clinical factors. A similar result was obtained in the prospective cohort with each SD reduction in HGS being associated with a 1.57-fold increased hazard ratio of fracture even after adjustment for clinical factors. A combination of HGS and femoral neck bone mineral density (FN BMD) T-score values (combined T-score), together with other clinical factors, had a better predictive power of incident fractures than FN BMD or HGS T-score alone with clinical factors. In addition, combined T-score has better sensitivity and specificity in predicting incidence fractures than FN BMD alone. This study is the first study to compare the predictive ability of HGS and BMD. We showed that HGS is an independent risk factor for major clinical fractures. Compared with using FN BMD T-score of −2.5 alone, HGS alone has a comparable predictive power to BMD, and the combined T-score may be useful to identify extra subjects at risk of clinical fractures with improved specificity.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-011-9297-2) contains supplementary material, which is available to authorized users.

Abstract 5792: Lower Ankle-Brachial Index Associated With Lipid-Rich Coronary Plaques in Patient Underwent Elective Coronary Intervention: Integrated Backscatter Ultrasound Analysis

Background Association between low Ankle Brachial Index (ABI) and cardiovascular events were demonstrated. The aim of this study is to evaluate association between ABI and coronary plaque radiofrequency characterization by integrated backscatter ultrasound (IB-IVUS). Methods From Jan.2006 to Dec. 2008 Total of 189 consecutive patients who underwent elective PCI following ABI measurements and IB-IVUS analysis were enrolled. The Color coded maps of tissue characteristics of each 1mm slice of target lesions were constructed and volume of each plaque components (calcification, fibrous and lipid core) was calculated. And percentage of lipid volume in the target lesion (% lipid; volume of lipid core/total plaque volume) was calculated. Results ABI significantly correlated with lipid volume of target lesion (r= −0.19, p&lt;0.05), but did not correlate with fibrous volume (r=0.09, P=0.2)(Figure ). ABI (r= −0.18, p&lt;0.01) and HDL-cholesterol (r= −0.14, p&lt;0.05) inversely correlated with %lipid. There was no significant association between %lipid and other clinical factors (age, gender, conventional risk factors, blood pressure, lipid-profile and HbA1c). In multiple regression analysis, ABI significantly associated with %lipid after adjusting for age, gender, prior revascularization of PAD (bypass surgery or angioplasty), systolic BP, LDL-cholesterol, HDL-cholesterol, triglyceride and HbA1c. Conclusion Our present findings provide the first evidence that decrease of ABI may be associated with progression of lipid-rich coronary plaques. After adjustment of other clinical factors, ABI independently associated with lipid-rich coronary plaque of coronary stenosis.