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Background: Cardiorenal syndrome comprises a heterogeneous group of disorders characterized by acute or chronic cardiac and renal dysfunction.Objective: The purpose of this study was to determine the effect of cardiorenal status using a dual-marker strategy with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and cystatin C on cardiac resynchronization therapy (CRT) outcomes.Methods: In 92 patients (age 66 ± 13 years; 80% male; left ventricular ejection fraction 26% ± 7%), NT-proBNP and cystatin C levels were measured at CRT implantation and at 1 month. NT-proBNP >1000 pg/mL and cystatin C >1 mg/L were considered high. Baseline cardiorenal patients were defined as having high NT-proBNP and cystatin C. At 1 month, CRT patients were categorized as (1) irreversible cardiorenal if cystatin C was persistently high; (2) progressive cardiorenal with transition from low to high cystatin C; (3) reversible cardiorenal with transition from high to low cystatin C; and (4) "normal" with stable low cystatin C. Outcomes were 6-month clinical and echocardiographic CRT response and 2 -year major adverse cardiovascular event (MACE).Results: Compared to patients with low NT-proBNP and cystatin C, cardiorenal patients had >9-fold increase risk of CRT nonresponse (odds ratio uncompensated 9.0; compensated 36.4; both P ≤.004) and >6-fold risk of MACE (hazard ratio uncompensated 8.5; P = .005). Compared to "normal" and reversible patients (referent), irreversible patients had a 9-fold increase for CRT nonresponse (odds ratio 9.1; P <.001) and had >4-fold risk of MACE (adjusted hazard ratio 5.1; P <.001). Irreversible patients were most likely echocardiographic CRT nonresponders.Conclusion: Cardiorenal status by NT-proBNP and cystatin C can identify high-risk CRT patients, and those with both elevated concentrations have worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT).Objective: We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time.Methods: In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE).Results: There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both).Conclusion: Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT. [ABSTRACT FROM AUTHOR]

Objectives The current meta-analysis aimed to evaluate the diagnostic performance of hybrid cardiac imaging techniques compared with stand-alone coronary computed tomography angiography (CTA) for assessment of obstructive coronary artery disease (CAD). Background The usefulness of coronary CTA for detecting obstructive CAD remains suboptimal at present. Myocardial perfusion imaging encompasses positron emission tomography, single-photon emission computed tomography, and cardiac magnetic resonance, which permit the identification of myocardial perfusion defects to detect significant CAD. A hybrid approach comprising myocardial perfusion imaging and coronary CTA may improve diagnostic performance for detecting obstructive CAD. Methods PubMed and Web of Knowledge were searched for relevant publications between January 1, 2000 and December 31, 2015. Studies using coronary CTA and hybrid imaging for diagnosis of obstructive CAD (a luminal diameter reduction of >50% or >70% by invasive coronary angiography) were included. In total, 12 articles comprising 951 patients and 1,973 vessels were identified, and a meta-analysis was performed to determine pooled sensitivity, specificity, and summary receiver-operating characteristic curves. Results On a per-patient basis, the pooled sensitivity of hybrid imaging was comparable to that of coronary CTA (91% vs. 90%; p = 0.28). However, specificity was higher for hybrid imaging versus coronary CTA (93% vs. 66%; p < 0.001). On a per-vessel basis, sensitivity for hybrid imaging against coronary CTA was comparable (84% vs. 89%; p = 0.29). Notably, hybrid imaging yielded a specificity of 95% versus 83% for coronary CTA (p < 0.001). Summary receiver-operating characteristic curves displayed improved discrimination for hybrid imaging beyond coronary CTA alone, on a per-vessel basis (area under the curve: 0.97 vs. 0.93; p = 0.047), although not on a per-patient level (area under the curve: 0.97 vs. 0.93; p = 0.132). Conclusions Hybrid cardiac imaging demonstrated improved diagnostic specificity for detection of obstructive CAD compared with stand-alone coronary CTA, yet improvement in overall diagnostic performance was relatively limited. [ABSTRACT FROM AUTHOR]

Background We aimed to develop a severity classification system of the main pulmonary artery diameter (mPA) and its ratio to the ascending aorta diameter (ratio PA) for the diagnosis and prognosis of pulmonary hypertension (PH) on computed tomography (CT) scans. Methods In 228 patients (136 with PH) undergoing right heart catheterization (RHC) and CT for dyspnea, we measured mPA and ratio PA. In a derivation cohort (n = 114), we determined cutpoints for a four-tier severity grading system that would maximize sensitivity and specificity, and validated it in a separate cohort (n = 114). Cutpoints for mPA were defined with ≤27 mm(F) and ≤29 mm(M) as the normal reference range; mild as >27 to <31 mm(F) and >29 to <31 mm(M); moderate≥31–34 mm; and severe>34 mm. Cutpoints for ratio PA were defined as normal ≤0.9; mild>0.9 to 1.0; moderate>1.0 to 1.1; and severe>1.1. Results Sensitivities for normal tier were 99% for mPA and 93% for ratio PA; while specificities for severe tier were 98% for mPA>34 mm and 100% for ratio PA>1.1. C-statistics for four-tier mPA and ratio PA were both 0.90 (derivation) and both 0.85 (validation). Severity of mPA and ratio PA corresponded to hemodynamics by RHC and echocardiography (both p < 0.001). Moderate-severe mPA values of ≥31 mm and ratio PA>1.1 had worse survival than normal values (all p ≤ 0.01). Conclusion A CT-based four-tier severity classification system of PA diameter and its ratio to the aortic diameter has high accuracy for PH diagnosis with increased mortality in patients with moderate-severe severity grades. These results may support clinical utilization on chest and cardiac CT reports. [ABSTRACT FROM AUTHOR]

Background Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. Methods and Results 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)–guided arm and the standard of care arm ( P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event ( P = 0.01). Conclusions NT-proBNP–guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed. [ABSTRACT FROM AUTHOR]

Background A significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention. Objective This study aimed to determine whether coronary sinus (CS) or baseline peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes. Methods In 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B–type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying “high-risk” individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years. Results NT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE. Conclusion Our findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To present outcome and toxicity results of the first real-time intraoperative MRI-guided interstitial approach to gynecologic cancer. Methods and Materials: From February 2004 to December 2006, 25 patients with gynecologic malignancies were enrolled and treated in a prospective clinical trial of real-time MRI-guided interstitial brachytherapy. This was followed by a confirmatory CT imaging scan. Statistical analyses included Kaplan–Meier estimates for overall and relapse-free survival. Results: MRI visualization of needles during placement permitted accurate placement with no inadvertent insertions. This prevented unnecessary normal-tissue perforation as confirmed by CT simulation. With a mean followup of 3.8 years (range, 2–6.8), 1-, 2-, and 3-year overall survival rates were 80%, 60% and 43%, respectively; corresponding relapse-free survival rates were 79%, 65%, and 59%, respectively. Actuarial acute toxicity rates for any grade were 0% at 0–14 days and 80% (all grade 1) at 14–90 days. Long-term (>180 days) actuarial toxicity rates were 8% gastrointestinal, 4% bladder and 4% vaginal. Conclusions: Real-time MRI guidance during insertion of interstitial needles followed by 3D-planning maximized opportunities for tumor targeting and sparing of normal tissues. Although image guidance requires additional anesthesia time, clinical outcomes indicate potential for a successful reduction in toxicity using 3D image-guided in addition to 3D image-planned brachytherapy. [Copyright &y& Elsevier]

Background: Total hip replacement (THR)/total knee replacement (TKR) studies do not uniformly measure patient centered domains, pain, and function. We aim to validate existing measures of pain and function within subscales of standard instruments to facilitate measurement.Methods: We evaluated baseline and 2-year pain and function for THR and TKR using Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS), with primary unilateral TKR (4796) and THR (4801). Construct validity was assessed by correlating HOOS/KOOS pain and activities of daily living (ADL), function quality of life (QOL), and satisfaction using Spearman correlation coefficients. Patient relevant thresholds for change in pain and function were anchored to improvement in QOL; minimally clinically important difference (MCID) corresponded to "a little improvement" and a really important difference (RID) to a "moderate improvement." Pain and ADL function scores were compared by quartiles using Kruskal-Wallis.Results: Two-year HOOS/KOOS pain and ADL function correlated with health-related QOL (KOOS pain and Short Form 12 Physical Component Scale ρ = 0.54; function ρ = 0.63). Comparing QOL by pain and function quartiles, the highest levels of pain relief and function were associated with the most improved QOL. MCID for pain was estimated at ≥20, and the RID ≥29; MCID for function ≥14, and the RID ≥23. The measures were responsive to change with large effect sizes (≥1.8).Conclusion: We confirm that HOOS/KOOS pain and ADL function subscales are valid measures of critical patient centered domains after THR/TKR, and achievable thresholds anchored to improved QOL. Cost-free availability and brevity makes them feasible, to be used in a core measurement set in total joint replacement trials. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory arthritis (IA) are at increased risk of prosthetic joint infections (PJI), yet differentiating between septic and aseptic failure is a challenge. The aim of our systematic review is to evaluate synovial biomarkers and their efficacy at diagnosing PJI in patients with IA.Methods: A comprehensive literature search was performed in the following databases from inception to January 2018: Ovid MEDLINE, Ovid EMBASE, and the Cochrane Library. Searches across the databases retrieved 367 results. Two of 5 reviewers independently screened a total of 298 citations. Discrepancies were resolved by a third reviewer. Twenty articles fit our criteria, but due to methodological differences findings could not be pooled for meta-analysis. For 5 studies, raw data were provided, pooled, and used to derive optimal diagnostic cut points.Results: Our final analysis included 1861 non-IA patients, including 426 patients with PJI, and 90 IA patients of whom 26 had PJI. There was a significant difference among the 4 groups for serum C-reactive protein (CRP), erythrocyte sedimentation rate, and synovial CRP, polymorphonuclear neutrophil percent, white blood cells, interleukin (IL)-6, IL-8, and IL-1b. Polymorphonuclear neutrophil percent had the highest sensitivity (95.2%) and specificity (85.0%) to detect infections with an optimum threshold of 78%.Conclusion: While levels of synovial white blood cells, IL-6, IL-8, and serum CRP appear higher in patients with IA, there is overlap with those who are not infected. Further studies are needed to explore diagnostic tests that will better detect PJI in patients with IA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Timing of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS). Methods and Materials: We performed a review of 159 patients with resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and 2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after ≤1 cycle of chemotherapy, whereas delayed CRT was defined as after >1 cycle. Cox multivariate analysis (MVA) was performed. Results: Median follow-up was 55 months. Seventy-four percent of patients received immediate CRT, and 26% patients received delayed CRT. Patients treated with delayed CRT were more likely to receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic antigen ≥1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph node positivity ratio and not receiving adjuvant gemcitabine were independently associated with worse OS. Conclusions: Timing of adjuvant CRT for resectable pancreatic cancer may not significantly affect LRC or OS. These findings support the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT until completion of chemotherapy should not significantly impact LRC. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the prevalence and significance of incidental, subcentimeter hepatic lesions in patients with a new diagnosis of pancreatic cancer. Materials and Methods: This Institutional Review Board-approved retrospective study included 101 patients [45% men, median age 63 years (34-85)] treated for localized pancreatic adenocarcinoma at Brigham and Women''s Hospital and Dana Farber Cancer Institute from January 1999 to December 2007. Initial staging and follow-up computed tomographic scans were reviewed to determine the frequency of liver lesions that were initially too small to characterize and later proved to be metastases. Clinical variables known to be prognostic for patients with pancreatic cancer were also recorded. Using Cox regression, we calculated adjusted hazard ratios to determine the association between presence of liver lesions and overall survival. Results: A total of 31 patients (30.7%) had subcentimeter hepatic lesions on staging scans. Of these patients, 21 (20.7% of total, 67.7% of patients with lesions) had eventual metastases to the liver. Finally, of this group, 5 patients (5.0% of total, 16.1% of patients with lesions) eventually had a metastatic focus at the specific site of the original lesion. Liver lesions predicted the occurrence of metastatic disease to the liver compared with patients without lesions (67.7% with lesions vs 44.4% without, P = .034). The presence of subcentimeter liver lesions at diagnosis was significantly associated with reduced overall survival (hazard ratio 1.65; 95% confidence interval 1.03-2.64, P = .036). Conclusions: Subcentimeter lesions in the liver are common in patients with a new diagnosis of pancreatic cancer. Approximately 16% of these lesions represent metastases. The presence of indeterminate liver lesions may be associated with reduced overall survival. [Copyright &y& Elsevier]

Background Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors. Methods HRQoL data were prospectively collected on PRT-treated patients aged 2–18 treated at Massachusetts General Hospital (MGH). Cross-sectional PedsQL data from XRT treated Lucile Packard Children’s Hospital (LPCH) patients provided the comparison data. Results Parent proxy HRQoL scores were reported at 3 years for the PRT cohort (PRT-C) and 2.9 years (median) for the XRT cohort (XRT-C). The total core HRQoL score for the PRT-C, XRT-C, and normative population differed from one another and was 75.9, 65.4 and 80.9 respectively ( p = 0.002; p = 0.024; p < 0.001). The PRT-C scored 10.3 and 10.5 points higher than the XRT-C in the physical (PhSD) and psychosocial (PsSD) summary domains of the total core score (TCS, p = 0.015; p = 0.001). The PRT-C showed no difference in PhSD compared with the normative population, but scored 6.1 points less in the PsSD ( p = 0.003). Compared to healthy controls, the XRT-C scored lower in all domains ( p < 0.001). Conclusions The HRQoL of pediatric brain tumor survivors treated with PRT compare favorably to those treated with XRT and similar to healthy controls in the PhSD. [ABSTRACT FROM AUTHOR]

Background: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP1-108, or C-type natriuretic peptide (CNP) is not well understood.Objectives: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays.Methods: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP1-108, and CNP were measured over 3 visits.Results: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change.Conclusions: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations. [ABSTRACT FROM AUTHOR]

Background Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects. Methods Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans. Results Target coverage was comparable between PT and IMRT plans with a mean CTV V 95 of 100% for both modalities ( p = 0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0–4.9). By site, mean integral dose for IMRT was 1.8 times higher for H&N ( p < 0.01) and GU ( p = 0.02), 2.0 times higher for trunk/extremity ( p < 0.01), and 3.5 times higher for orbit ( p < 0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients. Conclusions Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available. [ABSTRACT FROM AUTHOR]

Abstract: Background: Multi-detector cardiac computed tomography (CT) allows for simultaneous assessment of aortic distensibility (AD), coronary atherosclerosis, and thoracic aortic atherosclerosis. Objectives: We sought to determine the relationship of AD to the presence and morphological features in coronary and thoracic atherosclerosis. Methods: In 293 patients (53±12years, 63% male), retrospectively-gated MDCT were performed. We measured intraluminal aortic areas across 10 phases of the cardiac cycle (multiphase reformation 10% increments) at pre-defined locations to calculate the ascending, descending, and local AD (at locations of thoracic plaque). AD was calculated as maximum change in area/(minimum area×pulse pressure). Coronary and thoracic plaques were categorized as calcified, mixed, or non-calcified. Results: Ascending and descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (all p <0.0001) but not with non-calcified coronary plaque (p ≥0.46). Per 1mm Hg−1 10−3 increase in ascending and descending AD, there was an 18–29% adjusted risk reduction for having any coronary, calcified plaque, or mixed coronary plaque (ascending AD only) (all p ≤0.04). AD was not associated with non-calcified coronary plaque or when age was added to the models (all p >0.39). Local AD was lower at locations of calcified and mixed thoracic plaque when compared to non-calcified thoracic atherosclerosis (p <0.04). Conclusions: A stiffer, less distensible aorta is associated with coronary and thoracic atherosclerosis, particularly in the presence of calcified and mixed plaques, suggesting that the mechanism of atherosclerosis in small and large vessels is similar and influenced by advancing age. [Copyright &y& Elsevier]

Abstract: Background: Patients with large, high-grade extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of pre-operative chemotherapy consisting of mesna, adriamycin, ifosfamide and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and post-operative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this study is to assess outcomes in a recent cohort of patients treated on this regimen. Methods: We retrospectively reviewed records of 66 consecutive patients with STS of the extremity or trunk who were treated with the aforementioned regimen from May 2000 to April 2011. Clinicopathologic characteristics and patient outcomes were analysed. Results: Sixty-six patients were analysed and were equally divided between grade 2 and 3 tumours. Margins were negative in 57 (89%) patients and positive in seven (11%) patients. At a median follow-up of 46months, there were six (9%) locoregional and 20 (30%) distant recurrences. The locoregional and distant 5-year recurrence-free survival (RFS) rates were 91% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. Thirty-four (52%) patients had grade 3 or 4 acute haematologic chemotherapy-related toxicity. There were no statistically significant predictors of OS or RFS. Conclusions: For a contemporary cohort of patients with high-risk extremity and truncal STS, a regimen of neoadjuvant chemoradiotherapy and surgery continues to result in high rates of survival with tolerable short- and long-term toxicity. [Copyright &y& Elsevier]

Abstract: Objective: Pericoronary adipose tissue (PCAT) may create a pro-inflammatory state, contributing to the development of coronary artery disease (CAD). We sought to evaluate the feasibility of a novel volumetric PCAT quantification method using a novel threshold based computed tomography approach. In addition we determined the relation between PCAT volumes and CAD. Methods: In 51 patients (49.5±5.1 years, 64.8% male) who underwent 64-slice MDCT, we measured threshold-based PCAT volumes using distance and anatomic-based methods. Using the most reproducible method, we performed the proximal 40-mm distance measurement in three groups as stratified by coronary plaque and high-sensitivity C-reactive protein (hs-CRP) levels: Group 1 (presence of coronary plaque, hs-CRP >2.0mg/L); an intermediate group (Group 2, no plaque, hs-CRP >2.0mg/L); and Group 3 (no plaque, hs-CRP<1.0mg/L). We compared PCAT volumes to the presence of coronary plaque on a patient (n =51) and vessel (n =153) basis. On a subsegment basis (n =1224), we compared PCAT volume to the presence of plaque as well as plaque morphology. Results: Distance-based PCAT volume measurements yielded excellent reproducibility with intra-observer intraclass correlation (ICC) of 0.997 and inter-observer ICC of 0.951. On a both a per-patient and per-vessel analysis, adjusted PCAT volume was greater in patients with plaque (Group 1) than without plaque (Groups 2 and 3, p <0.001). No difference in PCAT volume was seen between high and low hs-CRP groups without plaque (p =0.51). Adjusted PCAT volumes were higher in subsegments with plaque as compared without (p <0.001). Additionally, adjusted PCAT volume was greatest in subsegments with mixed plaque followed by non-calcified plaque, calcified plaque, and the lowest volume in segments with no plaque (p <0.001). Conclusion: In this proof-of-concept study, threshold based PCAT volume assessment is feasible and highly reproducible. PCAT volume is increased in patients and vessels with coronary plaques. Surrounding vessel subsegments with coronary plaque, particularly mixed plaques, have greatest PCAT volume and highlight the effect of local PCAT in the development of coronary atherosclerosis. [Copyright &y& Elsevier]