Penetrating ulcer of the thoracic aorta: What is it? How do we recognize it? How do we manage it?

AbstractBackground: Although classic type A and B aortic dissections have been well described, less is known about the natural history of penetrating atherosclerotic ulcers of the thoracic aorta. This study differentiates penetrating ulcer from aortic dissection, determines the clinical features and natural history of these ulcers, and establishes appropriate correlates regarding optimal treatment. Methods: A retrospective review of patient records and imaging studies was conducted with 198 patients with initial diagnoses of aortic dissection (86 type A, 112 type B) at our institution from 1985 to 1997. Results: Of the 198 patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of computed tomographic scans, magnetic resonance images, angiograms, echocardiograms, intraoperative findings, or pathology reports. Two ulcers (13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the descending aorta. In comparison with those with type A or B aortic dissection, patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk for aortic rupture was higher among patients with penetrating ulcers (40.0%) than patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001). Conclusions: Accurate recognition and differentiation of penetrating ulcers from classic aortic dissection at initial presentation is critical for optimal treatment of these patients. For penetrating ulcer, the prognosis may be more serious than with classic type A or B aortic dissection. Surgical management is advocated for penetrating ulcers in the ascending aorta and for penetrating ulcers in the descending aorta that exhibit early clinical or radiologic signs of deterioration. (J Vasc Surg 1998;27:1006-16.

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery

British randomised controlled trial of AV and VV optimization ("BRAVO") study:rationale, design, and endpoints

Background Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources. Methods/Design BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014. Discussion If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented

Standard of Practice for the Endovascular Treatment of Thoracic Aortic Aneurysms and Type B Dissections

Thoracic endovascular aortic repair (TEVAR) represents a minimally invasive technique alternative to conventional open surgical reconstruction for the treatment of thoracic aortic pathologies. Rapid advances in endovascular technology and procedural breakthroughs have contributed to a dramatic transformation of the entire field of thoracic aortic surgery. TEVAR procedures can be challenging and, at times, extraordinarily difficult. They require seasoned endovascular experience and refined skills. Of all endovascular procedures, meticulous assessment of anatomy and preoperative procedure planning are absolutely paramount to produce optimal outcomes. These guidelines are intended for use in quality-improvement programs that assess the standard of care expected from all physicians who perform TEVAR procedures

Daily Chlorhexidine Bathing in General Hospital Units – Results of the ABATE Infection Trial (Active BAThing to Eliminate Infection)

Abstract Background: Universal decolonization with daily chlorhexidine (CHG) bathing with and without nasal decolonization has significantly reduced positive MRSA clinical cultures and bloodstream infections in adult ICUs in several clinical trials. We evaluated whether decolonization was similarly effective in a lower risk hospitalized population. Methods: We conducted a 2 arm cluster-randomized trial involving a 1-year baseline period (April 2013–March 2014) and a 21-month intervention period (June 2014–February 2016). All noncritical care units in a hospital were assigned to the same strategy. These were (1) Routine Care: routine bathing product and frequency and (2) Decolonization: CHG for routine daily bathing (2% leave-on CHG) or showering (4% rinse-off CHG) for all patients plus mupirocin for 5 days for known MRSA. Universal ICU decolonization was in place in both arms by September 2013. Differences between the arms in the outcome rates between the baseline and intervention periods were assessed with proportional hazards models, using shared frailties to account for clustering by hospital. The primary analysis was as-randomized and unadjusted. Primary outcome was any MRSA or VRE clinical isolate attributable to the unit. Secondary outcome was all-cause bloodstream infections. Additional analyses adjusted for age, gender, race, Medicaid insurer, surgery, and comorbidities. Results: We randomized 53 hospitals in 15 states. There were 194 adult units with 189,616 admissions in the baseline period and 340,350 in the intervention period. Common unit types included mixed medical surgical (30%), cardiac (20%), step-down (11%), medical (10%), surgical (10%), and oncology (4%). There were no significant differences between arms in the relative hazards for intervention vs. baseline for either outcome (Table and Figure). Adjusted analyses yielded similar results. Conclusion: Universal daily CHG bathing or showering plus targeted mupirocin for MRSA+ patients in non-critical care units did not reduce the combination of positive MRSA and VRE clinical cultures or bloodstream infections due to all pathogens. Further analyses to assess for any differential effects in high-risk subpopulations will be important. Disclosures S. S. Huang, Sage Products: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Clorox: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; 3M: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; E. Septimus, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; K. Kleinman, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Moody, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Hickok, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Heim, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; A. Gombosev, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Avery, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design K. Haffenreffer, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; L. Shimelman, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; M. K. Hayden, OpGen, Inc.: Receipt of donated laboratory services for project, Research support; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. A. Weinstein, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; OpGen Inc.: Receipt of donated laboratory services for project, Research support; C. Spencer-Smith, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. E. Kaganov, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. V. Murphy, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Forehand, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Lankiewicz, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. H. Coady, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design.; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. M. Portillo, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Patel Sarup, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Perlin, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Platt, Clorox: Receipt of contributed product, Conducting clinical studies in which participating healthcare facilities are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed produc

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4