tbuckley/cabot-search huggingface dataset:
Survival outcome of ampullary and duodenal adenocarcinomas.
Authors: Walid Labib Shaib, Rahul Sharma, Sungjin Kim, Zhengjia Chen, John S. Kauh, David A. Kooby, Shishir K. Maithel, Jerome Carl Landry, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2013)

e14579 Background: Adenocarcinomas of the duodenum are divided into two locations: ampullary (AMP) and duodenal (DA). AMP represents 2% of all gastrointestinal (GI) malignancies and commonly present with tumor related obstruction of the common bile duct. DA is rare, and constitutes 0.4% of GI but 45% of small bowel malignancies. The literature regarding treatment and outcome of DA and AMP is very limited. The objective of this project is to evaluate the outcome for these cancers. Methods: After IRB approval, AMP and DA patients were identified from Emory University database. A chart review from July 1995 to July 2012 was conducted. Data was collected for demographic characteristics, pathology, treatment and survival.Survival rates were estimated by Kaplan Meier method and compared with Log-rank test. A Cox proportional hazard model was fitted to estimate the adjusted effect of AMP versus DA on overall survival (OS). Results: A total of 162 patients with AMP (94) and DA (68) were identified. Median age at diagnosis for AMP was 62 and for DA was 63 years. Equal distribution of males and females was found in both locations. No difference was found comparing grade of the tumors. There was a difference in race. DA presented with larger primary tumor compared to AMP. DA presented with advanced stage. Treatment was driven by stage and included surgery, surgery followed by adjuvant chemotherapy (5-FU based) +/- radiation or chemotherapy alone. Median OS of 27.5 for AMP and 19.3 months for DA, not statistically significant difference. Adjusting for stage, no significant survival difference was observed (HR=0.88 95%CI=0.54 – 1.46, p=0.63). Conclusions: Race, size, stage and treatment were different comparing AMP to DA. Majority of AMP had early stage and were treated with surgery; DA tends to present at a late stage. When accounting for stage and location, the OS was not significantly different. [Table: see text]
THU0344 A rheumatology led pathway for the initial management of GCA improves diagnostic outcomes compared to the generalist
Authors: Z Farah, M Gulati, M Matheou, H Alam, S Hamdulay
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Giant Cell Arteritis (GCA) is a medical emergency requiring prompt and appropriate management to prevent complications. The British Society of Rheumatology (BSR) has set out guidelines on the appropriate management of suspected GCA targeting both primary and secondary-care physicians. Hospitals increasingly use care-pathways to facilitate appropriate initial management of GCA by non-rheumatologists. Evidence is limited, however, on the impact of such interventions on patient care. <h3>Objectives</h3> To evaluate the impact of designing a GCA care-pathway for non-rheumatologists (acute and general physicians) on patient care in terms of: (i) duration from referral to temporal artery biopsy (TAB) and rheumatology review; (ii) glucocorticoid therapy burden; and (iii) proportion of referrals with a final diagnosis of GCA <h3>Methods</h3> We performed a retrospective study of all patients diagnosed with GCA between 3 periods: prior to introducing a GCA pathway (2007–2009), rheumatology led GCA pathway (2010–2012), and non-rheumatology led GCA pathway (2012–2016). We identified patients from a TAB database and collected general demographic data, initiation of glucocorticoid therapy, referral for TAB and rheumatology clinic, date of TAB and clinic review, biopsy findings, and final diagnosis. <h3>Results</h3> Table 1 summarises the main findings. After introducing the rheumatology-led pathway (2010–2012), rate of referrals for TAB per month declined to 0.78, the proportion of patients having a TAB within 14 days of referral reached 100%, and the proportion of patients with a positive biopsy increased to 30% suggesting appropriate use of the pathway and an improvement in care. However introducing a non-rheumatology led GCA pathway (2012–2016), led to increased referral numbers. The proportion of TAB within 14 days decreased, and the proportion with a positive biopsy declined (17%). The non-rheumatology led GCA pathway was associated with higher glucocorticoid burden. In this cohort, 23/55 (41.8%) patients who were found not to have GCA received more than 21 days of high dose steroids (40–60mg Prednisolone) whilst awaiting rheumatology review. 4 patients whose final diagnosis was not GCA received high dose steroids for more than 30 days (max 109 days). <h3>Conclusions</h3> Availability of a rheumatology-led GCA pathway leads to improved care for patients with suspected GCA Easy access for referral of patients with headache as assessed by the non-specialist can lead to over-use of the pathway and inappropriate referrals Non-rheumatology-led GCA pathway can lead to a high glucocorticoid burden, especially in an elderly demographic with other comorbidities <h3>Disclosure of Interest</h3> None declared
THU0235 Exosome-delivered MIR-146A regulates senescence of bone marrow- mesenchymal stem cells from systemic lupus erythematosus patients through targeting IRAK1 and TRAF6
Authors: J Ji, Y Wu, X Kong, Z Zhang, Z Gu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Recent study suggests that microRNAs can be transferred between cells and mediate target gene repression. Our research group revealed the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients,which participated in the development of SLE. However, the relationship between senescence of MSCs and miRNAs remains unclear. <h3>Objectives</h3> In this study, we investigated whether exosomes act as intercellular messengers delivering microRNA that modulate the senescence of BM-MSCs from SLE patients and its possible mechanism. <h3>Methods</h3> Tewelve female SLE patients and healthy subjects were enrolled in the study. All patients were females, and their age distribution was similar to that of the cases. Serum were collected from these persons. All BM-MSCs were Isolated by density gradient centrifugation. Serum-derived exosomes were extracted by Total Exosome Isolation reagent and confirmed by transmission electron microscope and western blot. The internalization of exosomes was detected by immunofluorescence. QRT-PCR was used to distinguish the difference of expression of miR-146a in exosomes between normal group and SLE group. Different exosomes stimulated normal BM-MSCs, then detecting expression of miR146a by qRT-PCR, detecting expression of IRAK1 and TRAF6 by WB, observing the activity of β-gal of cells, the changes of cytoskeletal structure by F-actin staining and the distribution of cell cycle by flow cytometry. We used miRNA mimics and miRNA inhibitor to interfere the expression of miR-146a. <h3>Results</h3> Serum-derived exosomes could be taken up by BM-MSCs through the plasma membrane due to treatment of BM-MSCs with exosomes. After stimulation of exosomes in normal MSCs, miR146a was decreased, but, IRAK1 and TRAF6 was activated. And, the cell volume and the number of SA-β-gal positive in SLE BM-MSCs was increased. The organization of cytoskeleton was neatly disordered. The rate of cell proliferation was decreased. The miR-146a mimics in SLE BM-MSCs can significantly reverse the senescence. <h3>Conclusions</h3> Exosomes-delivered miR-146a in the serum of SLE patients can promote the senescence of BM-MSCs through targeting IRAK1 and TRAF6. Exosomes play an important role in the pathogenesis of SLE. <h3>Acknowledgements</h3> This research was supported by grants from the National Natural Science Foundation of China (81471603). <h3>Disclosure of Interest</h3> None declared
SAT0640 Diagnostic utility of detecting enthesitis by ultrasound in peripheral spondyloarthritis
Authors: K Fujikawa, Y Endo, A Mizokami, M Mine, A Kawakami
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To evaluate the diagnostic utility of detecting enthesitis by ultrasound in patients with peripheral spondyloarthritis (SpA). <h3>Methods</h3> A single-center cohort study was performed in patients with symptoms suggestive of peripheral SpA (inflammatory back pain, arthritis of the lower limbs, tenderness of the entheses and dactylitis). Patients with only axial symptoms in the absence of peripheral symptoms were excluded. Fourteen sites of enthesis (both sides of lateral epicondyle, quadriceps tendon insertion into the patella, patellar ligament insertion into the patella and tibial tuberosity, medial and lateral femoral condyles, and Achilles tendon) were assessed at baseline by ultrasound. Ultrasound assessment was made by Japan College of Rheumatology (JCR)-registered sonographers. Furthermore, articular synovitis and tenosynovitis of both wrist and finger joints as well as symptomatic sites were examined. Clinical, laboratory (CRP, HLA typing), radiological (X-ray and MRI of sacroiliac joint) findings and SpA classification criteria (Amor9s, ESSG and ASAS) were also evaluated. The gold standard was the diagnosis made by the JCR-certified rheumatologists during a six-month follow-up period. <h3>Results</h3> Between April 2014 and November 2016, one hundred-thirty six patients were consecutively enrolled. A definite diagnosis was obtained in 112 patients (72 SpA and 40 non-SpA). Diagnosis was not made in the remaining 24 patients. Seventy-two SpA patients (62 with undifferentiated SpA, 6 with psoriatic arthritis, 2 with AS, 1 with inflammatory bowel disease-associated arthritis and 1 with reactive arthritis) and 40 non-SpA patients were investigated in this study. In ultrasound findings, SpA patients showed power Doppler (PD) signals of the articular synovium (57%), tendon sheath synovium (71%) and enthesis (94%). A PD signal for at least one enthesis sites was the most useful finding for differentiation of SpA from non-SpA (sensitivity 94%; specificity 85%; accuracy 91%; positive likelihood ratio 6.3) regarding ultrasound findings. In logistic regression analysis, fulfillment of peripheral ASAS criteria, that of Amor9s criteria, and presence of PD signals at least one enthesis sites were independent variables to the contribution of diagnosis of SpA (Figure 1). <h3>Conclusions</h3> PD signals of entheses by ultrasound are useful for the diagnosis of SpA with peripheral joint symptoms. In addition to the consideration of axial SpA, the combination use of ultrasound with clinical classification criteria including ASAS and Amor9s criteria is beneficial to diagnose peripheral SpA. <h3>Disclosure of Interest</h3> None declared
Abstract P296: Intralipid Protects the Heart Against Ischemia/Reperfusion Injury More Efficiently than Cyclosporine-A
Authors: Jingyuan Li, Ji-Youn Youn, Hua Cai, Mansoureh Eghbali
Journal: Circulation Research (2011)

It has been shown that intralipid protects the heart against ischemia reperfusion (I/R) injury. Here we compared the cardioprotective effect of Intralipid (ILP) with cyclosporine-A (CsA), a potent inhibitor of the mitochondria permeability transition pore (mPTP) opening. Isolated hearts (Langendorff) from male mice were subjected to 20 minutes of global ischemia followed by reperfusion with Krebs Henseleit buffer (CTRL), additional 1% ILP (ILP group) or 1.5µM CsA (CsA group). The reperfusion duration was 40 min for measurement of cardiac function and infarct size, 10 min for measurement of mitochondrial calcium retention capacity and 5 min for superoxide production measurements using electron spin resonance. Post-ischemic administration of ILP improved the heart functional recovery even better than CsA as Rate pressure product (RPP) at the end of 40 min was significantly higher in ILP group compared to CsA group (13676±611 mmHg*beats/min (n=6) in ILP group vs. 7426±1158 mmHg*beats/min (n=3) in CsA, P&lt;0.01). Consistent with the heart function, the infarct size was also significantly smaller in ILP compared to CsA group (18.3±2.4% (n=9) in ILP vs. 29.9±2.0% (n=3) in CsA, P&lt;0.01). The heart functional recoveries were significantly higher and the infarct sizes were significantly smaller in both groups compared to CTRL (RPP=2999±863 mmHg*beats/min (n=6), the infarct size=54.8±2.9% (n=10)). ILP was as efficient as CSA in inhibiting mPTP opening as calcium retention capacity (CRC) was not significantly different between the mitochondria isolated from the heart which were reperfused with ILP or CSA (274.3±8.4 nM/mg-mitochondria protein (n=6) in ILP vs. 260.3±2.9 nM/mg-mitochondria protein (n=6) in CsA). The CRC in both groups were higher than CTRL (168.6±9.6 nM/mg mitochondria protein (n=7)). ILP prevented superoxide production in mitochondria similarly as CSA (0.344±0.1104 (n=4) in ILP vs. 0.5744±0.1445 (n=4) in CsA) which were significantly lower than CTRL (1±0.1197 (n=4), normalized to CTRL). In conclusion, although ILP inhibits the opening of the mPTP as efficiently as CsA, ILP is more effective than CsA in reducing the infarct size and improving the heart functional recovery.
TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup
Authors: David P. Labbé, Christopher J. Sweeney, Myles Brown, Phillip Galbo, Spencer Rosario, Kristine M. Wadosky, Sheng-Yu Ku, Martin Sjöström, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, R. Jeffrey Karnes, Edward M. Schaeffer, Robert B. Jenkins, Robert B. Den, Ashley E. Ross, Michaela Bowden, Ying Huang, Kathryn P. Gray, Felix Y. Feng, Daniel E. Spratt, David W. Goodrich, Kevin H. Eng, Leigh Ellis
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. Clin Cancer Res; 23(22); 7072–83. ©2017 AACR.
Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma
Authors: Kevin Bielamowicz, Kristen Fousek, Tiara T Byrd, Hebatalla Samaha, Malini Mukherjee, Nikita Aware, Meng-Fen Wu, Jordan S Orange, Pavel Sumazin, Tsz-Kwong Man, Sujith K Joseph, Meenakshi Hegde, Nabil Ahmed
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric antigen receptor (CAR) T cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of 2 glioma antigens offsets antigen escape and enhances T-cell effector functions, the interpatient variability in surface antigen expression between patients hinders the clinical impact of targeting 2 antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application.
AB0097 Methotrexate and low dose prednisolone downregulate osteoclast function in monocytes from early rheumatoid arthritis patients
Authors: IP Perpétuo, J Caetano-Lopes, AM Rodrigues, R Campanilho- Marques, C Ponte, H Canhão, M Ainola, JE Fonseca
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic, immune mediated inflammatory disease that is associated with bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. <h3>Objectives</h3> In this study we aimed to assess the effect of MTX and low dose prednisolone (MTX+PDN) on circulating osteoclast (OC) precursors and OC differentiation in RA patients. <h3>Methods</h3> RA patients before and at least 6 months after MTX therapy were analyzed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-κB (RANK) ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Serum quantification of bone turnover markers and cytokines and <i>in vitro</i> OC differentiation assays were performed. <h3>Results</h3> The number or RANKL<sup>+</sup> neutrophils increased in RA patients when compared to healthy donors (p=0.006) and after treatment with MTX+PDN their count was reduced to healthy control numbers (p=0.0155). Classical activation markers of monocytes such as HLA-DR, CD86, CCR2 and CD11b, and also RANK were increased in RA patients at baseline, comparing to control healthy donors. After MTX+PDN exposure, expression decreased to healthy control levels. Serum RANKL levels were increased at baseline comparing to healthy donors (p=0.0164) and normalized after therapy. Although the number of OC was not different between groups, resorbed area and resorbed area/pit were elevated when compared to controls (p=0.0436 and 0.0249, respectively) and reduced after treatment (p&lt;0.0001). <h3>Conclusions</h3> Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through a decrease in RANK surface expression in monocytes. <h3>Disclosure of Interest</h3> None declared
AB0578 Arterial aneurysms moroccan experience study of 37 cases
Authors: M Moudatir, M Moudatir
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behcet9s disease is a systemic vasculitis with a tropism for the venous system. Arterial involvement is uncommon (1%) and mainly represented by aneurysms that can be life-threatening. <h3>Objectives</h3> This retrospective study was conduced in the internal medicine department of the University Hospital Ibn Rochd of Casablanca, over a period of thirty-five years between 1980 and 2016. Where included all the cases of Behcet9s disease diagnosed in our service (1618 case). <h3>Methods</h3> We aimed to determine the epidemiological profile, the different possible clinical manifestations and to discuss both prognosis and treatment in such cases. <h3>Results</h3> 37 patients – 32 men and 5 women – presented arterial involvement in type of arterial aneurysm, which represents a rate of 2.35%. Mean age at diagnosis was 32 years old (ranges 17–54). This complication was the revealing event for Behcet9s disease in 2 cases, concomitant in 3 cases and occurring after an average of 6-year-period evolution of the disease in 32 cases. The aneurysm affected: the pulmonary artery (22 cases), the abdominal aorta (5 cases), the femoral artery (5 cases), the internal carotid artery (2 cases), the iliac artery (2 cases) and the middle cerebral artery (1 case). The aneurysm was associated with venous disease (18 cases), pulmonary embolism (2 cases) and intracardiac thrombus (1 case). The medical treatment has relying on anticoagulants (6 cases), anti-aggregating agents (9 cases), corticosteroids (36 cases), immunosuppressive drugs – cyclophosphamide (23 cases) and azathioprine (12 cases), while 7 patients underwent surgical intervention. Evolution was favorable in 23 patients and with negative outcome in 14 patients (9 relapses and 5 deaths). <h3>Conclusions</h3> Arterial aneurysms are the most common arterial complications in the context of Behcet9s disease, while the prognosis remains poor in the absence of early and appropriate management (corticosteroids, immunosuppressive agents, surgery). <h3>Disclosure of Interest</h3> None declared
Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest
Authors: Dorothy A. Perry, Joshua W. Salvin, Padraic Romfh, Peili Chen, Kalyani Krishnamurthy, Lindsay M. Thomson, Brian D. Polizzotti, Francis X. McGowan, Daryoosh Vakhshoori, John N. Kheir
Journal: Science Translational Medicine (2017)

Assessing the adequacy of oxygen delivery to tissues is vital, particularly in the fields of intensive care medicine and surgery. As oxygen delivery to a cell becomes deficient, changes in mitochondrial redox state precede changes in cellular function. We describe a technique for the continuous monitoring of the mitochondrial redox state on the epicardial surface using resonance Raman spectroscopy. We quantify the reduced fraction of specific electron transport chain cytochromes, a metric we name the resonance Raman reduced mitochondrial ratio (3RMR). As oxygen deficiency worsens, heme moieties within the electron transport chain become progressively more reduced, leading to an increase in 3RMR. Myocardial 3RMR increased from baseline values of 18.1 ± 5.9 to 44.0 ± 16.9% (P = 0.0039) after inferior vena cava occlusion in rodents (n = 8). To demonstrate the diagnostic power of this measurement, 3RMR was continuously measured in rodents (n = 31) ventilated with 5 to 8% inspired oxygen for 30 min. A 3RMR value exceeding 40% at 10 min predicted subsequent cardiac arrest with 95% sensitivity and 100% specificity [area under the curve (AUC), 0.98], outperforming all current measures, including contractility (AUC, 0.51) and ejection fraction (AUC, 0.39). 3RMR correlated with indices of intracellular redox state and energy production. This technique may permit the real-time identification of critical defects in organ-specific oxygen delivery.