tbuckley/cabot-search huggingface dataset:
THU0180 Impact of Progressive Spacing of TNF-Blocker Injections on Signs and Symptoms of Rheumatoid Arthritis Patients in DAS28 Remission: The Strass Randomized Controled Trial
Authors: B. Fautrel, T. Pham, J. Morel, T. Alfaiate, E. Dernis, P. Gaudin, X. Mariette, F. Tubach
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Step-down therapeutic strategies may be considered in established rheumatoid arthritis (RA) once remission is achieved. <h3>Objectives</h3> To compare the impact of a DAS28-driven step-down strategy based on progressive injection spacing (S arm) to a strategy maintaining the therapy at full regimen (M arm) in an equivalence randomized controlled trial conducted in established RA patients treated with etanercept (ETA) or adalimumab (ADA) in stable DAS28 remission. <h3>Methods</h3> Inclusion criteria were: RA ACR1987+, ETA or ADA &gt; 1 year as monotherapy or in combination, daily prednisone ≤ 5 mg/d, DAS28 remission &gt; 6 months, stable X-ray structural damage. Patients were randomized in 2 arms and followed 3-monthly for 18 months. In the S arm, the interval between 2 injections was increased by 50% every 3 months up to full stop at 4th step. If DAS28 remission was lost, tapering was suspended or reversed to the previous step based on DAS28 change. The primary endpoint was disease activity on repeated DAS28 measures (every 3 months over 18 months) under the hypothesis of non-inferiority (mixed linear model). <h3>Results</h3> 137 patients were included, 64 and 73 in the S and M arms. Main baseline characteristics were (mean / %): age 55 yrs, female 78%, RA duration 9.5 yrs, RF+ 68%, ACPA+ 78%, erosive disease 88%, DAS28 1.8, DAS44 1.0, HAQ 0.4, previous DMARDs 2.7, ETA 54 %, ADA 46 %. At 18 months, 24 (37.5%) of the S-arm patients had stopped and 23 (35.9%) tapered TNF-blockers. Mean DAS28 and HAQ were not significantly different between the 2 arms (figures). However, the equivalence between the 2 strategies was not demonstrated (p = 0.6). Predictors of persistent remission were low DAS28 at baseline and M strategy. There was no difference between ETA or ADA, either montotherapy or in combination. <h3>Image/graph</h3> <h3>Conclusions</h3> Spacing of TNF-blockers was feasible in 87% of patients. Although we failed to demonstrate the equivalence between the 2 strategies, the spacing strategy did not result in a significant increase in disease activity or functional impairment. (ClinicalTrials.gov n°: NCT00780793). <h3>Disclosure of Interest</h3> None Declared
F-18 FDG PET/CT Imaging of Solitary Genital Tuberculosis Mimicking Recurrent Lymphoma
Authors: Gilho Lee, Jai-Hyuen Lee, Seok-Gun Park
Journal: Clinical Nuclear Medicine (2011)

A 65-year-old man who had multiple lymph nodes swelling was pathologically diagnosed with diffuse large B cell lymphoma. After initiation of induction chemotherapy, F-18 FDG PET/CT showed a significantly decreased extent of previous lymphomatous lesions except for 2 newly developed focal hypermetabolic lesions in the prostate and left epididymis. The specimens from the prostate and orchiectomy revealed tuberculosis lesions. After a 3-month antituberculosis regimen, there was definitively decreased glucose uptake in the prostate on F-18 FDG PET. F-18 FDG PET may be helpful for characterizing genitourinary tuberculosis and monitoring antituberculosis treatment.
A Taiwanese Woman with Acute Cholangitis
Authors: A N Barkun, J S Barkun, J Baillie
Journal: Endoscopy (2000)

I am very pleased to introduce not one but two Guest Discussants, the Canadian dynamic duo of gastrointestinal endoscopy and surgery, Drs Alan and Jeff Barkun. After years of study, I am now able to tell these twins apart: Jeff is the one who looks confused when you call him “Alan,” and vice versa. Dr Alan Barkun spent some time at Duke University during his training. I have been pleased to watch his emergence as an expert in endoscopic outcomes research. Dr Jeff Barkun provides the important surgical balance in the Barkun Brothers team. We appreciate your willingness to review a case for us, gentlemen!
Abstract 5010: Characterization of a novel cell type in human renal proximal tubules with connection to renal cell carcinoma development.
Authors: Jennifer Hansson, Kjell Hultenby, Catharina Cramnert, David Lindgren, Håkan Axelson, Martin E. Johansson
Journal: Cancer Research (2013)

Abstract The proximal tubular segments of the kidney are extremely energy demanding, rendering this epithelium exceptionally sensitive to ischemic insults. Acute renal injury is a potentially life threatening condition, where the tubular cells detach and die. However, the tubules of injured kidneys have a substantial regenerative ability, and epithelial continuity, can with proper supportive care be restored. The cellular source of regeneration has been debated and until now the proximal tubules has been considered a completely homogenous cellular epithelium. Using an assay based on aldehyde dehydrogenase (ALDH) activity followed by FACS, we have recently discovered a cell with progenitor cell characteristics scattered within the proximal tubules of the kidney. These novel proximal tubule rare cells (PTRCs) expressed stem cell markers CD133 and CD24, as well as intermediate filaments not normally seen in PTs. The gene expression profile of these cells shows a striking resemblance to that of papillary renal cell carcinoma (pRCC) and the gene signatures are also associated with a worse prognosis in clear cell renal carcinoma. Additionally, cells positive for PTRC-markers were seen in regenerating tubules after acute kidney injury. We have characterized these cells further at an ultra structural level, using electron microscopy. The cells were small, flask shaped and had a more densely packed chromatin pattern and drastically fewer mitochondria than the surrounding proximal tubular cells, indicating a different metabolic state. We suggest that these cells, in contrast to the surrounding highly oxygen dependent proximal tubular cells, constitute renal reserve cell pool capable of surviving ischemic renal injury with a capacity to spearhead subsequent tubular repopulation. We suggest that the increased probability for survival of these cells is due to their low mitochondrial content, structural robustness and anti-apoptotic signaling. Also, due to the considerable transcriptional similarities between pRCC, renal adenomas and the PTRCs we hypothesize that pRCC may arise through multistep oncogenic transformation of PTRCs. Citation Format: Jennifer Hansson, Kjell Hultenby, Catharina Cramnert, David Lindgren, Håkan Axelson, Martin E. Johansson. Characterization of a novel cell type in human renal proximal tubules with connection to renal cell carcinoma development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5010. doi:10.1158/1538-7445.AM2013-5010
TCT-83 Watchman Left Atrial Appendage Closure in Atrial Fibrillation Patients with Contraindication to Oral Anticoagulation: the “Aspirin Plavix Registry” (ASAP)
Authors: Horst Sievert, Jens Wiebe, Nina Wunderlich, Gerhard Schuler, Sven Mobius-Winkler, Peter Sick, Peter Neuzil, Marc Miller, Vivek Reddy
Journal: Journal of the American College of Cardiology (2012)
DUAL ANTIPLATELET THERAPY BEYOND ONE YEAR FOLLOWING CORONARY STENTING IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION: A DUAL ANTIPLATELET THERAPY STUDY ANALYSIS
Authors: Laura Mauri, Dean Kereiakes, Donald Cutlip, Robert Yeh, Philippe Steg, Stephen Wiviott, Joseph Massaro
Journal: Journal of the American College of Cardiology (2016)
Diffusion of BMS181321, a Technetium-99m-Nitroimidazole, in a Cellular Multilayer System
Authors: T Melo, J Tunggal, J R Ballinger, A M Rauth
Journal: Clinical Nuclear Medicine (1998)

1 Department of Medical Biophysics and 2Faculty of Pharmacy, University of Toronto and Ontario Cancer Institute, Toronto, Ontario, Canada.
Abstract 2012: Off-target drug effects due to retroactivity in signaling pathways
Authors: Michelle Wynn, Alejandra Ventura, Hector Garcia, Sofia Merajver
Journal: Cancer Research (2010)

Abstract A majority of targeted cancer therapeutics involve the specific inhibition of a molecular target in a signal transduction pathway. It is well known that targeted therapies, such as kinase inhibitors, may have effects on pathways other than those specifically targeted, whether by non-specific interactions or by indirect pathway cross-talk effects. The simplest view of signal transduction entails a cascade of molecular events initiated by the recognition of a stimulus and culminating in the chemical alteration of an effector molecule. We have recently shown that cascades can exhibit bidirectional signal propagation without the addition of regulatory feedback connections via a phenomenon termed retroactivity. Thus, retroactivity represents another potential source of off-target effects in signaling cascades. We have extended our previous work to a computational model which allows us to characterize the significance of the upstream off-target effect via retroactivity with a series of simple signaling networks using physiologically relevant parameters values. We aim to understand the dynamics of cancer signaling by integrating systems biology based models of signaling dynamics into our experimental investigations of breast cancer with the intent of both directing experiments and making predictions. One of the signaling networks we studied takes the form of two independent signaling cascades which have no regulatory feedback connections but are activated by the same upstream kinase. Our results suggest that under physiologically relevant conditions the application of an inhibitor near the bottom of one cascade can produce a significant change in concentration of a protein in the other cascade, even without a regulatory feedback connection between the two cascades. Developing a deeper understanding of bidirectional signal propagation in signal transduction pathways will be vitally important in the effort to develop safer and more effective targeted cancer therapies. Our modeling results challenge the notion that information in cascades only flows in the cell surface-to-nucleus direction and suggests that a perturbation applied within a cascade can produce both an upstream and a downstream effect. The notion of an upstream off-target effect is completely novel and may have significant implications if the perturbation takes the form of an inhibitory therapeutic drug. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2012.
P607Cardiac sympathetic innervation determines regional heterogeneity in morphology and function of cardiomyocytes
Authors: N Pianca, T Zaglia, L Nalotto, M Franzoso, P Brum, M Sandri, M Mongillo
Journal: Cardiovascular Research (2014)

Purpose: Cardiac Sympathetic Neurons (cSNs) densely innervate the myocardium and operate physiologically both as short term enhancers of cardiac function, and as constitutive regulator of cardiomyocyte (CM) size, by controlling proteolysis through the β2-AR/FOXO3/MuRF-1 dependent signaling axis (1). The density of cSNs decreases progressively from the epi- to the endocardium. We here tested the hypothesis that such innervation pattern would reflect on the degree of constitutive β2-AR input to the different regions of the heart and thus heterogenously control myocardial proteolysis and cell size.

Methods: IF and morphometric analyses were performed on heart slices from neonatal and adult normal and KO hearts. Heart denervation was induced by 6-OH-DOPA (100mg/kg). Surgical dissection of the subepi- and subendocardium was set up.

Results: CM size is heterogenous throughout the mouse myocardium, with the cells in the outer layers (sEPI hereafter) being significantly larger than the similarly-oriented ones in the innermost (sENDO) layers (sEPI: 8590±2121 vs sENDO 4697±1433, in μm3; sEPI/sENDO CM size: 1.83±0.43). Such size differences, that parallel the ‘EPI-to-ENDO’; gradient in cSN density (cSNs/CM: sEPI 0.45±0.06 vs sENDO 0.15±0.02), are completely ablated upon cSN denervation (sEPI/sENDO CM size: 0.83±0.26), and are absent in both β2-AR-/- and MuRF1-/- mice. Interestingly, chronic treatment with either the β2-AR agonist clenbuterol (3mg/kg), or the β2-AR antagonist ICI118,551 (1mg/kg), which diffuse throughout the myocardium resulting in hypertrophic or atrophic remodeling, respectively, also abolish the sEPI-to-sENDO CM size difference, supporting the notion that SN control over CM morphology is operated regionally. In further support of the causal role of cSNs in controlling myocardial heterogeneity, sEPI/sENDO CMs size differences are not present immediately after birth and start to establish at P7, in parallel with the development of myocardial sympathetic innervation and, consistently, never establish in mice permanently denervated at P1. Furthermore, we demonstrated that proteolysis is differentially regulated in the sEPI and sENDO, as sympathetic denervation upregulated the muscle specific atrogenes MuRF1 and Atrogin-1 significantly more in the former than in the latter regions.

Conclusions: Constitutive activity of the cardiac SNs is required for the establishment and maintenance of the correct trophic CM properties. This is the first demonstration of an otherwise homogenous tissue that is shaped by a superimposed pattern of cSNs.

1. Zaglia et al. Cardiovasc Res, 2013
680 CLINICAL CHARACTERISTICS, TREATMENT AND PROGNOSIS OF NON-B NON-C HEPATOCELLULAR CARCINOMA: A LARGE RETROSPECTIVE MULTICENTER COHORT STUDY
Authors: R. Tateishi, T. Okanoue, K. Okita, K. Kiyosawa, M. Omata, H. Kumada, N. Hayashi, K. Koike
Journal: Journal of Hepatology (2013)
FRI0199 Usefulness of matrix metalloproteinase-3 as a predictor of total knee arthroplasty in patients with rheumatoid arthritis
Authors: T. Tsuchida
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The main goal of rheumatoid arthritis (RA) treatment is to maximize the patient's long-term QOL. In addition to achievement/maintenance of clinical remission, prevention of structural change such as joint destruction is essential for this goal. Serum matrix metalloproteinase 3 (MMP-3) has been reported to be a potential prognostic predictor for joint destruction.<sup>123</sup> However, most of the available data were collected from treatment-naive RA patients or those treated with non-biological disease modifying anti-rheumatic drugs (DMARDs); data with the use of biologicals are limited. <h3>Objectives</h3> Study the relationship between serum MMP-3 levels and joint destruction resulting in total knee arthroplasty (TKA) in RA patients receiving etanercept (ETN). <h3>Methods</h3> Our research data on the relationship between MRI findings of the knee and TKA in RA patients who started ETN treatment at our site (presented at the conference in 2012)<sup>4</sup> were used to retrospectively investigate the relationship between TKA and MMP-3 at baseline and post-implementation of ETN. Patients were followed after initial ETN dose until TKA or, in those without TKA, up to Week 104 to compare change in MMP-3 levels. Also, the association between knee MRI findings and MMP-3 change after starting ETN treatment was examined. <h3>Results</h3> A total of 116 patients were analyzed; 28 underwent TKA. The mean observation period was 74.7 and 100.8 weeks in patients with and without TKA, respectively. Patient background characteristics were similar between groups. No significant difference in the rate of concurrent use and mean dose of glucocorticoid, which is known to affect MMP-3, was observed. TKA patients had significantly higher mean MMP-3 of post-dosing ETN than non-TKA patients (210.0 vs 112.0 ng/ml, p=0.0002) and significantly lower reduction in MMP-3 from baseline (12.5 vs 65.0 ng/ml, p=0.0246). There was also a significant difference in the proportion of patients with normal MMP-3 levels at the final observation between groups (TKA, 10.7%; non-TKA, 33.0%; p=0.0278). (Table) Moreover, patients with worsening of knee MRI findings (synovitis, T1 low/T2 high signals) were significantly more likely to have elevated MMP-3 relative to baseline than those without worsening. <h3>Image/graph</h3> <h3>Conclusions</h3> Serum MMP-3 levels were associated with TKA. In patients without sufficient reduction in MMP-3 after starting biologicals, joint destruction is likely to progress. Serum MMP-3 measurement can be considered as a useful predictor of TKA and should be performed to monitor structural change. <h3>References</h3> Mamehara A, et al. <i>Kobe J. Med. Sci</i> 2010;56:E98-E107 Yamanaka H, et al. <i>Arthritis Rheum</i> 2000;43:852-858 Green MJ, et al. <i>Rheumatology</i> 2003;42:83–88 Tsuchida T. <i>Ann Rheum Dis</i> 2012;71(Suppl3):524 <h3>Disclosure of Interest</h3> None Declared
Abstract MS3-2: Advances in Breast Cancer Risk Assessment, Screening and Prevention: Adapting the Lessons to an Underserved Latina Population
Authors: JN Weitzel
Journal: Cancer Research (2010)

Abstract Breast cancer (BC) is the most common cancer and the leading cause of cancer death in Latina women. Mutations in BRCA genes are associated with 5% of all BC and a larger proportion of young women with BC. Genetic cancer risk assessment (GCRA) has the potential to identify persons at increased risk for cancer prior to the onset of disease, when early detection or prevention strategies would be most effective. Despite clinical studies documenting the efficacy of cancer risk reduction measures in high-risk individuals, low-income, underinsured or ethnic minority individuals have a disproportionate burden of cancer and limited access to GCRA. City of Hope Cancer Screening &amp; Prevention Program Network outreach clinics were established in two regional indigent healthcare delivery systems. Consultations are facilitated by an experienced bilingual cancer risk counselor/physician team and risk management recommendations are given based on BRCA test results or empiric risk estimates. We observed a high prevalence of deleterious BRCA mutations (25–34%) among Latinas seen in a large network of high-risk clinics from Texas to Northern California, and also identified a unique recurrent large BRCA1 rearrangement of presumed Mestizo origin. We also established that the BRCA1 185delAG detected in several independent Latina families shared a common ancestral origin with Jewish carrier families. The presence of additional recurrent mutations led us to pursue ancestry informed strategies for more cost-effective BRCA analyses in underserved Latina populations. Our clinical studies indicate that underserved patients embrace the opportunity for GCRA services, attend their scheduled consultations, have a high level of participation in follow-up surveys and show a positive impact on cancer screening and prevention behaviors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS3-2.
Abstract LB-189: BIRC5 (Survivin) is a prognostic biomarker and potential drug target for patients with malignant peripheral nerve sheath tumors.
Authors: Matthias Kolberg, Maren Høland, Trude H. Ågesen, Rolf I. Skotheim, Bodil Bjerkehagen, Kirsten S. Hall, Fredrik Mertens, Sigbjørn Smeland, Dina C. Lev, Ben Davidson, Ragnhild A. Lote
Journal: Cancer Research (2013)

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue cancer with high mortality, and there are currently few therapeutic options beyond surgery. We have performed a transcriptome study of 30 MPNSTs and 8 neurofibromas and used a tissue microarray (TMA) with cores from 63 MPNSTs to identify candidate genes and proteins for targeted therapy. The anti-apoptotic gene BIRC5 was one of the most significantly upregulated genes in MPNST vs neurofibroma. This gene is located on the long arm of chr 17, and we have previously shown common gains of 17q sequences and pinpointed BIRC5 as a potential target in MPNSTs. Recently BIRC5 was also identified as a potential drug target. Here, we show that MPNST patients with above median BIRC5 mRNA expression levels had significantly worse 5-year disease-specific survival (DSS: 26%) than patients with below median mRNA levels (DSS: 87%) (P=.0003). Immunohistochemical analyses showed that increased protein expression is also associated with a worse disease outcome (P=.02). We recently performed a meta-analysis on survival for NF1 associated MPNST and sporadic MPNST based on 1800 patients which suggest no difference between these groups. Our data suggest that MPNST patients who present tumors with high expression of BIRC5 might benefit from targeted treatment directed against BIRC5. Citation Format: Matthias Kolberg, Maren Høland, Trude H. Ågesen, Rolf I. Skotheim, Bodil Bjerkehagen, Kirsten S. Hall, Fredrik Mertens, Sigbjørn Smeland, Dina C. Lev, Ben Davidson, Ragnhild A. Lote. BIRC5 (Survivin) is a prognostic biomarker and potential drug target for patients with malignant peripheral nerve sheath tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-189. doi:10.1158/1538-7445.AM2013-LB-189
PARADOXICAL LOW FLOW LOW GRADIENT SEVERE AORTIC STENOSIS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION: IMPACT OF SURGERY VERSUS MEDICAL THERAPY
Authors: Zaher Fanari, Dimitrios Barmpouletos, Vivek Reddy, Sumaya Hammami, Zugui Zhang, William Weintraub, Erik Marshall
Journal: Journal of the American College of Cardiology (2016)
231 EFFECT OF ANTIVIRAL THERAPY ON CELL MEDIATED IMMUNITY IN LIVER TRANSPLANT RECIPIENTS WITH HCV
Authors: G.A. Woo, L. Arosemena, P. Tryphonopoulos, N. Agresti, W. Butt, S. Sclair, E.R. Schiff, A.G. Tzakis, P. Martin
Journal: Journal of Hepatology (2012)
The Utility of F-18 FDG PET/CT in the Evaluation of Pancreatic Intraductal Papillary Mucinous Neoplasm
Authors: Hye-Suk Hong, Mijin Yun, Arthur Cho, Jin-Young Choi, Myeong-Jin Kim, Ki Whang Kim, Yun Jung Choi, Jong Doo Lee
Journal: Clinical Nuclear Medicine (2010)

To assess the utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in evaluating pancreatic intraductal papillary mucinous neoplasm (IPMN).We included 31 patients with pancreatic IPMN who underwent F-18 FDG PET/CT and multidetector CT (MDCT). Each pancreatic lesion was classified as benign or malignant. On PET, the maximal standardized uptake value was measured in each pancreatic lesion.PET/CT was superior to MDCT in diagnosing malignant IPMN. All 22 concordant results gave accurate diagnoses. Of 9 discordant results, MDCT misdiagnosed 7 IPMNs, whereas PET/CT misinterpreted 2. Malignant IPMNs showed significantly higher maximal standardized uptake values (mean ± standard deviation, 6.7 ± 3.6) than benign IPMNs (mean ± standard deviation, 2.1 ± 1.0) (P < 0.001).F-18 FDG PET/CT outperformed MDCT in detecting malignant IPMN.
Effect of Peritonitis of Nonbiliary Origin on the Function of the Gall Bladder as Measured by Cholecystography, Its Frequency and Its Duration
Authors: Rafael Sanchez-Ubeda, Francis F. Ruzicka, Louis M. Rousselot
Journal: New England Journal of Medicine (1957)

IT has been known for some time that after an attack of acute pancreatitis an intrinsically "normal" gall bladder may not function temporarily (as evidenced by cholecystography).1 As far as we are aware it has not been determined how frequently this transient nonfunction occurs and how prolonged this effect can be. In relation to the management of pancreatitis this incomplete knowledge poses important practical questions. On the one hand, cholecystectomy is a satisfactory treatment for pancreatitis when it is accompanied by primary calculous acute cholecystitis. On the other hand, in the absence of intrinsic biliary disease, cholecystectomy in the treatment . . .