tbuckley/cabot-search huggingface dataset:
OP0069 Significantly Better Results for TNFI Combination Therapy with MTX Than TNFI Mono- and Combination Without MTX Therapy in Patients with RA: Results from the Dream Registry
Authors: S. Manders, W. Kievit, T. Jansen, J. Stolk, H. Visser, R. Bos, M. van de Laar, P. van Riel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although it is advised to treat Rheumatoid Arthritis (RA) patients with Methotrexate (MTX) as co-medication in the treatment with Tumor Necrosis Factor inhibitors (TNFi), there is a body of patients that is treated with TNFi mono-therapy or combination therapy without MTX in daily clinical practice. We hypothesize a difference in effectiveness and drug survival between TNFi mono-therapy, combination therapy (TNFi + MTX) and non MTX-DMARD combination therapy. <h3>Objectives</h3> To compare TNFi mono-therapy with TNFi combination therapy with and without MTX on drug survival and DAS28 over time in patients with RA. <h3>Methods</h3> Data from the DREAM registry was used. Patients starting with their first TNFi treatment were analyzed, comparing mono-therapy and combination therapy with and without MTX. Drug survival was analyzed with Kaplan-Meijer and Cox regression. Effectiveness on DAS28 was analyzed by repeated measure analyses. Both analyses were corrected for confounders (age, gender, disease duration, weight, erosive disease, rheumatoid factor, DAS28 + HAQ-DI at baseline). <h3>Results</h3> 261 patients started mono-therapy, 335 combination therapy without MTX, and 1337 with MTX. The 3 groups differed at some baseline characteristics: % female (74.3, 71.9, 66.9), disease duration (10.3, 10.3, 9.2), and DAS28 (5.15, 4.98, 4.87) and HAQ-DI at baseline (1.44, 1.45, 1.30) (p-value &lt; 0.1). Combination therapy with MTX had a significantly longer drug survival (Figure1), median time of use 6.0, 1.3 and 2.6 years respectively, (p-value=0.000), and significantly better DAS28 (Figure2) over time (p-value=0.000), both after correction for confounders, than the mono- and the combination without MTX therapy group. Combination therapy without MTX had a significantly longer drug survival than mono-therapy (p-value=0.000) but no better DAS28 over time (p-value=0.245). <h3>Image/graph</h3> <h3>Conclusions</h3> All 3 therapy strategies provide positive outcomes but combination therapy with MTX is significantly better than TNFi mono-therapy and combination therapy without MTX in daily practice. Therefore it is important that rheumatologists follow the recommendations of the clinical guidelines and prescribe TNFi with MTX as co-medication. If this is not possible, combination therapy without MTX is the next best alternative for better drug survival. <h3>Disclosure of Interest</h3> None Declared
S130 Tnf Driven Car Phosphorylation Promotes Trans Epithelial Migration Of Leukocytes
Authors: A. Hicks, P. Morton, A. Noble, E. Raynor, M. Parsons, G. Santis
Journal: Thorax (2014)

<h3></h3> Transepithelial migration (TEpM) of leukocytes during the inflammatory process requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) which binds to Junction Adhesion Molecule – L (JAM-L) on leukocytes during TEpM. Here we provide the first evidence that TEpM of THP1 cells requires, and is controlled by phosphorylation of the cytoplasmic tail of CAR. Our <i>in-vitro</i> data shows that these leukocyte cells can adhere to an epithelial layer but where the cytoplasmic tail of CAR is prevented from undergoing phosphorylation the leukocytes are unable to transmigrate. Furthermore we show that this CAR phosphorylation step is driven by TNFα signalling via a TNFR1-PI3K-PKCδ dependent signalling pathway. Interestingly our work demonstrates that THP1 cells can secrete TNFα thereby activating the CAR phosphorylation pathway leading to TEpM without addition of exogenous TNFα but where TNFα is added this process is augmented. We also use a mouse model to confirm that CAR phosphorylation in response to inflammatory stimuli occurs in-vivo. Both acute (a 24 h inhaled TNFα challenge) and chronic (a 34 day ovalbumin challenge) inflammatory conditions are studied. Using confocal microscopy techniques we show that the cytoplasmic tail of CAR is phosphorylated. Specifically this is seen at the cell membrane of epithelial cells of bronchioles with associated inflammatory cells in the interstitium. Taken together these data describe a novel method for the control of TEpM by transmigrating leukocytes that can also be heightened by the presence of pro-inflammatory cytokines during inflammation. This provides a novel target for controlling inflammation at the epithelium, a key component of the pathogenesis of many diseases including asthma.
Abstract 4846: Automated RNA and DNA purification from FFPE samples
Authors: Michelle Mandrekar, Douglas Horejsh, Samantha Lewis, Chris Moreland, Marjeta Urh
Journal: Cancer Research (2015)

Abstract Formalin-fixed, paraffin-embedded (FFPE) samples are commonly used for archiving pathology samples for use by many researchers including clinical research labs. These samples provide a valuable tool for retrospective studies of diseases such as cancer. Traditional methods for the purification of DNA or RNA from FFPE tissue samples are often labor intensive, include the use of hazardous organic reagents, and involve difficult pre-processing steps. Here, we describe development of automated methods for the purification of RNA or DNA from FFPE tissue sections using the Maxwell® RSC Instrument, which can process between 1 and 16 samples. DNA was purified from FFPE mouse brain, liver, lung, skin and spleen as well as FFPE human colon. RNA was purified from FFPE mouse brain, liver, lung, skin and spleen as well as FFPE human breast tissue. Eluates were tested for inhibition in qPCR or RT-qPCR. A comparison with another automated method was performed with FFPE mouse spleen and skin and a human tissue. The Maxwell RSC methods produced high quality amplifiable DNA or RNA from a variety of sample types with little or no inhibition. In addition, these methods simplified pre-processing, minimized hands-on time, and did not use hazardous organics. Citation Format: Michelle Mandrekar, Douglas Horejsh, Samantha Lewis, Chris Moreland, Marjeta Urh. Automated RNA and DNA purification from FFPE samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4846. doi:10.1158/1538-7445.AM2015-4846
NON-INVASIVE CALCULATION OF FRACTIONAL FLOW RESERVE FOR RECLASSIFICATION OF POTENTIALLY HEMODYNAMICALLY-SIGNIFICANT CORONARY ARTERY DISEASE BY CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY IN EMERGENCY DEPARTMENT CHEST PAIN PATIENTS
Authors: Harold Litt, Erin Greco, Souma Sengupta, Campbell Rogers, Christian Hamilton-Craig, Judd Hollander
Journal: Journal of the American College of Cardiology (2016)
AB0140 Investigation of joint regeneration mechanisms in NEWTS (notophthalmus viridescens)
Authors: S.A. Susanto, C. Schreiyäck, M. Geyer, T. Borchardt, U. Müller-Ladner, R.M. Dinser
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The adult red-spotted newt (<i>notophthalmus viridescens</i>) is able to regenerate damaged knee joints after local injury involving surgically induced defects, and collagenase induced joint instability. The mechanism behind this capacity that lacks in mammals is currently not understood. <h3>Objectives</h3> Investigating the molecular process of joint regeneration in newts and deducing the potential gene candidate <h3>Methods</h3> Transcriptome analysis with cDNA array derived from regenerating newt myocardium was carried out after surgical and collagenase, induced knee damage. We validated the differentially expressed genes in both instances using qRT-PCR. We conducted immunohistochemistry (IHC)and in situ hybridization (ISH) to investigate spatial distribution of the most promising deregulated genes. <h3>Results</h3> 88 from 260 significantly regulated gene transcripts had homology to gene transcripts in public DNA database. We selected the deregulated genes retinoic acid receptor response element 3 (RARR), periostin, tenascin-C (TN-C), olfactomedin, osteonektin, decorin, gamma B crystalline (GBC), thymosin β 4 and complement factor B for further analysis after qPCR-confirmation of deregulation. Tenascin C, the most upregulated gene, locates to the periosteum and perichondrium in newts and is additionally strongly expressed in the undifferentiated regeneration tissue after joint injury. We are currently analyzing the other candidate genes. <h3>Conclusions</h3> We found several gene candidates which may be central to the newts capacity for joint regeneration by employing cDNA array derived from regenerating newt myocardium. TN-C may be an important mediator of joint formation. <h3>References</h3> Matthias Geyer, Thilo Borchardt, Carina Schreiyäck, et al. Endogenous regenration after collagenase -induced knee joint damage in the adult newt notophthalmus viridescens. Ann Rheum Dis (2010). doi:10.1136/ard.2009.126136. James W. Godwin, Jeremy P. Brockes. Regeneration, tissue injury and the immune response. J. Anat. (2006) 209: 423-432 Thilo Borchardt, Mario Looso, Marc Bruckskotten, et al. Analysis of newly established EST databases reveals similarity between heart regeneration in newt and fish. BMC Genomic (2010): 11:4 <h3>Disclosure of Interest</h3> None Declared
OP0047 Successful control of disease activity and treatment with biologics increase the life expectancy in rheumatoid arthritis patients:
Authors: J. Listing, D. Pattloch, J. Kekow, J. Kaufmann, G.-R. Burmester, A. Zink, A. Strangfeld
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the impact of disease activity, functional capacity and treatment with biologic and non-biologic disease modifying anti-rheumatic drugs (bDMARDs, nbDMARDs) on mortality risk in patients with rheumatoid arthrits (RA) enrolled in the German biologics register RABBIT. <h3>Methods</h3> Disease activity (measured by the DAS28 score), functional capacity and treatment details with bDMARDs, nbDMARDs and glucocorticoids were assessed at fixed time points at follow-up. Cox proportional hazard regression was applied to investigate the influence of the time varying DAS28 scores, functional capacity and treatments on the mortality risk after adjustment for age, sex, 8 co-morbid conditions and smoking. The primary analysis was based on a risk window approach assuming the patient was exposed to bDMARD treatment up to 6 months (rituximab: 12 months) after the last dose. <h3>Results</h3> The mean disease duration of the 8,613 RA patients was 10.3 years. The mean observation time was 3.4 years. At baseline the mean DAS28 of the bDMARD patients was 5.9, of the nbDMARD patients 4.9. Five percent (426) patients died within a period of two years after the last visit. Compared to the general population the age and sex standardized mortality ratio was 1.6 [95%CI: 1.4 – 1.8] which corresponds to a shortening of the life expectancy in women and men of 3.5 years. Patients with a mean DAS28 over time below 4.0 had a normal life expectancy. In contrast, female and male patients with a mean DAS28 score at follow-up &gt;4.0 died 6.4 and 7.3 years earlier than age and sex matched subjects from the general population. This significant association between disease activity and the mortality risk was also observed by multivariate Cox regression within the patient sample. Adjusted for age, sex, co-morbid conditions and treatment each increase in the mean DAS28 score by one unit increased the mortality risk by 15% (adjusted hazard ratio [adjHR]: 1.15 p=0.002). Treatment with glucocorticoids also increased the mortality risk (adjHR per 5mg/d: 1.2 p=0.003). Patients exposed to TNFa inhibitors had a significantly lower mortality risk (adjHR: 0.65, Tab. 1). A similar result was found for rituximab and other biologics. With a conservative ever exposed approach, we again found no increased mortality risk for patients exposed to bDMARDs (adjHR=1.0). <h3>Conclusions</h3> In patients with long standing RA an effective treatment which leads to persisting control of disease activity increases the life expectancy. Controlled for demographic and clinical parameters and for clinical effectiveness (DAS28, GC dose), biologics are associated with a lower mortality than nbDMARDs. Supported by a joint, unconditional grant from Abbott, Amgen/Biovitrum, Bristol Myers Squibb, Essex, Pfizer, Roche, and UCB. <h3>Disclosure of Interest</h3> None Declared
P1-12-22: Impact on Survival of the Level of HER2/neu Gene Amplification in Patients with HER2−Positive (HER2+) Advanced Breast Cancer (AdvBrCa) Treated with Trastuzumab (H).
Authors: G Gullo, D Bettio, M Zuradelli, G Masci, L Giordano, C Bareggi, P Salvini, L Runza, A Santoro
Journal: Cancer Research (2011)

Abstract Background The level of HER2/neu (HER2) amplification, defined as HER2/centromeric region of chromosome 17 (CEP17) ratio at dual-color fluorescent in-situ hybridization (FISH) test presents wide variations in clinical practice but its clinical significance is still undefined. We designed this retrospective study to investigate the correlations between level of HER2 amplification in primary (T) and/or metastases (M) and outcome in a cohort of HER2+ AdvBrCa pts treated with a H-containing therapy. Methods Retrospective multicentric study designed according to REporting recommendations for tumor MARKer prognostic studies (REMARK). To be included pts must have all the following: metastatic or locally advanced (not amenable of curative surgery) BrCa, HER2+ tumour defined as score 3+ at immunohistochemistry or FISH positive, treatment with a H-containing regimen (no H in neo- or adjuvant setting was allowed), at least one tumour sample from T and/or M available, measurable or evaluable disease, adequate follow up (FU) information.Outcome parameters included event-free survival (EFS) and overall survival (OS). All FISH tests were prospectively performed in a central laboratory of cytogenetic specifically for this study and in accordance with the international guidelines on FISH testing. Results Ninety-one females were identified and 63 included in the final analysis. Forty-seven pts had one specimen available from T or M, 16 pts had two specimens from either T and a corresponding M. All M samples were obtained before treatment with H. Median FU time is 19.2 months (range 1.2−94.6). In 11 out of 16 cases (69%) with two tumour specimens HER2/CEP17 ratio was higher in M than in T with a statistically significant difference in the median HER2/CEP17 ratio between T (8.3, range: 3.1−18.4) and the corresponding M (10.9, range: 4.6−20.8) (p=0.004). The incremental gain in HER2/CEP17 ratio was associated with significantly shorter OS after trastuzumab-based therapy (p=0.023). A trend towards a correlation between increase in level of HER2 amplification assessed in M and shorter EFS and OS was observed. No statistically significant correlation was found between level of HER2 amplification assessed in T and EFS and OS. Conclusions Level of HER2 amplification reported as HER2/CEP17 ratio is a dynamic parameter in HER2+ AdvBrCa as it increases from T to the matched M in a significant proportion of pts. The gain in HER2 gene copies may represent a prognostic factor for shorter OS when pts with HER2+ AdvBrCa are treated with a H-based therapy. Further studies on the level of HER2 amplification in BrCa metastases are strongly warranted to better understand the biology of HER2−positive breast cancer and to better identify patients with a poorer prognosis after treatment with H. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-22.
Case 39-2015
Authors: Erica S. Shenoy, Peggy S. Lai, Jo-Anne O. Shepard, Richard L. Kradin
Journal: New England Journal of Medicine (2015)

A 22-year-old man was admitted to the intensive care unit in the winter because of hypoxemia and shock. A chest radiograph was notable for diffuse bilateral consolidations. A rapid influenza test was negative. Diagnostic test results were received.
AB0458 Anti-tumor necrosis factor-alpha therapy in refractory behçet uveitis: a single center experience
Authors: S. G. Yilmaz, K. Aksu, G. Keser, Z. Yilmaz, B. Sozeri, H. Ates
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the efficacy and safety of anti-tumor necrosis factor-alpha (anti-TNF-α) agents including infliximab (IFX) and adalimumab (ADA) in the treatment of refractory Behcet uveitis. <h3>Methods</h3> This retrospective study included 12 cases (M/F:7/5; mean age 31.5 ±9.3 years) with refractory Behçet uveitis with 21 eyes followed up by Ege University Department of Ophtalmology between 2010 and 2012. All the patients fulfilled the international criteria for Behçet's disease (BD). Visual acuity and yearly uveitis relapse rates were evaluated before and after commencement of anti-TNF treatment. <h3>Results</h3> Prior to anti-TNF treatment, 6 patients had used conventional immunosuppressive (IS) agents including azathioprine and cyclosporine, and 6 other patients had additionally used interferon-alpha 2a treatment. Before switching to anti-TNF agents, screening for latent tuberculosis was performed using the local guideline. The majority of the patients (n:10) received only IFX infusions 5 mg/kg at 0., 2nd, 6th weeks and in every 8 weeks thereafter. One patient received only ADA subcutaneous injections once in every two weeks, while the other used both agents, i.e. switched from IFX to ADA due to loss of clinical response. Altogether, there were 11 cases who used IFX. Among these cases, infusion periods had to be shortened in 6 cases, in order to control the activity of uveitis. Nevertheless, in three cases, uveitis relapses could not be controlled despite infusions in every four weeks. As mentioned above, one of them was switched to ADA and uveitis activity was controlled, while in two others IFX was stopped due to inefficacy, without having the opportunity of trying another anti-TNF agent. In the remaining single patient who was given only ADA, uveitis was regressed with no relapse. Overall, mean treatment period for anti-TNF agents was 11.6 ± 4.9 (6-21) months, and successful treatment response was observed in 10 out of 12 patients (80%). Considering the 13 eyes of 8 patients who completed one-year period with these anti-TNF agents, basal uveitis relapse rate of 3.4±1.2/year decreased to 0.8±1.0/year (p&lt;0.05). Potential vision was preserved in all of the 21 eyes and visual acuity with Snellen was increased at least two lines in 6 out of 21 eyes (28.6%). In 5 patients who completed the first year of anti-TNF treatment without any relapses, anti-TNF treatment could be stopped only in a single case using ADA, while anti-TNF treatment had to be continued in others. No adverse effect requiring cessation of anti-TNF agents was observed. <h3>Conclusions</h3> In line with the previous data, our findings also suggest that IFX and ADA may be tried in the treatment of Behçet uveitis resistant to other therapeutic approaches. <h3>Disclosure of Interest</h3> None Declared
Case 12-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, John T. Harrington, Robert B. Colvin
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 72-year-old man was admitted to the hospital because of chronic cutaneous ulcers and the recent onset of progressive renal failure.The patient had been in good health until five years earlier, when congestive failure developed. Nine months later a St. Jude prosthetic aortic valve was implanted at this hospital because of stenosis of a bicuspid aortic valve. Warfarin was begun. At discharge the urine and the urea nitrogen and the creatinine levels were normal.Fifteen months before admission the patient entered another hospital because of chronic nonhealing ulcers of the right leg that were suspected to . . .
RT-23 * THE ROLE OF GAMMA KNIFE RADIOSURGERY IN THE TREATMENT FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS
Authors: K. Mori, Y. Chiba, S. Toyota, T. Kumagai, S. Yamamoto, H. Sugano, T. Taki
Journal: Neuro-Oncology (2014)

To evaluate the role of gamma knife (GK) as a treatment modality for primary central nervous system lymphomas (PCNSL), we reviewed PCNSL patients who were treated with GK between November 2004 and May 2014, retrospectively. There were 29 cases (13 males and 16 females, ranged from 33 years old to 91 years old) with 210 treated lesions. Marginal dose was from 12Gy to 18 Gy. One hundred and nineteen lesions of 23 cases could be accessed and all of them showed partial response or complete response. In seven cases, GK was performed at initial treatment, in 18 cases at recurrence, and in four cases at both. Median age of initial treatment group were significantly higher than that of recurred group (77.8 y.o. and 63.6 y.o., p = 0.00268). Two cases of initial treatment group and 16 cases of recurrent group were treated with whole brain radiation therapy (WBRT). GK after first relapse, progression free survival more than six months were obtained for six cases (33.3%), and four of them were free from additional therapy more than one year. Otherwise, thirteen cases (59.1%) received GK repeatedly (2-6 times, median = 3), and interval between each therapy was from 22 to 513 days (median = 93days). We confirmed that GK has high potential for local control. And it was supposed that GK was used as an alternative to WBRT at initial treatment for elderly, or selected to recurrent cases after WBRT. These results showed the role of GK in the treatment for PCNSL is palliative care, now in Japan. But it is clear that there exist patients who can live longer without WBRT by GK. We conclude that GK will become to play a more positive role by modifying its timing and modalities used together.
TICAGRELOR AND ASPIRIN FOR THE PREVENTION OF CARDIOVASCULAR EVENTS AFTER CORONARY ARTERY BYPASS SURGERY: THE TAP-CABG STUDY
Authors: Jacqueline W.L. Saw, Graham Wong, John Mayo, Vicki Bernstein, G.B. John Mancini, Jian Ye, Peter Skarsgard, Andrew Starovoytov, Rebecca Fox, John Cairns
Journal: Journal of the American College of Cardiology (2015)
160 DONOR SPECIFIC ANTI-MHC CLASS II ANTIBODIES NEGATIVELY IMPACT ALLOGRAFT SURVIVAL FOLLOWING LIVER TRANSPLANTATION
Authors: S. Iacob, S. Beckebaum, M. Lindemann, F.M. Heinemann, V. Rebmann, G. Wu, H.J. Schmidt, I. Kabar, A. Radtke, H.A. Baba, V.R. Cicinnati
Journal: Journal of Hepatology (2013)