tbuckley/cabot-search huggingface dataset:
Phase I trial of sipuleucel-T combined with ipilimumab (SIPIPI) in progressive M-CRPC.
Authors: Mark C. Scholz, Sabrina Yep, Colleen Kelly, Khang N. Chau, Jeffrey S. Turner, Richard Y. Lam
Journal: Journal of Clinical Oncology (2016)

e16517 Background: Sipuleucel–T (SIP-T) and ipilimumab (IPI) have potentially synergistic anticancer effects. Post treatment increases in disease-specific immunoglobulins (IG) correlate with improved survival. Methods: Nine men with progressive metastatic castrate-resistant prostate cancer M-CRPC received a fixed dose SIP-T followed by IPI. 3 pts had SIP-T in combination with IPI at each of 3 dose levels as follows: 1 mg/kg 1 week after SIP-T, 1 mg/kg 1 & 4 weeks after SIP-T or 1 mg/kg after 1, 4 & 7 weeks after SIP-T. IG specific for the GM-CSF/PAP fusion protein (PA2024) and to prostatic acid phosphatase (PAP) were measured prior to SIP-T, prior to IPI, 1 & 5 weeks following IPI, a subsequently every two months x 2 and every 3 months x 4. PAP and PA2024 IgG and IgG-IgM titers were compared across the three dosages and across time points. Results: Median age, Gleason score and previous hormonal interventions were 77 yrs., 8 and 3 respectively. Metastatic site: Bone (8); Lymph node only (1). Previous adjuvant docetaxel (1). Previous abiraterone (3). IG titers increased with dose of IPI, but these increases were not statistically significant due to the low power with only 3 pts in each group. When combined into one group, statistically significant increases in IG were seen over time. The IG levels increased significantly from pre-SIP-T to post SIP-T (241-253% higher for IgG and 947-1943% higher for IgG-IgM) and again from pre-IPI to post-IPI (244-386% higher). Although the apex for IgG-IgM titers was higher than those for IgM, both titers returned to post-SIP-T (pre-IPI) levels after approximately 8 months. Side effects from SIP-T were minimal. IPI caused a transient grade 1 rash in 1 pt. Median follow up is 24 months (range 15-27). 3 pts died from progressive disease after 9, 18 and 20 months. In the 6 surviving patients treatment subsequent to SIPIPI included abiraterone (4), enzalutamide (3), spot XRT (2) and radium 223 (1). None have required chemo. Median PSA at 24 months is 1.3 (range 0.03-6.65). Conclusions: Ipilimumab increased immunoglobulins specific for the PAP fusion protein and PAP above the level acheived with SIP-T by 244 to 386%. Toxicity was negligible. After 2 years, the 6 surviving pts have a median PSA of 1.3. None have required salvage chemo.
AB1046 Could serum tweak level be an indicator of subclinical atherosclerosis in rheumatoid arthritis?
Authors: M Ucer, N Yilmaz, B Cengiz Elcioglu, T Sahin, P Gun Atak, S Yavuz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> TWEAK is a type 2 transmembrane glycoprotein of TNF family that has multiple functions such as angiogenesis, regulation of tissue production-destruction, proinflammatory cytokine release. TWEAK and Fn14 receptor interaction has an important role in pathogenesis of atherosclerosis. Our aim was to evaluate subclinical atherosclerosis and its association with serum sTWEAK, Fn14 and CD163 levels in RA patients. <h3>Methods</h3> One hundred Rheumatoid Arthritis (RA), 50 Spondyloarthritis (SpA) patients and 50 healthy controls (HC) were included in the study. Serum soluble TWEAK, CD163 and Fn14 levels were measured by ELISA tecnique. Subclinical atherosclerosis was evaluated by echocardiography, which includes carotis intima media thickness (cIMT), aortic strain, stiffness and elasticity. <h3>Results</h3> In RA group 73 (73%) patients were using DMARD9s and 27 (27%) were biological drugs, the mean DAS28 score was 3.49±1.31. At the end of the study, TWEAK levels were found significantly lower (RA; 942.4±305.9, AS; 1087.2±311.0 and HC; 1061.3±402.8 pg/ml, p=0.05), and Fn14 levels were significantly higher (RA; 509.4±861.4, AS; 163.5±249.0 and HC; 91.5±67.9 pg/ml, p&lt;0.01) in RA patients compare to both groups. In addition Fn14 levels were higher in RA patients using biological drugs and seropositive subgroups (1042±1363 vs. 312±451 pg/ml, p&lt;0.01 and 674±101 vs. 188±236 pg/ml, respectively, p&lt;0.01). Fn14 levels were correlated with disease duration (r=0.38, p&lt;0.01). CD163 levels were similar in all groups. Although there was not any difference in cIMT measurements among groups, aortic stiffness was increased (p=0.03), aortic strain and elasticity were decreased (p=0.03, p=0.02) in RA patients compare to healthy controls. Multivariate analysis showed cardiovascular parameters were only associated with age. <h3>Conclusions</h3> In this study we observed impaired aortic parameters showing subclinic atherosclerosis in RA patients. At the same time, decreased levels of serum sTWEAK and elevated levels of serum sFn14, were also shown in RA group. The difference in levels of serum soluble form of these biomarkers may be related to vascular damage in our RA patients who have low disease activity. However, further studies are needed to demonstrate association between atherosclerosis and these biomarkers in RA patients. <h3>Disclosure of Interest</h3> None declared
Bosutinib-related pneumonitis
Authors: Etienne-Marie Jutant, Véronique Meignin, David Montani, Abdellatif Tazi, Philippe Rousselot, Anne Bergeron
Journal: European Respiratory Journal (2017)

We read with interest the recent correspondences from Hickey et al . [1] and Riou et al . [2] reporting bosutinib-associated pulmonary arterial hypertension (PAH) and pleural effusion. Tyrosine kinase inhibitors (TKIs) have revolutionised the treatment of chronic myeloid leukaemia (CML). However, TKIs are associated with potentially serious lung complications, which are particularly associated with dasatinib; the incidence of dasatinib-induced pleural effusion ranges from 15% to 35% [3, 4]. Dasatinib-related PAH has been reported in ∼0.45% of dasatinib-treated patients [5]. Bosutinib (developed by Pfizer (New York, NY, USA) in 2015) is a second-generation TKI approved for patients with CML that is resistant or intolerant to imatinib, nilotinib or dasatinib [6]. Bosutinib can induce parenchymal, pleural and vascular lung disease <http://ow.ly/qMiQ30dMVK5>
AB0695 Dose tapering of infiximab in patients with spondyloarthritis
Authors: M Correyero, JC Nieto, CM González, A Lόpez, R González, C Saenz, L García-Montoya, FJL Longo, I Monteagudo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Infliximab have proven to be effective in spondyloarthritis. Previous studies suggest that patients in clinical remission may benefit from dose reduction or pharmacological tapering without relapse. <h3>Objectives</h3> To study the evolution of clinical activity and physical function in patients with spondyloarthritis, ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under Infliximab (IFX) tapering strategy. <h3>Methods</h3> This is a prospective single-centre observational study of patients diagnosed with AS and PsA treated with IFX (5 mg/kg/infusion) between January 1, 2012 and December 31, 2015. We included patients who achieved clinical remission or low activity index (expressed with BASDAI and BASFI) and decided to lower the dose of 5 to 4 mg/kg/infusion, maintaining the periodicity of the treatment in each patient. Demographic data (age, gender, time with IFX) daily activities, physical activity (BASDAI and BASFI) and laboratory data (ESR and CPR) were collected at the baseline visit prior to tapering, at the next infusion following dose reduction and the last infusion (between November 1st 2014 and December 31st, 2016). <h3>Results</h3> We included 18 patients (16 men) on IFX treatment with EA (16) or axial APs (2). The medians of age and time of evolution were 50.79 years (41.8–55.1) and 9.5 years (7.2–11.5), respectively. Table 1 shows the clinical and laboratory data obtained at the baseline visit, the next infusion and the last infusion. Fourteen patients (87.9%) continued with the dose of 4 mg/kg/infusion and are maintained in clinical remission. Four patients returned to the dose of 5 mg/kg/infusion due to loss of efficacy at dose reduction, with a mean follow-up of 17.6 months (17.0–19.1). Clinical remission was again achieved in the 4 patients, although one of them changed biological therapy due to loss of efficacy of IFX after 3 infusions with 5 mg/kg/infusion. <h3>Conclusions</h3> In our patients with spondyloarthritis dose reduction of IFX was well tolerated and safe, maintaining the clinical response measured by BASDAI and BASFI. In 3 out of 4 patients who worsened upon dose reduction, the 5 mg/kg/infusion dose recovered clinical remission. <h3>References</h3> Janta I et al. Clin Rheumatol. 2015;34: 935–42. Baraliakos X et al. RMD Open. 2016;2: e000272. <h3>Disclosure of Interest</h3> None declared
Bevacizumab or cetuximab plus chemotherapy after progression with bevacizumab plus chemotherapy in patients with wtKRAS metastatic colorectal cancer: A randomized phase II study (Prodige 18 –UNICANCER GI).
Authors: Sandrine Hiret, Christophe Borg, Aurelie Bertaut, Olivier Bouche, Antoine Adenis, Gael Deplanque, Eric Francois, Thierry Conroy, Francois Ghiringhelli, Gaetan Des Guetz, Jean-François Seitz, Pascal Artru, Trevor Stanbury, Marc G. Denis, Jaafar Bennouna
Journal: Journal of Clinical Oncology (2016)

3514 Background: Second-line treatment with chemotherapy plus bevacizumab (Bev) or cetuximab (Cet) is now recognized as a standard treatment in mCRC. The main objective of this French multicenter, prospective open randomized trial was to evaluate the Progression Free Survival (PFS) rate at 4 months in patients receiving chemotherapy plus Bev or Cet after failure with Bev plus chemotherapy. Methods: The main eligibility criteria were disease progression after first-line chemotherapy: 5-FU with irinotecan or oxaliplatin associated with bevacizumab in wtKRAS mCRC. Patients were treated with cross over chemotherapy (FOLFIRI or mFOLFOX6) with bevacizumab (Arm A) or cetuximab (Arm B) until progression or limiting toxicity. The tumor response was evaluated every 6 weeks until progression using RECIST 1.1. Results: 133 patients, 86 male(64.7%), PS 0 (n = 74, 57.8%), 1 (n = 54, 42.2%), in 25 sites in France, were included between October 2010 and May 2015. Most frequent chemotherapy regimens delivered were mFOLFOX6 + Bev (n = 41) or Cet (n = 42); FOLFIRI + Bev (n = 25) or Cet (n = 25). The PFS rate at 4 months was 79% in Arm A and 66.7% in Arm B (p = 0.09). Secondary objectives included median PFS: 7.1 months (Arm A) vs 5.6 months (Arm B) (HR = 1.43; 95%CI [0.99-2.06] p = 0.06), and median OS: 15.9 months (Arm A) vs 10.6 months (Arm B) (HR = 1.44; 95%CI [0.95-2.18] p = 0.08). Conclusions: In wtKRAS mCRC patients progressing after bevacizumab plus chemotherapy, continuation beyond progression with bevacizumab and crossover chemotherapy is associated with a numerically higher but not statistically significant median PFS and OS compared to cetuximab plus chemotherapy. Final data with KRAS and NRAS analysis will be presented at the meeting. Clinical trial information: NCT01442649.
SAT0350 Does a systemic sclerosis patient's clinical phenotype demonstrate his autoantibody status?
Authors: M Boonstra, JA Bakker, MK Ninaber, N Ajmone Marsan, TW Huizinga, JK Vries-Bouwstra de
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although antibody status has shown to improve clinical subsetting in Systemic sclerosis (SSc), it is far from perfect. For optimal clinical subsetting as well as for evaluating the possible pathogenic role of SSc specific antibodies, it is relevant to know to what extent clinical SSc phenotypes are determined by presence of these antibodies. <h3>Objectives</h3> To evaluate 1. if clinical relevant subsets of SSc patients are distinguishable using only clinical data, 2. how SSc specific autoantibodies are distributed among these subsets, and 3. whether adding antibody status to cluster analyses improves recognition of SSc subsets. <h3>Methods</h3> Using data from SSc patients of the Combined Care In Systemic Sclerosis (CCIS) cohort, Leiden University Medical Center, hierarchical clustering based on Ward Method was performed on the first obtained factor of principal component analysis of 7 organ systems (skin;lung;heart;kidney;muscle;vascular;gastro-intestinal) and time since non-Raynaud phenomenon. Clinical characteristics and prevalence of auto-antibodies within clusters was evaluated. We assessed whether adding autoantibody status as additional factor improved clinical subsetting. <h3>Results</h3> Of 407 SSc patients included, 371 patients (91%) fulfilled ACR/EULAR 2013 criteria. Prevalence of anti-centromere (ACA) was 37%, anti-topoisomerase (ATA) 24%, anti-RNAPIII 5%, anti-fibrillarin 4%, anti-Pm/Scl 5%. Cluster analysis identified clinically recognisable clusters of SSc patients based on absence of skin involvement (cluster 1), peripheral vascular involvement (cluster 2), fibrotic complications (cluster 4), and severe vascular complications (pulmonary arterial hypertension [PH], renal crises; cluster 5). Except for cluster 4, where ATA was dominant, in all clusters ACA was the most prevalent auto-antibody. No cluster associated with any of the more rare SSc specific auto-antibodies. Adding of auto-antibodies resulted in increased clinical overlap, with a frequency of PH between 6 – 8% and a frequency of digital ulcers between 24 – 39% in clusters 2,4 and 5. <h3>Conclusions</h3> Based on clinical data alone, relevant subgroups in SSc can be distinguished. Adding antibody status to cluster analyses increases overlap of clinical features between subgroups. These findings show that solely presence of SSc specific antibodies is of limited clinical relevance. For optimal risk stratification more complex serological findings as antibody titers might be additive. <h3>Disclosure of Interest</h3> None declared
AB0836 Performance of quantitative ultrasound and six osteoporosis risk indexes in menopausal women: validation and comparative evaluation study
Authors: I Ghozlani, A El Maataoui, M Ghazi, A Kherrab, R Niamane
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A number of questionnaire-based systems and the use of portable quantitative ultrasound scanners (QUS) have been devised in an attempt to produce a cost-effective method of screening for osteoporosis. <h3>Objectives</h3> to assess the sensitivity and specificity of different techniques and their ability to act as screening tools in relation to dual energy X-ray absorptiometry (DXA). <h3>Methods</h3> 295 white postmenopausal women aged over 60 were enrolled. Each subject completed a standardized questionnaire which permits the measure of six osteoporosis indexes and had bone mineral density (BMD) measured using QUS and DXA. Sensitivity and specificity of the different techniques in relation to DXA were plotted as receiver-operating characteristic (ROC) curves at DXA T-score total hip ≤ -2.5 (osteoporosis). <h3>Results</h3> BUA sensitivity and specificity values were respectively 76.8% and 51.2% at the total hip. The optimal cut-off T-score for QUS was -2 at the total hip. The osteoporosis self-assessment tool (OST) provided consistently the highest AUC (0.80) among the clinical tools and had the best sensitivity and specificity balance (90.2%&gt;44.5%). OST negative likelihood ratio was 0.22. <h3>Conclusions</h3> OST (based only on the weight and the age) performed slightly better than QUS and other risk questionnaires in predicting low BMD at the total hip. <h3>Disclosure of Interest</h3> None declared
SP0008 The future for health professionals in rheumatology
Authors: A De Thurah
Journal: Annals of the Rheumatic Diseases (2017)

In recent years the prevalence of rheumatic diseases has raised leading to increased outpatient activity; at the same time, a general lack of rheumatologists has been described (1). This has created new demands from patients and the health care system towards innovative models of care, e.g. nurse-led follow-up (2), direct access strategies (3) and tele-health interventions (1). In the future this will call for extended and specialized roles for health-professionals within rheumatology, and for future development of compatibility of training of health professionals within the European countries. Further, the current health-service development is confronting the population with increasing demands to understand and utilize health information and to navigate through this increasingly complex healthcare system. It requires that patients are capable of understanding and managing their health, and calls upon a strong focus on health-literate (HL) skills, and the formation of so-called HL organizations (4). In the future, health professionals within rheumatology will have a key role in supporting the development of HL responsive organizations through self-management strategies and patient centered care. The present presentation will address some of these future demands for health professionals in Rheumatology <h3>References</h3> Ward IM, Schmidt TW, Lappan C, Battafarano DF. How critical is tele-medicine to the rheumatology workforce? Arthritis Care Res (Hoboken). 2016 Feb 11. Primdahl J, Sorensen J, Horn HC, et al. Shared care or nursing consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis outpatients with low disease activity–patient outcomes from a 2-year, randomised controlled trial. Ann Rheum Dis. 2014 Feb;73(2):357–64. Hewlett S, Kirwan J, Pollock J, et al. Patient initiated outpatient follow up in rheumatoid arthritis: six year randomised controlled trial. BMJ. 2005 Jan 22;330(7484):171. Health Literacy; the solid facts. World health Organization, Regional Office [Internet]. 2013. Available from: http://www.euro.who.int/__data/assets/pdf_file/0008/190655/e96854.pdf. <h3>Disclosure of Interest</h3> None declared
Choosing a cancer surgeon: Analyzing factors in patient decision making using a best-worst scaling methodology.
Authors: Aslam Ejaz, Gaya Spolverato, Neda Amini, Yuhree Kim, John F Bridges, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2014)

6551 Background: Surgeon experience has been shown to influence outcomes for many types of cancer. The attributes and factors that patients utilize when selecting a hospital or surgeon for cancer treatment remain poorly defined. Methods: All patients with a cancer diagnosis seeking treatment at a surgical clinic at Johns Hopkins Hospital were asked to participate. A survey utilizing a best-worst scaling methodology was constructed to elicit the importance of various factors when selecting a cancer surgeon. Attributes were chosen based on an extensive review of the literature and a pre-test analysis. Attributes were grouped into four categories: surgeon reputation, surgeon qualifications, hospital-related and non-clinical factors. Results: 194 patients with a cancer diagnosis participated in the study (80.8% response rate). Median age was 62 years (IQR: 51.5, 70). Patients had a variety of primary tumor diagnoses with the most common being hepatobiliary (N=35, 18.1%) and breast (N=31, 16.1%). Among the attributes, patients placed the highest value on physician qualifications and hospital-related factors. Specifically, surgeon case-specific experience (coefficient: 2.52, SE 0.06) and the receipt of specialized training experience (coefficient: 2.28, SE 0.06) ranked highest (both P<0.001). Among hospital-related factors, hospital case-specific volume (coefficient: 1.31, SE 0.06; P<0.001) was most important. The lowest rated factors were parking availability (coefficient: -2.80, SE 0.064) and home-to-clinic distance (coefficient: -2.09, SE 0.06) (both P<0.001). The majority of patients reported their ideal surgeon to have at least 6 years of experience (N=153, 86.0%) and to have performed their specific procedure at least 50 times (N=144, 76.6%). After stratifying patients by education level and state of residence, the ranking of factors remained unchanged. Conclusions: Patients consider several factors when choosing a cancer surgeon. Surgeon qualifications and hospital-related factors appear to be most influential in their decision. Easier and more widespread dissemination of surgeon and hospital cancer data such as case volume may be useful for patients in the future.
AB0157 Trex 1 mutation in the members of a family with systemic lupus erythematosus and antiphospholipid syndrome
Authors: S Ugurlu, I Karacan, H Ozdogan, A Tolun, E Tahir Turanli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There are reports showing Three Prime Repair Exonuclease 1 (<i>TREX1</i>) mutations in atypical Systemic Lupus Erythematosus (SLE) patients. <h3>Objectives</h3> Here we report a family with SLE and Antiphospholipid Syndrome (aPL) who are positive for <i>TREX1</i> mutation and complicated with AA amyloidosis <h3>Methods</h3> DNA samples were extracted from peripheral blood samples of two affected (mother and daughter) and two unaffected individuals of the same family. Exome sequencing was performed for the daughter and data was processed according to GATK Best Practices recommendations. Exome variants were used to search for a rare candidate variant causing the disease. Identified variant was screened in four family members using Sanger sequencing. <h3>Results</h3> The index case (mother) was a 63 year-old woman who had developed polyarthritis and recurrent cerebrovascular accident (CVA) at the age of 44. She was positive for ANA, anti-ds-DNA and IgG anti-cardiolipin antibodies. On anticoagulant therapy she still experiences frequent CVAs. The daughter who is 43 years old had experienced depression, non-erosive arthritis and alopecia at the age of 13. She was positive for ANA, dsDNA and ACA and was treated with hydroxychloroquine, prednisolone, and rituximab. She had attacks of deep vein thrombosis despite anticoagulant therapy. A renal biopsy was performed because of an increase in her creatinine level, with no proteinuria and normal urinary sediment, which revealed AA amyloidosis. She was heterozygous for p.R202Q variant in <i>MEFV</i> gene. Further genetic testing was performed for the mother and the daughter as well as two other non-affected members of the family. Candidate variant search in exome data resulted a novel c.2T&gt;A (p.M1?) variant in <i>TREX1</i> gene. The variant was in heterozygous state for both affected members. Since the variant disrupts translation initiation codon (ATG/AAG), it is predicted to cause loss of complete protein production. <h3>Conclusions</h3> There is evidence that <i>TREX1</i> is involved in the pathogenesis of SLE, especially with neuropsychiatric disease. Here we report a familial SLE and aPL syndrome complicated with AA amyloidosis, with a novel <i>TREX1</i> variant. Such cases will increase our ability to understand the genetic spectrum of SLE and may allow the development of more effective therapies. <h3>Disclosure of Interest</h3> None declared