tbuckley/cabot-search huggingface dataset:
THU0729-HPR Patients and caregivers preferences related with the use of informatic technology tools for education in rheumatoid arthritis
Authors: S Henao, F Rodriguez, L Villarreal, P Santos-Moreno, M Cabrera, D Buitrago-Garcia, C Caicedo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting more than 1% of global population, it is a long term condition that causes pain, disability and affects the quality of life (1). It has been demonstrated that patient9s involvement with its treatment and disease management can be more effective than information-only given by the physician or a health care professional (2). <h3>Objectives</h3> To describe patient9s preferences regarding information technology tools for education and RA management in a specialized center in Bogotá Colombia. <h3>Methods</h3> We conducted a descriptive study where a survey was applied to a group of patients or care-givers attending to a patient-focused symposium in Bogotá Colombia. Descriptive epidemiology was done; percentages and averages were calculated for qualitative variables. <h3>Results</h3> We included 452 participants, 80% were patients and 20% caregivers, only 25% referred to assist to informative activities regarding disease management, 41% reported to have information regarding RA, also between 29% and 45% of patients acknowledged the role of the health-care team in the disease activity management. Regarding technology information tools patients considered that WhatsApp was the most important tool to received messages to disease management (40%) followed by YouTube and websites. 70% reported to have a computer or a mobile phone with internet connection, 60% reported to use Facebook while only 30% reported to use easily websites and twitter. <h3>Conclusions</h3> It is important to know the preferences and access that patients and caregivers have to informatics technology in order to create self-care programs that really are going to be used in this population. This survey is evidence not only to start an educational program in our specialized center but to the health care professionals and stakeholders in Colombia. <h3>References</h3> Prothero L, Georgopoulou S, de Souza S. Patient involvement in the development of a handbook for moderate rheumatoid arthritis. 2016. Vermaak V, Briffa NK, Langlands B, Inderjeeth C, McQuade J. Evaluation of a disease specific rheumatoid arthritis self-management education program, a single group repeated measures study. BMC musculoskeletal disorders. 2015;16:214. <h3>Disclosure of Interest</h3> None declared
THU0119 Assessment of rheumatoid cachexia and its association with clinical, functional and therapeutic outcomes
Authors: ALD Moro, V Hax, RCE Santo, T Fighera, W Kisaki, CV Brenol, RM Xavier
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic and inflammatory disease that besides articular symptoms leads to loss of muscle mass in presence of stable or increased fat mass (FM), condition defined as rheumatoid cachexia (RC). RC is associated with a worse prognosis, but it is still overlooked in clinical practice. <h3>Objectives</h3> To evaluate the prevalence of rheumatoid cachexia (RC) in patients with rheumatoid arthritis (RA) and determine its correlation with the features of RA, the level of physical activity and with the current therapy. <h3>Methods</h3> Ninety one RA patients in a cross-sectional study underwent total body dual-energy x-ray absorptiometry (DXA) for measurement of total and regional fat mass index (FMI; Kg/m<sup>2</sup>), lean mass index (LMI; Kg/m<sup>2</sup>), bone mineral content (BMC; Kg/m<sup>2</sup>) and fat free mass index (FFMI; Kg/m<sup>2</sup>) to assess the prevalence of RC. The associations of measures of body composition with RA features - age, diagnosis time, Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 joints (DAS 28), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) -, level of physical activity (measured by International Physical Activity Questionnaire – IPAQ) and current therapy were explored. <h3>Results</h3> Mean age was 56.8±7.3, disease duration 9 years (3 – 18), DAS28 3.65±1.32, HAQ 1.12 (0.25 – 1.87) and use duration of biological agents was 25 months (17.8 – 52.5). 17% of the patients had FFMI below the 10th percentile and FMI above the 25th percentile of a reference population and 33% of the patients had FFMI below the 25th percentile and FMI above the 50th percentile, condition known as RC, according to the more recently used definitions. FFMI correlated negatively only with age (r=-0.219; p=0.037) and disease duration (r<sub>s</sub>=-0.214; p=0.042). FMI correlated positively with CRP (r<sub>s</sub>=0.229; p=0.029), ESR (r<sub>s</sub>=0.235; p=0.025), DAS 28 (r<sub>s</sub>=0.273; p=0.009) and HAQ (r<sub>s</sub>=0.297; p=0.004). Among patients under biologics, 3.8% (n=1) had RC versus 23% (n=15) of those not taking biologics (p=0.033), according to the stricter definition. <h3>Conclusions</h3> The prevalence of RC was considerable and deserves additional research. Besides that, patients under biological therapy had lower prevalence of RC, suggesting a protective effect of biological agents. <h3>References</h3> Hugo M, Mehsen-Cetre N, Pierreisnard A, Schaeverbeke T, Gin H, Rigalleau V. Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry. Rheumatology. 2016; 55(7): 1202–09. Masuko K. Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis. Front Nutr 2014; 24: 1–20. <h3>Disclosure of Interest</h3> None declared
Charles Leonard Mansfield
Authors: Nick Mansfield
Journal: BMJ (2017)

Charles Leonard Mansfield did house jobs at the Belgrave and Bolingbroke hospitals. After two years’ national service with the Royal Army Medical Corps in Hong Kong, he trained as a general practitioner in south London before taking up a partnership at Knights Hill Surgery in Norwood in 1959. He remained a partner in this practice for 31 years as well as working as a clinical assistant in rheumatology. He served the local community …
Acalabrutinib, a second-generation bruton tyrosine kinase (Btk) inhibitor, in previously untreated chronic lymphocytic leukemia (CLL).
Authors: John C. Byrd, Jeffrey Alan Jones, Richard R. Furman, Deborah Marie Stephens, Steve Devereux, Jennifer R. Brown, Peter Hillmen, Ahmed M. Hamdy, Maria Fardis, Manal Tawashi, Min Hui Wang, Priti Patel, Diana Mittag, Fanny Krantz, Wayne Rothbaum, Raquel Izumi, Susan Mary O'Brien, William G. Wierda
Journal: Journal of Clinical Oncology (2016)

7521 Background: Btk is a kinase involved in B-cell receptor signaling and a critical therapeutic target in CLL. Acalabrutinib—an irreversible, selective Btk inhibitor has demonstrated clinical efficacy in relapsed CLL (Byrd NEJM 2015). Here, we present preliminary results from an ongoing Phase 1-2 study of acalabrutinib monotherapy in patients (pts) with previously untreated CLL. Methods: Pts with previously untreated CLL who met IWCLL 2008 criteria for treatment were eligible, irrespective of any cytopenias. Pts received oral acalabrutinib at 100 mg BID (n=37) or 200 mg QD (n=37). Pts had a median age of 64 (48-85) years, bulky lymph nodes ≥ 5 cm (47%) and unmutated IGHV gene (57%, 38/67). CLL responses were assessed per modified IWCLL criteria. Results: Results are presented through 07Dec2015 for the first 74 treated pts, including 72 evaluable for response. Median time on study (N=74) was 11 (1-15) months. Acalabrutinib was well tolerated with 97% (72/74) of pts continuing on study drug. Most AEs were Grade (Gr) ≤ 2. The most common Gr 1-2 AEs (≥ 15% pts) were headache (42%), diarrhea (35%), arthralgia (22%), contusion (18%), nausea (18%) and increased weight (18%). Gr 3-4 AEs that occurred in ≥ 2 pts were syncope (n=2, both Gr 3) and hypertension (n=2, both Gr 3). One Gr 5 event (pneumonia) has occurred. One Gr 3 upper GI bleed due to a gastric ulcer and aspirin use has occurred. No atrial fibrillation were reported. Clinical activity was observed with both dose schedules; Btk occupancy was highest with BID dosing (98% vs 93% predose at Day 28). All pts had a rapid reduction in lymphadenopathy. Treatment-related lymphocytosis occurred in 53% (39/74) of pts and resolved in 97% (38/39) of these pts. In general, lymphocytosis peaked at a median of 1 week and resolved by a median of 7 (3-15) weeks. Best ORR was 96% (PR=86%, PR+L=10%, SD=4%, PD=0%). Median time to response was 2 (2-8) months. No CLL progression or Richter's transformation have occurred. Conclusions: In pts with previously untreated CLL, a favorable safety profile and high response rates that appear durable were observed with acalabrutinib therapy. Based on these results, a Phase 3 trial has commenced (NCT02475681). Clinical trial information: NCT02029443.
THU0305 Epidemiology of anca-associated vasculitis in northern norway
Authors: AT Nilsen, RA Watts, W Koldingsnes
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The ANCA-associated vasculitides (AAV) have increased in prevalence since the 1980s, with granulomatosis with polyangiitis (GPA) being most prevalent in Caucasian population in circumpolar areas. This was also shown in a study on GPA in northern Norway between 1984 and 1998, which further showed an increasing incidence [1]. <h3>Objectives</h3> The present study aimed to investigate the subsequent 15-year period in the same region, now including all the AAVs. <h3>Methods</h3> The study area has 11 hospitals, no private specialist in rheumatology or nephrology, and an adult population of 371 928. We retrospectively searched all hospital databases, using ICD-10 codes potentially compatible with AAV. Patients diagnosed with AAV from 1999 through 2013 according to the European Medicines Agency (EMEA) algorithm, and for GPA also the subgroup fulfilling the American College of Rheumatology (ACR) 1990 criteria, were included. For prevalence data, patients residing in the area, but with AAV diagnosis prior to 1999, were included too. <h3>Results</h3> Using the EMEA algorithm, 90 incident cases were classified as GPA, 39 as microscopic polyangiitis (MPA) and 14 as eosinophilic granulomatosis with polyangiitis (EGPA). Within the GPA group, 78 patients also met the ACR criteria. The results for incidence and prevalence are given in Table 1: <h3>Conclusions</h3> The GPA incidence and prevalence in this study are the highest reported. Though the incidence has stabilized, prevalence is still increasing, albeit at a decelerating rate (Graph 1). Moreover, the total AAV prevalence doubled in the last 10 years, exceeding previous estimates. Incidence of MPA and EGPA are both within the range found elsewhere. But the MPA incidence appears to be rising reminiscent of GPA before the turn of the century. <h3>References</h3> Koldingsnes W, Nossent H. Epidemiology of Wegener9s granulomatosis in northern Norway. Arthritis Rheum. 2000;43(11):2481–2487. <h3>Disclosure of Interest</h3> None declared
AB0471 Wide heterogeneity in treatment protocols and inappropiate use of prednisolone for anti-ro/la associated-congenital heart block: a systematic review of 492 cases
Authors: A Erden, L Kilic, E Bilgin, A Fanouriakis, S Ceylan, B Hymabaccus, YZ Sener, F Gurler, A Sari, B Armagan, O Karadag, S Kiraz, D Boumpas, U Kalyoncu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Congenital heart block (CHB) risk is 1–2% in case of maternal anti SSA/Ro and/or anti SSB/La antibody positivity. CHB have significant mortality (20–30%) and available therapeutic options9 efficacy is contradictory. <h3>Objectives</h3> To review the literature regarding different treatment modalities for CHB. <h3>Methods</h3> We performed a systematic review (August 2015) on Pubmed, using the following MeSH terms: "neonatal lupus", "congenital heart block"; results were restricted to human studies and English language. 1125 articles were assessed in abstract form and, after employing exclusion criteria, 267 original articles/case reports were evaluated in full text. Finally, 199 studies were included, reporting on a total of 492 CHB patients. All administered treatments were assessed on a patient-by-patient basis. <h3>Results</h3> A total of 243 cases reported data for CHB treatment: glucocorticoids (GCs) in 106 (43.6%) cases, intravenous immunoglobulin (IVIG) in 14 (5.7%) cases, and hydroxychloroquine in 5 (2.0%) cases. 21 patients received plasmapheresis treatment. 134 (55.1%) cases received no treatment. Both GCs and IVIG were mostly used in cases with complete atrioventricular (AV) block (74.1% and 61.5% of cases, respectively). Different types of GCs were used: Dexamethasone in 54 (58.6%) patients, prednisolone in 27 (29.3%) and betamethasone in 11 (11.9%) patients (total 92 patients with available data). Dosing schemes and regimens were also widely heterogeneous, with fifteen different regimens used by different centres (Table). Regarding IVIG treatment, six different algorithms were used. Similarly, five different plasmapheresis protocols were used. <h3>Conclusions</h3> There is no consensus in the treatment of CHB. Drug selection and dosing regimens have wide heterogeneity. More than half cases received no treatment. Of note, prednisolone has often been used, despite its inability to cross the placenta. <h3>Disclosure of Interest</h3> None declared
Sequential Delivery of Cyclopeptide RA-V and Doxorubicin for Combination Therapy on Resistant Tumor and <i>In Situ</i> Monitoring of Cytochrome c Release
Authors: Huachao Chen, Yurong Wang, Yongrong Yao, Shenglin Qiao, Hao Wang, Ninghua Tan
Journal: Theranostics (2017)

A programmed drug delivery system that can achieve sequential release of multiple therapeutics under different stimulus holds great promise to enhance the treatment efficacy and overcome multi-drug resistance (MDR) in tumor.Herein, multi-organelle-targeted and pH/ cytochrome c (Cyt c) dual-responsive nanoparticles were designed for combination therapy on resistant tumor.In this system (designated DGLipo NPs), doxorubicin (Dox) was intercalated into the DNA duplex containing a Cyt c aptamer, which subsequently loaded in the dendrigraftpoly-L-lysines (DGL) cores of DGLipo NPs, while cyclopeptide RA-V was doped into the pH-sensitive liposomal shells.After dual modification with c(RGDfK) and mitochondria-penetrating peptide (MPP), DGLipo NPs could successively deliver the two drugs into lysosome and mitochondria of cancer cells, and achieve sequential drug release in virtue of the unique characteristic of these two organelles.The organelle-specific and spatiotemporally controlled release of Dox and RA-V led to enhanced therapeutic outcomes in MDR tumor.More significantly, the DGLipo NPs were successfully applied to monitor Cyt c release during mitochondria-mediated apoptotic process.This work represents a versatile strategy for precise combination therapy against resistant tumor with spatiotemporal control, and provides a potential tool for Cyt c-related apoptotic studies.
Genome-wide association study identifies new prostate cancer susceptibility loci
Authors: F R Schumacher, S I Berndt, A Siddig, K Jacobs, Z Wang, S Lindstrom, V L Stevens, C Chen, A M Mondul, R C Travis, D O Straml, R A Eeles, D F Easton, G Giles, G Severi, H Gronberg, F Wiklund, N E Allen, G L Andriolell, A Barricarte, H Boeing, de Mesquita Hbb., Crawford, W R Divers, C A Gonzalez, J M Garziano, E L Giovannucci, M Johansson, L Le Marchand, J Ma, S Sier, P Stattin, M J Stampfer, A Tjonneland, P Vineis, J Virtamo, U Voge, S J Weinstein, M Yeager, M J Thun, L N Kolonel, B E Henderson, D Albanes, R B Hayes, H S Feigelson, E Riboli, D J Hunter, S J Chanock, C A Haimanl, P Kraft
Journal: Cancer Research (2011)
Abstract 16905: Evaluation of Immediate Procedural Outcome After MitraClip Using Automated Quantitaive Real-time Volume Color Flow Doppler Transesophageal Echocardiography
Authors: Shizhen Liu, Vivek Rajagopal, William L Ballard, Sara Mobasseri, Venkateshwar Polsani, Hassan Sayegh, Federico Milla, Xiao Zhou, Zhen Qian, Randolph Martin, Tommaso Mansi, Helene Houle, Mani A Vannan
Journal: Circulation (2015)

Background: Current echocardiographic evaluation of residual MR after Mitra-Clip is based on a semi-quantitative scale (trace to 4+). We evaluated a previously validated quantitative approach using automated real-time volume color flow Doppler (3D-RTVCFD). Methods: 30 patients (age 82 ± 5) underwent Mitra-Clip implantation guided by 3D-RTVCFD TEE (Siemens SC2000, CA). In 10 patients, data to automatically quantify 3-D regurgitant volume (RV, ml) and fraction (RF, %) and anatomic regurgitant orifice area (AROA) was available (Figure, upper panel). All patients had conventional 2-D Echo data for assessment of MR severity using the standard integrated approach. Results: MR was severe (4+) in 8, and moderately severe (3+) in 2 patients at baseline. MR post Mitra-Clip was mild or trace in 6 (≤1+, Group 1), and moderate in 4 (Group 2) patients. At baseline, the (mean±SD) 3-D RV/RF was 54.5±19.9 ml/60.6±10.2% and the AROA was 0.6±0.2 cm2 for the whole group. Post Mitra-Clip, the 3-D RV/RF was 23.6±10.3 ml/37.0±13.9% (p&lt;0.01/p&lt;0.001 vs. baseline) and the AROA was 0.3±0.1 cm2 (p&lt;0.05). Both Group 1 and Group 2 had similar baseline RF, and both demonstrated a 39% and 38% decrease in RF post Mitra-clip, respectively (Figure, bottom graph). The decrease in AROA in both groups post Mitra-Clip was also significant (~53% in Group 1 and ~59% in Group 2). Thus, despite “moderate” residual MR using the semi-quantitative scale in Group 2, there was significant decreases in both RF and AROA. Conversely, in Group 1 some of the residual MR assessed as “mild” indeed had 3-D RF and AROA in the moderate range, post Mitra-clip. Conclusion: Automated quantitative 3-D real-time volume color flow Doppler TEE offers a quantitative assessment of residual MR post Mitra-clip immediately after the procedure. This may refine decision-making with regard to number of clips. Both accuracy of 3D RTVCFD TEE to quantify MR and it’s predictive value for mid- to long term procedural success need further studies.
Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance
Authors: Linda S. Nooij, Natalja T. ter Haar, Dina Ruano, Natalia Rakislova, Tom van Wezel, Vincent T.H.B.M. Smit, Baptist J.B.M.Z. Trimbos, Jaume Ordi, Mariette I.E. van Poelgeest, Tjalling Bosse
Journal: Clinical Cancer Research (2017)

Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers.Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort).Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower (P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV+, HPV-/p53wt, HPV-/p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV+, 16.3% for HPV-/p53wt and 22.6% for HPV-/p53abn tumors (P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis (P = 0.020).Conclusions: HPV- and HPV+ vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV-/p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV+ VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781-9. ©2017 AACR.
SAT0144 Tumor necrosis factor-alpha inhibitors and psychiatric side effects: results from the french pharmacovigilance database
Authors: CM Yelnik, L Gaboriau, N Petitpain, H Théophile, C Scalbert, E Delaporte, S Gautier, M Lambert
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although Tumor Necosis Factor alpha (TNF-α) is a major proinflammatory cytokine in the brain, potential psychiatric side effects of TNF-α inhibitors have been little investigated. Manic and psychotic disorders are not recognized as TNF-α inhibitors9 side effects even though few reports of such complications have been reported. <h3>Objectives</h3> This study reports cases with psychiatric symptoms (in the spectrum of psychotic and manic disorders) that occur during treatment with tumor necrosis factor alpha (TNF-α) inhibitors and aims to evaluate the role of these agents as causative factors. <h3>Methods</h3> We searched the French Pharmocovigilance Database for consecutive cases of positive psychiatric side effects reported during treatment with TNF-α inhibitors. Major psychiatric symptoms were defined, according to DSM-V, as mania and psychosis, and minor psychiatric symptoms as psychomotor agitation, euphoria, hallucinations, personality distortion, and increased libido. Each case had one major symptom or at least one minor symptom. <h3>Results</h3> Among 7912 consecutive cases of side effects registered in the database for TNF-α inhibitors, 184 reported psychiatric symptoms, and of these, 71 met inclusion criteria, whereas 113 met an exclusion criterion. Depression was the most frequent cause for exclusion. TNF-α inhibitors were the only medication suspected in 56 cases (79%). The time between beginning TNF-α inhibitors and onset of symptoms varied from hours to months with a median time of 49 days (IQR=156); initial symptoms mostly worsened under treatment. TNF-α inhibitors were withdrawn in 42 (61%) cases. The improvement of symptoms was significantly associated with treatment withdrawal (78% versus 22%, <i>p=0.01</i>). Relapses occurred after rechallenge of TNF-α inhibitors in three of four patients. <h3>Conclusions</h3> We report the first cohort of 71 cases with psychiatric symptoms in the spectrum of manic and psychotic disorders during treatment with TNF-α inhibitors. Our experience suggests that anti-TNFα therapy may cause manic or psychotic side effects. <h3>Disclosure of Interest</h3> None declared
Strategies to improve monitoring disease progression, assessing cardiovascular risk, and defining prognostic biomarkers in chronic kidney disease
Authors: Michelle J. Pena, Peter Stenvinkel, Matthias Kretzler, Dwomoa Adu, Sanjay Kumar Agarwal, Josef Coresh, Harold I. Feldman, Agnes B. Fogo, Ron T. Gansevoort, David C. Harris, Vivekanand Jha, Zhi-Hong Liu, Valerie A. Luyckx, Ziad A. Massy, Ravindra Mehta, Robert G. Nelson, Donal J. O'Donoghue, Gregorio T. Obrador, Charlotte J. Roberts, Laura Sola, Ernest K. Sumaili, Sajja Tatiyanupanwong, Bernadette Thomas, Andrzej Wiecek, Chirag R. Parikh, Hiddo J.L. Heerspink
Journal: Kidney International Supplements (2017)