tbuckley/cabot-search huggingface dataset:
Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia
Authors: F Nadeu, G Clot, J Delgado, D Martín-García, T Baumann, I Salaverria, S Beà, M Pinyol, P Jares, A Navarro, H Suárez-Cisneros, M Aymerich, M Rozman, N Villamor, D Colomer, M González, M Alcoceba, M J Terol, B Navarro, E Colado, ÁR Payer, X S Puente, C López-Otín, A López-Guillermo, A Enjuanes, E Campo
Journal: Leukemia (2017)

Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6–25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases. CNA tended to be acquired early in the evolution of the disease and remained stable, whereas the mutational heterogeneity increased in a subset of tumors. The prognostic impact of different genes was related to the size of the mutated clone. Combining mutations and CNA, we observed that the accumulation of driver alterations (mutational complexity) gradually shortened the time to first treatment independently of the clonal architecture, IGHV status and Binet stage. Conversely, the overall survival was associated with the increasing subclonal diversity of the tumors but it was related to the age of patients, IGHV and TP53 status of the tumors. In conclusion, our study reveals that both the mutational complexity and subclonal diversity influence the evolution of CLL.
AB0259 Predictors of high disease activity in a cohort of greek patients with acpa positive early rheumatoid arthritis
Authors: N Papadopoulos, A Gkagkalis, E Konstantinidou, L Mentesidou, G Tzatzagou, V Galanopoulou
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In Early Rheumatoid Arthritis, the presence of ACPA positivity is associated with increased disease activity. <h3>Objectives</h3> To investigate possible predictors, for high disease activity (DAS-28 &gt;5.1), in a cohort of Greek patients with ACPA positive early RA. <h3>Methods</h3> From 2000 until December 2016, 156 patients with ACPA positive early RA, were diagnosed and subsequently followed up as outpatients at the Rheumatology Unit of our hospital. Demographic, clinical, laboratory and therapeutic parameters were evaluated during every follow-up. At the end of the study (last visit during 2016), all the above parameters were re-evaluated, considering the high disase activity (DAS-28 &gt;5.1). The used methods were χ<sup>2</sup>, ANOVA, Binary Logistic Regression (BLR) and ROC Curve. <h3>Results</h3> From 156 patients, 25% were males, 37.8% were current smokers, 76.9% were RF positive, 34.6% presenting with extra-articular manifestations and 16% with anemia of chronic disease (ACD). At the time of diagnosis, Univariate analysis revealed that smokers, RF positivity, high levels of CRP, patients with extra-articular manifestations and those with ACD, corellate statstically significant with high disease activity (p=0.011, p=0.006, p=0.03, p=0.001 and p=0.001 respectively). Using the BRL we found that the odds ratio for DAS-28 &gt;5.1, were for smokers 2.95, for RF positivity 3.397 and for CRP 1.066 respectively. Based on the previous results the severity of disease can be predicted with sensitivity 80% (area unedr the curve: p&lt;0.001, CI=0.723–0.878) using the ROC curve. <h3>Conclusions</h3> |High Diseasae Activity in ACPA positive early RA, at diagnosis, is best predicted by smoking, RF positivity and high levels of CRP. <h3>References</h3> Aletaha D et al, Rheum Dis North Am 2006;32:9–44. ScottDL et al, Lancet 2020;376:1094–1108. Papadopoulos N et al, Clin Rev Allerg Immunol 2008;34:11–15. <h3>Disclosure of Interest</h3> None declared
AB0680 Analysis the causes and countermeasures of ignoring swallowing dysfunction in patients with polymyositis and dermatomyositis
Authors: Y Wen, Q MinLi, L Yan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The patients with Polymyositis and Dermatomyositis always ignored swallowing dysfunction and most of them eventually had no enough knowledge of this. For this situation, to find out the reasons and take appropriate measures was necessary. <h3>Objectives</h3> To analyze the causes of ignoring swallowing dysfunction in patients with Polymyositis and Dermatomyositis and to explore the corresponding preventive measures. <h3>Methods</h3> The clinical data of 47 patients with Polymyositis and Dermatomyositis in hospital from September 2012 to December 2013 was analyzed retrospectively. The swallowing function was evaluated by the water swallow test, and the patients9 knowledge of swallowing dysfunction was surveyed. <h3>Results</h3> Only 2 patients complained of choking during swallowing, with ignorance rate of 95.74%. Positive rate was 40.43% in water swallow test, of which grade II dysphagia proposition was 58%, III grade was 32%, IV grade was 10%. 100% of patients believed that sternal obstruction or dysphagia as swallowing dysfunction. 89.36% of patients didn9t think drinking water with bucking as swallowing dysfunction. <h3>Conclusions</h3> The symptoms of limb weakness in patients with Polymyositis and Dermatomyositis may obscure the presence of dysphagia. In addition, the patients do not have enough knowledge about dysphagia that to neglect the swallowing dysfunction. To improve detection rate of swallowing dysfunction in patients with Polymyositis and Dermatomyositis, earching detailed history by listing dysphagia performance and providing water swallow test is necessary. <h3>References</h3> Comparison between swallowing-related and limb muscle involvement in dermatomyositispatients. Kim SJ, Han TR, Jeong SJ, Beom JW. Scand J Rheumatol. 2010 Aug;39(4):336–40. <h3>Disclosure of Interest</h3> None declared
FRI0570 Osteoporosis and breast cancer: outcomes at a specialized osteoporosis clinic following a structured assessment
Authors: S Lopez-Salguero, JC Ordoñez, L Ranieri, M Andrés, J Ponce, I Ibero
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Women with breast cáncer (BC) are at risk for the development of bone loss and osteoporosis (OP) mainly due to adjuvant therapies. Aromatase inhibitors (AI) therapy fully suppresses estrogen synthesis, further exacerbating the increased bone resorption and leading to an excess fracture risk. Thus, a close monitoring of bone mineral metabolism is recommended. <h3>Objectives</h3> The aim of the present study was to analyze bone health status and clinical characteristics of women BC referred by oncologist to a specialized clinic and their outcomes during follow-up. <h3>Methods</h3> Retrospective analysis of consecutive female patients with recent BC and low bone mineral density (BMD) referred to the osteoporosis outpatient clinic for assessment, as agreed with oncologists. A descriptive analysis of epidemiological, clinical, laboratory, imaging, and dual energy x-ray absorptiometry (DEXA) data is presented, both at baseline and last visit. 95% confidence intervals (95% CI) were estimated for rate of fragility fractures (FF) at baseline and during follow-up. <h3>Results</h3> A total number of 156 female patients have been assessed up to January 2017; median aged 60.7 (SD±10.6) years old, 89% postmenopausal. BC was mainly non-methastasic (117; 75%), and 110 (70%) patients were on aromatase inhibitors (14 on anastrozole, 89 on letrozole, and 7 on exemestane). 36 patients (23%) were active smokers, and 17 (11%) had stopped smoking. At baseline, 37 patients (24.2%, 95CI% 20–37) had previous FF, mostly vertebral (19) or non-vertebral (13), and three cases had suffered from multiple FF. BMDs were at osteoporotic range at the lumbar spine (median T-score -2.6 p25/75 -2.2, -3.2) and osteopenic at both the femoral neck and hip (mediant T-score -1.9 p25/75 -1.1, -2.3). Regarding antiosteoporotic therapies, bisphosphonates were prescribed in 110 cases (70.5%), denosumab in 24 (15.3%), and raloxifene in two cases (1.2%); in the others (12.8%) only calcium plus vitamin D supplementation was recommended. A total of 107 patients were followed a median of 2.13 years (p25–75 1.23–3.18). During follow-up, new FF occurred in 13 patients (12.1%, 95% CI 6–19), that were vertebral in 8, non-vertebral in 4, both in one case, while no hip FF were detected. <h3>Conclusions</h3> outcomes of a structured assessment of female patients with BC and low BMD are reported here. Despite this, 12% of cases developed a new FF, highlighting the need for special attention to this singular, secondary form of osteoporosis. <h3>Disclosure of Interest</h3> None declared
Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma
Authors: Manuel Fankhauser, Maria A. S. Broggi, Lambert Potin, Natacha Bordry, Laura Jeanbart, Amanda W. Lund, Elodie Da Costa, Sylvie Hauert, Marcela Rincon-Restrepo, Christopher Tremblay, Elena Cabello, Krisztian Homicsko, Olivier Michielin, Douglas Hanahan, Daniel E. Speiser, Melody A. Swartz
Journal: Science Translational Medicine (2017)

Tumor lymphangiogenesis, a driver of immunosuppression and metastasis, also potentiates immunotherapy.
Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature
Authors: A. Eyraud, L. Scouppe, T. Barnetche, E. Forcade, E. Lazaro, P. Duffau, C. Richez, J. Seneschal, M.-E. Truchetet
Journal: British Journal of Dermatology (2017)

We aimed to assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) for skin sclerosis (SSc) and lung function in SSc. We performed a systematic literature review in the PubMed and Scopus databases from the earliest records to March 2016. We assessed study quality using the Cochrane tool for randomized studies, the Newcastle–Ottawa Scale for controlled cohort studies and an 18‐item quality‐appraisal checklist for case series. The primary outcome was the improvement of skin thickening using the modified Rodnan Skin Score (mRSS). The secondary outcome was efficacy on lung function, using diffusing capacity of the lungs for carbon monoxide and forced vital capacity (FVC). The safety of the procedure was evaluated. The literature search identified 431 citations. There were 38 studies involving a total of 344 patients who fulfilled our inclusion criteria. No meta‐analysis was performed due to a high heterogeneity. There was a significant improvement in mRSS in the majority of the reports (P < 0·05), and the results were sustained for up to 8 years after autologous HSCT. The randomized studies and the four cohort studies each showed a slight but statistically significant improvement in FVC at 1 or 2 years. The treatment‐related mortality calculated by pooling patients of 35 studies (336 patients with a follow‐up up to 146 months) was 8·3% after autologous HSCT and 1% in cyclophosphamide‐treated groups. Despite heterogeneity among the studies, we determined that autologous HSCT significantly improved cutaneous fibrosis and slightly improved FVC. Safety of autologous HSCT is acceptable given the severity of the disease. This systematic review was registered on PROSPERO, number CRD42016027951.
THU0073 Factors associated with treatment adherence in rheumatoid arthritis: a systematic literature review
Authors: ET Goh, AJX Soo, J Galloway, S Norton, E Nikiphorou
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Nonadherence to treatment in rheumatoid arthritis (RA) has been shown to negatively impact on treat to target goals and disease outcomes. Identifying and targeting potential factors influencing nonadherence is therefore crucial in optimising patient management. <h3>Objectives</h3> To determine factors associated with nonadherence in patients with RA. <h3>Methods</h3> An electronic search was performed by two independent reviewers using MEDLINE and focusing on articles published from inception to January 2017. The search strategy combined the thesaurus (MeSH) and expanded keyword searches of two concepts: RA and treatment adherence. Inclusion criteria included observational studies and clinical trials examining potential factors associated with nonadherence. Exclusion criteria included articles not in English or without online access and those with a focus on forms of therapy other than medication. Agreement between raters at the screening stage was high (97%, kappa=.87). <h3>Results</h3> The primary search yielded 1411 papers, from which 75 were eventually identified as suitable for full review (Figure). Of the 75 papers, 65 were based on observational studies and 10 on clinical trials. Factors associated with nonadherence were broadly categorized into patient-related factors (socio-demographic factors, patient perceptions [beliefs/knowledge/attitudes]), disease-related factors (disease duration/severity, comorbidities, functional disability) and treatment-related factors (drug type/ method of administration/duration/regimen complexity, combination therapy). The majority (70% of all included studies) of studies reported significant associations between patient-driven factors and nonadherence. Adherence was found to be negatively associated with socioeconomic status, health literacy, and beliefs/perceptions/knowledge of the disease and treatment. Studies reported poorer mental health state (n=6) and greater disability/pain (n=7) to be implicated in nonadherence. Disease duration was largely non-significant in treatment adherence, although a few studies reported a negative correlation (n=3). Combining biologics with DMARDs was associated with improved adherence. However, considering non-biologic DMARDs only, adherence rates were higher amongst monotherapy users. One study identified polypharmacy to be negatively associated with adherence. Drug side effects were associated with nonadherence (n=7). <h3>Conclusions</h3> Patient-related factors including personal perceptions were among key contributors to nonadherence to medication in RA patients. This highlights the need for addressing patient-driven perceptions, along with disease and treatment <h3>Acknowledgements</h3> Many thanks to Simon Coates and Julia Garthwaite of Library Services at University College London for their advice. <h3>Disclosure of Interest</h3> None declared
THU0114 Effects of smoking on baricitinib efficacy in patients with rheumatoid arthritis: pooled analysis from two phase 3 clinical trials
Authors: J Curtis, P Emery, G Burmester, V Arora, J Alam, D Muram, L Klareskog
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The efficacy of some rheumatoid arthritis (RA) therapies is reduced among patients who are smokers. <h3>Objectives</h3> This post-hoc analysis of two phase 3 studies assessed the effects of patient smoking status on the response to baricitinib treatment in patients with RA. <h3>Methods</h3> In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomized to placebo once-daily (QD) (N=488), baricitinib 4 mg QD (N=487), or adalimumab 40 mg biweekly (N=330).<sup>1</sup> In RA-BUILD (NCT01721057), patients with inadequate response to conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were randomized to placebo (N=228) or baricitinib (2 mg, N=229; or 4 mg, N=227) QD.<sup>2</sup> Patients continued background csDMARD therapy in both studies. This post-hoc analysis was conducted in the placebo (N=716) and baricitinib 4 mg (N=714) patients. Patient-reported smoking status was categorized as current (smokers) or not current (non-smokers). <h3>Results</h3> Among 1,430 evaluable patients who received placebo or baricitinib 4 mg, 290 (20.3%) were smokers. Smoking status at baseline did not affect the clinical results of treatment with baricitinib for 24 weeks; smokers who received placebo were numerically less likely than non-smokers receiving placebo to achieve most clinical outcomes (Table). Baricitinib9s effect on modified total Sharp score was more pronounced among nonsmokers (interaction p-value =0.07). ACR20/50/70=20%, 50%, and 70% improvement in American College of Rheumatology criteria; CDAI=Clinical Disease Activity Index; DAS28-hsCRP=Disease Activity Score 28-high sensitivity C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index; mTSS=modified total Sharp score; SDAI=Simple Disease Activity Index. <h3>Conclusions</h3> This analysis of smokers and non-smokers in two RA trials demonstrated that the beneficial effect of baricitinib treatment versus placebo was similar on all clinical endpoints, but may differ for structural damage progression. <h3>References</h3> Taylor PC et al. Arthritis Rheumatol 2015;67(suppl 10) abst 2L. Dougados M et al. Ann Rheum Dis 2017;76:88–95. <h3>Disclosure of Interest</h3> J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche/Genentech, Corrona, UCB, Myriad, Eli Lilly and Company, Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche/Genentech, Corrona, UCB, Myriad, Eli Lilly and Company, Employee of: University of Alabama at Birmingham, P. Emery Consultant for: Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, Eli Lilly and Company, G. Burmester Consultant for: Eli Lilly and Company, V. Arora Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, D. Muram Employee of: Eli Lilly and Company, L. Klareskog Grant/research support from: Janssen, Pfizer, BMS, GSK, AbbVie, Roche.
The Durability of Antireflux Surgery
Authors: Stuart J. Spechler
Journal: JAMA (2017)

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High-dose interleukin-2 (HD IL-2) for advanced melanoma: a single center experience from the University of Pittsburgh Cancer Institute
Authors: Diwakar Davar, Fei Ding, Melissa Saul, Cindy Sander, Ahmad A. Tarhini, John M. Kirkwood, Hussein A. Tawbi
Journal: Journal for ImmunoTherapy of Cancer (2017)

Durable remissions are observed in a fraction of metastatic melanoma patients treated with high-dose interleukin-2 (HD IL-2). Early studies reported overall (OR) and complete response (CR) rates of 16% and 8% respectively. Toxicity limited use to specialized centers with standardized protocols. We report on 243 patients treated at the University of Pittsburgh in a non-intensive care unit (ICU) oncology specialty setting.Clinical and radiological data were collected on 243 patients treated between 1992 and 2015. Each HD IL-2 cycle was given over 5 days, cycles were repeated after 9 days and courses (2 cycles) were repeated every 6-9 weeks in patients with stable or responding disease, for up to 3 courses total. Influence of baseline characteristics on outcomes was assessed using Kaplan-Meier estimates and Cox proportional hazards analysis.Two hundred forty-three patients received 692 cycles (5270 doses) between 1992 and 2015. Two hundred thirty-seven patients were evaluable for response: OR rate 18.1% with CR rate 8.0%. Median overall survival (OS) 9.6 months in the entire cohort but 64.9 months in responders. Median number of cycles delivered was 2,and median number of doses per cycle was 8. Toxicity was consistent with prior reports. HD IL-2 required ICU transfers in 11 patients and 1 death was attributed to HD IL-2. Pre-treatment lactate dehydrogenase (LDH) levels correlated significantly with progression-free survival [1-2× upper limit normal (ULN) HR 1.95; >2× ULN HR 2.32] and overall survival (1-2× ULN HR 1.67; >2× ULN 2.49). Response to HD IL-2 and site of metastatic disease also correlated significantly with progression-free and overall survival.In this large series of patients spanning more than two decades, OR/CR rates with HD IL-2 were 18.1%/8.0% respectively. Toxicity data was consistent with prior reports. Pre-treatment LDH values and site(s) of metastatic disease may be useful markers to select patients at greater likelihood of benefit to HD IL-2 therapy.
THU0072 Risk of revision, prosthetic joint infection and death following total hip or knee arthroplasty in patients with rheumatoid arthritis – a nationwide cohort study from denmark
Authors: RL Cordtz, LE Kristensen, S Overgaard, A Odgaard, H Lindegaard, L Dreyer
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Studies have shown that rheumatoid arthritis (RA) patients are at increased risk of prosthetic joint infection (PJI) but with non-uniform results for mortality risk, following total hip and knee arthroplasty (THA and TKA, respectively). The impact of biological DMARD (bDMARD) treatment on the risk of these outcomes is unknown. <h3>Objectives</h3> To investigate the risk of revision, PJI and death following THA and TKA in 1) RA compared with osteoarthritis (OA) patients and 2) RA patients treated with bDMARDs compared with those not. <h3>Methods</h3> Register-based cohort study linking the National Patient Register, DANBIO, Danish Hip Arthroplasty Register and Danish Knee Arthroplasty Register. <i>Follow-up:</i> from date of THA/TKA to date of any of the outcomes, to 10 years of follow-up or end of 2014, whichever came first. <i>Statistics:</i> Fine-Gray competing risks analyses to calculate confounder adjusted sub-Hazard Ratios (aSHR) with 95% confidence intervals (95% CI) for revision and PJI; Cox proportional hazard models to calculate aHR for risk of death. <h3>Results</h3> We identified 3913 RA and 120 499 OA patients. In DANBIO, 360 bDMARD and 1586 not-bDMARD treated RA patients were eligible for analysis. See Table for results. <h3>Conclusions</h3> We report an increased risk of death and PJI but a lower risk of revision in patients with RA compared with OA following THA and TKA. In RA patients, prednisolone, but not bDMARD treatment within the year prior and/or following THA and TKA was associated with an increased risk of death. <h3>Disclosure of Interest</h3> R. Cordtz: None declared, L. E. Kristensen: None declared, S. Overgaard Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Celgene, BMS, MSD, Novartis, Eli Lilly, Janssen Pharmaceuticals, A. Odgaard: None declared, H. Lindegaard: None declared, L. Dreyer Consultant for: LD has received fees for speaking and consultancy by MSD, UCB and Janssen pharmaceuticals.