tbuckley/cabot-search huggingface dataset:
THU0604 The assessment of the dutch quality registry rheumatoid arthritis quality indicators in three pilot hospitals
Authors: S Mahmood, L van Tuyl, P van Riel, S Rongen, D van Schaardenburg, C Allaart, R van den Berg, H Moens, R Landewé
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> While practical guidelines and recommendations play an important role in the treatment of RA, rheumatologists often tend to deviate from these guidelines (1). This may result in disparity of quality of care among individual doctors and hospitals. To establish the best possible care, quality measures are needed. These aim to quantify the quality of the delivered care and will form the foundation of quality registries. Standardization of care processes in combination with public reporting of performance (by means of a quality registry) has been suggested to improve quality of care (2). <h3>Objectives</h3> To develop feasible quality indicators (QIs), endorsed by the different stakeholders of the Dutch Quality registry Rheumatoid Arthritis (DQRA). <h3>Methods</h3> An expert group of 8 rheumatologists, 2 patient representatives and 1 healthcare insurer representative developed a minimal set of QIs via a Delphi-like procedure (3), endorsed by the Dutch Society for Rheumatology. Since October 2015, these QIs have been registered by rheumatologists and rheumatology nurses, once a year in 26 hospitals, along with a patient evaluation questionnaire regarding the received care. To determine whether it is feasible to collect these QIs in daily practice, retrospective data from three hospitals was obtained (hospital A (university), B and C (non-academic)). Feasibility was determined by evaluation of: Completeness of registered data (figure 1) Possibility to calculate disease activity categories (remission, low-high disease activity) Possibility to calculate changes over time in disease activity categories Extraction of data regarding (b)DMARD use <h3>Results</h3> Selected QIs are: 1. Percentage of patients in a certain disease activity category 2. Percentage of patients using a certain (b)DMARD 3. Patient reported experience with received care Hospital B provided only data from one year (2014) and was not able to extract data on medication from their electronic record system. <h3>Conclusions</h3> The DQRA is the first to incorporate perspectives from three stakeholders (patients, physicians and healthcare insurers) and successfully formed a limited set of QI. Collection of these indicators was feasible in two out of the three participating hospitals and offers insight in differences in provided and perceived care for RA patients. <h3>References</h3> Mahmood et al. Best Pract Res Clin Rheumatol 2015. Chassin et al. Health Aff 2002. Mahmood et al. ARD 2016. <h3>Disclosure of Interest</h3> None declared
Checkpoint inhibitor is active against large cell neuroendocrine carcinoma with high tumor mutation burden
Authors: Victoria E. Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
Journal: Journal for ImmunoTherapy of Cancer (2017)

Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined.We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody.Immunotherapy with checkpoint inhibitors is an effective treatment option for patients with metastatic LCNEC, even if PD-L1 expression is negative.
A Much-Needed Corrective on Drug Development Costs
Authors: Merrill Goozner
Journal: JAMA Internal Medicine (2017)

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Re: Good: Bevacizumab for retinopathy of prematurity: treatment when pathology is embedded in a normally developing vascular system ( Ophthalmology . 2016;123:1843-1844)
Authors: Michael P. Blair, Michael J. Shapiro, Audina M. Berrocal, Michael P. Blair, R.V. Paul Chan, Anna Ells, José María Garcia Gonzalez, Vishak J. John, Kamiar Mireskandari, Timothy Murray, Polly Quiram, Michael J. Shapiro, Sui Chien Wong, Wei-Chi Wu
Journal: Ophthalmology (2017)
SP0048 Targeting of angiogenesis
Authors: S Tas
Journal: Annals of the Rheumatic Diseases (2017)

Angiogenesis is de novo capillary outgrowth from pre-existing blood vessels. This process not only is crucial for normal development, but also has an important role in supplying oxygen and nutrients to inflamed tissues, as well as in facilitating the migration of inflammatory cells to the synovium in rheumatoid arthritis, spondyloarthritis, and other tissues in systemic autoimmune diseases. Neovascularization is dependent on the balance of proangiogenic and antiangiogenic mediators, including growth factors, cytokines, chemokines, cell adhesion molecules and matrix metalloproteinases. In this lecture I will provide an overview of the various pathways that govern these angiogenic processes and discusses potential approaches to interfere with pathological angiogenesis, and thereby ameliorate inflammatory disease, by targeting these pathways specifically in endothelial cells. Key Messages: In chronic inflammatory diseases, angiogenesis enables increased delivery of oxygen and nutrients to immune cell populations accumulating in inflamed tissues, and contributes to further immune cell infiltration Angiogenesis is driven not only by hypoxia, but also by proinflammatory mediators produced by immune and stromal cells Many pathways downstream of these proinflammatory stimuli contribute to various cellular processes involved in angiogenesis Targeting proangiogenic pathways to inhibit neovascularization has been successfully exploited in several cancers, and may also prove beneficial in the treatment of chronic inflammatory diseases <h3>Disclosure of Interest</h3> None declared
OP0341 Can pain in hand osteoarthritis be associated with mri collateral ligament abnormalities?
Authors: AL Tan, M-A D'Agostino, E Hensor, A Grainger, P Emery, D McGonagle
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Many patients with hand osteoarthritis (OA) have little symptoms. Bone oedema and synovitis have been associated to pain in OA, but inflammation involving ligaments has not been studied, likely limited by inadequate MRI resolution. We have previously found significant ligament pathology in early and established hand OA (HOA) [1]. <h3>Objectives</h3> We hypothesise that the well innervated ligaments are key to a better understanding of the relationship between joint structure and pain in HOA. This research aims to see if small joint collateral ligament abnormalities are worth exploring further in relationship to pain in HOA. <h3>Methods</h3> High-resolution contrast enhanced MRI of 26 joints in 15 patients (mean (SD) age 58.3 (8.2), 13F:2M) and 10 in 5 healthy controls (age 38 (5.6); 4F:1M) were scanned using a microscopy MRI coil. 15 joints in 8 patients were painful [median (IQR) pain VAS 4 (3, 7)). Joints were scored blinded to clinical data for joint fluid, capsule/synovitis, extracapsular oedema, collateral ligament thickening/oedema/degeneration, extensor and flexor tendons, bone oedema and cysts. All structures were graded 0–3 for normal, mild, moderate, severe, as defined in OMERACT HOAMRIS where available [2]. Proportions of joints with any level of abnormality (score&gt;0) were calculated according to pain status (present/absent). <h3>Results</h3> All OA patients with and without pain had ligament abnormalities. Substantive differences in proportion of joints between healthy controls and OA patients were seen for all pathologies except tendons (no tendon abnormalities were found in all groups). Proportions of joints with capsular/synovium, extra capsular changes and proximal cysts differed between OA joints with and without pain but no substantive differences in pathology score were found. Of painful joints, 93% (14) had both ligament and capsular/synovium or extracapsular abnormality present, compared to 45% (5) of non-painful joints. <h3>Conclusions</h3> Modifiable abnormalities involving capsular/synovium and extracapsular areas may be more frequently seen in painful OA joints. The presence of collateral ligament abnormalities in HOA joints, whether painful or not, suggest that the severity of ligament abnormalities in small joint OA and the degree of pain may be an important area to investigate further. <h3>References</h3> Tan AL, et al. Ann Rheum Dis. 2006 Oct;65(10):1267–72. Haugen IK, et al. J Rheumatol. 2014 Feb;41(2):386–91. <h3>Acknowledgements</h3> Funded by NIHR. <h3>Disclosure of Interest</h3> None declared
Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association
Authors: Sean van Diepen, Jason N. Katz, Nancy M. Albert, Timothy D. Henry, Alice K. Jacobs, Navin K. Kapur, Ahmet Kilic, Venu Menon, E. Magnus Ohman, Nancy K. Sweitzer, Holger Thiele, Jeffrey B. Washam, Mauricio G. Cohen
Journal: Circulation (2017)

Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities.
SAT0140 Effect of obesity in response to biologics in rheumatoid arthritis
Authors: A Khan, S Sukumaran, M Kanitkar, A-S Zafar, S Shah, S Adnan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Obesity epidemic has impacted practically every area of health including care of patients with RA. Adipose tissue is an active organ that produces pro-inflammatory molecules. A significant treatment challenge remains is the standard dose of RA medications may not attain same concentrations at sites of inflammation in obese vs non-obese patients thus making them less effective. <h3>Objectives</h3> The study aim was to determine whether obesity represents a risk factor for a poor remission in RA requiring biologic therapies. Obesity may be associated with more severe and refractory inflammation through increased levels of inflammatory adipocytokines leptin, resistin or visfatin or decreased levels of the anti-inflammatory adipocytokine adiponectin. We retrospectively analysed 178 patients diagnosed with RA at East Kent University Hospitals. <h3>Methods</h3> Data analysed for age, sex, disease duration, prior DMARD, positivity RF and anti-CCP antibodies and response to biologics DAS28 score pre-treatment and at 6 months were analysed.Main aim was to analyse any difference between obese and non-obese patients in terms of their response to treatment. Obese patients were defined with a BMI of 30 or above. <h3>Results</h3> See Table 1. Results suggested that there were significant differences between two groups for sex, duration of disease, RF and CRP. There was also some evidence of difference between groups in terms of their age and pre-treatment DAS28 score but these differences were only of borderline statistical significance. There was smaller proportion of males in the obese group with 20% male compared to 36% of non-obese patients. Obese patients had on average a longer disease duration with a median of 12 years compared to a median of 8 years for the non-obese group. The RF status also varied between groups with a much higher proportion of patients in the negative category for the obese group. CRP values were significantly lower in the obese group with a median of 24 compared to 35 in the non-obese group. Non-obese had the best response with 48% good response compared to18% of the non-obese group with post treatment mean DAS28 score of 3.2 and mean reduction of 2.4. <h3>Conclusions</h3> Obesity is important factor that impacts treatment and outcome in RA. Future clinical studies to elucidate the pharmacokinetics of specific biologic agents in relation to BMI should provide further clinical guidance. <h3>References</h3> Gόmez et al.What9s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol.2011. <h3>Disclosure of Interest</h3> None declared
AB0221 Impact of small to medium dose of prednisolone on bone mineral density among early rheumatoid arthritis patients
Authors: HM Lam, MC Wan, LS Tam
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recent randomized trials in rheumatoid arthritis (RA) using low to medium dose of corticosteroid showed that bone mineral density (BMD) loss over 2 years was not significantly different from that with placebo. Another study in early RA and undifferentiated arthritis even showed a positive correlation between cumulative glucocorticoid (GC) dose with an increase in BMD at the ultradistal forearm. Whether the use of prednisolone (pred) can prevent bone loss in early RA patients remained controversial. <h3>Objectives</h3> The aim of this study was to investigate the impact of small dose pred (≤10mg/day) on BMD in early RA patients. <h3>Methods</h3> Data from 107 patients ((age: 53.3±11.92 years; females: 79 [73.8%], median disease duration at entry: 7-month (IQR, 4–12)) from the Hong Kong early arthritis registry (Clinical Rheumatology Systematic Treat to Target in Asia Leadership [CRYSTAL] project)were analyzed. In this register, clinical and treatment information were recorded systematically, including cumulative GC dose. Hip, spine and forearm BMDs were measured by duel-energy X-ray absorptiometry (DXA) at baseline and month 12. Patients were categorized into three groups according to pred use (never/&lt;3/≥3 months) during the first year of follow-up. Patients who ever took&gt;10mg/day of pred were excluded. The change in BMD was compared between groups and between the two time points. <h3>Results</h3> The baseline characteristics of patients were shown in Table 1. Patients who required ≥3 months of pred treatment are older, with a shorter disease duration and a higher disease activity. Significant differences in the percentage change of BMD in forearm was found among the groups (Pred never/Pred&lt;3 months/Pred≥3 months: -2.99±4.21/-1.05±3.10/-0.65±3.45, <i>p</i>=0.045). Post-hoc analysis revealed that the percentage reduction of forearm BMD was significantly less in the Pred ≥3 months group compared to the Pred never group (<i>p</i>=0.043). After adjusting for age, gender, disease duration and baseline DAS-CRP, the changes in forearm BMD was still significantly different among the three groups (<i>p</i>=0.015). No significant differences in the changes of hip and spine BMD were observed. Significant changes in forearm BMD were observed between baseline and month 12 only in the Pred never group (0.54±0.08/0.53±0.0 <i>p</i>&lt;0.001,graph1). <h3>Conclusions</h3> Small to medium dose of prednisolone might protect bone loss in forearm among early RA patients. These results need to be further validated. <h3>References</h3> Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years. Ann N Y Acad Sci 2014. <h3>Disclosure of Interest</h3> None declared
FRI0536 The method of calculating the probable value of t-score in patients with multifocal atherocalcification
Authors: AN Kokov, V Masenko, S Semenov, O Barbarash
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To determine probable value of T-score for early detection of osteopenic syndrome in patients with multifocal atherosclerosis based on the multislice computed tomography (MSCT) evaluation of vascular calcification. <h3>Methods</h3> 186 male (60±6,7 years) with multifocal atherosclerosis. All the patients underwent the measurement of BMD with X-ray absorptiometry. Moreover, calcium scores (CS) of coronary and brachiocephalic arteries were obtained using Agatston method. <h3>Results</h3> T-score values of lumbar vertebrae -1.07 [-1.54;-0.40], T-score of the proximal femur -2.01 [-2.71;-1.49]. Calcification of the coronary arteries: CS=471.8 [118.2;916,8] and carotid arteries: CS=113.9 [44.5;300.8]. Factors that affect the probable value of T-score in patients with known rates of calcification of the coronary and carotid arteries were obtained by regression analysis. These factors were equivalent density of coronary calcinoses (p=0,0046), the volume of the carotid calcifications (p=0,0039), the mass of calcifications of the carotid arteries (p=0,0054) and the presence of a stenosis of the carotid arteries (p=0.0001).The predictive model for estimating the probable value of T-score has been is designed using regression coefficients of each of the factors. The value is equal to the Fisher statistic F=9,52, p-value &lt;0.000001, multiple correlation model9s coefficient is 0.753. <h3>Conclusions</h3> The results of this study indicate that rates of calcification of the carotid and coronary arteries, resulting in the planned survey on MSCT patients with multifocal atherosclerosis have a high predictive capacity for assessing the probable value of the T-score and early detection of osteopenic syndrome in these patients. <h3>Disclosure of Interest</h3> None declared
Phase 1 study with expansion cohorts of cabozantinib (C) + abiraterone (A) in metastatic castration resistant prostate cancer (mCRPC): Investigator-sponsored study.
Authors: Christopher Sweeney, Kathryn P. Gray, Lauren Christine Harshman, Mary-Ellen Taplin, Amanda Fredericks Pace, Kathryn Dumas, Jeffrey G. Supko, Katherine A. Zukotynski, Brandon David Bernard, Mark Pomerantz, Aymen Elfiky, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2015)

5037 Background: A and C (multi-tyrosine kinase inhibitor including MET and VEGFRs) have complementary mechanisms of action and activity in CRPC. In vivo work with LAPC4-CR (castration and A resistant cell line) has shown the combination has enhanced activity. Methods: Phase 1, 3 + 3 trial with A fixed at 1,000 mg/day and prednisone 5mg BID and escalating daily doses of C (20mg, 40mg, 60mg) in pts with mCRPC was conducted. Cycles were 28 days. Results: 27 patients were enrolled with a median follow-up of 9.2 months (Range: 1.6-29.4 months). 11 pts had prior docetaxel therapy. No DLTs in the first 28 day cycle of dose escalation cohorts. The 60 mg C cohort had Gr 2 adverse events (AEs) of myalgias (2), fatigue (2) and DVT (1) in cycles 2 and 3 necessitating a dose reduction to 40 mg (no change to A). Due to a preferable tolerability profile, the 20mg and 40mg C cohorts were expanded to a total of 12 pts each. See Table for activity data. Gr 3 treatment related AEs: 5 pts at 20mg C [skin infection (1); diarrhea (1); anemia (1); transaminase (1); hypophosphatemia (1)]; 7 pts at 40mg C [hypertension (1); hypophosphatemia (2); transaminase (1); colitis (1); lipase incr. (1); thromboembolic (1)]. Dose reductions: 5 pts on 40mg C; none on 20mg C. 1 pt had A dose reduction [hypokalemia with Atrial Fib (1)]. The steady-state trough concentration PK data of A and C did not indicate a drug-drug interaction. Conclusions: C at either 20mg or 40 mg is tolerable when combined with standard dose A/pred. The long term tolerability and preliminary efficacy data support the investigation of this combination for further clinical development in mCRPC. Clinical trial information: NCT01574937. 20 mg N = 12 40mg N = 12 Median Age (yrs) 66 62 Median baseline PSA 41 15 Prior chemo 5 (41.7%) 4 (33.3%) Gleason 8-10 10 (83.3%) 9 (75.0%) Visceral mets 2 1 Opiate use baseline 5 5 PSA decline > 90% > 75% 6 (50%) 7 (58%) 3 (25%) 5 (42%) Median time on therapy Months (Q1,Q3) - 11 pts still on Rx 17 (10,28) 8 (7,17) Pts with any Gr 3 AEs due to Rx 5 (31%) 7 (58%)
Acute kidney injury is a risk factor for subsequent proteinuria
Authors: Sharidan K. Parr, Michael E. Matheny, Khaled Abdel-Kader, Robert A. Greevy, Aihua Bian, James Fly, Guanhua Chen, Theodore Speroff, Adriana M. Hung, T. Alp Ikizler, Edward D. Siew
Journal: Kidney International (2017)