tbuckley/cabot-search huggingface dataset:
SAT0480 Evaluation of standardised teaching of modified rodnan skin score assessment in systemic sclerosis
Authors: A.H. Low, S.-A. Ng, V. Berrocal, B. Brennan, G. Chan, S.-C. Ng, D. Khanna
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The modified Rodnan skin score (mRSS) is a standard outcome measure for skin involvement in systemic sclerosis (SSc) clinical trials. Training assessors reduces variability in mRSS measurement. <h3>Objectives</h3> Our objective is to report the inter- and intra-observer variability of mRSS scoring using newly developed standardised training guidelines by the Scleroderma Clinical Trials Consortium (SCTC). <h3>Methods</h3> Two SSc experts (DK/AL), 2 facilitators, 52 rheumatology trainees and 8 SSc patients fulfilling the 2013 American College of Rheumatology criteria participated in a SSc skin scoring workshop. Eight SSc patients were examined by 2 SSc experts and facilitators together and consensus scores reached. All trainees attended a talk on mRSS skin scoring by an SSc expert (DK), followed by a video and live demonstration by an expert examining a patient exhibiting different aspects of skin scoring. Each trainee subsequently performed mRSS scoring on 4 SSc patients independently. This concluded the teaching session for mRSS scoring. The mRSS scoring for each trainee was compared to the consensus expert mRSS, and a score of ≤5 in 3 out of 4 patients is considered acceptable inter-observer variability, as determined by SCTC guidelines. Two days after training, 12 trainees, 2 facilitators and 2 experts re-assessed independently the mRSS of 2 SSc patients whom they had examined previously. The repeat day 2 mRSS score for each trainee was compared to the baseline mRSS score, and a score of ≤3 is considered acceptable intra-observer variability. We computed the inter- and intra-observer variability using a linear mixed model with an intercept term and random effects for patient, rater and patient by rater with the following values representing the degrees of agreement:&lt;0 –poor; 0–0.20 –slight; 0.21–0.40 –fair; 0.41–0.60 –moderate; 0.61–0.80 –substantial; and 0.81–1.00 –almost perfect agreement. <h3>Results</h3> For the first group of assessors involving 52 trainees, 65.4% of them achieved acceptable inter-observer variability, with inter-observer variability of 0.71, inter-observer mean of 8.64 and within-patient standard deviation (SD) of 4.25. For the second group of assessors who returned 2 days after training (n=14), compared to the experts' scores, the inter-observer and intra-observer variability was 0.73 and 0.85 respectively. The inter-observer mean was 7.39 with a within-patient SD of 3.65. The intra-observer mean was 6.92 and within-patient SD was 2.73. <h3>Conclusions</h3> There was substantial inter-observer reliability and excellent intra-observer reliability. This is the first study examining the training of assessors using the SCTC training guidelines and our results support the importance of standardised teaching for mRSS. <h3>Disclosure of Interest</h3> None declared
Heparin-Induced Thrombocytopenia
Authors: Andreas Greinacher
Journal: New England Journal of Medicine (2015)

HIT is characterized by a platelet-count fall of more than 50% at 5 to 10 days after the start of heparin and hypercoagulability. Platelet factor 4–heparin antibody testing has a high negative, but low positive, predictive value. Treatment involves therapeutic-dose anticoagulation.
Review: Ultrasound-assisted lumbar puncture (LP) does not increase procedural success but reduces traumatic LPs
Authors: Jonathan M. Kirschner, Benton R. Hunter
Journal: Annals of Internal Medicine (2019)

ACP Journal Club15 January 2019Review: Ultrasound-assisted lumbar puncture (LP) does not increase procedural success but reduces traumatic LPsJonathan M. Kirschner, MD, Benton R. Hunter, MDJonathan M. Kirschner, MDIndiana University School of Medicine, Indianapolis, Indiana, USA (J.M.K., B.R.H.), Benton R. Hunter, MDIndiana University School of Medicine, Indianapolis, Indiana, USA (J.M.K., B.R.H.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2019-170-2-009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGottlieb M, Holladay D, Peksa GD. Ultrasound-assisted lumbar punctures: a systematic review and meta-analysis. Acad Emerg Med. 2018. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/30129102Clinical Impact RatingsEmergency Med: Critical Care: Neurology: References1 Williams P, Tait G, Wijeratne T. Success rate of elective lumbar puncture at a major Melbourne neurology unit. Surg Neurol Int. 2018;9:12. [PMID: 29416909] Google Scholar2 Tosato DM, Tuttle DJ, Moore GH, Esterly K. Success rates for lumbar puncture in newborns. Pediatric Research. 1997;41:182. www.nature.com/articles/pr19971258 (accessed 13 Nov 2018). Google Scholar3 Perry JJ, Alyahya B, Sivilotti ML, et al. Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study. BMJ. 2015;350:h568. [PMID: 25694274] Google Scholar Author, Article, and Disclosure InformationAffiliations: Indiana University School of Medicine, Indianapolis, Indiana, USA (J.M.K., B.R.H.)This article was published at Annals.org on 1 January 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byState‐of‐the‐art of lumbar puncture and its place in the journey of patients with Alzheimer's diseasePoint-of-care ultrasound (POCUS) for hospitalists and general internists 15 January 2019Volume 170, Issue 2Page: JC9KeywordsChildrenEmergency departmentIntensive care unitsInterleukinsLumbar punctureNeurologyNumber needed to treatOdds ratioSystematic reviewsUltrasound imaging ePublished: 15 January 2019 Issue Published: 15 January 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
FRI0481 Giant cell arteritis and inflammatory bowel disease – is there a connexion? results from a population-based study
Authors: Y. Yavne, S. Tiosano, A. Watad, D. Comaneshter, A.D. Cohen, H. Amital
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Giant cell arteritis (GCA) is an autoimmune disorder which primarily affects large vessels, whilst inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), mainly targets the gut. Co-existence of the two maladies has been reported sporadically in the literature<sup>1–3</sup>. <h3>Objectives</h3> The purpose of this study was to assess the authenticity of such an association in a large, cross-sectional study. <h3>Methods</h3> Utilising data derived from the Clalit Health Services' registry, the largest health maintenance organisation in Israel, we compared the proportion of CD and UC in GCA patients with age- and gender-matched controls. Univariate analysis was performed using Chi-square and student <i>t</i>-test and a multivariate analysis was performed using a logistic regression model. <h3>Results</h3> The study included 5,657 GCA patients and 28 298 age- and gender-matched controls. GCA patients had a significantly increased proportion of both CD and UC in comparison with controls (0.81% vs. 0.12% and 0.69% vs. 0.2%, <i>p-value</i>&lt;0.001, respectively). The strength of the association between GCA and IBD was negatively correlated with the patients' age; thus the association was most robust amongst younger patients aged 18–44 (OR=13.2, figure 1). The association between GCA and IBD remained significant when evaluated independently of confounding factors (OR=2.367, <i>p-value</i>&lt;0.001, table 1). <h3>Conclusions</h3> The probability that GCA patients may also suffer from IBD is increased in comparison with age- and gender-matched controls. Our findings indicate that this association is most prominent in younger patients (&lt;70). Screening for IBD amongst GCA patients in this age group may be warranted. <h3>References</h3> [1] Colombat M, et al. Giant cell arteritis localized to the colon associated with Crohn's disease. Histopathology2001;38(1):21–24. [2] Sy, Alice, et al. Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients and systematic review of the literature. Seminars in arthritis and rheumatism2016;45(4);Elsevier. [3] Sanges, Sébastien, et al. Giant cell arteritis and ulcerative colitis: An unusual association. Seminars in arthritis and rheumatism2016;46(1)Elsevier. <h3>Disclosure of Interest</h3> None declared
Abstract P196: A Large Genetic Effect of APOC3 A43T SNP on Serum Triglycerides is Mediated by Serum APO-CIII Levels in Amerindians
Authors: Wen-Chi Hsueh, Mary F Walter, Anup Nair, Robert L Hanson
Journal: Circulation (2018)

Introduction: Using a population-based linkage analysis approach, we previously identified a major locus for serum triglyceride (TG) levels in Pima Indians, which largely reflects the effect of a functional SNP (p.(Ala43Thr), A43T, or rs147210663) in the APOC3 gene. This non-synonymous SNP is extremely rare in non-Amerindian populations and more common in the Pima Indians (frequency of the T43 allele≈3%). This SNP alters the structure of APO-CIII, which leads to loss of its function and to lower circulating levels of APO-CIII. Its effect size reduces TG level by approximately 1 SD unit (per allele), which is among the largest effects for any complex trait reported to date. Hypothesis: To further explore the functional mechanism underlying this association, we analyzed the relationships among A43T, TG and APO-CIII levels; we hypothesized that the APOC3 A43T SNP effect on TG is mediated through circulating APO-CIII in the blood. Methods: We measured serum APO-CIII level in 411 randomly selected Amerindian subjects from a larger cohort study with both the A43T genotype and TG levels measured; this included 22 carriers of a T43 allele (frequency=2.7%). All analyses were modeled using linear regressions based on cross-sectional data, with age, sex, diabetes status, and population admixture included as covariates. The natural logarithms of APO-CIII and TG levels were taken to reduce skewness. Results: The phenotypic correlation between APO-CIII and TG was 0.68. We found a strong association between the A43T SNP and TG levels (β=-0.78±0.21 SD unit per copy of the T43 allele, p=0.00026, explaining 3.2% variance) that was greatly attenuated with further adjustment for APO-CIII levels (β=-0.04±0.17 SD unit, p=0.81, explaining 0.01% variance). On the other hand, there was also a strong association between the A43T SNP and APO-CIII levels (β=-1.22±0.21 SD unit, p=1.2х10 -7 , explaining 6.5% variance), which remained significant even after adjustment for the TG effect (β=-0.61±0.16 SD unit, p=0.00016, explaining 3.4% variance). Formal mediation analysis, conducted by the Sobel method, suggested significant and virtually complete mediation of the A43T effect on TG through APO-CIII levels (p=5.2х10 -7 , percent mediation=95%). Conclusion: Our results suggest that the APOC3 A43T SNP effect on TG may be primarily mediated through APO-CIII, and lend further strength to the possibility of making APO-CIII a therapeutic target for CVD interventions. We are in the process of expanding our analysis to a much larger sample.
SAT0109 Ultrasonic evaluation of joint involvement in established ra: active synovitis predicts sustained treatment changes in suspected biologic failure
Authors: R.L. Batten, O. Mohammed, L. Probert, D. Wright, I. Atchia
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> EULAR guidelines recommend treatment of rheumatoid arthritis (RA) targeted to remission.<sup>1</sup> Biologic switching should be considered where there is at least moderate disease activity (DAS28 &gt;3.2). The role of ultrasound (US) in guiding treatment is perhaps less clear. D'Agostino et al have proposed a novel algorithm based on current best evidence.<sup>2</sup> <h3>Objectives</h3> We present a case series of 30 RA patients with perceived biologic failure. By applying the algorithm to this group of patients we reviewed the impact of musculoskeletal ultrasound findings on treatment changes when compared to DAS28 assessment alone. <h3>Methods</h3> All patients had US of the Backhaus 7 joints on the most affected side, and any additional symptomatic joints. A global OMERACT-EULAR synovitis score (GLOESS) was calculated for each patient.<sup>3</sup> DAS28 was calculated at the time of US, and clinician opinion to continue or switch biologic was documented pre and post US. Patient notes were reviewed at 6 months to assess whether treatment changes were sustained. <h3>Results</h3> 26 patients had DAS28 &gt;3.2. Of these, 10 were found to have GLOESS &gt;6 and subsequently switched biologic therapy. 4 patients had DAS28 &lt;3.2, despite clinical suspicion of persistent inflammatory disease. Of these patients, 2 were found to have GLOESS &gt;6, and subsequently switched to an alternative biologic. At 6 months 20/24 patient's management remained consistent with previous US findings, 2 patients escalated treatment despite a previously negative US, 1 patient declined escalation (although US showed synovitis), 1 patient switched due to intolerance and 6 were lost to follow-up. <h3>Conclusions</h3> US significantly reduced the need to switch treatment in this cohort of patients compared with DAS28. Longitudinal follow up supports the validity of US to determine those with active disease whilst on a biologic. The use of US may prevent over-treatment, and subsequently reduce morbidity and financial cost. Further work is needed to evaluate the clinical impact and cost effectiveness of routine US prior considering a change in biologic therapy. <h3>References:</h3> [1] Smolen JS, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631-7. [2] D9Agostino MA, et al. Novel algorithms for the pragmatic use of ultrasound in the management of patients with rheumatoid arthritis: from diagnosis to remission. Annals of the Rheumatic Diseases 2016;75:1902-1908. [3] D9Agostino MA. Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study. RMD Open 2016 May;5;2(1). <h3>Disclosure of Interest:</h3> None declared
Targeting Oncogenic Polyamines in Refractory Pediatric Leukemias Using the Anti-Protozoan Drug Α-Difluoromethylornithine (DFMO) in Combination with GC7 and Aurothioglucose
Authors: Bradley Hofmann, Sunand Kannappan, Gupta Mehul, Chunfen Zhang, Susan Chi, Derek Hanson, Ronald Anderson, Aru Narendran
Journal: Blood (2018)
Surgeon is suspended for cancelling laparotomy on patient with perforated colon
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant surgeon at Royal Oldham Hospital who cancelled a planned laparotomy on an elderly patient with a perforated sigmoid colon, then gave mutually contradictory accounts to the patient’s family and to a coroner investigating her death, has been suspended for 12 months by a medical practitioners’ tribunal.

Saad Masud Salman told the patient’s family in December 2015 that he had placed her on conservative treatment because he had seen her on the days following her consent to the operation and had noted an improvement in her clinical condition, which he observed continuing through the following weekend.

But three months later he told …
Eradication of Neuroblastoma by T Cells Redirected with an Optimized GD2-Specific Chimeric Antigen Receptor and Interleukin-15
Authors: Yuhui Chen, Chuang Sun, Elisa Landoni, Leonid Metelitsa, Gianpietro Dotti, Barbara Savoldo
Journal: Clinical Cancer Research (2019)

Abstract Purpose: A delay in encountering the cognate antigen while in the circulation, and the suboptimal costimulation received at the tumor site are key reasons for the limited activity of chimeric antigen receptor–redirected T cells (CAR-T) in solid tumors. We have explored the benefits of incorporating the IL15 cytokine within the CAR cassette to provide both a survival signal before antigen encounter, and an additional cytokine signaling at the tumor site using a neuroblastoma tumor model. Experimental Design: We optimized the construct for the CAR specific for the NB-antigen GD2 without (GD2.CAR) or with IL15 (GD2.CAR.15). We then compared the expansion, phenotype, and antitumor activity of T cells transduced with these constructs against an array of neuroblastoma cell lines in vitro and in vivo using a xenogeneic metastatic model of neuroblastoma. Results: We observed that optimized GD2.CAR.15-Ts have reduced expression of the PD-1 receptor, are enriched in stem cell–like cells, and have superior antitumor activity upon repetitive tumor exposures in vitro and in vivo as compared with GD2.CAR-Ts. Tumor rechallenge experiments in vivo further highlighted the role of IL15 in promoting enhanced CAR-T antitumor activity and survival, both in the peripheral blood and tissues. Finally, the inclusion of the inducible caspase-9 gene (iC9) safety switch warranted effective on demand elimination of the engineered GD2.CAR.15-Ts. Conclusions: Our results guide new therapeutic options for GD2.CAR-Ts in patients with neuroblastoma, and CAR-T development for a broad range of solid tumors.
P058 Chemokine CCL18 enriched in synovial fluid is involved in joint destruction through promoting migration of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Y-Q Mo, G-C Zhang, J Jing, J-D Ma, L Dai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator. <h3>Introduction</h3> CC chemokine ligand 18 (CCL18) which is either constitutively expressed or induced in monocytes/macrophages and dendritic cells has been reported to be highly expressed in peripheral blood and synovial fluid of rheumatoid arthritis (RA) patients compared with healthy controls, indicating the possible role of CCL18 in the development and pathogenesis of RA. <h3>Objectives</h3> To explore the association of serum and synovial fluid CCL18 with clinical and radiographic outcome in RA and its potential effect on RA fibroblast-like synoviocytes (FLS). <h3>Methods</h3> Consecutive patients with active RA (DAS28-CRP&gt;2.6) were recruited. Synovial fluid was collected from inflamed joints if available. Demographic and clinical data were collected according to the 2017 EULAR recommendation. Serum and synovial fluid CCL18 was detected by ELISA. RA-FLS was cultured <i>in vitro</i> with RA synovial fluid and neutralizing antibody to CCL18. Migration/invasion ability was analyzed by Transwell assay. <h3>Results</h3> Among 83 RA patients, age (median and IQR, similarly hereinafter) was 50 (41∼58) years old and 65 patients (78%) were female, with median disease duration 36 (12∼102) months, median DAS28-CRP 5.0 (4.6∼6.1). Serum CCL18 was 107 (80∼126) ng/mL, which was significantly higher than healthy controls [n=25, 51 (29∼70) ng/mL, p&lt;0.001]. Serum CCL18 correlated slightly but significantly with CRP (r=0.385, p&lt;0.001), ESR (r=0.239, p=0.03), PrGA (r=0.249, p=0.03), DAS28-CRP (r=0.368, p=0.001), DAS28-ESR (r=0.336, p=0.003), SDAI (r=0.360, p=0.001), CDAI (r=0.328, p=0.004) and HAQ (r=0.325, p=0.004). Synovial fluid CCL18 of 31 patients was 719 (415∼1271) ng/mL, which was significantly higher than corresponding serum level (Paired test, p&lt;0.001). Among them, 13 patients who were treated according to treat to target strategy received X–ray assessment of hand/wrist both at baseline and month 12. Six patients who had one–year radiographic progression (a change of the Sharp/van der Heijde modified sharp score ≥0.5 units) showed higher synovial fluid CCL18 than other 7 patients without radiographic progression [1481 (1244∼2034) ng/mL vs. 458 (405∼681) ng/mL, p=0.004). When incubated with RA synovial fluid, the migration ability of RA-FLS was significantly increased; but this effect was Inhibited by neutralizing antibody to CCL18. <h3>Conclusions</h3> CCL18 elevates especially in synovial fluid of RA patients, which may correlate with one-year radiographic progression through promoting migration of RA-FLS. <h3>Disclosure of Interest</h3> None declared.
Identification of Potent BH3-Mimetic Combinations Targeting Pro-Survival Pathways in Human B-Cell Acute Lymphoblastic Leukemia
Authors: Donia M Moujalled, Diane T Hanna, Giovanna Pomilio, Veronique Litalien, Shaun Fleming, Marie Chanrion, Ana-Leticia Maragno, Laurence Kraus-Berthier, Seong Lin Khaw, Guillaume Lessene, David Huang, Andrew W. Roberts, Olivier Geneste, Paul G Ekert, Ashley P Ng, Andrew H Wei
Journal: Blood (2018)
SAT0497 Follow-up of disease activity in hungarian patients with idiopathic inflammatory myopathy
Authors: L. Bodoki, M. Nagy-Vincze, Z. Griger, Z. Szekanecz, K. Dankó
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Assessing disease activity in patients with myositis is an important goal. A method called Disease Activity Core Set Measures was established by International Myositis Assessment and Clinical Studies Group (IMACS) for evaluating activity of myositis. This assesses the manifestations of myositis which are thought to be reversible that result directly from the inflammatory process. <h3>Objectives</h3> In this prospective study authors aimed to monitoring disease activity in Hungarian myositis patients treated at the Autoimmune Outpatient Clinic, Department of Clinical Immunology, University of Debrecen. First, disease activity data of poly (PM) – and dermatomyositis (DM) patients were compared. Secondly, by patients with active disease, the correlations between the components of Disease Activity Core Set Measures were studied. <h3>Methods</h3> During the three-year follow-up period, at every single visit, authors evaluated disease activity using factors of Disease Activity Core Set Measures and patients filled Health Assessment Questionnaire (HAQ). Only those patients who appeared at least three times during the follow-up period were selected. Statistical analysis was made using SPSS 17.0 statistical software. <h3>Results</h3> Collection of data from 219 patients (age: 44.93 years, female: male ratio 2.98:1) happened in a total of 1101 outpatient visits. The 107 PM patients had statistically significant higher physician and patient visual analogue (VAS) and myositis disease activity assessment tools scores than the 61 DM patients, with the exception of cardiovascular disease activity. Activity of skin lesions was significant higher in DM patients. By the 44 patients, who had an active disease, the MMT scores gave significant negative correlations with HAQ scores (R=−0.536 and p&lt;0.001) and CK levels (R=−0.387 and p&lt;0.001). The physician and patient VAS gave strong negative correlations with MMT scores (R=−0.714 and p&lt;0.001 and R=−0.730 and p&lt;0.001, respectively) and positive correlations with HAQ scores and CK levels (physician VAS vs. HAQ R=0.691 and p&lt;0.001; patient VAS vs. HAQ R=0.629 and p&lt;0.001; physician VAS vs. CK R=0.622 and p&lt;0.001; patient VAS vs. CK R=0.615 and p&lt;0.001). <h3>Conclusions</h3> As far as we know, this is the first study which compares the activities of PM and DM patients based on the IMACS system. According to our data, we can conclude that PM patients had more severe muscle symptoms and extramuscular manifestations. Secondly, as seen in other previous studies, calculations in patients with active myositis showed a clear correlation between the most important components of Disease Activity Core Set Measures. <h3>Disclosure of Interest</h3> None declared
Abstract 20690: B-Cell Deficiency in Mice With Hypomorphic c-myb Causes Diuresis and Reduces Blood Pressure
Authors: Luke S Dingwell, Eric A Shikatani, Rickvinder Besla, Andrew S Levy, Danny Dinh, Abdul Momen, Hangjun Zhang, Talat Afroze, Michelle Chen, Craig Simmons, Phyllis Billia, Jennifer Gommerman, Rohan John, Clinton Robbins, Scott Heximer, James Scholey, Steffen-Sebastian Bolz, Mansoor Husain
Journal: Circulation (2017)

Background: We previously showed that mice homozygous for a hypomorphic c-myb allele with reduced c-Myb activity (hh) have low blood pressure (BP), are resistant to DOCA-salt hypertension, and show...