tbuckley/cabot-search huggingface dataset:
Remission maintenance after tocilizumab dose-tapering and interruption in patients with giant cell arteritis: an open-label, 18-month, prospective, pilot study
Authors: Carlotta Nannini, Laura Niccoli, Stelvio Sestini, Iashar Laghai, Angela Coppola, Fabrizio Cantini
Journal: Annals of the Rheumatic Diseases (2019)

In the GiACTA trial,1 tocilizumab (TCZ) combined with prednisone (PDN) was significantly superior to PDN alone to obtain the remission in patients with giant cell arteritis (GCA) with and without concomitant large vessel vasculitis (LVV). To date, no data on the management of patients achieving the remission with TCZ monotherapy after a short course of combined treatment with CS are available.

To investigate the persistence of remission after TCZ interruption, we designed an open-label, prospective trial of 15 consecutive patients meeting the American College of Rheumatology 1990 criteria for GCA.2 Four patients had refractory GCA and 11 were new diagnoses (clinical and demographic data: see online supplementary table S1). All had concomitant thoracic LVV evidenced by 18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. Total vascular score (TVS), maximal standardised uptake value (SUVmax) and target to background ratio …
OP0214 DISTURBED PD-L1 UPREGULATION IS CHARACTERISTIC OF ANERGIC B CELLS IN SLE
Authors: Ana-Luisa Stefanski, Annika Wiedemann, Karin Reiter, Andreia Lino, Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Prior studies on systemic lupus erythematosus (SLE) B cells reported an altered responsiveness to TLR9 stimulation, such as proliferation, cytokine production as well as indications for impaired T and B cell interaction [1]. The role of co-inhibitory and co-stimulatory (check-point) molecules in this setting has not been delineated in detail so far. <h3>Objectives</h3> Assess the expression of co-inhibitory (PD-1, PD-L1 and PD-L2) and co-stimulatory molecules (CD86 and CD40) by SLE B cells after <i>in vitro</i> stimulation and their potential contribution for B cell hyporesponsiveness in SLE. <h3>Methods</h3> PBMCs from 10 SLE patients and 10 healthy donors (HD) were stimulated with IL-2/IL-10, anti (α) - B cell receptor (BCR), CpG and CD40L alone or in combination. Expression of PD-1, PD-L1, PD-L2 as well as CD86, CD40 on CD19+CD20+ B cell subsets after 48h stimulation was analyzed by FACS. CD71 was employed to measure proliferation of CD19<sup>+</sup>CD20<sup>+</sup> B cells after 48h stimulation. <h3>Results</h3> SLE B cells exhibited a substantially decreased upregulation of PD-L1 (p = 0,0006) and CD86 (p = 0,0188, Fig.1) associated with significantly reduced B cell proliferation (p = 0,0039) after 48h stimulation with CpG alone and in combination compared with HD. While TLR9 engagement in SLE B cells appeared to be abnormal, activation of CD40 resulted into a consistent upregulation of both, inhibitory and stimulatory molecules. PD-L1 was positively correlated with B cell proliferation (p = 0.003). Notably, the expression of PD-L1 and CD86 correlated inversely with Siglec-1, as surrogate marker for interferon signature (p &lt; 0,0001 and p = 0.0021 respectively). PD-L1 expression correlated inversely with cSLEDAI (p = 0.0087). <h3>Conclusion</h3> Hyporesponsive/anergic lupus B cells are characterized by a functionally diminished PD-L1 and CD86 upregulation associated with reduced proliferation and clinical activity. The data mandate evaluations of innovative therapeutic interventions in SLE. <h3>Reference</h3> [1] Schrezenmeier, E., et al., Postactivated B cells in systemic lupus erythematosus: update on translational aspects and therapeutic considerations. Curr Opin Rheumatol, 2018. <h3>Disclosure of Interests</h3> Ana-Luisa Stefanski: None declared, Annika Wiedemann: None declared, Karin Reiter: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Eli Lilly, Janssen, Roche, UCB Pharma, Consultant for: Eli Lilly, Janssen, Roche, UCB Pharma, Speakers bureau: Eli Lilly, Janssen
AB1175 FACET JOINTS INVOLVEMENT IN RHEUMATOID ARTHRITIS: A CROSS-SECTIONAL STUDY
Authors: Tatiana Reitblat, Lina Linov, Fadi Badeer, Azaria Simonovich, Leonid Kalichman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Even it is accepted among rheumatologists that rheumatoid arthritis (RA) does not involve the facet joints (FJs) of the spine, the issue is still under debate. Studies that described a prevalence of the FJs in rheumatoid arthritis patients are scarce. <h3>Objectives</h3> To compare the prevalence of FJs changes between patients with RA and age and sex-matched peers. <h3>Methods</h3> We compared computed tomography (CT) scans of 34 patients with RA, who suffered from low back pain, and 70 age and sex-matched controls-people without RA, with low back pain. The changes in FJs were evaluated according to the score proposed by Kalichman et al: joint space narrowing, marginal osteophytes, articular process hypertrophy, subchondral sclerosis, inter-joint vacuum phenomenon, and subchondral cysts. The characteristic joint changes of RA were also evaluated. Disease activity characteristics, duration of RA, age, and gender were taken from patients' clinical charts. <h3>Results</h3> Prevalence of facet joints changes in patients with RA and group of age and sex-matched controls were not significantly different at any spinal level or in total L5-S1 score. Marginal erosions, that are characteristic feature of joint change in RA, were not found in any subject with RA in our sample. In subjects with RA, individuals with affected FJs and without affected FJs have no difference in any disease parameters and markers (Tables 1 and 2). <h3>Conclusion</h3> In our samples of CT scans we did not find a difference in facet joints changes between the subject with RA and control group. The occurrence of FJs changes among subjects with RA had no correlation with disease duration and activity. According to the findings, we may assume, that facet joints of the lumbar spine are not involved in the inflammatory process of RA, and patients' low back pain is not due to inflammation in this region of the spine. CRP– C-reactive protein; ESR – Erythrocyte sedimentation rate; DAS-Disease Activity Score; CDAI – Clinical Disease Activity Index; SDAI – Simple Disease Activity Index. <h3>References</h3> [1] Kalichman L, Li L, Kim DH, Guermazi A, et al. 2008. Facet Joint Osteoarthritis and Low Back Pain in the Community-Based Population. Spine 33:2560-2565. [2] van der Heijde D, Dankert T, Nieman F, et al. 1999. Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheumatology (Oxford) 38:941-947. <h3>Disclosure of Interests</h3> Tatiana Reitblat Consultant for: Abbvie, Eli Lilly, Lina Linov: None declared, Fadi Badeer: None declared, Azaria Simonovich: None declared, Leonid Kalichman: None declared
Abstract 12440: Impact of Changes in the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care on Neurologically Intact Survival
Authors: Ken Nagao, Hiroshi Nonogi, Naohiro Yonemoto, David F Gaieski, Noritoshi Ito, Morimasa Takayama, Shinichi Shirai, Singo Furuya, Sigemasa Tani, Tsukasa Yagi, Eizo Tachibana, Takeshi Kimura, Keijiro Saku
Journal: Circulation (2016)

Introduction: The AHA and International Liaison Committee on Resuscitation (ILCOR) published the Guidelines 2000 for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC). Since 2000, the ILCOR has reported the International Consensus on CPR and ECC Science with Treatment Recommendations (CoSTR) in 5-year cycles. However, few nationwide studies have investigated the efficacy of changes in the CPR guidelines. Methods: A total of 1,136,283 adult patients who received CPR after out-of-hospital cardiac arrest (OHCA) between 2005 and 2014 were included from the All-Japan Utstein Registry, a prospective, nationwide, population-based registry. We divided the study patients into 3 groups according to each guideline era (the G2000 era was cases in 2005, the CoSTR2005 era from 2006 to 2010 and the CoSTR2010 era from 2011 to 2014). The primary endpoint was favorable 30-day neurological outcome after OHCA. Multiple logistic regression analysis for primary endpoint was performed to adjust for possible confounders due to imbalances in baseline characteristics. Results: Of the 1,136,283 patients, 100,509 (8.8%) were in the G2000 era, 549,147 (48.3%) in the CoSTR2005 era and 486,627 (42.8%) in the CoSTR2010 era. Baseline characteristics exhibited significant differences among the three groups, including age, sex, time interval from call receipt to paramedic arrival at patient’s side, arrest witnessed, bystander CPR, initial arrest rhythm, advanced CPR, cause of OHCA, etc. After adjustment for resuscitation, the CoSTR2005 and the CoSTR2010 (reference, the G2000) were independent predictor of favorable 30-day neurological outcome (the CoSTR2005: adjusted OR, 1.588; 95% CI: 1.488-1.696, and the CoSTR2010: adjusted OR, 2.100; 95% CI: 1.966-2.242, respectively) and the subgroups of patients with even unwitnessed OHCA (the CoSTR2005: adjusted OR, 1.210; 95% CI: 1.057-1.386, and the CoSTR2010: adjusted OR, 1.484; 95% CI: 1.296-1.700, respectively). Conclusions: In a nationwide study for all adult patients with OHCA, the CoSTR2005 had favorable neurological outcome 1.6 times as high as the G2000, and also the CoSTR2010 had it 2.2 times. The neurologically intact survival increased each time the CPR guidelines were changed.
THU0469 CLUES TO RECOGNIZE SECONDARY FIBROMYALGIA IN PATIENTS WITH OSTEOARTHRITIS ACCORDING TO A FIBROMYALGIA ASSESSMENT SCREENING TOOL OF SCALES ON A MULTIDIMENSIONAL HEALTH ASSESSMENT QUESTIONNAIRE (MDHAQ/FAST3-F)
Authors: Mariam Riad, Isabel Castrejon, Joel Block, Theodore Pincus
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> A multidimensional health assessment questionnaire (MDHAQ) includes scales for a self-report painful joint count, symptom checklist, and fatigue visual analog scale (VAS), which may be compiled into a fibromyalgia assessment screening tool (FAST3-F), in addition to physical function, pain VAS, and patient global VAS, compiled into routine assessment of patient index data (RAPID3). FAST3-F agrees &gt;80% with 2011 formal fibromyalgia (FM) criteria in rheumatoid arthritis (RA) patients who have secondary FM. <h3>Objectives:</h3> To recognize clues to secondary FM in osteoarthritis (OA) patients seen in routine care, according to FAST3-F, and to analyze MDHAQ demographic and other clinical data in OA patients who did or did not meet MDHAQ/FAST3-F criteria for secondary FM. <h3>Methods:</h3> All patients complete an MDHAQ at all visits prior to seeing the rheumatologist at an academic rheumatology site. The 2-page MDHAQ includes RAPID3 to analyze clinical status, and a cumulative 0–3 FAST3-F scale to recognize FM, FAST3-F is scored 0-3, with 1 point each for 0-10 fatigue VAS ≥6, 0-54 self-report joint count ≥16, and 0-60 symptom checklist ≥16. FAST3-F scores of ≥2/3 agree &gt;80% with formal 2011 FM revised diagnostic criteria, based on data for area under the curve (AUC) on receiver operator characteristic (ROC) curves. A two-sample t test was used to compare the two groups; p values were considered significant if ≤0.05. <h3>Results:</h3> Among 173 OA patients, 55 (32%) met FAST3–F criteria of ≥2/3 for secondary FM. Patients who met criteria had lower formal educational level (p=0.01-Table), but did not differ significantly from those who did not meet criteria according to age, sex, or body mass index (BMI) (Table). MDHAQ scores for physical function, pain, patient global assessment, RAPID3, poor sleep quality, anxiety, and depression were significantly higher in the FAST3-F positive than negative patients (p&lt;0.001-Table). Abbreviations: FAST3-F= fibromyalgia assessment screening tool, BMI=body mass index <h3>Conclusion:</h3> MDHAQ/FAST3-F provides clues to identify OA patients with secondary FM in routine care. Nonetheless a definitive diagnosis requires a physician. The findings may be useful to recognize a basis for poor responses in clinical care, clinical trials, and other clinical research, and enhance understanding of pain mechanisms in OA versus FM versus OA with FM. <h3><b>Disclosure of Interests:</b>&nbsp;:</h3> None declared
PS1584 A PHASE II DOSE‐FINDING STUDY OF DALTEPARIN IN CHILDREN WITH VTE WITH OR WITHOUT CANCER
Authors: L. Hartman, I. Nurmeev, P. Svirin, N. Sherman, K. Wolter, J.L. Yan, D. Jani, N. Goldenberg
Journal: HemaSphere (2019)

Background: Venous thromboembolism (VTE) is an important clinical concern in children with or without cancer. Experience with dalteparin, a low molecular weight heparin, in the treatment of VTE in adults with cancer has been extensively published, but data in children are limited. Aims: We sought to determine the twice‐daily dalteparin dose required to achieve target Anti‐Xa levels of 0.5–1.0 IU/mL, as well as its pharmacodynamics (PD), efficacy, and safety in the treatment of VTE in children &lt;19 years old, with or without cancer. Methods: This prospective, multi‐center, Phase 2, open‐label study consisted of 3 phases: 1) Dose Adjustment Phase of up to 7 days, in which Anti‐Xa levels were measured following the first, second or third dose of dalteparin, until achievement of the target level; 2) PD Phase of up to 7 days, to obtain 2 randomized PD plasma samples for Anti‐Xa determination; and 3) Follow‐Up Phase, to complete up to 90 days of anticoagulant therapy. Patients were assessed for symptomatic new or progressive (i.e., recurrent) VTE as well as clinically relevant bleeding during treatment. Surveillance VTE imaging was performed at 90 ± 14 days. Results: The safety population consisted of 38 patients who received at least 1 dose of dalteparin (&lt;2 years: n = 3; ≥2 to &lt;8 years: n = 8; ≥8 to &lt;12 years, n = 7; ≥12 to &lt;19 years: n = 20). Twenty‐six patients (68%) had a diagnosis of cancer at baseline, of which 23 (88%) were haematological malignancies. The median [range] dalteparin dose required to achieve target Anti‐Xa levels decreased with age (&lt;2 years: 207.5 IU/kg [201.5–213.5 IU/kg]; ≥2 to &lt;8 years: 128.15 IU/kg [123.9–180.3 IU/kg]; ≥8 to &lt;12 years: 125 IU/kg [124.5–152.6 IU/kg]; ≥12 to &lt;19 years: 116.7 IU/kg [99.1–159 IU/kg]) (Figure). Therapeutic Anti‐Xa levels were achieved in 90% of patients within a mean (SD) of 2.6 days (1.54 days); the mean (SD) number of dose adjustments per patient was 0.7 (0.98). One patient (3%) developed symptomatic recurrent VTE. No patients reported clinically‐relevant bleeding. Four patients (11%) had treatment‐related serious adverse events. 62% of patients had complete resolution of their VTE at the end of the 90‐day reporting period. Summary/Conclusion: Twice‐daily dalteparin dosing achieved therapeutic levels in 90% of children with or without cancer, with a satisfactory tolerability profile. The median therapeutic doses of dalteparin were higher for the two youngest age cohort groups (&lt;2 years and 2 to &lt;8 years). image NCT00952380 Sources of Research Support: This study was sponsored by Pfizer Ltd.
SP0184 DON”T DELAY, CONNECT TODAY IN FINLAND: A VIDEO TO PROMOTE EARLY DIAGNOSIS
Authors: Maria Ekroth
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Positive Encounter - Don"t Delay Connect Today <h3>Background:</h3> Too often people suffer the symptoms of rheumatoid arthritis for too long before they visit a doctor. The positive encounter between physician and patient can lead to a good relationship, follow-up care and positive health outcomes. We conducted a survey about the need for a treatment plan and found that less than 30% of patients know their treatment plan and patients who do know their plan are better committed and more satisfied with their physicians. 72% of survey respondents who know their treatment plan are happy with their treatment as whole. Of the remainder, only 33% are satisfied. <h3>Objectives:</h3> The aim of this campaign is to illustrate and inform people of the symptoms of rheumatoid arthritis and encourage them to visit a doctor, enabling the doctor to assist the patient. To give advice to patients on how to prepare for a doctor's appointment. The campaign also includes a section directed at rheumatologists and rheumatology nurses, that advises on the importance of the encounter and the creation of the treatment plan. To increase awareness about our association, and to recruit new members <h3>Methods:</h3> Video for patients and the wider public. Video for rheumatologists and rheumatism professionals. Mailing of brochures on the importance of the treatment plan to all Finnish rheumatologists and arthritis treatment units. We also thanked doctors and attached a fruit gift card. We sent flyers and posters to our member associations. Members have handed out materials directed at patients locally. They have distributed them to libraries, municipalities, sports centres… and given away fliers at the events. <h3>Results:</h3> Patients have reported being better prepared for the visits and having written down important questions in advance. We achieved attention value amongst professionals and were invited to design a national treatment path with rheumatism professionals for children with JIA. All the main hospitals are involved and will start to use it. Free TV air time was offered for the patient video on the national main TV channel. The Finnish Society for Rheumatology offered us the possibility of promoting our campaign at the Scandinavian Congress of Rheumatology. <h3>Conclusion:</h3> The campaign was successful. <h3>References:</h3> [1] www.youtube.com/watch?v=Y2_z8cxDvaA [2] https://www.youtube.com/watch?v=vkDf7C-VPoY [3] https://www.reumaliitto.fi/fi/reumaliitto/uutiset/reumaliiton-tilaisuus-eduskunnassa-viestit-vaaleihin-2019 [4] https://www.reumaliitto.fi/fi/hoidonlaatu <h3>Disclosure of Interests:</h3> None declared
AB1348 PERSPECTIVES OF PATIENTS WITH INFLAMMATORY ARTHRITIS REGARDING CARDIOVASCULAR RISK: A QUALITATIVE STUDY
Authors: Iris Navarro-Millan, Sarah Young, Sally Shurbaji, Chastity Mcdavid, Anna Cornelius-Schecter, Bernadette Johnson, Andrea Cherrington, Liana Fraenkel, Jeffrey Curtis, Monika Safford
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Cardiovascular disease (CVD) is the most common cause of death among patients with inflammatory arthritis (IA) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS). <h3>Objectives:</h3> To elicit perspectives of patients with IA to inform the design of a patient-centered intervention for a CVD risk reduction intervention. <h3>Methods:</h3> This was a qualitative study guided by Bandura's Social Cognitive Theory, placing special emphasis on knowledge about the relationship between arthritis and CVD as well as barriers and facilitators to receiving healthcare related to CVD risk such as screening and management for hyperlipidemia. We recruited patients from a single academic center with either RA, PsA, or AS to participate in focus groups. Data were analyzed thematically. <h3>Results:</h3> We conducted three focus groups with a total of 17 participants (5 participants in two and 7 participants in one of the focus groups) of mean age 56 (SD+7.7) years; 15 were women; 3 were on a statin; and 1 previously had a stroke. Barrier Themes 1-2: 1) Need for more information about arthritis, prognosis, and IA medications; 2) Lack of knowledge about how IA increases cardiovascular disease (CVD) risk. Facilitator Themes 3-5: 3) Lifestyle changes to reduce overall CVD risk; 4) Potential roles for peer coaches; and 5) Improving doctor-patient communication about IA, medications, and CVD risk. Patients expressed that improving Themes 2 and 5 could facilitate CVD screening. <h3>Conclusion:</h3> Education about increased CVD risk could help activate patients with IA engage in CVD risk reduction strategies. Peer coaches appears to be a reasonable tool towards that goal. <h3>Disclosure of Interests:</h3> Iris Navarro-Millan: None declared, Sarah Young: None declared, Sally Shurbaji: None declared, Chastity McDavid: None declared, Anna Cornelius-Schecter: None declared, Bernadette Johnson: None declared, Andrea Cherrington: None declared, Liana Fraenkel: None declared, Jeffrey Curtis: None declared, Monika Safford Grant/research support from: Amgen
Providing palliative medicine consultants with GP skills
Authors: Holly Young
Journal: BMJ (2019)

Mitchell and colleagues say that primary care teams are crucial in initiating and delivering effective palliative care.1 Implementing the Shape of Training review will see specialty trainees entering a dual accredited palliative medicine and internal medicine curriculum in 2022, increasing the number of medical consultants taking part in the acute medical take but not necessarily improving training in palliative medicine.2

Foresight …
Abstract P234: Genetic Variants of the Kallikrein-kinin System Associated with the Salt Sensitivity of Blood Pressure: The GenSalt Study
Authors: Dongfeng Gu, Qi Zhao, Tanika N Kelly, James E Hixson, Dabeeru C Rao, Jie Cao, Jing Chen, Jianxin Li, Jichun Chen, Xu Ji, Dongsheng Hu, Xushan Wang, De-Pei Liu, Jiang He
Journal: Circulation (2012)

The kallikrein-kinin system (KKS) has been implicated in the pathogenesis of salt-sensitive hypertension in animal models. We comprehensively examined the association between genetic variants of the KKS and blood pressure (BP) response to dietary sodium intervention among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was carried out among 1,906 GenSalt participants from rural areas of north China. Nine BP measurements were obtained at baseline and on the last three days of each intervention period using a random-zero sphygmomanometer. The percentage changes in mean BP from baseline to low-sodium intervention and from low-sodium to high-sodium intervention were used to assess individual salt-sensitivity. A total of 205 tagSNPs and functional SNPs of eleven genes of the KKS ( BDKRB1 , BDKRB2 , CPN1 , CPN2 , CPM , ECE1 , KLK1 , KLKB1 , KNG1 , MME , SERPINA4 ) were selected and genotyped in this study. Single marker analyses were conducted using the Family Based Association Test program. Genetic variants in the bradykinin receptor B2 ( BDKRB2 ) and endothelin converting enzyme 1 ( ECE1 ) genes showed significant associations with salt sensitivity even after adjusting for multiple testing using the false discovery rate method. SNP rs11847625 of BDKRB2 was significantly associated with systolic BP (SBP) response to low-sodium intervention ( P = 0.0001). Compared to its major allele G, carriers of the minor allele C had greater SBP decrease during low-sodium intervention. Furthermore, a haplotype containing allele C was associated with greater SBP increase to high-sodium intervention ( P = 0.0009). Seven SNPs of ECE1 , one of the degrading enzymes of kinins, were significantly associated with diastolic BP (DBP) response to low-sodium intervention ( P values ranged from 0.0003 to 0.002). Two haplotypes in the linkage disequilibrium block including these seven SNPs were significantly associated with DBP response to low-sodium intervention (P=0.0004 and 0.003, respectively). Our study found that the genetic variants of the KKS were associated with salt sensitivity of BP. Replication and functional studies of the identified variants are warranted in the future.