tbuckley/cabot-search huggingface dataset:
FRI0097 Expression of uncoupling protein-1 in subcutaneous fat reduces the total cholesterol level and cardiovascular risk in female ra pateints
Authors: L.I. Lyngfelt, M.C. Erlandsson, M. Nadali, K.M. Andersson, S.T. Silfverswärd, R. Pullerits, M.I. Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To improve understanding of fat-related molecular mechanisms behind the increased cardiovascular (CV) morbidity in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Transcription of uncoupling protein 1 (UCP1) was measured in the subcutaneous fat tissue and serum levels of lipoproteins, adipokines, and inflammation markers in 185 middle-aged female patients (mean age 51 years) with RA and compared between the groups stratified by the total cholesterol (TC) levels and the body mass index (BMI). The risk of dying of CV disease within 5 years was calculated electronically using the strategy proposed by Pocock et al.<sup>1</sup> <h3>Results</h3> CVR was highest (risk score 27.76, 5 year CVR 0.67%) in the patients combining high TC (&gt;5.1 mmol/L) and high BMI (&gt;25 kg/m2), while those with low levels of TC and BMI had lowest CVR (risk score 10.82, CVR 0.11%). CVR was significantly decreased if either TC (TC<sup>lo</sup>BMI<sup>hi</sup>) or BMI (TC<sup>hi</sup>BMI<sup>lo</sup>) was low (p=0.017 and p=0.014, respectively). With the exception of TC<sup>lo</sup>BMI<sup>lo</sup> group, these groups had no difference with respect to age, disease duration, inflammation defined by serum IL6 and IL1, and disease activity measured by DAS28. TC<sup>lo</sup>BMI<sup>hi</sup>patients had an overall increase in fat expression of UCP1 (p=0.047) that has the cholesterol lowering capacity and may explain low TC levels in this group. In contrast, TC<sup>hi</sup>BMI<sup>lo</sup>patients had high prevalence of cases with unmeasurable UCP1 expression and higher levels of serum adiponectin (p=0.053) and HDL (p&lt;10–5). Measurable expression of UCP1 was found in 79%. In total cohort, the patients with measurable UCP1 had higher inflammation and RA activity presented by IL-6 (p=0.0001), IL1b (p=0.037) and DAS28 (p=0.0086), compared to those with no UCP1 expression. TC<sup>lo</sup>BMI<sup>hi</sup>patients had an overall increase in fat expression of UCP1 (p=0.047) and lowest prevalence of cases with no UCP1 expression (6.2%). <h3>Conclusions</h3> The study shows that UCP-1 expression in subcutaneous fat may be a CV protective mechanism in RA patients. The inflammation seems to be the driving force of UCP1 expression in RA. <h3>Reference</h3> [1] Pocock SJ, McCormack V, Gueyffier F, Boutitie F, Fagard RH, Boissel JP. A score for predicting risk of death from cardiovascular disease in adults with raised blood pressure, based on individual patient data from randomised controlled trials. BMJ2001;323:75–81. <h3>Disclosure of Interest</h3> None declared
SAT0694 Determinants of trajectories of multi-site pain in knee osteoarthritis: a 10.7-year prospective study in older adults
Authors: F. Pan, J. Tian, F. Cicuttini, C. Ding, G. Jones
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Pain in osteoarthritis (OA) is very common especially in elderly and commonly occurs at multiple sites. Multi-site pain (MSP) has been shown to be associated with more severe symptoms and worse health-related quality of life compared to single-site pain. Limited evidence exists about understanding the course of MSP and its determinants. <h3>Objectives</h3> To identify distinct trajectories of MSP over 10.7 years in an older population, and to examine risk factors for identified trajectories. <h3>Methods</h3> 1099 participants (mean age 63 years) from the population-based Tasmanian Older Adult Cohort study were recruited at baseline. 875, 768 and 563 participants attended years 2.6, 5.1 and 10.7 follow-up, respectively. Demographic, psychological, lifestyle and comorbidities data were obtained at baseline. Knee radiographic OA was assessed by X-ray at baseline. Group-based trajectory modelling was applied to identify distinct trajectories of MSP. Multi-nominal logistic regression was used for the analyses with adjustment for potential confounders. <h3>Results</h3> Three distinct MSP trajectories were identified: a group of participants with 'no MSP' (11%), a group with 'fluctuating MSP' (38%), and a group with 'persistent MSP' over time (51%). In multivariable analyses with the 'no MSP' trajectory as reference, emotional problems and comorbidity were significantly associated with both 'fluctuating MSP' and 'persistent MSP' trajectory. In addition, female sex, being obese and radiographic knee OA predicted the trajectory of 'persistent MSP' in the whole population. Results were similar with emotional problems (relative risk [RR]: 2.57 for 'fluctuating MSP' and 5.70 for 'persistent MSP', both p&lt;0.05), being obese (RR: 3.80 for 'persistent MSP', p=0.007) and comorbidity (RR: 2.45, p=0.010) in either 'fluctuating MSP' or 'persistent MSP' trajectory in those with radiographic knee OA. <h3>Conclusions</h3> MSP trajectories appear stable once established and can be predicted by factors both peripheral and central in origin. <h3>Disclosure of Interest</h3> None declared
More than two thirds of medical students cut down spending on essentials, survey finds
Authors: Laura Nunez-Mulder
Journal: BMJ (2019)

Seven out of 10 UK medical students are cutting down on essentials such as heating, food, or professional clothes in order to economise, a BMA survey has suggested.1

Some 639 medical students were polled in the latest survey, published on 16 January. The proportion spending less on essentials was 70% (449 of 637 respondents). This compared with 67.6% (399 of 590) in a BMA survey in 2013 which looked specifically at first year medical students.2 The latest survey included respondents from all undergraduate years and those …
SAT0508 Ace-inhibitors in arterial hypertension in ssc patients display a risk factor for scleroderma renal crisis – a eustar analysis
Authors: S. Adler, P.A. Varisco, O. Distler, L. Buetikofer, O. Kowal-Bielecka, Y. Allanore, G. Riemekasten, P.M. Villiger
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Scleroderma renal crisis (SRC) represents a rare but life-threatening manifestation in systemic sclerosis (SSc). Survival remains poor despite therapeutic use of ACE inhibitors (ACEi). Factors influencing the risk of SRC are not well characterised. In particular, ACEi are discussed as promoting but also as protecting SRC. <h3>Objectives</h3> To investigate the effect of ACEi on SRC incidence in prospectively collected data of a cohort of SSc patients. <h3>Methods</h3> EUSTAR database analysis with focus on arterial hypertension, antihypertensive medication and glucocorticoids. Subgroup analysis of a dataset with defined documentation of medication from January 2009 until November 2017. <h3>Results</h3> Out of 14'524 patients in the database we identified 7'648 patients with at least one follow-up after 2009. 102 patients developed SRC in 27'450 person-years (py), representing an incidence of 3.72 (3.06–4.51) per 1'000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity and onset, arterial hypertension, tendon friction rubs, SCL70 and ACA positivity, 78 of 6083 patients developed SRC. Herein, use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.07 (95% confidence interval (CI):1.28–3.36). Calcium channel blockers (CCB), angiotensin receptor blockers, endothelin receptor antagonists and glucocorticoids did not influence SRC incidence. Medication strategies were not altered after renal crisis. Cumulative mortality 5 years after renal crisis was 18.6% (95% CI: 13.0%–26.3%). <h3>Conclusions</h3> This EUSTAR analysis supports the notion that ACEi should be avoided in arterial hypertension in SSc patients. Alternative antihypertensive drugs as CCB might be preferred. <h3>References</h3> [1] Hudson M, Baron M, Tatibouet S, Furst DE, Khanna D, International Scleroderma Renal Crisis Study I. Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey. Seminars in arthritis and rheumatism2014;43(5):666–72. [2] Guillevin L, Berezne A, Seror R, Teixeira L, Pourrat J, Mahr A, et al. Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatology (Oxford)2012;51(3):460–7. [3] Mouthon L, Bussone G, Berezne A, Noel LH, Guillevin L. Scleroderma renal crisis. The Journal of rheumatology. 2014;41(6):1040–8. [4] Shanmugam VK, Steen VD. Renal disease in scleroderma: an update on evaluation, risk stratification, pathogenesis and management. Current opinion in rheumatology2012;24(6):669–76. <h3>Acknowledgements</h3> We acknowledge the work of all participating EUSTAR centres for contributing to this work. <h3>Disclosure of Interest</h3> None declared
Factors That Influence Treatment Decision-Making: Perspectives of 1147 Chronic Lymphocytic Leukemia (CLL) Patients in the United States
Authors: Brian Koffman, Betsy Dennison, Kaitlin Kennard, John C. Byrd, Richard R. Furman, John M. Pagel, Matthew S Davids, Chadi Nabhan, Neil E. Kay, Tanya Siddiqi, Danielle M. Brander, William G. Wierda, Deborah M. Stephens, Brian T. Hill, Javier Pinilla Ibarz, Bruce Cheson, Steven T Rosen, Farrukh T. Awan, Michael Y. Choi, Thomas E Henry, Lindsey E. Roeker, Anthony R. Mato
Journal: Blood (2018)
The Next Wave of Stroma-Targeting Therapy in Pancreatic Cancer
Authors: Huocong Huang, Rolf A. Brekken
Journal: Cancer Research (2019)

Abstract The stroma of pancreatic ductal adenocarcinoma (PDA) forms a major barrier to therapy and immune surveillance. Elahi-Gedwillo and colleagues demonstrate that halofuginone has potent antifibrotic activity in PDA by directly inhibiting the activation of pancreatic stellate cells, thereby reducing the deposition of extracellular matrix components, including collagen and hyaluronic acid. As a result, halofuginone improves drug delivery and the infiltration of favorable immune cells such as immune-stimulatory myeloid cells and cytotoxic T cells. Despite recent controversies regarding targeting stroma in PDA, this study highlights that modifying the stroma of PDA remains an attractive strategy to improve the efficacy of therapy. See related article by Elahi-Gedwillo et al., p. 372
SAT0544 Comparing the clinical profile of adults and children with behÇet’s syndrome in the uk
Authors: S. Myers, E. Makmur, L. Hanns, D. Huskard, P. Brogan, N. Ambrose
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's syndrome (BS) is a rare multi-system inflammatory disorder and most commonly presents in young adults. Clinical phenotypic variance across geographical regions is recognised but there has been no UK publication assessing UK BS patients' variance by age groups. BS is primarily a clinical diagnosis, and there is significant diagnostic delay in the UK. Exploration of the phenotype in UK adults and children may help clinicians diagnose BS more effectively. <h3>Objectives</h3> Describe and compare the clinical features of adults and children with BS in a UK population. <h3>Methods</h3> We examined and compared two cumulative databases of clinical features of BS patients. The paediatric database was collected Great Ormond Street Hospital for Children, London (n=46). The adult database was collected at the Hammersmith Hospital, London (n=560). <h3>Results</h3> Oral ulcers were common for both paediatric (97.8%) and adult (96.6%) populations. Genital ulceration also did not differ between paediatric (73.9%) and adult (75.7%) groups. Eye involvement was rare in children (4.3%) versus adults (37%) (p&lt;0.001). Skin involvement was more common in the adult cohort (55.4% vs. 21.7%, p&lt;0.001). There was a trend towards increased vascular involvement in adults (17.5%) versus children (6.5%). The children had higher gastrointestinal involvement compared to adults (21.7% vs. 4.5%, p&lt;0.001) <h3>Conclusions</h3> Paediatric BS patients displayed less ocular and skin manifestations compared to the adult BS patients. The BS UK phenotype differs from international cohorts. This information will be valuable in helping clinicians diagnose BS in UK adult and paediatric populations. <h3>Disclosure of Interest</h3> None declared
SAT0607 Drugs used off label in a rheumatology service of a terciary hospital
Authors: D. Martinez-Quintanilla Jimenez, N. García Castañeda, P. Moreno Fresneda, M. Perez Abanades, R. Garcia De Vicuña, I.G. Alvaro, E. Tomero Muriel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The use of drugs off-label (DOL) is not uncommon in Rheumatology daily clinical practice for the treatment of patients with immune-mediated inflammatory diseases (IMID). <h3>Objectives</h3> To analyse the use of DOL requested by the Rheumatology Service. <h3>Methods</h3> We reviewed the medical records of all patients registered in the DOL database of the Hospital Pharmacy Service between July 2009 and March 2017. The following variables were collected: date of approval and start of the drug, physician, disease, reason for indication, sex and age of the patients, response to treatment according to the global assessment of the responsible physician, date and reason of withdrawal. A descriptive study of the variables collected through STATA 12 is carried out. <h3>Results</h3> 225 DOL were requested for a total of 174 patients. Women were 78.7%, with an average age of 56.5 years (sd 1.15). In most patients (77%) a single drug was requested. In 37 patients were requested between two (16.4%) and seven drugs (0.5%). The indications of the DOL in our database were: connective tissue diseases (CTD: 46.6%), vasculitis (23%), rheumatoid arthritis (RA: 5.2%) and spondyloarthritis (SPA:8%). Other diseases (17.2%) are included in two heterogeneous groups classified according to their ethiology (autoimmune (8.6%) or not (8.6%). 39.5% of the drugs requested were conventional synthetic DMARDs (csDMARDs), 38.2% biological DMARDs (bDMARDs), 7.5% were antivirals, 2.6% vasodilators and 12% other drugs. Conventional synthetic DMASDs (csDMARDs) represented 39.5% of request, biological DMARDs (bDMARDs) 38.2%, antiviral drugs 7.5%, vasodilator drugs 2.6% and other drugs 12%. Tables 1 and 2 show csDMARDs and bDMARDs respectively, according to the indication. The effectiveness of the DOL was variable, ranging between 0% and 76.5%. The most effective were antiviral drugs, used to treat viral infections in immunosuppressed patients (76.5%), tocilizumab (72.2%) and rituximab (61.1%). By contrast, the least effective were anakinra (0%) and TNF blockers (31.8%). The cs DMARDs group had an effectiveness of 53.9% (Mycophenolate stands out with 75% effectiveness). The disease groups that responded best to DOL therapy were connective tissue and vasculitis, with 58% and 53.7% of effectiveness. <h3>Conclusions</h3> Rheumatic diseases for which DOL is most commonly requested are connective tissue and vasculitis, as a consequence of the absence of specific indications for these pathologies. In our experience, rituximab is a good option in the treatment of connective tissue diseases, which contrasts with the results of some clinical trials. Tocilizumab is a good therapeutic option in the treatment of vasculitis, a group that includes Giant Cell Arteritis, as recently confirmed with its approval for this indication. <h3>Disclosure of Interest</h3> None declared
NHS long term plan: all patients to have access to online GP consultations by 2023-24
Authors: Gareth Iacobucci
Journal: BMJ (2019)

On Monday NHS England published its long term plan for the NHS.1 Here we summarise how it intends to prioritise services over the next 10 years in specific areas.

By 2023-24 every patient in England will be able to access “digital first” NHS primary care consultations from either their own GP or a digital GP provider. Outpatient services will be redesigned to enable more cases to be handled remotely and electronically, avoiding up to a third of face-to-face outpatient visits (up to 30 million appointments a year). All acute, community, and mental health providers will be “fully digitised” across all locations and departments by 2024. In 2019-20 100 000 women will be able to access their maternity record digitally, with coverage extended to the whole country by 2023-24. Decision support and artificial intelligence will help eliminate variation across the country and help patients to managing their conditions themselves.

Mental …
Abstract 18673: JNK Inhibition Restores Endothelial Function in Type 2 Diabetes Mellitus
Authors: Rosa Breton-Romero, Bihua Feng, Monika Holbrook, Melissa G Farb, Jessica L Fetterman, Erika A Linder, Brittany D Berk, Nobuyuki Masaki, Robert M Weisbrod, Elica Inagaki, Noyan Gokce, Jose J Fuster, Kenneth Walsh, Naomi M Hamburg
Journal: Circulation (2015)

Introduction: Diabetes mellitus type 2 is an increasingly public health problem and it is a major cause in the development of cardiovascular diseases. Endothelial dysfunction is a key mechanism that contributes to the pathogenesis of cardiovascular diseases and is a well-known feature of clinical diabetes. Prior studies have demonstrated an impaired nitric oxide bioavailability and a reduced endothelium-dependent vasodilation under diabetic conditions and in animal models, JNK activity has been widely described to be involved in systemic insulin resistance. Hypothesis: Our study aimed to evaluate the involvement of JNK in endothelial dysfunction, studying its potential role in altered eNOS activation and NO synthesis in diabetic patients. Methods: We measured endothelial function and JNK activity in freshly isolated endothelial cells from diabetic patients (n=38) and nondiabetic controls (n=40). Results: ECs from diabetic patients displayed impaired eNOS activation and reduced NO release after insulin and A23187 stimulation, consistent with the presence of endothelial dysfunction. JNK activation was higher in diabetic (**P=0.003), and was associated with lower flow-mediated dilation (r=-0.53, *P=0.02). In endothelial cells from diabetic patients, treatment with JNK chemical inhibitor (SP600125) restored eNOS activation and insulin response (***P&lt;0.001). Nitric oxide bioactivity after A23187 stimuli with diabetes was also recovered in endothelial cells from patients with diabetes. Conclusions: In summary, our data suggest that JNK activation contributes to vascular insulin resistance and endothelial dysfunction in patients with type 2 diabetes and may represent a target in novel therapeutic opportunities.
Immunologic Correlates of the Abscopal Effect in a SMARCB1/INI1-negative Poorly Differentiated Chordoma after EZH2 Inhibition and Radiotherapy
Authors: Mrinal M. Gounder, Guo Zhu, Lev Roshal, Eric Lis, Scott R. Daigle, Steven J. Blakemore, Neil R. Michaud, Meera Hameed, Travis J. Hollmann
Journal: Clinical Cancer Research (2019)

Abstract Purpose: We sought to determine the mechanism of an exceptional response in a patient diagnosed with a SMARCB1/INI1-negative chordoma treated with tazemetostat, an EZH2 inhibitor, and followed by radiotherapy. Patient and Methods: In an attempt to investigate the mechanism behind this apparent abscopal effect, we interrogated tumor tissues obtained over the clinical course. We utilized next-generation sequencing, standard IHC, and employed a novel methodology of multiplex immunofluorescence analysis. Results: We report an exceptional and durable response (2+ years) in a patient with SMARCB1-deleted, metastatic, poorly differentiated chordoma, a lethal disease with an overall survival of 6 months. The patient was treated for 4 weeks with tazemetostat, an EZH2 inhibitor, in a phase II clinical trial. At the time of progression she underwent radiation to the primary site and unexpectedly had a complete response at distant metastatic sites. We evaluated baseline and on-treatment tumor biopsies and demonstrate that tazemetostat resulted in pharmacodynamic inhibition of EZH2 as seen by decrease in histone trimethylation at H3K27. Tazemetostat resulted in a significant increase in intratumoral and stromal infiltration by proliferative (high Ki-67), CD8+ T cells, FoxP3+ regulatory T cells, and immune cells expressing checkpoint regulators PD-1 and LAG-3. These changes were pronounced in the stroma. Conclusions: These observations are the first demonstration in patient samples confirming that EZH2 inhibition can promote a sustained antitumor response that ultimately leads to T-cell exhaustion and checkpoint activation. This suggests that targeted alteration of the epigenetic landscape may sensitize some tumors to checkpoint inhibitors.
Low iron promotes megakaryocytic commitment of megakaryocytic-erythroid progenitors in humans and mice
Authors: Juliana Xavier-Ferrucio, Vanessa Scanlon, Xiuqi Li, Ping-Xia Zhang, Larisa Lozovatsky, Nadia Ayala-Lopez, Toma Tebaldi, Stephanie Halene, Chang Cao, Mark D. Fleming, Karin E. Finberg, Diane S. Krause
Journal: Blood (2019)
FRI0222 Association between blood lead levels and gout: the united states national health and nutrition examination survey 2007–2014
Authors: T.T. Cheung, M.F. Tsoi, B.M.Y. Cheung, W.C.S. Lau
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lead is a heavy metal with no physiological role in humans. It is well known that cxcessive exposure to lead is associated with cardiovascular, gastrointestinal and neurological complications. However, recent studies have demonstrated that lead can increase the tubular reabsorption of urate, resulting in hyperuricaemia and the development of gout. Although blood lead levels are dropping in the US general population, the association between low blood lead levels ad gout remains inconclusive. <h3>Objectives</h3> To evaluate the relationship between serum blood lead levels and the development of gout in the US general population. <h3>Methods</h3> Adult participants with blood lead measurements and self reported gout in NHANES 2007–2014 were included in the analysis. Results were analysed using SPSS complex sample module version 22. Logistic regression with sample weight adjustment was used to study the association between blood lead levels and gout. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. Sub-group analysis was conducted in participants with blood lead level &lt;5 µg/dL. <h3>Results</h3> 18837 adult participants were included in the analysis. 18 270 participants had blood lead levels below 5 ug/dL (The current reference range for acceptable blood lead levels in healthy persons without excessive exposure to environment source of lead). The prevalence of gout increased with blood lead levels. In the total population, the odd ratio of gout was 4.96 in subjects with blood lead levels above 2.21 ug/dL. After adjusting for body mass index, hypertension, renal function and use of diuretics, the odd ratio of gout was 2.65 which remained significant. The subgroup analysis of subjects with blood lead levels below 5 ug/ml showed similar findings. The risk of gout is increased when blood lead levels are higher than 1.43 ug/dL. <h3>Conclusions</h3> Low blood lead levels are associated with gout. The risk of gout is increased when the blood lead level is higher than 1.43 ug/dL. Therefore, measures should be taken to minimise the environmental exposure to lead. <h3>Disclosure of Interest</h3> None declared
Abstract 17879: Vortex Formation Time Changes With Age in Children
Authors: Aparna Kulkarni, Daisuke Morisawa, Daisy Gonzalez, Arash Kheradvar
Journal: Circulation (2017)

Background: Vortex formation time (VFT) is a dimensionless index derived using echocardiography parameters; it is a reliable indicator for assessment of left ventricular (LV) diastolic function. Th...