tbuckley/cabot-search huggingface dataset:
Guideline Recommendations for Statin Therapy
Authors: David C. Grossman, Susan J. Curry, Douglas K. Owens
Journal: JAMA (2017)

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Abstract 11392: Chronic Low-Level Transcutaneous Electrical Stimulation of the Auricular Branch of the Vagus Nerve: A New Approach to Attenuate Neural Remodeling and Reduce Ventricular Arrhythmias in a Post-Infarction Canine Model
Authors: Song y Wang, Li L Yu, Zhi B Lu, Zhuo Wang, Bing Huang, Kai Liao, Gao W Saren, Kang Yang, Yuan y Qu, Bo He, Wen B He, Hong Jiang
Journal: Circulation (2014)

Introduction: Left stellate ganglion (LSG) and cardiac neural remodeling, which are associated with ventricular arrhythmias (VAs) in post-infarction model, can be attenuated by low-level vagus nerve stimulation. However, whether chronic low-level transcutaneous electrical stimulation at the tragus, where the auricular branch of vagus nerve innervate, can attenuate neural remodeling both in heart and LSG and then reduce VAs is unknown. Hypothesis: We hypothesized that chronic low-level tragus stimulation (LL-TS) would attenuate cardiac and LSG nerve remodeling and then reduce inducibility of VAs in a post-infarction model. Methods: Twenty beagles after ligating coronary artery were randomly divided into normal control (NC, n=4), MI treated with LL-TS (MI-TS n=8)and MI treated with shame LL-TS (MI-NTS, n=8)groups. LL-TS was performed at 80% below the threshold, at which sinus rate or atrioventricular conduction slowing can be initially induced, for 2 hours a day for 2 months. Left stellate ganglionic nerve activity (SGNA) and left thoracic vagal nerve activity (VNA) was recorded. Slope of ventricular restitution curves (Smax) and programmed ventricular stimulation were performed to evaluate VAs. Nerve sprouting, nerve synaptic density and associated protein expression both in LSG and hearts were evaluated by immunostaining or Western blotting. Results: Two months later, the increased SGNA induced by MI was attenuated by LL-TS. However, the increased VNA was strengthened.In the MI-TS group, the number of sympathetic nerves both in peri-infarct zone and LSG were reduced, while the parasympathetic nerve fibers were increased compared to MI-NTS group. Moreover, the expression of synaptophysin, NGF in peri-infarct as well as in LSG in the MI-TS group was significantly lower than the MI-NTS group, while the level of SK2 was much higher.Chronic LL-TS also significantly decreased the Smax, LF/HF ratio and arrhythmia score of programmed ventricular stimulation induced VAs. Conclusions: These findings suggested that chronic LL-TS augmented cardiac vagal and reduced sympathetic tone, attenuated cardiac and LSG nerve remodeling, regulated nerve associated protein expression and potentially contributed to reducing vulnerability to VAs.
SP0105 Macrophages, metabolism and inflammation
Authors: NOS Camara
Journal: Annals of the Rheumatic Diseases (2017)

Macrophages are a heterogeneity population implicated in several diseases and correlated with distinct tissue outcomes after injury. M2 macrophages have been associated with tissue repair whereas M1 macrophages participate in early phase of tissue damage. Recent works have also suggested that upon activation, macrophages can use distinguished nutrients as source of energy and these metabolic pathways lead to their activation and differentiation. Nutrient sensors are intimae associated with innate receptors and therefore connected with inflammatory response. Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome through frustrated phagocytosis. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher levels in some diseases, before the appearance of crystals. sUA can be released in a hypoxic environment and triggers NLRP3 through the production of mitochondrial ROS, with increased maximum and reserve oxygen consumption ratio (OCR) and higher VDAC protein levels. This process is followed by ASC speck formation, caspase-1 activation and IL-1β release. These findings may have profound implications for inflammatory-related diseases. Support: FAPESP and CNPq. <h3>Disclosure of Interest</h3> N. Camara Grant/research support from: FAPESP, CNPq
THU0738-HPR Promoting physical activity in rheumatoid arthritis: developing a theory-based behaviour change intervention
Authors: L Larkin, A Fraser, S Gallagher, N Kennedy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Physical activity has numerous benefits for people who have RA, however interventions targeting physical activity behaviour in people who have RA have had limited efficacy [1]. <h3>Objectives</h3> To develop a theory-based behaviour change intervention to promote physical activity in people who have RA. <h3>Methods</h3> Development was guided by the UK9s Medical Research Council Complex Interventions framework [2] and consisted of three components; 1. Narrative review which explored the use of behaviour change theory in previous interventions 2. Systematic review which examined the content and structure of previous interventions 3. Qualitative study which explored the preferences of key stakeholders (people who have RA and health professionals) about the design of the intervention. <h3>Results</h3> Previous interventions lacked consideration of behaviour change theory in design and delivery, and there was a large degree of variance in content, structure and delivery. Lack of knowledge of current physical activity recommendations for people who have RA was highlighted in the qualitative study, and delivery preferences were identified. Intervention development was mapped to the Behaviour Change Wheel [3] and employed the Theory of Planned Behaviour as it9s theoretical basis. The proposed intervention is outlined in Table 1. <h3>Conclusions</h3> We have developed a theory-based intervention which considers the preferences of key stakeholders. Future research will determine the feasibility and effectiveness of this intervention. <h3>References</h3> Larkin et al (2015) Behaviour change interventions to promote physical activity in rheumatoid arthritis: a systematic review. Rheum Intl 35(10):1631–40. Craig et al (2008) Developing and evaluating complex interventions: new guidance, BMJ (Clinical research ed.), 337, a1655. Michie et al (2014) The Behaviour Change Wheel: A Guide to Designing Interventions., Silverback Publishing: Great Britain. <h3>Disclosure of Interest</h3> None declared
Beta2 responsiveness in flow-limited COPD patients with respiratory failure
Authors: C.A. Volta, E.R. Righini, R. Alvisi, A. Ferraresi, A. Bocchi, E. Marangoni, V. Pavoni, R. Ragazzi, M. Verri, G. Gritti, J. Milic Emili
Journal: Intensive Care Medicine (1998)
FRI0596 Anakinra treatment in patients with familial mediterranean fever: a single-center experience (case series)
Authors: B Ergezen, S Ugurlu, H Ozdogan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Approximately in 5 to 10% of FMF patients there is insufficient response and/or intolerance to colchicine treatment. Several reports have pointed out the efficacy of IL-1 blockade in colchicine resistant FMF subgroup. <h3>Objectives</h3> To review the patients followed in our center with FMF who received Anakinra, an anti-IL-1 receptor antagonist, in terms of outcome and side effects. <h3>Methods</h3> 43 FMF patients who were treated with Anakinra were retrospectively reviewed with regard to indication, effect on disease activity and acute phase response, adverse events and patient global assessment. <h3>Results</h3> There were 43 patients with FMF (20 M/ 23 F) who were treated with Anakinra for various indications (colchicine resistant recurrent febrile attacks in 39, colchicine related side effects in 3, both in 1). The mean age of the patients was 31.73±9.56 years. The mean duration of the disease was 19.90±10.52 years. There were various co-existing pathologies among this study group like Ankylosing Spondylitis (4), Psoriasis (1), Behçet9s disease (1), Gout (1), Vasculitis (1), Adult-onset Still9s disease (1), Polyarthritis Nodosa (1) and Celiac disease (1). The mean colchicine dose was 1.84±0.31 mg/d. As for the dosage, 35 patients were on 100 mg/day, 6 were 100 mg on alternate days, 2 were on 200 mg/day. The mean duration of anakinra treatment was 10.76±13.64 months. After the initiation of anakinra 29 patients became attack-free, 9 patients reported more than 50% decrease, 3 patients less than 50% decrease, and 2 patients no change in the frequency of the attacks. Mean patient global assessment decreased from 7.55±2.34 to 2.82±2.63 under Anakinra treatment (p&lt;0.001). As for the adverse events, eight patients (%18) had allergic reactions under Anakinra treatment (severe disseminated rash in 1 patient and severe injection site reaction in 4 patients and tolerable injection side reaction in 3) which necessitated termination of treatment in 5 patients. Anakinra was stopped because of genital warts and urinary tract infection in one other patient. Worsening of psoriatic lesions was observed in another patient. There were no adverse events in the remaining 41 patients during the course of treatment. On the other hand, treatment was terminated due to inadequate response in 11 (25%), remission in 2 and patient preference in 3 patients. Nineteen patients are still on Anakinra treatment for 10.09±14.51 months. <h3>Conclusions</h3> Anakinra is an effective and relatively safe alternative treatment in FMF patients with inadequate response or intolerance to colchicine, however approximately one fourth of the patients stop anakinra for insufficient response. <h3>Disclosure of Interest</h3> None declared
FRI0389 Foot involvement in patients with systemic sclerosis: a single-centre report
Authors: G Cuomo, D Ruta, E Frongillo, L Pirro, A Del Mastro, C Romano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Foot involvement can be a source of morbidity and disability in patients with systemic sclerosis (SSc). Some studies have previously reported severity, echographic and radiographic manifestations of foot involvement in SSc (1,2). <h3>Objectives</h3> The aim of our study was to assess the nature and prevalence of foot problems in patients with SSc reporting a single centre experience. <h3>Methods</h3> A podiatrist and a rheumatologist assessed 81 (76 female) consecutive patients attending our SSc outpatient clinic. The mean age was 50 years (range 21–70). Thirteen (16%) had diffuse cutaneous SSc with a median disease duration from Raynaud9s Phenomenon of 5 years (range 3 –19); 68 (84%) had limited cutaneous SSc with a median disease duration of 11.5 years (range 1–41). The overall median disease duration was 11 years (range 1–41). Thirty (37%) were anticentromere antibodies positive, thirty five (43%) anti-scl70 antibodies positive. The two investigators evaluated the presence of the following features: colour changes, pain, previous ulceration, current ulceration, pre-ulceration (discoloration and thinning of the skin), toenail changes, hyperkeratosis, calcinosis, onychomycosis, dry skin, skin sclerosis, warts, scleredema, flatfoot. The presence of paresthesias, cramps, metatarsalgia were also investigated. <h3>Results</h3> The diagram reports the prevalence of foot manifestations in the 81 SSc patients. Most SSc patients suffer from symptoms related to their feet, particularly dry skin (70%), hyperkeratosis (plantar 58%, finger V 63%), Raynaund9s phenomenon (59%), cramps (55%). No statistically significant differences were found between diffuse and limited SSc groups. <h3>Conclusions</h3> Our study suggests that, in patients with SSc, foot problems are common and potentially disabling. A careful assessment of the feet should always be performed in these patients, in order to identify problems at an early stage. <h3>References</h3> La Montagna G et al. Semin Arthritis Rheum 2002. Sari-Kouzel H et al. Rheumatology (Oxford) 2001. <h3>Disclosure of Interest</h3> None declared
Blood-based biomarkers in patients (pts) with metastatic colorectal cancer (mCRC) treated with FOLFOX or FOLFIRI plus bevacizumab (Bev), cetuximab (Cetux), or Bev plus Cetux: Results from CALGB 80405 (Alliance).
Authors: Andrew B. Nixon, Alexander Sibley, Ace Joseph Hatch, Yingmiao Liu, Chen Jiang, Flora Mulkey, Mark D. Starr, John C. Brady, Donna Niedzwiecki, Federico Innocenti, Alan P. Venook, Howard S. Hochster, Heinz-Josef Lenz, Bert H. O'Neil, Kouros Owzar, Herbert Hurwitz
Journal: Journal of Clinical Oncology (2016)

3597 Background: CALGB 80405 was a randomized phase III trial comparing FOLFOX or FOLFIRI + Bev, Cetux or both. Results showed no significant differences between Bev and Cetux in progression-free survival (PFS) or overall survival (OS). The primary objective of our study was to validate 7 biomarkers previously identified to be predictive for outcome for either Bev or Cetux. Methods: Baselineplasma samples were analyzed via multiplex ELISA technology for Ang-2, sCD73, sHER3, HGF, IL-6, SDF-1, and VEGF-D. The markers were correlated with PFS and OS using univariate Cox proportional hazards models stratified by chemotherapy (chemo); predictive markers were tested by adding a treatment by analyte interaction term to the model. Exploratory analyses included a chemo by biologic by marker term. Results: Baseline samples were available from 715 KRAS wild type pts treated with Bev or Cetux. No prespecified biomarkers were predictive for OS or PFS after multiple testing correction. However, lower levels of VEGF-D were associated with greater benefit from Bev for PFS (uncorrected interaction p = 0.049; HR 0.69 [95% CI 0.48-1.00]). Based on exploratory analyses, a potential 3-way interaction between chemo, biologic, and VEGF-D levels with respect to PFS was observed (p = 0.028). In subset analyses, VEGF-D was found to predict for benefit from Bev in pts treated with FOLFOX (p = 0.0028; HR 0.50 [95% CI 0.31-0.79]), but not in pts treated with FOLFIRI (p = 0.53; HR 1.27 [95% CI 0.59-2.73]). IL-6 was strongly prognostic for PFS and OS (p < 0.0001). Conclusions: While the pre-specified criteria for validation of these markers was not met, these data suggest a role for VEGF-D in mediating resistance to Bev, particularly for pts receiving FOLFOX. These findings are consistent with prior observations and highlight the potential importance of alternate VEGF ligands in response to anti-VEGF therapeutics. In addition, IL-6 was found to be strongly prognostic, highlighting the importance of inflammation in mCRC. Additional analyses are ongoing. Support: U10CA180821, U10CA180882. ClinicalTrials.gov Id: NCT00265850
FRI0730 The need for hospital admission for systemic lupus erythematosus in western australia leads to a doubling of the all-cause mortality risk as seen in controls, especially for medicare reliant and male patients
Authors: WD Raymond, D Preen, C Inderjeeth, H Keen, J Nossent
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hospitalisation for Systemic Lupus Erythematosus (SLE) is a significant event. <h3>Objectives</h3> We aimed to understand the factors leading to an incident admission and its impact on long term outcome in SLE patients in Western Australia (WA). <h3>Methods</h3> Using whole-population data linkage of hospital admissions, cancer registrations and death records in WA from 1980 to 2015, we performed a retrospective comparative analysis for all patients admitted with a first ever primary diagnosis of SLE (ICD-9-CM 695.4, 710.0, ICD-10-AM L93.0 &amp; M32). For SLE patients, we analysed annual incident hospitalisation rates and compared patient characteristics, all-cause mortality and cancer risk (by Kaplan-Meier and Cox regression) versus age- and gender-matched controls free of rheumatic disease. <h3>Results</h3> The incident hospitalisation rate for SLE (mean 20.9/million/year (CI: 11–35) showed little variation. SLE patients were younger, more likely to be Indigenous, uninsured, have kidney and cardiovascular disorders and to die during their first hospitalisation (Table 1). Cancer risk was equivalent, but a first admission for SLE doubled the risk of subsequent death (OR=1.99, CI: 1.5– 2.7, p&lt;0.001) (Figure 1/Table 2). Medicare reliance (OR 1.7, CI: 1.4 – 1.9, p=0.001) and male gender (OR 1.4, CI: 1.0 – 1.8, p&lt;0.04) were the strongest independent predictors of death. <h3>Conclusions</h3> Hospitalisation rates for SLE in WA have not decreased over 25 years. Once hospital-based management for SLE was required, the risk of all-cause mortality doubled compared to age and gender-matched controls. This risk was greatest in Medicare reliant or male SLE patients and not due to increased cancer risk. <h3>Disclosure of Interest</h3> None declared
Romosozumab — Promising or Practice Changing?
Authors: Clifford J Rosen
Journal: New England Journal of Medicine (2017)

Over the past decade, the osteoporosis landscape has changed. Even though more treatment options are available, fewer measurements of bone mass are being performed and fewer prescriptions for antiosteoporosis agents are being written — the last probably related to concerns about known side effects of bisphosphonates, such as atypical femoral fractures and osteonecrosis of the jaw. Even among patients with osteoporosis who have had a fracture and are then prescribed bisphosphonates, 70% are nonadherent within a year.1 Denosumab, another antiresorptive agent with proven efficacy, is rarely associated with atypical fractures and requires that patients continue to receive therapy indefinitely. Teriparatide, . . .
Contradictory effects of mitochondria‐ and non‐mitochondria‐targeted antioxidants on hepatocarcinogenesis by altering DNA repair in mice
Authors: Bibo Wang, Jing Fu, Ting Yu, An Xu, Wenhao Qin, Zhishi Yang, Yao Chen, Hongyang Wang
Journal: Hepatology (2017)

Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, antioxidants may still play a role in cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non‐mitochondrial‐ and mitochondrial‐targeted antioxidants. Utilizing mouse models of chemical hepatocarcinogenesis, we showed that administration of non‐mitochondria‐targeted antioxidants N ‐acetylcysteine (NAC) and the soluble vitamin E analog, Trolox, prevented tumorigenesis, whereas administration of mitochondria‐targeted antioxidants SS‐31 (the mitochondria‐targeted peptide) and Mito‐Q (a derivative of ubiquinone) facilitated tumorigenesis. RNA sequencing revealed that NAC and SS‐31 caused very different changes in the oxidation‐reduction state and DNA damage response. In diethylnitrosamine (DEN)‐treated primary hepatocytes, NAC and Trolox alleviated DNA damage by activating ataxia‐telangiectasia mutated (ATM)/ATM and Rad3‐related (ATR) for DNA repair whereas SS‐31 and Mito‐Q aggravated damage by inactivating them. Interestingly, partial recovery of SS‐31‐scavengened mitochondrial reactive oxygen species (mtROS) could alleviate SS‐31‐aggravated DNA damage. Localization of ATM between mitochondria and nuclei was altered after NAC and SS‐31 treatment. Furthermore, blockage of phospho‐ATR (p‐ATR) led to the recurrence of NAC‐ameliorated DEN HCC. In contrast, reactivation of p‐ATR blocked SS‐31‐promoted DEN HCC. Conclusion: These results demonstrate that the type of antioxidants plays a previously unappreciated role in hepatocarcinogenesis, and provide a mechanistic rationale for exploring the therapeutic use of antioxidants for liver cancer. (H epatology 2018;67:623‐635).
AB0602 Carotid atheroesclerotic plaques detected by ultrasound in systemic sclerosis patients under 55 years old
Authors: I Sanz Pérez, F Martínez Valle, A Guillén del Castillo, N Pizzi, R Solans Laque, E Callejas Moragas, I Gonzalez Nieto, V Fonollosa Pla, CP Simeόn Aznar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In Systemic sclerosis (SSc), as in other autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus, cardiovascular events are one of the most frequent causes of mortality not attributed to the disease itself. <h3>Objectives</h3> The aim of this study was to assess the presence of subclinical atherosclerosis by carotid Doppler ultrasound in SSc patients under 55 years. <h3>Methods</h3> We conducted a cross-sectional study that included 78 SSc patients without cardiovascular events from H. Vall d9Hebron cohort (Barcelona). Carotid Doppler ultrasound was performed to measure the Carotid Intima Media Thickness (CIMT) of common carotid artery (CCA) and detection of cholesterol plaques in CCA, bulb and internal and external carotid arteries, according to Mannheim consensus criteria. The results were compared to a healthy cohort from Barcelona, adjusted to age and sex<sup>1</sup>. We used SCORE for populations with low risk and REGICOR as cardiovascular risk assessment charts. <h3>Results</h3> Risk factors and SSc related features are described in table 1. Twenty three patients (29.5%) had carotid plaques (CP) being the presence of CP statistically significant compared to the healthy cohort (29.5% vs 15.6%; p&lt;0.05; IC 0.04–0.24). None of the patients were catalogued as high risk according to SCORE chart. According to REGICOR chart, 4 patients (5.1%) were catalogued as intermediate risk and none as high risk. The four intermediate risk patients had CP. Carotid Intima Media Thickness mean (CIMTm) and maximum (CIMTmax), were statistically significant increased compared to the healthy cohort (CIMTm 0,57 vs 0,53; p&lt;0,05 and CIMTmax 0,74 vs 0,61; p&lt;0,05). We performed multivariate regression analysis. Age, CIMTmax, low High Density Lipid (HDL), the presence of pulmonary hypertension, and Diffuse cutaneous SSc patients were independent factors for the presence of CP. <h3>Conclusions</h3> SSc patients under 55 years old often have subclinical atheromatous disease which could be detected by carotid ultrasound. Risk charts do not correlate with the presence of subclinical atheromatous disease. The presence of carotid plaque is more frequent in SSc patients with pulmonary hypertension, diffuse cutaneous subtype and patients with low HDL. CIMT could be useful although it is currently not recommended in cardiovascular risk guidelines. <h3>References</h3> Junyent M, Gilabert R, Núñez I, Corbella E, Vela M, Zambόn D, et al. Carotid ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness values and plaque frequency in a Spanish community cohort. Med Clin (Barc). 2005;125(20):770–4. <h3>Disclosure of Interest</h3> None declared