tbuckley/cabot-search huggingface dataset:
AB0140 The role of raf kinase inhibitory protein in rheumatoid arthritis
Authors: Y.-H. Cheon, Y.S. Suh, S.M. Yi, M. Kim, S.-I. Lee, H.S. Noh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of the joints and is characterised by immune cell infiltration, synovial hyperplasia, and destruction of cartilage and underlying bone <sup>1</sup>. Raf kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, has been implicated as a suppressor of metastasis and NF-κB pathway in cancers <sup>2</sup>. <h3>Objectives</h3> The NF-κB and ERK pathways are considered to be one of the most important pro-inflammatory signalling pathways in RA. Therefore, RKIP might be a potential therapeutic target for RA. However, whether and how RKIP regulates RA is not fully understood. The present study was performed to examine whether and how RKIP are differentially regulated in RA. <h3>Methods</h3> The expressions of RKIP were assessed in synovial tissue, fluid and fibroblast-like synoviocytes (FLS) from patients with RA and osteoarthritis (OA) by immunofluorescence staining and western blotting. RA- or OA-FLS were infected with either a recombinant adenoviral RKIP overexpressing vector (Ad-RKIP) or shRNA-expressing vector (Ad-shRKIP). Control cells infected with a GFP-targeted recombinant adenoviral vector (Ad-shGFP) (figure 1C). And then, we investigated the effects of RKIP on the migratory activity and invasion rates of FLS by transwell migration and invasion assay. <h3>Results</h3> Here, we show that RKIP expression is inversely correlated with RA. The levels of RKIP were significantly decreased in fibroblast-like synoviocytes (FLS), synovial fluid and synovium of RA patients compare to OA patients. And also find that migration and invasion of RA-FLS were significantly increased by the inhibition of RKIP compare to OA-FLS. Knockdown of RKIP in RA or OA-FLS resulted in a dramatic increase of MMP3 and IL6. We also found osteoclastogenesis of RAW cells were increased by the knockdown of RKIP. <h3>Conclusions</h3> Our data identify a role of RKIP in RA and suggest that further studies on the potential involvement of RKIP will be beneficial in better understanding the pathology of and providing a new target for treatment for RA. <h3>References</h3> [1] Ospelt C. Synovial fibroblasts in 2017. RMD Open2017;3(2):e000471. [2] Yesilkanal AE, Rosner MR. Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer. Crit Rev Oncog. 2014;19:447–454. [3] Noh HS, Hah YS, Ha JH, Kang MY, Zada S, Rha SY, Kang SS, Kim HJ, Park J, Byun J, Hahm JR, Shin JK, Jeong S, Lee Y, Kim DR. Regulation of the epithelial to mesenchymal transition and metastasis by Raf kinase inhibitory protein-dependent Notch1 activity. Oncotarget2016;7(4):4632–46. <h3>Disclosure of Interest</h3> None declared
SAT0369 Comparison of risk factors for cardiovascular diseases in pts with cppd gout and osteoarthritis
Authors: S. Vladimirov, M. Eliseev, O. Zhelyabina, M. Chikina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The data on rates of comorbidities and risk factors for cardiovascular disease in CPPD is insufficient. <h3>Objectives</h3> To compare the rates of cardiovascular diseases, risk factors and the risk of death from cardiovascular disease in pts with CPPD, OA and gout. <h3>Methods</h3> The study included 488 patients: 232 CPPD (111 m and 121 f) pts, 60 OA (19 m and 41 f) pts and 196 (169 m and 27 f) gout pts. The OA diagnosis was established based on ACR criteria, the CPPD diagnosis – on McCarty criteria, and gout diagnosis – on the detection of monosodium urate crystals in synovial fluid. The mean age in CPPD pts was 57.6±18.2 y., OA pts – 57.5±8.5 y., and gout pts- 52.7±12.2 y. Serum levels of cholesterol, glucose, uric acid, and hsCRP were obtained in all pts, and thorough evaluation for cardiovascular diseases was performedas well as including SCORE (Systematic COronary Risk Evaluation) scale assessment. Statistica 10.0, and Biostatistics were used for statistical data processing. Differences were considered to be statistically significant at p&lt;0.05. <h3>Results</h3> Obtained data are presented in table 1. High or very high risk of cardiovascular death (SCORE scale) was identified in 47.8% of CPPD pts, was comparable to that in gout pts (48.9%) and exceeded the same in OA pts (33%) (p&lt;0.05). Higher probability of myocardial infarction (MI), chronic heart failure (CHF), chronic kidney disease stage ≥2 (CKD) and higher mean serum CRP levels were established in CPPD and gout patients as compared to OA pts. There was no difference in rates of stroke, thrombosis, arterial hypertension (AH), ischaemic disease (ICD), diabetes mellitus (DM 2), or in average glucose and cholesterol levels between CPPD, OA and gout pts. Average serum levels of uric acid were higher in patients with gout. <h3>Conclusions</h3> Cardiovascular risk in CPPD pts may be underestimated and suggests the need for further research. <h3>Disclosure of Interest</h3> None declared
Preparation and characterization of nanoparticles from quaternized cyclodextrin-grafted chitosan associated with hyaluronic acid for cosmetics
Authors: Sakhiran Sakulwech, Nattaya Lourith, Uracha Ruktanonchai, Mayuree Kanlayavattanakul
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Hyaluronic acid (HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin and, thus, limits its benefits to topical effects. Thus, the objective of this study is to prepare nanoparticles of quaternized cyclodextrin-grafted chitosan (QCD-g-CS) associated with HA in different molar ratios of QCD-g-CS and HA. The conjugation of the carboxylic moieties of HA and the amides of QCD-g-CS was confirmed by Fourier-transform infrared spectroscopy. Thus, the system was optimized to create nanoparticles with a small size (235.63 ± 21.89 nm), narrow polydispersity index (0.13 ± 0.02), and zeta potential of 16.07 ± 0.65 mV. The association efficiency and loading efficiency were determined by ultra-performance liquid chromatography as 86.77 ± 0.69% and 10.85 ± 0.09%, respectively. The spherical morphology of the obtained nanoparticles was confirmed by transmission electron microscopy. Moreover, the in-vitro hydrating ability was significantly higher (P < 0.001) than that of bulk HA (3.29 ± 0.41 and 1.71 ± 0.05 g water/g sample, respectively). The safety of these nanoparticles at concentrations in the range of 0.01–0.10 mg/ml was confirmed via tests on human skin fibroblasts. Together, these results demonstrate that the developed nanoparticles are promising for future applications in cosmetics.
Tissue Compatibility of SN‐38‐Loaded Anticancer Nanofiber Matrices
Authors: Alejandro Manzanares, Camilo A. Restrepo‐Perdomo, Gaia Botteri, Helena Castillo‐Ecija, Guillem Pascual‐Pasto, Francesc Cano, Laura Garcia‐Alvarez, Carles Monterrubio, Bonaventura Ruiz, Manuel Vazquez‐Carrera, Mariona Suñol, Jaume Mora, Jose A. Tornero, Alejandro Sosnik, Angel M. Carcaboso
Journal: Advanced Healthcare Materials (2018)

Abstract Delivery of chemotherapy in the surgical bed has shown preclinical activity to control cancer progression upon subtotal resection of pediatric solid tumors, but whether this new treatment is safe for tumor‐adjacent healthy tissues remains unknown. Here, Wistar rats are used to study the anatomic and functional impact of electrospun nanofiber matrices eluting SN‐38—a potent chemotherapeutic agent—on several body sites where pediatric tumors such as neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma arise. Blank and SN‐38‐loaded matrices embracing the femoral neurovascular bundle or in direct contact with abdominal viscera (liver, kidney, urinary bladder, intestine, and uterus) are placed. Foreign body tissue reaction to the implants is observed though no histologic damage in any tissue/organ. Skin healing is normal. Tissue reaction is similar for SN‐38‐loaded and blank matrices, with the exception of the hepatic capsule that is thicker for the former although within the limits consistent with mild foreign body reaction. Tissue and organ function is completely conserved after local treatments, as assessed by the rotarod test (forelimb function), hematologic tests (liver and renal function), and control of clinical signs. Overall, these findings support the clinical translation of SN‐38‐loaded nanofiber matrices to improve local control strategies of surgically resected tumors.
OP0206-HPR Outpatient follow up on demand for patients with rheumatoid arthritis – a two-year randomised controlled trial
Authors: A.-M.T. Sweeney, O.R. Madsen, L. Dreyer, A. Hansen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Medical treatment and care are often life-long in patients with rheumatoid arthritis (RA). During periods of stable illness, patients typically attend routine visits every 3–8 months at the rheumatology outpatient clinic. The arthritis may flare up between scheduled medical visits, but it may be difficult to get acute appointments with the rheumatologist. Scheduled routine visits may be in a stable and 'good' period without any symptoms and with no need for control and adjustment of treatment and care. Consequently, there is a demand for developing outpatient control procedures that cater to the needs of the individual patient and which support the patient's experience of active participation in the control and treatment of their own disease. <h3>Objectives</h3> To compare a new outpatient system based on patient self-controlled outpatient follow up (Open Outpatient Clinic System (OOCS)) with traditional scheduled routine visits at a rheumatology outpatient clinic. <h3>Methods</h3> A two-year RCT with RA patients aged 18 to 80 years with a disease duration of at least one year. Patients were recruited consecutively from the rheumatology outpatient clinic of a major university hospital in the Copenhagen area of (Denmark from Feb 2015 to Jan 2017) Patients were randomised electronically and stratified regarding bio-medicine. Joints were examined by a blinded rheumatologist. Patients in the intervention group received information about the disease, symptoms, treatment and use of the OOCS. Appointments for the control group were scheduled according to routine procedures. Outcome measures were collected at baseline, year 1 and year 2. Clinical parameters: Disease Activity Score 28 (DAS28), CRP, Visual Analogue Scale (VAS) pain and fatigue, number of tender and swollen joints (28 joints), X-ray of hands and feet. Psychological parameters: VAS patient satisfaction, VAS patient trust, VAS patient involvement and quality of life (EQ-5D). <h3>Results</h3> 289 patients were included, 253 completed the 1 st year, 158 the 2nd year. The OOCS at year one and two was comparable to traditional scheduled routine procedures regarding clinical and psychological outcome measures. No radiological progression was detected. Patients in the intervention group made more phone calls to the clinic (244 versus 55) and had fewer visits compared to the control group (424 versus 513). Main results are shown in the table 1. <h3>Conclusions</h3> The OOCS met RA patient preferences for RA appointments and was comparable with traditional scheduled routine procedures regarding clinical and psychological outcomes after one year. Thus, the OOCS could provide a basis for a future organisation of outpatient care for patients with RA. <h3>Disclosure of Interest</h3> None declared
Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity
Authors: Qing Zhang, Jiacheng Bi, Xiaodong Zheng, Yongyan Chen, Hua Wang, Wenyong Wu, Zhengguang Wang, Qiang Wu, Hui Peng, Haiming Wei, Rui Sun, Zhigang Tian
Journal: Nature Immunology (2018)
Single-guidewire double-tip cannulation for difficult biliary access: the DTC technique
Authors: Tomazo Franzini, Rodrigo Rocha, Hugo Guedes, Vitor Brunaldi, Juan Serrano, Antônio Madruga Neto, Eduardo Moura
Journal: Endoscopy (2018)

The double-guidewire technique (DGT) for difficult biliary cannulation was first described by Dumonceau et al. in 1998 [1]. Over recent years, DGT has become an important advanced technique after unsuccessful standard retrograde cannulation (guidewire-assisted or contrast-assisted), especially when unintentional pancreatic duct cannulation occurs [2]. The success rate of DGT for biliary cannulation in randomized controlled trials ranges from 66.6 % to 92.5 % [3]. We describe a similar alternative to DGT using a single guidewire with two hydrophilic tips.
SAT0703 Racial disparities in gout and hyperuricemia – a united states general population study
Authors: M. Chen-Xu, C. Yokose, H.K. Choi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although African-Americans (AAs) have a higher prevalence of risk factors for gout and hyperuricemia (e.g., hypertension, obesity, and chronic kidney disease [CKD]) than Whites, data on their disease burden of gout and hyperuricemia remains scarce. <h3>Objectives</h3> To examine potential racial/ethnic disparities in the prevalence of gout and hyperuricemia, using a nationally-representative sample of United States (US) adults over the past 10 years (The National Health and Nutrition Examination Survey [NHANES] 2007–16). <h3>Methods</h3> Using data from 26 332 participants aged ≥20 years (13 539 females and 12 793 males) from NHANES 2007–16, we calculated the age-standardised prevalence of gout and hyperuricemia by race/ethnicity. Gout was defined by report of a diagnosis by a health professional, and hyperuricemia as a serum urate &gt;7.0 mg/dL (0.42 mmol/L) from participants' blood samples. Logistic regression was used to adjust for covariates, while taking into account clusters and strata of the complex survey design of NHANES. <h3>Results</h3> The age-standardised prevalence of gout was 3.7% for Whites and 4.7% for AAs, with the age-standardised prevalence of hyperuricemia being 12.7% and 14.9% for Whites and AAs, respectively. Compared to Whites, AAs had a 65% higher odds of gout among females (age-adjusted OR, 1.65; 95% CI, 1.14 to 2.38) and a 31% higher odds of gout among males (age-adjusted OR, 1.31; 95% CI, 1.05 to 1.63). Further adjustment by body-mass index (BMI) attenuated these associations to non-significance for both sexes (table 1). AA females had a higher odds of hyperuricemia than White females (age-adjusted OR, 2.17; 95% CI, 1.72 to 2.73), but not males (age-adjusted OR, 1.08; 95% CI, 0.95 to 1.22; <i>P</i> for interaction=0.002) (table 1). Among females, this association attenuated after further adjustment for BMI, hypertension, CKD, type 2 diabetes mellitus, household income, and education, but remained significant (adjusted OR, 1.52; 95% CI, 1.19 to 1.95). <h3>Conclusions</h3> These nationally-representative data indicate that AAs have a larger disease burden of gout and hyperuricemia than Whites, particularly among women. This burden appears to be at least partly due to a higher prevalence of risk factors for hyperuricemia in AAs.<sup>1</sup> <h3>Reference</h3> [1] Flegal KM, et al. JAMA2016Jun 7;315(21):2284–2291. <h3>Disclosure of Interest</h3> M. Chen-Xu: None declared, C. Yokose: None declared, H. Choi Grant/research support from: Ironwood and Ardea/AstraZeneca, Consultant for: Horizon and Selecta
PARE0006 A summary of key findings from the sjögren’s syndrome foundation’s national patient survey related to treatments and medications used
Authors: S. Taylor, K.M. Hammitt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sjögren's is a systemic autoimmune disease that affects the entire body. The purpose of this major national patient survey was to gain an understanding from adults who have been diagnosed with Sjögren's about the impact of the disease on their quality of life, including information on the treatments and medications used to manage the disease. <h3>Methods</h3> The<i></i> Sjögren's Syndrome Foundation (SSF) conducted the <i>Living with Sjögren's</i> survey between May 11 and July 11, 2016. Participants were recruited by Harris Poll from a pool of 9,252 active SSF patient members. The survey was conducted among adults aged 18 years or older who reported having been clinically diagnosed with Sjögren's by a physician or other medical professional. The survey asked closed-ended questions about patient experiences with Sjögren's and the impact it has on their quality of life. <h3>Results</h3> There were 3,072 survey responses (33% response rate), 2,963 of which were included in the analyses. Survey respondents were 96% female and 4% male; 32% were aged 60 years or less. On average, respondents reported using 8.8 medications and treatments to help manage their Sjogren's symptoms, with an average of more than four prescription medications and treatments. When comparing patients living with Sjogren's between 0–4 years and 5–9 years, respondents in the latter group reported using slightly more treatments, on average (8.7), compared to those living with Sjogren's for a shorter period (8.2 mean). Nearly all respondents (97%) reported using eye drops, artificial tears, or non-prescription eye ointments. Other medications reportedly used by a majority of respondents include ibuprofen or other anti-inflammatory agents (81%), disesase-modifying anti-rheumatic drugs (DMARDS) (67%), over-the-counter or prescription fluoride (67%), and corticosteroids (62%). Notably, patients 60 years and younger were significantly more likely than patients older than 60 years to have used health food supplements or remedies (90% vs. 87%), exercise (88% vs. 83%), and alternative therapies (70% vs. 58%) in attempt to treat their Sjogren's. Nearly all respondents (96%) indicated they wished that additional treatments for Sjogren's were available. Specifically, respondents indicated a need for new treatments for fatigue (63%), brain fog/forgetfulness (53%), sleep problems (51%), joint pain or swelling (48%) and muscle pain (43%). <h3>Conclusions</h3> Patients reported relying on a large number and variety of treatments to manage their Sjogren's as well as the need for new treatment options to treat the various manifestations of the disease. The findings from this survey will help to inform and support future SSF efforts to increase public and professional awareness of Sjögren's and encourage research into new treatments and a cure. <h3>Disclosure of Interest</h3> None declared
<i>Notes from the Field:</i> Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae from Less Common Enterobacteriaceae Genera — United States, 2014–2017
Authors: Maroya S. Walters, Medora Witwer, Yeon-Kyeng Lee, Valerie Albrecht, David Lonsway, J. Kamile Rasheed, Melissa Anacker, Paula Snippes-Vagnone, Ruth Lynfield, Alexander J. Kallen
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Infections with carbapenemase-producing carbapenemresistant Enterobacteriaceae (CP-CRE) are associated with high mortality rates (1).Carbapenemases encoded on plasmids can move between bacterial strains and have the potential to rapidly increase the proportion of Enterobacteriaceae resistant to carbapenems; as such, CP-CRE have been a particular focus of public health response.Although the Enterobacteriaceae family includes approximately 50 recognized genera, surveillance for CP-CRE has focused on the organisms most associated with clinical infections: Klebsiella spp., Enterobacter spp., and Escherichia coli (2,3).CRE from other, less commonly encountered genera (hereafter referred to as less common genera) have generally not been targeted for carbapenemase testing, in part, because some of these organisms possess intrinsic resistance to the carbapenem imipenem and others express species-specific chromosomal carbapenemases.However, these organisms can also harbor plasmid-mediated carbapenemases.This report describes CP-CRE from less common genera identified through reference testing at CDC and surveillance at the Minnesota Department of Health (MDH) Public Health Laboratory.CDC's Clinical and Environmental Microbiology Branch performs molecular testing on submitted CRE to detect Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-mediated metallo-β-lactamase (VIM), active-on-imipenem (IMP), and OXA-48-type carbapenemases.During January 1, 2014-May 25, 2017, CDC identified 1,039 CP-CRE, including 63 (6.1%) from the less common genera.Isolates from the less common genera were submitted by 23 states; Iowa (10; 16%) and Pennsylvania (seven; 11%) contributed the most.KPCproducing Citrobacter spp.(27; 42.9%) was the most common organism-mechanism combination identified (Table ).CRE producing a carbapenemase other than KPC are historically uncommon in the United States and often associated with health care exposures outside the United States.Epidemiologic data were available for 20 of 28 patients with non-KPC-CP-CRE from less common genera passively
Elective Nodal Irradiation Attenuates the Combinatorial Efficacy of Stereotactic Radiation Therapy and Immunotherapy
Authors: Ariel E. Marciscano, Ali Ghasemzadeh, Thomas R. Nirschl, Debebe Theodros, Christina M. Kochel, Brian J. Francica, Yuki Muroyama, Robert A. Anders, Andrew B. Sharabi, Esteban Velarde, Wendy Mao, Kunal R. Chaudhary, Matthew G. Chaimowitz, John Wong, Mark J. Selby, Kent B. Thudium, Alan J. Korman, David Ulmert, Daniel L.J. Thorek, Theodore L. DeWeese, Charles G. Drake
Journal: Clinical Cancer Research (2018)

Abstract Purpose: In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of radiotherapy with immune checkpoint blockade (ICB). Experimental Design: We developed a preclinical model to compare stereotactic radiotherapy (Tumor RT) with or without ENI to examine immunologic differences between radiotherapy techniques that spare or irradiate the DLN. Results: Tumor RT was associated with upregulation of an intratumoral T-cell chemoattractant chemokine signature (CXCR3, CCR5-related) that resulted in robust infiltration of antigen-specific CD8+ effector T cells as well as FoxP3+ regulatory T cells (Tregs). The addition of ENI attenuated chemokine expression, restrained immune infiltration, and adversely affected survival when combined with ICB, especially with anti-CLTA4 therapy. The combination of stereotactic radiotherapy and ICB led to long-term survival in a subset of mice and was associated with favorable CD8 effector-to-Treg ratios and increased intratumoral density of antigen-specific CD8+ T cells. Although radiotherapy technique (Tumor RT vs. ENI) affected initial tumor control and survival, the ability to reject tumor upon rechallenge was partially dependent upon the mechanism of action of ICB; as radiotherapy/anti-CTLA4 was superior to radiotherapy/anti-PD-1. Conclusions: Our results highlight that irradiation of the DLN restrains adaptive immune responses through altered chemokine expression and CD8+ T-cell trafficking. These data have implications for combining radiotherapy and ICB, long-term survival, and induction of immunologic memory. Clinically, the immunomodulatory effect of the radiotherapy strategy should be considered when combining stereotactic radiotherapy with immunotherapy. Clin Cancer Res; 24(20); 5058–71. ©2018 AACR.