tbuckley/cabot-search huggingface dataset:
THU0093 Nadph oxidases associated production of reactive oxygen species in rheumatoid arthritis
Authors: S.-J. Yoo, S.W. Kang, J. Kim, I.S. Yoo, C.K. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Reactive oxygen species (ROS) is produced during metabolism of Oxygen. ROS is important in cell signalling and homeostasis. Production of ROS can be elevated in stressful condition. Oxidative stress has been known to be related with the disease like infection and malignancy. NADPH oxidases (Nox) are membrane proteins which produce ROS. <h3>Objectives</h3> In this study we aimed to investigate the role of Nox in rheumatoid arthritis (RA) associated with production of ROS. <h3>Methods</h3> Nox and Granulocyte macrophage colony-stimulating factor (GMCSF) messenger ribonucleic acid (mRNA) were analysed in fibroblast like synoviocyte (FLS) of patients with RA and osteoarthritis (OA) by reverse transcription polymerase chain reaction. Amount of ROS which is produced in FLS of patients with RA and OA is determined using the cell permeant fluoroprobe 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA) by flowcytometry. Same experiments were performed after treatment with cytokine, interleukin (IL)−17 and tumour necrosis factor-α (TNF-α). <h3>Results</h3> Among Nox subunits (Nox1, Nox2, Nox4, Nox5, DUOX1, DUOX2, NOXA1, NOXO1), NOXA1 and NOXO1 mRNA were expressed higher in RA FLS than in OA FLS. After treatment with IL-17 and TNF-α for 24 hours GMCSF, Nox1 and NOXO1 mRNA in RA FLS were elevated. Amount of ROS production was also elevated after treatment with IL-17 and TNF-α. When RA FLS were treated with bromopyruvic acid (BrPa), glucolysis inhibitor by inhibition of hexokinase II, GMCSF mRNA and ROS were decreased and Nox1 and Nox4 mRNA showed no diffrence. <h3>Conclusions</h3> Several factors may be involved between ROS and Nox in RA FLS. Both ROS and Nox were elevated in inflammatory condition in RA FLS. From this result we expect that Nox-targeted therapy may be effective for treatment with RA. <h3>References</h3> [1] Drummond GR, Selemidis S, Griendling KK, Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov2011;10:453–71. [2] Neumann E, Lefèvre S, Zimmermann B, Gay S, Müller-Ladner U. Rheumatoid arthritis progression mediated by activated synovial fibroblasts. Trends Mol Med2010;16:458–68. [3] Rodiño-Janeiro BK, Paradela-Dobarro B, Castiñeiras-Landeira MI, Raposeiras-Roubín S, González-Juanatey JR, Alvarez E. Current status of NADPH oxidase research in cardiovascular pharmacology. Vasc Health Risk Manag2013;9:401–28. [4] Xiao C, Li J, Dong X, He X, Niu X, Liu C, Zhong G, Bauer R, Yang D, Lu A. Anti-oxidativeand TNF-α suppressive activities of puerarin derivative (4AC) in RAW264.7 cells and collagen-induced arthritic rats. Eur J Pharmacol2011;666:242–50. [5] Yun JM, Chien A, Jialal I, Devaraj S. Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights. J Nutr Biochem2012;23:699–705. <h3>Disclosure of Interest</h3> None declared
OP0215 Time-related trends in opioid purchases among patients with early inflammatory arthritides
Authors: P. Muilu, V. Rantalaiho, H. Kautiainen, L.J. Virta, K. Puolakka
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treatment outcomes in inflammatory arthritis (IA) have improved during the past decades; however, pain management remains a great challenge. There has been a concern of overprescription of opioids during recent years. <h3>Objectives</h3> The aim of this study was to explore the frequency of opioid users in patients with newly-onset IA in comparison with the general Finnish population and discover the proportion of long-term opioid users. <h3>Methods</h3> From the nationwide register maintained by the Social Insurance Institution of Finland we collected all incident adult patients with the five most common IAs between 2010–14. For each case, three eligible controls were randomly selected and individually matched according to age, sex, and place of residence. Opioid purchases between 2009–2015 were obtained from the drug prescription register and evaluated one year before and after the index date (decision of special reimbursement for antirheumatic drugs), further dividing the observation time into 3 month periods. Long-term use was defined as opioid purchases at least in three of these periods per year. All opioids from mild to strong were included. <h3>Results</h3> Data on different diagnosis groups are presented in table 1. The proportion of opioid purchasers among IA patients and their controls are shown in figure 1A-E. Also, odds ratio for long-term opioid use after the index date is shown in figure 1F. <h3>Conclusions</h3> IA patients are more likely to buy opioids one year before and one year after the diagnosis and presciption of antirheumatic medication than controls from the general population. The opioid purchases peak just before the index date in most IA patients. Long-term opioid use is also more common among patients with newly-onset IA, especially among those with SpA. <h3>Disclosure of Interest</h3> P. Muilu Grant/research support from: Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, Rheumatology Research Foundation, and Finnish Cultural Foundation., V. Rantalaiho Grant/research support from: Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, and Tampereen Reumayhdistys, H. Kautiainen: None declared, L. Virta: None declared, K. Puolakka: None declared
AB1292 Metabolic syndrome and its components among hispanic ra patients: a case control study
Authors: D.A. Galarza-Delgado, J.R. Azpiri-López, I.J. Colunga-Pedraza, A.H. Guillén-Lozoya, E.E. Abundis-Márquez, J.A. Dávila-Jiménez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Metabolic syndrome (MetS) comprises a group of risk factors for type 2 diabetes and cardiovascular diseases. MetS is responsible for a three-fold increase in the risk of atherosclerotic cardiovascular diseases (ASCVD) and increased mortality compared to general population.<sup>1</sup> The frequency of MetS in RA patients is 14% to 56%. However, although many studies have reported a higher prevalence of MetS among RA patients, a number of studies have reported a higher prevalence of MetS in healthy controls.<sup>2</sup> Despite the importance of detection of MetS and its role in RA patients, information is scarce. <h3>Objectives</h3> To compare the prevalence of MetS among Mexican-mestizo RA-patients and matched controls. <h3>Methods</h3> Design: observational, cross-sectional, case-control study. Patients of 40 to 75 years old who fulfilled the 2010 ACR/EULAR and/or the 1987 ACR classification criteria for RA were consecutively enrolled. Patients with any other rheumatic disease were excluded. Our study used ATP III Criteria (Abdominal obesity: Men&gt;102 cm Women&gt;88 cm; Triglyceride level ≥150 mg/dL; HDL:&lt;40 mg/dL for men&lt;50 mg/dL for women; Blood pressure ≥130/≥85 mmHg; Fasting glucose ≥100 mg/dL) to classify patients with MetS. <h3>Results</h3> There were no differences in any independent variable of these patients. However there was a higher prevalence of high blood pressure in controls than RA patients (See Table 1). <h3>Conclusions</h3> There is no difference in the diagnosis of MetS in RA patients than control population. However, the role of the diagnosis of MetS in patients with RA represents an important task in the management of the disease in order to reduce its high cardiovascular risk. <h3>References</h3> [1] Hallajzadeh, J., Safiri, S., Mansournia, M. A., Khoramdad, M., Izadi, N., Almasi-Hashiani, A., Karamzad, N. (2017). Metabolic syndrome and its components among rheumatoid arthritis patients: A comprehensive updated systematic review and meta-analysis. PloS one, 12(3), e0170361. [2] Zafar Z, H.Mahmud T, Rasheed A, AhmedWagan A. Frequency of metabolic syndrome in Pakistani cohort of patients with rheumatoid arthritis. J Pak Med Assoc. 2016; 66(6):671–6. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared
Resection of a giant gastric mass using an ultrasonic scalpel with endoscopic assistance
Authors: Xiang-lei Yuan, Shui-fang Wang, Lian-song Ye, Chun-cheng Wu, Xian-hui Zeng, Naveed Khan, Bing Hu
Journal: Endoscopy (2018)

A 55-year-old woman presented with melena of 4 days’ duration. Upper endoscopy showed a giant pedunculated mass, about 6 cm in size, in the gastric cardia, with hyperemia and erosion ([Fig. 1]). Histopathology of biopsies found no evidence of malignancy, and endoscopic ultrasonography showed a low-echoic mass with nonhomogeneous echo ([Fig. 2]). Considering the high risk of bleeding associated with endoscopic resection of such a thick stalk of the mass, and because the patient refused recommended surgical resection, we planned to resect the mass by using an ultrasonic scalpel through a gastric fistula formed by percutaneous endoscopic gastrostomy (PEG).
FRI0295 Inhibition of cathepsin s leads to suppression of antigen specific t cells from patients with primary sjÖgren syndrome
Authors: P. Hargreaves, M. Theron, F.A. Kolb, M. Manchester, B. Reis, A. Tiaden, D. Kyburz, T. Manigold
Journal: Annals of the Rheumatic Diseases (2018)

Objectives: In this study, we explored for the first time the frequency and phenotype of circulating ILCs in pSS and SLE and their relation to the IFN signature.Methods: Frequencies and phenotypes of ILC subsets and pDCs were assessed by flow cytometry in peripheral blood of patients with pSS (n=20), SLE (n=20) and healthy controls (n=17).Patients were stratified by the presence or absence of an IFN signature as assessed by RT-qPCR on peripheral blood mononuclear cells as previously described.Brkic ARD 2013 Results: Results ILC1 numbers were increased in peripheral blood of patients with SLE as compared to healthy controls and in pSS patients ILC1 numbers correlated with disease activity (ESSDAI score), serum IgG levels and anti-SSB autoantibodies (all p<0.05).Numbers of ILC1, ILC2 or ILC3 did not significantly differ between patients with SLE and pSS.However, patients with a high expression of the type I IFN signature had significantly decreased numbers of ILC2 and ILC3 (p=0.04 and p=0.02, respectively).The decrease of ILC2s and ILC3s was related to increased expression of Fas (CD95) on these cells in patients with a high type I IFN signature (both p=0.01).Conclusions: Both in SLE and pSS, a type I IFN signature is related to reduced numbers of circulating ILC2s and ILC3s in association with increased Fas expression on these cells possibly rendering them more susceptible to Fas/FasLdependent apoptosis at peripheral sites.
How We Measure Surgical Trainee Performance Matters
Authors: Ira L. Leeds, Sandra R. DiBrito, Bethany C. Sacks
Journal: JAMA Surgery (2018)

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NHS must work harder to retain clinical workforce, says NHS Confederation chief
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A lack of qualified clinical staff is likely to be “the biggest impediment” to the NHS making effective use of extra funding expected from the government, the chief executive of the body representing NHS organisations in England has warned.

In a keynote speech to the NHS Confederation conference in Manchester on 14 June, Niall Dickson said that the NHS must act quickly to tackle a workforce crisis that was one of the biggest obstacles to creating a sustainable system and managing growing demand over the next 10-15 years.

He …
Association of Somatic Driver Alterations With Prognosis in Postmenopausal, Hormone Receptor–Positive, HER2-Negative Early Breast Cancer
Authors: Stephen J. Luen, Rebecca Asher, Chee Khoon Lee, Peter Savas, Roswitha Kammler, Patrizia Dell’Orto, Olivia Maria Biasi, David Demanse, Lellean JeBailey, Sinead Dolan, Wolfgang Hackl, Beat Thuerlimann, Giuseppe Viale, Marco Colleoni, Meredith M. Regan, Sherene Loi
Journal: JAMA Oncology (2018)

A range of somatic driver alterations has been described in estrogen receptor-positive, HER2-negative (ER+/HER2-) early breast cancer (BC); however, the clinical relevance is unknown.To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit associated with endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole.The Breast International Group (BIG) 1-98 trial randomized 8010 postmenopausal patients with hormone receptor-positive, operable, invasive BC to monotherapy with letrozole, tamoxifen, or a sequential strategy for 5 years. Driver alterations were characterized using next-generation sequencing in primary tumors from a subset of 764 patients from 7329 eligible patients with ER+/HER2- BC, with 841 distant recurrences after a median of 8.1 years of follow-up. To correct for the oversampling of distant recurrences, weighted analysis methods were used. This analysis was conducted from April 4, 2016, to November 30, 2016.The prevalence of driver alterations, associations with clinicopathologic factors, distant recurrence-free interval, and treatment interactions were analyzed. Multivariable analyses were performed to adjust for clinicopathologic factors.Of 764 samples, 538 (70.4%), including 140 distant recurrence events, were successfully sequenced. Nineteen driver alterations were observed with 5% or greater frequency, with a mean of 4 alterations (range, 0-15) per tumor. PIK3CA mutations were the most common (49%) and were significantly associated with reduction in the risk for distant recurrence (hazard ratio [HR], 0.57; 95% CI, 0.38-0.85; P = .006). TP53 mutations (HR, 1.92; 95% CI, 1.21-3.04; P = .006), amplifications on 11q13 (HR, 2.14; 95% CI, 1.36-3.37; P = .001) and 8p11 (HR, 3.02; 95% CI, 1.88-4.84; P < .001), and increasing number of driver alterations (HR per additional alteration, 1.18; 95% CI, 1.11-1.25; P < .001) were associated with significantly greater risk. Amplifications on 11q13 and 8p11 remained significant predictors in multivariable analysis, but not PIK3CA and TP53 mutations. Patients with tumors harboring kinase or helical domain PIK3CA mutations derived significantly greater benefit from letrozole over tamoxifen than patients whose tumors did not (P interaction = .002).In ER+/HER2- postmenopausal, early-stage BC, amplifications on 11q13 and 8p11 were significantly associated with increased risk for distant recurrence and PIK3CA mutations were predictive of greater magnitude of benefit from letrozole. With these findings, DNA-based classification may aid adjuvant treatment decision making in this setting.ClinicalTrials.gov Identifier: NCT00004205.
AB1288 Prediction of amenorrhea in female rheumatoid arthritis patients with tripterygium wilfordii hook f
Authors: C. Zhang, Y. Xu, M. Liu, X. He, C. Lu, A. Lu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> The Chinese anti-inflammatory and immunosuppressive herbal remedy <i>Tripterygium wilfordii Hook F</i> (TwHF) is a widely used and effective treatment for rheumatoid arthritis (RA). Ovarian failure is one of the most important adverse effects among pre-menopausal women with TwHF therapy. <h3>Objectives</h3> To construct a statistical model for pre-treatment prediction of amenorrhea after TwHF therapy. <h3>Methods</h3> In this retrospective study, potential predictors of amenorrhea including demographic and clinical data were retrieved. Multivariate logistic regression models were used to evaluate the association between pre-treatment variables and amenorrhea. The probability of amenorrhea was calculated for combinations of pre-treatment variables. <h3>Results</h3> Post-TwHF therapy amenorrhea rate was 10.9% (70 of 641). The mean age was 36.2±5.5 years, mean body mass index 22.5±7.5 kg/m2. Age was the strongest determinant of this adverse effect. In the final model, age &gt;36 years, cumulative dose &gt;4000 mg, and WBC&lt;4.1 × 10^9/L, were predictive of amenorrhea with adjusted odds ratios of 1.7 for TwHF therapy vs disease modifying antirheumatic drug (95% CI,1.2–3.2, p=0.017), 3.1 age &gt;40 years (95% CI,1.8–4.7, p&lt;0.001), 2.8 cumulative dose &gt;6000 mg (95% CI,1.6–4.3, p&lt;0.001), and 2.7 for WBC&lt;3.5 × 10^9/L (95% CI,1.4–6.3, p=0.012). The probability of amenorrhea can be as high as 76% or as low as 9% depending on the age, cumulative dose, WBC and the type of combination treatments employed. <h3>Conclusions</h3> This is first study to identify pre-treatment factors predictive of amenorrhea following TwHF therapy. Our model allows for optimum patient counselling and will help clarify expectations for the probability of amenorrhea following TwHF therapy. <h3>Reference</h3> [1] Chi Zhang, et al: Safety profiles of tripterygium wilfordii hook f: a systematic review and meta-analysis. Front. Pharmacol. 7:402, 2016. <h3>Acknowledgements</h3> The study was supported by the National Natural Science Foundation of China (No. 81503449). <h3>Disclosure of Interest</h3> None declared
AB1149 Cystic fibrosis and inflammatory arthritis requiring immunosuppression: a worrying combination?
Authors: M.E.T. Ibrahim, E. Clarke, K. Martin, D. Peckham, A. Jones, A. Horsley, P. Watson, J.E. Freeston
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inflammatory arthritis is a recognised complication of cystic fibrosis (CF) with an estimated prevalence of 2.3<sup>[i]</sup> to 8.5%<sup>[ii]</sup> of CF patients. Cystic fibrosis associated arthritis (CFA) constitutes the majority of this, but other there may be other co-morbid rheumatic disease. Concerns about use of immunosuppression in the context of chronic pulmonary infection, and consequent risk of destabilisation, may limit use of these medications when clinically indicated. Immunosuppressive therapy is used in patients with CF lung disease who have inflammatory rheumatic disease, inflammatory bowel disease, or who have had a liver transplant for CF-related liver disease. Some data on those receiving immunosuppression post-transplant has been published and reassuringly reported fewer courses of intravenous antibiotics following transplant.<sup>[iii]</sup> Reports of immunosuppressants being used in other contexts, including arthritis, are more sporadic. <h3>Objectives</h3> To assess prior use and safety outcomes of immunosuppressant therapy in adults with CF. <h3>Methods</h3> A retrospective case note review of patients with CF receiving disease modifying anti-rheumatic drugs from 2 large adult CF centres (total &gt;700 patients) from electronic records spanning 3–10 years. <h3>Results</h3> 41 patients were identified: 7 post liver transplant, 1 with inflammatory bowel disease, 1 with IgA nephropathy; 32 with inflammatory arthritis. There was one possible case of increased pulmonary exacerbation associated with methotrexate; they remained on treatment at the time of the study. There was no evidence that immunosuppression resulted in a fall in lung function necessitating cessation of treatment in any of these cases. Three patients stopped hydroxychloroquine and 1 patient stopped methotrexate due to non-respiratory side effects. Four of 7 patients responded to treatment with sulfasalazine for inflammatory arthritis, 3 stopped due to non-respiratory side effects. <h3>Conclusions</h3> No patients had immunosuppression stopped because of deterioration in lung disease. Steroids were not included in this analysis because duration and dose varied widely. However, it is important to note that they are frequently used in CF (particularly for allergic bronchopulmonary aspergillosis). Indeed 14% of all CF patients in these centres have had steroids in the last 6 months, of whom nearly half received a course of more than 6 months duration. Whilst our results are reassuring, the numbers remain small. Decisions must be made in conjunction with the multidisciplinary team, but CF in itself should not delay or stop treatment with immunosuppression where it is indicated. <h3>References</h3> [1] Rush, P. J., A. Shore, et al. (1986). [2] Bourke, S., M. Rooney, et al. (1987). [3] Dowman, J. K., D. Watson, et al. (2012). <h3>Disclosure of Interest</h3> None declared
Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study
Authors: Andrew Conway Morris, Deepankar Datta, Manu Shankar-Hari, Jacqueline Stephen, Christopher J. Weir, Jillian Rennie, Jean Antonelli, Anthony Bateman, Noel Warner, Kevin Judge, Jim Keenan, Alice Wang, Tony Burpee, K. Alun Brown, Sion M. Lewis, Tracey Mare, Alistair I. Roy, Gillian Hulme, Ian Dimmick, Adriano G. Rossi, A. John Simpson, Timothy S. Walsh
Journal: Intensive Care Medicine (2018)

Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.The study was registered with clinicaltrials.gov (NCT02186522).