tbuckley/cabot-search huggingface dataset:
FRI0269 Deficiency of glucocorticoid-induced leucine zipper (GILZ) disinhibits ifn pathways and exacerbates nephritis in the lyn-deficient murine model of lupus
Authors: C.T. Nataraja, E.F. Morand, J. Thomas, J. Harris, S.A. Jones
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease of unknown etiology. Lyn-deficient mice develop lupus-like autoimmunity due to hyperactive B cells resulting in excess IL-6 production, and cyclical exacerbation of inflammation by further activation of B and T cells. Tsantikos et al., 2010 C57BL/6 mice deficient in glucocorticoid-induced leucine zipper (GILZ), an intracellular protein involved in glucocorticoid effects on immunity, develop lupus-like autoimmunity and excess B cell activation. Jones et al., 2016. However, the effect of GILZ in lupus-prone mice is unknown. <h3>Objectives</h3> We aim to test the hypothesis that GILZ modulates autoimmunity in the lyn deficient murine model of lupus. <h3>Methods</h3> We generated GILZ-deficient mice on a <i>lyn</i>-deficient background (GILZ-lyn double knock out (DKO)) and compared them to WT and lynKO mice. The effects of GILZ deficiency on spleen weight, nephritis, Type I interferon-induced genes (ISG) and autoantibodies were examined. <h3>Results</h3> We observed heightened lupus-like autoimmunity in GILZ-lyn DKO mice, compared to LynKO, that include increased spleen weights (p=0.041) and more severe glomerulonephritis, especially segmental necrosis. A panel of ISG (<i>ifi44, usp18, oas3, cxcl10, isg15, mx1, irf7, stat1</i> and <i>ifit3)</i> and an overall ISG score was significantly increased (p=0.0023) in GILZ-lyn DKO mice compared to LynKO. In contrast, serum autoantibodies (dsDNA, Sm, histone, Jo-1, Scl-70, SSA, SSB, U1RNP, Ro52,) were not increased in GILZ-lyn DKO mice compared to LynKO mice. <h3>Conclusions</h3> In LynKO lupus-prone mice, spleen weight, glomerulonephritis, and ISG profiles were significantly exacerbated by GILZ deficiency, while autoantibody titres were unaffected. This suggests that endogenous GILZ exerts an inhibitory effect on IFN pathways, in this lupus model. Therefore, GILZ potentially regulates the cycle of inflammation in SLE by inhibiting IFN responses downstream of autoantibodies. A GILZ-based treatment could be a potential therapeutic strategy in SLE. <h3>References</h3> [1] Jones SA, Toh AE, Odobasic D, Oudin MA, Cheng Q, Lee JP, … Morand EF. Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus. Ann Rheum Dis, 2016;75(4):739–747. doi:10.1136/annrheumdis-2015-207744 [2] Tsantikos E, Oracki SA, Quilici C, Anderson GP, Tarlinton DM, Hibbs ML. Autoimmune disease in Lyn-deficient mice is dependent on an inflammatory environment established by IL-6. J Immunol2010;184(3):1348–1360. doi:10.4049/jimmunol.0901878 <h3>Acknowledgements</h3> NHMRC <h3>Disclosure of Interest</h3> None declared
What’s hot that the other lot got
Authors: Emmanuel Okenyi, Nikki Jahnke
Journal: Thorax (2019)

Heroin smoking, rather than injection, has become more prevalent over the last 30 years. Drug smokers have a significant burden of respiratory morbidity with higher hospital admission rates compared with the general chronic obstructive pulmonary disease (COPD) population; this may in part be due to limited engagement with conventional health services. Burhan and colleagues ( Chest 2018; doi: 10.1016/j.chest.2018.08.1049) performed a cross-sectional study in Liverpool to investigate the prevalence and severity of COPD in this population, and the acceptability of attaching COPD screening services to community specialist drug services. Of the 1082 patients approached to participate, 753 completed the full assessment, 70% had some form of airways disease, with 260 (35%), 155 (21%) and 112 (15%) found to have COPD, asthma and asthma–COPD overlap, respectively. Interestingly, around half of participants who had reported a previous COPD diagnosis did not have evidence of irreversible obstructive spirometry, reiterating the importance of objective assessment of respiratory disease, even in a high-risk population. Longer duration, rather than quantity per se, of tobacco and illicit drug inhalation were associated with increased risk of …
Combined Impact of Aberrant Immunophenotypes, Somatic Mutations and Cytogenetic Aberrations on the Probability of Developing Myelodysplasia in Patients with Cytopenias of Undetermined Significance
Authors: Wolfgang Kern, Manja Meggendorfer, Constance Baer, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2018)
Therapeutic Targeting of an RNA Splicing Factor Network for the Treatment of Myeloid Neoplasms
Authors: Sydney X. Lu, Eric Wang, Alessandro Pastore, Chen Xufeng, Jochen Imig, Stanley C Lee, Yohana Ghebrechristos, Akihide Yoshimi, Lillian E Bitner, Michelle Ki, Andreas Kloetgen, Kuan-Ting Lin, Raoul Tibes, Adrian R. Krainer, Taisuke Uehara, Takashi Owa, Iannis Aifantis, Omar I Abdel-Wahab
Journal: Blood (2018)
An Observational Study of Deep Learning and Automated Evaluation of Cervical Images for Cancer Screening
Authors: Liming Hu, David Bell, Sameer Antani, Zhiyun Xue, Kai Yu, Matthew P Horning, Noni Gachuhi, Benjamin Wilson, Mayoore S Jaiswal, Brian Befano, L Rodney Long, Rolando Herrero, Mark H Einstein, Robert D Burk, Maria Demarco, Julia C Gage, Ana Cecilia Rodriguez, Nicolas Wentzensen, Mark Schiffman
Journal: JNCI Journal of the National Cancer Institute (2018)

Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a "deep learning"-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer.A population-based longitudinal cohort of 9406 women ages 18-94 years in Guanacaste, Costa Rica was followed for 7 years (1993-2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera ("cervicography"), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0-1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided.Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P < .001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P < .001). A single visual screening round restricted to women at the prime screening ages of 25-49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ [AIS]) diagnosed cumulatively in the entire adult population (ages 18-94 years) while referring 11.0% for management.The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.
Inflammatory bowel disease and new-onset psychiatric disorders in pregnancy and post partum: a population-based cohort study
Authors: Simone N Vigod, Paul Kurdyak, Hilary K Brown, Geoffrey C Nguyen, Laura E Targownik, Cynthia H Seow, M Ellen Kuenzig, Eric I Benchimol
Journal: Gut (2019)

Objective Patients with inflammatory bowel disease (IBD) have an elevated risk of mental illness. We determined the incidence and correlates of new-onset mental illness associated with IBD during pregnancy and post partum. Design This cohort study using population-based health administrative data included all women with a singleton live birth in Ontario, Canada (2002–2014). The incidence of new-onset mental illness from conception to 1-year post partum was compared between 3721 women with and 798 908 without IBD, generating adjusted HRs (aHR). Logistic regression was used to identify correlates of new-onset mental illness in the IBD group. Results About 22.7% of women with IBD had new-onset mental illness versus 20.4% without, corresponding to incidence rates of 150.2 and 132.8 per 1000 patient-years (aHR 1.12, 95% CI 1.05 to 1.20), or one extra case of new-onset mental illness per 43 pregnant women with IBD. The risk was elevated in the post partum (aHR 1.20, 95% CI 1.09 to 1.31), but not during pregnancy, and for Crohn’s disease (aHR 1.12, 95% CI 1.02 to 1.23), but not ulcerative colitis. The risk was specifically elevated for a new-onset mood or anxiety disorder (aHR 1.14, 95% CI 1.04 to 1.26) and alcohol or substance use disorders (aHR 2.73, 95% CI 1.42 to 5.26). Predictors of a mental illness diagnosis were maternal age, delivery year, medical comorbidity, number of prenatal visits, family physician obstetrical care and infant mortality. Conclusion Women with IBD were at an increased risk of new-onset psychiatric diagnosis in the postpartum period, but not during pregnancy. Providers should look to increase opportunities for prevention, early identification and treatment accordingly.
Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?
Authors: Musa Yilmaz, Feng Wang, Sanam Loghavi, Carlos Bueso-Ramos, Curtis Gumbs, Latasha Little, Xingzhi Song, Jianhua Zhang, Tapan Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Nicholas Short, Guillermo Garcia-Manero, Zeev Estrov, Hagop Kantarjian, Andrew Futreal, Koichi Takahashi, Farhad Ravandi
Journal: Blood Cancer Journal (2019)

Abstract Late relapse, defined as relapse arising after at least 5 years of remission, is rare and occurs in 1–3% of patients with acute myeloid leukemia (AML). The underlying mechanisms of late relapse remain poorly understood. We identified patients with AML who achieved remission with standard induction chemotherapy and relapsed after at least five years of remission ( n = 15). Whole exome sequencing was performed in available bone marrow samples obtained at diagnosis ( n = 10), remission ( n = 6), and first relapse ( n = 10). A total of 41 driver mutations were identified, of which 11 were primary tumor-specific, 17 relapse-specific, and 13 shared (detected both in primary and relapsed tumor samples). We demonstrated that 12 of 13 shared mutations were in epigenetic modifier and spliceosome genes. Longitudinal genomic characterization revealed that in eight of 10 patients the founder leukemic clone persisted after chemotherapy and established the basis of relapse years later. Understanding the mechanisms of such quiescence in leukemic cells may help designing future strategies aimed at increasing remission duration in patients with AML.
SAT0731-HPR Early postoperative outcomes of unilateral versus bilateral total knee arthroplasty
Authors: M. Eymir, B. Ünver, V. Karatosun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Many patients in need of total knee arthroplasty (TKA) have bilateral symptoms and require surgery to both extremities. Performance of a bilateral procedure under a single anaesthetic provides a reduced hospitalisation time, an isolated anaesthesia risk, a single rehabilitation, and substantial cost savings. However, previous studies' reports vary from unilateral TKA producing better outcomes than bilateral TKA, the 2 procedures producing no significant difference, and bilateral TKA producing a better outcome than unilateral TKA. There is a need for new studies to examine the differences between unilateral and bilateral TKA in terms of the early postoperative outcomes. <h3>Objectives</h3> The aim of this study was to compare the effect of the unilateral and bilateral TKA on the early postoperative outcomes. <h3>Methods</h3> The study group consisted of 71 patients (106 knees), who underwent primary TKR because of arthrosis were stratified either unilateral or bilateral TKA status. The mean age of unilateral (n=36) subjects were 66.00±10.71 years, and the mean age of bilateral (n=35) subjects were 64.17±7.61 years. Patients were evaluated regarding the knee function score (Hospital for Special Surgery (HSS) score), pain (Numeric Pain Rating Scale (NPRS)), knee range of motion, length of hospital stay, the day of active straight leg raise, the day of knee flexion angle achieved 70 degrees, quality of life (Short-Form 12 Health Survey (SF-12)). Functional activities were evaluated using the Iowa Level of Assistance Scale and walking speed was evaluated using the Iowa Ambulation Velocity Scale. Patients were evaluated preoperatively and at discharge. All patients underwent the same rehabilitation program. <h3>Results</h3> At baseline, demographic and anthropometric characteristics were similar in groups and there was no statistically difference between groups (p&gt;0.05). When the patients' knee range of motion were compared, there were statistically differences (p=0.027) between groups after surgery. The unilateral group had better results in terms of postoperative knee flexion degree. There were no statistical differences in terms of the pain degree, HSS score, length of hospital stay, the day of active straight leg raise, the day of knee flexion angle achieved 70 degrees, IOWA help level and IOWA walking speed, SF-12 score between groups before and after TKA (p&gt;0.05). <h3>Conclusions</h3> According to our results, the unilateral group had better result in term of postoperative knee flexion degree. On the other hand, the bilateral method may provide an advantage in terms of a single rehabilitation, and substantial cost savings. Therefore, in this comparison to obtain more comprehensive results studies on larger series are needed. In this way, a more uniform and objective data can be achieved. <h3>Disclosure of Interest</h3> None declared
FRI0578 Increased vein wall thickness in behÇet’s syndrome
Authors: M. Gjoni, E.S. Durmaz, S. Akbaş, A.S. Dikici, I. Mihmanlı, H. Yazıcı, E. Seyahi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lower extremity vein thrombosis (LEVT) is the key feature of vascular involvement in Behçet's syndrome (BS). Vein wall thickness (VWT) is proposed to be a surrogate marker of venous disease. A pilot MR study done in 7 BS patients and controls, had demonstrated increased VWT and signal enhancement in the lower extremity veins of BS patients without vascular disease.<sup>1</sup> Another study, using USG, found that VWT was increased among BS patients without vascular disease compared to patients with ankylosing spondylitis and healthy controls.<sup>2</sup> <h3>Objectives</h3> We reassessed VWT in proximal lower extremity veins in BS patients with LEVT and suitable controls in a formal, masked protocol. <h3>Methods</h3> We studied 47 (40 M/ 7 F) BS patients with LEVT, 50 (43 M/ 7 F) BS patients without any vascular involvement and 38 (31 M/ 7 F) age and gender matched apparently healthy controls. Two independent radiologists, blinded to the diagnosis of BS, used USG to measure VWT of common femoral vein (CFV), superficial femoral vein (SFV) and vena saphena magna (VSM) in both legs. <h3>Results</h3> As shown in table 1, mean age at disease onset and the disease duration were similar between BS study groups. The mean age at thrombosis onset of the patients with LEVT was 26.4±5.8 years. There was good concordance between the 2 observers (kappa: 0.9) The mean VWT was significantly increased among both BS patients with LEVT and those without any vascular involvement when compared to the healthy controls while those with LEVT had the thickest veins. <h3>Conclusions</h3> VWT of proximal deep and superficial lower extremity veins was found to be increased among BS patients without any clinical and radiological vascular involvement. <h3>References</h3> [1] Ambrose N, et al. Magnetic resonance imaging of vein wall thickness in patients with Behçet's syndrome. Clin Exp Rheumatol. 2014. [2] Alibaz-Oner F, et al. Venous vessel wall thickness in lower extremity is increased in male behcet's disease patients without vascular involvement. Ann Rheum Dis76(Suppl 2):417. <h3>Disclosure of Interest</h3> None declared
THU0364 Relationship between disease activity index scores and physician global assessment in early and non-early systemic lupus erythematosus
Authors: M. Garabajiu, V. Sadovici-Bobeica, L. Mazur-Nicorici, M. Cebanu, V. Salaru, M. Mazur
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To evaluate the disease activity and to compare it to physician's global assessment in patients with early (early SLE) and non-early systemic lupus erythematosus <h3>Methods</h3> Performed case-control study included SLE patients that fulfilled .SLICC classification criteria, 2012. The research included two groups: patients with early SLE – first group (disease duration less than 24 months) and non-early SLE – second group (disease duration more than 24 months). The disease activity was assessed by SLEDAI-2K and SLAM. Physician global assessment (PhGA) was rated by 0–100 numeric score. We correlated disease activity indices with physician global assessment by Pearson coefficient. <h3>Results</h3> A total of 96 SLE patients were analysed. First group included 45 patients with female:male ratio 14:1. The second group included 51 patients, female:male ratio 1:49. The disease activity indices: SLEDAI and SLAM denoted high disease activity level in both groups. PhGA didn't correlate with SLEDAI (r=0,28, p&gt;0,05) in the first group, while a statistically significant correlation was determined with SLAM index (r=0,39, p=0.007). In the second group we found a moderate statistical significant correlation of PhGA with SLAM (r=0,53, p=0.0001) and weak, but also statistical significant relationship with SLEDAI (r=0,35, p=0.01). There is a better correlation of PhGA assessment and SLAM in both study groups, which can be explained by the presence of subjective components in appreciation of this index. Patient's better appreciation of their condition in the group with longer disease duration (statistical significant correlation of PhGA and both indices:SLAM and SLEDAI), probably, is beacause this patients know better to appreciate their disease, and patients with early SLE tend to underestimate their general condition. <h3>Conclusions</h3> In patients with early SLE PhGA correlated with SLAM, while in patients with non-early lupus PhGA correlated with both insices - SLAM and SLEDAI-2K. A better correlation of PhGA with SLAM can be esplained by the presence of multiple components in this tool and also subjective data as fatigue or cognitive disfunction. <h3>Disclosure of Interest</h3> None declared
Abstract 12241: Delayed Time to Intrinsicoid Deflection on the 12-Lead ECG and Myocardial Scarring From the Multi-Ethnic Study of Atherosclerosis
Authors: Navid Darouian, Wesley T O'Neal, David A Bluemke, Joao A Lima, Elsayed Z Soliman, Matthew J Budoff
Journal: Circulation (2017)

Background: Delayed time to intrinsicoid deflection (DID) is an ECG finding associated heart failure (HF) independent of left ventricular hypertrophy (LVH). Myocardial scarring has been postulated ...
AB0317 Do mechanical and inflammatory rheumatologic diseases lead to the same sleep disorders?
Authors: W. Hamdi, M. Boudokhane, I. Cherif, D. Kaffel, K. Maatallah, M. Kchir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sleep disorders are frequent feature of chronic rheumatologic diseases. They are reported in inflammatory diseases as well as in mechanical disorders but they are not systematically assessed by clinicians. It is necessary to identify the frequency and factors associated to sleep problems in order to reduce their impact on patient's quality of life. <h3>Objectives</h3> We aim to describe the sleep pattern in inflammatory and mechanical chronic rheumatologic diseases and to assess factors associated with sleep disorders. <h3>Methods</h3> We conducted a cross-sectional study during 1 year including Tunisian patients with chronic inflammatory rheumatism (rheumatoid arthritis: RA according to the criteria ACR 1987 and axial spondyloarthritis: AS according to modified NEW YORK criteria) and patients with mechanical disorders (chronic low back pain and primitive knee osteoarthritis). Sleep has been evaluated by the MOS-SS questionnary. For each group specific disease parameters were assessed at the same time of the administration of the questionnary. <h3>Results</h3> We collected 120 patients with chronic inflammatory rheumatism (group 1) and 80 patients with mechanical disorder (group2). Group 1 was composed of 70 RA and 50 SPA including 65 women and 55 men. The average age was 46.95 [18.75]. Group 2 was composed of 40 chronic low back pain and 40 primitive knee osteoarthritis including 48 women and 32 men. The average age was 51.95 [18.82]. Sleep disorders were frequent in both groups, but they were more noticeable in Group 1 patients than Group 2 patients 53.68% vs 26.38% (p=0.00). Risk factors for sleep disorders in rheumatoid arthritis were disease activity (p=0.00) and functional impairment (p=0.00). In patients with spondyloarthritis, risk factors for sleep impairment were disease activity (BASDAI (p=0.00), ASDAS vs (p=0.00) et ASDAS CRP (p=0.00)) and impaired quality of life (p=0.00). The factors involved in sleep disorders in chronic low back pain was the reduced lumbar spine mobility assessed by the finger-to-ground distance (p=0.00) and the schober index (p=0.01) and functional impairment assessed by Eiffel questionnaire (p=0.00). In patients with knee osteoarthritis the Lequesne index (p=0.008), the knee extension limitation (p=0.00) and the radiological damage (p=0.004) were associated to sleep impairment. <h3>Conclusions</h3> Our results illustrate the frequency of sleep disorders in chronic rheumatic diseases. They should not be under estimated in patients with mechanical disorders. A better control of the factors associated to sleep impairment for each disease should help promoting a better sleep quality in patients with chronic rheumatologic diseases. <h3>Disclosure of Interest</h3> None declared
Prevalence of eosinophilic colitis and the diagnoses associated with colonic eosinophilia
Authors: Lauren A. DiTommaso, Chen E. Rosenberg, Michael D. Eby, Amy Tasco, Margaret H. Collins, John L. Lyles, Philip E. Putnam, Vincent A. Mukkada, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2019)
Three Decades of Autologous Stem Cell Transplantation for Myeloma; Trends in Early Mortality and Survival
Authors: M Hasib Sidiqi, Mohammed A Aljama, Angela Dispenzieri, Eli Muchtar, Francis K. Buadi, Rahma Warsame, Martha Q. Lacy, David Dingli, Nelson Leung, Wilson I Gonsalves, Prashant Kapoor, Taxiarchis Kourelis, William J. Hogan, Shaji K. Kumar, Morie A. Gertz
Journal: Blood (2018)
Association of Patient Comorbid Conditions With Cancer Clinical Trial Participation
Authors: Joseph M. Unger, Dawn L. Hershman, Mark E. Fleury, Riha Vaidya
Journal: JAMA Oncology (2019)

The American Society of Clinical Oncology (ASCO), Friends of Cancer Research, and the US Food and Drug Administration recently recommended modernizing criteria related to comorbidities routinely used to exclude patients from cancer clinical trials. The goal was to design clinical trial eligibility such that trial results better reflect real-world cancer patient populations, to improve clinical trial participation, and to increase patient access to new treatments in trials. Yet despite the assumed influence of comorbidities on trial participation, the relationship between patients' comorbidity profile at diagnosis and trial participation has not been explicitly examined using patient-level data.