tbuckley/cabot-search huggingface dataset:
High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals
Authors: Morten O. Holmström, Shamaila M. Ahmad, Uffe Klausen, Simone K. Bendtsen, Evelina Martinenaite, Caroline H. Riley, Inge M. Svane, Lasse Kjær, Vibe Skov, Christina Ellervik, Niels Pallisgaard, Hans C. Hasselbalch, Mads H. Andersen
Journal: Blood Cancer Journal (2019)

Abstract Mutations in exon 9 of the calreticulin gene ( CALR ) frequently occur in patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from the mutant CALR C-terminus, and CALR -mutant-specific T cells recognize autologous CALR -mutant malignant cells. This study investigated whether CALR -mutant-specific T cells occur naturally in CALR wt MPN-patients and in healthy individuals. Specific immune responses against epitopes in the mutant CALR peptide sequence were detected in both CALR wt MPN-patients and in healthy individuals. Healthy donors displayed more frequent and stronger CALR-mutant specific T-cell responses compared to the responses identified in CALR -mutant MPN-patients. Several T-cell responses were identified in healthy donors directly ex vivo. Importantly, by running functional analyses on live-sorted immune cells from healthy donors, we showed that circulating CALR -mutant-specific immune cells are T-memory cells. These findings suggest, that healthy individuals acquire a CALR exon 9 mutation, but the immune system reacts and clears the mutant cells, and during this reaction generates CALR -mutant specific T-memory cells. We believe that these findings provide the evidence for tumor immune surveillance in MPN.
Addition of Gemtuzumab Ozogamicin (GO) to Fludarabine, Cytarabine and G-CSF (FLAG) Based Induction Regimen Results in Better Early Molecular Response and Relapse Free Survival Compared to Idarubicin (FLAG-Ida) in Newly Diagnosed Core Binding Factor Leukemia
Authors: Gautam Borthakur, Jorge E. Cortes, Guillermo Garcia-Manero, Keyur Patel, Farhad Ravandi, Tapan M. Kadia, Naveen Pemmaraju, Naval G. Daver, Musa Yilmaz, Zeev E. Estrov, Maro N. Ohanian, Rita Maduike, Hagop M. Kantarjian
Journal: Blood (2018)
SAT0389 Mri predictive factors for positive ct-guided biopsy in suspected septic spondylodiscitis
Authors: E. Chotard, H. Jacquier, P. Richette, C. Rioux, V. Joly, E. Palazzo, M. Forien, G. Jelin, Y. Yazdanpanah, P. Dieudé, S. Ottaviani
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Septic spondylodiscitis is an infection involving intervertebral disc and adjacent vertebral endplates that could lead to neurological complications. Magnetic resonance imaging (MRI) is the main imaging modality to suspect spondylodiscitis. However, MRI features predictive for septic spondylodiscitis are still lacking. <h3>Objectives</h3> To assess the MRI features associated with microbial pathogen detection by CT-guided biopsy among patients with suspected septic spondylodiscitis. <h3>Methods</h3> Between May 2007 and July 2017, we retrospectively analysed patients who underwent MRI and CT-guided biopsy for suspicion of septic spondylodiscitis. Baseline clinical and biological characteristics were collected. MRIs were analysed by one physician blinded to clinical data. The following MRI features were assessed when available: oedema or contrast-enhancement of intervertebral disk, adjacent vertebrae, epidural and paravertebral space, presence of abscess and paravertebral oedema size. A positive biopsy was defined by pathogen identification on culture or by direct microscopy examination. <h3>Results</h3> Fifty-one patients (54.9% of males, mean ±SD age of 59.2±19.1 years) were analysed. Lumbar spine (n=38) was the most affected site. A total of 26 (51%) patients had a CT-guided biopsy positive for a bacterial pathogen, mainly <i>mycobacterium tuberculosis</i> (n=7) and <i>staphylococcus aureus</i> (n=7). Disc size reduction, more than 50% of endplate oedema, loss of intradiscal cleft and abscess were the MRI findings associated with detection of bacterial pathogen by biopsy with a frequency of 100%, 92%, 81% and 50%, respectively. Size of paravertebral oedema was statistically higher in positive CT-guided biopsy than those negative (20.5±12.6 <i>vs</i>. 11.0±9.8 mm, p=0.004). The highest specific MRI finding for bacterial pathogen detection was the presence of paravertebral abscess (80%). <h3>Conclusions</h3> Our study showed that loss of intradiscal cleft, abscess and a large endplate oedema were the best predictive factors for a positive CT-guided biopsy. Size of paravertebral oedema is also associated with detection of bacterial pathogen. Physician must be aware of these MRI findings to better determine which patients should have a CT-guided biopsy. <h3>Disclosure of Interest</h3> None declared
AB0158 Histological and serological characteristics contribute to divergent outcomes for indigenous patients with lupus nephritis
Authors: J. Nossent, W. Raymond, A. Kang, M. Ognejovic, A. Chakera, D. Wong
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Renal outcomes for Indigenous Australians (IA) with Lupus Nephritis (LN) are worse than for other ethnic groups. <h3>Objectives</h3> To investigate whether differences in renal biopsy findings can explain the worse renal outcome in Indigenous patients <h3>Methods</h3> A single centre cohort study of 83 SLE patients undergoing a first renal biopsy at our institution for LN evaluation. Histological assessment included review of ISN classification, A/AC/C sub classification, NIH tubulointerstitial activity and chronicity indices, tubulointerstitial index, semiquantitative IF scores for IgG, IgM, IgA, C3 and C1q deposits, localisation of electron dense deposits (EDD) and presence of thrombosis, vasculitis and tubuloreticular inclusions (TRI). Differences in histological and routine clinical findings including autoantibody profiles between IA patients (n=11) and the pooled data from Asian (n=29) and Caucasian (n=43) patients were analysed by non-parametric statistical methods. <h3>Results</h3> IA patients were younger at diagnosis (31 vs 38.5 years., p=0.08) and their biopsies contained fewer glomeruli (11 vs 21, p&lt;0.01), more class I/II (28 vs 15%) and no class V lesions (0 vs 21%) (p=0.06 for overall comparison). IA patients were less likely to have cellular crescents (0 vs. 25%, p=0.03), more likely to have fibrous crescents and a low tubulointerstitial index (p=0.08). The overall AI (5.1 vs 4.9) and CI scores (1.1 vs. 1.3) or presence of full house IF deposits (67 vs 71%), renal thrombosis (0 vs 4%) or TRI (55 vs. 39%) was similar across groups (all p&gt;0.3). IA patients had lower eGFR (43 vs 65, p=0.025), more often carried anti-SSA52kd Ab (73 vs 33%, p=0.02) and during a mean follow-up of almost nine years, had a higher proportion of patients developing ESRD (18 vs 3%, p=0.02). <h3>Conclusions</h3> IA patients with SLE who develop LN have fewer glomeruli, an increased frequency of mesangial abnormalities with absence of cellular crescents and membranous nephropathy and a high prevalence of anti-SSA 52KD Ab. Although based on small numbers, this suggests that lower nephron mass and immunological pathways involving IFN-inducible anti-SSA expression may contribute to LN development and worse renal outcome in Indigenous patients. <h3>Acknowledgements</h3> Supported by an unrestricted grant from the Arthritis Foundation of Western Australia. We acknowledge the contribution by drs Brandon Wong and Kimberly Minats in data collection. <h3>Disclosure of Interest</h3> None declared
WWOX Inhibits Metastasis of Triple-Negative Breast Cancer Cells via Modulation of miRNAs
Authors: Saleh Khawaled, Sung Suk Suh, Suhaib K. Abdeen, Jonathan Monin, Rosario Distefano, Giovanni Nigita, Carlo M. Croce, Rami I. Aqeilan
Journal: Cancer Research (2019)

Triple-negative breast cancer (TNBC) is a heterogeneous, highly aggressive, and difficult to treat tumor type. The tumor suppressor WWOX spans FRA16D, a common fragile site that is commonly altered in breast cancer. Despite recent progress, the role of WWOX in TNBC metastasis is unknown. Here we report that WWOX inactivation correlates with advanced stages of TNBC and that its levels are frequently altered in TNBC cells. Ectopic restoration of WWOX in WWOX-negative TNBC cells inhibited metastasis while its depletion in WWOX-positive TNBC cells promoted metastasis. WWOX was a negative regulator of c-MYC, which regulated miR-146a expression and consequently fibronectin levels, contributing to an epithelial status of the cell. Treatment of TNBC cells with anti-miR-146a rescued the WWOX antimetastatic phenotype. Moreover, overexpression of MYC in WWOX-expressing TNBC cells overrode WWOX effects on miR-146a and fibronectin levels. Altogether, our data uncover an essential role for WWOX in antagonizing TNBC progression and highlight its potential use as a biomarker for metastasis. SIGNIFICANCE: These findings highlight the mechanism by which the tumor suppressor WWOX regulates metastasis of triple-negative breast cancer.See related commentary by Sharma, p. 1746.
Abstract P336: The Association Between Goal-Striving Stress, Sleep Duration and Sleep Quality in the Jackson Heart Study
Authors: Loretta Cain, LáShauntá Glover, Dayna Johnson, Mario Sims
Journal: Circulation (2018)

Introduction: Research shows that compared to non-Hispanic whites, African Americans (AAs) have poorer sleep quality, lower mean sleep duration, and a higher prevalence of sleep-disordered breathing. AAs also report more frequent exposures to certain stressors over the life course, which may impact physiological processes that may impair sleep. Goal-striving-stress (GSS), the discrepancy between aspiration and achievement, weighted by the subjective probability of success, and the level of disappointment experienced if goals are not reached, may be an important stressor among AA’s that may influence sleep; however this has yet to be explored. The objective of this study was to assess the relationship between GSS and sleep duration and sleep quality in AAs. Hypothesis: We assessed the hypothesis that high (versus low) GSS would be associated with short or long sleep duration and poor sleep quality. Methods: We utilized data from the baseline exam of the Jackson Heart Study (JHS; n=5306), an AA sample of women and men, 35-84 years old. There were a total of 5082 participants in the sample; 63.34% female with a mean age of 55.30 (± 12.75) and mean sleep duration of 6.43 hours (±1.51). The sample was categorized into GSS tertiles: low (n=2121), moderate (n=1716), high (n=1296). Participants self-reported sleep duration (hours) and rated their sleep quality. Sleep duration was categorized as short ( &lt; 6 hours), normal (7 or 8 hours) and long ( &gt; 9 hours). Sleep quality was categorized as high (good/very good/excellent) and low (fair/poor). Logistic regression models were used to obtain odds ratios (OR, 95% confidence interval-CI) to assess the associations of GSS levels with sleep duration and sleep quality categories. Models were adjusted for sex, age, socioeconomic status, health behaviors, discrimination, and health outcomes. Results: Significant results showed that participants who reported high (versus low) GSS had a 29% increased odds [1.29 (1.10, 1.52)] of short (versus normal) sleep after full adjustment. Participants who reported high (versus low) GSS had a 42% increased odds [1.42 (1.20, 1.67)] of low (versus high) sleep quality after full adjustment. Conclusion In conclusion, the deficit between goal aspiration and achievement is associated with short sleep duration and poor sleep quality. Potential interventions should consider the extent to which GSS may contribute to the development of short sleep duration and poor sleep quality.
AB1026 Clinical characteristics and risk factors for gout attack during the postsurgical period
Authors: H. Jeong, Y.H. Eun, E.-J. Park, H. Kim, J.Y. Chai, J. Lee, C.H. Jeon
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To evaluate the clinical features and risk factors for gout attack during the postsurgical period in patients with gout. <h3>Methods</h3> Seventy patients who had histories of gout and had been consulted to rheumatologic clinic before surgery under general anaesthesia at a single tertiary hospital were included. Clinical characteristics of patients who developed postsurgical gout attack were compared with patients who did not developed gout attack. <h3>Results</h3> Among 70 patients, 31 (44.3%) patients developed gout attack during postsurgical period. Mean time of gout attack after surgery was 3.7±4.9 days. Most of attacks involved lower extremity joints (83.9%) and tended to monoarticular involvement (61.3%). Knee joint (26%) and foot except 1st metatarsophalangeal (MTP) joint (26%) were more frequently involved than 1st MTP joint (13%). Uric acid levels before surgery (OR 1.46, 95% CI 1.13–1.88, p=0.004) and amount of uric acid changes between before and after surgery (OR 1.62, 95% CI 1.21–2.18, p=0.001) were risk factors for postsurgical gout attack. Taking medications for gout including uric acid lowering agents and/or colchicine reduced the risk of postsurgical gout attack (OR 0.11, 95% CI 0.04–0.32, p&lt;0.001). Operation time, amount of blood loss during surgery, amount of fluid administration during surgery, and surgery site were not significantly associated with postsurgical gout attack. <h3>Conclusions</h3> Adequate uric acid control and taking medications for gout could prevent the postsurgical gout attack. <h3>Disclosure of Interest</h3> None declared
AB1116 Macrophage activation syndrome: an experience from a tertiary paediatriccare setting in eastern india
Authors: P.P. Giri, P. PAL, J. bhatia
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Macrophage activation syndrome (MAS) is a rare but potentially fatal complication of systemic inflammatory disorders occurring most commonly in Systemic arthritis(SJIA) but also being increasingly reported in SLE, Kawasaki disease and Periodic Fever Syndromes. We present a series of 29 cases of MAS encountered in the last 9 years in a tertiary paediatric care setting in eastern India. <h3>Objectives</h3> The objective of this study is to evaluate the clinical features, laboratory findings and outcome in MAS; to assess the treatment response to different therapies and to identify the poor prognostic factors. <h3>Methods</h3> It is a prospective analysis of data of patients diagnosed as having <sup>MAS, between July 2008</sup> and April 2017, admitted in the Department of Paediatrics at Institute Of Child Health, Kolkata. All patients with Haemophagocytic Lymphohistiocytosis (HLH) secondary to autoimmune or inflammatory connective tissue diseases were included whereas HLH secondary to infections were excluded. Diagnosis of HLH was based on the <sup>HLH 2004</sup> criteria. MAS diagnostic criteria for SJIA was laid down in 2014. ,<sup>Post 2014</sup> we used those criteria in SJIA patients. The data noted were the clinical and laboratory features, treatment details, the response to therapy and outcome. <h3>Results</h3> Twenty nine (n=29) patients were found to have MAS with the primary illness being SJIA in 24 (83%), SLE in 4 (14%) and Kawasaki Disease in 1 (3%). The mean age at presentation was 5 years 3 months. The male female ratio was 1.2:1. Neurological, cardiac, renal and pulmonary involvement was seen in 21 (72%), 14 (48%), 6 (20%) and 5 (17%) patients respectively. Pulse methyl prednisolone (30 mg/kg) for 3 days was given in 27 patients. Two patients received hydrocortisone in SJIA MAS secondary to infections (chickenpox, Hepatitis A). In patients unresponsive to steroids IVIG and/or cyclosporine was used. 19 (65%) patients survived whereas 10 (35%) died. Of the 10 who succumbed, the <sup>HLH 2004</sup> protocol (including etoposide) was used in 2 who were refractory to pulse methylprednisolone +cyclosporine +IV Ig, but without any success. 2 patients on Tocilizumab had silent MAS. Ferritin &gt;50000 ng/ml was seen in 11 patients of which 8 died. Chi square test of significance was done and p value (0.001) was significant for mortality in patients with ferritin &gt;50000 ng/ml, with a positive correlation (0.613). Patients with cardiovascular involvement especially pericardial effusion in SJIA was observed to have higher mortality but no statistical correlation could be made <h3>Conclusions</h3> MAS is a fatal complication with a high mortality rate of 35% in our series. Ferritin levels&gt;50,000 ng/ml was associated with high mortality. Early and aggressive intervention with optimal intensive care support maybe life saving. <h3>Disclosure of Interest</h3> None declared
AB0606 Neuropsychiatric lupus in a sample of egyptian patients with systemic lupus erythematosus: prevalence and clinical characteristics
Authors: M. Eissa, B.M. Medhat, A. Moghazy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Neuropsychiatric (NP) lupus is common among patient with systemic lupus erythematosus (SLE). It occurs in about 30%–56% of all SLE patients. However, the diagnosis of neuropsychiatric SLE (NPSLE) remains difficult. Neuropsychiatric lupus (NPL) can present with a wide variety of clinical manifestations. <h3>Objectives</h3> The aim is to determine prevalence of NPSLE among a sample of Egyptian SLE patients from a single centre and to describe its features and characteristics. <h3>Methods</h3> The study included 301 adult SLE patients from Cairo University Hospital. The patients are classified according to the Systemic Lupus International Collaborative Clinics (SLICC) criteria for SLE. Neuropsychiatric manifestations were recorded using the ACR NPSLE nomenclature and case definitions (1999) Global disease activity was quantified by the SLE Disease Activity Index 2000 (SLEDAI-2K) at first and at last visit of the patient. Systemic Lupus International Collaborative Clinics/ACR Damage Index (SLICC/ACR-DI) was used to measure damage. The period of data collection took 4 months. The collected data included demographic, clinical, serologic data and medications. <h3>Results</h3> 301 SLE patients (87.4%) females and (12.6%) males with mean age 30.7±9.2 years and disease duration 72 months (2–288) were included. 101 (33.5%) were diagnosed as having NPSLE. The highest NP manifestation in frequency is headache (55.4%) followed by psychosis (33.7%) then seizures (21.8%). NP manifestation is the onset of the disease in 42.6% of all NPSLE patients. Compared to non-NPSLE group, NPSLE group is significantly older at onset of disease and have longer disease duration (p&lt;0.05). They are significantly more active at the onset of the disease than non-NPSLE and have significantly more disease damage (p&lt;0.05). Regarding clinical manifestations of lupus; NPSLE are significantly higher in frequency of discoid rash, cutaneous vasculitis, serositis, secondary anti-phospholipid syndrome (APS), associated avascular necrosis of the joints and osteoporosis (p&lt;0.05). Anti-cardiolipin IgM anti bodies are significantly more frequent in NPSLE group (p&lt;0.05). Notably, frequency of psychosis, superior sagittal thrombosis and cerebrovascular disease were significantly higher in NPSL with positive APS than those with negative APS (p&lt;0.05). <h3>Conclusions</h3> NPL is common in SLE, its prevalence is about 30% in Egyptian SLE patients. NPSLE patients may present diverse clinical manifestations most commonly headache, psychosis and seizures. NPL is different from non-NPL and presence of APS has an impact on clinical presentation of NP involvement in the patients. <h3>Disclosure of Interest</h3> None declared
Abstract 17544: Type 2 MI in Young Adults is Associated With High Cardiovascular Mortality: An 8-Year Follow-Up
Authors: Ankur Gupta, Avinainder Singh, Arman Qamar, Bradley Collins, Patrycja Galazka, Candace Wu, Ersilia M DeFilippis, Josh Klein, Jon Hainer, Petr Jarolim, Ravi V Shah, Marcelo F Di Carli, James L Januzzi, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2017)

Introduction: Recent studies have suggested that patients with type 2 myocardial infarction (T2MI) have worse prognosis than patients with type 1 myocardial infarction (T1MI). However, long-term ca...
AB0756 Mda 5 dermatomyosistis and response to rituximab in a small cohort at our institution
Authors: F. Berianu, V.J. Maya, B. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treatment for anti-melanoma differentiation-associated gene 5 antibody (MDA 5) Dermatomyositis is posing challenging to clinician and there is currently no consensus on therapy. The MDA5 was recently classified as a myositis-specific antibody (MSA), and has been associated with rapidly progressive interstitial lung disease (ILD), amyopathic dermatomyositis (aDM), mechanic's hands, ulcerations, inflammatory arthritis, and increased mortality. <h3>Objectives</h3> This study sought to characterised response to Rituximab in a small cohort of patients with MDA 5 DM at our institution. <h3>Methods</h3> A retrospective chart review was done to identify all MDA5 positive patients who were evaluated at our centre from 2015 to 2017 with suspected myositis and had myositis-associated autoantibodies tested using a commercial panel (MyoMarker Panel 3). For all patients who were positive for MDA5, we collected clinical information on the presence of myopathy, skin involvement and ILD, data on the autoantibody profile, PFTs and high resolution CT pattern along with therapy response. <h3>Results</h3> 11 were positive for MDA5. 7 were females and 4 were males, with mean age 56.6 years. Eight patients were treated with Rituximab from which seven had ILD at presentation: 4 NSIP, 2 with organising pneumonia, one had UIP and one had fatal acute interstitial pneumonitis 2 months after onset of mechanics' hands and inflammatory arthritis. Three patients without ILD were treated with other DMARDs. All had responded well to Rituximab with improvement in skin ulceration, inflammatory arthritis and mechanics' hands and most patients had stable ILD except for one patient with fulminant interstitial pneumonitis for with Cytoxan was added without any additional benefit. <h3>Conclusions</h3> Rituximab is a good management option for all manifestation of MDA 5 DM. Further studies are needed to elucidate the association of MSA and the clinical manifestations and response to treatment response of patients with inflammatory myopathies. <h3>References</h3> [1] Br J Dermatol. 2017Feb;176(2):395–402 [2] Am J Pathol. 2016Mar;186(3):691–700. [3] Arthritis Care Res. 2016May;68(5):689–94. [4] J Bras Pneumol. 2011Feb; 37(1): 100–109 [5] Arthritis Care Res (Hoboken). 2013Aug; 65(8): 1307–1315 <h3>Disclosure of Interest</h3> None declared