tbuckley/cabot-search huggingface dataset:
THU0453 Efficacy of ab initio or very early introduction of immunosuppressive therapy in giant cell arteritis: a multicenter retrospective observational study
Authors: L. Quartuccio, E. Cavallaro, F. Angelotti, R. Capecchi, G. Vitiello, D. Cammelli, A. Tavoni, S. De Vita
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Glucocorticoids (GC) remain the mainstay of treatment of giant cell arteritis (GCA). However, relapses occur in up to 50% of patients when GC are tapered and prolonged courses of GC are associated with serious side effects. In this setting, the outcome is frequently determined by GC-related adverse events (AEs). Thus, several studies have been conducted on the effectiveness of a GC-sparing immunosuppressive therapy (IT), with conflicting results. <h3>Objectives</h3> To evaluate the effectiveness of IT in a series of GCA patients, in: 1) reducing the risk of GCA relapse; 2) lowering the exposure to GC therapy; 3) minimising the occurrence of steroid-induced AEs. <h3>Methods</h3> We performed a multicenter retrospective observational study including 69 patients (75,4% females; mean age ±SD 68,7±7,8 y; median follow-up time 40 months [range 26–65]) diagnosed with GCA, all receiving an adjunctive IT given ab initio (71%) or within 3 months from the start of GC. All but 17 patients (with extracranic involvement) fulfilled the GCA ACR classification criteria. Risk of first relapse of GCA, GC exposure and main AEs were retrospectively analysed. Results were compared with those reported in other studies, all characterised by a lower use of IT. <h3>Results</h3> all patients received GC plus IT: methotrexate up to 20 mg/week in 63 patients, cyclophosphamide in 22, tocilizumab in 12. In the follow-up, a first relapse of GCA occurred in 14 (20,3%) of patients. The rates of first relapse at 12, 24, 36 and 48 weeks were 4,3%, 11,6%, 15,9% and 15,9%, respectively, in comparison with rates of 24,3%, 41,6%, 61%, 64,9%, respectively, in the GC monotherapy arm in the meta-analysis by Mahr,<sup>1</sup> where similar data were available. The median daily prednisone dose at beginning was 50 mg, and decreased to 10 mg at 3 months and to 5 mg at 6 months. The median time required to reduce prednisone to 7.5 mg/day and 5 mg/ was 3 and 5 months respectively (vs. 6.5 and 7.5 months in series by Proven,<sup>2</sup> where similar data were available). In our cohort, lower cumulative GC use was accompanied by a reduction of AEs, without further toxicity (tab.1). <h3>Conclusions</h3> The use of IT ab initio or very early in the treatment of GCA appears to be effective and safe, lowering the risk of relapses, reducing GC dose and the rate of GC-related AEs. Therefore, the present data support the early introduction of IT in the treatment of GCA. <h3>References</h3> [1] Mahr AD, et al. Arthritis Rheum2007;56(8):2789–97. [2] Proven A, et al. Arthritis Rheum 2003 49(5):703–8.[3] Souza AW, Okamoto KY, Abrantes F, et al. Clinics (Sao Paulo) 2013;68:317–322.[4] Alba MA, et al. Medicine (Baltimore) 2014;93(<sup>5</sup>:194–201.[5] Labarca C, et al. Rheumatology (Oxford) 2016;55(<sup>2</sup>:347–56.Disclosure of Interest: None declared
Assessing Brain Metabolism With 7-T Proton Magnetic Resonance Spectroscopy in Patients With First-Episode Psychosis
Authors: Anna M. Wang, Subechhya Pradhan, Jennifer M. Coughlin, Aditi Trivedi, Samantha L. DuBois, Jeffrey L. Crawford, Thomas W. Sedlak, Fredrick C. Nucifora, Gerald Nestadt, Leslie G. Nucifora, David J. Schretlen, Akira Sawa, Peter B. Barker
Journal: JAMA Psychiatry (2019)

The use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants.To compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance.Cross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated.Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests.The mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate (F1,162 = 8.63, P = .02), N-acetylaspartate (F1,161 = 5.93, P = .03), GABA (F1,163 = 6.38, P = .03), and glutathione (F1,162 = 4.79, P = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N-acetylaspartate in the orbitofrontal region (F1,136 = 7.23, P = .05) and thalamus (F1,133 = 6.78, P = .03); and lower levels of glutathione in the thalamus (F1,135 = 7.57, P = .03). Among patients with FEP, N-acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed (r = 0.48; P < .001), visual (r = 0.33; P = .04) and working (r = 0.38; P = .01) memory, and overall cognitive performance (r = 0.38; P = .01).Seven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis.
Levofloxacin pharmacokinetics, pharmacodynamics and outcome in multidrug-resistant tuberculosis patients
Authors: Samiksha Ghimire, Bhagwan Maharjan, Erwin M. Jongedijk, Jos G.W. Kosterink, Gokarna R. Ghimire, Daan J. Touw, Tjip S. van der Werf, Bhabana Shrestha, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2019)

<b>50% of MDR-TB patients with higher MICs do not have enough Lfx exposure with currently prescribed once-daily dosing of 750–1000 mg. Therefore, it is suggested that MDR-TB patients should receive higher 1250–1500 mg Lfx dosages.</b>http://ow.ly/ZQsN30nuNBx
THU0014 Genetic screening for identifying human genes regulating fibrosis in systemic sclerosis
Authors: M. Krishnan, U. Unniyampurathu, S. Albani, A.H.L. Low
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a prototypic multi-systemic fibrotic disease. Fibrosis involves exacerbated collagen production. A lack of effective therapies has partly been due to incomplete understanding of the mechanisms of fibrosis and inadequate subsetting of this heterogeneous disease to allow targeted treatment. Identification of a collagen-synthesis gene signature in SSc will enhance our ability to molecularly subset SSc patients. We reasoned that there exists several unidentified genes regulating collagen synthesis, whose dysregulation play key roles in fibrosis underlying SSc. <h3>Objectives</h3> To discover novel genes/pathways involved in elevated collagen synthesis <h3>Methods</h3> We conducted a pioneering forward-genetics approach using genome-wide ribonucleic acid interference-(RNAi) –screening. We performed RNAi-screening in dermal fibroblasts from three patients with early diffuse cutaneous systemic sclerosis (onset from the first non-Raynaud's manifestation of less than 3 years). Dermal fibroblasts were immortalised using ectopic expression of human telomerase. The assay used a collagen promoter driver reporter system for identifying genes regulating collagen transcription. <h3>Results</h3> The genetic screen identified 187 genes whose silencing altered the activation of collagen promoter activity. This included 82% and 18% positive and negative regulators, respectively. A system-level view of genes and signalling pathways regulating collagen synthesis was generated using bioinformatics analysis. <h3>Conclusions</h3> We anticipate that this catalogue of collagen expression regulating genes will help to unravel the dysregulated genetic regulatory modules of fibrosis and may aid in the diagnostics of different clinical subsets of SSc. <h3>Disclosure of Interest</h3> None declared
AB0259 Clinical management of seronegative and seropositive rheumatoid arthritis: a comparative study
Authors: K. Lee, S.-T. Choi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are associated with poor radiologic outcomes in patients with rheumatoid arthritis (RA). In general, RA patients positive for RF or ACPA (SPRA) are considered to manifest an aggressive disease course compared with seronegative RA patients (SNRA). However, the relationship between seropositivity and measures of disease severity other than radiologic outcome is disputed. <h3>Objectives</h3> In this study, we sought to compare the clinical presentations and treatment outcomes of SNRA and SPRA patients. <h3>Methods</h3> A total of 241 patients diagnosed with <sup>DMARD-naïve RA under either 1987</sup> American College of Rheumatology (ACR) criteria or 2010 ACR/European League Against Rheumatism (EULAR) criteria were identified (40 with SNRA and 201 with SPRA). We investigated the disease activity measures including ESR, CRP, patient VAS, 28 tender/swollen joint count (28 TJC, 28 SJC) and DAS28 as well as radiologic outcomes at baseline, 1 and 2 years after conventional treatment with DMARD. <h3>Results</h3> Age, sex and disease duration were similar between SNRA and SPRA. However, the baseline 28 TJC (4.7±2.9 vs. 3.3±2.7, p=0.004), 28 SJC (4.3±3.0 vs. 2.9±2.3, p=0.001) and DAS28 (5.1±1.0 vs. 4.7±1.0, p=0.043) components were significantly higher in SNRA than in SPRA. Over 2 years of similar treatment with DMARDs, all disease activity measures significantly improved in both groups. Notably, ΔDAS28 from baseline at 1 year was significantly greater in SNRA compared with SPRA (−2.9±1.2 vs. −2.2±1.8, p=0.002). Radiologic outcomes at baseline and at 1- or 2 year follow-up were similar between the 2 groups <h3>Conclusions</h3> SNRA patients manifested more active disease at baseline, but showed a better response to treatment compared with SPRA. SNRA does not appear to be a benign subtype of RA <h3>Disclosure of Interest</h3> None declared
Mohs micrographic surgery for eyelid sebaceous carcinoma: A multicenter cohort of 360 patients
Authors: Chuandi Zhou, Fan Wu, Peiwei Chai, Yingyun Shi, Juan Ye, Xin Shi, Jia Tan, Yi Ding, Yingxiu Luo, Bita Esmaeli, Renbing Jia, Xianqun Fan
Journal: Journal of the American Academy of Dermatology (2019)
Prognostic Factors, Outcomes and Clinical Characteristics in Patients with Transformed Follicular Lymphoma (t-FL): Cohort Study of 172 Patients
Authors: Preetesh Jain, Loretta J. Nastoupil, Rashmi Kanagal-Shamanna, Graciela M. Nogueras González, Mansoor Noorani, Jorge Enrique Romaguera, Luis Fayad, Felipe Samaniego, Jason R. Westin, L. Jeffrey Medeiros, Sattva Neelapu, Michael Wang, Nathan H. Fowler
Journal: Blood (2018)
USP5 promotes epithelial-mesenchymal transition by stabilizing SLUG in hepatocellular carcinoma
Authors: Jing Meng, Xiaoyu Ai, Yueyang Lei, Weilong Zhong, Baoxin Qian, Kailiang Qiao, Xiaorui Wang, Bijiao Zhou, Hongzhi Wang, Longcong Huai, Xiaoyun Zhang, Jingxia Han, Yinyin Xue, Yuan Liang, Honggang Zhou, Shuang Chen, Tao Sun, Cheng Yang
Journal: Theranostics (2019)

Rationale: The role of SLUG in epithelial-mesenchymal transition during tumor progression has been thoroughly studied, but its precise regulation remains poorly explored. Methods: The affinity purification, mass spectrometry and CO-IP were performed to identify the interaction between SLUG and ubiquitin-specific protease 5 (USP5). Cycloheximide chase assays and deubiquitination assays confirmed that the effect of USP5 on the deubiquitin of SLUG. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional regulation of E-cadherin by SLUG effected by USP5. EMT related markers was detected by western blotting and immunofluorescence. Molecular docking, SPR sensor (biacore) and co-location were detected to prove Formononetin targets USP5. Bioinformatics analysis was used to study the relation of USP5 and SLUG to malignancy degree of HCC. Cell migration, invasion in HCC cells and xenografts model in nude mouse were conducted to detect the promotion of USP5 and the inhibition of Formononetin on EMT. Results: USP5 interacts with and stabilizes SLUG to regulate its abundance through USP5 deubiquitination activities in epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC). USP5 is highly expressed and positively correlated with SLUG expression in HCC with high malignancy. Knockdown of USP5 inhibits SLUG deubiquitination and inhibits HCC cells proliferation, metastasis, and invasion, while overexpression of USP5 promotes SLUG stability and EMT in vitro and in vivo. Through virtual screening, we found that Formononetin exhibits excellent binding to USP5. Moreover, Formononetin inhibits deubiquitinating activities of USP5 to SLUG and consequently impedes the EMT and malignant progression of HCC. Conclusion: Our findings reveal that USP5 serve as a potential target for tumor intervention and provide a preliminary antitumor therapy for inhibit EMT by targeting USP5 or its interaction with SLUG in HCC.
AB0010 Evaluation of sensitivity to dna damaging agents and efficiency of dna repair in human peripheral blood mononuclear cellsfrom patients with dermatomyositis and polymyositis
Authors: O. Brzezinska, A. Macieja, A. Lewandowska-Polak, J. Sarnik, M. Kubicka, J. Makowska, T. Popławski
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Idiopathic inflammatory myopathies (IIM) being one of the connective tissue diseases are a group of diseases with not fully understood pathology. The common features are production of autoantibodies, abnormal immune response against self-antigens and inflammatory process leading to destruction of muscle cells and internal organ involvement. Patients with inflammatory myopathies have higher risk of developing cancers. One of the processes that can attribute to increased risk of cancers can be genomic instability and impaired DNA repair. <h3>Objectives</h3> The aim of the study was to assess the processes of endogenous and exogenous DNA damage and its repair in patients with IIM as compared to healthy controls. <h3>Methods</h3> The study included 10 patients (9 men and 1 woman, mean age 46,6±16,5) with idiopathic inflammatory myopathies (dermatomyositis or polymyositis) as well as 7 healthy control individuals (4 men and 3 women, mean age 33,8±9,8). DNA damage and repair were investigated by the comet assay. To perform the comet assay human peripheral blood mononuclear cells (PBMCs) were isolated and incubated with tert-butyl hydroperoxide (t-BOOH) or bleomycin. Both compounds are common DNA damaging agents – t-BOOH induces oxidative DNA lesions whereas bleomycin induces also DNA double strand breaks (DSBs). To test the DNA repair capability, PBMCs were allowed to recover for 2 hour. The level of endogenous DNA lesions was also investigated. <h3>Results</h3> The levels of endogenous DNA damage were not statistically significantly different between tested groups (IIM-3,3±3,6% vs 3,2±3,8% in control; p=0,648). The extent of the DNA damage induced by bleomycin (IIM-23,3±19,5% vs 9,8±5,9% in control) as well as oxidative stress (IIM-14,7±16,2% vs 10,4±7,4% in control) was significantly higher in PBMS derived from IIM patients than in healthy counterparts (p&lt;0,001). Kinetic curves of DNA repair are different but the background mechanism underlying observed differences in the repair curve between healthy subjects and patients need to be evaluated further. <h3>Conclusions</h3> Understanding the etiology of this phenomena in these diseases may provide insight into disease pathogenesis and explain the increased susceptibility of patients to malignancies. Finding the patients with increased DNA instability could potentially serve as a biomarker and indicate the group of patients who should be carefully screened for neoplasmatic disorder. <h3>Disclosure of Interest</h3> None declared
Botulinum Toxin Type A for the Treatment of Lower Limb Spasticity after Stroke
Authors: Andrea Santamato, Nicoletta Cinone, Francesco Panza, Sara Letizia, Luigi Santoro, Madia Lozupone, Antonio Daniele, Alessandro Picelli, Alessio Baricich, Domenico Intiso, Maurizio Ranieri
Journal: Drugs (2019)
Abstract 18963: Associations Between Severe Mental Illness and Healthcare Expenditure After Acute Myocardial Infarction: A Nationwide Retrospective Cohort Study
Authors: Bing Yue, Shuyang Fang, Xin Wei, Allen Weiss, Eyal Herzog
Journal: Circulation (2017)

Introduction: Severe mental illness (SMI), including schizophrenia and bipolar disorder, are associated with higher incidence, mortality and healthcare burden of acute myocardial infarction (AMI). We investigated the impact of SMI on healthcare cost and length of inpatient stay among patients with AMI. Methods: We conducted a nationwide retrospective cohort study among patients admitted to acute care hospitals with a primary diagnosis of AMI during year 2014 utilizing the National Inpatient Sample (NIS) database. Schizophrenia and bipolar disorder were identified using secondary inpatient diagnosis codes from the index hospitalization. Outcomes included length of stay (LOS), healthcare cost and overall inpatient mortality. Multivariate linear and logistic regression analyses were used to adjust for demographic and clinical variables. Results: Among 121, 738 patients admitted for AMI, about 3% have history of SMI, they tend to be younger (mean age in years: 61 vs. 67), more likely to be female (47% vs. 39%...
AB1170 First results of the rheumatoid arthritis handscan registry leeuwarden
Authors: A. Al Hasan, R. Bos, N. Veeger, D. Zhang, L. Hendriks, F. Wink, A. Schilder, F. Reimann, K. Bergsma
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The handscan is a new technologic device which uses diffuse optical transmission in combination with blood flow modulation. It is a non-invasive measurement of joint inflammation potentially more sensitive than the clinical evaluation of the joints by a rheumatologist[.<sup>1</sup> However, more clinical data is necessary before this new device can be implemented in the daily clinical practice. <h3>Objectives</h3> This study investigates the additional value of the handscan in decision making in the daily practice for patients with rheumatoid arthritis. <h3>Methods</h3> At our outpatient clinic we started a registry for rheumatoid arthritis patients with a disease duration of at least two years. During this period, a handscan will be made for all patients before every regular visit. Both the patient and the treating rheumatologist will be blinded to the handscan outcome. Primary outcome is the association between DAS28 score and the total optical score (TOS) of the handscan per visit. <h3>Results</h3> The study started in December 2017, until now 100 patients are included. The mean age was 61.1 years, the mean disease duration at time of inclusion 11.2 years, 67% were rheumatoid factor positive, 51% were anti-CCP positive. In figure 1 we show the association between DAS28 and the TOS in a linear model. Currently there is no validated cut off point for the TOS (negative or positive score for inflammation). In our group of 100 patients the median TOS was 10, the most discriminating TOS was found to be 17 using chi-square test as depicted in table 1. <h3>Conclusions</h3> In this preliminary evaluation of the first 100 patients, we observed a limited positive correlation between the total optical score of the handscan and the DAS28. The TOS above 17 associates with moderate to severe disease activity. The definite clinical value of the handscan needs to be determined with longitudinal measurements and it's predictive value versus the DAS28. The ongoing current registry aims to answer these questions. <h3>Reference</h3> [1] Van Onna M, Ten Cate DF, Tsoi KL, et al. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique. Ann Rheum Dis2016;75:511–8. doi:10.1136/annrheumdis-2015-207315 <h3>Disclosure of Interest</h3> A. Al Hasan Grant/research support from: this reserach is supported by an unrestricted grant from Stichting De Friesland, R. Bos Grant/research support from: this reserach is supported by an unrestricted grant from Stichting De Friesland, N. Veeger: None declared, D. Zhang: None declared, L. Hendriks: None declared, F. Wink: None declared, A. Schilder: None declared, F. Reimann: None declared, K. Bergsma: None declared
Cord Blood Units (CBU) Selected for Transplantation from a Single CB Bank over 10 Years: High Correlation of Potency/Quality Among Pre-Cryopreservation and Post-Thaw Segment Measurements and Time to Engraftment
Authors: Maria S. Albano, Ludy Dobrila, Michal Tarnawski, Dorothy Sung, Emeline Masson Frenet, Cynthia Romeo, Tracy Zhu, Chiseko Watanabe, Dan Zamfir, Siddarth Krishnan, Pablo Rubinstein, Andromachi Scaradavou
Journal: Blood (2018)
Chimeric antigen receptor modified T cell therapy in B cell non‐Hodgkin lymphomas
Authors: Adam Levin, Nirav N. Shah
Journal: American Journal of Hematology (2019)

Chimeric antigen receptor modified T (CAR‐T) cell therapy against the CD19 antigen has revolutionized the therapeutic landscape for patients with relapsed, refractory B cell non‐Hodgkin lymphoma (NHL). Currently, there are two FDA approved products (axicabtagene ciloleucel and tisagenlecleucel) for B cell NHL, with several other constructs under clinical investigation. This review will focus on the clinical outcomes, toxicity profile, and differences among candidate CD19 CAR‐T cell products for major subtypes of B cell NHL including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Lastly, we will describe novel CAR‐T constructs currently under exploration in B cell NHL.