tbuckley/cabot-search huggingface dataset:
FRI0367 Association of vitality and subsequent physical functioning in systemic lupus erythematosus: analysis of data from the german lula cohort 2002 – 2013
Authors: J. Mucke, G. Chehab, R. Fischer-Betz, J. Richter, B. Winkler-Rohlfing, M. Schneider, R. Brinks
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Fatigue, defined as loss of vitality, is a major burden in patients with systemic lupus erythematosus (SLE). It is well-known from cross-sectional studies that fatigue is associated with physical functioning (PF) whereas the effect of fatigue on subsequent PF has not yet been further looked on. <h3>Methods</h3> Data from the German <i>Lupus-Langzeitstudie</i> (LuLa) cohort was used to explore the effect of self-reported vitality on PF. The ongoing LuLa study comprises patients from the German SLE self-help group. The current analysis uses data from 2002 to 2013. We looked for associations between the PF score (outcome) and the vitality score of the SF-12 questionnaire in one to four years preceding the outcome. Statistical analysis was accomplished by a linear mixed regression model (LMM) adjusting for the potential confounders age, sex, disease duration and disease activity as surveyed by the Systemic Lupus Activity Questionnaire score (SLAQ). <h3>Results</h3> 1511 patients (93.3% women) provided data with a total of 7841 person-years of observation. Median age at study entry was 46 (interquartile range: 37 to 57). The table 1 shows the regression coefficients of the vitality score (and 95% confidence intervals, CI) estimated by the LMM without and with adjusting for age, sex, disease duration and SLAQ. <h3>Conclusions</h3> We found evidence that self-reported vitality in patients with SLE is associated with PF in the subsequent years. The data indicate a "window of opportunity" for treating fatigue symptoms of up to four years for maintenance of PF. <h3>Disclosure of Interest</h3> J. Mucke: None declared, G. Chehab Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study, R. Fischer-Betz Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study, J. Richter Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study, B. Winkler-Rohlfing: None declared, M. Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study, R. Brinks: None declared
Association Between Autologous Stem Cell Transplant and Survival Among Californians With Multiple Myeloma
Authors: Aaron S Rosenberg, Ann Brunson, Brian A Jonas, Theresa H M Keegan, Ted Wun
Journal: JNCI Journal of the National Cancer Institute (2018)

Autologous hematopoietic stem cell transplant (aHSCT) is an efficacious treatment for newly diagnosed multiple myeloma patients. However, as rapid advances have resulted in other highly efficacious and less intensive therapies, the role of aHSCT has been questioned.We utilized population-based data to identify 13 494 newly diagnosed patients younger than age 80 years between 1998 and 2012. Patient characteristics of aHSCT and non-aHSCT groups were balanced using inverse probability weighting of a propensity score predicting aHSCT use. Multivariable models adjusted for baseline comorbidities, demographics, and socioeconomic status estimated the adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) of death.Twenty point eight percent (2807) of patients underwent aHSCT, and this rate increased over time from 15.4% in 1998-2002 to 23.9% in 2008-2012. aHSCT was utilized among 37.6% and 11.5% of patients younger than age 60 years and 60 to 79 years, respectively. The median time to aHSCT was 9.4 months, and 89% of all aHSCTs occurred within two years of diagnosis. The median overall survival from time of aHSCT was 72.9 months (95% confidence interval [CI] = 68 to 78). Autologous HSCT at any time was associated with improved survival (aHR = 0.83, 95% CI = 0.75 to 0.92). Among aHSCT recipients, transplant more than 12 months after diagnosis (vs ≤12 months) was associated with worse survival (aHR = 1.33, 95% CI = 1.16 to 1.51). The positive effect of aHSCT on overall survival was similar across study time periods and age groups.In the era of highly efficacious induction therapies, aHSCT remained infrequently used but continued to be associated with improved survival for multiple myeloma patients and should be considered for newly diagnosed patients.
AB1072 The median nerve cross-sectional area may be a parameter of follow- up after treatment in patients with carpal tunnel syndrome?
Authors: B. Mansiz-Kaplan, I. Yagci, G. Akyuz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy in general population. Diagnosis of CTS depends on clinical symptoms, physical examination and electrophysiological findings. In recent years, diagnostic value of median nerve ultrasonography has increased particularly for the CTS. To aim of this study compare the electrophysiological and ultrasonographic findings at CTS patients who treated with splinting at night during three months. <h3>Methods</h3> The patients, who were diagnosed with mild or moderate CTS, received a fabricated night orthotic which held the wrist in a neutral position during three months. All patients were evaluated clinically, electrophysiologically, and ultrasonographically before treatment and at 3 months by blind physicians. Pain was evaluated using Visual Analogue Scala (VAS) Boston Carpal Tunnel Questionnare was used to evaluated symptom severity and functional capacity. In electrophysiologic evaluation median nerve conduction studies was recorded. Median nerve cross-sectional areas (M-CSA) were measured by ultrasonography at the level of radio-ulnar joint, pisiform bone, and hook of hamate. After treatment, 68 patients were divided into two groups according to whether there was a%50 reduction in VAS. <h3>Results:</h3> The study was completed with 68 patients and 114 hands. While in group 1, in which VAS reduction was less than%50, there were 38 hands; in group 2, in which VAS reduction wan more than%50, there were 76 hands. There were no differences improvement of symptom severity, nerve conduction studies parameters, M-CSA at the level of radio-ulnar joint between groups. Improvement of functional capacitiy and descrease of M-CSA at the level of pisiform bone and hook of hamate were significantly better in group 2 (p&lt;0.05). <h3>Conclusions:</h3> After conservative treatment, while M-CSA was consistent with clinical findings, this consistency has not been observed with nerve conduction studies. M-CSA may be used to follow-up after receiving conservative treatment in patient with CTS. <h3>Disclosure of Interest:</h3> None declared
Two Hormones for One Receptor: Evolution, Biochemistry, Actions, and Pathophysiology of LH and hCG
Authors: Livio Casarini, Daniele Santi, Giulia Brigante, Manuela Simoni
Journal: Endocrine Reviews (2018)

LH and chorionic gonadotropin (CG) are glycoproteins fundamental to sexual development and reproduction. Because they act on the same receptor (LHCGR), the general consensus has been that LH and human CG (hCG) are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ~85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in an ~90-minute half-life molecule targeting the gonads to regulate gametogenesis and androgen synthesis. Trophoblast hCG, the "pregnancy hormone," exists in several isoforms and glycosylation variants with long half-lives (hours) and angiogenic potential and acts on luteinized ovarian cells as progestational. The different molecular features of LH and hCG lead to hormone-specific LHCGR binding and intracellular signaling cascades. In ovarian cells, LH action is preferentially exerted through kinases, phosphorylated extracellular-regulated kinase 1/2 (pERK1/2) and phosphorylated AKT (also known as protein kinase B), resulting in irreplaceable proliferative/antiapoptotic signals and partial agonism on progesterone production in vitro. In contrast, hCG displays notable cAMP/protein kinase A (PKA)-mediated steroidogenic and proapoptotic potential, which is masked by estrogen action in vivo. In vitro data have been confirmed by a large data set from assisted reproduction, because the steroidogenic potential of hCG positively affects the number of retrieved oocytes, and LH affects the pregnancy rate (per oocyte number). Leydig cell in vitro exposure to hCG results in qualitatively similar cAMP/PKA and pERK1/2 activation compared with LH and testosterone. The supposed equivalence of LH and hCG has been disproved by such data, highlighting their sex-specific functions and thus deeming it an oversight caused by incomplete understanding of clinical data.
Diffuse 18F-FDG Avidity in Liver Associated With X-Linked Protoporphyria on PET/CT
Authors: Zhanli Fu, Meng Liu, Xueqi Chen, Xing Yang, Qian Li
Journal: Clinical Nuclear Medicine (2018)

Abstract An 18 F-FDG PET/CT was performed on a 43-year-old woman with photosensitive skin rash, abnormal liver function, and pancytopenia, which demonstrated prominent hepatomegaly, splenomegaly, and diffuse liver 18 F-FDG avidity. The liver biopsy revealed intrahepatic cholestasis with biliary fibrosis resulting from the deposition of protoporphyrin. X-linked erythroid-specific 5-aminolevulinate synthase gene analysis proved the diagnosis of X-linked protoporphyria.
Flightless-I Blocks p62-Mediated Recognition of LC3 to Impede Selective Autophagy and Promote Breast Cancer Progression
Authors: Jian-Ping He, Pei-Pei Hou, Qi-Tao Chen, Wei-Jia Wang, Xiao-Yu Sun, Peng-Bo Yang, Ying-Ping Li, Lu-Ming Yao, Xiaotong Li, Xin-Dong Jiang, Kun-Yi Chien, Zhi-Ming Zhang, Qiu-Wan Wu, Allison J. Cowin, Qiao Wu, Hang-Zi Chen
Journal: Cancer Research (2018)

Abstract p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here, we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded the development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlated with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer. Significance: Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer.Cancer Res; 78(17); 4853–64. ©2018 AACR.
OP0043 Predictors of drug-free remission in rheumatoid arthritis: results from the prospective biomarkers of remission in rheumatoid arthritis(BIORRA) study
Authors: K.F. Baker, A. Skelton, D. Lendrem, B. Thompson, A.G. Pratt, J.D. Isaacs
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Remission is now a realistic and achievable target for many patients with rheumatoid arthritis (RA) using disease-modifying anti-rheumatic drugs (DMARDs) prescribed in modern treat-to-target regimens. However, DMARDs carry risks of potentially serious adverse effects, and require regular and expensive blood monitoring. Recent studies suggest that half of patients with RA in remission can discontinue DMARDs without a flare of arthritis activity, though this cannot currently be reliably predicted. <h3>Objectives</h3> To identify baseline biomarkers that can predict sustained drug-free remission (DFR) versus arthritis flare following DMARD cessation. <h3>Methods</h3> Patients with established RA satisfying clinical (disease activity in 28 joints with CRP [DAS28-CRP]&lt;2.4) and ultrasound (absence of power Doppler synovitis on a blinded 7-joint scan) remission criteria discontinued conventional synthetic DMARDs (methotrexate, sulfasalazine, and/or hydroxychloroquine) and were monitored for 6 months. The primary outcome was time-to-flare, defined as DAS28-CRP≥2.4. Baseline clinical and ultrasound parameters (synovial/tenosynovial greyscale and joint erosions), circulating levels of 26 cytokines/chemokines, and gene expression by peripheral CD4 +T cells (RNA sequencing) were assessed for their ability to predict time-to-flare and flare/DFR status by multivariate Cox regression and receiver-operating characteristic (ROC) analysis. <h3>Results</h3> 44 patients were eligible for DMARD cessation (table 1); 23 (52%) experienced an arthritis flare at a median (IQR) of 48 (31.5–86.5) days. A composite score incorporating five variables (three genes [currently subject to patent application], one cytokine [IL-27], and one clinical [ACR/EULAR Boolean remission]) differentiated future flare and DFR with an area under the ROC curve of 0.96 (95% CI: 0.92 to 1.00), sensitivity 0.91 (0.78–1.00) and specificity 0.95 (0.84–1.00) (figure 1). <h3>Conclusions</h3> Our study provides proof-of-concept evidence for the existence of biomarkers of DFR in RA. If validated in an external cohort, these biomarkers may hold promise in guiding DMARD withdrawal, with consequent minimisation of medication adverse events and healthcare costs. <h3>Acknowledgements</h3> KB was supported by the Wellcome Trust [102595/Z/13/A] and the NIHR Newcastle Biomedical Research Centre [BH136167/PD0045]. A patent application is currently in process regarding the gene expression biomarkers, the identify of which will subsequently be disclosed. <h3>Disclosure of Interest</h3> None declared
OP0052 Microparticles as potential biomarkers of disease activity in anti-neutrophil cytoplasmic antibody – associated vasculitis
Authors: A. Antovic, M. Kostic, F. Mobarrez, A. Nordin, J. Vojinovic, A. Bruchfeld, I. Gunnarsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Microparticles (MPs) are submicron particles, which are released from plasma membrane upon cell activation and during the early phase of apoptosis. Increased levels of circulating MPs, mainly of endothelial cell origin, but also platelet derived, have been shown to correlate with autoinflammatory disease activity, such as anti-neutrophil cytoplasm antibody (ANCA) – associated vasculitis (AAV). <h3>Objectives</h3> The aim was to evaluate levels of activity markers expressed on MPs from patients with AAV, during active disease and remission, compared to healthy control subjects. <h3>Methods</h3> Our study included 46 AAV patients and 23 healthy age and gender matched control subjects. We analysed the concentration of MPs in plasma by flow cytometry. MPs were phenotyped by expression: CD142 (tissue factor-TF), anti-H3cit (citrulinated Histone 3 directed against neutrophil extracellular traps – NETs), anti-pentraxin3 (pentraxin3), HMGB1 (high mobility group box 1 protein-HMGB1), anti-TWEAK (tumour necrosis factor-like weak inducer of apoptosis-TWEAK), anti-plasminogen (plasminogen), anti-C3a (C3a) and anti-C5a (C5a). The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS), where active disease was defined as BVAS ≥1 and inactive (remission) as BVAS=0. <h3>Results</h3> Half of the patients group<sup><sup>23</sup></sup> had active vasculitis (13 male/10 female, mean age 61±14 years) and 23 had inactive disease (12 male/11 female, mean age 64±13 years). Concentration of MPs expressing TF, H3cit, pentraxin-3 and HMGB1 in active patients were significantly higher than in those in remission and healthy controls (p&lt;0.01, p&lt;0.0001, respectively). MPs expressing C5a and C3a were significantly higher in both active and inactive patients compared to controls (p&lt;0.001). Additionally, levels of MPs expressing C5a and C3a strongly correlated with BVAS in patients with active disease (r=0.78, p&lt;0.0001; r=0.5, p&lt;0.01, respectively), while there was no significant correlation between other explored markers and BVAS. <h3>Conclusions</h3> Our results support recently postulated role of the complement system in AAV pathogenesis and disease activity. Evaluated proteins expressed on MPs, especially C5a and C3a, could be used as potential biomarkers which might reflect inflammation and disease activity in AAV patients. Further investigations are necessary to confirm our preliminary results and to validate the most promising biomarker in AAV. <h3>Disclosure of Interest</h3> None declared
AB0516 Therapeutic strategies and prognosis in chinese patients with serologically active clinically quiescent systemic lupus erythematosus
Authors: H. Huang, L. Mou, Y. Hao, Z. Zhang, W. Zhou
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> SACQ patients with SLE appears to account for 6%–12% of all patients with SLE, but there is disagreement about whether such patients are indeed clinically stable, especially in Chinese patients. And there is no conclusion as to what kind of treatment should be taken for such patients. <h3>Objectives</h3> The aim of our study was to identify the frequency and outcome of SACQ patients with SLE. And we tried to find out potential predictors of flare. <h3>Methods</h3> 682 patients with systemic lupus erythematosus who were followed up for more than 6 months at Peking University First Hospital from January 2007 to December 2015 were summarised. SACQ was defined as an at least a 6 month period with persistent serologic activity and without clinical activity and could be taking a daily dose of prednisone or equivalent less than 7.5 mg. Serologically quiescent clinically quiescent (SQCQ) patients and serologically active clinically active (SACA) patients served as control groups. Data including demographics, initial symptoms, duration to SACQ, treatments before and after SACQ, and characteristics of the flare group were analysed. <h3>Results</h3> Of the 682 patients, 170 were SACQ patients (24.9%), 187 were SQCQ patients, and 325 were SACA patients (47.7%). SQCQ patients (38.61±15.08 years old) were older at study start than did SACQ patients (38.61±15.08 years vs. 32.09±14.35 years, p=0.000), but there was no significant difference between that of SACQ and SACA patients. 56 of the 170 SACQ patients (32.9%) experienced flare. Corticosteroids (OR 1.323, 95% CI 1.135 to 1.542; p=0.000) was an independent risk factor for flare, while antimalarials (OR 0.040, 95% CI 0.004 to 0.418; p=0.007) and immunosuppressants (OR 0.321, 95% CI 0.153 to 0.673; p=0.003) were protective factors. <h3>Conclusions</h3> SLE patients with SACQ remained relatively stable, with 32.9% of patients relapsed. The group of flare patients took greater use of corticosteroids than non-flare ones, whereas antimalarials and immunosuppressants agents were protective factors. <h3>References</h3> [1] Gladman DD, Urowitz MB, Keystone EC. Serologically active clinically quiescent systemic lupus erythematosus: a discordance between clinical and serologic features. Am J Med1979;66:210–5. [2] Huang WN, Tso TK, Wu HC, Yang HF, Tsay GJ. Impaired phagocytosis of apoptotic cell material in serologically active clinically quiescent patients with systemic lupus erythematosis. Int J Rheum Dis2016;19:1310–6. [3] Steiman AJ, Gladman DD, Ibañez D, Urowitz MB. Prolonged serologically active clinically quiescent systemic lupus erythematosus: frequency and outcome. J Rheumatol2010;37:1822–7. <h3>Disclosure of Interest</h3> None declared
Validation of Modified ALBI Grade for More Detailed Assessment of Hepatic Function in Hepatocellular Carcinoma Patients: A Multicenter Analysis
Authors: Atsushi Hiraoka, Takashi Kumada, Kunihiko Tsuji, Koichi Takaguchi, Ei Itobayashi, Kazuya Kariyama, Hironori Ochi, Kazuto Tajiri, Masashi Hirooka, Noritomo Shimada, Toru Ishikawa, Yoshihiko Tachi, Toshifumi Tada, Hidenori Toyoda, Kazuhiro Nouso, Kouji Joko, Yoichi Hiasa, Kojiro Michitaka, Masatoshi Kudo
Journal: Liver Cancer (2018)

&lt;b&gt;&lt;i&gt;Background/Aim:&lt;/i&gt;&lt;/b&gt; The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. &lt;b&gt;&lt;i&gt;Materials/Methods:&lt;/i&gt;&lt;/b&gt; We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, &lt;i&gt;n&lt;/i&gt; = 2,357) and validation (validation group: V group, &lt;i&gt;n&lt;/i&gt; = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.