tbuckley/cabot-search huggingface dataset:
Eduardo “Eddie” Méndez: In Memoriam (1972–2018)
Authors: Christopher J. Kemp
Journal: Clinical Cancer Research (2018)

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The cancer research community has lost one its most promising rising stars. Eduardo “Eddie” Mendez passed away January 5, 2018, at the age of 45 after a 2-year battle with cancer. His most recent work is published in this issue of Clinical Cancer Research . Few are blessed
Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition)
Authors: Jian Zhou, Hui-Chuan Sun, Zheng Wang, Wen-Ming  Cong, Jian-Hua Wang, Meng-Su Zeng, Jia-Mei Yang, Ping Bie, Lian-Xin Liu, Tian-Fu Wen, Guo-Hong Han, Mao-Qiang Wang, Rui-Bao Liu, Li-Gong Lu, Zheng-Gang Ren, Min-Shan Chen, Zhao-Chong Zeng, Ping Liang, Chang-Hong Liang, Min Chen, Fu-Hua Yan, Wen-Ping Wang, Yuan Ji, Wen-Wu Cheng, Chao-Liu Dai, Wei-Dong Jia, Ya-Ming Li, Ye-Xiong Li, Jun Liang, Tian-Shu Liu, Guo-Yue Lv, Yi-Lei Mao, Wei-Xin Ren, Hong-Cheng Shi, Wen-Tao Wang, Xiao-Ying Wang, Bao-Cai Xing, Jian-Ming Xu, Jian-Yong Yang, Ye-Fa Yang, Sheng-Long Ye, Zheng-Yu Yin, Bo-Heng Zhang, Shui-Jun Zhang, Wei-Ping Zhou, Ji-Ye Zhu, Rong Liu, Ying-Hong Shi, Yong-Sheng Xiao, Zhi Dai, Gao-Jun Teng, Jian-Qiang Cai, Wei-Lin Wang, Jia-Hong Dong, Qiang Li, Feng Shen, Shu-Kui Qin, Jia Fan
Journal: Liver Cancer (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
AB0551 Obstetrical morbidity related to anti-ssa antibodies: data from a french monocentric retrospective study
Authors: L. Plaçais, F. Carrat, L. Carbillon, P. Nicaise, A. Benbara, O. Fain, A. Mekinian
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Obstetrical morbidity is an issue among autoimmune diseases patients. Anti-SSA positivity is well known for it's effect on fetus and risk of congenital heart block but no evidence has been yet found for its effect on obstetrical morbidity <h3>Objectives</h3> To investigate anti-SSA positivity effect among a large monocentric cohort of obstetrical morbidity patients and to evaluate the efficacity of different treatment regimens <h3>Methods</h3> All women who were seen from January 2010 to January 2015 in Jean-Verdier University Hospital for obstetrical morbidities were retrospectively included. All patients had been tested for anti-nuclear antibodies and anti-SSA/Ro and anti-SSB/La antibodies. <h3>Results</h3> We included 244 women (median age 34 years [interquartile range 21–53]) with 869 pregnancies overall. In 27 (11%) patients with anti-SSA antibodies, the median age at the time of pregnancy was 29.5 (17–40) years, with mean number of 3.66 pregnancies per woman. For these 27 patients, 83/99 pregnancies (84%) had an adverse obstetrical outcome: fetal loss (n=65; at a median of 20 (4–38) weeks' gestation), preeclampsia (n=15), intrauterine growth restriction (n=7), prematurity (n=7), and congenital heart block (n=2). In comparing women with obstetrical antiphospholipid syndrome and unexplained adverse complications, there was no major difference in frequency of recurrent miscarriages, preterm deliveries, preeclampsia or fetal loss. Among factors associated with obstetrical outcome and fetal loss, aspirin and hydroxychloroquine treatments were significantly associated with a favourable obstetrical outcome: odds ratio 0.05 [95% confidence interval 0.01; 0.37] (p=0.003) and 0.15 [0.02; 0.98] (p=0.04). <h3>Conclusions</h3> Women with unexplained recurrent obstetrical complications should be screened for anti-SSA antibodies. The benefit of aspirin and hydroxychloroquine treatment to improve the obstetrical outcome should be confirmed in prospective studies. <h3>Disclosure of Interest</h3> None declared
FRI0160 Interleukin-17a induces inflammatory response via nlrp3 inflammasome in ankylosing spondylitis
Authors: D. Kim, S.-W. Lee, J.J. Song, Y.-B. Park, M.-C. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inflammasomes are cytoplasmic multiprotein complexes that recognise various exogenous and endogenous danger signals in myeloid cells, particularly macrophages. Inflammasome activation eventually induces inflammatory responses in macrophages by activating gasdermin-d-mediated pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)−1β and IL-18 in a caspase-1-dependent manner. The production of IL-1 has been found to be highly induced in AS<sup>1</sup> and caspase-1 level was significantly elevated in spondyloarthritis patients than in those with other arthritic diseases,<sup>2</sup> suggesting the possibility that inflammasomes might be involved in pathogenesis of ankylosing spondylitis (AS). However, few studies have addressedd the roles of inflammasomes in AS. <h3>Objectives</h3> This study was performed to investigate the role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the peripheral blood mononuclear cells (PBMCs) from AS patients. <h3>Methods</h3> PBMCs from 11 patients and 9 healthy controls were isolated and mRNA expression levels of NLRP3 inflammasome, pro-IL-1β, IL-1β, pro-caspase-1, and caspase-1 were determined using quantitative real-time PCR. IL-17A (100 ng/mL) was added to the cell cultures, then, cytokine expression, signalling pathways, and inflammasome machinery are determined using real-time RT-PCR and Western blot. After transfection of siNLRP3 to AS PBMCs, mRNA and proteins levels of IL-1β and caspase-1 were determined using real time PCR and western blot. <h3>Results</h3> Expressions of NLRP3, IL-1β, and caspase-1 mRNAs, but not IL-18, were increased in PBMCs from AS patients compared to controls. Incubation of AS PBMCs with IL-17A significantly increased NLRP3, IL-1β, IL-18, and caspase-1 expressions in AS PBMCs. Western blot showed IL-17A treatment induced the phosphorylation of Akt, p38 MAPK, and NF-κB p65 in AS PBMCs. Down-regulation of NLRP3 by transfection of siRNA decreased mRNA expressions and productions of IL-1β and caspase-1 in AS PBMCs. <h3>Conclusions</h3> Activity of NLRP3 inflammasome was increased in AS patients and IL-17A potentiated the activation of NLRP3 inflammasome. Our data suggest the possible role of NLRP3 inflammasome in inflammatory response in AS. <h3>References</h3> [1] Tan AL, Marzo-Ortega H, O'Connor P, Fraser A, Emery P, McGonagle D. Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis. 2004;63:1041–1045. [2] Son CN, Bang SY, Kim JH, Choi CB, Kim TH, Jun JB. Caspase-1 level in synovial fluid is high in patients with spondyloarthropathy but not in patients with gout. J Korean Med Sci. 2013;28:1289–1292. <h3>Disclosure of Interest</h3> None declared
SP0049 Head games with gca and gcs
Authors: M. Matza
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Case 1: This is a 65 y/o woman with osteoporosis, depression and recently diagnosed polymyalgia rheumatica characterised by shoulder and hip girdle pain and stiffness with elevated inflammatory markers. She developed recurrent symptoms and new-onset jaw and tongue claudication in the setting of a prednisone taper. She was found to have a bulging right temporal artery and biopsy confirmed giant cell arteritis. She was placed on prednisone 60 mg daily with resolution of her symptoms, but developed worsening symptoms of depression and anxiety with insomnia on high dose prednisone. She subsequently attempted suicide by intentional medication overdose and carbon monoxide poisoning. She was admitted to the psychiatry ward and additionally found to have a varicella zoster skin rash. Upon resolution of the zoster infection she was started on tocilizumab by subcutaneous injection weekly and prednisone was successfully tapered over 4.5 months without recurrence of symptoms. Case 2: This is a 63 y/o man with ITP on monthly rituximab and chronic prednisone 10 mg daily, hypertension, hyperlipidemia and osteoarthritis who developed worsening shoulder and neck pain for two months with more recent onset of scalp tenderness and left-sided vision changes for two weeks. He was found to have left optic neuropathy, elevated inflammatory markers, and an MRI demonstrating enhancement of the left temporal artery. Left temporal artery biopsy was normal. He was given pulse dose intravenous methylprednisolone for suspected giant cell arteritis and transitioned to high dose oral prednisone with improvement in musculoskeletal symptoms, inflammatory markers and stabilisation of his vision. He subsequently developed insomnia, hyperactivity and talkativeness and was diagnosed with steroid-induced mania, which improved with antipsychotics and benzodiazepines as per the psychiatry service. He was discharged home and after three days developed new vision loss of the right eye on prednisone 60 mg daily. On exam, he was found to have progressive visual field loss of the left eye and new inferior visual field loss of the right eye with disc oedema of the right optic nerve. Right temporal artery biopsy was negative. He was again given pulse dose intravenous methylprednisolone followed by oral methylprednisolone and ultimately received tocilizumab intravenously prior to discharge. <h3>Disclosure of Interest</h3> None declared
Statins enhance efficacy of venetoclax in blood cancers
Authors: J. Scott Lee, Andrew Roberts, Dennis Juarez, Thanh-Trang T. Vo, Shruti Bhatt, Lee-or Herzog, Sharmila Mallya, Richard J. Bellin, Suresh K. Agarwal, Ahmed Hamed Salem, Tu Xu, Jia Jia, Lingxiao Li, John R. Hanna, Matthew S. Davids, Angela G. Fleischman, Susan O’Brien, Lloyd T. Lam, Joel D. Leverson, Anthony Letai, Jonathan H. Schatz, David A. Fruman
Journal: Science Translational Medicine (2018)

Statins have shown promise as anticancer agents in experimental and epidemiologic research. However, any benefit that they provide is likely context-dependent, for example, applicable only to certain cancers or in combination with specific anticancer drugs. We report that inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) using statins enhances the proapoptotic activity of the B cell lymphoma-2 (BCL2) inhibitor venetoclax (ABT-199) in primary leukemia and lymphoma cells but not in normal human peripheral blood mononuclear cells. By blocking mevalonate production, HMGCR inhibition suppressed protein geranylgeranylation, resulting in up-regulation of proapoptotic protein p53 up-regulated modulator of apoptosis (PUMA). In support of these findings, dynamic BH3 profiling confirmed that statins primed cells for apoptosis. Furthermore, in retrospective analyses of three clinical studies of chronic lymphocytic leukemia, background statin use was associated with enhanced response to venetoclax, as demonstrated by more frequent complete responses. Together, this work provides mechanistic justification and clinical evidence to warrant prospective clinical investigation of this combination in hematologic malignancies.
AB0789 How does the duration of the disease influence the quality of life?
Authors: N. Loghin-Oprea, S. Vetrila, L. Mazur-Nicorici, V. Salaru, M. Mazur
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is noticed that over the last decades the prognostic in patients with Idiopathic Inflammatory Myopathies (IIM) – a group of autoimmune disease characterised by muscle involvement, has improved along with increasement of disease duration and thus affects the quality of life. <h3>Objectives</h3> To assess the patient's quality of life related to the duration of the disease. <h3>Methods</h3> We performed a cross-sectional study from December 2015 to December 2017, the patients included fulfilled the Bohan and Peter<sup>1</sup> criteria for IIM. Demographic and clinical data were collected using a special questionnaire. Consistent with the objective the study group was divided in two subgroups by disease duration 1-less than 24 months and second subgroup maore than 2 years. In order to estimate the quality of life (QoL) was applied Short Form-8 with 8 items for 8 domains and two components: mental and physical. Statistical data was analysed using MedCalc software version 12. <h3>Results</h3> There were 67 patients enrolled in the study, including 51 females and 16 males with a F:M ratio of 3.2:1, mean age 53.1±12.5 (range 25–78). The disease mean disease duration was 8.3±5.3 (range 0.5–12) years, there were 16 patients in the subgroup with the disease duration less than 2 years. The mean physical component was 36.48±9.05 and the mental component – 41.69±9.62 points, determined as reduced quality of life. Regarding the QoL of patients from subgroup 1, we found the physical component – 38.15±8.83 and the mental was 40.95±9.22 points. In the second subgroup we appreciated the physical and the mental component – 35.77±9.14 and 42.01±9.86 points, respectively. It was identified moderate correlation (r=0.49 p&lt;0.005) between the both domains of the QoL and disease duration till 2 years, for the duration of more than 2 years we found moderate correlation (r=0.51 p&lt;0.005) with mental compound and a weak one for physical domain (r=0.24 p&lt;0.005). <h3>Conclusions</h3> Patients with idiopathic inflammatory myopathies had reduced quality of life by both domains. Disease duration in patients with early idiopathic inflammatory myopathies – less than 2 years, has a greater impact on patient's quality of life. <h3>Reference</h3> [1] Bohan A, Peter JB. N Engl J Med1975Feb 13;292(7):344–7. <h3>Disclosure of Interest</h3> None declared
Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity
Authors: Maria B. Asparuhova, Jordi Caballé-Serrano, Daniel Buser, Vivianne Chappuis
Journal: International Journal of Oral Science (2018)

Abstract Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral (DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant ( P &lt; 0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2 was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.
SAT0623 Clinical features and treatment of idiopathic recurrent acute pleuro-pericarditis
Authors: K. Dietz, H.-M. Lorenz, N. Blank
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Idiopathic recurrent acute pleuro-pericarditis (IRAP) is an increasingly recognised autoinflammatory disease comprising post-pericardiotomy-syndrome, recurrent pericarditis and post-myocardial-infarction-syndrome. Different autoimmune mechanisms were discussed in the past. Recently, IRAP is considered as an autoinflammatory disease. Therapeutic options comprise colchicine, prednisolone and interleukin (IL)−1beta blockingagents. <h3>Objectives</h3> to investigate whether idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum and to identify treatment options. <h3>Methods</h3> This study analyses demographic, clinical and laboratory features of post-interventional and idiopathic pleuro-pericarditis and adult onset Still's disease (AOSD) as a reference. Patients with infectious disease, connective tissue disease, chronic heart failure, renal failure and other non-exsudative effusions were excluded from this analysis. Patients with IRAP were treated with colchicine, prednisolone and IL1β blocking agents. <h3>Results</h3> Between 2005 and 2017 66 cases of idiopathic and post-interventional pleuro-pericarditis were identified and compared to 83 cases of AOSD. Clinical and laboratory features suggest that idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum which is identical with IRAP. Prednisolone was started with 25 mg to 125 mg and tapered to less than 7 mg or discontinued if not effective. 47 of 66 patients (71%) were treated with prednisolone and 10/47 (21%) were in remission with no need of any further therapeutically escalation. Colchicine was given to 44/66 patients (67%) and 29/44 (66%) were in complete remission. Four of 66 patients (6%) did not respond or had contraindications against colchicine or prednisolone and were treated with anakinra. Of these patients 4/4 (100%) were in remission. During the follow-up period of 20 patient*months 2 of 4 patients maintained the remission with anakinra every 2nd day and two patients discontinued anakinra and remained in remission. <h3>Conclusions</h3> 1. post-pericardectomy-syndrome, post-myocardial-infarction-syndrome and idiopa-thic recurrent pericarditis represent a clinical spectrum of autoinflammatory diseases. 2. treatment options comprise colchicine as a first-line therapy, prednisolone and anti-IL1 blocking agents. <h3>Acknowledgements</h3> none. <h3>Disclosure of Interest</h3> None declared
SAT0609 Venous vessel wall thickness in lower extremity is increased in male behcet’s disease patients with and without vascular involvement
Authors: F. Alibaz-Oner, R. Ergelen, A. Mutis, Z. Erturk, R. Asadov, T. Ergun, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vascular involvement is seen in up to 40% of the patients with Behcet's Disease (BD), especially in young males and is one of the major causes of mortality and morbidity. Lower extremity vein thrombosis due to vascular inflammation is the most frequent form of vascular involvement in BD. Recently, assessment of vessel wall thickness (VWT) and venous dilatation by US is suggested to be valuable in patients with vascular inflammation. <h3>Objectives</h3> In this study, we investigated whether vessel wall thickness or dilatation is present in young male BD patients prone to venous vascular disease. <h3>Methods</h3> Thirthy male patients with BD without major organ involvement and 29 male patients with Vascular BD(VBD) followed in Marmara University Behcet's Clinics, 24 healthy male controls and 27 male patients with Ankylosing Spondylitis (AS) were included the study. Bilateral lower extremity venous doppler ultrasonography (US) was performed by an experienced radiologist blinded to cases. No patients except VBD were under immunosuppressive treatment. Bilateral common femoral vein (CFV) wall thickness and great/small saphenous vein dilatations were examined. Behçet Syndrome Activity Score (BSAS) was used for the general assessment of disease activity. In 10 patients, CFV wall thickness was measured by 2 different radiologist (RE, RA) in the same day to calculate "inter-observer reliability". Correlation between radiologists was good. (r=0.765, p&lt;0.001). <h3>Results</h3> The mean disease duration was 9.1±6 years in patients with BD. BSAS score was 24±17. All venous measurements were significantly higher in BD compared to AS and healthy controls (p&lt;0.001 for all, table 1). When we compared mucucutaneous BD and VBD, all measurements of patients with VBD were higher than mucocutaneous BD. But only left CFV thickness and width of right great saphenous vein reached the statistical significance (p&lt;0.001, an p=0.028, respectively, figure 1). There were no correlations between BSAS, acute phase reactants and venous wall measurements. <h3>Conclusions</h3> In our study, an increased venous vessel wall thickness in lower extremity was shown in male BD patients with or without vascular involvement. As a similar change was not observed in controls, we think, increased VWT might be an early sign of venous inflammation in patients with BD rather than a result of non-specific systemic inflammation. <h3>Disclosure of Interest</h3> None declared
Irregular Narrow Complex Tachycardia in the Setting of Congenital Heart Disease
Authors: Adam Oesterle, Zian H. Tseng
Journal: JAMA Internal Medicine (2018)

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Prenatal and Postnatal Intervention for a Congenital Lung Mass
Authors: Laura A. Galganski, Jamie E. Anderson, Payam Saadai
Journal: JAMA Surgery (2018)

A 9-month-old infant with a prenatal history of fetal hydrops treated with a thoracoamniotic shunt and a postnatal history of pleural effusion presents with a lung mass that has a feeding vessel. What is your diagnosis?