tbuckley/cabot-search huggingface dataset:
THU0063 IL-1 family cytokines and receptors in IGG4-related disease
Authors: R Capecchi, P Italiani, I Puxeddu, F Pratesi, A Tavoni, D Boraschi, P Migliorini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect almost any organ, characterized by lymphoplasmocytoid infiltrate, obliterative phlebitis and storiform fibrosis often associated with eosinophilia and increased levels of IgG4. Cytotoxic CD4 T cells producing IL-1b [D1], TGFb1 and IFN-gare detectable in peripheral blood of patients and high IL-18 expression has been found in affected organs. <h3>Objectives</h3> To evaluate the role of IL-1 family cytokines in IgG4-RD, by analyzing cytokines and receptors in sera. <h3>Methods</h3> Nine patients fulfilling the proposed criteria (Umehara, 2012) for the diagnosis of IgG4-RD were recruited. Cytokines of the IL-1 family (IL-1a, IL-1b, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, sIL-1R4) and antagonists (IL-1Ra, IL-18BP) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated using the law of mass action. <h3>Results</h3> Most patients had a multiorgan disease; retroperitoneum, salivary glands, pancreas and lymph nodes were most frequently affected. IL-18 (p=0.007) and free IL-18 (p&lt;0.0001), sIL-1R1 (p=0.0005), sIL-1R2 (p=0.0013), and sIL-1R4 (p=0.0006) were significantly increased in IgG4-RD sera compared with healthy controls. <h3>Conclusions</h3> In IgG4-RD patients, at variance with other autoimmune or autoinflammatory conditions, the increase in IL-18 levels is not counterbalanced by IL-18BP, leading to high levels of free IL-18.The free cytokine may affect T cell subset balance and induce IFN-g production. The parallel increase of sIL-1R1 and sIL-1R2 suggests an efficient dampening of inflammatory IL-1bsignaling at the tissue level, while high levels of sIL-1R4 may be associated with vascular remodeling and fibrosis, as observed in animal models of obesity and in human cardiovascular disorders. <h3>Disclosure of Interest</h3> None declared
Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression
Authors: Shancheng Ren, Gong-Hong Wei, Dongbing Liu, Liguo Wang, Yong Hou, Shida Zhu, Lihua Peng, Qin Zhang, Yanbing Cheng, Hong Su, Xiuqing Zhou, Jibin Zhang, Fuqiang Li, Hancheng Zheng, Zhikun Zhao, Changjun Yin, Zengquan He, Xin Gao, Haiyen E. Zhau, Chia-Yi Chu, Jason Boyang Wu, Colin Collins, Stanislav V. Volik, Robert Bell, Jiaoti Huang, Kui Wu, Danfeng Xu, Dingwei Ye, Yongwei Yu, Lianhui Zhu, Meng Qiao, Hang-Mao Lee, Yuehong Yang, Yasheng Zhu, Xiaolei Shi, Rui Chen, Yang Wang, Weidong Xu, Yanqiong Cheng, Chuanliang Xu, Xu Gao, Tie Zhou, Bo Yang, Jianguo Hou, Li Liu, Zhensheng Zhang, Yao Zhu, Chao Qin, Pengfei Shao, Jun Pang, Leland W.K. Chung, Jianfeng Xu, Chin-Lee Wu, Weide Zhong, Xun Xu, Yingrui Li, Xiuqing Zhang, Jian Wang, Huanming Yang, Jun Wang, Haojie Huang, Yinghao Sun
Journal: European Urology (2017)
Neutrophil transfer of <i>miR-223</i> to lung epithelial cells dampens acute lung injury in mice
Authors: Viola Neudecker, Kelley S. Brodsky, Eric T. Clambey, Eric P. Schmidt, Thomas A. Packard, Bennett Davenport, Theodore J. Standiford, Tingting Weng, Ashley A. Fletcher, Lea Barthel, Joanne C. Masterson, Glenn T. Furuta, Chunyan Cai, Michael R. Blackburn, Adit A. Ginde, Michael W. Graner, William J. Janssen, Rachel L. Zemans, Christopher M. Evans, Ellen L. Burnham, Dirk Homann, Marc Moss, Simone Kreth, Kai Zacharowski, Peter M. Henson, Holger K. Eltzschig
Journal: Science Translational Medicine (2017)

Intercellular transfer of miR-223 from neutrophils to alveolar epithelial cells reduces lung inflammation in a mouse model of ventilator-induced lung injury or pulmonary bacterial infection.
Laparoscopic near-infrared fluorescent imaging as an alternative option for sentinel lymph node mapping in endometrial cancer: A prospective study
Authors: Salih Taşkın, Yavuz Emre Şükür, Duygu Altın, Cevriye Cansız Ersöz, Batuhan Turgay, Duygu Kankaya, Mete Güngör, Fırat Ortaç
Journal: International Journal of Surgery (2017)
SAT0384 Risk of myocardial infarction and cerebrovascular accident in ankylosing spondylitis: a general population-based study
Authors: ACL So, J Chan, EC Sayre, JA Avina-Zubieta
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There is conflicting data on the risk of myocardial infarction (MI) and cerebrovascular accidents (CVA) in patients with Ankylosing Spondylitis (AS). <h3>Objectives</h3> 1) To assess the future risk of newly recorded MI and CVA events among incident cases of AS compared to non-AS controls from the general population by utilizing physician billing, medication, and hospitalization data that covers the entire province of British Columbia (BC), Canada. <h3>Methods</h3> Our data includes all outpatient visits and hospitalizations (1990–2012) and all dispensed medications (1996–2012) for all BC residents. We conducted a retrospective matched cohort study of all patients &gt;18 years of age satisfying the following criteria: 1) two ICD-9 or 10 codes (720.0 or M45) for AS at least two months apart and within a 2-year period by any physician or hospitalization; 2) all AS cases had at least a 7-year run-in period before the 1st ICD code for AS in order to consider the case as incident. Each AS patient was matched with up to 10 controls by birth year, sex, and entry cohort time. The outcomes were a newly recorded MI (ICD-9-CM: 410 or ICD-10-CM: I21) or CVA (ICD-9 codes: 433–434, ICD-10 codes: I63-I66) event from hospital or death certificates. We estimated relative risks (RRs), adjusting for age, sex, and entry cohort time as well as multivariable models adjusting for confounders including glucocorticoids and non-steroidal anti-inflammatory drugs using a Cox proportional hazard model. <h3>Results</h3> 7,190 individuals with newly diagnosed AS were identified (48.7% female, mean age of 45.8 yrs). 7,148 and 7,107 were free of previous CVA/MI, respectively. 80 developed CVA (incidence rate=1.8 per 1000 patient years) and 115 had MI (incidence rate=2.6 per 1,000 patient years) (Table 1). The age-, sex-, and entry-time-matched RR for CVA was 1.60 (95% CI, 1.25–2.03) and MI was 1.52 (95% CI, 1.24–1.85). When adjusted for cardiovascular risk factors (obesity, angina, COPD, hospitalizations in year before index date, Charlson9s comorbidity index, oral glucocorticoids, cardiovascular drugs, anti-diabetic medication, HRT, contraceptives, fibrates, statins, NSAIDs, and Cox-2 inhibitors), the estimated RR was 1.34 (1.04–1.73) for CVA and 1.21 (0.98–1.49) for MI. <h3>Conclusions</h3> This large population-based study demonstrates an increased risk of CVA, but not for MI. These findings support that increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted for AS patients. <h3>Disclosure of Interest</h3> None declared
Reactive Oxygen Species Produced by NADPH Oxidase Contribute to Cardiac Pathology in a Mouse Model of Sickle Cell Disease
Authors: Georgios E Christakopoulos, Satheesh Chonat, Inigo Valiente-Alandi, Diamantis G Konstantinidis, Amanda Schleper, Nihal Bakeer, Anastacia Loberg, Burns C Blaxall, Yi Zheng, Jeanne James, Punam Malik, Theodosia A Kalfa
Journal: Blood (2016)
Phase 1b/2 trial of ribociclib+binimetinib in metastatic <i>NRAS</i>-mutant melanoma: Safety, efficacy, and recommended phase 2 dose (RP2D).
Authors: Martin H. Schuler, Paolo A. Ascierto, Filip Yves Francine Leon De Vos, Michael Andrew Postow, Carla M.L.- Van Herpen, Matteo S. Carlino, Jeffrey A. Sosman, Carola Berking, Georgina V. Long, Amy Weise, Ralf Gutzmer, Martin Kaatz, Grant A. McArthur, Gary Schwartz, Adil Daud, Kati Maharry, Padmaja Yerramilli-Rao, Lisa Zimmer, Viviana Bozon, Rodabe Navroze Amaria
Journal: Journal of Clinical Oncology (2017)

9519 Background: Simultaneous inhibition of MEK and CDK4/6 may suppress MAPK pathway activation and cell-cycle checkpoint dysregulation in NRAS-mutant melanoma, resulting in enhanced antitumor activity. Phase 1b data are reported. Methods: The phase 1b primary objective was to determine maximum tolerated dose (MTD)/RP2D. A 28-d cycle of oral ribociclib (RIBO) once daily (QD) for 21 d + oral binimetinib (BINI) twice daily (BID) for 28 d, and a 21-d cycle of RIBO QD + BINI BID, both for 14 d per cycle, were evaluated. Secondary objectives were to evaluate efficacy, safety and pharmacodynamics. Results: Based on dose escalation (van Herpen, ESMO 2015), MTD was 600mg RIBO/45mg BINI for the 21-d and 200/45 for the 28-d regimens. Due to promising activity, the 28-d cycle was selected as RP2D(unconfirmed partial response [PR] with limited follow-up occurred in 35% of pts). This finding was supported by comparable and manageable safety and the Bayesian logistic regression model.As of Jan 2017, the RP2D was received by 16 pts in phase 1b (ECOG PS 0/1/2, 63%/31%/6%; elevated lactate dehydrogenase, 44%; stage IVM1c disease, 50%; prior ipilimumab [ipi], 44%; prior anti–programmed death [PD]-1/PD-L1, 31%). Median (range) exposure was 4 (0–13) mo. Common adverse events (AEs) were increased blood creatine phosphokinase, elevated AST, peripheral edema, acneiform dermatitis, diarrhea and fatigue. Common grade 3/4 AEs were elevated AST and ALT (19%/6%), nausea (19%/0%), rash (19%/0%), vomiting (6%/6%) and neutropenia (12%/0%). Confirmed PR (cPR) occurred in 4 pts (25%; time to response, 48–168 d), stable disease in 7 pts (44%), disease progression in 3 pts (19%); 2 pts (12%) were not evaluable. Among cPR pts, 3 had prior ipi and/or anti–PD-1/PD-L1. Median progression-free survival (mPFS) was 6.7 (95% CI, 3.5–9.2) mo. Sequence analysis of synchronous non- RAS genetic alterations will be presented. Conclusions: Combined RIBO/BINI at the selected RP2D had a manageable safety profile and favorable efficacy (based on mPFS) for NRAS-mutant melanoma in phase 1b. Based on these promising data, the phase 2 expansion is underway to assess antitumor activity at the RP2D. Clinical trial information: NCT01781572.
Antibiotics are recommended in preterm labour to stop group B streptococcal transmission
Authors: Susan Mayor
Journal: BMJ (2017)

Women who go into preterm labour before 37 weeks of pregnancy should be offered antibiotics to prevent transmission of group B streptococcal (GBS) disease to their offspring, new guidelines from the Royal College of Obstetricians and Gynaecologists have recommended.1

“This guidance provides clear advice to doctors and midwives on which women should be offered antibiotics to avoid passing GBS infection on to their babies,” said Peter Brocklehurst, professor of women’s health at the University of Birmingham and coauthor of the guideline. “In particular, we hope to reduce the number of early onset group B strep infections and neonatal deaths in babies born before 37 weeks.” …
FRI0007 Methyl gallate inhibits osteoclast formation and function through suppressing the AKT and BTK-PLCγ2-CA2+ signaling, and prevents LPS-induced bone loss
Authors: M-S Lee, JM Baek, J-Y Kim, W-H Yoo, S-J Hong, C-H Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methyl gallate, a plant-derived phenolic constituent has been known to possess numerous pharmacological features against inflammation, oxidation, and cancer. But so far, there have been no evidences to describe relationship between methyl gallate and bone metabolism. <h3>Objectives</h3> In order to propose a promising candidate for osteoporosis, we performed experiments in this study by using methyl gallate. <h3>Methods</h3> we performed screening of methyl gallate utilizing TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis through western blotting and quantitative RT-PCR. Also, we assessed the role of methyl gallate on characteristics of mature osteoclasts. we used LPS-induced bone loss mice as a model of osteoporosis and analyzed using micro-CT system and the right femurs were stained with TRAP and H&amp;E. <h3>Results</h3> we observed that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca<sup>2+</sup> signaling. The blockade of these pathways was reconfirmed through transduction of CA-Akt retrovirus and evaluation of Ca<sup>2+</sup> influx intensity stained with Fluo-3/AM. Indeed, methyl gallate down-regulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that the administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of LPS in vivo through micro-CT and histology. <h3>Conclusions</h3> Consequently, the overall data strongly indicated that methyl gallate could be a useful substance for development of plant-based anti-osteoporotic agent. <h3>Disclosure of Interest</h3> None declared
Factors to Consider for Reducing US Opioid-Related Deaths: Looking Beyond Access—Reply
Authors: Silvia S. Martins, Julian Santaella-Tenorio, Deborah S. Hasin
Journal: JAMA Psychiatry (2017)

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AB0941 Patients profile at orthogeriatric unit: new model of care
Authors: S Hammami, A Meziani, A Ioana, C Dumont, V Latteur
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fractures in elderly patients its a prevalent problem. Older patients due their characteristics requires a specific care. The orthogeriatric Unit has been shown to be one of the most beneficial units. It is important to evaluate the model of care <h3>Objectives</h3> Evaluate the main variables of fractures patients treated at a orthogeriatric Unit and their complications <h3>Methods</h3> This is a partially concurrent prospective study, taking place in a large urban academic hospital GHdC in Belgium. The participants were 87 consecutive elderly people, admitted directly to a geriatric-based orthogeriatric ward. <h3>Results</h3> A total of 87 patients were included. The average age was 85.2±5.2 years, 20 male, 67 female. Most of them (n=44,52%) were admitted for a hip fractures, 44% (n=38) were transferred from emergency department, ISAR score was 3.9±1.1, Preoperative stay was less than 24 h for 54% of our population, Mini nutritional assessment was 18.7±4.3, Mini mental state examination was 20.6±6.4, the Cumulative Illness Rating Scale was 17.1±4.5, the mean number of medicine was 6.8±3.3, Activity of Daily Living 15 days after admission was 12.2±5.5. Delirium was the principal complication 55% (n=44). Mean hospital stay between admission and discharge/transfer to convalescence unit was 23.8±12.9. In-hospital mortality was 11% (n=10) <h3>Conclusions</h3> Fractures is a frequent and disabling pathology among geriatric fragile population, its treatment requires an interdisciplinary approach. This must be managed by the collaboration between geriatrician and orthopedist. We believe that the orthogeriatric Unit providing subacute and acute care will improve the general outcome of fragile geriatric patients <h3>References</h3> González-Montalvo JI et al The orthogeriatric unit for acute patients: a new model of care that improves efficiency in the management of patients with hip fracture. Hip Int. 2010 Apr-Jun;20(2):229–35. Smith TO et al Factors predicting incidence of post-operative delirium in older people following hip fracture surgery: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2017 Jan 17. <h3>Acknowledgements</h3> Geriatric multidisciplinary team working in GHdC Charleroi Belgium. <h3>Disclosure of Interest</h3> None declared
SAT0531 Matrix assisted laser desorption ionization imaging mass spectrometry applied to human osteoarthritis cartilage reveals the intra-tissue metabolic heterogeneity
Authors: M Eveque-Mourroux, P Emans, T Welting, A Boonen, R Heeren, B Cillero-Pastor
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis (OA) is one of the most common diseases, caused by a chronic degenerative disorder of the joint. OA can be related to the metabolic syndrome or metabolic abnormalities being recently defined as a subtype of the disease<sup>1</sup>. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) technology allows for the investigation of the bimolecular distribution of proteins, lipids or metabolites through the in situ analysis of tissue sections. In order to better understand the metabolic OA phenotype, the study of the endogenous metabolic profiles using MALDI-IMS should be considered. <h3>Objectives</h3> The main goal of this study is to apply MALDI-IMS methodology to study the metabolic spatial distribution of cartilage and to reveal intra-tissue and inter-patient heterogeneity. <h3>Methods</h3> Human OA cartilage was obtained from donors undergoing total knee joint replacement. Samples were heat stabilized by a stabilizer system, before being snap frozen. Cartilage punches were sectioned at 12 μm thickness in a cryostat and deposited on indium tin oxide (ITO) glass slides. 9-Aminoacridine (9AA) and N-(1-Naphthyl) Ethylenediamine DihydroChloride (NEDC) matrices were sprayed on the tissues. MALDI-MS profiling and imaging experiments were performed using different mass spectrometers. Data were analyzed by different software dedicated to mass spectrometry. <h3>Results</h3> Results showed that 9AA and NEDC matrices were both able to extract several and different compounds. MALDI-MS/MS was employed with 9AA matrix for molecular identification, confirming for the first time the presence of several metabolites in cartilage such as adenosine triphosphate, adenosine diphosphate, uridine triphosphate or N-Acetylglucosamine. Punches from lesioned and non-lesioned areas from the same OA patient were heat stabilized and sprayed with NEDC matrix. MALDI-IMS experiments at 40-μm of spatial resolution showed a different metabolic distribution between deep and superficial areas but also between lesioned and non-lesioned regions suggesting an evidence in the existence of intra-tissue heterogeneity (figure 1). <h3>Conclusions</h3> MALDI-IMS methodology is a useful technique for metabolite profiling of cartilage and could be employed to study OA patient heterogeneity. This fact will be especially relevant for OA patients suffering of metabolic syndrome. <h3>References</h3> Zhuo, Q., et al. (2012). Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol 8(12): 729–737. <h3>Disclosure of Interest</h3> None declared
Impact of the timing of hepatitis B virus (HBV) identification and anti-HBV therapy initiation on the risk of adverse liver outcomes in patients receiving cancer therapy.
Authors: Jessica Hwang, Maria E. Suarez-Almazor, Scott B. Cantor, Andrea G. Barbo, Heather Y. Lin, Sairah Ahmed, Mariana Chavez-Mac Gregor, Christian Donato-Santana, Cathy Eng, Alessandra Ferrajoli, Michael Fisch, Peter McLaughlin, George R. Simon, Gabriela Rondon, Elizabeth J. Shpall, Anna S. F. Lok
Journal: Journal of Clinical Oncology (2017)

6503 Background: Patients with cancer and hepatitis B virus (HBV) infection receiving cancer therapy are at risk for HBV reactivation. We aimed to determine the impact of early vs. late HBV identification and early vs. late/no anti-HBV therapy on adverse liver outcomes of patients with cancer with chronic (HBsAg+/anti-HBc+) or past (HBsAg-/anti-HBc+) HBV infection. Methods: We retrospectively studied adult patients with solid or hematologic malignancies who received chemotherapy during 2004-2011. Adverse liver-related events included hepatitis flares, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariable hazard models to determine predictors of outcomes. Early was defined as at the initiation of cancer therapy and late as after therapy initiation. Results: There were 18,688 study patients (80.4% had solid tumors). Among patients with hematologic malignancies, 89.6% had HBV testing of which 90.4% was early. Among patients with solid tumors, 10.8% had HBV testing of which 46.4% was early. Prevalence of chronic HBV was 1.1% (52/4905) and past HBV was 7.1% (350/4905). Among patients with chronic HBV with hematologic or solid malignancy, those identified late had 2.95 times (1.45-6.01) higher risk of liver failure than those identified early. Among chronic HBV patients, 59% (23/39) with early testing had early initiation of anti-HBV therapy, while all of those tested late had late/no initiation of anti-HBV therapy. Predictors of liver failure were male sex, chronic HBV, and late HBV identification for patients with solid tumors, and allogeneic SCT for patients with hematologic malignancies. Conclusions: Early HBV identification correlated with early anti-HBV therapy initiation and reduced risk of liver failure after chemotherapy in chronic HBV patients with solid tumors or hematologic malignancies as well as patients with past HBV and solid tumors.
The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction
Authors: Francois T.H. Yu, Xucai Chen, Adam C. Straub, John J. Pacella
Journal: Theranostics (2017)

Rationale: Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction (MVO).MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death.We have shown, both in in vitro and in vivo models, that ultrasound (US) and microbubble (MB) therapy (termed "sonoreperfusion" or "SRP") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established.Objective: In this study, we investigated the role of nitric oxide (NO) during SRP. Methods and results:We first demonstrated in plated cells that US-stimulated MB oscillations induced a 6-fold increase in endothelial nitric oxide synthase (eNOS) phosphorylation in vitro.We then monitored the kinetics of intramuscular NO and perfusion flow rate responses following 2-min of SRP therapy in the rat hindlimb muscle, with and without blockade of eNOS with LNAME.Following SRP, we found that starting at 6 minutes, intramuscular NO increased significantly over 30 min and was higher than baseline after 13 min.Concomitant contrast enhanced burst reperfusion imaging confirmed that there was a marked increase in perfusion flow rate at 6 and 10 min post SRP compared to baseline (>2.5 fold).The increases in intramuscular NO and perfusion rate were blunted with LNAME.Finally, we tested the hypothesis that NO plays a role in SRP by assessing reperfusion efficacy in a previously described rat hindlimb model of MVO during blockade of eNOS.After US treatment 1, microvascular blood volume was restored to baseline in the MB+US group, but remained low in the LNAME group.Perfusion rates increased in the MB+US group after US treatment 2 but not in the MB+US+LNAME group.Conclusions: These data strongly support that MB oscillations can activate the eNOS pathway leading to increased blood perfusion and that NO plays a significant role in SRP efficacy.