tbuckley/cabot-search huggingface dataset:
SAT0309 Can we foresee sle in itp patients? to distinguish itp patients with high risk of sle by a nationwide cohort study-based decision tree
Authors: T-H Li, Y-S Chang, C-Y Tsai
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immune thrombocytopenic purpura (ITP) is an autoimmune-associated thrombocytopenia which is occasionally the initial presentation of systemic lupus erythematosus (SLE), and thus periodical following up has been suggested. Whereas long-term surveillance on all ITP patients would be time and cost-consuming, and thus to distinguish those with high probability of SLE development among ITP patients should be more practical. <h3>Objectives</h3> To distinguish ITP patients with high risk of SLE development by a decision tree model. <h3>Methods</h3> We enrolled ITP patients without previous SLE diagnosis from the National Health Insurance research database between 1997 and 2012 and identified those certificated with catastrophic illness of SLE during follow up, by which the diagnosis was reconfirmed by another rheumatologists. We also analyzed the symptoms and comorbidities as well as the dose of average oral steroid to derive the decision trees, which classified the ITP patients with different probability of development of SLE. <h3>Results</h3> A total of 10,265 ITP patients were enrolled, among whom 80 patients developed SLE while following-up. The whole ITP patients were allocated to training group (7,186 patients including 57 with SLE) and testing group (3,079 patients including 23 with SLE); the former was used for derivation of the decision-tree based model and the latter for validation of the previously mentioned model, and provided high sensitivity (78.2%), specificity (99.2%) and negative prediction value (99.8%, Fig.). To reduce the complexity, we also pruned our decision tree to propose less-complicated models. <h3>Conclusions</h3> We derived classification decision tree suitable for various clinical scenarios of ITP patients, among whom those with high probability of development of SLE would be distinguished. <h3>References</h3> Balsalobre Aznar J, Herráez Herrera P, Porta Etessam J, Torres Martín C, Bermell Serrano JC, Núñez Lόpez R, et al. Idiopathic thrombocytopenic purpura as first manifestation of systemic lupus erythematosus lupus. An Med Interna. 1999;16:611–4. Risk factors for future development of systemic lupus erythematosus in children with idiopathic thrombocytopenic purpura. Pediatr Blood Cancer. 2006;47(5 Suppl):657–9. <h3>Disclosure of Interest</h3> None declared
FRI0614 Frequency of organ manifestations in chronic sarcoidosis
Authors: R Bergner, K de Groot, GA Müller, P Korsten
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chronic sarcoidosis is a systemic disease of unknown etiology, characterized by the histological finding of granulomas in involved organ systems. The most often affected organ is the lung with approximately 90–95%. Systematic data of organ manifestations other than the lung are scarce and show a wide range from 1–2% up to 50% depending on the series. <h3>Methods</h3> We analyzed data of newly diagnosed chronic sarcoidosis in 3 tertiary hospitals. We analyzed data on organ manifestations (OM), type of OM and laboratory findings. The certainty of OM was classified as grade 0 (not investigated), grade 1 (no sign of OM), grade 2 (clinical sign of OM), grade 3 (signs of OM in laboratory findings or imaging) and grade 4 (histological proven OM), respectively. <h3>Results</h3> We included 151 patients with biopsy-proven chronic sarcoidosis. Mean age was 50.8±15 years with a male predominance (87 [57.2%] vs. 65 [42.8%] patients). Except for 3 patients, all demonstrated pulmonary involvement. The predominant type of lung involvement was type I (mediastinal lymph node enlargement) in 54.2% and type II (mediastinal lymph node enlargement and interstitial involvement) in 27.7%. 96.5% of patients were investigated for an affection of the kidneys, 97.3% for hepatic, 92.7% for skin involvement, 68.8% for ocular manifestations, 67.5% for ear, nose, throat (ENT) manifestations and 92% for cardiac manifestations, respectively. Grade 3 (imaging/laboratory) and grade 4 (histology) findings were seen in the kidneys in 7.6/22.8%, in the liver in 13.3/11.9%, in the heart in 10.6/0.7%, in the eyes in 6.6/ <h3>Conclusions</h3> OM in chronic sarcoidosis are more frequent than suggested in the current literature, especially renal and hepatic. About 20% of patients with chronic sarcoidosis suffered from moderate to severe CKD due to sarcoidosis, which is a major organ complication contributing to overall morbidity. We recommend a systematic screening for OM in all patients with chronic sarcoidosis as it is performed in other systemic rheumatic disease. <h3>Disclosure of Interest</h3> None declared
Bronchial hyperresponsiveness and obesity in middle age: insights from an Australian cohort
Authors: John A. Burgess, Melanie C. Matheson, Fei Diao, David P. Johns, Bircan Erbas, Adrian J. Lowe, Lyle C. Gurrin, Caroline J. Lodge, Paul S. Thomas, Stephen Morrison, Bruce R. Thompson, Iain Feather, Jennifer L. Perret, Michael J. Abramson, Graham G. Giles, John L. Hopper, Shyamali C. Dharmage, Eugene H. Walters
Journal: European Respiratory Journal (2017)

The association between obesity and bronchial hyperresponsiveness (BHR) is incompletely characterised. Using the 2006 follow-up of the Tasmanian Longitudinal Health Study, we measured the association between obesity and BHR and whether it was mediated by small airway closure or modified by asthma and sex of the patient. A methacholine challenge measured BHR. Multivariable logistic regression measured associations between body mass index (BMI) and BHR, adjusting for sex, asthma, smoking, corticosteroid use, family history and lung function. Mediation by airway closure was also measured. Each increase in BMI of 1 kg·m −2 was associated with a 5% increase in the odds of BHR (OR 1.05, 95% CI 1.01–1.09) and 43% of this association was mediated by airway closure. In a multivariable model, BMI (OR 1.06, 95% CI 1.00–1.16) was associated with BHR independent of female sex (OR 3.26, 95% CI 1.95–5.45), atopy (OR 2.30, 95% CI 1.34–3.94), current asthma (OR 5.74, 95% CI 2.79–11.82), remitted asthma (OR 2.35, 95% CI 1.27–4.35), low socioeconomic status (OR 2.11, 95% CI 1.03–4.31) and forced expiratory volume in 1 s/forced vital capacity (OR 0.86, 95% CI 0.82–0.91). Asthma modified the association with an increasing probability of BHR as BMI increased, only in those with no or remitted asthma. An important fraction of the BMI/BHR association was mediated via airway closure. Conflicting findings in previous studies could be explained by failure to consider this intermediate step.
ACC/AHA guidelines for coronary artery bypass graft surgery
Authors: Kim A. Eagle, Robert A. Guyton, Ravin Davidoff, Gordon A. Ewy, James Fonger, Timothy J. Gardner, John Parker Gott, Howard C. Herrmann, Robert A. Marlow, William C. Nugent, Gerald T. O’Connor, Thomas A. Orszulak, Richard E. Rieselbach, William L. Winters, Salim Yusuf, Raymond J. Gibbons, Joseph S. Alpert, Kim A. Eagle, Timothy J. Gardner, Arthur Garson, Gabriel Gregoratos, Richard O. Russell, Sidney C. Smith
Journal: Journal of the American College of Cardiology (1999)
<i>BMJ</i>papers on ear growth and didgeridoo for sleep apnea win Ig Nobel awards
Authors: Janice Hopkins Tanne
Journal: BMJ (2017)

Two papers published in The BMJ have won Ig Nobel awards, which are given for “research that first makes you laugh and then makes you think,” at the 27th annual ceremony on 14 September at Harvard University in Cambridge, Massachusetts.

The Ig Nobel peace prize was awarded to a Swiss, Canadian, and Dutch team at the University of Zurich for showing in a 2006 paper that playing the didgeridoo was a good treatment for sleep apnea and snoring.1 The Ig Nobel anatomy prize went to British GP James Heathcote, of Bromley, for research published in 1995 on how ears grow bigger with age.2

The event was produced by the science humor magazine Annals of Improbable Research and Harvard student organizations. Winners received a document signed by an actual Nobel laureate and a cash prize of a Zimbabwean 10 trillion dollar (£0; €0; $0) note.

Didgeridoo playing for sleep apnea was discovered by Alex Suarez, a patient who couldn’t tolerate the usual treatment, a mask that produces continuous positive airway pressure. Playing the didgeridoo strengthened the muscles …
CBX8 Suppresses Tumor Metastasis via Repressing Snail in Esophageal Squamous Cell Carcinoma
Authors: Gang Wang, Jianjun Tang, Weixiang Zhan, Ruhua Zhang, Meifang Zhang, Dan Liao, Xin Wang, Yuanzhong Wu, Tiebang Kang
Journal: Theranostics (2017)

The poor clinical outcome and prognosis of esophageal squamous cell carcinoma (ESCC) is mainly attributed to its highly invasive and metastatic nature, making it urgent to further elicit the molecular mechanisms of the metastasis of ESCC.The function of each polycomb chromobox (CBX) protein in cancer is cell-type-dependent.Although CBX8 has been reported to promote the esophageal squamous cell carcinoma (ESCC) tumorigenesis, its role in ESCC metastasis has not been explored yet.In this study, we report that the inhibition of cell migration, invasion, and metastasis in ESCC requires CBX8-mediated repression of Snail, a key transcription factor that induces epithelial-to-mesenchymal transition (EMT), and that CBX8 inversely correlated with Snail in the ESCC tissues.Moreover, this novel function of CBX8 is dependent on its binding with the Snail promoter, which in turn suppresses the transcription of Snail.Collectively, CBX8 may play paradoxical roles in ESCC, inhibiting metastasis while promoting cell proliferation.
Acute Diarrheal Infections in Adults
Authors: Mary Acree, Andrew M. Davis
Journal: JAMA (2017)

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THU0665 Can one give up basdai in favor of asdas in monitoring spondyloarthritis patients on biologics?
Authors: C Cobilinschi, D Opris-Belinski, R Ionescu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Disease activity in SpA is widely evaluated through BASDAI or ASDAS with no proven superiority between the two, in spite the more objective evaluation of ASDAS through the inflammatory markers. <h3>Objectives</h3> The aim of this study was to evaluate the clinical quality and discriminating power between the above indices when subdividing patients with anti-TNF therapy according to their disease status indicated by BASDAI, ASDAS or PtGA. <h3>Methods</h3> This prospective, observational study included 100 patients with definite SpA on biological therapy.Demographic, clinical and laboratory data was collected. Statistical analysis was performed with SPSS 20.0. <h3>Results</h3> When used as an external criterion PtGA showed that 12% of patients had active disease with a PtGA of over 5 while 88% were classified as low disease activity.Mean ASDAS-CRP and ASDAS-ESR in the active group were 3.39 and 3.24.Mean BASDAI score in the high activity group according to PtGA was 5.66.We showed that both ASDAS scores had good discriminating capacities, with similar values when using the SMD (2.0034 [95% CI 1.29–2.71]).Based on PtGA,BASDAI outperformed ASDAS scores with a SMD of 3.3391 [95% CI 2.5334–4.1447]. ROC curves of the disease activity scores by using the PtGA ≥5 as variable of high disease activity state showed the following: for ASDAS-CRP, ASDAS-ESR and BASDAI the AUCs (<i>area under curve</i>) were 0.89 (P=0.05; 95% CI 0.80–0.99), 0.88 (P&lt;0.001; 95% CI 0.77–0.99), and 0.99 (P=0.009; 95% CI 0.97–1.00).For CRP and ESR the AUCs were 0.81 and 0.79. This shows the high accuracy of the three scores in assessing SpA activity,but with a lower fidelity of the inflammatory markers alone.When dividing patients according to BASDAI score,14% showed a more active disease than the rest of 86% who had low disease activity.Mean ASDAS-CRP scores in the first group was 3.31.When correlating disease activity scores for the entire study group we observed that BASDAI correlated to both ASDAS scores (r=0.65 and 0.71, P&lt;0.001) and that PtGA showed a stronger correlation to BASDAI (r=0.912, P&lt;0.01) than ASDAS and to acute phase reactants. <h3>Conclusions</h3> This study shows that disease activity scores have good discriminatory powers. BASDAI surpassed ASDAS scores when relating to the PtGA. According to Van der Heijde et al.(1), the only situation in which BASDAI can outperform ASDAS is when assessing the PASS (<i>patient acceptable symptom state</i>). However, ASDAS-CRP had better discriminatory power than ASDAS-ESR or acute phase reactants. This demonstrates that ASDAS-CRP is a more objective evaluation that can better differentiate patients with high or low disease activity. <h3>References</h3> D van der Heijde,ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis, Ann. Rheum. Dis,vol. 68,Dec 2009. <h3>Disclosure of Interest</h3> None declared
SAT0524 Utility of tocilizumab in clinical manifestations of erosive osteoarthrosis of hands regional hospital issste puebla, mΈxico
Authors: JM Sánchez Huerta, J Gálvez-Romero, W Lόpez-Rodriguez, A Lόpez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Erosive osteoarthritis (EOA) is a form of severe involvement of osteoarthrosis in the hands, characterized by inflammation of the synovium of the proximal interphalangeal (PIF) and distal joints (DIF); the last ones are the most affected in a symmetrical manner. Inhibition of interleukin 6 (IL-6) in joints with osteoarthrosis helps to improve the production of the cartilaginous matrix and microfractures of articular cartilage. <h3>Objectives</h3> To know if the application of TCZ is useful for the control of the clinical manifestations of EOA of the hands. <h3>Methods</h3> Twenty-four patients with EOA were studied, 18 females and 6 males with ages ranging from 42 to 72 years, with an evolution time of 4 to 30 years. The application of TCZ was intravenous (8 mg/kg of body weight per month). Articular pain in the PIF and distal joints was evaluated by the visual analogue scale (VAS) (0 to 10) and joint pain (0 to 50), morning stiffness (0 to 10), and functional limitation (0–90) by the AUSCAN index. <h3>Results</h3> The VAS showed improvement of 30% (0% to 100%). The AUSCAN index showed improved pain (16.2), morning stiffness (0.6) and functional limitation (17.5). Decreased ESR, CRP, and IL-6 levels less than 1.56 to 59.1 pg/ml. <h3>Conclusions</h3> IV Tocilizumab is useful for the control of the clinical manifestations of OAE of the hands. More precise studies are needed to evaluate the improvement of the cartilaginous matrix in EOA by TCZ. <h3>Disclosure of Interest</h3> None declared
Biomimetic Artificial Basilar Membranes for Next‐Generation Cochlear Implants
Authors: Jongmoon Jang, Jeong Hun Jang, Hongsoo Choi
Journal: Advanced Healthcare Materials (2017)

Abstract Patients with sensorineural hearing loss can recover their hearing using a cochlear implant (CI). However, there is a need to develop next‐generation CIs to overcome the limitations of conventional CIs caused by extracorporeal devices. Recently, artificial basilar membranes (ABMs) are actively studied for next‐generation CIs. The ABM is an acoustic transducer that mimics the mechanical frequency selectivity of the BM and acoustic‐to‐electrical energy conversion of hair cells. This paper presents recent progress in biomimetic ABMs. First, the characteristics of frequency selectivity of the ABMs by the trapezoidal membrane and beam array are addressed. Second, to reflect the latest research of energy conversion technologies, ABMs using various piezoelectric materials and triboelectric‐based ABMs are discussed. Third, in vivo evaluations of the ABMs in animal models are discussed according to the target position for implantation. Finally, future perspectives of ABM studies for the development of practical hearing devices are discussed.
Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology
Authors: Thomas Knoll, Muhammad Imran Omar, Steven Maclennan, Virginia Hernández, Steven Canfield, Yuhong Yuan, Max Bruins, Lorenzo Marconi, Hein Van Poppel, James N’Dow, Richard Sylvester
Journal: European Urology (2017)
代謝:マウスで見られるコレステロールの胆汁酸への低温誘導性の変換は腸のマイクロバイオームを適合させ,適応性熱産生を促進する
Authors: Worthmann Anna, John Clara, Baguhl Miriam, Schaltenberg Nicola, Heine Markus, Schlein Christian, Evangelakos Ioannis, Scheja Ludger, Heeren Joerg, Ruehlemann Malte C, Heinsen Femke‐Anouska, Franke Andre, Mineo Chieko, Shaul Philip W, Fischer Markus, Dandri Maura, Kremoser Claus
Journal: Nature Medicine (2017)
THU0222 Prophylactic and therapeutic administration of an ANTI-CD40 antagonist antibody blocks and reverses proteinuria and nephritis in NZB/W-F1 mice
Authors: S Perper, S Westmoreland, Z Liu, M Duval, J Seagal, B McRae, S Clarke
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The CD40-CD40L pathway is a potential target for the treatment of autoimmune diseases, as CD40 is a costimulatory receptor on antigen presenting cells (APCs) critical for the induction and maintenance of an immune response through binding CD40L on T cells. In the absence of CD40, both humoral and cellular responses to foreign antigens are severely impaired. In particular, disruption of this pathway prevents the development of disease in lupus-prone mice. <h3>Objectives</h3> The objective of this work is to evaluate whether prophylactic and therapeutic treatment with an antagonistic anti-CD40 antibody prevents and reverses nephritis and other manifestations of lupus in lupus-prone mice. <h3>Methods</h3> NZB/W-F<sub>1</sub> mice were i.p. administered anti-CD40 prophylactically or therapeutically at various doses once or twice per week. Prophylactic treatment of NZB/W-F<sub>1</sub> mice began at 26 weeks of age and continued for 9 weeks, while therapeutic treatment was initiated in NZB/W-F<sub>1</sub> mice after they developed severe proteinuria (urine protein ≥300 mg/dL). Proteinuria was monitored weekly by urinalysis, and at study termination blood and spleen cells were analyzed by flow cytometry. Additionally, histological analysis of kidney, spleen, and salivary glands were performed, as well as gene transcription analysis of the kidney by microarray. <h3>Results</h3> As expected, prophylactic and therapeutic administration reduced the number of splenic germinal center (GC) B cells and T follicular helper cells (Tfh). Prophylactic treatment blocked development of proteinuria and extended survival in NZB/W-F<sub>1</sub> mice. Significantly, therapeutic anti-CD40 treatment reversed established, severe proteinuria in NZB/W-F<sub>1</sub> mice and extended their survival. In agreement, the kidneys and salivary glands of treated mice exhibited reduced inflammation compared to control mice, and the kidneys exhibited lower CD40, IFN-I and chemokine gene signatures compared to controls. Interestingly, anti-CD40 decreased expression of genes in kidney belonging to the "hepatic fibrosis" pathway, possibly explaining the improvement of kidney function. <h3>Conclusions</h3> Anti-CD40 treatment prevents the onset and reverses ongoing nephritis and sialadenitis in NZB/W-F<sub>1</sub> mice. Resolution of ongoing nephritis results in restoration of low or normal urine protein levels. Thus, treatment with an antagonistic anti-CD40 is a strong candidate for clinical study in SLE. <h3>Disclosure of Interest</h3> S. Perper Employee of: Abbvie, S. Westmoreland Employee of: Abbvie, Z. Liu Employee of: Abbvie, M. Duval Employee of: Abbvie, J. Seagal Employee of: Abbvie, B. McRae Employee of: Abbvie, S. Clarke Employee of: Abbvie
Reply to: “Direct-acting antiviral therapy in patients with hepatocellular cancer: The timing of treatment is everything” and “More extended indication of DAA therapy in patients with HCC, affordability, and further statistical considerations”
Authors: Lauren A. Beste, Pamela K. Green, Kristin Berry, Matthew J. Kogut, Stephen K. Allison, George N. Ioannou
Journal: Journal of Hepatology (2017)
Caveolae-Mediated Endocytosis Is Critical for Albumin Cellular Uptake and Response to Albumin-Bound Chemotherapy
Authors: Moumita Chatterjee, Edgar Ben-Josef, Ryan Robb, Marall Vedaie, Star Seum, Krishnan Thirumoorthy, Kamalakannan Palanichamy, Matthew Harbrecht, Arnab Chakravarti, Terence M. Williams
Journal: Cancer Research (2017)

Nab-paclitaxel, a nanoparticle conjugate of paclitaxel to human albumin, exhibits efficacy in pancreatic cancer, non-small cell lung cancer and breast cancer. However, there is a lack of predictive biomarkers to identify patients who might benefit most from its administration. This study addresses this gap in knowledge by identifying that caveolin-1 (Cav-1) is a candidate mechanism-based biomarker. Caveolae are small membrane invaginations important for transendothelial albumin uptake. Cav-1, the principal structural component of caveolae, is overexpressed in the cancers noted above that respond to nab-paclitaxel. Thus, we hypothesized that Cav-1 may be critical for albumin uptake in tumors and perhaps determine their response to this drug. Cav-1 protein levels correlated positively with nab-paclitaxel sensitivity. RNAi-mediated attenuation of Cav-1 expression reduced uptake of albumin and nab-paclitaxel in cancer cells and rendered them resistant to nab-paclitaxel-induced apoptosis. Conversely, Cav-1 overexpression enhanced sensitivity to nab-paclitaxel. Selection for cellular resistance to nab-paclitaxel in cell culture correlated with a loss of Cav-1 expression. In mouse xenograft models, cancer cells, where Cav-1 was attenuated, exhibited resistance to the antitumor effects of nab-paclitaxel therapy. Overall, our findings suggest Cav-1 as a predictive biomarker for the response to nab-paclitaxel and other albumin-based cancer therapeutic drugs. Cancer Res; 77(21); 5925-37. ©2017 AACR.