tbuckley/cabot-search huggingface dataset:
SAT0191 Patterns of interstitial lung disease in rheumatoid arthritis and abatacept. multicenter study of 63 patients
Authors: C Fernández-Díaz, S Castañeda, C Ojeda, A Olivé, P Carreira, T Perez-Sandoval, M Retuerto, E Cervantes, S Rodriguez, B Robles, B Hernandez, A Urruticoechea, O Maiz, D Palma, L Arboleya, G Bonilla, I Rodriguez, C Delgado, R Exposito, A Ruibal, J Blanco, M Rodriguez, J Bernal, P Vela, B Alvarez, C Fito, J Narvaez, M Moreno, M Lopez, N Mena, S Romero, C Aguilera, S Ordoñez, I Villa, V Mora, M Gonzalez-Gay, J Hernandez, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Disease modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX), leflunomide (LFN) or antiTNFα have been implicated in development/exacerbation of Interstitial lung disease (ILD)of rheumatoid arthritis (RA). Several radiological patterns of ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii) obliterating bronchitis (OB), and iv) Organized pneumonia (OP) <h3>Objectives</h3> To assess the response to Abatacept (ABA) in these patterns of ILD <h3>Methods</h3> Multicenter study of RA-ILD treated with ABA. ILD was diagnosed by high-resolution CT scan (HRCT) and classified in radiological patterns (Travis et al). We consider 3 subgroups: a) UIP, b) NSIP and c) "other" (OB, OP or mixed). ABA was used at iv or sc standard dose. We assessed: a) Dyspnea (Medical Research Council-modified scale; significant variations≥1); B) Respiratory function tests; significant changes≥10% in forced vital capacity (FVC) and DLCO≤10%, c) HRCT, d) DAS28. A comparative study was performed for the quantitative (U-Mann-Whitney) and qualitative variables (Fisher test) between the baseline and 3, 6 and 12 months. <h3>Results</h3> We included 63 patients (27 women/36 men), mean age; 63.1±9.6 years. At ABA onset the RA had a median evolution of 6.8 [2–13.6] years and the ILD of 1 [0.3–3.03]. RA was seropositive in 85.7%. The diagnosis of ILD was confirmed by biopsy (n=18). The ILD was related to DMARDs: MTX (4), etanercept (3), adalimumab (3), certolizumab (2), Infliximab (1). ABA was used in monotherapy (26) or combined with other DMARDs (37); LFN (15), Cyclosporin (1), sulfasalazine (4), MTX (6), hydroxychloroquine (10), azathioprine (4), chloroquine (1). Table 1 shows the evolution in the available cases. A significant improvement in dyspnea and HRCT was observed in the NIU type. DLCO remained stable in most patients regardless of the radiological pattern. The activity of RA (DAS28) also improved. <h3>Conclusions</h3> ABA appears to be effective in ILD associated-RA, including the pattern of poor prognosis (UIP). <h3>References</h3> Travis WD et al. J Respir Crit Care Med 2013 188:733–748. <h3>Disclosure of Interest</h3> None declared
Short- and Long-Term Survival in Metastatic Pancreatic Adenocarcinoma, 1993–2013
Authors: Talia Golan, Tal Sella, Ofer Margalit, Uri Amit, Naama Halpern, Dan Aderka, Einat Shacham-Shmueli, Damien Urban, Yaacov Richard Lawrence
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: During the past 2 decades, numerous clinical trials have focused on improving outcomes in patients with metastatic pancreatic cancer (mPDAC). The efficacy of new treatments has been demonstrated among highly selected patients in randomized phase III trials; hence, it is not clear to what extent these advances are reflected within the broader mPDAC population. Materials and Methods: Survival statistics were extracted from the SEER database for patients diagnosed with mPDAC between 1993 and 2013. Survival was analyzed using the Kaplan-Meier method and proportional hazard models. Results: The study population consisted of 57,263 patients diagnosed with mPDAC between 1993 and 2013; 52% were male, with a median age of 69 years (range, 15-104). Superior prognosis correlated with younger age, being married, tumor located within the head of the pancreas, lower grade disease, and more recent year of diagnosis. Median overall survival (OS) remained stable at 2 months between 1993 and 2013. Improvements in OS were seen for younger patients (age <50 years) and those with a more recent year of diagnosis (2009-2013). The percentage of patients who died within 2 months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%; P<.0001). The percentage of patients surviving ≥12 months improved from 4.9% in 1993 to 12.7% in 2013 (P<.0001). Conclusions: In recent years a modest improvement in OS has been seen among younger patients with mPDAC. The percentage of patients living beyond 1 year has significantly increased over time; however, the percentage of those dying within 2 months remains substantial.
Phase I evaluation of lapatinib (L) and epirubicin (E) in patients (pts) with anthracycline (anth)-naive metastatic breast cancer (MBC)
Authors: R. A. O'Connor, M. J. Kennedy, S. R. McDermott, D. Tryfanopoulos, C. McCreery, D. Collins, O. Martynyuk, R. Gethins, B. Moulton, J. Crown
Journal: Journal of Clinical Oncology (2009)

1107 Background: HER-2 alteration confers enhanced anth sensitivity in MBC, although HER-2 is not a target for anth. Topoisomerase 2A (Topo) is a target for anth. Topo amplification has been reported to occur only with HER-2 amplification, in approximately 1/3 of HER-2 amplified BC, providing a rationale for anth + trastuzumab(H) therapy in MBC with co-ampified HER-2/Topo. T+anth is cardiotoxic. L may have similar single agent activity, but less cardiotoxicity than H. L competes with anth for p-glycoprotein and might enhance its activity. The cardiac safety of L + anth needed to be established. Methods: We conducted a phase I evaluation of fixed dose lapatinib (1250 mg/day) with escalating doses of epirubicin (Epi-planned dose levels I-IV :75/80/90/100 mg/m 2 ) in pts with HER-2±, anth-naive metastatic BC. Epirubicin was administered q3 weeks. A minimum of 3 (if no dose-limiting toxicity) and a maximum of 6 pts were treated per dose level. Ejection fractions were performed at base line and after every second cycle; BNP and troponin after every cycle. Results: 9 pts were treated, 3 level I, 6 level II. Dose level I was declared the maximum tolerated dose following two occurrences of dose-limiting toxicity in level II. 1 pt experienced febrile neutropenia,1 had &gt; 20% decrease in LVEF. To date there have been 3 PRs by RECIST out of 8 evaluable patients which represents a response rate of 37.5%. Conclusions: Using classic phase I criteria, the combination of L 1250 mg together with Epi 75 mg/m 2 combination is relatively well tolerated and suitable for further investigation in a phase II study of HER-2+veTopo+ve MBC patients. We will conduct such a study in pts with HER-2+Topo+ metastatic BC. [Table: see text]
Pulmonary CCR2<sup>+</sup>CD4<sup>+</sup>T cells are immune regulatory and attenuate lung fibrosis development
Authors: Katrin Milger, Yingyan Yu, Eva Brudy, Martin Irmler, Alla Skapenko, Michael Mayinger, Mareike Lehmann, Johannes Beckers, Frank Reichenberger, Jürgen Behr, Oliver Eickelberg, Melanie Königshoff, Susanne Krauss-Etschmann
Journal: Thorax (2017)

Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2+CD4+ T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2+ cell populations might either increase or decrease disease pathogenesis depending on their subtype.To investigate the role of CCR2+CD4+ T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis.Pulmonary CCR2+CD4+ T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments.Frequencies of CCR2+CD4+ T cells were increased in experimental fibrosis-specifically the CD62L-CD44+ effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2+CD4+ T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2+CD4+ T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3+ CD25+ cells within bronchoalveolar lavage fluid CCR2+CD4+ T cells as compared with CCR2-CD4+ T cells.Pulmonary CCR2+CD4+ T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease.
03.14 Comparison of immunosuppressive potential of rheumatoid adipose mesenchymal stem cells derived from articular and subcutaneous adipose tissues
Authors: Urszula Skalska, Ewa Kuca-Warnawin, Tomasz Burakowski, Anna Kornatka, Iwona Janicka, Urszula Musiałowicz, Ewa Kontny
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory properties, but their activity is dependent on signals provided by local microenvironment. It is likely that proinflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASC) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) have been analysed. <h3>Materials and methods</h3> Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from 8 RA patients undergoing total knee joint replacement surgery. Then, ASCs were isolated accordingly to routinely applied procedure. ASCs were treated or not with IFNγ and TNF. To evaluate immunomodulatory properties of AT- and Sc-ASCs, co-cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have been set and then, select parameters of PBMCs function have been measured. Proliferation of activated PBMCs (flow cytometry and <sup>3</sup>H-thymidine incorporation method), secretion of IL-10 and IL-17A in co-culture supernatants (ELISA tests) and T regulatory FoxP3<sup>+</sup> cells (Tregs) percentage have been evaluated (flow cytometry). <h3>Results</h3> AT- and Sc-ASCs activity <i>in vitro</i> is comparable. Unstimulated AT- and Sc-ASCs inhibit PBMCs proliferation and induce IL-10 secretion but increase also IL-17A production by PBMCs. In the majority of cases, ASCs presence causes increase of Tregs number. Under IFNγ and TNF stimulation ASCs exert stronger antiproliferative potential toward activated PBMCs than unstimulated ASCs, but decrease IL-10 secretion in co-cultures. Importantly, interindividual differences in the level of immunosuppressiveness of ASCs from different patients occur, especially relating to their antiproliferative potential. <h3>Conclusions</h3> Our study demonstrates that immunosuppressive function of ASCs derived from two different sources, that is infrapatellar fat pad and subcutaneous adipose tissue, are comparable. Subcutaneous adipose tissue is isolated from the site of sutures – the localization close to the inflamed joint. Thus, it seems that conditions in the two adipose tissue sources are not very distinct which results in similar activity of AT- and Sc-ASCs. <h3>Acknowledgements</h3> This work was supported by the Polish National Science Centre grant no. 2015/17/D/NZ5/02219 and by the statutory grant of National Institute of Geriatrics, Rheumatology and Rehabilitation no. S/33.
皮膚条件のための入力脂質ベース送達媒体と画像診断の展望」を用いた皮膚癌部位のための実行可能なドラッグデリバリー技術としてのリポソームシステム【Powered by NICT】
Authors: Akhtar Naseem, A Khan Riaz
Journal: Progress in Lipid Research (2016)
Abstract 14828: Recombinant Human Soluble Thrombomodulin Prevents Acute Lung Injury in a Rat Cardiopulmonary Bypass Model
Authors: Shingo Hirao, Kenji Minakata, Hidetoshi Masumoto, Shuji Setozaki, Kazuhiro Yamazaki, Tadashi Ikeda, Ryuzo Sakata
Journal: Circulation (2016)

Backgrounds: Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate secretion of ...
Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia
Authors: James S. Ware, Louise V. Wain, Sarath K. Channavajjhala, Victoria E. Jackson, Elizabeth Edwards, Run Lu, Keith Siew, Wenjing Jia, Nick Shrine, Sue Kinnear, Mahli Jalland, Amanda P. Henry, Jenny Clayton, Kevin M. O’Shaughnessy, Martin D. Tobin, Victor L. Schuster, Stuart Cook, Ian P. Hall, Mark Glover
Journal: Journal of Clinical Investigation (2017)

Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH patients with the p.A396T variant demonstrated increased urinary excretion of prostaglandin E2 and metabolites. Moreover, the SLCO2A1 phospho-mimic p.A396E showed loss of transporter function in vitro. These findings indicate that the phenotype of TIH involves a more extensive metabolic derangement than previously recognized. We propose one mechanism underlying TIH development in a subgroup of patients in which SLCO2A1 regulation is altered.
02.40 Lack of obesity-related features in adipocytes and inflammatory cells in the infrapatellar fat pad (ifp) of oa patients
Authors: Anja de Jong, Inge Klein-Wieringa, Stefan Andersen, Joanneke Kwekkeboom, Linda Herb-van Toorn, Badelog de Lange-Brokaar, Danny van Delft, John Garcia, Wu Wei, Huub van der Heide, Yvonne Bastiaansen-Jenniskens, Gerjo van Osch, Anne-Marie Zuurmond, Vedrana Stojanovic-Susulic, Rob Nelissen, René Toes, Margreet Kloppenburg, Andreea Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Obesity is associated with the development and progression of osteoarthritis (OA). The infrapatellar fat pad (IFP) could contribute to this association due to its localization in the knee joint and secretion of inflammatory mediators. However, little is known about the effects of obesity on the IFP. Therefore, the aim of this study was to investigate the presence of obesity-related features in adipocytes and infiltrating immune cells in the IFP of OA patients. <h3>Materials and methods</h3> IFP volume was determined by MRI in 79 knee OA patients. IFP and subcutaneous adipose tissue (SCAT) were obtained from 106 knee OA patients (total n=155: 68% women, mean age 65 years, mean (SD) body mass index (BMI) 29.9 kg/m<sup>2</sup> (5.7)) undergoing joint replacement surgery. Crown-like structures (CLS) were determined using immunohistochemistry. Adipocyte size was determined by light microscopy and histology. Stromal vascular fraction (SVF) cells were characterised by flow cytometry. <h3>Results</h3> IFP volume (mean(SD) 23.6 (5.4) mm<sup>3</sup>) associated with gender and height, but not with BMI. Likewise, volume and size of IFP adipocytes (mean 271 pl, mean 1933 μm) was not correlated with BMI. Few CLS were observed in IFP and the number did not correlate with BMI. Moreover, high BMI was not associated with higher SVF immune cell numbers in IFP, nor with changes in their phenotype. No molecular differences were observed with BMI, besides an increase in TNFα expression. Extensive characterisation of IFP macrophages revealed that CD206 and CD163, usually associated with an anti-inflammatory phenotype were the most abundantly expressed surface markers on macrophages (81% and 41% respectively), while macrophages produced predominantly IL-6 and TNFα, but little IL-10. Interestingly, surface marker and cytokine expression revealed that CD163<sup>+</sup> macrophages had an activated and pro-inflammatory phenotype. <h3>Conclusions</h3> Obesity-related differences usually observed in SCAT and visceral adipose tissue could not be detected in IFP of OA patients, a fat depot implicated in OA pathogenesis.
Abstract 13804: Differential Outcome of Medical Therapy Compared With Percutaneous and Surgical Coronary Revascularization in Individuals With Chronic Kidney Disease at Low, Medium, or High Cardiovascular Risk
Authors: Charles A Herzog, Shuling Li, Tanya Natwick, Craig Solid, David M Charytan
Journal: Circulation (2016)

Introduction: Comparisons of medical therapy (MT) and percutaneous (PCI) or surgical coronary revascularization (CABG) for the treatment of coronary artery disease (CAD) in the setting of chronic kidney disease (CKD) have suggested that MT is inferior, but may be confounded by failure to adequately account for baseline cardiovascular disease (CVD) risk and by the nihilistic definition of MT as absence of revascularization rather than active titration of MT. Hypothesis: MT is superior to revascularization in CKD pts at low CV risk but PCI and CABG are superior to MT when CV risk is high. Methods: The 20% Medicare sample was used to identify pts in 2007-2012 with CKD, assess outcomes, and define risk groups: Low risk: angiography or stress testing in the absence of prior CVD; Medium risk: stress test or angiography with prior CVD history; High risk: admission for acute coronary syndrome (ACS). PCI and CABG were defined on the basis of procedures within 60 days of risk group entry. MT included non-PCI/CABG pts with addition of new CV medication during the same time frame. R esults: For low risk pts 1000 had PCI, 571 CABG, and 6848 MT. For medium risk 1751 PCI, 718 CABG and 9670 MT pts. For high risk 4542 PCI, 1481 CABG and 8287 MT pts. All-cause mortality rates increased across risk groups, consistent with excellent performance of our classification metric. Mortality rates per hundred pt years were lowest with MT in the low risk group—PCI 9.1, CABG 8.9, MT 8.1--and medium risk groups—PCI 13.5, CABG 14.6, MT 13.2. In contrast, survival was markedly better with CABG or PCI in high risk pts—PCI 18.4, CABG 13.1, MT 33.5 ( Table ). Conclusions: The relative benefits of MT and coronary revascularization in the setting of CKD vary according to pre-treatment CV risk. For pts at low or moderate risk, MT, PCI, and CABG have similar survival. In contrast, revascularization, particularly CABG, is associated with markedly improved survival (and higher ESRD rate) compared to MT after ACS.
カチオン性脂質支援プロドラッグナノ粒子によるシスプラチンに対する腫瘍耐性の克服【Powered by NICT】
Authors: Cao Zhi-Ting, Chen Zhi-Yao, Sun Chun-Yang, Li Hong-Jun, Wang Hong-Xia, Cheng Qin-Qin, Zuo Zu-Qi, Wang Ji-Long, Liu Yang-Zhong, Wang Yu-Cai, Wang Jun
Journal: Biomaterials (2016)
A Phase 2 Randomized Controlled Study of Tralokinumab in Subjects with Idiopathic Pulmonary Fibrosis
Authors: Joseph M. Parker, Ian N. Glaspole, Lisa H. Lancaster, Tarik J. Haddad, Dewei She, Stephanie L. Roseti, Jon P. Fiening, Ethan P. Grant, Chris M. Kell, Kevin R. Flaherty
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

IL-13 is a potential therapeutic target for idiopathic pulmonary fibrosis (IPF); preclinical data suggest a role in tissue fibrosis, and expression is increased in subjects with rapidly progressing disease.Investigate efficacy and safety of tralokinumab, a human anti-IL-13 monoclonal antibody, in subjects with mild to moderate IPF.Subjects received tralokinumab (400 or 800 mg), or placebo, intravenously every 4 weeks for 68 weeks. The primary endpoint was change from baseline to Week 52 in percent predicted FVC in the intention-to-treat population. Exploratory analyses included assessment of clinical response in subgroups with baseline serum periostin concentration above/below median.The study was stopped due to lack of efficacy after interim analysis. Neither tralokinumab 400 mg nor tralokinumab 800 mg met the primary endpoint; least-squares mean difference (95% confidence interval) percent predicted FVC from baseline to Week 52: -1.77 (-4.13 to 0.59) (P = 0.140) and -1.41 (-3.73 to 0.91) (P = 0.234), respectively. The primary endpoint was also not met in either treatment group in subgroups defined by periostin baseline concentration. The percentage of subjects with decline in percent predicted FVC greater than or equal to 10% at Week 52 was numerically greater for tralokinumab-treated subjects compared with placebo. The most common treatment-emergent adverse events for tralokinumab 400 mg, tralokinumab 800 mg, and placebo were cough (17.5, 30.5, 22.8%), IPF progression and exacerbation (21.1, 16.9, 22.8%), and upper respiratory tract infection (17.5, 20.3, 12.3%), respectively.Tralokinumab demonstrated an acceptable safety and tolerability profile but did not achieve key efficacy endpoints. Clinical trial registered with www.clinicaltrials.gov (NCT01629667).
Gene Editing Using CRISPR
Authors: Anthony L. Komaroff
Journal: JAMA (2017)

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電子移動誘起反応性酸素種に基づく銀ナノ粒子を埋込んだチタンの抗菌効果【Powered by NICT】
Authors: Wang Guomin, Jin Weihong, Qasim Abdul Mateen, Gao Ang, Peng Xiang, Li Wan, Feng Hongqing, K Chu Paul
Journal: Biomaterials (2017)