tbuckley/cabot-search huggingface dataset:
Phase I clinical and pharmacology study of the novel epothilone analog BMS-247550 given weekly in patients advanced solid tumors
Authors: Ahmad Awada, Howard H.A. Burris, Dominique de Valeriola, Alain Hendlisz, A.C. Huart, Thierry Gil, D. Crabeels, C Moerman, Martine Piccart-Gebhart
Journal: Clinical Cancer Research (2001)
AB0374 Nontuberculous mycobacterium infections in patients with rheumatoid arthritis: a single-centre experience in japan
Authors: M. Hayashi, K. Funamura, M. Maeda, T. Kanamono
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <h3>Objectives</h3> Nontuberculous mycobacteria (NTM) infection has been increasing in both general population and immunocompromised patients in Japan. This study aimed to identify the incidence and clinical characteristics of NTM infections in patients with rheumatoid arthritis (RA). <h3>Methods</h3> We performed a cross-sectional analysis and assessed 11 RA patients, who were all female, complicated with NTM (mean age, 66.6 years) at our institute. We examined Steinbrocker Stage and Class, disease duration, positivity of anti-CCP antibody and rheumatoid factor, HAQ-DI, DAS28-ESR, NTM species, radiological features, methotrexate use and dosage, prednisolone use and dosage, biological agent use, and anti-NTM therapy. <h3>Results</h3> Average values obtained with SD were as follows: age (years), 66.6±8.0; Steinbrocker Stage I, 1; II, 0; III, 1; and IV, 9; Class 1, 2; 2, 5; 3, 4; and 4, 0; disease duration (months), 274.9±126.9; positivity of anti-CCP antibody, 80.0%; positivity of rheumatoid factor, 100%; HAQ-DI, 1.35±0.72; DAS28-ESR, 3.61±0.90; detection by sputum culture, 81.8%; NTM species, <i>M. avium</i>, 8 cases and <i>M. intracellulare</i>, 3 cases; bronchiectasis, 90.9%; interstitial pneumonia, 0%; methotrexate use and dosage (mg/week); 63.6% and 7.4±3.4; prednisolone use and dosage (mg/day); 81.8% and 4.3±2.0; biological agent use, 45.5%; and anti-NTM therapy, 36.4%. <h3>Conclusions</h3> At our institute, RA patients complicated with NTM were long-standing, had high disease activities and worse HAQ-DI. In all five patients (45.5%) who were treated with biologics, 3 who had preceding episodes of NTM infection were treated with anti-NTM therapy before treatment with biologics, and the other 2 who had asymptomatic NTM infection after treatment with biologics were not treated with anti-NTM therapy thereafter. In RA patients who are treated with biologics, it is necessary to perform sputum cultures constantly to detect possible NTM infections. This finding is important in the management of RA complicated with NTM. <h3>Disclosure of Interest</h3> None declared
AB1416-HPR Risk factors associated with fracture risk in women with breast adenocarcinoma in a seville cohort
Authors: G.M Paz, Paloma Muñoz Reinoso, Isabel González Agudo, Juan Piedra, Juan Povedano, Blanca Hernández Cruz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Introduction: Women with breast cancer have a higher risk of osteoporotic fractures than the rest of the population of the same sex and age. This problem is due to multiple factors among which are the treatments to which they are subjected. Among them, chemical castration, chemo and/or radiotherapy, corticosteroids, surgery, monoclonal antibodies against HER-2 and aromatase inhibitors are related to increased bone resorption. <h3>Objectives</h3> Objectives: To assess the prevalence of and factors associated with fragility fractures in women with breast adenocarcinoma. <h3>Methods</h3> Patients and methods: Prospective, cross-sectional study in progress. In a multidisciplinary consultation of OP and Oncology of two third-level centres in Seville, women diagnosed with breast cancer are treated. The factors associated with the presence of vertebral and peripheral fragility fractures in these patients at the time of the first evaluation were analysed. <h3>Results</h3> Results: 409 women were included in this analysis, evaluated between September 2014 and December 2017. The median age (Q1-Q3) was 63 55–68 years. 38 (9%) fragility fractures were observed, 22 (5.4%) vertebral and 18 (4.4%) peripheral. Three patients presented peripheral and vertebral fractures. Factors such as smoking, family history, menopause age, exercise, sun exposure, milk consumption or BMI were not associated with fragility fractures. The t-score in the femoral neck or spine was also not associated with fragility fractures. Of the 88 patients treated with tamoxifen, 6 (6.8%) had fragility fractures compared to 32/320 (10%) of those who did not receive tamoxifen (p=0.367). They presented fragility fractures 22/215 (10%) women with letrozole compared to 16/194 (8%) that were not treated with letrozole (p=0.490). At the time of the first evaluation, the mean (SD) of the FRAX was 6.1 (5.3) in women without fractures and 11.7 (7.7) in those with fragility fractures (p&lt;0.001). In the logistic regression, the only variable associated independently was the FRAX [FRAX &gt;10, adjusted OR 8.9 (3.9–20.4), p&lt;0.001]. The best logistic regression model explained 12% of fragility fractures <h3>Conclusions</h3> Conclusion: In women with breast cancer, FRAX is the only clinical variable associated independently with the presence of fragility fractures in our <h3>Disclosure of Interest</h3> None declared
THU0637 Evaluations of complement pathways in igg4 related disease
Authors: S. Fukui, Y. Fujita, T. Origuchi, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In IgG4 related disease (IgG4-RD), hypocomplementemia is known to be seen. Complement pathways consist of three pathways, classical, alternative, and lectin pathways. Although IgG1 and IgG3 have ability to activate complement, IgG4 is known to be ineffective at activating complement. <h3>Objectives</h3> We attempted to elucidate which complement pathway is mainly associated with IgG4-RD. <h3>Methods</h3> Levels of complement elements and complement-associated elements, C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, Factor D, Factor I, mannose-binding lectin (MBL), Factor B, Factor H, and properdin in preserved sera of patients with IgG4-RD at diagnosis and at remission were measured using multiplex bead-based assay. We compared complement levels at diagnosis of IgG4RD patients with those of sex-matched healthy donors. <h3>Results</h3> This study included 28 IgG4-RD patients and sex-matched 28 healthy donors. The median age at diagnosis and healthy donors' age were 65 [interquartile range (IQR): 55–70] and 64 (IQR:56–73), respectively. Patients with IgG4-RD at diagnosis had significantly higher levels of C5 and C5a [33347 ng/mL vs. 30375 ng/mL (median), p=0.0293, 16417 pg/mL vs. 7083 pg/mL, p&lt;0.0001, respectively] and significantly lower levels of C4, C4b, and Factor D (219671 ng/mL vs. 325596 ng/mL, p=0.0140, 8784 ng/mL vs. 16285 ng/mL, p=0.0101, 4569 ng/mL vs. 5482 ng/mL, p=0.0299, respectively) compared to healthy donors. Levels of C5, C5a, C4, C4b, and Factor D were not different in two groups which were divided by clinical manifestations at diagnosis except for lower C4b levels in patients with lymphadenopathy compared with patients without lymphadenopathy. There were no differences in MBL, which was associated with the lectin pathway. In remission after the administrations of prednisolone, levels of C5a significantly decreased compared to levels of C5a at diagnosis (16305 pg/mL to 10029 pg/mL, p=0.0043). Other complement factors did not change significantly. <h3>Conclusions</h3> The classical complement pathway may be associated with IgG4-RD rather than the alternative pathway and the lectin pathway based on results except for Factor D. <h3>Disclosure of Interest</h3> None declared
AB0005 Hla class ii in paraguayan immune-mediated inflammatory patients
Authors: I. Acosta-Colman, S. Cabrera-Villalba, G. Avila-Pedretti, M.E. Acosta Hetter, M. Vazquez, A. Ayala Lugo, V. Jolie, L. Roman, M. Melo, M. González, M. Duarte, H. Torio, M.T. Martínez de Filártiga
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immune-mediated inflammatory disease (IMID) is a concept used to describe a group of conditions that share common inflammatory pathways leading to systemic inflammation. The best-known genetic factor for IMID susceptibility is the human leukocyte antigen (HLA) haplotypes. Nowadays, there is a lack of information about HLA profile in Paraguayan patients with IMIDs. <h3>Objectives</h3> To identify HLA alleles associated with susceptibility to develop an IMID in Paraguayan patients controlled in a reference centre. <h3>Methods</h3> Paraguayan IMID patients were recruited from the Rheumatology Department of Hospital de Clínicas, Paraguay. IMID <i>HLA II</i> frequencies where compared with a control group of 50 unrelated individuals without disease and from the same geographic origin. Genotyping for HLA was performed using Luminex PCR technology. The association analysis with the IMIDs risk was performed using the chi-square allelic test. <h3>Results</h3> 249 IMID patients (95 lupus,104 rheumatoid arthritis and 50 systemic sclerosis) where included. Of these 84,4% were women with an average age of 43,4 (±14). Comparing the haplotypes profiles for the 5 HLA class II genes between the patients and the healthy controls, in the risk association analysis, the association of the known risk allele was corroborated HLADRB1*03:01 (p=2e-06, OR:14,97). A significant association was identified between the allele HLADRB1<i>*</i> 08:02 (p=0.0271, OR:0,13) and HLADRB1<i>*</i> 08:07 (p=0.0133, OR: 0.08). In the gene <i>HLADQA1</i>, 1 allele associated with the IMIDs were found, the HLADQA1*04:01 (p=1.4e-05, OR: 0.06). In the <i>HLADPB1</i> gene 3 alleles associated with the IMIDs were identified: HLADPB1*02:01 (p=4.2e-05, OR: 82.91), HLADPB1*03:01 (p=2e-06, OR: 14.97), HLADPB1*04:01 (p=1.5e-05 OR: 34.55). Different associations between IMIDs and alleles was identify (table 1). <h3>Conclusions</h3> In the genetic association analysis, already known associations have been replicated and new ones previously unpublished have been identified in Paraguayan IMIDs patients. This is the first genetic association study in IMID patients Paraguayan origin. <h3>Disclosure of Interest</h3> None declared
THU0089 Il-17a+gm-csf+ neutrophils are the major infiltrating cells in interstitial lung disease in an autoimmune arthritis model
Authors: O.C. Kwon, E.-J. Lee, E.-J. Chang, W.J. Seo, J.S. Oh, S. Hong, C.-K. Lee, B. Yoo, Y.-G. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Discrepancy in the effect of biologic agents on synovial and lung inflammation exists, indicating that the nature of inflammation in the synovium and lung may be different in RA. <h3>Objectives</h3> To gain a better understanding of the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD. <h3>Methods</h3> We injected curdlan in SKG mice at 8 weeks of age, and identified the presence of ILD by PET-MRI at 20 weeks post-injection and histological analysis at 22 weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22 weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed. <h3>Results</h3> At 20 weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b<sup>+</sup>Gr1<sup>+</sup> neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-α. Compared with 14 weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and IL-7Rα had increased at 22 weeks post-injection, whereas those of IFN-γ, IL-22, IL-6, and TNF-α remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-α, were observed in immunofluorescent-stained lung tissue. <h3>Conclusions</h3> We found that IL-17A<sup>+</sup>GM-CSF<sup>+</sup> neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-α in ILD development. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
Some men who were unable to access PrEP through NHS trial are now HIV positive, charities report
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Large numbers of gay and bisexual men trying to access pre-exposure prophylaxis (PreP) against HIV infection through NHS England’s trial have been turned away because clinics have run out of places, and some are now infected with the virus, charities have told The BMJ .

The first clinic began offering PreP through the three year trial in October 2017 after NHS England lost a legal battle over funding prevention with the drug Truvada (tenofovir disoproxil/emtricitabine).12 The trial originally had 10 000 places, but this number was boosted to 13 000 last summer. Now NHS England has …
THU0263 Analysis on characteristics of 82 patients with ankylosing spondylitisin japan
Authors: K. Tada, S. Kobayashi, E. Hayashi, M. Ogasawara, H. Inoue, K. Yamaji, N. Tamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is the prototype of spondyloarthritis, which affects sacroiliac joints, spine, peripheral joints and enthuses. HLA-B27 is known to be related with AS and there is a considerable number of patients suffering from AS among other rheumatic diseases. In Japan, however, the prevalence of AS was reported to be less than 0.1% much lower than western countries and also other East Asian countries <sup>1) 2) 3)</sup>. This is due to the low frequency of HLA-B27 in Japanese (0.3%) compared to 5%–10% in the countries mentioned above. Because of small number of AS patients, clinical features and HLA-B27 positivity has not been well investigated in Japanese patients with AS. Since our hospital has an outpatient specialising in AS and there are many patients, we conducted a survey on AS <h3>Objectives</h3> In this study, we examined the characteristics of patients with AS in our hospital and compared the data of patients with AS in Japan and overseas. <h3>Methods</h3> We conducted a questionnaire survey on patients fulfilling the modified New York criteria for AS. A questionnaire included demographic data and histories. We also retrospectively investigated the data of blood test, radiographs and the presence of inflammatory back pain (IBP), HLA-B27, enthesitis, dactylitis, radiographic sacroiliitis and extra-articular manifestation. <h3>Results</h3> A total of 82 patients (82.9% male) including Japanese (68), Chinese,<sup>9</sup> Korean<sup>5</sup> with AS who fulfilled the modified New York criteria were enrolled from May in 2013 to April in 2016. Of 68 patients with HLA-B27 test result, 61 patients (89.7%) were HLA-B27 positive. Of 54 Japanese patients, 48 patients (88.9%) were HLA-B27 positive. IBP, enthesitis, dactylitis, bamboo spine and uveitis were found in 67 patients (81.7%), 31 patients (37.8%), 5 patients (6.1%), 44 patients (53.7%) and 30 patients (36.6%), respectively. <h3>Conclusions</h3> In Japanese AS patients, the prevalence of HLA-B27 was high (almost 90%) and other characteristics were similar with those of Western countries. In Japan where the frequency of HLA-B27 is very low, B27 positivity is considered to have high diagnostic value. <h3>References</h3> [1] Hukuda S, Minami M, Saito T, Spondyloarthropathies in Japan; Nationwide questionnaire survey performed by the japan ankylosing spondylitis society. J Rheumatol2001;28: 554–559. [2] Calin A, Fries JF. Striking prevalence of ankylosing spondylitis in "healthy" W27 positive males and gemales. N Engl J Med. 1975;293:835–839. [3] Akkoc N, Khan MA. Overestimation of the prevalence of ankylosing spondylitis in the Berlin study: comment on the article by Braun, et al. Arthritis Rheum2005;52–4048–4049. <h3>Disclosure of Interest</h3> None declared
Abstract P051: Association of Subclinical Hypoglycemia with Incident Cardiovascular Disease and All-cause Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Morgana Mongraw-Chaffin, Alain G Bertoni, Sherita Hill Golden, Nestoras Mathioudakis, Dorothy D Sears, Moyses Szklo, Cheryl A Anderson
Journal: Circulation (2017)

Trials of intensive glucose control have not improved cardiovascular disease (CVD) risk in type 2 diabetes; however data are inconsistent about the effects of maintaining below normal glucose levels in the general population. Further, it has been suggested that fasting glucose and HbA1c in the lower ranges have a different relationship with CVD and mortality. In 5992 participants from the Multi-Ethnic Study of Atherosclerosis, free of CVD at baseline, we used logistic regression to investigate the associations of low fasting glucose (&lt;80mg/dL) and HbA1c (&lt;5.0%), from baseline and averaged across follow-up over 13 years, with incident CVD and mortality. We used the normal range (80 to &lt;100mg/dL and 5.0 to &lt;5.7%) as reference. We excluded participants with diabetes at baseline from the low, normal, and impaired groups at baseline, and excluded participants with diabetes at any visit from those groups for averaged values. We matched covariates to the visit of glycemic data collection. Participants with low fasting glucose were more likely to be younger, female, Asian, use glucose lowering medication, have lower BMI and be normotensive. Those with low HbA1c were more likely to be younger, Asian or Hispanic, and have higher income at baseline. Adjusted for age, sex, race/ethnicity, education, and income, glucose and HbA1c in the impaired (100 to &lt;126mg/dL and 5.7 to &lt;6.5%) and diabetic ranges (≥126mg/dL and ≥6.5%) at baseline were significantly associated with increased CVD and mortality. Low baseline glucose and low baseline HbA1c were positively, but not significantly, associated with mortality; while low average glucose and low average HbA1c were both strongly and significantly associated with increased risk of mortality (Figure). The relationships between fasting glucose and HbA1c with mortality are J-shaped at baseline, but strongly and significantly U-shaped when average levels are used. Consistently low fasting glucose or HbA1c may be better markers for risk from subclinical hypoglycemia than a single low measurement.
Blossoming 20: The Energetic Regulator's Birthday Unveils its Versatility in Cardiac Diseases
Authors: Jianjun Lv, Chao Deng, Shuai Jiang, Ting Ji, Zhi Yang, Zheng Wang, Yang Yang
Journal: Theranostics (2019)

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) was first identified in 1998 as a PGC-1 family member that regulates adaptive thermogenesis and mitochondrial function following cold exposure in brown adipose tissue. The PGC-1 family has drawn widespread attention over the past two decades as the energetic regulator. We recently summarized a review regarding PGC-1 signaling pathway and its mechanisms in cardiac metabolism. In this review, we elaborate upon the PGC-1 signaling network and highlight the recent progress of its versatile roles in cardiac diseases, including myocardial hypertrophy, peripartum and diabetic cardiomyopathy, and heart failure. The information reviewed here may be useful in future studies, which may increase the potential of this energetic regulator as a therapeutic target.
Abstract 16195: Relationship Between Left Ventricular Mass and Central Blood Pressure During Exercise
Authors: Masatake Kobayashi, Hiroshi Kobayashi, Yoichi Iwasaki, Yuto Kumai, Yasuhiko Tsunoda, Mamoru Aiga, Kazutaka Oshima, Mineko Kino, Shiro Iwanaga, Akira Yamashina, Kenji Takazawa
Journal: Circulation (2013)

Background: We reported that central blood pressure after exercise increases with age. On the other hand, it is said that the elevation of central blood pressure had association with the increase o...
Children's Oncology Group (COG) AALL0434: Successful Disease Control without Cranial Radiation in Newly Diagnosed T Lymphoblastic Lymphoma (T-LL)
Authors: Robert James Hayashi, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Brent Wood, Michelle L. Hermiston, David T Teachey, Sherrie L. Perkins, Rodney R. Miles, Elizabeth A. Raetz, Mignon L. Loh, Naomi Winick, William L. Carroll, Stephen P. Hunger, Megan S. Lim, Catherine M. Bollard, Thomas G. Gross
Journal: Blood (2018)
AB0922 Metabolic syndrome is associated with active disease in psoriatic arthritis and may contribute to development of syndesmophytes
Authors: P. Sanci, G. Kenar, B. Zengin, S. Uslu, A. Koken, H. Yarkan, H. Ellidokuz, G. Can, M. Birlik, F. Onen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> An increased prevalence of metabolic syndrome (MetS) has been reported in psoriatic arthritis (PsA) suggesting an association between the inflammation and MetS. <h3>Objectives</h3> The aim of this study is to investigate its relationship with disease activity in patients with PsA. We also evaluated whether an association exists between MetS and axial involvement in PsA. <h3>Methods</h3> This study included patients with PsA followed in the Rheumatology outpatient clinic at Dokuz Eylul University. Age-matched patients with Takayasu arteritis (TA), an inflammatory systemic disease, were enrolled as diseased controls. The NCEP-ACT III criteria were used to identify subjects with MetS. Disease activity was assessed in patients with PsA by using several parameters including BASDAI, ASDAS, VAS patients' and physician' global, Tender and Swollen joint assessment (28/68), DAS28, DAPSA, CPDAI and SPARCC Enthesitis Index. ESR and serum CRP levels were measured. BASFI and BASMI were used to evaluate functional status and HAQ, ASQoL and DLQI to evaluate health and PASI to measure the severity of psoriasis. Hand and pelvis X-rays and sacroiliac joint MRIs were performed when indicated. <h3>Results</h3> There were 104 PsA patients (63.5% F; mean age: 50.9±13.0 years) who fulfilled the CASPAR criteria and 28 TA patients (89% F, mean age: 46.3±9.1) who fulfilled the <sup>ACR 1990</sup> criteria. The prevalence of MetS was found to be considerably higher in PsA patients compared to TA patients (45.2% and 21.4% respectively, p&lt;0.001). In the comparison of PsA patients with and without MetS, no differences were found regarding treatment frequencies of NSAIDs, glucocorticoids, DMARDs and anti-TNFs and also mean glucocorticoid dosages. PsA patients with MetS had higher BASDAI, BASFI, BASMI, VAS, ASqOL, CPDAI, ASDAS and HAQ scores compared to PsA patients without MetS (table 1). More patients with syndesmophytes were found among PsA patients with MetS compared to those without MetS (p=0.027). There were no differences in indexes related predominantly peripheral involvement, such as tender and swollen joint counts, enthesitis score and presence of dactylitis. In multivariable regression analysis, presence of syndesmophytes had no relationship with MetS, but still related with ESR and BASMI. <h3>Conclusions</h3> This study demonstrates a higher prevalence of MetS in PsA patients compared to TA. It also suggests that MetS might be associated with high disease activity and more severe disease especially in patients with axial involvement. <h3>Disclosure of Interest</h3> None declared
Characterizing Population Heterogeneity and Signaling Changes in Chronic Myeloid Leukemia Stem and Progenitor Cells upon Combined Treatment with Imatinib and MEK Inhibitors Using Quantitative Single Cell Phospho-Imaging
Authors: Anna Reister Schultz, Thomas Jacob, Christopher A. Eide, Samantha L Savage, Motomi Mori, Jeffrey W. Tyner, Cristina E. Tognon, Tania Q. Vu, Brian J. Druker
Journal: Blood (2018)