tbuckley/cabot-search huggingface dataset:
AB0048 Serum cxcl13 levels in patients with systemic lupus erythematosus and its correlation to disease activity and lupus nephritis
Authors: A.M. Abdalla, E.A.E. Baraka, M. El-Bhissy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterised by the production of pathogenic autoantibodies against nuclear structures.<sup>1</sup> B lymphocyte chemoattractant (BLC) or CXC motif ligand 13 (CXCL13) play an important regulatory role of B1 and B2 cell trafficking for activation of autoreactive T helper cells.<sup>2</sup> CXCL13 can induce trafficking of the CXCR5 +T lymphocyte subset designated as follicular helper T lymphocytes which are specifically involved in production of autoantibodies during the development of lupus.<sup>3</sup> <h3>Objectives</h3> To detect serum CXCL13 levels in SLE patients and determine its relation to the disease activity and lupus nephritis <h3>Methods</h3> The study included 32 SLE patients and 20 healthy individuals as a control group. Patients' group was further subdivided according to disease activity and renal involvement. Serum samples from all studied individuals were analysed for the concentrations of CXCL13 by ELISA. <h3>Results</h3> There was a high statistically significant increase (p&lt;0.001) in the mean of serum CXCL13 on comparing its levels in SLE patients [242 (121.5–855.6) pg/ml] versus control group [73.8 (22.8–120.3) pg/ml], and on comparing its levels in lupus nephritis patients [542.4 (171–855.6) pg/ml] versus other patients without lupus nephritis [212.9 (121.5–580.5) pg/ml]. Moreover, CXCL13 Concentrations were correlated with SLEDAI (r=0.771, p&lt;0.001) and double-stranded DNA titres (r=374, p&lt;0.05). <h3>Conclusions</h3> Our data suggest that CXCL13 has an important role in pathogenesis of SLE and lupus nephritis. Also, pharmacological regulation of CXCL13 and its receptor CXCR5 may be a useful therapy in lupus nephritis. <h3>Acknowledgements</h3> Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. ;<sup>Journal of Clinical Pathology. 2003</sup>56(<sup>7</sup>:481–490. Legler, DF, Loetscher, M, Roos, RS, Clark–Lewis, I, Baggiolini, M, Moser, B. B–cell–attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. ;<sup>J Exp Med 1998</sup> 187: 655–660 Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. ;<sup>J Exp Med. 2000</sup>192:1553–62. <h3>Disclosure of Interest</h3> None declared
NQO1-dependent, Tumor-selective Radiosensitization of Non–small Cell Lung Cancers
Authors: Edward A. Motea, Xiumei Huang, Naveen Singh, Jessica A. Kilgore, Noelle S. Williams, Xian-Jin Xie, David E. Gerber, Muhammad S. Beg, Erik A. Bey, David A. Boothman
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Development of tumor-specific therapies for the treatment of recalcitrant non–small cell lung cancers (NSCLC) is urgently needed. Here, we investigated the ability of β-lapachone (β-lap, ARQ761 in clinical form) to selectively potentiate the effects of ionizing radiation (IR, 1–3 Gy) in NSCLCs that overexpress NAD(P)H:Quinone Oxidoreductase 1 (NQO1). Experimental Design: The mechanism of lethality of low-dose IR in combination with sublethal doses of β-lap was evaluated in NSCLC lines in vitro and validated in subcutaneous and orthotopic xenograft models in vivo. Pharmacokinetics and pharmacodynamics (PK/PD) studies comparing single versus cotreatments were performed to validate therapeutic efficacy and mechanism of action. Results: β-Lap administration after IR treatment hyperactivated PARP, greatly lowered NAD+/ATP levels, and increased double-strand break (DSB) lesions over time in vitro. Radiosensitization of orthotopic, as well as subcutaneous, NSCLCs occurred with high apparent cures (&amp;gt;70%), even though 1/8 β-lap doses reach subcutaneous versus orthotopic tumors. No methemoglobinemia or long-term toxicities were noted in any normal tissues, including mouse liver that expresses the highest level of NQO1 (∼12 units) of any normal tissue. PK/PD responses confirm that IR + β-lap treatments hyperactivate PARP activity, greatly lower NAD+/ATP levels, and dramatically inhibit DSB repair in exposed NQO1+ cancer tissue, whereas low NQO1 levels and high levels of catalase in associated normal tissue were protective. Conclusions: Our data suggest that combination of sublethal doses of β-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + β-lap against patients with NQO1+ NSCLCs.
Factors That Explain Differences in Abstinence Between Black and White Smokers: A Prospective Intervention Study
Authors: Nicole L Nollen, Matthew S Mayo, Lisa Sanderson Cox, Neal L Benowitz, Rachel F Tyndale, Edward F Ellerbeck, Taneisha S Scheuermann, Jasjit S Ahluwalia
Journal: JNCI Journal of the National Cancer Institute (2019)

Black-white differences in smoking abstinence are not well understood. This trial sought to confirm previously reported differences in quitting between blacks and whites and to identify factors underlying this difference.During enrollment, 224 black and 225 white low-income smokers were stratified on race and within race on age and sex to ensure balance on these factors known to impact abstinence. The intervention included varenicline for 12 weeks and six guideline-based smoking cessation counseling sessions. The primary endpoint was cotinine-verified 7-day point prevalence smoking abstinence at week 26. A priori socioeconomic, smoking, treatment process (eg, treatment utilization, side effects, withdrawal relief), psychosocial, and biological factors were assessed to investigate race differences in abstinence. Unadjusted odds ratios (OR) were used to compare abstinence between blacks and whites. Adjusted odds ratios from logistic regression models were used to examine predictors of abstinence. All statistical tests were two-sided.Blacks were less likely to achieve abstinence at week 26 (14.3% vs 24.4%, OR = 0.51, 95% confidence interval [CI] = 0.32 to 0.83, P = .007). Utilizing best subsets logistic regression, five factors associated with race jointly predicted abstinence: home ownership (yes/no, OR = 3.03, 95% CI = 1.72 to 5.35, P < .001), study visits completed (range = 0-6, OR = 2.81, 95% CI = 1.88 to 4.20, P < .001), income (household member/$1000, OR = 1.03, 95% CI = 1.01 to 1.06, P = .02), plasma cotinine (per 1 ng/mL, OR = 0.997, 95% CI = 0.994 to 0.999, P = .002), and neighborhood problems (range = 10-30, OR = 0.88, 95% CI = 0.81 to 0.96, P = .003).The race difference in abstinence was fully explained by lack of home ownership, lower income, greater neighborhood problems, higher baseline cotinine, and higher visit completion, which were disproportionately represented among blacks. Findings illuminate factors that make it harder for blacks in the United States to quit smoking relative to whites and provide important areas for future studies to reduce tobacco-related health disparities.
AB0055 Hydroxychloroquine inhibits soluble cd154 production through ca2+ and pkc signalling pathway
Authors: C.H. Tung, J.-M. Hsu, M.-C. Lu, N.-S. Lai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Over-expression of membranous CD154 and soluble CD154 (sCD154) in T lymphocytes is important in pathogenesis of autoimmune diseases. PKC pathway induces sCD154 production through promoting shedding of membranous CD154. Objectives: Hydroxychloroquine (HCQ) has been used in the treatment of autoimmune diseases for decades. We sought to identify the effects of HCQ on sCD154 and a possibly regulatory mechanism. Methods: CD4 +T cells were isolated from the blood of healthy donor. After stimulated with ionomycin +PMA and various concentrations of HCQ, concentration of sCD154 in the medium, expression of membranous CD154, Ca<sup>2+</sup> pathway and PKC signalling pathway were assessed. Results: HCQ attenuated intracellular sustained calcium storage release and membranous CD154 synthesis in activated T cells. Besides, HCQ inhibited PKC activation and subsequently shedding of membranous CD154. Conclusions: HCQ inhibited production of sCD154 in activated T cells through suppressing Ca<sup>2+</sup> and PKC signalling pathway. These findings provide one of the mechanistic insights into HCQ treatment. <h3>References</h3> [1] Alaaeddine N, Hassan GS, Yacoub D, Mourad W. CD154: an immunoinflammatory mediator in systemic lupus erythematosus and rheumatoid arthritis. Clin Dev Immunol. 2012:490148. [2] Goules A, Tzioufas AG, Manousakis MN, Kirou KA, Crow MK, Routsias JG. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun2006;26:165–71. [3] Matthies KM, Newman JL, Hodzic A, Wingett DG. Differential regulation of soluble and membrane CD40L proteins in T cells. Cell Immunol. 2006;241:47–58. [4] Wu SF, Chang CB, Hsu JM, Lu MC, Lai NS, Li C, Tung CH. Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther2017Aug 9;19(1):183. <h3>Disclosure of Interest</h3> None declared
A Phase II Study of the Hyper-CVAD Regimen in Sequential Combination with Blinatumomab As Frontline Therapy for Adults with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Authors: Guillaume Richard-Carpentier, Hagop M. Kantarjian, Nicholas J Short, Farhad Ravandi, Alessandra Ferrajoli, Heather M Schroeder, Maria Khouri, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Jorge E. Cortes, Nitin Jain, Marina Y. Konopleva, Koichi Takahashi, Koji Sasaki, Rebecca E. Garris, Elias J. Jabbour
Journal: Blood (2018)
SAT0554 Preoperative physical function influences on stair climbing ability 1 month after total knee arthroplasty
Authors: B.R. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> This study was undertaken to identify preoperative physical performance factors predictive of stair climbing ability 1 month following total knee arthroplasty. <h3>Methods</h3> In this prospective cohort study, we assessed a total of 84 patients (8 males and 76 females; average age 72.0±6.0 years) who underwent a primary unilateral total knee arthroplasty (TKA). Before and 1 month after TKA, patients completed physical performance tests including stair climbing test (SCT), 6 min walk test(6MWT), timed up and go test (TUG), isometric knee flexor and extensor strength of the surgical and non-surgical knees, and instrumental gait analysis for spatiotemporal parameters. Self-reported disease-specific physical function measured by using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and self –reported quality of life measured by using Euro QOL five dimensions (EQ-5D) questionnaire. <h3>Results</h3> In the bivariate analyses, the postoperative SCT-ascent had a significant positive correlation with the SCT-ascent (r=0.29, p=0.01), SCT-descent (r=0.28, p=0.01), TUG (r=0.37, p&lt;0.01), preoperative age (r=0.25, p=0.02), and a significant negative correlation with the preoperative 6MWT (r=−0.33, p&lt;0.01), peak torque (PT) extensor of surgical knee (r=−0.29, p=0.01), PT flexor of surgical knee (r=−0.26, p=0.02), PT extensor of the non-surgical knee (r=−0.26, p=0.02), PT flexor of the nonsurgical knee(r=−0.25, p=0.02). The postoperative SCT-descent had a significant positive correlation with the SCT-ascent (r=0.28 p=0.01), SCT-descent (r=0.40, p&lt;0.01), TUG (r=0.38, p&lt;0.01), preoperative age (r=0.27, p=0.01), WOMAC function (r=0.30, p&lt;0.01), and a significant negative correlation with 6-MWT (r=−0.33, p&lt;0.01), PT extensor of surgical knee (r=−0.23 p=0.04), PT flexor of surgical knee (r=−0.24, p=0.03), PT extensor of the nonsurgical knee (r=−0.25, p=0.03), PT flexor of the nonsurgical knee(r=−0.23, p=0.03). In the linear regression analyses, the postoperative SCT-ascent had a significant positive correlation with the preoperative TUG (ß=0.28, p&lt;0.01), PT extensor of surgical knee (ß=−0.23, p=0.03) and the postoperative SCT-descent had a significant positive correlation with preoperative SCT-descent (r=0.28, p=0.01), and the age (ß=0.20, p=0.04). <h3>Conclusions</h3> This study demonstrated that preoperative physical function influenced on postoperative stair climbing ability 1 month after TKA. Using variables easily measured before surgery, it may be possible to predict with good accuracy for postoperative stair climbing ability. In addition, these results could be of importance in determining variable preoperative rehabilitation strategies to improve stair climbing ability, especially focusing on balance, endurance and strengthening exercises. <h3>Disclosure of Interest</h3> None declared
AB0916 Efficacy and predictive factors of clinical response to tnf inhibitors in patients with axial and peripheral psoriatic arthritis
Authors: D. Benavent, C. Plasencia, V. Navarro-Compán, B. Hernández-Breijo, A. Villalba, D. Peiteado, M. de Diego, P. Bogas, E. Fernández, A. Balsa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with psoriatic arthritis (PsA) may have predominant axial (axPsA) or peripheral (pPsA) manifestations. The development of TNF inhibitors (TNFi) has changed the course of PsA. However, most published data is focused on pPsA but almost no data is available for TNFi response in axPsA. <h3>Objectives</h3> to analyse the efficacy and the predictive factors of clinical response in patients with axPsA and pPsA starting treatment with TNFi in clinical practice. <h3>Methods</h3> An observational study analysing data from a prospective cohort including 93 patients (pts) with axPsA or pPsA treated with TNFi from 2002–2018 was conducted. Demographic information, disease activity indexes (ASDAS for axPsA and DAS28 for pPsA) and laboratory tests were collected before starting TNFi (baseline visit) and 6 months later (6 m visit). At 6 m, the percentage of pts achieving inactive disease (ASDAS &lt;1.3) for axPsA or remission (DAS28 &lt;2.6) for pPsA as well as the percentage of pts achieving clinical improvement (defined as ASDAS-clinically important improvement=delta-ASDAS&gt;1.1 or delta-DAS28 &gt;1.2) were determined. Baseline predictor factors of inactive disease/remission and clinical improvement at 6 m were identified using a univariable and multivariable binary regression models adjusted for confounder factors. <h3>Results</h3> Out of 93 included pts, 45 pts had predominant axPsA and 48 pPsA. Administered TNFi was etanercept for most pts (42%), infliximab in 29%, adalimumab in 22% and golimumab in 7%. Baseline characteristics are shown in table 1. Male sex was more frequent in axPsA vs pPsA (62% vs 42%; p=0.04, respectively). In axPsA, 55% clinically improved and 32% pts achieved inactive disease. After multivariable analysis, male gender (OR 25.8, p=0.01) and higher baseline ASDAS (OR 6.3, p=0.01) were associated as independent predictors of clinical improvement at 6 m. Also, male gender (OR 15.7, p=0.03) and lower BMI (OR 0.7, p=0.03) were associated as independent predictor factors for achieving inactive disease. In pPsA, 48% pts clinically improved and 33% pts were on remission at 6 m. The percentage of pts on remission tended to be higher in males than females (47% vs 20%; p=0.08, respectively). However, after running the regression analyses, none of the baseline predictor factors was significantly associated neither with clinical improvement nor with remission in patients with pPsA. <h3>Conclusions</h3> In clinical practice, 1 out of 3 pts with PsA is on remission 6 m after initiating a TNFi, and 1 out of 2 clinically improve; both proportions are similar for axPsA and pPsA. Male gender, higher baseline disease activity and lower BMI are associated with more probability to achieve inactive disease or an important clinical improvement in axPsA. <h3>Disclosure of Interest</h3> None declared
99.3% of Inhibitors in Severe Hemophilia a Develop before Exposure Day 75. Time to Change Definition of Previously Treated Patients; Data from 1038 Patients with Severe Hemophilia a of the Pednet Registry
Authors: Marijke Van den Berg, Kathelijn Fischer, Elena Santagostino, Herve Chambost, Karin Kurnik, Gili Kenet, Christoph Male, Anne Rafowicz, Helen Platokouki, Susanna Ranta, Christel Van Geet, Johannes Oldenburg, Ri Liesner, Segolene Claeyssens, Nadine Gretenkort-Andersson, Anne Mäkipernaa, Torben Stamm Mikkelsen, Manuel Carcao, Beatrice Nolan, Liz Chalmers, A.R. Cid, Teresa Álvarez-Roman, Carmen Altisent, Georges Rivard, Claudio Molinari, Martina Buehrlen, Rainer Kobelt, Carmen Escuriola, Manuela Carvalho, Christoph Koenigs, Mike Williams, Rolf Ljung
Journal: Blood (2018)
Abstract 20778: Implementing an EHR-Based Phenotyping Algorithm to Detect Familial Hypercholesterolemia Cases in the eMERGE Network
Authors: Maya S Safarova, Kenneth M Borthwick, Agnes S Sundaresan, Maurine Tong, Wei-Qi Wei, Vivian S Gainer, Barbara Benoit, Elizabeth Wood Karlson, Iftikhar J Kullo
Journal: Circulation (2017)

Introduction: In most countries <20% of prevalent cases of familial hypercholesterolemia (FH) are diagnosed. There is an unmet need to develop EHR-based strategies to increase detection and control of FH. Objective: We assessed performance and portability of an electronic phenotyping algorithm for FH in the electronic MEdical Records and GEnomics (eMERGE) Network. Methods: Using the Phenotype KnowledgeBase (PheKB) platform, we deployed an electronic algorithm to ascertain FH at 5 adult sites. Family history of premature ASCVD/FH, findings of tendon xanthomas and corneal arcus were assessed using natural language processing (NLP) systems. LDL cholesterol levels, secondary hypercholesterolemia, and medications were ascertained from structured data sources. Personal history of premature ASCVD was defined using both code-based and NLP systems. Implementation was assessed by a 15-question survey at each site, including a 5-point Likert scale (very difficult/undesirable to excellent/very desirable) for ease of ...
FRI0566 Oedema-fibrosis in systemic sclerosis: comparison of a parametric cardiovascular magnetic resonance model to the lake louise criteria
Authors: G. Markousis-Mavrogenis, L. Koutsogeorgopoulou, D. Apostolou, G. Katsifis, P. Argyriou, S. Velitsista, L. Papa, M. Kanoupaki, E. Agelopoulos, E. Vernardos, G. Kanoupakis, G. Kolovou, S.I. Mavrogeni
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Myocardial disease is a major cause of death in systemic sclerosis (SSc). We hypothesised that the in SSc patients with suspected myocarditis, the Lake Louise criteria underdiagnose myocarditis compared to diagnostic models that incorporate parametric cardiovascular magnetic resonance (CMR) indices (extracellular volume fraction [ECV], native T1- and T2-mapping). <h3>Methods</h3> 32 patients with diffuse SSc (dSSc) and a clinical suspicion of myocarditis were prospectively evaluated with a 1.5 T scanner using the Lake Louise criteria, and the aforementioned parametric indices were determined. The Lake Louise criteria were compared with parametric indices individually and in two models (with and without taking late gadolinium enhancement [LGE] into account), with regard to diagnostic agreement. <h3>Results</h3> Native T1-mapping and ECV individually had the greatest discordance with the Lake Louise criteria. The presence or absence of LGE in the proposed parametric models did not lead to changes in identified patient proportions. Native T1-mapping led to the same proportion of diagnosis of myocarditis as either parametric model, with the exception of 2 patients. Most importantly, patients identified only by parametric models, had a significantly subtler presentation than those identified by the Lake Louise criteria, as exemplified by significantly lower T2 ratio, early gadolinium enhancement and T2-mapping values. <h3>Conclusions</h3> In dcSSc patients with a clinical suspicion of myocarditis, novel parametric models including native T1-mapping, T2-mapping and ECV, identified a significantly greater proportion of patients with myocarditis compared to those identified by the Lake Louise criteria, and native T1 mapping had the greatest utility in this cohort. <h3>Disclosure of Interest</h3> None declared
Overdose Deaths Involving Fentanyl and Fentanyl Analogs — New York City, 2000–2017
Authors: Cody Colon-Berezin, Michelle L. Nolan, Jaclyn Blachman-Forshay, Denise Paone
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Unintentional drug overdose deaths have climbed to record high levels, claiming approximately 70,000 lives in the United States in 2017 alone (1). The emergence of illicitly manufactured fentanyl* (a synthetic, short-acting opioid with 50-100 times the potency of morphine) mixed into heroin, cocaine, and counterfeit pills, with or without the users' knowledge, has increased the risk for fatal overdose (2,3). The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducts routine overdose mortality surveillance by linking death certificates with toxicology findings from the NYC Office of the Chief Medical Examiner (OCME). A 55% increase in the rate of fatal drug overdose in NYC was observed from 2015 to 2017, resulting in the highest number of overdose deaths recorded since systematic reporting began in 2000. Toxicology data indicate that this unprecedented increase in overdose deaths is attributable to fentanyl. Early identification of increased fentanyl involvement enabled DOHMH to respond rapidly to the opioid overdose epidemic by increasing awareness of the risks associated with fentanyl and developing effective risk reduction messaging. These results strongly suggest that, wherever possible, jurisdictions should consider integrating toxicology findings into routine overdose surveillance and work with local medical examiners or coroners to include fentanyl in the literal text on death certificates.
Abstract 14663: National Trends, Predictors of Use, and In-Hospital Outcomes in Mechanical Circulatory Support for Cardiogenic Shock
Authors: Jordan B Strom, Yuansong Zhao, Changyu Shen, Robert W Yeh
Journal: Circulation (2017)

Introduction: Despite rising rates of cardiogenic shock, data on trends and in-hospital outcomes of short-term non-durable mechanical circulatory support (MCS) are limited. Methods: Adults in the N...