tbuckley/cabot-search huggingface dataset:
FRI0014 Multiplex Screening of Cytokines in The Search for Disease Activity Markers of SLE
Authors: S. Eketjäll, H. Idborg, J.T. Gustafsson, A. Zickert, M. Kvarnström, V. Oke, P. Susanne, P.-J. Jakobsson, I. Gunnarsson, E. Svenungsson
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> There is presently no consensus on how to best measure disease activity in systemic lupus erythematosus (SLE). Available validated measures, such as SLE Disease Activity Index (SLEDAI) and SLE Activity Measure (SLAM), are composite scores that in addition to laboratory tests require investigation by a physician. These scores are insensitive to change and have failed to differentiate treatment responses in clinical trials. It would be an important step forward, for clinical practice and for clinical trials, if one or several biomarkers could be used as proxies for disease activity in SLE. <h3>Objectives</h3> Our objective is to evaluate cytokines, in combination with basic laboratory tests, as potential disease activity biomarkers. <h3>Methods</h3> In a cross-sectional setting we examined 433 patients with SLE (fulfilling four or more of the 1982 revised ACR criteria) and 322 age and gender matched population controls. Disease activity was assessed according to both SLEDAI and SLAM by a rheumatologist. Basic laboratory tests and analyses on MSD 30-plex cytokine assay (Mesoscale Discovery, K15054D) were performed on fasting blood samples (total &gt;50 potential biomarkers). The discriminatory power for investigated biomarkers was tested between patients and controls. Spearman correlations with SLAM/SLEDAI scores were calculated among patients. <h3>Results</h3> Many potential biomarkers discriminated between patients and controls. Best discriminatory power was observed for TNF-α (p=7x10<sup>–63</sup>), IL-6 (p=2.5x10<sup>–40</sup>), orosomucoid (p=7.1x10<sup>–38</sup>), plasma (P)-albumin (p=1.6x10<sup>–36</sup>) and sedimentation rate (SR) (p=5.6x10<sup>–34</sup>). The strongest correlations with SLEDAI/SLAM were observed for TNF-α (Spearman ρ=0.32, p=6.0x10<sup>–12</sup> for SLEDAI and Spearman ρ=0.34, p=5.0x10<sup>–13</sup> for SLAM), and for P-albumin (Spearman ρ=-0.33, p=9.0x10<sup>–13</sup> for SLEDAI and Spearman ρ=-0.31, p=5.0x10<sup>–11</sup> for SLAM). As SR is part of SLAM, expected positive correlations were observed (Spearman ρ=0.27, p=7.7x10<sup>-9</sup> for SLEDAI and Spearman ρ=0.48, p=4.0x10<sup>–25</sup> for SLAM). <h3>Conclusions</h3> Of more than 50 investigated biomarkers TNF-α was the best discriminator between SLE patients and controls. Furthermore TNF-α was the biomarker, which correlated best with disease activity. These correlations were further improved by the ratio between TNF-α and P-albumin. We propose that the TNF-α/P-albumin ratio merits further investigations as a clinically useful biomarker for diagnostic and surveillance purposes in SLE. <h3>Disclosure of Interest</h3> None declared
Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Quality of life in patients randomly assigned to treatment groups.
Journal: Circulation (1983)

To evaluate the comparative effects of medical and surgical therapy on quality of life of patients with stable ischemic heart disease, 780 patients who had been randomly assigned to medical or surgical therapy in the CASS were systematically followed for a mean of 5.5. years. Analysis was performed according to original treatment assignment. Patients in the surgical group had significantly less chest pain, fewer activity limitations, and required less therapy with nitrates and beta-blockers. Treadmill exercise tests performed 6, 18, and 60 months after entry documented significantly longer treadmill time, less exercise-induced angina, and less ST segment depression among surgical group patients. However, employment status and recreational status did not differ significantly between medical and surgical groups. Total number of hospitalizations after randomization was higher in the surgical group owing primarily to rehospitalization during the first year of follow-up for the coronary artery bypass graft surgery. Risk factors, including high blood pressure, cigarette smoking, high cholesterol levels, overweight, and poor exercise habits remained similar between medical and surgical groups. This randomized collaborative study shows that coronary artery bypass graft surgery improves the quality of life as manifested by relief of chest pain, improvement in both subjective and objective measurements of functional status, and a diminished requirement for drug therapy. However, no significant effect on employment or recreational status was observed.
<i>TP53</i> and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: John S. Welch, Allegra A. Petti, Christopher A. Miller, Catrina C. Fronick, Michelle O’Laughlin, Robert S. Fulton, Richard K. Wilson, Jack D. Baty, Eric J. Duncavage, Bevan Tandon, Yi-Shan Lee, Lukas D. Wartman, Geoffrey L. Uy, Armin Ghobadi, Michael H. Tomasson, Iskra Pusic, Rizwan Romee, Todd A. Fehniger, Keith E. Stockerl-Goldstein, Ravi Vij, Stephen T. Oh, Camille N. Abboud, Amanda F. Cashen, Mark A. Schroeder, Meagan A. Jacoby, Sharon E. Heath, Kierstin Luber, Megan R. Janke, Andrew Hantel, Niloufer Khan, Madina J. Sukhanova, Randall W. Knoebel, Wendy Stock, Timothy A. Graubert, Matthew J. Walter, Peter Westervelt, Daniel C. Link, John F. DiPersio, Timothy J. Ley
Journal: New England Journal of Medicine (2016)

The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.Of the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).
Enhanced Immunological Responses Following K562/GM-CSF/CD40L Vaccine Plus Lenalidomide in High-Risk Myelodysplastic Syndrome
Authors: John Powers, Eric Padron, Jason Dubovsky, Emmanuel Berchmans, Tyler Farnum, Fanqi Bai, Eva Sahakian, Jamil Ahmed, Rami S. Komrokji, Jeffrey E. Lancet, Alan F. List, Douglas G McNeel, Sophie Dessureault, Scott Antonia, Eduardo M. Sotomayor, P.K. Epling-Burnette, Javier Pinilla-Ibarz
Journal: Blood (2011)
Absolute Lymphocyte Count Recovery Predicts Superior Survival and Is Independent of the International Prognostic Index in Patients Treated with CHOP or R-CHOP Chemotherapy for Diffuse Large B Cell Lymphoma.
Authors: Luis F. Porrata, Kay M. Ristow, Susan M. Geyer, Svetomir N. Markovic, Daniel O. Persky, Joseph P. Colgan, William L. White, Thomas E. Witzig, David J. Inwards, Stephen M. Ansell, Ivana N. Micallef, Patrick B. Johnston, Thomas M. Habermann
Journal: Blood (2005)
Sequential Chemotherapy Followed by Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation (allo-SCT) in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML): A Survey From the Acute Leukemia Working Party of EBMT
Authors: Olle Ringden, Myriam Labopin, Hans Jochem Kolb, Mauricette Michallet, Nicolaus Kröger, Arnold Ganser, Donald Bunjes, Michael Hallek, Lothar Kanz, Rainer Schwerdtfeger, Ernst Holler, Renate Arnold, Anne Huynh, Arnon Nagler, Christoph Schmid, Mohamad Mohty
Journal: Blood (2012)
CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling
Authors: Xia Fang, Chiqi Chen, Fangzhen Xia, Zhuo Yu, Yaping Zhang, Feifei Zhang, Hao Gu, Jiangbo Wan, Xiaocui Zhang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Li Xie, Junke Zheng
Journal: Journal of Hematology & Oncology (2016)

CD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown. We established an MLL-AF9-induced acute myeloid leukemia (AML) model with wild-type (WT) and CD274-null mice to elucidate the role of CD274 in the cell fates of LICs, including self-renewal, differentiation, cell cycle, and apoptosis. RNA sequencing was performed to reveal the potential downstream targets, the results of which were further validated both in vitro and in vivo. In silico analysis indicated that CD274 level was inversely correlated with the overall survival of AML patients. In Mac-1+/c-Kit+ mouse LICs, CD274 was expressed at a much higher level than in the normal hematopoietic stem cells (HSCs). The survival of the mice with CD274-null leukemia cells was dramatically extended during the serial transplantation compared with that of their WT counterparts. CD274 deletion led to a significant decrease in LIC frequency and arrest in the G1 phase of the cell cycle. Interestingly, CD274 is not required for the maintenance of HSC pool as shown in our previous study. Mechanistically, we demonstrated that the levels of both phospho-JNK and Cyclin D2 were strikingly downregulated in CD274-null LICs. The overexpression of Cyclin D2 fully rescued the loss of function of CD274. Moreover, CD274 was directly associated with JNK and enhanced the downstream signaling to increase the Cyclin D2 level, promoting leukemia development. The surface immune molecule CD274 plays a critical role in the proliferation of LICs. The CD274/JNK/Cyclin D2 pathway promotes the cell cycle entry of LICs, which may serve as a novel therapeutic target for the treatment of leukemia.
The Different Dynamics of Chimerism Evolution Determines the Success of Myeloablative, Reduced Intensity Conditioning and T-Cell Depleted Allogeneic Stem Cell Transplantation.
Authors: Ismael Buño, Pascual Balsalobre, Ainhoa Simón, Gustavo Iglesias, Cintia Manzano, Rafael Carrión, David Serrano, Alfonso Gómez-Pineda, José L. Díez-Martín
Journal: Blood (2005)
THU0500 Frequency of IL-1 Gene Cluster Polymorphism and Its Relationship with Clinical Findings in Patients with Gout: Table 1.
Authors: B. Can, A. Balkarli, L. Elmas, C.C. Karatay, E. Tepeli, A. Kaya, V. Cobankara
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> IL-1β has role in promotion of acute gout inflammation. The relationship of IL-1 with comorbid conditions and many other disorders has been investigated previously. Gout is an auto-inflammatory disease. Activation of IL-1 gene can contribute to pathogenesis. <h3>Methods</h3> The study included 70 patients with gout and 106 age- and sex-matched healthy volunteers. By using genomic DNA isolated from patients and healthy volunteers, 5 polymorphic gene regions (rs16944, rs2234650, rs1800587, rs1143634 and rs315952) were analyzed by using PCR. Genotyping was performed by using Melting Curve Genotyping analysis. <h3>Results</h3> Mean age was 57.73 ± 10.2 years in the patient group and 57.42 ± 8.53 years in the control group. The frequency of IL1 rs16944 gene polymorphism of heterozygous (AG) genotype was found to be increased in the patient group compared to controls (61.4% vs. 40.6%; p=0.01). Genotype distribution of remaining gene polymorphisms was similar in both groups. When each gene polymorphism was assessed regarding allele frequency, no significant difference was detected between patient and control groups (p&gt;0.05). It was seen that CRP values (p=0.011) and number of attacks per year (p=0.035) were higher in patients with rs2234650 wild type (CC).The haplotype analysis was performed for rs2234650, rs1143634 and rs315952 which could have significant association with disease. Similar haplotype distribution was observed in both groups. <h3>Conclusions</h3> Although there was no significant difference in the distribution of IL-1 gene polymorphism, it is seen that the presence of some genotypes could affect clinical course of gout. <h3>Disclosure of Interest</h3> None declared
Antithymocyte Globulin at Clinically Relevant Concentration Kills Leukemic Blasts
Authors: Rosy Dabas, Rachelle Lee, Maria Theresa Servito, Poonam Dharmani Khan, Monica Modi, Tiffany Van Slyke, Joanne Luider, Caylib Durand, Loree Larratt, Joseph Brandwein, Andrew Daly, Faisal M Khan, Jan Storek
Journal: Blood (2015)
Kinetics of Chimerism Conversion to Total Donor Profile: Impact on Transplant Outcome after Reduced Intensity Conditioning Allogeneic Transplantation.
Authors: Mauricette Michallet, Quoc-Hung Le, Anne-Sophie Michallet, Franck E. Nicolini, Anne Thiebaut, Emmanuelle Tavernier, Hanadi Rafii, Samira Mahmoudi, Daniela Revesz, Aline Praire, Elodie Gadolet, Valerie Dubois, Lucette Gebuhrer
Journal: Blood (2004)
A Common but Overlooked Mechanism of BCR-ABL1 Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.
Authors: Jean-Marie Bruey, Hagop M. Kantarjian, Wanlong Ma, Chen-Hsiung Yeh, Tai-Sung Lee, Susan O'Brien, Francis Giles, Zeev Estrov, Jorge Cortes-Franco, Maher Albitar
Journal: Blood (2009)
PTU-123 “Have Your Second Baby First, and Have ‘EM Young”: Risks of Obstetric Trauma and Anorectal Dysfunction after Obstetric Injury: Abstract PTU-123 Table 1
Authors: E Athanasakos, A Raeburn, A Vashisht, N Zarate, A Emmanuel
Journal: Gut (2016)

<h3>Introduction</h3> Traumatic vaginal delivery is closely correlated with attenuation of anorectal structure and function, and hence symptoms of faecal urgency (FU) and incontinence (FI). We aim to describe the immediate clinical and physiological effect of overt perineal trauma in patients within 6 months of injury. <h3>Methods</h3> One hundred consecutive postpartum (3–6 months) patients who sustained an obstetric tear at delivery were studied over a 13 month period. Mean age was 33 years (range 22–51 years old), 75 women were older than 30 years. All patients underwent anorectal physiology (ARP) and endoanal ultrasound (EAUS) as per Unit protocol. <h3>Results</h3> Cohort: 84 of these obstetric tears were first vaginal delivery; of 16 who were multiparous, 11 had also sustained tears in their first delivery. Ten women sustained a 2<sup>nd</sup> degree tear, 84 a 3<sup>rd</sup> degree tear (3 a=45; 3 b=33; 3 c=6) and 6 women a 4<sup>th</sup> degree tear. Instrumentation was necessary in 55 of cases (43 forceps, 11 ventouse and 1 combination). Regarding other risk factors, birth weight was over 4 kg in 26 and 32 required an episiotomy. The table shows symptom burden at median 4 months; 60 patients were symptomatic, presenting with more than one troublesome symptom. Investigation: ARP demonstrated 17 with reduced resting sphincter pressure, 43 reduced voluntary squeeze and 27 inadequate endurance squeeze. Only 33 women had entirely normal manometry. Rectal hypersensitivity defined as two reduced thresholds to rectal mechanical distension was found in 11 patients. Similarly, abnormal anal and rectal electrosensory thresholds were seen in 20 and 5 women respectively. There was a significant correlation between those patients who had 3<sup>rd</sup> degree tears and hypersensitivity to maximum balloon distension (p = 0.007) and reduced anal sensitivity (p = 0.005). Immediate post-partum repair is often unsuccessful, 56 women had a persistently disrupted or scarred external sphincter and 22 had a disrupted internal anal sphincter on EAUS. <h3>Conclusion</h3> Maternal age over 30 and first delivery are disproportionately correlated to the likelihood of severe obstetric tears. The majority of women experience symptoms, of which the commonest are FU, FI and flatus incontinence. Sphincter disruption is often persistent despite attempted repair, and is associated with rectal hypersensitivity. Systematic investigation and clinical assessment is recommended to improve clinical management and offer counselling in regards to risks associated with future deliveries. <h3>Disclosure of Interest</h3> None Declared
Cancer Related Anemia in the Era of Erythropoietin Stimulating Agents (ESA)Uncertainty: A Single Cancer Institution Experience.
Authors: Hikmat Abdel-Razeq, Shadi B Hijjawi, Hazem Abdulelah, Yousef Ismael, Rula Amarin, Majid Asawaeer, Jamilah Shubeilat, Haitham Shaheen, Alaa Addasi, Dalia Al-Rimawi, Luna Zaru
Journal: Blood (2009)
Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma
Authors: Brian I. Rini, David F. McDermott, Hans Hammers, William Bro, Ronald M. Bukowski, Bernard Faba, Jo Faba, Robert A. Figlin, Thomas Hutson, Eric Jonasch, Richard W. Joseph, Bradley C. Leibovich, Thomas Olencki, Allan J. Pantuck, David I. Quinn, Virginia Seery, Martin H. Voss, Christopher G. Wood, Laura S. Wood, Michael B. Atkins
Journal: Journal for ImmunoTherapy of Cancer (2016)

Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.
Immune Reconstitution At Days 30 and 100 Following Allogeneic Stem Cell Transplant and Association with Subsequent Development of Chronic Graft-Versus-Host Disease
Authors: Samantha M. Jaglowski, Sumithira Vasu, Susan Geyer, Anissa Bingman, Patrick Elder, Jianhua Yu, William Blum, Rebecca B Klisovic, Sam Penza, Yvonne A Efebera, Craig C. Hofmeister, Don M. Benson, Natarajan Muthusamy, Steven M. Devine, Leslie A Andritsos, Gerard Lozanski
Journal: Blood (2012)
PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors Resistant to Immune Checkpoint Inhibitors
Authors: Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak, John Stagg
Journal: Cancer Research (2016)

Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab, and patients have a worse prognosis. Because type I and II IFNs are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long-lasting CD8+ T cell-dependent antitumor immunity. Remarkably, polyI:C and CpG was superior to combined PD-1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb therapy. Local injection of CpG and polyI:C in a primary tumor significantly enhanced the activity of systemic anti-ErbB2 mAb against a distant untreated tumor. Type I and II IFNs, as well as natural killer cells and CD8+ T cells, were indispensible to the synergistic activity of the combination treatment. Because synthetic RNA analogues and CpG oligodeoxynucleotides have been safely used in clinical trials, our study supports combination treatments with anti-ErbB2 mAbs. Cancer Res; 77(2); 312-9. ©2016 AACR.
Number of locums has doubled since 2009
Authors: Tom Moberly
Journal: BMJ (2016)

The number of hospital doctors choosing to work as locums has almost doubled since 2009, National Statistics data show (fig 1). Between 2009 and 2015 the number of locum doctors in hospitals rose by 96%, from 8176 in 2009 to 16 002 in 2015. This represents a 12% average annual rise. On average, 1304 more doctors each year are choosing …