tbuckley/cabot-search huggingface dataset:
Allogeneic CAR T cell therapies for leukemia
Authors: Waseem Qasim
Journal: American Journal of Hematology (2019)

Allogeneic chimeric antigen receptor T (CAR T) cells can offer advantages over autologous T cell therapies, including the availability of “fit” cells for production, and elimination of risks associated with inadvertent transduction of leukemic blasts. However, allogeneic T cell therapies must address HLA barriers and conventionally rely on the availability of a suitable HLA‐matched donor if graft‐vs‐host‐disease and rejection effects are to be avoided. More recently, the incorporation of additional genome editing manipulations, to disrupt T cell receptor expression and address other critical pathways have been explored. Clinical trials are underway investigating non‐HLA matched T cells expressing anti‐CD19 CARs for the treatment of B cell acute lymphoblastic leukemia (B‐ALL) and anti‐CD123 CAR for acute myeloid leukemia (AML). Such approaches continue to be refined and improved to widen accessibility and reduce the cost of T cell therapies for a wider range of conditions.
Long-Term Outcomes of IMiD Based Trials in Patients with Immunoglobulin Light Chain Amyloidosis (AL): A Pooled Analysis
Authors: Rahma Warsame, Betsy Laplant, Kristine Laumann, Shaji K Kumar, Morie A. Gertz, Robert A Kyle, Martha Q Lacy, David Dingli, Nelson Leung, Francis K Buadi, Suzanne R. Hayman, Prashant Kapoor, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Wilson I Gonsalves, Taxiarchis Kourelis, Stephen J. Russell, Steven Zeldenrust, Yi Lin, Eli Muchtar, Ronald S. Go, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2017)
AB0173 Overwhelming inflammation increased susceptibility of sle-prone mice to pulmonary bactreial infection
Authors: W. Li, X. Tang, S. Huang, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Aside from the disease itself, infections represent the major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Inherent defects in immune system play an important role in increasing rates of infection. However, the underlying mechanism of this dificiency remains largely unknown. <h3>Methods</h3> Lupus-prone mice B6/<i>lpr</i> were anaesthetized and infected with 1×10^8 CFU of <i>Haemophilus influenzae</i> (Hi) intranasally. Then bacterial clearance, body weight change and lung pathology were monitored. Apoptosis of lung cells was analysed by TUNEL assay. Both innate and adaptive immune response in the lung cells determined by flow cytometry. Cytokines in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. <h3>Results</h3> Although both wild-type (WT) and B6/<i>lpr</i> mice survived after pulmonary Hi infection, a delay of bacterial clearance and inflammatory resolution was observed in B6/<i>lpr</i> mice. Tissue damage was more severe in the lungs of B6/<i>lpr</i> mice, as more apoptotic cells were detected on Day2 after infection. Cells from lupus-prone lungs produced more pro-inflammatory cytokines IL-6, MCP-1 and KC. TNF-α is comparable between the two groups. NK, γδ T and CD4 T cells are required for control bacterial infection. We that compared with WT controls, in response to infection fewer NK cells were detected in B6/<i>lpr</i> lungs. The numbers of γδ and CD4 T cells were not different, but their ability to secrete IFN-γ was significant lower in B6/<i>lpr</i> mice. <h3>Conclusions</h3> The increased susceptibility of SLE-prone mice to pulmonary <i>Haemophilus influenzae</i> infection may due to the elevated inflammatory responses and the deficient production of IFN-γ by immune cells. <h3>Disclosure of Interest</h3> None declared
FRI0160 Chemokine and cytokine profile in systemic vasculitides
Authors: L Magrini, F Conti, FR Spinelli, M Bombardieri, G Borsetti, MD Cipriani, C Alessandri, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic vasculitides include a heterogeneous group of clinical syndromes characterised by inflammation and necrosis of blood vessel walls. Any type of vessels throughout the body may be involved with protean clinical manifestations, and pathogenetic mechanisms remain mainly unknown. <h3>Objectives</h3> Aim of our study was to test the hypothesis that chemokines, cytokines, and eosinophilic inflammation markers could be involved in systemic vasculitides pathogenetic process. <h3>Methods</h3> We studied 19 patients with systemic vasculitides diagnosed according to ACR 1990 criteria: 7 pts. with Churg-Strauss vasculitide (CS), 7 pts. with Wegener’s Granulomatosis (GW), 5 pts. with Panarteritis Nodosa (PAN) and 24 normal healthy subjects (NHS) as controls. Serum levels of the following mediators: macrophage inflammatory protein 1α (MIP1α), monocyte chemotactic protein 1 (MCP1), RANTES, interleukin 5 (IL5), granulocyte macrophage-colony stimulating factor (GM-CSF) and eosinophil cationic protein (ECP) were tested by ELISA. For the statistical analysis U-Mann Whitney test has been used. <h3>Results</h3> Among chemokines, serum levels of MCP1and RANTES were significantly higher in systemic vasculitides than NHS (p &lt; 0.001 and p &lt; 0.007 respectively), while no differences were demonstrated in MIP1α serum levels. Regarding cytokines studied, IL5 and GM-CSF serum levels were significantly higher in systemic vasculitides than NHS (p &lt; 0.001). Also ECP serum levels resulted increased in systemic vasculitides than NHS (p &lt; 0.04) with a significative correlation between ECP levels and blood eosinophilia in vasculitides patients. Furthermore, a specific subgroup analysis showed that serum levels of RANTES, IL5, and ECP resulted increased mainly in CS and GW, while MCP1 and GM-CSF mainly in CS and PAN. <h3>Conclusion</h3> Our study demonstrate the increased production of chemokines and cytokines in systemic vasculitides patients. Moreover, the finding of higher ECP serum levels in our patients induce us to hypothesise that eosinophils are actively involved in vasculitides etiopathogenesis. <h3>References</h3> Nowack R, <i>et al</i>. New developments in pathogenesis of systemic vasculitis. Curr Opin Rheumatol. 1998;10:3–11 Priori R, <i>et al</i>. Churg-Strauss syndrome during pregnancy after steroid withdrawal. Lancet 1998;352:1599–600
Treatment Response and Long-Term Survival in Multiple Myeloma in the GMMG-HD4 Trial - Neither Profit All Molecular Entities Alike, Nor Are Remissions to Different Regimen Equal
Authors: Anja Seckinger, Hans Jürgen Salwender, Hans Martin, Christof Scheid, Thomas Hielscher, Uta Bertsch, Manuela Hummel, Anna Jauch, Wolfgang Knauf, Martina Emde, Susanne Beck, Kai Neben, Henk M. Lokhorst, Bronno van der Holt, Ulrich Duehrsen, Jan Dürig, Hans-Walter Lindemann, Ingo Schmidt-Wolf, Mathias Haenel, Bernd Lathan, Marc S Raab, Carsten Müller-Tidow, Pieter Sonneveld, Igor Wolfgang Blau, Jens Hillengass, Katja Weisel, Hartmut Goldschmidt, Dirk Hose
Journal: Blood (2018)
Abstract 19163: A Novel Key Role of LDL and its Receptor in Pre-clinical and Clinical Pulmonary Hypertension
Authors: Soban Umar, Shayan Moazeni, Mylene Vaillancourt, Christine Cunningham, Nancy Cao, Sara Mottahedan, Srinivasa Reddy, Abbas Ardehali, Aman Mahajan, Mohamad Navab, Mansoureh Eghbali
Journal: Circulation (2017)

Introduction: Recently, we and others reported a critical role for oxidized lipids in pathogenesis of pulmonary hypertension (PH). However, LDL and its receptor (LDL-R), which binds and internalize...
FRI0213 The performance of 12 flare definitions including the assessment of spondyloarthritis international society (ASAS)-endorsed definition of clinically important worsening in asdas in patients with axial spondyloarthritis treated with adalimumab for 5 years
Authors: S. Juhl Pedersen, I.J. Sørensen, A.G. Loft, J. Hindrup, G. Kollerup, G. Thamsborg, K. Asmussen, O. Hendricks, J. Nørregaard, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In 2016 the Assessment of Spondyloarthritis International Society (ASAS) published proposals for 12 definitions of ′flare′(ref. 1) for patients with axial spondyloarthritis (axSpA). The definitions are based on pain, BASDAI and ASDAS (see table 1). In January 2018, ASAS published the ASAS-endorsed definition of clinically important worsening based on ASDAS (ΔASDAS≥0.9)(ref. 2). <h3>Objectives</h3> The aim of this study was to describe the frequency of ′flares′ as detected by the 12 flare definitions including the ASAS-endorsed definition. <h3>Methods</h3> Data from an investigator-initiated double-blinded randomised placebo-controlled trial of adalimumab versus placebo of 12 weeks with a 5 year open-label extension (NCT00477893, ref. 3) were used for this study. The number of patients experiencing a flare at each visit according to the 12 ASAS ′flare′ definitions was recorded for 20 study visits performed from two weeks after initiation of treatment and to year 5. <h3>Results</h3> 52 patients started treatment and 41 (79%) patients completed the 5 year follow-up visit. The total number (percentage) of study visits where pain, BASDAI and ASDAS flares could be calculated was 879 (84.5%), 875 (84.1%) and 842 (81.0%), respectively. The mean (SD) number of patients with a flare per visit ranged from 0.7 (1.2) to 3.8 (2.2) and the median (inter-quartile-range (IQR)) from 0 (0–1) to 5(3–7) (table 1). The mean number of patients per visit with a flare was significantly higher when the definition "change in ASDAS≥0.6" (p&lt;0.0001 to p=0.001, t-test) and "change ASDAS≥0.6 AND observed ASDAS≥1.3" (p&lt;0.0001 to p=0.04) were applied, and the mean number of patients was significantly lower when the BASDAI flare definitions were applied (p&lt;0.0001 to p=0.02). <h3>Conclusions</h3> The frequency of flares as detected by the 12 ASAS flare definitions for patients with axial spondyloarthritis differed substantially. The ASAS-endorsed definition performed well. <h3>References</h3> [1] Gossec, et al. Ann Rheum Dis2016;68(2):418–29. [2] Molto, et al. Ann Rheum Dis. 2018;77(1):124–127. [3] Pedersen, et al. Arthritis Rheumatism2016;68:418–29. <h3>Disclosure of Interest</h3> None declared
SP0138 Why not all effective interventions are worthwhile
Authors: F. Guillemin
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Economic decisions in the health sector should be made to reach both efficiency and improvement of health in the most equitable way in the population. Comparative assessment of innovation with usual or current standard practice allows measuring the incremental benefit per individual. The comparison should bear both on effectiveness, ie health effect, and on costs of alternatives, considering appropriate stakeholders and payers. Moreover, according to diseases and treatment target, the time horizon should be relevant to its expected effect, from a few weeks for painkillers to a lifetime for disease modifying drugs in inflammatory arthritis, joint prosthesis in osteoarthritis, or prevention of osteoporosis. Various scenarios can result from an economic analysis, with four possibilities for a new treatment or health care technology: more efficient at lower cost (optimal), less efficient at higher cost (worse issue), less efficient at lower cost (needing a decision to lose some effectiveness), or more efficient at higher cost – ie cost-effective – (needing to identify what the society is ready to pay off). This is done by calculating an incremental cost-effectiveness ratio, illustrating a marginal benefit per individual, at best using data from clinical trials. Therefore, not all effective interventions can be candidate for diffusion. Because there is a need to make decisions before larger diffusion of the innovation, a set of methods are also available to anticipate its potential benefit, using a modelling approach. Sensitivity analyses are also conducted in varying conditions of application in reasonable range, using deterministic and stochastic methods. More recently, another perspective has been developed, ie the calculation of the net budgetary impact. This approach allows an extension of the costs to the targeted people in the whole population at a country level. It should take all indirect costs into account. Using these approaches, it is possible to observe that sometimes promising health technology sometimes need to be abandoned, given the too high cost to society for low additional benefit to individuals. <h3>Disclosure of Interest</h3> None declared
THU0706 Presence of extractable nuclear antigens (ENA) antibodies in a large population-based cohort from the netherlands
Authors: S. Arends, L. Brouwer, C. Roozendaal, B. Doestzada, H. Bootsma, K. de Leeuw
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Previous studies have demonstrated that years before the clinical onset of auto-immune diseases, auto-antibodies can already be present in the blood of these patients. However, it is also known that some individuals can have these auto-antibodies and will never develop an auto-immune disease. So far, little information is available on the presence of Extractable Nuclear Antigens antibodies (anti-ENA) in the general population in relation to the risk of developing an auto-immune disease. <h3>Objectives</h3> To estimate the prevalence of anti-ENA and their association with the presence of known risk factors of Systemic Lupus Erythematosus (SLE) and Sjögren Syndrome (SS) in the general Dutch population. <h3>Methods</h3> Lifelines is a prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 135 participants were analysed. The detection of anti-ENA was performed using the ENA-CTD (connective tissue disease) screen on the Phadia-250 analyser with a ratio &gt;1.0 are considered positive. An extensive questionnaire was taken on demographic and clinical information (e.g. early musculoskeletal symptoms). Furthermore, some general blood parameters were available. SLE and SS were defined by a combination of self-reported SLE or SS, specific medication use and visiting a medical specialist within the last year. Characteristics were compared between 3 groups: SLE/SS patients, anti-ENA positive, and anti-ENA negative participants (without defined SLE/SS). <h3>Results</h3> Of the total 40 135 consecutive individuals, 41 were detected as having defined SLE or SS of whom 48% were anti-ENA positive SLE/SS patients were older and more often female. Of the remaining individuals,<sup>40,094</sup> 1089 (2.7%) were anti-ENA positive and anti-ENA positivity was also significantly associated with older age and female gender in this population. No significant associations were found for smoking and alcohol intake. As might be expected, SLE/SS patients reported more often complaints concerning fatigue, joint pain and joint stiffness. But also anti-ENA-positive participants reported significantly more often joint stiffness compared to anti-ENA-negative participants. Interestingly, levels of haemoglobin, leucocytes and lymphocytes were significantly decreased in anti-ENA-positive participants compared to anti-ENA-negative participants. <h3>Conclusions</h3> In this large population-based study, the prevalence of anti-ENA-positivity was 2.8% for the total group and 2.7% when excluding patients with SLE or SS. Older age, female gender, joint complaints and lower levels of haemoglobin, leucocytes and lymphocytes were more frequently present in anti-ENA-positive participants. Longitudinal studies are performed up to 15 years to investigate which individuals might develop SLE or SS to be able to develop prediction models. <h3>Disclosure of Interest</h3> None declared
Benefits of Empiric Nutritional and Medical Therapy for Semen Parameters and Pregnancy and Live Birth Rates in Couples with Idiopathic Infertility: A Systematic Review and Meta-analysis
Authors: Muhammad Imran Omar, Raj Prasenjit Pal, Brian D. Kelly, Harman Maxim Bruins, Yuhong Yuan, Thorsten Diemer, Csilla Krausz, Herman Tournaye, Zsolt Kopa, Andreas Jungwirth, Suks Minhas
Journal: European Urology (2019)
AB0959 Consumption of dairy products in relation to presence of clinical knee osteoarthritis: the maastricht study
Authors: K. Denissen, A. Boonen, J. Nielen, A. Feitsma, E. van den Heuvel, P. Emans, S. Sep, C. Stehouwer, M. van Dongen, P. Dagnelie, S. Eussen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA).<sup>1, 2</sup> There is lack of information on the role of specific other dairy product categories. <h3>Objectives</h3> To explore the association between dairy consumption and presence of clinical knee OA in individuals aged 40–75 year participating in the Maastricht Study. <h3>Methods</h3> Presence of clinical knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria.<sup>3</sup> Data on dairy consumption was appraised by a 253-item Food Frequency Questionnaire covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI), while correcting for relevant factors. <h3>Results</h3> Of the 3010 participants included in this study, 427 individuals (14%) were classified as having clinical knee OA. Significant inverse associations were observed between presence of clinical knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50–0.92) for full-fat dairy, and 0.75 (95%CI 0.56–0.99) for Dutch cheese. No significant associations were found for other dairy product categories. <h3>Conclusions</h3> In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with lower presence of clinical knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA. <h3>References</h3> [1] Kacar C, et al. Clin Exp Rheumatol. 2004;22(4):473–6. [2] Lu B, et al. Arthritis Care Res. 2014;66(6):802–9. [3] Altman R, et al. Arthritis Rheum. 1986;29(8):1039–49. <h3>Acknowledgements</h3> The authors thank all the voluntary participants from the Maastricht Study as well as the funding bodies. <h3>Disclosure of Interest</h3> K. Denissen: None declared, A. Boonen: None declared, J. Nielen: None declared, A. Feitsma Employee of: FrieslandCampina, a dairy company, E. van den Heuvel Employee of: FrieslandCampina, a dairy company, P. Emans: None declared, S. Sep: None declared, C. Stehouwer: None declared, M. van Dongen: None declared, P. Dagnelie: None declared, S. Eussen: None declared
Translation control of the immune checkpoint in cancer and its therapeutic targeting
Authors: Yichen Xu, Mauro Poggio, Hyun Yong Jin, Zhen Shi, Craig M. Forester, Ying Wang, Craig R. Stumpf, Lingru Xue, Emily Devericks, Lomon So, Hao G. Nguyen, Alice Griselin, John D. Gordan, Sarah E Umetsu, Siegfried H. Reich, Stephen T. Worland, Saurabh Asthana, Maria Barna, Kevin R. Webster, John T. Cunningham, Davide Ruggero
Journal: Nature Medicine (2019)
From Measuring Disease Burden to Designing and Evaluating Solutions—Global Surgery Research in Evolution
Authors: Jessica H. Beard, Margaret M. Ajiko, Jenny Löfgren
Journal: JAMA Network Open (2019)

Tessa Concepcion, MSGH; Mubarak Mohamed, CRNA; Shugri Dahir, MD; Edna Adan Ismail, PhD, SRN; Dan Poenaru, MD; Henry E. Rice, MD; Emily R. Smith, PhD, MSPH; for the Global Initiative for Children’s Surgery
Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins
Authors: Ying Han, Zhonggao Gao, Liqing Chen, Lin Kang, Wei Huang, Mingji Jin, Qiming Wang, You Han Bae
Journal: Acta Pharmaceutica Sinica B (2019)

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.
Immunocytokines with Target Cell-Restricted IL-15 Activity for Induction of NK Cell Reactivity Against Acute Myeloid Leukemia (AML)
Authors: Bastian J. Schmied, Latifa Zekri, Martin Pflügler, Melanie Märklin, Lothar Kanz, Gundram Jung, Helmut R. Salih
Journal: Blood (2018)
SAT0327 Baseline characteristics and reasons for apremilast prescription in a large italian cohort of psoriatic arthritis patients
Authors: E.G. Favalli, C. Zuccaro, M. Biggioggero, C. Selmi, R. Bucci, F. D’onofrio, G. Carlino, L. Santo, A. Semeraro, S. Monti, D. Mazzotta, F. Atzeni, R. Caporali, F. Iannone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There are no real-world data for the profiling of patients with psoriatic arthritis (PsA) receiving the phosphodiesterase-4 inhibitor apremilast. <h3>Objectives</h3> To retrospectively evaluate the baseline characteristics and the reasons for apremilast prescription in a large Italian multicenter cohort of PsA cases (<b>R</b>eal-life <b>AP</b>remilast for <b>P</b>soriatic arthritis <b>E</b>valuation <b>R</b>egistry, RAPPER). <h3>Methods</h3> Data were retrospectively extracted from the RAPPER registry which includes all PsA cases treated with apremilast in 11 Italian tertiary rheumatology centres between January 2017 and December 2017. Descriptive analysis of baseline characteristics of study population included demographics, previous treatments before apremilast, pattern of PsA involvement, disease activity indices, and prevalence of comorbidities (computed by the Rheumatic Disease Comorbidity Index [RDCI]<sup>1</sup>). Reasons for apremilast choice were also analysed. <h3>Results</h3> We studied 97 patients with PsA (61% women; mean [±standard deviation, SD] age 56.7±11.9 years; mean disease duration 10±13.1 years) who received apremilast as first-line targeted disease modifying drug (51.5%) or after the failure of at least one biologic agent (48.5%). In 75%, 33%, 11%, and 63% of patients there were articular (57% asymmetric oligoarthritis; mean Disease Activity in PSoriatic Arthritis [DAPSA] 22.55±11.55), entheseal (mean Leeds Enthesitis Index [LEI] 2.63±1.42), axial (mean Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 6.02±2.40), and skin/ungueal (mean body surface area [BSA] 1.71±3.44) involvement, respectively. Two thirds (64%) of patients had at least one comorbidity (mean RDCI 1.20) and the prevalence of conditions is reported in table 1. The main reasons for apremilast prescription were contraindication to biologic agents (66%), lack of poor prognostic factors (35%), comorbidities (34%), risk of infections (33%), and history of malignancy (22.6%), whereas a preference for an oral drug drove the choice only in 7% of patients. <h3>Conclusions</h3> Based on our analysis, apremilast is mainly used in PsA with oligoarthritis, enthesitis, mild skin involvement, and low risk of disease progression, carrying comorbidities (especially history of infections and malignancies) with contraindications to the use of biologic drugs. <h3>Reference</h3> [1] England BR, Sayles H, Mikuls TR, et al. Validation of the rheumatic disease comorbidity index. Arthritis Care Res2015;67(6):865–72. <h3>Disclosure of Interest</h3> None declared