tbuckley/cabot-search huggingface dataset:
FRI0332 The extent of tubulointerstitial inflammation predicts the prognosis of treated patients with lupus nephritis
Authors: S.J. Lee, Y.J. Kim, S. Jae Seok, N.R. Kim, E.J. Nam, Y.M. Kang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lupus nephritis is common clinical manifestation and contributes significantly to mortality of systemic lupus erythematosus (SLE) <h3>Objectives</h3> Recently it has been reported that severity of tubulointerstitial inflammation (TII) predicts subsequent renal failure. However, it has not yet been reported what histologic features affect the survival rate in patients with lupus nephritis who had conventional treatment. <h3>Methods</h3> Seventy-six patients with lupus nephritis, who had conventional treatment and renal biopsy, were enrolled in this study. The extent of tubulointerstitial lymphocytic infiltrates was semi-quantitated (grade 1–4) using standard histochemical staining. This was then compared to other established lupus nephritis classification (ISN/RPN classification) which focuses on histologic changes of the glomerulus as well as clinical and laboratory characteristics. Follow-up data were obtained and survival analysis was carried out to determine the predictive values for subsequent mortality. <h3>Results</h3> TII was a common pathologic finding, 64% percent of biopsy samples were graded as 1, 11% as 2, 14% as 3, and 11% as 4. In 29% of biopsies (22/76), there were well circumscribed lymphocyte aggregates in tubulointerstitium and 5% of biopsies (4/76), structures like germinal centre (GC) were observed. When TII was divided into mild (grade 1–2) and severe (grade 3–4), lymphocyte aggregates and GC formation were more common in patients with severe TII (15/19, 4/19) than those with mild TII (7/57, 0/57) (p&lt;0.001 and p=0.004, respectively). Patients with severe TII or lymphocyte aggregates were significantly higher in serum creatinine, but not with double-stranded DNA (ds DNA) antibodies, serum complement 3, SLE disease activity (SLEDAI) and degree of proteinuria at the time of biopsies compared to those without. The mean follow-up time was 62.9±47.0 months and overall, 9 patients died as a result of disease progression (n=6) and infection (n=3). Patients with severe TII, lymphocyte aggregates or GC formation were at greater risk for mortality compared to those without. However, both glomerular proliferation and laboratory markers including baseline ds DNA, complement, SLEDAI and degree of proteinuria did not affect on long term mortality. After multivariate logistic analysis including SLEDAI and histologic features, only GC formation provided poor prognostic information for mortality (hazard ratio 24.5, 95% confidence interval 2.2–274.6; p=0.009). <h3>Conclusions</h3> TII severity, especially GC formation, was independent predictor for a worse outcome in lupus nephritis patients with conventional treatment. A larger study is needed to confirm whether the presence of GC formation influences disease outcome. <h3>Disclosure of Interest</h3> None declared
Friendship: a ticket to a healthier life
Authors: Rebecca Coombes
Journal: BMJ (2019)

“The Fish Friday Ladies”—Pat, Sheila, Geraldine, Joyce, and Marian—make their weekly Friday bus trip into High Wycombe to go shopping and have a spot of lunch at their favourite fish and chip cafe.

This portrayal of their friendship is just one in a series of 40 images captured …
AB0151 Characterization of the plasmatic glycoprotein and lipoprotein profiles of systemic lupus erythematosus by nuclear magnetic resonance spectroscopy
Authors: A. Julià, F.J. Lopez-Longo, J.J. Perez Venegas, A. Olive, J.L. Andreu, M.A. Aguirre-Zamorano, P. Vela, J.M. Nolla, J.L. Marenco de la Fuente, A. Zea, J.M. Pego-Reigosa, M. Freire, E. Diez, E. Rodriguez, P. Carreira, R. Blanco, V. Martinez Taboada, M. Lopez Lasanta, M. Lopez, A. Fernandez-Nebro, S. Marsal
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with systemic inflammatory processes. Chronic inflammation alters the of the number and type of non-cellular elements, including lipoproteins and glycoproteins. <h3>Objectives</h3> Here we investigate the plasmatic lipoprotein and glycoprotein profiles associated with SLE. <h3>Methods</h3> Plasma samples were obtained from 50 healthy control individuals and 50 SLE patients. All patients fulfilled the ACR criteria for classification of SLE. <sup>1</sup>H-NMR was used to determine the lipoprotein and glycoprotein profiles from cases and controls. For the lipoprotein profiles, VLDL, LDL, IDL and HDL concentration, lipid composition and particle properties were quantified. The glycoprotein profile was decomposed in four reproducible peak regions LMW, Glyc-B, Glyc-A, Glyc-Lipid and baseline, and quantified for concentration, position and aggregation state. Association analysis to disease was performed using logistic regression fitting for age, gender and body mass index. Classifiers were built using recursive-partition algorithm and classification accuracy was evaluated using receiver operating curves. <h3>Results</h3> We found a significant perturbation of the lipoprotein profile in SLE patients compared to controls. A statistically significant (P&lt;0.05) reduction of cholesterol-LDL and HDL lipoproteins as well as an increase in triglyceride VLDL was found in SLE. Particle number for LDLs, were found to be reduced compared to controls (P&lt;0.05), and mostly due to lower quantities of large LDL particles (P&lt;0.005). The glycoprotein profile was also significantly altered for several NMR measures. The most significant changes were related to the reduction of the width and area of the Glyc-Lipid peak in SLE patients (P&lt;0.005 and P&lt;0.05, respectively). Using the plasma molecular patterns to predict the presence of SLE, we found a significant classifier for the lipoprotein pattern (ROC AUC(95%CI)=0.85(0.78–0.93)), and an optimal classifier for the glycoprotein pattern (ROC AUC(95%CI)=0.90(0.84–0.97)) <h3>Conclusions</h3> SLE is characterized by perturbations of the plasmatic lipoprotein and glycoprotein profiles. The increase of triglyceride VLDL in patients compared to controls, could explain the increased risk for cardiovascular disease observed in SLE. Our results also show that SLE patients have a significantly different glycoprotein profile compared to controls. In both cases, plasmatic <sup>1</sup>H-NMR profiling could be a valuable source of informative biomarkers for SLE. <h3>Disclosure of Interest</h3> None declared
A Phase II Lysa Study of Obinutuzumab Combined with Lenalidomide for Advanced Untretated Follicular B-Cell Lymphoma in Need of Systemic Therapy
Authors: Franck Morschhauser, Gilles Andre Salles, Rene-Olivier Casasnovas, Pierre Feugier, Krimo Bouabdallah, Guillaume Cartron, Reda Bouabdallah, Emmanuelle Nicolas-Virelizier, Marie Maerevoet, Sylvia Snauwaert, Christophe Fruchart, Steven LE Gouill, Cécile Moluçon-Chabrot, Caroline Delette, Lysiane Molina, Herve Tilly, Catherine Thieblemont, Eric Van Den Neste, Fontanet Bijou, Bettina Fabiani, Corinne Haioun, Roch Houot
Journal: Blood (2018)
No Cell Left Unturned: Intraductal Papillary Mucinous Neoplasm Heterogeneity
Authors: Yasmin G. Hernandez-Barco, Nabeel Bardeesy, David T. Ting
Journal: Clinical Cancer Research (2019)

Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic cancer precursor lesion with established genetic features, but the cellular ecosystem of these tumors remains to be fully characterized. This study utilizes single-cell RNA sequencing to describe the dynamic landscape of epithelial, immune, and stromal cells during IPMN progression to invasive cancer.See related article by Bernard et al., p. 2194.
Rationalizing antimicrobial therapy in the ICU: a narrative review
Authors: Jean-François Timsit, Matteo Bassetti, Olaf Cremer, George Daikos, Jan de Waele, Andre Kallil, Eric Kipnis, Marin Kollef, Kevin Laupland, Jose-Artur Paiva, Jesús Rodríguez-Baño, Étienne Ruppé, Jorge Salluh, Fabio Silvio Taccone, Emmanuel Weiss, François Barbier
Journal: Intensive Care Medicine (2019)
Medication Co-payment Vouchers, Adherence With Antiplatelet Therapy, and Adverse Cardiovascular Events After Myocardial Infarction
Authors: Cynthia A. Jackevicius, Dennis T. Ko
Journal: JAMA (2019)

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The Optimal Alternative Donor Transplant for Pediatric Patients with Acute Leukemia: A Comparison between Alfa-Beta T-Cell and B-Cell Depleted Haplo-SCT and UCBT
Authors: Franco Locatelli, Myriam Labopin, Nicole Santoro, Jean-Hugues Dalle, Amal Al-Seraihy, Fernanda Volt, Mikhail Maschan, Charlotte Jubert, Marco Zecca, Eefke J. Petersen, Miguel Ángel Díaz Pérez, Gerard Michel, Elena Skorobogatova, Cristina Díaz de Heredia, Tracey OBrien, Chantal Kenzey, Vanderson Rocha, Eliane Gluckman, Peter Bader, Annalisa Ruggeri
Journal: Blood (2018)
Endogenous glucocorticoids prevent gastric metaplasia by suppressing spontaneous inflammation
Authors: Jonathan T. Busada, Sivapriya Ramamoorthy, Derek W. Cain, Xiaojiang Xu, Donald N. Cook, John A. Cidlowski
Journal: Journal of Clinical Investigation (2019)

In the stomach, chronic inflammation causes metaplasia and creates a favorable environment for the evolution of gastric cancer. Glucocorticoids are steroid hormones that repress proinflammatory stimuli, but their role in the stomach is unknown. In this study, we show that endogenous glucocorticoids are required to maintain gastric homeostasis. Removal of circulating glucocorticoids in mice by adrenalectomy resulted in the rapid onset of spontaneous gastric inflammation, oxyntic atrophy, and spasmolytic polypeptide-expressing metaplasia (SPEM), a putative precursor of gastric cancer. SPEM and oxyntic atrophy occurred independently of lymphocytes. However, depletion of monocytes and macrophages by clodronate treatment or inhibition of gastric monocyte infiltration using the Cx3cr1 knockout mouse model prevented SPEM development. Our results highlight the requirement for endogenous glucocorticoid signaling within the stomach to prevent spontaneous gastric inflammation and metaplasia, and suggest that glucocorticoid deficiency may lead to gastric cancer development.
THU0597 Pulmonary manifestations in mixed connective tissue disease with juvenile and adult onset – are there any differences?
Authors: S.O. Hetlevik, S. Reiseter, Ø. Molberg, B. Flatø, R. Gunnarsson, T.M. Aaløkken, M.B. Lund, V. Lilleby
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Mixed connective tissue disease (MCTD) presents in childhood in 7%–23% of cases, but there is limited knowledge about the comparability of juvenile and adult onset of the disease. A common and serious manifestation is interstitial lung disease (ILD), possibly more common in adult MCTD according to a retrospective report[.<sup>1</sup> <h3>Objectives</h3> To compare disease variables in juvenile and adult onset MCTD, particularly regarding pulmonary manifestations, after long-term follow-up. <h3>Methods</h3> Two cohorts consisting of, respectively, 52 patients with juvenile onset MCTD and 90 patients with adult onset MCTD from all regions of Norway were compared. Inclusion criteria were fulfilment of the Kasukawa- or the Alarcon-Segovia criteria. Patients with onset of symptoms before the age of 18 years were considered to have juvenile onset. All patients were clinically examined, including high resolution CT and pulmonary function tests. <h3>Results</h3> Mean age at examination was 28.0 (SD 10.3) in juvenile onset, and 54.3 (SD 13.0) in adult onset MCTD (p&lt;0.001). Age at disease onset was 14.4 (SD4.4) and 37.9 (SD 15.1) years, respectively. Patient and disease characteristics are shown in table 1. Juvenile patients had higher levels of anti-RNP, but lower ESR and CRP compared to adult onset patients. ILD was found in 27% of juvenile and 43% of adult patients (p=0.051), and more adult onset patients had ILD in &gt;20% of total lung volume (TLV). Adult onset patients had lower forced expiratory volume in 1 s (FEV1), but similar diffusing capacity (DLCO) and forced vital capacity (FVC) as the juvenile patients. <h3>Conclusions</h3> ILD tended to be more frequent in patients with adult onset MCTD than in those with juvenile onset, although not statistically significant. More patients with adult onset had affection of &gt;20% of TLV. Juvenile and adult patients with similar disease duration had comparable degree of ILD. Juvenile MCTD patients showed higher levels of anti-RNP, but lower ESR and CRP than patients with adult MCTD. <h3>Reference</h3> [1] Kotajima L, Aotsuka S, Sumiya M, et al. Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan. J Rheumatol1996;23:1088–94. <h3>Disclosure of Interest</h3> None declared
Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies
Authors: Nabil G Seidah, Annik Prat, Angela Pirillo, Alberico Luigi Catapano, Giuseppe Danilo Norata
Journal: Cardiovascular Research (2019)

Since the discovery of the role of proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of low-density lipoprotein cholesterol (LDL-C) in 2003, a paradigm shift in the treatment of hypercholesterolaemia has occurred. The PCSK9 secreted into the circulation is a major downregulator of the low-density lipoprotein receptor (LDLR) protein, as it chaperones it to endosomes/lysosomes for degradation. Humans with loss-of-function of PCSK9 exhibit exceedingly low levels of LDL-C and are protected from atherosclerosis. As a consequence, innovative strategies to modulate the levels of PCSK9 have been developed. Since 2015 inhibitory monoclonal antibodies (evolocumab and alirocumab) are commercially available. When subcutaneously injected every 2-4 weeks, they trigger a ∼60% LDL-C lowering and a 15% reduction in the risk of cardiovascular events. Another promising approach consists of a liver-targetable specific PCSK9 siRNA which results in ∼50-60% LDL-C lowering that lasts up to 6 months (Phases II-III clinical trials). Other strategies under consideration include: (i) antibodies targeting the C-terminal domain of PCSK9, thereby inhibiting the trafficking of PCSK9-LDLR to lysosomes; (ii) small molecules that either prevent PCSK9 binding to the LDLR, its trafficking to lysosomes or its secretion from cells; (iii) complete silencing of PCSK9 by CRISPR-Cas9 strategies; (iv) PCSK9 vaccines that inhibit the activity of circulating PCSK9. Time will tell whether other strategies can be as potent and safe as monoclonal antibodies to lower LDL-C levels.
Bendamustine in Combination with Gemcitabine and Vinorelbine (BEGEV) Is an Effective Regimen for Heavily Pretreated, Relapsed/Refractory Hodgkin Lymphoma Patients: A Multicenter, Retrospective Real-World Study
Authors: Antonio Russo, Alessandro Pulsoni, Simonetta Viviani, Francesca Ricci, Rita Mazza, Massimo Magagnoli, Lucia Morello, Francesco Landi, Anna Guidetti, Michele Merli, Marcello Rodari, Alessandra Serrao, Giorgia Annechini, Andrea Nervini, Laura Giordano, Luca Castagna, Francesco Passamonti, Arturo Chiti, Paolo Corradini, Armando Santoro, Carmelo Carlo-Stella
Journal: Blood (2018)
The Myeloid Cell Compartment—Cell by Cell
Authors: Kevin Bassler, Jonas Schulte-Schrepping, Stefanie Warnat-Herresthal, Anna C. Aschenbrenner, Joachim L. Schultze
Journal: Annual Review of Immunology (2019)

Myeloid cells are a major cellular compartment of the immune system comprising monocytes, dendritic cells, tissue macrophages, and granulocytes. Models of cellular ontogeny, activation, differentiation, and tissue-specific functions of myeloid cells have been revisited during the last years with surprising results; for example, most tissue macrophages are yolk sac derived, monocytes and macrophages follow a multidimensional model of activation, and tissue signals have a significant impact on the functionality of all these cells. While these exciting results have brought these cells back to center stage, their enormous plasticity and heterogeneity, during both homeostasis and disease, are far from understood. At the same time, the ongoing revolution in single-cell genomics, with single-cell RNA sequencing (scRNA-seq) leading the way, promises to change this. Prevailing models of hematopoiesis with distinct intermediates are challenged by scRNA-seq data suggesting more continuous developmental trajectories in the myeloid cell compartment. Cell subset structures previously defined by protein marker expression need to be revised based on unbiased analyses of scRNA-seq data. Particularly in inflammatory conditions, myeloid cells exhibit substantially vaster heterogeneity than previously anticipated, and work performed within large international projects, such as the Human Cell Atlas, has already revealed novel tissue macrophage subsets. Based on these exciting developments, we propose the next steps to a full understanding of the myeloid cell compartment in health and diseases.
Comprehensive Genomic Analysis of IDH Inhibitor-Treated AML Samples Delineates Molecular Mechanisms of Differentiation and Heterogeneous Patterns of Acquired Resistance
Authors: Feng Wang, Kiyomi Morita, Courtney D. DiNardo, Keyur Patel, Kyle MacBeth, Alessandra Tosolini, Mark G. Frattini, Jairo Matthews, Latasha Little, Curtis Gumbs, Samantha Tippen, Xingzhi Song, Jianhua Zhang, Erika Thompson, Tapan M. Kadia, Guillermo Garcia-Manero, Elias J. Jabbour, Farhad Ravandi, Marina Y. Konopleva, Hagop M. Kantarjian, Andrew Futreal, Koichi Takahashi
Journal: Blood (2018)
Abstract 13007: Prognostic Significance of Persistent D-dimer Elevation in Patients With Acute Decompensated Heart Failure
Authors: Yasuhiro Hamatani, Toshiyuki Nagai, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
Journal: Circulation (2015)

Backgrounds: Heart failure is associated with a prothrombotic state. D-dimer (DD) is a marker of fibrin turn over, and increased DD levels predict poor outcomes in patients with chronic heart failure. However, data regarding the DD level in patients with acute heart failure (AHF) are limited. Methods: Of 651 consecutive AHF patients who admitted to our institution between January 2013 and March 2015 from prospective registry, patients with acute coronary syndrome, oral anticoagulant therapy, and venous thromboembolism were excluded. Finally, 296 patients were divided into two groups according to the higher DD (above 2.7 μg/ml, the median), or lower DD (below 2.7 μg/ml) on admission. DD level was measured within 24 hours from admission and at discharge. Results: Although patients with higher DD were older (77±11 vs. 73±14 years; P&lt;0.01), other baseline characteristics in terms of sex, NYHA classification, prevalence of co-morbidities including atrial fibrillation, and echocardiographic parameters including left ventricular ejection fraction were comparable between the two groups. During the median follow-up of 281 days, 4 patients died during hospitalization and 19 patients died after discharge. Kaplan-Meier curves for all-cause mortality are shown in the figure. Higher DD level on admission was associated with higher mortality (HR: 2.78, 95% CI: 1.19-7.25, P=0.02), even after adjustment by age. At discharge, DD level was persistently elevated (above 2.7 μg/ml) in 62% of patients with higher DD on admission. Among patients with higher DD on admission, persistent elevation of DD level during hospitalization was associated with higher mortality after discharge (HR: 7.00, 95% CI: 1.33-128.52, P=0.02). Conclusions: In patients with AHF, higher DD level on admission, especially persistently higher DD level during hospitalization, was associated with higher all-cause mortality, suggesting an importance of DD level as a prognostic surrogate marker of AHF.
PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group
Authors: Michael Fuchs, Helen Goergen, Carsten Kobe, Hans Eich, Christian Baues, Richard Greil, Stephanie Sasse, Josée M Zijlstra, Andreas Lohri, Andreas Rosenwald, Bastian von Tresckow, Volker Diehl, Georg Kuhnert, Markus Dietlein, Peter Borchmann, Andreas Engert
Journal: Blood (2018)