tbuckley/cabot-search huggingface dataset:
Novel patterns of response under immunotherapy
Authors: E. Borcoman, Y. Kanjanapan, S. Champiat, S. Kato, V. Servois, R. Kurzrock, S. Goel, P. Bedard, C. Le Tourneau
Journal: Annals of Oncology (2019)

Novel patterns of response and progression to immunotherapy have been reported that are not observed with conventional cytotoxic or targeted anticancer treatments. A major breakthrough with immunotherapy is its potential to achieve durable responses in a subset of patients with advanced cancer that can be maintained several years even after stopping the treatment. No standardized definition of durable response exists in the literature, and the optimal duration of treatment in case of durable response is not clearly established. However, the majority of patients do not respond to immunotherapy. Initially reported in advanced melanoma patients, pseudoprogression occurs when tumor index lesions regress after initial progression, supporting the concept of treating some patients beyond progression. Overall, reported rates of pseudoprogression never exceeded 10%, meaning that the large majority of patients who have a disease progression will not eventually respond to treatment. The decision to pursue treatment beyond progression must therefore only be taken in carefully selected patients with clinical benefit, who did not experience severe toxicities with immunotherapy. Conversely, rapid progressions, called hyperprogressions, were reported by several teams with rates ranging from 4% to 29%. These observations need to be confirmed from randomized trials. It is essential to interrupt the treatment in patients with hyperprogression, in order to switch to another potentially active treatment. Finally, some patients experience dissociated responses, with some lesions shrinking and others growing. Local treatment with surgery or radiotherapy for growing lesions may be considered. Several immune-specific-related response criteria were developed to better capture benefits of immunotherapy. These criteria only address the pseudoprogression pattern of response, and do not capture the other patterns of response such as hyperprogression and dissociated response. The classic RECIST remains a reasonable and meaningful method to assess response to immunotherapy in the clinic.
TNF-α-Induced Bone Marrow Stromal Progenitor Alterations Enhance Leukemic Stem Cell Growth and Treatment Resistance Via Increased CXCL1-CXCR2 Signaling
Authors: Puneet Agarwal, Hui Li, Kwangmin Choi, Robert S. Welner, Jianbo He, Ravi Bhatia
Journal: Blood (2018)
Phase 2 Study of Ruxolitinib in Patients with Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia
Authors: Kim-Hien Dao, Robert H. Collins, Jorge E. Cortes, Michael W. Deininger, Brian J. Druker, Jason R. Gotlib, Tara Alyson Macey, Stephen T Oh, Jeffrey W. Tyner, Elliott F. Winton
Journal: Blood (2018)
AB1048 Evolution of infectious sacroiliitis according to the germ
Authors: H. Ben Abla, S. rekik, S. boussaid, H. ajlani, H. sahli, I. cheour, M. elleuch
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> infectious sacroiliitis is a rather rare rheumatological emergency that has a misleading semiology because of the deep condition of the joint, the germ responsible plays an important role in this semiology and in its evolution <h3>Methods</h3> This is a retrospective study of 42 patients who have been hospitalised in the LA Rabta for Infectious Sacrolillitis from 1999 to 2017.the epidemiological data (age/sex) were recorded as well as the clinical radiolological and biological data (symptoms, inflammatory assessment, x-rays, CT scan and/or IRM, biopsy). <h3>Results</h3> fourty two patients were included in this study.the average age is 36,7 years old, sex distribution is: 19 women 23 men. banal sprouts are responsible in 48.15% of cases: Staphylococcus aureus 28.7% eschirichia coli 17.07% and 2.38% streptococcus. the progression was favourable in 87.4% of the cases under appropriate antibiotic therapy for the rest: 2.38% deaths, 2.38% state of septic shock, 7.84% of complication inherent to the treatments.tuberculosis is responsible for 37.2% of infectious sacroiliitis with a favourable evolution in 77.6%, a complication related to treatment is noted in 17.64%, a subcutaneous abscess 2.34%, mutifocal bone tuberculosis 2.38%.brucellosis sacroiliitis is diagnosed in14.65% of cases, the evolution is favourable in 7.51%, in 4.76% a rapid progression towards ankylosis was noted despite appropriate antibiotic therapy, 2.38% a progression towards brucellosis chronic <h3>Conclusions</h3> common germs are most responsible during infectious sacroiliitis and seem to have the best prognosis, tuberculosis is responsible for various complication and its treatment is at high risk of iatrogenic which limits the therapeutic choice of the clinician. chronicity is the most feared development during Brucella sacroillitis as antibiotic therapy is no longer effective <h3>Disclosure of Interest</h3> None declared
AB1282 Type of patient referral to early arthritis clinic (FLOW AND FATE)
Authors: A.A. Negm, A.M. Marzooqi, J. Al Saleh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Early Arthritis clinic (EAC) has a major contribution in Rheumatology outpatient services. Clinically, it gives a unique opportunity to assess, diagnose and classify various Rheumatic and Musculoskeletal diseases (RMD) during the initial phase of the disease process. Studying the patient's profile of EAC population aids in better management from the epidemiologic point of view. The average referral to EAC in Dubai hospital is 2 weeks over the last 5 years. <h3>Objectives</h3> The current study was conducted to explore the characteristics and common diagnoses of patients referred to EAC Rheumatology clinic in Dubai Hospital. <h3>Methods</h3> A review of the Electronic Medical Record of 117 patient presented to EAC between August 22nd 2017 and December 31st 2017. The following data were extracted from EMR and patient's files: Type of patient referral to EAC, initial visit diagnosis as well as concordance between initial diagnosis and established diagnosis. <h3>Results</h3> Autoimmune Rheumatic Diseases (ARDs) represents 41.1% of new cases diagnosed in the EAC. The number and percentage of the whole new cases diagnosis is as shown in the following table while the type/percentage of patient presentation to EAC is shown in the graph. Occasionally, patients' clinical features were inconclusive at the initial presentation. Knowing that most patients presented within two weeks of symptoms onset to EAC, hence classification at initial visit was difficult in 16.2% (others or undifferentiated inflammatory arthritis). on review of the initial visit diagnoses and the final established diagnoses after 3 months, we have found 97 of 117 has the same diagnosis, i.e. 82.9% concordance. <h3>Conclusions</h3> Early Arthritis Clinic grants an efficient access to patients with inflammatory and inflammatory back pain. However, a need of a standardised tool to triage patients with different musculoskeletal diseases to prevent delayed appointments to EAC. We suggest adding Osteoporosis (Bone metabolic disorders), Undifferentiated (arthritis, CTD, SPA) and non-Rheumatic diseases to initial diagnosis to increase the current concordance. <h3>Disclosure of Interest</h3> None declared
THU0576 Cardiovascular risk in long-term juvenile idiopathic arthritis
Authors: I. Aranda-Valera, I. Arias de la Rosa, R. Roldan Molina, C. Ábalos-Aguilera, C. Pérez-Sánchez, A. Escudero, R. López-Pedrera, E. Collantes-Estévez, N. Barbarroja
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile Idiopathic Arthritis (JIA) is one of the more common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity, including physical disability. The long-term risk of cardiovascular disease for individuals with Juvenile Idiopathic Arthritis (JIA) remains uncertain. <h3>Objectives</h3> This study aims to determine whether adults with JIA in remission and medium-long duration of the disease have an increased risk of cardiovascular disease. <h3>Methods</h3> This is a cross-sectional study including 25 patients (14 females and 11 males) diagnosed with JIA according to the International League of Associations for Rheumatology criteria ILAR 2001 were compared to 20 age- and sex-matched controls. Remission was determined by JADAS27 &lt;1 and according to Wallace criteria. An extensive clinical analysis including body index mass, lipid profile, HOMA-IR and intra-arterial blood pressure was performed. Intima media thickness of the common carotid artery (CIMT) was measured as a marker of subclinical atherosclerosis. Different proinflammatory cytokines (TNFa, IL1b and IL6), molecules involved in the endothelium dysfunction (VEGF and E-Selectin) and adipokines (resistin and visfatin) were analysed on serum by ELISA. <h3>Results</h3> Mean duration of the disease was 13.31±1.14 years. Mean age was 27.21±0.68. Time in remission was 3.52±0.84 years. Metabolic comordibities such as obesity and metabolic syndrome were more prevalent in our cohort of JIA patients compared to controls. Levels of cholesterol were significantly elevated in patients. However, HOMA-IR values and intra-arterial pressure were not significant increased in JIA patients. CIMT was higher in JIA patients compared to controls (0.44±0.009 vs 0.41±0.017, p=0.078), although it did not reach the statistical significance. Serum levels of cytokines (including TNFa, IL6 and IL1b), adipokines (such as resistin and visfatin), and VEGF were significantly augmented in the cases vs healthy donors. In addition, IMT values significantly correlated with the disease duration (r=0.439, p=0.046) and serum VEGF levels (r=0.498, p=0.030). <h3>Conclusions</h3> In our cohort of JIA patients the increased CIMT was not associated with inflammatory markers, but disease duration. Although patients were in clinical remission, the serum levels of inflammatory cytokines, adipokines and VEGF were elevated, molecules with a relevant role in the onset and progression of endothelial dysfunction and atherosclerosis. These results might suggest that long-term JIA patients could have higher cardiovascular risk, although they are in sustained remission. <h3>Disclosure of Interest</h3> None declared
Interruption of oral clindamycin plus rifampicin therapy in patients with hidradenitis suppurativa: An observational study to assess prevalence and causes
Authors: Luca Schneller-Pavelescu, Eduardo Vergara-de Caso, Antonio Martorell, Jorge Romaní, Mireya Lázaro, Eva Vilarrasa, Blanca Díaz-Ley, Igor Vázquez-Osorio, Juan Manuel Segura Palacios, José Manuel Azaña, Marcos A. González-López, Javier Cañueto, Alejandro Molina-Leyva, Maria Leiva-Salinas, Francisco José Navarro-Triviño, José Sánchez-Payá, José C. Pascual
Journal: Journal of the American Academy of Dermatology (2019)
Abstract 19707: Clinical Significance of Vitamin D Levels in Cardiac Surgery
Authors: Julia Ney, Karin Amrein, Daren K Heyland, Rolf Rossaint, Gernot Marx, Andreas Goetzenich, Christian Stoppe
Journal: Circulation (2017)

Introduction: Despite the well-known mechanisms of Vitamin D (e.g. calcium absorption and bone health), knowledge about its functional role and clinical relevance for patients undergoing cardiac su...
THU0366 Study of the role of micro-rna 20a expression in systemic lupus erythematosus in an egyptian cohort
Authors: M.S. Elkhalifa, M. Zehairy, M. Tayel, A. Elkeraie, D. Elkaffash, N. Baddour
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Micro-RNAs are small noncoding RNAs that act as cytoplasmic post-transcriptional gene expression regulators by targeting their complementary messenger RNA. They regulate several inflammatory, immunologic and oncogenic pathways.<sup>(1)</sup> MicroRNAs are differentially expressed in patients with systemic lupus erythematosus (SLE), especially in association with lupus nephritis.<sup> (2,3)</sup> The positive miRNA list in SLE patients in different studies presents relatively limited overlap. The heterogeneity of patient ethnicity and variety in detection method may in part explain some of the discrepancies.<sup>(4)</sup> <h3>Objectives</h3> to study the role of micro-RNA 20a expression in SLE in an Egyptian cohort and its role as a potential biomarker of lupus nephritis. <h3>Methods</h3> Expression levels of micro-RNA-20a extracted from peripheral blood mono-nuclear cells determined using quantitative reverse transcription–polymerase chain reaction assay. A total of 90 plasma samples were obtained from 30 SLE patients without clinical and laboratory evidence of lupus nephritis, 30 SLE patients with lupus nephritis and 30 healthy control subjects. <h3>Results</h3> The expression of micro-RNA-20a in SLE patients was significantly lower than the expression in normal healthy control, p&lt;0.001. In addition the Roc curve of micro-RNA-20a showed that micro-RNA-20a expression levels can significantly discriminate between lupus patients with and without lupus nephritis at a cut off level ≤9.3 ×10–6 with a specificity of 76.67% and sensitivity of 96.67%. We also found a significant correlation between micro-RNA-20a expression levels and the pathological activity index of renal biopsy, while there was no significant correlation between micro-RNA-20a expression level and the pathological chronicity index. <h3>Conclusions</h3> The expression level of micro-RNA-20a could be considered a diagnostic marker of SLE. Also, the expression level of micro-RNA-20a could be considered a potential biomarker for recognition of renal involvement in SLE patients. <h3>References</h3> [1] Schetter AJ, Heegaard NH, Harris CC. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis2010;31:37–49. [2] Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus2007;16:939–46. [3] Te JL, Dozmorov IM, Guthridge JM, Nguyen KL, Cavett JW, Kelly JA, et al. Identification of unique microRNA signature associated with lupus nephritis. PLoS One2010;5(5): e10344. [4] Wang Z, Chang C, Peng M, Lu Q. Translating epigenetics into clinic: focus on lupus. Clin Epigenetics2017; 9:78. <h3>Disclosure of Interest</h3> None declared
Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial
Authors: Anne Boerekamps, Anja De Weggheleire, Guido E van den Berk, Fanny N Lauw, Mark A A Claassen, Dirk Posthouwer, Wouter F Bierman, Sebastiaan J Hullegie, Stephanie Popping, David A C M van de Vijver, Anthonius S M Dofferhoff, Gert Jan Kootstra, Eliane M Leyten, Jan den Hollander, Marjo E van Kasteren, Robert Soetekouw, Heidi S M Ammerlaan, Janke Schinkel, Eric Florence, Joop E Arends, Bart J A Rijnders
Journal: The Lancet. Gastroenterology & hepatology (2019)
AB0160 Loss of let-7 microrna upregulates il-6 in bone marrow-derived mesenchymal stem cells triggering treg/th17 imbalance in patients with systemic lupus erythematosus
Authors: L. Geng, X. Xu, J. Liang, C. Zhao, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) patients exist an imbalance between CD4+CD25+FoxP3+ T regulatory (Treg) and IL-17-producing cells (Th17). Correction of this Treg/Th17 imbalance may have therapeutic impact for SLE patients. Our previous study demonstrated that bone marrow derived mesenchymal stem cells (BMSCs) from SLE patients are defective in immune modulation, which might be involved in Treg/Th17 imbalance and disease onset, but the mechanisms are not clear yet. The expression imbalance of microRNAs (miRNAs) can cause cell dysfunction, which participates in a variety of diseases development. As an important computer predicted target of let-7, interlukin-6 (IL-6) is an important negative immune regulatory factors secreted by BMSCs. Our previous experiments found that the expressions of let-7 are markedly down-regulated in SLE BMSCs by microRNA array analysis, and the synthesis of IL-6 is significantly higher in SLE BMSCs compared to normal controls. <h3>Objectives</h3> To investigate whether loss of let-7 could play its role in SLE BMSCs immune modulation defects by directly up-regulating IL-6 mRNA, which might contribute to Treg/Th17 imbalance in PBMCs from SLE patients, to further understand the pathogenesis of SLE. <h3>Methods</h3> BMSCs were isolated, cultured and expanded from iliac crest bone marrow of four healthy donors and four SLE patients. Real-time PCR was used to further determine the let-7 expression and IL-6 mRNA level in BMSCs from healthy controls and SLE patients. The important computer predicted target of let-7, IL-6 was determined using the luciferase reporter assay. Let-7-mimics, let-7-inhibitor, and let-7-negative control were transfected to BMSCs with using Lipofectamine 2000. BMSCs from healthy controls and SLE patients were co-cultured with PBMCs from SLE patients for 72 hours to detect their effect on the ratio of Treg/Th17. <h3>Results</h3> Compared to normal controls, the expression of let-7 was markedly down-regulated in BMSCs from SLE patients by RT-PCR, and the synthesis of IL-6 mRNA and protein levels were significantly higher in BMSCs from SLE patients. Compared to let-7-negative controls, transfection of BMSCs with let-7-mimics markedly lower synthesis of TGF-β1 mRNA, and let-7-inhibitor led to an opposite effect. The mean value of Treg/Th17 was significantly decreased in PBMCs from SLE patients compared to normal controls. Transfection of normal BMSCs with let-7-inhibitor caused significant downregulation of Treg/Th17 compared to let-7-negative controls, while transfection with let-7-mimics led to an opposite effect. <h3>Conclusions</h3> SLE patients exist an imbalance between Treg and Th17 cells, which might be associated with up-regulation of IL-6 secretion of BMSCs by loss of let-7. <h3>Disclosure of Interest</h3> None declared
SP0008 A ra with persistant high disease activity under biological treatment: how does changing diagnosis change management and outcome?
Authors: A.P. Trouvin
Journal: Annals of the Rheumatic Diseases (2018)

1. Justify the inclusion of these extra-spinal manifestations in the set of classification criteria of axial spondyloarthritis 2. Justify specific investigations (mainly interview and physical exam ) of the patients at the time of the diagnosis 3. Justify a systematic monitoring of these different extra-spinal manifestations during the entire course of the disease
Scaffold-facilitated locomotor improvement post complete spinal cord injury: Motor axon regeneration versus endogenous neuronal relay formation
Authors: Xing Li, Dingyang Liu, Zhifeng Xiao, Yannan Zhao, Sufang Han, Bing Chen, Jianwu Dai
Journal: Biomaterials (2019)

Complete transected spinal cord injury (SCI) severely influences the quality of life and mortality rates of animals and patients. In the past decade, many simple and combinatorial therapeutic treatments have been tested in improving locomotor function in animals with this extraordinarily challenging SCI. The potential mechanism for promotion of locomotor function relies either on direct motor axon regeneration through the lesion gap or indirect neuronal relay bridging to functionally reconnect transected spinal stumps. In this review, we first compare the advantages and problems of complete transection SCI animal models with other prevailing SCI models used in motor axon regeneration research. Next, we enumerate some of the popular bio-scaffolds utilized in complete SCI repair in the last decade. Then, the current state of motor axon regeneration as well as its role on locomotor improvement of animals after complete SCI is discussed. Last, the current approach of directing endogenous neuronal relays formation to achieve motor function recovery by well-designed functional bio-scaffolds implantation in complete transected SCI animals is reviewed. Although facilitating neuronal relays formation by bio-scaffolds implantation appears to be more practical and feasible than directing motor axon regeneration in promoting locomotor outcome in animals after complete SCI, there are still challenges in neuronal relays formation, maintaining and debugging for spinal cord regenerative repair.
Distinct Gene Expression Patterns of Minimal Residual Disease (MRD) Cells in High-Risk AML Patients Identified By RNA-Sequencing
Authors: Christopher B. Benton, Ahmed Al Rawi, Feng Wang, Jianhua Zhang, Jeffrey L. Jorgensen, Hong Mu, Wendy Schober, Zoe Alaniz, Curtis Gumbs, Andy Futreal, Guillermo Garcia-Manero, Hagop M. Kantarjian, Nicholas Navin, Marina Y. Konopleva, Michael Andreeff
Journal: Blood (2018)
Endoscopic drainage of a jejunopancreatic pseudocyst with an electrocautery-enhanced lumen-apposing metal stent
Authors: Toshiaki Terauchi, Satoshi Shinozaki, Kiyoto Mori, Alan Lefor, Hiroharu Shinozaki
Journal: Endoscopy (2019)

A 30-year-old man who was a known alcohol drinker (216 g/day) developed acute pancreatitis and a hemothorax after blunt trauma. He subsequently developed severe obstructive symptoms 12 weeks after the injury, which were caused by a 14-cm pancreatic pseudocyst (PPC) in the pancreatic tail, posterior to the transverse mesocolon ([Fig. 1]). The PPC abutted the proximal jejunum and was not apposed to the stomach, thereby precluding transgastric drainage.
Does senescence promote fitness in Caenorhabditis elegans by causing death?
Authors: Jennifer N. Lohr, Evgeniy R. Galimov, David Gems
Journal: Ageing Research Reviews (2019)

A widely appreciated conclusion from evolutionary theory is that senescence (aging) is of no adaptive value to the individual that it afflicts. Yet studies of Caenorhabditis elegans and Saccharomyces cerevisiae are increasingly revealing the presence of processes which actively cause senescence and death, leading some biogerontologists to wonder about the established theory. Here we argue that programmed death that increases fitness could occur in C. elegans and S. cerevisiae, and that this is consistent with the classic evolutionary theory of aging. This is because of the special conditions under which these organisms have evolved, particularly the existence of clonal populations with limited dispersal and, in the case of C. elegans, the brevity of the reproductive period caused by protandrous hermaphroditism. Under these conditions, death-promoting mechanisms could promote worm fitness by enhancing inclusive fitness, or worm colony fitness through group selection. Such altruistic, adaptive death is not expected to evolve in organisms with outbred, dispersed populations (e.g. most vertebrate species). The plausibility of adaptive death in C. elegans is supported by computer modelling studies, and new knowledge about the ecology of this species. To support these arguments we also review the biology of adaptive death, and distinguish three forms: consumer sacrifice, biomass sacrifice and defensive sacrifice.
Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus
Authors: Richard Furie, Victoria P. Werth, Joseph F. Merola, Lauren Stevenson, Taylor L. Reynolds, Himanshu Naik, Wenting Wang, Romy Christmann, Agnes Gardet, Alex Pellerin, Stefan Hamann, Pavan Auluck, Catherine Barbey, Parul Gulati, Dania Rabah, Nathalie Franchimont
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Plasmacytoid DCs (pDC) produce large amounts of type I IFN (IFN-I), cytokines convincingly linked to systemic lupus erythematosus (SLE) pathogenesis. BIIB059 is a humanized mAb that binds blood DC antigen 2 (BDCA2), a pDC-specific receptor that inhibits the production of IFN-I and other inflammatory mediators when ligated. A first-in-human study was conducted to assess safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects of single BIIB059 doses in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of biological activity and preliminary clinical response in the SLE cohort.