tbuckley/cabot-search huggingface dataset:
<scp>HLA</scp> Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome
Authors: Mark Asquith, Peter R. Sternes, Mary‐Ellen Costello, Lisa Karstens, Sarah Diamond, Tammy M. Martin, Zhixiu Li, Mhairi S. Marshall, Timothy D. Spector, Kim‐Anh le Cao, James T. Rosenbaum, Matthew A. Brown
Journal: Arthritis & Rheumatology (2019)

Objective HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype–disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis ( AS ) and rheumatoid arthritis ( RA ). Both AS and RA patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of HLA –B27 and HLA – DRB 1 RA risk alleles on the composition of the intestinal microbiome in healthy individuals. Methods Five hundred sixty‐eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the Twins UK cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal RNA bacterial marker gene. All subjects were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data. Results Associations were observed between the overall microbial composition and both the HLA –B27 genotype and the HLA – DRB 1 RA risk allele ( P = 0.0002 and P = 0.00001, respectively). These associations were replicated using the stool samples from the Twins UK cohort ( P = 0.023 and P = 0.033, respectively). Conclusion This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA ‐B27 and HLA – DRB 1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases.
PS914 CONDITIONAL MEF2C EXPRESSION IN THE MOUSE THYMUS DRIVES DEVELOPMENT OF T/B-BIPHENOTYPIC LYMPHOID LEUKEMIA/LYMPHOMA
Authors: K. Canté-Barrett, Y. van Helsdingen, S. Goossens, E. Vroegindeweij, J. Meijerink
Journal: HemaSphere (2019)

Background: Central Nervous System (CNS) relapses are still one of the main causes of morbimortality in childhood acute lymphoblastic leukaemia (ALL) patients despite the reduction achieved by CNS-directed prophylactic chemotherapy. Although CNS colonization by ALL cells has been already associated to both increased survival and enhanced chemoresistance of blasts to intrathecal therapy, the mechanisms of protection and tumour cell maintenance in this compartment, as well as the interactions established between ALL and CNS cells, still need to be better understood. Aims: We propose in vivo and in vitro studies aimed at determining the location of leukaemia cells in the choroid plexus (CP) and the relevance of their interaction with stromal fibroblastic cells to create a tumour supportive microenvironment. Also, we explore the contribution of stromal cells to the ALL chemoresistance. Methods: Brain histopathology evaluation of immunodeficient NSG mice transplanted with human primary ALL cells or the Nalm-6 cell line was performed by using electron and fluorescence microscopy. Leukemic co-cultures with human CP cells in the presence or absence of different concentrations of chemotherapeutic drugs were used for viability assays. Changes in CP microenvironment were further tested by RT-qPCR, flow cytometry, ELISA and CBA assays. Results: The histological analysis of a xenograft model of ALL revealed the presence of leukaemic cells not only in the cerebral ventricles floating in the cerebrospinal fluid, but also interacting with the CP epithelium and within the CP stroma of those animals with CNS infiltration. The proximity of ALL cells to CP capillaries suggests they may easily enter through this fenestrated endothelium. Evaluation of interactions between leukaemic cells and stromal cells showed an upregulated expression of very late antigen-4 (VLA-4) in ALL cells and vascular cell adhesion molecule (VCAM1) in CP fibroblasts. Furthermore, in these co-cultures, ALL cells exhibited a reduced cell proliferation and an enhanced cell viability following treatment with chemotherapeutic agents. However, the blockade of VCAM1-VLA-4 interaction was found to impair those effects suggesting that VCAM1-VLA-4 interactions are, at least in part, responsible of protecting leukemic cells from cell death. Summary/Conclusion: Choroid plexus is proposed as a possible sanctuary for leukemic cells. There, ALL cells may remain attached to fibroblasts in a dormant state and protected from intrathecal chemotherapy treatment, thus favouring later relapses.
Randomized, Open-Label, Non-Inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients with Relapsed or Refractory Multiple Myeloma: Columba Update
Authors: Saad Z. Usmani, Maria-Victoria Mateos, Hareth Nahi, Sebastian Grosicki, Vladimir I. Vorobyev, Ivan Spicka, Vania T.M. Hungria, Sibirina Korenkova, Max Flogegard, Joan Bladé, Philippe Moreau, Martin F. Kaiser, Shinsuke Iida, Jacob P. Laubach, Tara Masterson, Kristen Anne Lantz, Lisa O'Rourke, Christoph Heuck, Xiang Qin, Dolly A. Parasrampuria, Ming Qi, Nizar Bahlis
Journal: Blood (2019)
Abstract 17721: Deficiency of Hypoxia Inducible Factor-1α in SM-22α-Expressing Bone Marrow-Derived Cells Alleviates Neointimal Formation Following Wire-induced Vascular Injury
Authors: Yusaku Maeda, Shuhei Tomita, Masaki Murakami, Hisatsugu Kurobe, Masaki Imanishi, Yasushi Yoshida, Yoichiro Hirata, Yoshitaka Kihira, Yuki Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Tetsuya Kitagawa, Masataka Sata, Toshiaki Tamaki
Journal: Circulation (2012)

Introduction: It have suggested that activation of Hypoxia Inducible Factor-1α (HIF-1α) links to cell proliferation and resistance to apoptosis in vascular smooth muscle cells (VSMCs) and that its ...
CT-guided fine-needle aspiration biopsy of pulmonary lesions under 15 mm of diameter: results on 68 consecutive patients
Authors: D. Tosi, D. Tosi, R. Carrinola, A. Palleschi, P. Mendogni, L. Rosso, I. Righi, N. Fusco, S. Ferrero, M. Nosotti, C. Bareggi
Journal: Annals of Oncology (2016)
PF771 CHIMERISM MONITORING BY QPCR, A ROBUST PERFORMANCE FROM 0.05% TO 100%
Authors: E.E. Bouwmans, H.W. M. van Deutekom, R. Malestein, B. Luiken, E.H. Rozemuller, M.T. Penning
Journal: HemaSphere (2019)

Background: Investigating the chimeric status after stem cell transplantation is required for the detection of adverse transplant events. In comparison to STR analysis, qPCR allows for a quick and easy measurement with better sensitivity that can be as low as 0.05% for the recipient chimeric status. In comparison to STR analysis this is a substantial improvement. Aims: The presumption is that qPCR is most accurate in its detection of percentages below 20–30% and less accurate for higher percentages. Here however, we provide evidence that qPCR data can be trusted regardless the level of measured percentage. Methods: We have collected the data of 19 studies, spanning 6 years, from the UK NEQAS ‘Post‐Stem Cell Transplant Chimerism Monitoring’ trial. Each study consisted of four samples; one from the recipient, one from the donor and two samples with a chimeric status representing two time points after transplantation. The recipient and donor samples were genotyped applying the KMRtype workflow (GenDx) and the chimeric mixtures were then examined with all found informative assays applying the KMRtrack workflow (GenDx). Tests were performed on either a Viia7 or QuantStudio 6 qPCR system (Thermo Fisher). Collected data was compared with the results reported by UK NEQAS, which are based on the results from all participating labs. From this comparison the standard deviation and relative error of the qPCR assay were calculated and plotted in an overview. Results: The chimerism percentages obtained covered a full range of chimeric status from 0 to 100%. When comparing the qPCR data with the data provided by UK NEQAS it indeed shows a higher absolute deviation with higher percentages in the qPCR data. However, in the qPCR data the relative error is the same throughout the whole range of chimeric status. Summary/Conclusion: From these results we can conclude that the qPCR technique is able to accurately detect genetic material in a chimeric mixture, not only in the lower levels but confidently from 0.05% to 100%.
Nivolumab for Treatment of Advanced, Refractory, High-Risk Multiple Myeloma
Authors: Sharmilan Thanendrarajan, Jerry Puryear, Carolina D. Schinke, Frits van Rhee, Maurizio Zangari, Pankaj Mathur, Meera Mohan, Sandra Susanibar, Jorge Jo Kamimoto, Shadiqul Hoque, Muthukumar Radhakrishnan, Phil Farmer, Leo Rasche, Niels Weinhold, Brian A Walker, Faith E. Davies, Gareth J. Morgan
Journal: Blood (2017)
Abstract 1453: Evidence for Increased Neointima Formation in Podocan Knockout Mice compared to C57/BL6 Wild Type Mice After Arterial Denudating Injury
Authors: Randolph Hutter, Li Huang, Carolina Valdiviezo, Antonia Hutter, Juan Jose Badimon, Paul Klotman
Journal: Circulation (2006)

Background: Acute arterial lesions form when endothelial and smooth muscle cells proliferate and migrate to sites of injury. This activity is regulated in part by small leucin-rich repeat proteins ...
Immediate tissue expander breast reconstruction following mastectomy in pregnancy-associated breast cancer.
Authors: Katherina Zabicki Calvillo, Diana L. Caragacianu, Yoon S. Chun, Stephanie Caterson, Jennifer Ruth Bellon, Julia S. Wong, Susan Troyan, Esther Rhei, Laura Stewart Dominici, Katherine E. Economy, Nadine M. Tung, Lidia Schapira, Jane L. Meisel, Ann Partridge, Erica L. Mayer
Journal: Journal of Clinical Oncology (2013)

1133 Background: Management of pregnancy-associated breast cancer (PABC) requires balancing benefits of therapy with potential risks to the developing fetus. Surgical management can be influenced by gestational age of fetus and tumor stage. Minimal data describe surgical and obstetrical outcomes after mastectomy with immediate breast reconstruction (IR) in a pregnant patient (pt). Methods: Pts who underwent IR after mastectomy were identified within a multi-institutional PABC cohort. Retrospective chart review was performed for outcomes including adverse intraoperative events, immediate postoperative complications, gestational age at delivery and fetal weight. Other parameters evaluated included stage at presentation, duration of surgery, and use of delayed reconstruction in pts who did not receive IR. Results: Within a cohort of 79 PABC pts, 25 (32%) had mastectomy while pregnant, 8 (32%) of whom had IC; 17 (68%) did not undergo IR. Mean gestational age at time of IR was 16.6 weeks (range 10-30) and all IR utilized tissue expander (TE) placement followed by permanent implant placement in 7 pts. In the IR cohort, 1 (12.5%) pt was stage 0, 3 (37.5%) stage I and 4 (50%) stage IIB. There were no intraoperative or immediate postoperative surgical complications. The mean duration of surgery was 198 min with IR (7 pts) vs. 157 min without IR (available for 12 pts). All women who underwent IR delivered at, or close to, term infants of normal birthweight. One pt had pre-term labor after surgery at 29 weeks which resolved with tocolysis. Mean gestational age at delivery was 37.3 weeks in the IR cohort vs. 36.3 weeks in the non-IR cohort. No fetal abnormalities or major obstetrical complications were seen after IR. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 pts (25%) in the IR cohort and cosmetic outcome was not adversely affected. Conclusions: This report represents one of the largest series describing IR after mastectomy in PABC. Results suggest immediate tissue expander placement after mastectomy may increase duration of surgery but does not lead to adverse obstetrical or fetal outcomes. IR with tissue expanders may preserve reconstructive options when PMRT is indicated.
AB0478 PREGNANCY OUTCOME IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH HYDROXYCHLOROQUINE: 10 YEARS EXPERIENCE
Authors: Kyaw Min Tun, Rahana Rahman, Ixora Kamisan Atan, Ani Amelia Zainuddin, Ruslinda Mustafar, Mohd Shahrir Mohamed Said
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Pregnancy in SLE patients is closely associated with the usage of hydroxychloroquine [1]. <h3>Objectives:</h3> To determine pregnancy outcomes in women with Systemic Lupus Erythematosus who were treated with hydroxychloroquine in Universiti Kebangsaan Malaysia Medical Centre. <h3>Methods:</h3> Pregnant women with Systemic Lupus Erythematosus who had antenatal follow up and delivery in Universiti Kebangsaan Malaysia Medical Centre between 1<sup>st</sup>January 2007 and 1<sup>st</sup> January 2017 were retrospectively analyzed. Data collection was done via medical case notes and laboratory investigations. Study population was categorised into two groups based on hydroxychloroquine treatment during pregnancy. Incomplete pregnancy records were excluded. <h3>Results:</h3> There were 82 completed pregnancies included with 47 (57.3%) in HCQ group and 35 (42.7%) in non HCQ group. Amongst HCQ users, there were significantly more pregnancies with musculoskeletal involvement (p=0.03), heavier mean neonatal birth weight (p=0.02) and prolonged duration of pregnancy (<i>p</i>=0.001). In non-HCQ users, the rate of recurrent miscarriages (<i>p</i>=0.003), incidence of hypertension (<i>p</i>=0.01) and gestational diabetes mellitus (p=0.01) and concurrent medical illness (p=0.005) were significantly more. Hydroxychloroquine use during pregnancy was protective against hypertension (p=0.001) and the gestational age at delivery had significant effect on the neonatal birth weight (p=0.001). However, duration of the disease had significant negative effect on the neonatal birth weight (p=0.016). <h3>Conclusion:</h3> HCQ enhance better neonatal outcomes and reduce adverse pregnancy outcome and antenatal complications such as hypertension and diabetes. <h3>References</h3> [1] M Leroux, C Desveaux, M Parcevaux. Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study. Lupus 2015. https://doi.org/10.1177/0961203315591027 <h3>Disclosure of Interests:</h3> Kyaw Min Tun: None declared, Rahana Rahman: None declared, Ixora Kamisan @ Atan: None declared, Ani Amelia Zainuddin: None declared, Ruslinda Mustafar: None declared, Mohd Shahrir Mohamed Said Paid instructor for: Eli Lilly, Speakers bureau: Eli Lilly
Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo
Authors: Zhiwei Liao, Rongjin Luo, Gaocai Li, Yu Song, Shengfeng Zhan, Kangcheng Zhao, Wenbin Hua, Yukun Zhang, Xinghuo Wu, Cao Yang
Journal: Theranostics (2019)

Objectives: Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell apoptosis which is related to excessive endoplasmic reticulum (ER) stress in the intervertebral disc (IVD) could aggravate IDD progression. Many studies have shown the therapeutic potential of exosomes derived from bone marrow mesenchymal stem cells (MSC-exos) in degenerative diseases. We hypothesized that the delivery of MSC-exos could modulate ER stress and inhibit excessive NP cell apoptosis during IDD. Methods: The ER stress levels were measured in normal or degenerative NP tissues for contrast. The effects of MSC-exos were testified in advanced glycation end products (AGEs) -induced ER stress in human NP cells. The mechanism involving AKT and ERK signaling pathways was investigated using RNA interference or signaling inhibitors. Histological or immunohistochemical analysis and TUNEL staining were used for evaluating MSC-exos therapeutic effects in vivo. Results: The ER stress level and apoptotic rate was elevated in degenerative IVD tissues. MSC-exos could attenuate ER stress-induced apoptosis by activating AKT and ERK signaling. Moreover, delivery of MSC-exos in vivo modulated ER stress-related apoptosis and retarded IDD progression in a rat tail model. Conclusions: These results highlight the therapeutic effects of exosomes in preventing IDD progression. Our work is the first to demonstrate that MSC-exos could modulate ER stress-induced apoptosis during AGEs-associated IVD degeneration.
AB0801 RELIABILITY OF A NOVEL ULTRASONOGRAPHIC SCALE FOR ACTIVITY OF KNEE OSTEOARTHRITIS
Authors: Mohammed A. Mortada, Ghada Dawa, Amany Ebaid, Lobna Kotb, Youmna A. Amer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Knee osteoarthritis <h3>Objectives</h3> To assess the reliability of a novel ultrasonographic scale of activity in knee osteoarthritis (OA) <h3>Methods</h3> A cross-sectional observational study included 110 patients with knee pain who fulfilled the American College of Rheumatology (ACR) criteria for knee osteoarthritis (OA). All patients were subjected to clinical assessment WOMAC scale (Western Ontario and McMaster Universities Index of Osteoarthritis and global visual analog scale) and functional assessment using health assessment questionnaire (HAQ). Ultrasonographic assessment of activity was done By 3 rheumatologists with different levels of experience in musculoskeletal Ultrasonography (1-12 years). Ultrasonographic assessments were done according to (MOAKA scale) that was proposed by the first author (table 1). <h3>Results</h3> There were high kappa values both in intraobserver and interobserver evaluation of activity of knee OA using the proposed (MOAKA) ultrasonographic scale (0.85 and 0.75 respectively). There were positive correlations between MOAKA score and all WOMAC subscales (pain, stiffness and function) (r=0.4, P=0.02, r=0.35, P=0.001 and r=0.4, P=0.01) respectively. Also there were a strong positive correlation between MOAKA scale and both (VAS and HAQ) (r=0.86, P=0.001 and r=0.71, P=0.001) <h3>Conclusion</h3> US can reliably detect the activity of Knee OA. Good agreement was found between the proposed US grading scale and WOMAC &amp; HAQ scores. MOAKA US scale is simple and reliable. <h3>Disclosure of Interests</h3> None declared
Mechanobiology of Macrophages: How Physical Factors Coregulate Macrophage Plasticity and Phagocytosis
Authors: Nikhil Jain, Jens Moeller, Viola Vogel
Journal: Annual Review of Biomedical Engineering (2019)

In addition to their early-recognized functions in host defense and the clearance of apoptotic cell debris, macrophages play vital roles in tissue development, homeostasis, and repair. If misregulated, they steer the progression of many inflammatory diseases. Much progress has been made in understanding the mechanisms underlying macrophage signaling, transcriptomics, and proteomics, under physiological and pathological conditions. Yet, the detailed mechanisms that tune circulating monocytes/macrophages and tissue-resident macrophage polarization, differentiation, specification, and their functional plasticity remain elusive. We review how physical factors affect macrophage phenotype and function, including how they hunt for particles and pathogens, as well as the implications for phagocytosis, autophagy, and polarization from proinflammatory to prohealing phenotype. We further discuss how this knowledge can be harnessed in regenerative medicine and for the design of new drugs and immune-modulatory drug delivery systems, biomaterials, and tissue scaffolds.
SP0179 ORTHOSES AND ASSISTIVE DEVICES FOR THE HAND
Authors: Nina Osteras
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> This presentation will summarize the scientific evidence for the effects of orthoses and assistive devices for the hand. The main focus will be on hand osteoarthritis. The presentation will shed light on how orthoses and assistive devices may facilitate participation. <h3>Disclosure of Interests:</h3> None declared
Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation
Authors: Hejin Jia, Zhenguang Wang, Yao Wang, Yang Liu, Hanren Dai, Chuan Tong, Yelei Guo, Bo Guo, Dongdong Ti, Xiao Han, Qingming Yang, Zhiqiang Wu, Weidong Han
Journal: Journal of Hematology & Oncology (2019)

Chimeric antigen receptor T (CAR-T) cell therapy simultaneously against CD19 and CD22 is an attractive strategy to address the antigen escape relapse after CD19-directed CAR-T cell therapies. However, the potential of optimizing the durability of remission by this approach in patients with B cell acute lymphoblastic leukemia (B-ALL) remains a critical unanswered question so far. We treated an adult patient with relapsed and refractory B-ALL after haploidentical hematopoietic stem cell transplantation (HSCT) by administering haploidentical CAR-T cells targeting both CD19 and CD22 following preparative lymphodepleting chemotherapy. This patient has remained in minimal residual disease-negative remission for more than 14 months and has been tapered off graft versus host disease prophylaxis. CAR simultaneously targeting CD19 and CD22 has the potential of inducing long-term remission in patients with B-ALL.