tbuckley/cabot-search huggingface dataset:
Reassessing the safety concerns of utilizing blood donations from patients with hemochromatosis
Authors: Adam C. Winters, Douglas Tremblay, Suzanne Arinsburg, John Mascarenhas, Thomas D. Schiano
Journal: Hepatology (2017)

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus, and cardiomyopathy. Treatment of HH involves regular phlebotomy to reduce the systemic iron burden. In many countries—including the United States—numerous blood centers do not accept donated blood obtained from HH patients during therapeutic phlebotomy and there are inconsistent positions regarding this globally. This refusal of blood is borne out of a few concerns. First, there is a theoretical increase in the infectious risk of these blood products, particularly by siderophilic organisms such as Yersinia enterocolitica . Second, given the increased incidence of hepatitis C infection from nonvoluntary donors in the 1970s, there is a concern that blood units from HH donors may harbor additional risk given the nonvoluntary nature of their presentation. In this review, we examine the existing biological and clinical data concerning infectious risk and summarize clinical experience from centers allowing HH donors, and demonstrate that blood from HH patients is safe and should be allowed into the donor pool. We conclude that there is no convincing evidence to exclude this population from serving as blood donors. (H epatology 2018;67:1150–1157)
FRI0578 Odontoid fractures in the elderly: an unknown osteoporotic fracture?
Authors: LL Natella, N Bronsard, J Allia, L Hekayem, L Euller-Ziegler, F De Peretti, V Breuil
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Current WHO definition of osteoporosis excludes cervical fractures. However, in atraumatic odontoid fractures, mainly reported by orthopedic surgeons, bone status has not been described yet [1]. <h3>Objectives</h3> To investigate bone status in elderly patients sustaining a low energy odontoid fracture. <h3>Methods</h3> We conducted a prospective study from January 2016 to January 2017 in patients &gt;65 years old, hospitalized in Nice University hospital for low energy odontoid fracture. An evaluation of bone status was proposed within 3 months after fracture event. Evaluation included demographic data, clinical risk factors of osteoporosis, bone mineral density (BMD) at spine and hip and vertebral fracture assessment (VFA) by dual X-ray absorptiometry and serum analysis to detect secondary osteoporosis. <h3>Results</h3> 38 patients were hospitalized for odontoid fracture: 8 patients &lt;65 years always after a major trauma (mean age 37.1±14.5 y) and 30 patients ≥65 years including 3 after a high energy impact. 27 odontoid fractures followed a low energy impact: 18 women and 9 men, mean age 83.8 y. (±10.7). 8 patients died before bone status assessment (5 men and 3 women), 6 died during hospitalization with a mean delay of 3.5 days (±1.87) and 2 after discharge (1 month and 5 month). 3 patients refused bone status evaluation, 5 were lost to follow-up and 1 is awaiting evaluation. Finally 10 patients had bone status evaluation, all women, mean age 84.2 y. (±8.9). None had parental history of hip fracture, 1 had an early menopause, 1 received aromatase inhibitors for breast cancer and 2 had a history of steroid therapy (&gt;3 months). 3 patients had previously received hormone replacement therapy, 1 received bisphosphonate for 5 years and 4 had calcium + vitamin D supplements. Lumbar spine mean T-score was -1.45 (±1.08), femoral neck: -2.37 (±0.040) and total hip: -1.99 (±0.6). VFA analysis revealed 4 unknown vertebral fractures. The table summarizes population bone status: 8 patients out of 10 fulfilled diagnostic criteria of osteoporosis, including 6 with previous fractures. 2 patients with T-score &gt; -1.DS didn9t have hip BMD assessment because of bilateral hip replacement but had previous major osteoporotic fractures. No secondary osteoporosis was detected. Serum vitamin D concentration was &lt;30 ng/ml in 5 patients, including 2 with concentration &lt;10 ng/ml. <h3>Conclusions</h3> Our study reveals that odontoid fractures mainly occur in elderly osteoporotic patients after a low energy impact. Although WHO osteoporosis definition excludes cervical fractures, odontoid fracture may be considered as an osteoporotic fracture. Further studies are required to confirm these results. <h3>References</h3> Watanabe M, et al. Analysis of predisposing factors in elderly people with type II odontoid fracture. Spine J. 2014 Jun 1; 14(6):861–6. <h3>Disclosure of Interest</h3> None declared
AB0338 Heads-up! sarcoidosis and rheumatoid arthritis co-exist
Authors: L Zickuhr, R Hajj-Ali
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Sarcoidosis and rheumatoid arthritis (RA) uncommonly co-occur. How dual diagnosis affects these patients9 clinical phenotype is unknown. <h3>Objectives</h3> To characterize the clinical and laboratory phenotype and to increase awareness of the coexistence of sarcoidosis and RA. <h3>Methods</h3> We searched PubMed from 1980–2016 for relevant articles using key words "sarcoidosis" and "rheumatoid arthritis," excluding cases with tumor necrosis factor inhibitors. We found 12 cases, omitted 5 lacking clinical detail, and added 2 from our experience at the Cleveland Clinic. Clinical features, laboratory and imaging findings were reviewed and summarized. <h3>Results</h3> Females comprised 7/9 cases (77%). Our cases are the first to describe men with dual diagnosis. Of the 8 cases reporting ethnicity, 4 (50%) were white. The mean age at time of diagnosis was 35.3 years for RA and 51.0 years for sarcoidosis. In 5/9 cases (55%), RA preceded sarcoidosis. RA affected the hands in 8/9 patients (88.9%). Of the 8 cases reporting symptoms of sarcoidosis, 5 (62.5%) had dyspnea. All cases (100%) had elevated rheumatoid factor (RF) and, when checked, anti-citrullinated peptide (anti-CCP) antibodies. Angiotensin converting enzyme (ACE) was elevated in 6/9 patients (66.6%). Of the 5 patients with joint imaging, 4 (80%) had inflammatory changes. All sarcoidosis (100%) was biopsy-proven. One case (11.1%) demonstrated concomitant pulmonary RA and sarcoidosis. <h3>Conclusions</h3> Sarcoidosis and RA coexist in seropositive patients, most commonly in women in their fourth through sixth decades of life. RA preceded sarcoidosis about half the time. Hand arthritis and dyspnea were the most common symptoms for RA and sarcoidosis, respectively. Awareness of this dual diagnosis may help identify RA and sarcoidosis earlier and prevent treatment delay. <h3>References</h3> Enzenauer RJ and West SG. Sarcoidosis in autoimmune disease. Arth &amp; Rheum, 1992; 22(1):1–17. Menard O, et al. Association of histologically proven rheumatoid arthritis with pulmonary sarcoidosis. Eur Respir J, 1995; 8;472–3. Kobak S, et al. Co-occurrence of rheumatoid arthritis and sarcoidosis. BMJ Case Rep, 2015;1–3. Kucera, MRF. A possible association of rheumatoid arthritis and sarcoidosis. Chest, 1989; 95:604–06. Leo G, et al. Simultaneous pulmonary involvement, histologically proven, of sarcoidosis and rheumatoid arthritis. Clin Exp Rheumatol, 2009;27(1):164. Takashita M, et al. Mutilating rheumatoid arthritis associated with sarcoidosis: A case report. Clin rheum, 1995;14(5):576–9. <h3>Disclosure of Interest</h3> None declared
AB1002 Clinical and ultrasound prevalence of peripheral enthesitis in an algerian cohort of spondyloarthritis
Authors: A Haddouche, S Haid, S Bencheikh, S Slimani, A Abdessemed, N Brahimi, A Ladjouze
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Algerian Spondyloarthritis (SpA) is characterized by a high prevalence and more severe axial and articular lesions compared to the caucasian population, What about enthesitis involvement? <h3>Objectives</h3> To estimate the global and site-specific clinical and ultrasound prevalence of peripheral enthesitis in an Algerian cohort of SpA <h3>Methods</h3> AA monocenter prospective study of all SpA ≥18 years meting the ASA criteria for SpA followed in a rheumatology center at EHS Ben Aknoun over a period from January 2015 to April 2016 Demographic, clinical, lab and ultrasound characteristics were noted. Fifteen enthesic sites were investigated: insertions of supra-spinatus, sub-scapular, medial and lateral epicondylar tendons, triceps brachialis, gluteus medius, quadriceps proximal and distal insertion (patellar ligament, medial and lateral collateral ligament), Achilles tendon, plantar aponeurosis. These sites were assessed clinically and ultrasonographically during the same consultation to determine the global and site-specific clinical and ultrasound prevalence of peripheral enthesitis. Elementary ultrasonographic lesions were noted. The comparison between clinical and ultrasound prevalence was performed using the Mac Nemar test using the SPSS software. <h3>Results</h3> A total of 208 patients were included, mainly men (63.5%). The mean age was 40.2±11.7 years. The mean duration of the SpA was 11.8±8.7 years. Axial radiographic SpA was the most frequent phenotype (69.2%) and ankylosing spondylarthritis was the most frequent sub-group (57.7%). At examination, 88.9% had an active disease (ASDAS-vs and/or ASDAS-crp&gt;1.3) and 64.4% of SpAs were taking NSAID 6240 entheses were assessed clinically and 7072 entheses examined with ultrasound Figure 1 summarizes the prevalence of elementary ultrasound lesions per site. <h3>Conclusions</h3> In this cohort and as expected, ultrasound (with at least one elementary lesion) was superior to clinical examination for the detection of peripheral enthesitis (83.2 vs. 44.2%, P&lt;0.001). Interesting sites to explore according to the prevalence and to the presence of a Doppler signal (&lt;2mm/cortical) would be insertions of the calcaneal, quadricipital, patellar, gluteal, plantar aponeurosis and triceps brachialis tendons. <h3>Disclosure of Interest</h3> None declared
SP0132 Viruses driving vasculitis
Authors: L Calabrese
Journal: Annals of the Rheumatic Diseases (2017)

Viruses have long been associated with varying forms of vasculitis in both pre-clinical models and human diseases. Immunopathogenic mechanisms have varied and include direct vascular invasion, immune complex mediated and more recently novel mechanisms which include autoinflammatory like responses. This discussion will review major advances in the field of medical virology as it applies to rheumatic diseases, especially vascular inflammatory disease, including an introduction to the human and more specifically vascular microviromes. Major forms of virally mediated vasculitis will be discussed with an emphasis on new viral vasculitis syndromes largely defined by next generation sequencing and their potential clinical impact. <h3>Disclosure of Interest</h3> None declared
FRI0474 Does axial spondyloarthritis phenotype correlate with imaging morphotype?
Authors: X Baraliakos, A Szumski, HE Jones, L Gensler
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Traditionally, radiographic imaging was used to describe morphological differences between various types of axial SpA (axSpA). The advent of MRI has advanced understanding of disease, enabled earlier diagnosis and visualization of structural changes, and facilitated the identification of non-radiographic axial SpA (nr-axSpA). The magnitude of the pathologic changes in the axial skeleton is used to quantify inflammatory and structural outcomes of clinical trials and treatment of patients with axSpA. <h3>Objectives</h3> To examine the MRI morphology of sacroiliitis (SI) and vertebral corner lesions in patients with primary (1°, no psoriasis) and secondary (2°, with psoriasis) axSpA. <h3>Methods</h3> This posthoc analysis was performed on data from patients with axSpA enrolled in the EMBARK trial (NCT01258738). Only patients with baseline MRI lesions were included. Symmetric and asymmetric SI, structural lesions, and corner inflammatory lesions were analyzed in 1° axSpA vs 2° axSpA patients. Data were analyzed using one-way analysis of variance for continuous parameters, chi-square tests, or Fisher9s exact tests for categorical parameters. <h3>Results</h3> The baseline demographics and disease characteristics between the 122 patients with 1° axSpA and 19 with 2° axSpA were similar. Asymmetric sacroiliitis was seen in significantly fewer 1° (43%) vs 2° (68%) axSpA patients. There were no differences in mean SpondyloArthritis Research Consortium of Canada (SPARCC) scores between 1° and 2° axSpA for any of the 4 SI joint (SIJ) quadrants. However, the lower iliac quadrants had the highest SPARCC SIJ score and the upper iliac quadrants had the lowest SPARCC SIJ scores. When analyzing the 4 spine quadrants (lower/upper anterior and lower/upper posterior), 1° patients had higher total SPARCC spine scores than 2° patients for all 4 quadrants at baseline. Collapsing the 4 quadrants shows that 1° axSpA patients had higher SPARCC MRI of the entire spine (23 discovertebral units [DVU]; mean=5.7) compared with 2° axSpA patients (mean=2.7). <h3>Conclusions</h3> We found 1° axSpA patients had more symmetric sacroiliitis and extensive spinal bone marrow edema compared with 2° axSpA patients. In addition, women appeared to have more asymmetric sacroiliitis. These data may help physicians accurately diagnose patients and decide best treatment options. <h3>Disclosure of Interest</h3> X. Baraliakos: None declared, A. Szumski Employee of: inVentiv, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, L. Gensler Consultant for: AbbVie, Janssen, Novartis, Pfizer
Annals Story Slam - A Story of Stories
Authors: Lisa Richardson
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - A Story of StoriesFREELisa Richardson, MDLisa Richardson, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0052 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Story of Stories "A Story of Stories," by Dr. Lisa Richardson (Duration 06:34)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Lisa Richardson, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, Lisa.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival
Authors: Gaëlle Müller-Greven, Cathleen R. Carlin, Monica E. Burgett, Manmeet S. Ahluwalia, Adam Lauko, Amy S. Nowacki, Cameron J. Herting, Maha A. Qadan, Markus Bredel, Steven A. Toms, Justin D. Lathia, Dolores Hambardzumyan, Jann N. Sarkaria, Petra Hamerlik, Candece L. Gladson
Journal: Clinical Cancer Research (2017)

Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors.Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133+ cells derived from GBM tumors in vitro Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors.Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2+/CD44+ tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133+/Sox2+-GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133+ GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133+ cell survival.Conclusions: We demonstrate that bevacizumab is internalized by Sox2+/CD44+-GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133+ cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059-71. ©2017 AACR.
DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A
Authors: Yung-Hsin Huang, Jianzhong Su, Yong Lei, Lorenzo Brunetti, Michael C. Gundry, Xiaotian Zhang, Mira Jeong, Wei Li, Margaret A. Goodell
Journal: Genome biology (2017)

DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function to regions of DNA methylation is limited by the poor correlation between global patterns of DNA methylation and gene expression.Here, we utilize nuclease-deactivated Cas9 protein fused to repetitive peptide epitopes (SunTag) recruiting multiple copies of antibody-fused de novo DNA methyltransferase 3A (DNMT3A) (dCas9-SunTag-DNMT3A) to amplify the local DNMT3A concentration to methylate genomic sites of interest. We demonstrate that dCas9-SunTag-DNMT3A dramatically increases CpG methylation at the HOXA5 locus in human embryonic kidney (HEK293T) cells. Furthermore, using a single guide RNA, dCas9-SunTag-DNMT3A is able to methylate a 4.5-kb genomic region and repress HOXA5 gene expression. Reduced representation bisulfite sequencing and RNA-seq show that dCas9-SunTag-DNMT3A methylates regions of interest with minimal impact on the global DNA methylome and transcriptome.This effective and precise tool enables site-specific manipulation of DNA methylation and may be used to address the relationship between DNA methylation and gene expression.
Postmarketing Adverse Events Related to the CardioMEMS HF System
Authors: Muthiah Vaduganathan, Ersilia M. DeFilippis, Gregg C. Fonarow, Javed Butler, Mandeep R. Mehra
Journal: JAMA Cardiology (2017)

This analysis of postmarketing data related to a wireless pulmonary artery sensor finds approximately 2.8% of patients experience adverse events.
Fabrication of Trabecular Bone‐Templated Tissue‐Engineered Constructs by 3D Inkjet Printing
Authors: Joseph P. Vanderburgh, Shanik J. Fernando, Alyssa R. Merkel, Julie A. Sterling, Scott A. Guelcher
Journal: Advanced Healthcare Materials (2017)

3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the <100 micrometer-scale trabecular architecture essential for investigating the cellular response to the morphometric properties of bone. In this study, it is hypothesized that the architecture of trabecular bone regulates osteoblast differentiation and mineralization. To test this hypothesis, human bone-templated 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function.
Influence of Tetrabromobisphenol A, with or without Concurrent Triclosan, upon Bisphenol A and Estradiol Concentrations in Mice
Authors: Tyler Pollock, Leanna Mantella, Vanessa Reali, Denys deCatanzaro
Journal: Environmental Health Perspectives (2017)

Background: Humans are commonly exposed to multiple environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antimicrobial agent), and bisphenol A (BPA; polycarbonate plastics). These chemicals are readily absorbed and may interact with each other. Objectives: We sought to determine whether TBBPA, given alone or in combination with triclosan, can modulate the concentrations of BPA and 17β-estradiol (E2). Methods: Female and male CF-1 mice were each given a subcutaneous injection of 0–27mg TBBPA, with or without concurrent 0.33mg triclosan, followed by dietary administration of 50μg/kg body weight 14C-BPA. Radioactivity was measured in blood serum and tissues through liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were each given a subcutaneous injection of 0 or 1mg TBBPA and E2 was measured in urine 2–12 h after injection. Results: Doses as low as 1mg TBBPA significantly elevated 14C-BPA concentrations in the uterus and ovaries of females; in the testes, epididymides, vesicular-coagulating glands, and preputial glands of males; and in blood serum, heart, lungs, and kidneys of both sexes; urinary E2 concentrations were also elevated. Lower doses of TBBPA or triclosan that had no effects on their own elevated 14C-BPA concentrations when the two substances were given concurrently. Conclusion: These data indicate that TBBPA, triclosan, and BPA interact in vivo, consistent with evidence that TBBPA and triclosan inhibit enzymes that are critical for BPA and E2 metabolism. https://doi.org/10.1289/EHP1329