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Very early systemic sclerosis

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https://read.qxmd.com/read/30770717/lysyl-oxidase-a-possible-role-in-systemic-sclerosis-associated-pulmonary-hypertension-a-multicentre-study
#1
Zahava Vadasz, Alexandra Balbir Gurman, Pierluigi Meroni, Dominique Farge, Yair Levi, Francesca Ingegnoli, Yolada Braun-Moscovici, Itzhak Rosner, Gleb Slobodin, Michael Rozenbaum, Nizar Jiries, Lisa Kaly, Nina Boulman, Karina Zilber, Shira Ginsberg, Abid Awisat, Yair Goldberg, Michael Lurie, Maria-Rosa Ghigna, Christophe Guignabert, Marc Humbert, Doron Rimar
OBJECTIVE: Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. METHODS: A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls...
February 15, 2019: Rheumatology
https://read.qxmd.com/read/30599428/the-role-of-vestibular-evoked-myogenic-potentials-in-multiple-sclerosis-related-vertigo-a-systematic-review-of-the-literature
#2
Arianna Di Stadio, L Dipietro, M Ralli, A Greco, G Ricci, E Bernitsas
BACKGROUND: Vertigo is a common symptom of multiple sclerosis (MS) that can be caused by a central or peripheral involvement of the vestibular pathways. Magnetic Resonance Imaging (MRI) is commonly used to evaluate progression of MS but is not sensitive enough to detect small lesions. Vestibular evoked myogenic potentials (VEMPs) are commonly used to evaluate function of vestibular-cochlear pathways. The aim of this literature review is to evaluate the role of VEMPs in patients with MS-related vertigo as a tool to detect demyelinating lesions in the vestibular pathways of MS patients and to monitor MS progression...
December 24, 2018: Multiple Sclerosis and related Disorders
https://read.qxmd.com/read/30517716/severe-gastrointestinal-disease-in-very-early-systemic-sclerosis-is-associated-with-early-mortality
#3
Nicolas Richard, Marie Hudson, Mianbo Wang, Geneviève Gyger, Susanna Proudman, Wendy Stevens, Mandana Nikpour, Murray Baron
Objectives: To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort. Methods: SSc subjects with <2 years of disease duration were identified from two multicentre cohorts. Severe GI disease was defined as: malabsorption, hyperalimentation, pseudo-obstruction and/or ⩾10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. Kaplan-Meier, multivariate logistic regression and Cox proportional hazard analyses were performed to determine the cumulative incidence rate, independent clinical correlates and mortality rate associated with severe GI disease...
December 4, 2018: Rheumatology
https://read.qxmd.com/read/30277866/dickkopf-1-is-downregulated-early-and-universally-in-the-skin-of-patients-with-systemic-sclerosis-despite-normal-circulating-levels
#4
Dimitrios Daoussis, Dionysios J Papachristou, Theodoros Dimitroulas, Theodoros Sidiropoulos, Ioannis Antonopoulos, Andrew P Andonopoulos, Stamatis-Nick Liossis
OBJECTIVES: The activity of the Wnt pathway, a critical mediator of fibrosis, is regulated by Dickkopf-1 (Dkk-1). Dkk-1 is absent from scleroderma skin in contrast to skin from healthy subjects where it is clearly expressed. There are no data on circulating levels and function of Dkk-1 in patients with systemic sclerosis (SSc). Our objectives are to assess: i) circulating and functional levels of Dkk-1 in patients with SSc and ii) whether the striking lack of Dkk-1 skin expression is also evident in a) clinically uninvolved skin from patients with SSc and b) very early disease prior to skin thickening...
July 2018: Clinical and Experimental Rheumatology
https://read.qxmd.com/read/30276930/abnormal-esophageal-motility-during-a-solid-test-meal-in-systemic-sclerosis-detection-even-in-very-early-disease-and-association-with-disease-progression
#5
Simon Bütikofer, Suzana Jordan, Matthias Sauter, Michael Hollenstein, Henriette Heinrich, Natália Freitas-Queiroz, Thomas Kuntzen, Daphne Ang, Marcos Oberacher, Britta Maurer, Werner Schwizer, Mark Fox, Oliver Distler, Benjamin Misselwitz
OBJECTIVE: This study assessed whether high-resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression. METHODS: This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls...
October 1, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://read.qxmd.com/read/30245744/neurological-complications-of-immune-checkpoint-inhibitors-what-happens-when-you-take-the-brakes-off-the-immune-system
#6
REVIEW
Marinos C Dalakas
Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis...
2018: Therapeutic Advances in Neurological Disorders
https://read.qxmd.com/read/30209761/early-p2x7r-dependent-activation-of-microglia-during-the-asymptomatic-phase-of-autoimmune-encephalomyelitis
#7
Tomasz Grygorowicz, Lidia Strużyńska
Microglia-mediated neuroinflammation accompanies many central nervous system (CNS) diseases, including multiple sclerosis (MS), and is strongly dependent on the purinergic P2X7 receptor. The nature of the inflammatory response in MS is studied for decades indicating, that proinflammatory microgliosis is involved in advanced stages of MS and is associated with active tissue damage and neurological dysfunctions. Evidence on the role of microgliosis in initial stages of the disease is scarce. Thus, in the present study, we investigated the time course of microglial activation in rat brain subjected to experimental autoimmune encephalomyelitis (EAE) which is the animal model of MS...
September 12, 2018: Inflammopharmacology
https://read.qxmd.com/read/30183599/from-vedoss-to-established-systemic-sclerosis-diagnosis-according-to-acr-eular-2013-classification-criteria-a-french-italian-capillaroscopic-survey
#8
Massimiliano Vasile, Jerome Avouac, Iliana Sciarra, Katia Stefanantoni, Nicoletta Iannace, Elena Cravotto, Guido Valesini, Yannick Allanore, Valeria Riccieri
OBJECTIVES: Nailfold capillaroscopy (NC) shows microcirculatory abnormalities in systemic sclerosis (SSc). The inclusion of NC specific abnormalities increases the sensitivity of both 2013 ACR/EULAR and VEDOSS (Very Early Diagnosis of Systemic Sclerosis) classification criteria. We aimed to detect NC features able to predict progression toward established SSc in VEDOSS patients. METHODS: Sixty-six VEDOSS patients were enrolled. They had a clinical follow-up and underwent NC once a year, considering morphological parameters, appropriate pattern and semi- quantitative rating scale...
July 2018: Clinical and Experimental Rheumatology
https://read.qxmd.com/read/30134971/hit-hard-and-early-analysing-the-effects-of-high-dose-methylprednisolone-on-nailfold-capillary-changes-and-biomarkers-in-very-early-systemic-sclerosis-study-protocol-for-a-12-week-randomised-controlled-trial
#9
Wieneke M T van den Hombergh, Brigit E Kersten, Hanneke K A Knaapen-Hans, Rogier M Thurlings, Peter M van der Kraan, Frank H J van den Hoogen, Jaap Fransen, Madelon C Vonk
BACKGROUND: Mounting evidence indicates that inflammatory mechanisms drive systemic sclerosis (SSc) vasculopathy and fibrosis, especially early in the disease. Therefore, patients with very early SSc could benefit from early treatments targeting inflammation. Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. Several studies have demonstrated a mixed response to treatment with glucocorticoids in SSc, probably because it is seldom initiated at very early stages of the disease...
August 22, 2018: Trials
https://read.qxmd.com/read/30021803/slit2-robo4-axis-may-contribute-to-endothelial-cell-dysfunction-and-angiogenesis-disturbance-in-systemic-sclerosis
#10
Eloisa Romano, Mirko Manetti, Irene Rosa, Bianca Saveria Fioretto, Lidia Ibba-Manneschi, Marco Matucci-Cerinic, Serena Guiducci
OBJECTIVE: In systemic sclerosis (SSc), early microvascular injury is followed by impaired angiogenesis and peripheral capillary loss. Here, we investigated the possible contribution of the neurovascular guidance molecule Slit2 and its Roundabout (Robo) receptors to SSc-related endothelial cell dysfunction. METHODS: Circulating Slit2 levels were measured in patients with SSc and healthy controls. Slit2, Robo1 and Robo4 expression was investigated in SSc and healthy skin biopsies and explanted dermal microvascular endothelial cells (MVECs)...
November 2018: Annals of the Rheumatic Diseases
https://read.qxmd.com/read/29985736/immunotherapy-of-systemic-sclerosis
#11
Christina G Katsiari, Theodora Simopoulou, Ioannis Alexiou, Lazaros I Sakkas
Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, immune activation, and extensive collagen deposition. Microvasculopathy and immune activation occur very early in the disease process. Evidence from animal models and in vitro studies indicate that T-cells and B-cells activate fibroblasts to produce collagen. Traditional immunosuppressants, cyclophosphamide(CyP), methotrexate(MTX), and more recently mycophenolate mofetil(MMF), may prove more effective if used very early in the disease course...
July 9, 2018: Human Vaccines & Immunotherapeutics
https://read.qxmd.com/read/29799415/induction-or-escalation-therapy-for-patients-with-multiple-sclerosis
#12
REVIEW
E Le Page, G Edan
The concept of induction followed by a long-term maintenance treatment has attracted much attention for the treatment of multiple sclerosis over the 30 past years. It was first demonstrated by the combination of induction therapy with mitoxantrone (six-monthly courses) followed by maintenance therapy with an immunomodulatory treatment such as an interferon-β or glatiramer acetate. Long-term observational studies confirmed that this therapeutic regimen provides a rapid reduction in disease activity and sustained disease control up to at least five years in 60% of patients...
June 2018: Revue Neurologique
https://read.qxmd.com/read/29787578/mth1-driven-expression-of-htdp-43-results-in-typical-als-ftld-neuropathological-symptoms
#13
Barbara Scherz, Roland Rabl, Stefanie Flunkert, Siegfried Rohler, Joerg Neddens, Nicole Taub, Magdalena Temmel, Ute Panzenboeck, Vera Niederkofler, Robert Zimmermann, Birgit Hutter-Paier
Transgenic mouse models are indispensable tools to mimic human diseases and analyze the effectiveness of related new drugs. For a long time amyotrophic lateral sclerosis (ALS) research depended on only a few mouse models that exhibit a very strong and early phenotype, e.g. SOD1 mice, resulting in a short treatment time window. By now, several models are available that need to be characterized to highlight characteristics of each model. Here we further characterized the mThy1-hTDP-43 transgenic mouse model TAR6/6 that overexpresses wild type human TARDBP, also called TDP-43, under control of the neuronal Thy-1 promoter presented by Wils and colleagues, 2010, by using biochemical, histological and behavioral readouts...
2018: PloS One
https://read.qxmd.com/read/29659729/t-helper-17-1-cells-associate-with-multiple-sclerosis-disease-activity-perspectives-for-early-intervention
#14
Jamie van Langelaar, Roos M van der Vuurst de Vries, Malou Janssen, Annet F Wierenga-Wolf, Isis M Spilt, Theodora A Siepman, Wendy Dankers, Georges M G M Verjans, Helga E de Vries, Erik Lubberts, Rogier Q Hintzen, Marvin M van Luijn
Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients...
May 1, 2018: Brain: a Journal of Neurology
https://read.qxmd.com/read/29650983/myotube-elasticity-of-an-amyotrophic-lateral-sclerosis-mouse-model
#15
Béla Varga, Marta Martin-Fernandez, Cécile Hilaire, Ana Sanchez-Vicente, Julie Areias, Céline Salsac, Frédéric J G Cuisinier, Cédric Raoul, Frédérique Scamps, Csilla Gergely
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor system leading to generalized paralysis and death of patients. The understanding of early pathogenic mechanisms will help to define early diagnostics criteria that will eventually provide basis for efficient therapeutics. Early symptoms of ALS usually include muscle weakness or stiffness. Therefore, mechanical response of differentiated myotubes from primary cultures of mice, expressing the ALS-causing SOD1 G93A mutation, was examined by atomic force microscopy...
April 12, 2018: Scientific Reports
https://read.qxmd.com/read/29625335/cerebrospinal-fluid-il-10-as-an-early-stage-discriminative-marker-between-multiple-sclerosis-and-neuro-beh%C3%A3-et-disease
#16
Meriam Belghith, Khadija Bahrini, Mariem Kchaou, Olfa Maghrebi, Samir Belal, Mohamed Ridha Barbouche
Multiple Sclerosis (MS) and Neuro-Behçet's Disease (NBD) are two recurrent disorders affecting the central nervous system (CNS) by causing inflammation and irreversible damage. Inaugural clinical symptoms for both diseases might be very similar and definitive diagnosis could be delayed. The present study aimed to find out possible differences at early stages in the transcription factors/cytokines expression profiles in blood and cerebrospinal fluid (CSF) of MS and NBD patients which could be useful discriminative markers...
August 2018: Cytokine
https://read.qxmd.com/read/29469817/novel-optical-assessments-of-tissue-composition-and-viability-using-fluorescence-spectroscopy-and-tissue-oxygenation-spectrophotometry-in-patients-with-systemic-sclerosis-a-pilot-study
#17
John Allen, Costanzo Di Maria, Samuel G Urwin, Alan Murray, Lesley Ottewell, Bridget Griffiths
OBJECTIVE: Patients with systemic sclerosis (SSc) experience significant morbidity and mortality, therefore, the development of tests to aid its early diagnosis are very important. The aim of this pilot study was to assess the diagnostic value of novel optical non-invasive skin fluorescence spectroscopy (FS) and tissue oxygen saturation (TOS) viability measurements in patients with established SSc. APPROACH: Two groups were studied, comprising 14 SSc patients and nine healthy controls (93% and 73% females, respectively)...
April 3, 2018: Physiological Measurement
https://read.qxmd.com/read/29320840/microvascular-damage-evaluation-in-systemic-sclerosis-the-role-of-nailfold-videocapillaroscopy-and-laser-techniques
#18
REVIEW
B Ruaro, A Sulli, V Smith, C Pizzorni, S Paolino, E Alessandri, M Cutolo
Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc...
December 21, 2017: Reumatismo
https://read.qxmd.com/read/28993902/cardiac-involvement-in-undifferentiated-connective-tissue-disease-at-risk-for-systemic-sclerosis-otherwise-referred-to-as-very-early-early-systemic-sclerosis-a-tdi-study
#19
Michele D'Alto, Antonella Riccardi, Paola Argiento, Ilaria Di Stefano, Emanuele Romeo, Agostino Mattera Iacono, Antonello D'Andrea, Serena Fasano, Alessandro Sanduzzi, Marialuisa Bocchino, Ludovico Docimo, Salvatore Tolone, Maria Giovanna Russo, Gabriele Valentini
Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI)...
May 2018: Clinical and Experimental Medicine
https://read.qxmd.com/read/28992170/points-to-consider-raynaud-s-phenomenon-in-systemic-sclerosis
#20
REVIEW
Maurizio Cutolo, Vanessa Smith, Daniel E Furst, Dinesh Khanna, Ariane L Herrick
RP is an exaggerated vasospastic response to cold or emotion. Randomized, double-blind, placebo-controlled trials with either parallel group or cross-over trials should be mainly considered. Cross-over design, which is good for early phase trials of immediate or very short-term outcomes, is important in a condition as heterogeneous as RP: a wash-out period between treatment arms should always be included to minimize the possibility of a period (carry-over) effect. Duration of RP trials is usually constrained by the need to complete these over a single season, usually winter when the weather is colder...
September 1, 2017: Rheumatology
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