Recent advances in myositis
|
|
- Sabina Hancock
- 5 years ago
- Views:
Transcription
1 Recent advances in myositis Dr Hector Chinoy PhD Senior Lecturer / Honorary Consultant Rheumatologist Salford Royal NHS Foundation Trust Manchester Academic Health Science Centre The University of Manchester, UK
2 Planned Layout what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
3 Planned Layout what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
4 Idiopathic inflammatory myopathy (IIM): A heterogeneous group of rare autoimmune muscle disorders Rare disease, annual incidence 5-10/million 2 peaks of onset: (5-15 years) (30-50 years) Different IIM subtypes with commonality of myositis Extra-muscular features eg skin, lung, cardiac, malignancy Patterns of disease (rule of 1/3 s): Monogenic Relapsing/remitting Chronic persistent Lack of evidence base for treatment Steroid & immunoresponsive Treatment phases: induction/maintenance of remission
5 How do patients present with inflammatory myopathy? Insidious onset of proximal weakness Dyspnoea Fatigue Skin abnormalities (including ulceration) Myalgia Dysphagia Weight loss Raynaud s Dry, cracked hands Arthralgia/arthritis
6 ATP ADP Creatine ATP ADP + H + Features of Myositis Creatine Kinase Creatine phosphate
7 Clues on bloods Low creatinine High ferritin High ALT Raised Troponin T Negative ANA
8 Many causes of raised CK! 1. Muscle trauma a) Muscle injury / Needle stick b) EMG c) Surgery d) Convulsions, delirium tremens 2. Diseases affecting muscle a) Myocardial infarction b) Rhabdomyolysis g) Infectious myositis c) Metabolic myopathies d) Carnitine palmityltransferase II deficiency e) Mitochondrial myopathies 3. Drug/toxin-induced myopathy f) Dystrophinopathies h) Amyotrophic lateral sclerosis i) Neuromyotonias h) Idiopathic inflammatory myopathy a) Lipid-lowering agents, especially statins b) Alcoholic myopathy c) Drugs of abuse: e.g. cocaine, amphetamines, phencyclidine d) Malignant hyperthermia / neuroleptic malignant syndrome e) Other meds: e.g. zidovudine, colchicine, chloroquine, ipecac 4. Drug-induced CK elevation Inhibition of excretion: e.g. barbiturates, morphine, diazepam 5. Endocrine and metabolic abnormalities a) Hypothyroidism b) Hypokalemia c) Hyperosmolar state or ketoacidosis d) Diabetic nephrotic syndrome with oedema e) Renal failure 6. Elevation without disease a) Strenuous, prolonged, and/or unaccustomed exercise b) Ethnic group (black > white) c) Increased muscle mass Adapted from Targoff 2002
9 Differential diagnosis of muscle weakness Inherited myopathies Muscular dystrophies: Duchenne s, fascioscapulohumeral, limb girdle, Becker s, Emery Dreifuss, distal, ocular Congenital myopathies: nemaline, mitochondrial, centronuclear, central core Neurologic Denervating conditions: spinal muscular atrophies, amyotrophic lateral sclerosis Neuromuscular junction disorders: Eaton-Lambert syndrome, myasthenia gravis Myotonic disease: dystrophia myotonica, myotonia congenita, PROMM Other: Guillain-Barre syndrome, chronic autoimmune polyneuropathy Metabolic Endocrine myopathies Drug-induced myopathies Infections Other CTDs Miscellaneous Glycogen storage diseases: acid maltase deficiency, McArdle s, PFK Lipid storage myopathies: carnitine palmityltransferase II deficiency Nutritional: vitamin E deficiency, malabsorption Other: uraemia, hepatic failure, alcoholism, acute intermittent porphyria, diabetic plexopathy Hyper/hypothyroidism, acromegaly, Cushing s syndrome, Addison s disease, vitamin D deficiency, hyper/hypocalcaemia, hypokalaemia Statins, D-penicillamine, clofibrate, chloroquine, amiodarone, vincristine, zidovudine Acute viral: influenza, hep B, echovirus, rickettsia, coxsackie, rubella, vaccines Bacterial pyomyositis: staphylococcus, streptococcus, clostridium perfringens, leprosy Parasites: toxoplasma, trichinella, schistosoma, cysticercus Rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus Periodic paralyses, carcinomatous neuromyopathy, acute rhabdomyolysis, myositis ossificans, microembolisation by atheroma or carcinoma Oddis CV, Rheum Dis Clin North Am 2002;28:
10 what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
11 Polymyositis Inclusion Body Myositis Necrotizing Myopathy Dermatomyositis Idiopathic Inflammatory Myopathy Malignancy Myositis-CTD overlap Juvenile dermatomyositis
12 Bohan and Peter diagnostic criteria for polymyositis / dermatomyositis. 1 Symmetrical weakness of limb-girdle muscles and anterior neck flexors 2 Muscle biopsy evidence typical of myositis 3 Elevation of serum skeletal muscle enzymes, particularly CK 4 Typical EMG features of myositis 5 Typical DM rash, including heliotrope and Gottron s papules For the diagnosis of PM: Definite: Probable: Possible: All of items of items of items 1-4 For the diagnosis of DM: Definite: Probable: Possible: Item 5 plus 3 of items 1-4 Item 5 plus 2 of items 1-4 Item 5 plus 1 of items 1-4 Exclusion criteria: congenital muscular dystrophies, central or peripheral neurological disease, infectious myositis, metabolic/endocrine myopathies and myasthenia gravis. Bohan A, Peter JB, N Eng J Med 1975
13 New classification criteria for myositis Tjarnlund et al, Ann Rheum Dis 2013 Vol 72, suppl 3, p60 biostatistics/calculators/iim/
14 Extra-muscular features of Inflammatory Myopathy Hughes M, Lilleker JB, Herrick AL, Chinoy H. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity. Ann Rheum Dis May;74(5):795-8 Slides courtesy of IMACS, Prof Oddis & McHugh
15 Myositis: effects of muscle damage Photo courtesy of Prof R Coop
16 Heliotrope rash Violaceous to erythematous discrete or confluent macules confined to the upper eyelids
17 Gottron s papules Erythematous to violaceous papules and plaques over the extensor surfaces of MCP and IP joints & other large joints in a symmetric distribution
18 Nail changes
19 V / Shawl sign Discrete, confluent macular erythema over lower anterior neck, upper anterior chest & shawl distribution V SIGN SHAWL SIGN
20 what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
21 Myositis-Spectrum Disease Autoantibodies Autoantibody HLA formation Other genes Infections UV Specific signs & symptoms Environmental risk factors Slide adapted from Dr Gunawardena Hood E: Environ Health Perspect 2003, 111:A274 A276.
22 Always worth Checking ANA pattern for clues Gunawardena H. The Clinical Features of Myositis-Associated Autoantibodies: a Review. Clin Rev Allergy Immunol Feb;52(1):45-57.
23 Myositis Spectrum Disease Antibodies & Clinical Associations in Adult Myositis Betteridge Z, McHugh N. Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med Jul;280(1):8-23
24 Anti-synthetase / anti-pm-scl: Remember Interstitial Lung Disease Jo-1: anti-synthetase syndrome PM-Scl: myositis/scleroderma overlap syndrome Pictures courtesy of Drs Herrick, Oddis & Wedderburn
25 Anti-synthetase / anti-pm-scl: Remember Interstitial Lung Disease Jo-1: anti-synthetase syndrome REMEMBER - PATIENTS MAY PRESENT WITHOUT CLINICAL MYOSITIS PM-Scl: myositis/scleroderma overlap syndrome Pictures courtesy of Drs Herrick, Oddis & Wedderburn
26 Reported Clinical Associations ILD (67-100%) Rapidly Progressing ILD (RP-ILD) (22-100%) Anti-MDA5 (anti-cadm140) Skin manifestations Gottron s Papules Periungal Ulceration (skin and mouth) Hand Swelling Arthritis Palmar Papules Mechanics Hands Panniculitis Alopecia Fiorentino et al J Am Acad Dermatol 2011;65:25-34 Sato et al Arthritis Rheum 2005;52: Nakashima et al Rheumatol 2010;49: Kobayashi et al J Pediatr 2011;158:675-7 JDM Associations Skin and Oral Ulcers No known association with Periungal, Gottron s Papules, Arthritis or Alopecia ILD? Slide adapted from Dr Betteridge
27 Anti-TIF1g: diagnostic utility in cancer associated myositis SENSITIVITY Pooled sensitivity for cancer-associated myositis SPECIFICITY Trallero-Araguás et al, Arthritis Rheum 2012;64:
28 what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
29 Case 1: Mrs SH 57 year old female, type II DM 1 year post-simvastatin 3 month history of marked proximal weakness CK 11,384 EMG: fibrillations & brief duration simple and complex motor unit potentials
30 MR images T1 STIR
31 Muscle biopsy H&E stained section showing necrotic fibres with macrophage infiltrates
32 Clinical features of anti-hmg CoA reductase (HMGCR) positive patients (45/750, 6%) Features Age Female 58% 52 ± 16 years Statin exposure 30/45 (67%) (24/26, 92% >50 years) CPK Proximal weakness 96% Irritable EMG 73% Necrosis on biopsy 100% Inflammation on biopsy 9,718 ± 7,383 iu/l 20% Anti-HMGCR Ab not found in majority of statintreated subjects, including those with self-limited statin-associated myopathy Strong HLA association Cases v controls analysis (41:164) HLA-DRB1*11 p=4.29x10-5, OR=5.60, 95% CI= (unpublished data, our lab) Mammen A et al. Arthritis Rheum 2011;63: Mammen A et al. Arthritis Care Res (Hoboken). 2012;64:269-72
33 Statin-related myotoxicity phenotype classification Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, et al. Clin Pharmacol Ther Oct;96(4): doi: /clpt
34 Statin-related myotoxicity phenotype classification Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, et al. Clin Pharmacol Ther Oct;96(4): doi: /clpt
35 Case 2: Mr HW 81 year old male 2 year history progressive muscle weakness Unable to dress himself, loss of grip CK 450 Quads / forearm wasting Wrist flexor weakness Prednisolone 30mg for 6/52 no difference
36 MR thigh images T1 STIR
37 Two vacuolated fibres with basophilic rimming, one with an amphophilic inclusion body (H&E x60)
38 Features of sporadic Inclusion Body Myositis >50, male predominance Slowly progressive, affects distal & proximal musculature, often asymmetrically Selective quads & finger flexor weakness CK < 5x ULN Tend to be antibody negative, but may be Ro+ Not immunoresponsive
39 what is myositis? how do we classify myositis? myositis disease spectrum antibodies case presentations how do we assess and treat myositis?
40 Myositis Core Set Measures 1. Manual muscle testing (MMT-8) 2. Patient global visual analogue scale recorded on a 10cm scale 3. Physician global visual analogue scale recorded on a 10cm scale 4. Health Assessment Questionnaire disability index 5. At least one muscle enzyme (CK, AST, ALT, aldolase, LDH) 6. Global extramuscular disease activity (composite of constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiac activity) score recorded on 10cm VAS scale on Myositis Disease Activity Assessment Tool (MDAAT)) Rider LG et al. Arthritis Rheum 2004;50:
41 Version 1.0 SEPT 2009 Study ID: Study Visit Date: / / Study visit number (Circle): 1, 2, 3, 4, 5, 6, 7 MANUAL MUSCLE TESTING Completed by: Consultant Completed for: All patients Completed at: All study visits MMT SCORING: Muscle groups Left (0-10) Right (0-10) Axial (0-10) Axial (0-20) Neck Flexors - - MMT8** Neck Extensors - - Proximal (0-160) Shoulder elevators (Trapezius) - Shoulder abductors (Deltoid Middle) MMT8** - Elbow flexors (Bicepts Brachii) MMT8** - Hip extensors (Gluteus Maximus) MMT8** - Hip abductors (Gluteus Medius) MMT8** - Hip flexors (Iliopsoas) - Knee flexors (Hamstrings) - Knee extensors (Quadriceps) MMT8** - Distal (0-80) Wrist Extensors MMT8** - Wrist Flexors - Ankle Dorsiflexors MMT8** - Ankle Plantar Flexors - MMT MMT8 highlighted in boxes (MMT8**) MMT Axial + Proximal + Distal (all 26) MMT GRADING: FUNCTION OF THE MUSCLE GRADE No No contraction felt in muscle 0 / 0 Movement Feeble contraction felt in muscle, but no movement of part T / 1 MOVEMENT IN HORIZONTAL PLANE Test Moves through partial range of motion 1 / 2- Movement Moves through complete range of motion 2 / 2 ANTIGRAVITY POSITION Moves through partial range of motion 3 / 2+ Test Gradual release from test position 4 / 3- Position Holds test position (no added pressure) 5 / 3 Holds test position against slight pressure 6 / 3+ Holds test position against slight to moderate pressure 7 / 4- Holds test position against moderate pressure 8 / 4 Holds test position against moderate to strong pressure 9 / 4+ Holds test position against strong pressure 10 / 5
42 Induction of remission (1) 40-60mg prednisolone / day (~0.75mg/kg) or if severe disease, initial methylprednisolone mg 2-3 doses alternate days Continue dose until CK <2x ULN Then reduce by 10mg/wk to 40mg, then 5mg/wk to 15mg, then 2.5mg/wk to mg daily, then further gradual reductions once established on a 2 nd line agent Carstens PO, Schmidt J. Diagnosis, pathogenesis and treatment of myositis: recent advances. Clin Exp Immunol Mar;175(3): doi: /cei
43 Induction of remission (2) If CK not improving after 4-5 weeks Check diagnosis (?+antibody, biopsy, EMG, 2 nd opinion) Add in methylprednisolone if not done so already IV cyclophosphamide EUROLUPUS or CYCLOPS (gauge severity) IVIG 2g/kg over 5 days IV Rituximab
44 Maintanance of remission: Early introduction of disease modifying treatment Early introduction of DMARDs (may overlap with induction of remission) Disease resistance Methotrexate 10-25mg/wk Azathioprine 2.5-3mg/kg (check TPMT levels) Consider adding ciclosporin 3mg/kg to MTX Consider adding MTX/AZA to MMF Mycophenolate mofetil 2-3g/day Tacrolimus 2-5mg bd Cyclophosphamide Rituximab Tocilizumab
45 Inflammatory myopathy: useful hints to help clinical judgement in diagnostics and treatment course Heterogenous collection of diseases Awareness of antibody status may be helpful Help predict clinical phenotype Aid planned investigations / treatment type, length and intensity Use combination of modalities, including MR, to aid diagnostics/assessment of disease activity Evidence base for treatment slowly improving, still unmet need in tailoring treatments
46 Acknowledgements The patients! The University of Manchester Janine Lamb Hector Chinoy Robert G. Cooper William Ollier Simon Rothwell Joanna Parkes James Lilleker Alex Oldroyd Philip Day Fiona Marriage Joanna Cobb John Bowes Hazel Platt Nicolas Pipis MYOGEN Ingrid E. Lundberg Frederick W. Miller Peter K. Gregersen Jiri Vencovsky Katalin Danko Vidya Limaye Albert Selva-O'Callaghan Lauren M. Pachman Ann M. Reed Lisa G. Rider Øyvind Molberg Olivier Benveniste Pernille Mathiesen Timothy Radstake Andrea Doria Jan De Bleecker Boel De Paepe Britta Maurer Leonid Padyukov Terrance P. O'Hanlon Annette Lee Euromyositis Committee Lucy Wedderburn Gouchun Wang Louise Diedrichson Jens Schmidt Jiri Vencovsky Paula Oakley Olivier Benveniste Ingrid Lundberg Zitelab Niels Krogh Mikkel Abildtoft UKMYONET / MYOPROSP Patrick Gordon David Isenberg Mike Hanna Pedro Machado Harsha Gunawardena David Isenberg Patrick Kiely James Miller Bath Neil McHugh Zoe Betteridge
47 MYONET Manchester myositis research Useful sites ositis IMACS resources including muscle biopsy video Freely accessible reviews on myositis and Abs Antibodies Myositis review Statin myotoxicitiy and classification Treatment reviews Free resources 1 st myositis international conference
Interstitial Lung Disease (ILD) Diagnostic Insights Offered by CTD Serology
Interstitial Lung Disease (ILD) Diagnostic Insights Offered by CTD Serology Robert G Cooper Prof of Medicine (Muscle and Rheumatology) Normal Alveolar Physiology Contrast with ILD Pathologies Impairing
More informationThe many faces of myositis. Marianne de Visser Academic Medical Centre Dept of Neurology Amsterdam The Netherlands
The many faces of myositis Marianne de Visser Academic Medical Centre Dept of Neurology Amsterdam The Netherlands Outline of the presentation Classification Diagnosis Therapy Prognosis Diagnostic criteria
More informationHow to assess myositis disease activity in a busy general rheumatology clinic
How to assess myositis disease activity in a busy general rheumatology clinic Patrick Gordon Consultant Rheumatologist / Honorary Senior Lecturer King s Health Partners Email: patrick.gordon2@nhs.net Many
More informationPOLYMYOSITIS (PM) DERMATOMYOSITIS (DM) Body myositis Eosinophilic myositis Giant cell myositis Focal / localised myositis Myopathies caused by
POLYMYOSITIS (PM) DERMATOMYOSITIS (DM) Body myositis Eosinophilic myositis Giant cell myositis Focal / localised myositis Myopathies caused by infections, drugs, toxins Definition Epidemiology Pathogenesis
More informationCase 1: History of J.H. Outside Evaluation. Outside Labs. Question #1
Case 1: History of J.H. 64 yo man seen at UCSF 6-256 25-07. 9 months ago onset progressive weakness of arms and legs, with muscle atrophy in arms. 4 months ago red scaly rash on face, back of hands and
More informationAutoantibodies andprognosis. Jiří Vencovský Institute of Rheumatology, Prague, Czech Republic
Autoantibodies andprognosis Jiří Vencovský Institute of Rheumatology, Prague, Czech Republic HeterogeneityofIIMs Diagnosis Polymyositis Dermatomyositis IBM Necrotising myopathy Paraneoplastic Amyopathic
More informationClinical Commissioning Policy Proposition:
Clinical Commissioning Policy Proposition: Rituximab for the treatment of dermatomyositis and polymyositis (Adults) Reference: NHS England A13X05/01 Information Reader Box (IRB) to be inserted on inside
More informationRheumatology E-learning. University of Szeged Department of Rheumatology and Immunology
Rheumatology E-learning University of Szeged Department of Rheumatology and Immunology Introduction Idiopathic inflammatory myopathies (IIM) are a group of systemic diseases characterized by an immune
More informationSignificance of antibody testing in idiopathic inflammatory myopathies
2/0/20 Significance of antibody testing in idiopathic inflammatory myopathies Jiří Vencovský Institute of Rheumatology, Prague Diagnosis Polymyositis Juvenile DM (JPM) Paraneoplastic Myositis in overlap
More information4/16/2018. Demystifying weakness: how to approach refractory myositis. Objectives. Disclosures. Off-label uses for medications will be discussed
Demystifying weakness: how to approach refractory myositis Jemima Albayda, MD Assistant Professor Johns Hopkins Myositis center Disclosures Off-label uses for medications will be discussed Objectives To
More informationIdiopathic inflammatory muscle diseases. Dr. Paul Etau Ekwom MBChB, MMED Kenyatta National Hospital, Nairobi-Kenya
Idiopathic inflammatory muscle diseases. Dr. Paul Etau Ekwom MBChB, MMED Kenyatta National Hospital, Nairobi-Kenya I.W, 28 YRS, FEMALE SHOP STEWARD Referred to KNH on 16/06/09 from Thika Nursing Home Weakness
More informationInflammatory Myopathies 4 th year MBBS. Marwan Adwan MBChB, MSc, MRCPI, MRCP(rheum) Consultant Rheumatologist
Inflammatory Myopathies 4 th year MBBS Marwan Adwan MBChB, MSc, MRCPI, MRCP(rheum) Consultant Rheumatologist Case A 64 woman presents with erythematous itchy rash over back of hands & forehead. For 1 month
More informationDiseases of Muscle and Neuromuscular Junction
Diseases of Muscle and Neuromuscular Junction Diseases of Muscle and Neuromuscular Junction Neuromuscular Junction Muscle Myastenia Gravis Eaton-Lambert Syndrome Toxic Infllammatory Denervation Atrophy
More informationMyositis 101. Steven R. Ytterberg, M.D. Division of Rheumatology Mayo Clinic, Rochester, MN
Myositis 101 Steven R. Ytterberg, M.D. Rheumatology Mayo Clinic, Rochester, MN Myositis Association Annual Conference Louisville, KY Sept. 6 & 7, 2018 Disclosures Consulting: Dynavax Pfizer Off-label use:
More informationMyositis and Your Lungs
Myositis and Your Lungs 2013 TMA Annual Patient Meeting Louisville, Kentucky Chester V. Oddis, MD University of Pittsburgh Director, Myositis Center Myositis Heterogeneous group of autoimmune syndromes
More information2/23/18. Disclosures. Rheumatic Diseases of Childhood. Making Room for Rheumatology. I have nothing to disclose. James J.
Making Room for Rheumatology James J. Nocton, MD Disclosures I have nothing to disclose Rheumatic Diseases of Childhood Juvenile Idiopathic Arthritis (JIA) Systemic Lupus Erythematosus (SLE) Juvenile Dermatomyositis
More informationAutoantibodies in Idiopathic Inflammatory Myopathies. Vidya Limaye Rheumatology Department Royal Adelaide Hospital
Autoantibodies in Idiopathic Inflammatory Myopathies Vidya Limaye Rheumatology Department Royal Adelaide Hospital Idiopathic Inflammatory Myopathies (IIM) Heterogeneous group of systemic autoimmune syndromes
More informationAutoantibodies in the Idiopathic Inflammatory Myopathies
Autoantibodies in the Idiopathic Inflammatory Myopathies Steven R. Ytterberg, M.D. Division of Rheumatology Mayo Clinic Rochester, MN The Myositis Association Annual Conference St. Louis, MO Sept. 25,
More informationDisorders of Muscle. Disorders of Muscle. Muscle Groups Involved in Myopathy. Needle Examination of EMG. History. Muscle Biopsy
Disorders of Muscle Disorders of Muscle Zakia Bell, M.D. Associate Professor of Neurology and Physical Medicine & Rehabilitation Virginia Commonwealth University Cardinal symptom of diseases of the muscle
More informationWhat are Autoantibodies and how do they work in Myositis?
What are Autoantibodies and how do they work in Myositis? Neil McHugh, University of Bath and Royal National Hospital for Rheumatic Diseases Orlando September 2015 Royal National Hospital for Rheumatic
More informationStation 1: Muscle Structure Table 3: Muscle Structure. Station 1: Muscle Contraction
The Muscular System Name: HASPI Medical Anatomy & Physiology 09a Lab Activity Answer Sheet Period: Date: Station 1: Muscle Structure Table 3: Muscle Structure A K B L C M D N E O F P G Q H R I S J T Station
More informationCritical Illness Polyneuropathy CIP and Critical Illness Myopathy CIM. Andrzej Sladkowski
Critical Illness Polyneuropathy CIP and Critical Illness Myopathy CIM Andrzej Sladkowski Potential causes of weakness in the ICU-1 Muscle disease Critical illness myopathy Inflammatory myopathy Hypokalemic
More informationHUNGARIAN MYOSITIS COHORT
CLINICAL ADVANCES OF ANTI- TIF1Γ AUTOANTIBODY IN A HUNGARIAN MYOSITIS COHORT Melinda Nagy-Vincze 1, Zoltán Griger 1, Levente Bodoki 1, Zsuzsa Szankai 1, Zoe E. Betteridge 2, Katalin Dankó 1 1 University
More informationPedsCases Podcast Scripts
Pedss Podcast Scripts This is a text version of a podcast from Pedscases.com on Juvenile Dermatomyositis. These podcasts are designed to give medical students an overview of key topics in pediatrics. The
More informationL. Nandini Moorthy, MD MS 2012
L. Nandini Moorthy, MD MS 2012 L Nandini Moorthy, MD MS 09 17 yo Ashkenazi male with proximal muscle pain and weakness, mild malar erythema and erythema over knees and dorsal aspect of PIPs Mild tenderness
More informationDiscovery, Understanding, and Progress in Myositis
Discovery, Understanding, and Progress in Myositis Steven Ytterberg, M.D. TMA Annual Patient Conference New Orleans, LA Sept. 2, 2016 Disclosures Financial: Dynavax Corp. Pfizer Mallinckrodt American Board
More informationIdiopathic inflammatory myopathies
Myositis and cancer Idiopathic inflammatory myopathies Primary idiopathic polymyositis Primary idiopathic dermatomyositis Juvenile poly/dermatomyositis Myositis associated with another CTD Myositis associated
More informationObjectives. Non-Traumatic Muscle Pathologies. Abnormal Muscle Signal Intensity. Inflammatory Myositis. Polymyostis / Dermatomyositis.
Non-Traumatic Muscle Pathologies Ali Naraghi Division of Musculoskeletal Radiology Joint Department of Medical Imaging University of Toronto Objectives Define the range of non-traumatic pathologies affecting
More informationIDIOPATHIC INFLAMMATORY MYOPATHIES AND RELATED DISORDERS. Franclo Henning Division of Neurology Tygerberg Hospital
IDIOPATHIC INFLAMMATORY MYOPATHIES AND RELATED DISORDERS Franclo Henning Division of Neurology Tygerberg Hospital Classification systems Clinical (Bohan and Peter) Clinico-pathological (Dalakas & others)
More informationIdiopathic inflammatory myopathies excluding inclusion body myositis
Idiopathic inflammatory myopathies excluding inclusion body myositis Marianne de Visser, Dept. of Neurology, Academic Medical Centre, Amsterdam, The Netherlands The idiopathic inflammatory myopathies (IIMs),
More informationMYOSITIS. A physician s guide to the
MYOSITIS A physician s guide to the TABLE OF CONTENTS Myositis basics... 1 contents... 3 Causes... 7... 11 Affected populations... 15 Diagnosis... 17... 25... 31 PHYSICIAN S GUIDE TO MYOSITIS matory
More information2 nd Global Conference on Myositis May 5-8, 2017 Bolger Center, Potomac, MD, USA All Times Listed are US Eastern Standard Time
2 nd Global Conference on Myositis May 5-8, 2017 Bolger Center, Potomac, MD, USA All Times Listed are US Eastern Standard Time Friday May 5 7:00-8:00 am Pre-Conference Registration Pathology Pre-Conference
More informationIMACS FORM 07b: MYOSITIS DISEASE ACTIVITY ASSESSMENT TOOL, Version
IMACS FORM 07b: MYOSITIS ASSESSMENT TOOL, Version 2 2005 Subject s IMACS number: ASSESSOR: Date Assessed: Assessment number: The clinical features recorded are based upon the previous 4 weeks and the judgment
More informationMuscle Pathology Surgical Pathology Unknown Conference. November, 2008 Philip Boyer, M.D., Ph.D.
Muscle Pathology Surgical Pathology Unknown Conference November, 2008 Philip Boyer, M.D., Ph.D. Etiologic Approach to Differential Diagnosis Symptoms / Signs / Imaging / Biopsy / CSF Analysis Normal Abnormal
More informationEDX in Myopathies Limitations. EDX in Myopathies Utility Causes of Myopathy. Myopathy: Issues for Electromyographers
Electrodiagnostic Assessment of Myopathy Myopathy: Issues for Electromyographers Often perceived as challenging Ian Grant Division of Neurology QEII Health Sciences Centre Halifax NS CNSF EMG Course June
More informationOverview of Diagnostic Autoantibodies in Inflammatory Myopathy
Overview of Diagnostic Autoantibodies in Inflammatory Myopathy Minoru Satoh, M.D., Ph.D. Research Associate Professor of Medicine Division of Rheumatology and Clinical Immunology University of Florida
More informationMyosites du sujet âgé
Myosites du sujet âgé Olivier Benveniste Département de Médecine Interne Centre de Référence Maladies Neuro-Musculaires Equipe Muscle Inflammatoire U974 Groupe Hospitalier Pitié-Salpêtrière Myositis classification
More informationThe Elevated CK ROBERT HAWKINS, M.D.
The Elevated CK ROBERT HAWKINS, M.D. What is the difference between CK and CPK One has a P in it. One has kinase in it, the other has phosphokinase in it. There is no true difference. A kinase is, by definition,
More informationCNEMG. Myopathy, Stålberg. At rest denervation and spec spontaneous activity (myotonia, CRD, neuromyotonia) MUP number of fibres in recorded area
clincial heredity biochem MYOPATHY biopsy Erik Stålberg Uppsala, Sweden imaging genetics Electrodes A B C MU D E Conc EMG signals from 2-15 muscle fibres CNEMG At rest denervation and spec spontaneous
More information2 nd Global Conference on Myositis May 5-8, 2017 Bolger Center, Potomac, MD, USA All Times Listed are US Eastern Standard Time
2 nd Global Conference on Myositis May 5-8, 2017 Bolger Center, Potomac, MD, USA All Times Listed are US Eastern Standard Time Friday May 5 7:00-8:00 am Pre-Conference Registration Pathology Pre-Conference
More informationIndex. Phys Med Rehabil Clin N Am 14 (2003) Note: Page numbers of article titles are in boldface type.
Phys Med Rehabil Clin N Am 14 (2003) 445 453 Index Note: Page numbers of article titles are in boldface type. A Acid maltase deficiencies, electrodiagnosis of, 420, 422 Acquired peripheral neuropathy,
More informationArthritis Superspeciality Center, Hubli, Karnataka and 2 Department of Rheumatology, SDM Medical College, Dharwad, Karnataka, India.
JOURNAL OF CASE REPORTS 2015;5(1):147-151 A Rare Case of Juvenile Dermatomyositis Vikram Haridas 1,2, Kiran Haridas 1 1,2 Arthritis Superspeciality Center, Hubli, Karnataka and 2 Department of Rheumatology,
More informationJeopardy. What s the rash? $100 $100 $100 $100 $100 $200 $200 $200 $200 $200 $300 $300 $300 $300 $300 $400 $400 $400 $400 $400
Jeopardy Antibodies & more antibodies Aching joints What s the rash? Potpourri Image Challenge $100 $100 $100 $100 $100 $200 $200 $200 $200 $200 $300 $300 $300 $300 $300 $400 $400 $400 $400 $400 $500 $500
More informationFavorable rituximab response in patients with refractory idiopathic inflammatory myopathies
de Souza et al. Advances in Rheumatology (2018) 58:31 https://doi.org/10.1186/s42358-018-0030-z Advances in Rheumatology RESEARCH Favorable rituximab response in patients with refractory idiopathic inflammatory
More informationJUVENILE DERMATOMYOSITIS
JUVENILE DERMATOMYOSITIS - how to diagnose, how to treat? Miloš Nikolić, MD, PhD Professor and Chairman Department of Dermatology, Division of Pediatric Dermatology University of Belgrade, School of Medicine,
More informationGenetic diagnosis of limb girdle muscular dystrophy type 2A, A Case Report
Genetic diagnosis of limb girdle muscular dystrophy type 2A, A Case Report Roshanak Jazayeri, MD, PhD Assistant Professor of Medical Genetics Faculty of Medicine, Alborz University of Medical Sciences
More informationASSESSMENT OF STRENGTH IN CHILDREN WITH JUVENILE DERMATOMYOSITIS
ASSESSMENT OF STRENGTH IN CHILDREN WITH JUVENILE DERMATOMYOSITIS CURE JM STANFORD SCHOOL OF MEDICINE OCTOBER 3, 2014 Minal Jain, PT, DSc, PCS Research Coordinator, Physical Therapy Section Rehabilitation
More informationDermatomyositis Advice from Experts: Improving Your Medical Dermatology Diagnostic and Management Skills Jeffrey P. Callen, MD Professor of Medicine
Dermatomyositis Advice from Experts: Improving Your Medical Dermatology Diagnostic and Management Skills Jeffrey P. Callen, MD Professor of Medicine (Dermatology) University of Louisville Learning Objectives
More informationCASE REPORT. Introduction. Case Report
doi: 10.2169/internalmedicine.9553-17 http://internmed.jp CASE REPORT Successful Treatment of Rapidly Progressive Unclassifiable Idiopathic Interstitial Pneumonia with Anti-melanoma Differentiation-associated
More informationCase Report Repository Corticotropin Injection for Treatment of Idiopathic Inflammatory Myopathies
Case Reports in Rheumatology Volume 2016, Article ID 9068061, 4 pages http://dx.doi.org/10.1155/2016/9068061 Case Report Repository Corticotropin Injection for Treatment of Idiopathic Inflammatory Myopathies
More informationACR 2017 SAN DIEGO HIGHLIGHTS - INFLAMMATORY MYOPATHIES. Nikolaos Marketos Rheumatologist Volos,
ACR 2017 SAN DIEGO HIGHLIGHTS - INFLAMMATORY MYOPATHIES Nikolaos Marketos Rheumatologist Volos, 1-6-2018 No disclosures Epidemiology PM & DM Peak 5 15 yrs & 30-50 yrs : = 2-3 : 1 IBM > 50yrs : = 1 : 3
More informationEvolving Uses of IVIG in myositis
Evolving Uses of IVIG in myositis Rossitza I. Chichkova, MD, MS Associate Professor Depts of Neurology and Internal Medicine University of South Florida, Tampa, FL Immune Function In Normal State: Protects
More informationMyositis and Autoimmune ILD
Myositis and Autoimmune ILD 2018 AURA Annual Meeting Sedona, Arizona June 2, 2018 Chester V. Oddis, MD Director, Myositis Center University of Pittsburgh Disclosures Genentech: Clinical trial support Idera:
More informationRHEUMATOLOGY OVERVIEW. Carmelita J. Colbert, MD Assistant Professor of Medicine Division of Rheumatology Loyola University Medical Center
RHEUMATOLOGY OVERVIEW Carmelita J. Colbert, MD Assistant Professor of Medicine Division of Rheumatology Loyola University Medical Center What is Rheumatology? Medical science devoted to the rheumatic diseases
More informationTMA San Diego September 7, 2017
Myositis 101: Clinical Features, Diagnosis and Management Namita Goyal, MD Associate Professor of Neurology Director, Neuromuscular Medicine Fellowship Director, Neuromuscular Diagnostic Laboratory Associate
More informationA48-year-old Hispanic woman
Jamie Goodall, MS4, and Richard P. Usatine, MD University of Texas Health Science Center at San Antonio Skin rash and muscle weakness The patient s facial rash was spreading and she was having difficulty
More informationDR.JANANI RAVI DR.GNANABALAN S UNIT DR.MEHTA CHILDREN HOSPITAL
DR.JANANI RAVI DR.GNANABALAN S UNIT DR.MEHTA CHILDREN HOSPITAL 1 ½ year old girl c/o *Prolonged fever 20 days *Puffiness of face and legs 20 days *Rash in the lower limbs 20 days Child was suspected to
More informationDermatomyositis with Rapidly Progressive Interstitial Lung Disease Treated with Rituximab: A Report of 3 Cases in Japan
CASE REPORT Dermatomyositis with Rapidly Progressive Interstitial Lung Disease Treated with Rituximab: A Report of 3 Cases in Japan Kenichiro Tokunaga 1 and Noboru Hagino 2 Abstract We performed a retrospective
More informationThe idiopathic inflammatory myopathies
REVIEW Idiopathic Inflammatory Myopathies: Current Trends in Pathogenesis, Clinical Features, and Up-to-Date Treatment Recommendations Floranne C. Ernste, MD, and Ann M. Reed, MD Abstract Recently, there
More informationWhat your autoantibodies tell us about your disease. Mark Gourley, MD
What your autoantibodies tell us about your disease Mark Gourley, MD The Importance of the Immune System Defends us against foreign invaders Self (cancer) and Nonself (virus, bacteria, etc.) But, if the
More informationLong-term follow-up of sporadic inclusion body myositis treated with intravenous immunoglobulin: a retrospective study of 16 patients
Long-term follow-up of sporadic inclusion body myositis treated with intravenous immunoglobulin: a retrospective study of 16 patients C. Dobloug, R. Walle-Hansen, J.T. Gran, Ø. Molberg Section of Rheumatology,
More informationHASPI Medical Anatomy & Physiology 09a Lab Activity
HASPI Medical Anatomy & Physiology 09a Lab Activity Name(s): Period: Date: http://www.fallingpixel.com/products/33817/mains/0000-malemuscular_1.jpg The Muscular System The main function of the muscular
More informationAcute Emergencies in Rheumatology
Acute Emergencies in Rheumatology Clare Higgens Northwick Park hospital and St George s Hospital London Acute Rheumatological Emergencies The Acute Hot joint Inflammatory back pain.. Systemic lupus erythematosus(sle)
More informationEssential Rheumatology. Dr Ellen Bruce Consultant Rheumatologist CMFT
Essential Rheumatology Dr Ellen Bruce Consultant Rheumatologist CMFT Saving the best for last! Apparently people recall best the first and last thing they re told. Far too difficult to include everything.
More informationCURRENT ESSENTIALS IN INFLAMMATORY MYOPATHIES
CURRENT ESSENTIALS IN INFLAMMATORY MYOPATHIES Maren Breithaupt, 1 Jens Schmidt 1,2 1. Clinic for Neurology, University Medical Center Göttingen, Göttingen, Germany 2. Department of Neuroimmunology, Institute
More informationClinical features of seven Japanese patients with anti-pl- antibody frequent positivity for anti-cyclic citrullinated peptide antibody
Cace report Clinical features of seven Japanese patients with anti-pl- antibody frequent positivity for anti-cyclic citrullinated peptide antibody Yoichiro Akiyama 1, Takao Nagashima 1, Masahiro Iwamoto
More informationValidation of Manual Muscle Testing and a Subset of Eight Muscles for Adult and Juvenile Idiopathic Inflammatory Myopathies
Arthritis Care & Research Vol. 62, No. 4, April 2010, pp 465 472 DOI 10.1002/acr.20035 2010, American College of Rheumatology ORIGINAL ARTICLE Validation of Manual Muscle Testing and a Subset of Eight
More information1 DOS CME Course 2011
Statin Myopathy February 23, 2011 Jinny Tavee, MD Associate Professor Neurological Institute Cleveland Clinic Foundation 1 Case 1 50 y/o woman with hyperlipidemia presents with one year history of deep
More informationUnderstanding Myositis Medications
Understanding Myositis Medications 2015 TMA Annual Patient Conference Orlando, Florida Chester V. Oddis, MD University of Pittsburgh Director, Myositis Center Disclosures Mallinckrodt: Research Grant Genentech:
More informationPublications List. 1. General factsheets. 2. Medical conditions factsheets
Publications List We produce a wide range of publications, from factsheets about specific medical conditions to comprehensive guides on adapting your home. To order a free publication: Call the Information
More informationRituximab Therapy for Myopathy Associated With Anti Signal Recognition Particle Antibodies: A Case Series
Arthritis Care & Research Vol. 62, No. 9, September 2010, pp 1328 1334 DOI 10.1002/acr.20219 2010, American College of Rheumatology ORIGINAL ARTICLE Rituximab Therapy for Myopathy Associated With Anti
More information2- and 6-minute walk tests equally well assess walking capability in neuromuscular diseases
2- and 6-minute walk tests equally well assess walking capability in neuromuscular diseases Linda Kahr Andersen, PT, MSc Copenhagen Neuromuscular Center Background The 6MWT widely used to measure treatment
More informationSCLERODERMA SPECTRUM DISEASE
SCLERODERMA SPECTRUM DISEASE Mohammed A. Omair MBBS, SF Rheum Consultant Rheumatologist Assistant Professor King Saud University President of the Charitable Association for Rheumatic Diseases Agenda Background
More informationBudsakorn Darawankul, MD. Maharat Nakhon Ratchasima Hospital
Budsakorn Darawankul, MD. Maharat Nakhon Ratchasima Hospital Outline What is ANA? How to detect ANA? Clinical application Common autoantibody in ANA diseases Outline What is ANA? How to detect ANA? Clinical
More informationinvestigations. We will also discuss some rare neuromuscular problems presenting for the first time in later life.
Musculoskeletal 29 Muscle disorders in the elderly Myopathy is the term used to describe diseases of the muscle that are not attributable to nerve dysfunction. It is an umbrella term that encompasses myopathies
More informationClinical Aspects of Peripheral Nerve and Muscle Disease. Roy Weller Clinical Neurosciences University of Southampton School of Medicine
Clinical Aspects of Peripheral Nerve and Muscle Disease Roy Weller Clinical Neurosciences University of Southampton School of Medicine Normal Nerves 1. Anterior Horn Cell 2. Dorsal root ganglion cell 3.
More informationGenetics of Inclusion Body Myositis
Genetics of Inclusion Body Myositis Thomas Lloyd, MD, PhD Associate Professor of Neurology and Neuroscience Co-director, Johns Hopkins Myositis Center Sporadic IBM (IBM) Age at onset usually > 50 Prevalence
More information*Pari Basharat ABSTRACT OVERVIEW OF IDIOPATHIC INFLAMMATORY MYOPATHIES
IDIOPATHIC INFLAMMATORY MYOPATHIES: ASSOCIATION WITH OVERLAP MYOSITIS AND SYNDROMES: CLASSIFICATION, CLINICAL CHARACTERISTICS, AND ASSOCIATED AUTOANTIBODIES *Pari Basharat University of Western Ontario,
More informationClinical Laboratory. 14:42:00 SSA-52 (Ro52) (ENA) Antibody, IgG 1 AU/mL [0-40] Oct-18
Clinical Laboratory Procedure Result Units Ref Interval Accession Collected Received Rheumatoid Factor
More informationPaediatric rheumatology. A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases
Paediatric rheumatology A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases J.O. Sato 1 *, A.M.E. Sallum 2 *, V.P.L. Ferriani 3, R. Marini 4, S.B. Sacchetti
More informationA CRP B FBC C LFT D blood culture E uric acid
1 A 39 year old lady with rheumatoid arthritis is admitted to hospital with a hot, swollen and painful right knee. Which is the most important blood test? A CRP B FBC C LFT D blood culture E uric acid
More informationCorrespondence should be addressed to Yasuhiro Shimojima;
Hindawi Case Reports in Rheumatology Volume 2017, Article ID 5386797, 6 pages https://doi.org/10.1155/2017/5386797 Case Report Effective Administration of Rituximab in Anti-MDA5 Antibody Positive Dermatomyositis
More informationTools to Aid in the Accurate Diagnosis of. Connective Tissue Disease
Connective Tissue Disease Tools to Aid in the Accurate Diagnosis of Connective Tissue Disease Connective Tissue Disease High quality assays and novel tests Inova offers a complete array of assay methods,
More informationMyasthenia gravis. David Hilton-Jones Oxford Neuromuscular Centre
Myasthenia gravis David Hilton-Jones Oxford Neuromuscular Centre SWIM, Taunton, 2018 Myasthenia gravis Autoimmune disease Nature of Role of thymus Myasthenia gravis Autoimmune disease Nature of Role of
More informationIndex. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A Acid a-glucosidase deficiency (Pompe disease), 208, 237, 241, 293 Actin defects, in myopathies, 280 Acyl-coenzyme A dehydrogenase deficiency,
More informationSCLERODERMA OVERLAP SYNDROME: A CASE REPORT Diwakar K. Singh 1, Nataraju H. V 2
SCLERODERMA OVERLAP SYNDROME: A Diwakar K. Singh 1, Nataraju H. V 2 HOW TO CITE THIS ARTICLE: Diwakar K. Singh, Nataraju H. V. Scleroderma Overlap Syndrome: A Case Report. Journal of Evolution of Medical
More informationINCREASING INCIDENCE OF IMMUNE MEDIATED NECROTIZING MYOPATHY SINGLE CENTRE EXPERIENCE
INCREASING INCIDENCE OF IMMUNE MEDIATED NECROTIZING MYOPATHY SINGLE CENTRE EXPERIENCE Martin Klein 1,2*, Heřman Mann 1,2*, Lenka Pleštilová 1,2, Josef Zámečník 3, Zoe Betteridge 4, Neil McHugh 4, Jiří
More informationIII./10.4. Diagnosis. Introduction. A.) Laboratory tests. Laboratory tests, electrophysiology, muscle biopsy, genetic testing, imaging techniques
III./10.4. Diagnosis Laboratory tests, electrophysiology, muscle biopsy, genetic testing, imaging techniques After studying this chapter, you will become familiar with the most commonly used diagnostic
More informationMuscular Dystrophies. Pinki Munot Consultant Paediatric Neurologist Great Ormond Street Hospital Practical Neurology Study days April 2018
Muscular Dystrophies Pinki Munot Consultant Paediatric Neurologist Great Ormond Street Hospital Practical Neurology Study days April 2018 Definition and classification Clinical guide to recognize muscular
More informationPhysiotherapy in Juvenile Dermatomyositis
Journal of Research and Practice on the Musculoskeletal System JOURNAL OF RESEARCH AND PRACTICE Review Article Physiotherapy in Juvenile Dermatomyositis Theodora Polychronopoulou Physiotherapist, Athens,
More informationSTUDIES ON INTERLEUKIN-1 IN IDIOPATHIC INFLAMMATORY MYOPATHIES
From the Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden STUDIES ON INTERLEUKIN-1 IN IDIOPATHIC INFLAMMATORY MYOPATHIES Christina Dorph Stockholm 2009 All previously
More informationTest Name Results Units Bio. Ref. Interval
LL - LL-ROHINI (NATIONAL REFERENCE 135091593 Age 25 Years Gender Male 30/8/2017 91600AM 30/8/2017 93946AM 31/8/2017 84826AM Ref By Final COLLAGEN DISEASES ANTIBODY ANEL ANTI NUCLEAR ANTIBODY / FACTOR (ANA/ANF),
More informationTwo simple, reliable and valid tests of proximal muscle function, and their application to the management of idiopathic inflammatory myositis
Rheumatology 26;45:874 879 Advance Access publication 31 January 26 Two simple, reliable and valid tests of proximal muscle function, and their application to the management of idiopathic inflammatory
More informationThis month, we are very pleased to introduce some new tests for Scleroderma as well as some test changes to our existing scleroderma tests/panels.
February 20, 2017 Client Letter Test Update February 2017 Dear Colleague: This month, we are very pleased to introduce some new tests for Scleroderma as well as some test changes to our existing scleroderma
More informationClinical Laboratory. [None
Clinical Laboratory Procedure Result Units Ref Interval Accession Collected Received Double-Stranded DNA (dsdna) Ab IgG ELISA Detected * [None 18-289-900151 Detected] Double-Stranded DNA (dsdna) Ab IgG
More informationEXTENDED REPORT. Clinical and epidemiological research
Additional supplementary tables is published online only. To view the fi les please visit the journal online (http://ard.bmj.com/ content/71/6.toc). 1 Rheumatic Diseases Centre, Manchester Academic Health
More informationChronic focal polymyositis in the adult
Journal of Neurology, Neurosurgery, and Psychiatry, 1981, 44, 419-425 Chronic focal polymyositis in the adult N E BHARUCHA AND J A MORGAN-HUGHES From the Institute of Neurology, Queen Square, London S
More informationIdentifying statin-associated autoimmune necrotizing myopathy
REVIEW CME CREDIT EDUCATIONAL OBJECTIVE: Readers will recognize autoimmune necrotizing myopathy if it occurs in their patients taking statins JEMIMA ALBAYDA, MD Division of Rheumatology, Department of
More informationRheumatology Potpourri. Dr. Philip A. Baer Seacourses Asia CME December 2017
Rheumatology Potpourri Dr. Philip A. Baer Seacourses Asia CME December 2017 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted
More informationDOWNLOAD OR READ : MYOPATHIES AND MUSCLE DISEASES HANDBOOK OF CLINICAL NEUROLOGY PDF EBOOK EPUB MOBI
DOWNLOAD OR READ : MYOPATHIES AND MUSCLE DISEASES HANDBOOK OF CLINICAL NEUROLOGY PDF EBOOK EPUB MOBI Page 1 Page 2 myopathies and muscle diseases handbook of clinical neurology myopathies and muscle diseases
More information