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Clinical Reasoning
RESIDENT & FELLOW SECTION Clinical Reasoning: Section Editor A 49-year-old woman with progressive Mitchell S.V. Elkind, MD, MS motor deficit Ana Monteiro, MD SECTION 1 strength, and difficulty protruding the tongue, without Amélia Mendes, MD A previously healthy 49-year-old woman presented with fasciculations or atrophy. Symmetrical tetraparesis Fernando Silveira, MD progressive motor deficit. The complaints started the (proximal-greater-than-distal weakness) and increased Lígia Castro, MD year before with weakness of the right arm. Over the tone were noted, with severe pain upon mobilization Goreti Nadais, MD subsequent months, she developed weakness in the left and palpation of joints and muscles. Deep tendon reflexes arm, followed by both legs, and, finally, difficulty speak- were brisk and symmetric, with bilateral flexor plantar ing, with nasal voice, and swallowing. It was increasingly responses. There was atrophy of the interosseous muscles Correspondence to difficult to attend to her chores, and, by the time she of the hands and shoulder girdle muscle wasting. Dr. Monteiro: sought medical attention, she needed help with all daily [email protected] Questions for consideration: activities. In the last few weeks, she also complained of diffuse joint and muscle pain. Medical and family history 1. How do you localize the symptoms: upper motor were unremarkable. neuron (UMN) or lower motor neuron (LMN), Neurologic examination showed bilateral facial weak- neuromuscular junction (NMJ), peripheral nerve, ness, severe dysarthria, dysphonia and dysphagia (nau- or muscle? What is the broad differential? seous reflex preserved), decreased shoulder elevation 2. What findings on examination would be helpful? GO TO SECTION 2 Supplemental data at Neurology.org From the Departments of Neurology (A. -
An Overview of Various Diagnostic Methods to Detect Antinuclear Antibodies of Connective Tissue Diseases
DOI: 10.7860/NJLM/2021/48042:2492 Review Article An Overview of Various Diagnostic Methods to Detect Antinuclear Antibodies of Microbiology Section Microbiology Connective Tissue Diseases SAIKEERTHANA DURAISAMY ABSTRACT Antinuclear Antibodies (ANA) are present in many autoimmune disorders and these disorders are collectively called as Connective Tissue Diseases (CTD). There are various CTDs which include Systemic Lupus Erythematosus (SLE), Sjogren’s syndrome, Systemic Sclerosis (SS), Inflammatory Myositis (IM), Mixed Connective Tissue Disorder (MCTD) and Rheumatoid Arthritis (RA). Detection of ANAs in these CTDs is highly sensitive and is of utmost importance. The ANAs specific to SLE includes antidouble stranded Deoxyribonucleic Acid (antidsDNA), single stranded DNA (ssDNA). Scleroderma or Systemic Sclerosis (SS) is an immune mediated rheumatic disease where autoantibodies like topoisomerase 1, Ribonucleic Acid (RNA) polymerase 1 and fibrillarin are useful in diagnosis. Idiopathic Inflammatory Myositis (IIM) such as polymyositis and dermatomyositis are characterised by the presence of autoantibodies like PM-scl (Polymyositis-Scleromyositis), Mi-1 (Myositis specific autoantibody found in idiopathic inflammatory myositis), Mi-2 and Ku (DNA Binding Protein in dermatomyositis). Antibody titres against polypeptides on the U1 Ribonucleoprotein (U1RNP) is useful in the detection mixed CTD. Sjogren’s syndrome is characterised by the presence of serum autoantibodies against two ribonucleoproteinic complexes like Ro/SSA (Extractable nuclear antigen found in Sjogren's syndrome related antigen A auto antibodies) and La/SSB (Extractable nuclear antigen found in Sjogren's syndrome or lupus erythematous). ANA analysis can be done by techniques like indirect immunofluorescence method, Enzyme Linked Immuno Sorbent Assay (ELISA), Immunoprecipitation in agar and western blotting. All these diagnostic methods give precise identification of these antibodies with high accuracy. -
Percutaneous Conchotome Muscle Biopsy. a Useful Diagnostic and Assessment Tool CHRISTINA DORPH, INGER NENNESMO, and INGRID E
Percutaneous Conchotome Muscle Biopsy. A Useful Diagnostic and Assessment Tool CHRISTINA DORPH, INGER NENNESMO, and INGRID E. LUNDBERG ABSTRACT. Objective. To evaluate the diagnostic yield, performance simplicity, and safety of the percutaneous conchotome muscle biopsy technique for clinical and research purposes in an outpatient rheuma- tology clinic. Methods. Biopsies taken by rheumatologists in an outpatient clinic during 1996 and 1997 were eval- uated for histopathological and clinical diagnoses. Results. A total of 149 biopsies were performed on 122 patients. Physicians learned the method easily. Samples were of adequate size and quality to allow for diagnostics. In total 106 biopsies were taken due to different diagnostic suspicions: 24 polymyositis (PM) or dermatomyositis (DM); 43 PM, DM, or vasculitis in addition to another rheumatic condition; 19 systemic vasculitis; and 20 myalgias. Criteria for definite or probable PM/DM were fulfilled in 21 patients, 18 with positive biopsies. Thirteen patients received vasculitis as clinical diagnosis, 3 with positive biopsies. No patient with myalgia had a biopsy with inflammatory changes. Fifteen of 43 rebiopsies performed to assess disease activity had signs of active inflammation. In 48% there were changes in immuno- suppressive therapy after biopsy results. Four complications occurred; one was a serious subfascial hematoma. Conclusion. The percutaneous conchotome muscle biopsy technique gives a good size sample that allows for diagnostic evaluation and has a high yield in patients with myositis. It is a simple proce- dure, easy to learn and to perform, with a low complication rate and minimum discomfort for the patient. The method can preferably be used as a diagnostic tool and to perform repeated biopsies to assess the effect of a given therapy for both clinical and research purposes. -
Autoantibodies in Systemic Autoimmune Diseases K
umschlag_neutral.qxd 03.10.2007 10:53 Seite 1 2nd edition Karsten Conrad, Werner Schößler, Falk Hiepe, Marvin J. Fritzler Autoantibodies are a very heterogeneous group of antibodies with respect to their specificity, induction, effects, and clinical signifi- cance. Testing for autoantibodies can be helpful or necessary for the diagnosis, differential diagnosis, prognostication, or monitoring of Autoantibodies in Systemic autoimmune diseases. In case of limited (forme fruste) disease or a single disease manifestation, the detection of serum autoantibodies can play an Autoimmune Diseases important role in raising the suspicion of evolving disease and forecasting prog- nosis. This book and reference guide is intended to assist the physician in under- A Diagnostic Reference standing and interpreting the variety of autoantibodies that are being used as diagnostic and prognostic tools for patients with systemic rheumatic diseases. Autoantibodies observed in systemic autoimmune diseases are described in alphabetical order in Part 1 of this reference guide. In Part 2, systemic autoim- mune disorders as well as symptoms that indicate the possible presence of an autoimmune disease are listed. Systemic manifestations of organ-specific autoim- mune diseases will not be covered in this volume. Guide marks were inserted to K. Conrad, W.K. Conrad, Hiepe, M. J. Fritzler F. Schößler, ensure fast and easy cross-reference between symptoms, a given autoimmune disease and associated autoantibodies. Although the landscape of autoantibody testing continues to change, this information will be a useful and valuable refer- ence for many years to come. AUTOANTIGENS, AUTOANTIBODIES, AUTOIMMUNITY Autoantibodies in Systemic Autoimmune Diseases Autoimmune in Systemic Autoantibodies Volume 2, second Edition – 2007 ISBN 978-3-89967-420-0 www.pabst-publishers.com PABST Autoantibodies in Systemic Autoimmune Diseases A Diagnostic Reference Karsten Conrad, Werner Schößler, Falk Hiepe, Marvin J. -
That Are Not Lielu Uutuullittu
THAT ARE NOT LIELUUS009987356B2 UUTUULLITTU (12 ) United States Patent ( 10 ) Patent No. : US 9 ,987 , 356 B2 Reimann et al. ( 45) Date of Patent : Jun . 5 , 2018 (54 ) ANTI -CD40 ANTIBODIES AND METHODS 762 A 12 / 1997 Queen et al. 5 , 801, 227 A 9 / 1998 Fanslow , III et al. OF ADMINISTERING THEREOF 5 , 874 ,082 A 2 / 1999 de Boer 6 ,004 , 552 A 12 / 1999 de Boer et al. ( 75 ) Inventors: Keith A . Reimann , Marblehead , MA 6 ,051 ,228 A 4 / 2000 Aruffo et al. (US ) ; Rijian Wang , Saugus, MA (US ) ; 6 ,054 ,297 A 4 / 2000 Carter et al . Christian P . Larsen , Atlanta , GA (US ) 6 ,056 , 959 A 5 /2000 de Boer et al. 6 , 132 , 978 A 10 /2000 Gelfand et al. 6 , 280 , 957 B18 / 2001 Sayegh et al. ( 73) Assignees : Beth Israel Deaconess Medical 6 , 312 ,693 B1 11/ 2001 Aruffo et al. Center , Inc ., Boston , MA (US ) ; Emory 6 , 315 , 998 B111 / 2001 de Boer et al. University , Atlanta , GA (US ) 6 , 413 ,514 B1 7 / 2002 Aruffo et al. 6 , 632, 927 B2 10 /2003 Adair et al. ( * ) Notice : Subject to any disclaimer , the term of this 7 ,063 , 845 B2 6 / 2006 Mikayama et al. patent is extended or adjusted under 35 7 , 193 , 064 B2 3 / 2007 Mikayama et al. 7 , 288 , 251 B2 10 / 2007 Bedian et al . U . S . C . 154 ( b ) by 464 days . 7 , 361 , 345 B2 4 /2008 de Boer et al. 7 , 445 , 780 B2 11/ 2008 Chu et al. (21 ) Appl . No. -
Autoantibodies and Anti-Microbial Antibodies
bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Autoantibodies and anti-microbial antibodies: Homology of the protein sequences of human autoantigens and the microbes with implication of microbial etiology in autoimmune diseases Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC Charleston, WV 25301 Correspondence: Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC. 500 Donnally St., Suite 303 Charleston, WV 25301 Email: [email protected] Tel: 304 444 7505 1 bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Abstract Autoimmune disease is a group of diverse clinical syndromes with defining autoantibodies within the circulation. The pathogenesis of autoantibodies in autoimmune disease is poorly understood. In this study, human autoantigens in all known autoimmune diseases were examined for the amino acid sequences in comparison to the microbial proteins including bacterial and fungal proteins by searching Genbank protein databases. Homologies between the human autoantigens and the microbial proteins were ranked high, medium, and low based on the default search parameters at the NCBI protein databases. Totally 64 human protein autoantigens important for a variety of autoimmune diseases were examined, and 26 autoantigens were ranked high, 19 ranked medium to bacterial proteins (69%) and 27 ranked high and 16 ranked medium to fungal proteins (66%) in their respective amino acid sequence homologies. -
Scleroderma, Myositis and Related Syndromes [4] Giordano J, Khung S, Duhamel A, Hossein-Foucher C, Bellèvre D, Lam- Blin N, Et Al
Scientific Abstracts 1229 Ann Rheum Dis: first published as 10.1136/annrheumdis-2021-eular.75 on 19 May 2021. Downloaded from Scleroderma, myositis and related syndromes [4] Giordano J, Khung S, Duhamel A, Hossein-Foucher C, Bellèvre D, Lam- blin N, et al. Lung perfusion characteristics in pulmonary arterial hyper- tension and peripheral forms of chronic thromboembolic pulmonary AB0401 CAN DUAL-ENERGY CT LUNG PERFUSION hypertension: Dual-energy CT experience in 31 patients. Eur Radiol. 2017 DETECT ABNORMALITIES AT THE LEVEL OF LUNG Apr;27(4):1631–9. CIRCULATION IN SYSTEMIC SCLEROSIS (SSC)? Disclosure of Interests: None declared PRELIMINARY EXPERIENCE IN 101 PATIENTS DOI: 10.1136/annrheumdis-2021-eular.69 V. Koether1,2, A. Dupont3, J. Labreuche4, P. Felloni3, T. Perez3, P. Degroote5, E. Hachulla1,2,6, J. Remy3, M. Remy-Jardin3, D. Launay1,2,6. 1Lille, CHU Lille, AB0402 SELF-ASSESSMENT OF SCLERODERMA SKIN Service de Médecine Interne et Immunologie Clinique, Centre de référence THICKNESS: DEVELOPMENT AND VALIDATION OF des maladies autoimmunes systémiques rares du Nord et Nord-Ouest de THE PASTUL QUESTIONNAIRE 2 France (CeRAINO), Lille, France; Lille, Université de Lille, U1286 - INFINITE 1,2 1 1 1 J. Spierings , V. Ong , C. Denton . Royal Free and University College - Institute for Translational Research in Inflammation, Lille, France; 3Lille, Medical School, University College London, Division of Medicine, Department From the Department of Thoracic Imaging, Hôpital Calmette, Lille, France; 4 of Inflammation, Centre for Rheumatology and Connective -
Diagnosis and Treatment of Dermatomyositis-Systemic Lupus
Diagnosis and Treatment of Dermatomyositis-Systemic Lupus Erythematosus Overlap Syndrome Preston Williams1; Benjamin McKinney, MD2 1Texas A&M College of Medicine; 2Baylor University Medical Center Family Medicine Residency Introduction Case Description Discussion Dermatomyositis is an autoimmune condition classically A punch biopsy of her rash showed atrophic epithelium with This case of overlap syndrome between dermatomyositis and characterized by symmetric proximal muscle weakness, dyskeratotic keratinocytes, vacuolar interface changes, superficial systemic lupus erythematosus presents a rare but important inflammatory muscle changes, and dermatologic abnormalities.1 perivascular and lichenoid inflammation, and pigment challenge to the primary care physician. Our patient presented Several studies have shown that the inflammatory myopathies, incontinence consistent with systemic lupus erythematosus initially with arthralgias and fatigue, symptoms more such as dermatomyositis, commonly overlap with other (SLE). The patient was started on prednisone 40 mg daily for a 2- characteristic of systemic lupus erythematosus. However, these connective tissue disorders, significantly complicating the week taper to 10 mg and hydroxychloroquine 200 mg daily with symptoms were followed by a facial rash that involved the diagnosis.2 The reported incidence of overlap syndrome ranges marked improvement in symptoms. Further lab work-up was nasolabial folds and periorbital regions more in line with from 11% to 40% in patients diagnosed with significant -
CXCL10 Could Drive Longer Duration of Mechanical Ventilation During COVID-19 ARDS
Blot et al. Critical Care (2020) 24:632 https://doi.org/10.1186/s13054-020-03328-0 RESEARCH Open Access CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS Mathieu Blot1,2*, Marine Jacquier2,9, Ludwig-Serge Aho Glele10, Guillaume Beltramo3, Maxime Nguyen2,4, Philippe Bonniaud3, Sebastien Prin9, Pascal Andreu9, Belaid Bouhemad2,4, Jean-Baptiste Bour5, Christine Binquet6, Lionel Piroth1,6, Jean-Paul Pais de Barros2,7, David Masson2,8, Jean-Pierre Quenot2,6,9, Pierre-Emmanuel Charles2,9 and Pneumochondrie study group Abstract Background: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). Methods: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. Results: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL- 10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. -
Supplemental File Supplemental Table 1: Co-Morbidity Definitions
Supplemental File Supplemental Table 1: Co-morbidity definitions NCD group UK Biobank self-reported illnesses included Hypertension Hypertension Essential hypertension Chronic cardiac disease Angina Cardiomyopathy Heart attack/myocardial infarction heart failure/pulmonary oedema Hypertrophic cardiomyopathy Coronary angioplasty (ptca) +/- stent Coronary artery bypass grafts Triple heart bypass Chronic respiratory disease Asthma Bronchiectasis Chronic obstructive airways disease/COPD Emphysema Emphysema/chronic bronchitis Fibrosing alveolitis/unspecified alveolitis Interstitial lung disease Other chronic respiratory problems Pulmonary fibrosis Diabetes Diabetes Diabetic eye disease Diabetic nephropathy Diabetic neuropathy/ulcers Type 1 diabetes Type 2 diabetes Cancer Any cancer diagnosis during lifetime Chronic liver disease Liver failure/cirrhosis Non-infective hepatitis Oesophageal varices Primary biliary cirrhosis Chronic kidney disease Diabetic nephropathy Immunoglobulin A (IgA) nephropathy Kidney nephropathy Polycystic kidney Renal failure not requiring dialysis Renal failure requiring dialysis Renal/kidney failure Prior stroke/TIA Brain haemorrhage Ischaemic stroke Stroke Subarachnoid haemorrhage Transient ischaemic attack (TIA) Other neurology disease Cerebral palsy Epilepsy Motor neurone disease Multiple sclerosis Myasthenia gravis Parkinson’s disease Psychiatric disease Depression Mania/bipolar disorder/manic depression Postnatal depression Schizophrenia Chronic inflammatory and Ankylosing spondylitis autoimmune rheumatic disease -
Nutritional Implications of GI-Related Scleroderma
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #148 Carol Rees Parrish, M.S., R.D., Series Editor Nutritional Implications of GI-Related Scleroderma Soumya Chatterjee Scleroderma (SSc) is an autoimmune disease characterized by progressive fibrosis of skin and various internal organs, including the lungs, heart, kidneys, and the gastrointestinal (GI) tract. Second only to skin disease, GI tract involvement is the next most common manifestation of SSc. Any part of the GI tract may be affected, leading to considerable impairment of quality of life. When GI involvement is extensive, severe malnutrition can occur and it can even result in death in about 20% of patients. Early recognition and management may alter the long-term outcome. Effective collaboration with gastroenterologists in the evaluation and management of SSc in a multispecialty partnership model has the potential to produce better outcomes and improve survival in these patients. This article discusses the nutritional implications and current evidence-based management recommendations for the wide range of GI manifestations in SSc. INTRODUCTION cleroderma, or systemic sclerosis (SSc), is originally coined (Gr., ‘skleros’ = thickening, ‘dermos’ an autoimmune disease of unclear etiology, = skin). There are two main subtypes of SSc, based on Scharacterized by progressive fibrosis of skin the extent of skin hardening: and various internal organs, an ongoing occlusive • limited SSc (lcSSc, formerly CREST syndrome) microvasculopathy, and abnormalities of the immune only involving the distal extremities (beyond system. There is wide variability in the prevalence of elbows and knees) and face. SSc worldwide. In the United States, about 250 cases per million Americans are afflicted with this disease. • diffuse SSc (dcSSc), where skin tightening is Progressive skin thickening is an integral part of the widespread, including the trunk and proximal disease, explaining how the term ‘scleroderma’ was extremities. -
Rheumatology Connections
IN THIS ISSUE Advances in the Diagnosis of CNS Vasculitis 3 | Association of Anti-PM-Scl Antibody-Associated Systemic Sclerosis & Inclusion Body Myositis 4 | Pregnancy & Rheumatoid Arthritis 6 | Rheumatology Education 7 | Pregnancy & Vasculitis 8 | Chronic Inflammation in Rheumatic Disease 10 | Predicting Anti-TNF-Therapy Responsiveness 12 | PROMIS in Inflammatory Eye Disease 13 | Rheumatic Immune-Related Adverse Events 14 Rheumatology Connections An Update for Physicians | Summer 2020 The Role of Chronic, Systemic Inflammation in Rheumatic Disease p. 10 24275_CCFBCH_20RHE1867409_ACG.indd 1 6/25/20 9:16 AM Cleveland Clinic’s Rheumatology From the Chair of Rheumatic and Immunologic Diseases Program is ranked among the top 2 in the nation in U.S. News & World Report’s “America’s Best Dear Colleagues, Hospitals” survey. As the Summer 2020 issue of Rheumatology Connections goes to print, I cannot believe how much has changed in just a few months. These are truly unprecedented times. The evolving COVID-19 pandemic has had a profound impact on clinical care, education and research. Rheumatology Connections, published by I continue to be inspired by the compassion and unwavering commitment of the medical Cleveland Clinic’s Department of Rheumatic and community to serve those in need. Immunologic Diseases, provides information on leading-edge diagnostic and management I have great admiration for the physicians who have continued to care for patients with chronic techniques as well as current research for physicians. rheumatic diseases with empathy and dedication throughout the pandemic. At Cleveland Clinic, our rheumatologists were nimble and flexible in converting as many patient visits as possible to Please direct any correspondence to: telehealth consultations.