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1. Criteria for Differentiation of Non-Bacterial and Haematogenous Osteomyelitis: A Case-Control Study With Prospective Verification of the Outcomes

Author

Mikhail M. Kostik, Olga L. Kopchak, Alexey I. Taschilkin, Vyacheslav I. Zorin, Alexey S. Maletin, and Alexander Yu. Mushkin

Subjects
children, non-bacterial osteomyelitis, chronic recurrent multifocal osteomyelitis, haematogenous osteomyelitis, diagnosis, criteria, sensitivity, specificity, Pediatrics, RJ1-570
Abstract

Background. Patients with haematogenous and non-bacterial osteomyelitis have similar clinical symptoms (pain in the nidus area, soft tissue swelling, fever) and laboratory signs (increased erythrocyte sedimentation rate, leukocyte count, C-reactive protein concentration). The criteria for distinguishing these two states are not determined. Objective. Our aim was to determine diagnostic criteria to differentiate haematogenous and non-bacterial osteomyelitis. Methods. The study included data of patients under the age of 18 years with non-bacterial or haematogenous osteomyelitis hospitalised to two clinical centres from 2009 to 2016. The diagnosis was established and re-verified according to archival data (medical history) and after two years of observation (at least once a year). Clinical, anamnestic and laboratory data (haemoglobin, leukocytes, leukocyte formula, platelets, ESR and C-reactive protein, CRP) as well as the results of radiation diagnostics (X-ray, CT scan, MRI or osteosyntigraphy) obtained at the disease onset were taken into account as potential diagnostic criteria. Results. Out of 145 patients with non-bacterial or haematogenous osteomyelitis, the diagnosis was re-verified in 138, of them non-bacterial osteomyelitis — in 91, haematogenous osteomyelitis — in 47. The following criteria had the highest diagnostic value for establishing cases of non-bacterial osteomyelitis: detection of bone destruction foci surrounded by osteosclerosis area [sensitivity (Se) 1.0; specificity (Sp) 0.79]; absence of fever (Se 0.66; Sp 0.92); the number of bone destruction foci > 1 (Se 0.73; Sp 1.0); CRP 55 mg/L (Se 0.94; Sp 0.73); negative results of bacteriological examination of the material from the bone destruction focus (Se 1.0; Sp 0.67). Conclusion. Diagnostic criteria for differentiation of non-bacterial and haematogenous osteomyelitis have been described. Further research on the efficacy of using these criteria to reduce the risk of diagnostic errors, decrease the diagnostic pause, reduce the risk of non-bacterial osteomyelitis complications is needed.

Published
2019
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2. DIFFERENTIAL DIAGNOSIS OF SYSTEMIC-ONSET JUVENILE ARTHRITIS AND RHEUMATIC MASKS OF ONCOHEMATOLOGICAL DISEASES: A RETROSPECTIVE COHORT STUDY

Author

Mikhail M. Kostik, Eugenia A. Isupova, Ekaterina A. Shilova, Ilya S. Avrusin, Yuri Y. Korin, Irina A. Chikova, Margarita F. Dubko, Vera V. Masalova, Ludmila S. Snegireva, Tatyana L. Kornishina, Ekaterina V. Gaidar, Olga V. Kalashnikova, Tatyana F. Panova, Olga L. Kopchak, and Vyacheslav G. Chasnyk

Subjects
systemic juvenile idiopathic arthritis, leukemia, malignant neoplasms, differential diagnosis, Pediatrics, RJ1-570
Abstract

Background. Patients with malignant oncohematological diseases (OHD) may have such symptoms as fever, lymphadenopathy, hepatosplenomegaly, joint pain, arthritis, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration, anemia that require differentiation from clinical implications of systemic juvenile idiopathic arthritis (sJIA).Objective. Our aim was to determine diagnostic criteria that can differentiate rheumatic masks of OHD from sJIA.Methods. The retrospective study included 86 children with sJIA and 21 children with OHD who had rheumatic masks and were hospitalized in rheumatological departments with an initial diagnosis of sJIA. OHD were represented by acute lymphoblastic leukemia (n = 17), neuroblastoma (n = 1), and lymphomas (n = 3).Results. Blast cells in the peripheral blood test were detected in 9/17 (53%) patients with acute leukemia at different times from the appearance of complaints and hospitalization. Diagnostic criteria for differentiating OHD from sJIA were the number of active joints 3 (diagnostic odds ratio, OR, 4.4, 95% confidence interval, CI, 1.5–13.2), CRP concentration < 15 mg/L (OR 5.6, 95% CI 1.7–18.4), platelets 307 109/L (OR 22.9, 95% CI 4.9–107.0), white blood cells 8.9 109/L (OR 50.2, 95% CI 6.3–401.3), albumin > 43.3% (OR 28.8, 95% CI 5.6–149.2), absence of exanthema (OR 39.8, 95% CI 8.4–188.5). The most frequent symptoms with the greatest specificity were night pain (sensitivity 0.57, specificity 1.0), bone pain (sensitivity 0.95, specificity 1.0), pathological fractures (sensitivity 0.14, specificity 1.0).Conclusion. The identified diagnostic criteria can be used for differential diagnosis of OHD with rheumatic masks and sJIA.

Published
2017
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3. DIFFERENTIATED APPROACH TO NON-BACTERIAL OSTEOMYELITIS TREATMENT IN CHILDREN: THE RETROSPECTIVE STUDY RESULTS

Author

Mikhail M. Kostik, Olga L. Kopchak, Irina A. Chikova, Eugenia A. Isupova, Vera V. Masalova, Margarita F. Dubko, Ludmila S. Snegireva, Olga V. Kalashnikova, Alexandr Y. Mushkin, and Vyacheslav G. Chasnyk

Subjects
children, non-bacterial osteomyelitis, pamidronic acid, tnf α inhibitors, Pediatrics, RJ1-570
Abstract

Differentiated Approach to Non-Bacterial Osteomyelitis Treatment in Children: the Retrospective Study Results Background. Low efficacy of the therapy of children with non-bacterial osteomyelitis remains a topical problem of modern pediatrics and rheumatology. Objective: Our aim was to assess the efficacy and safety of non-bacterial osteomyelitis treatment in children. Methods. A retrospective study of the case records of children with non-bacterial osteomyelitis has been carried out. The therapy efficacy (remission) was assessed by the following criteria: absence of fever, pain, clinically active lesions, laboratory disease activity. Laboratory and radiological methods were carried out during diagnosis of the pathological process, and subsequently every 3–6–12 months to assess disease activity depending on the initial injury extent of the skeleton. Clinical activity assessment was carried out by means of a visual analogue scale. Results. We analyzed treatment results of 52 children (68 therapy courses) with non-bacterial osteomyelitis. Nonsteroidal anti-inflammatory drugs were administered to 19 patients, sulfasalazine — to 7, methotrexate — to 9, pamidronic acid — to 18, inhibitors of tumour necrosis factor (TNF) α — to 15. Remission was achieved in 10 (53%) 4 (57%) 4 (44%), 16 (89%), and 11 (73%) patients (p = 0.001), respectively. Adverse events during treatment occurred in 21 (40%) children. No serious adverse events were reported. Conclusion. The efficacy of different regimens has been shown. It was found that pamidronic acid drug and TNF inhibitors were the most effective in treating children with non-bacterial osteomyelitis.

Published
2016
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4. Vertebral form of non-bacterial osteomyelitis: clinical and laboratory features and treatment characteristics

Author

Olga L. Kopchak, Aleksandr Yu. Mushkin, Mikhail M. Kostik, and Aleksey S. Maletin

Subjects
non-bacterial osteomyelitis, chronic recurrent multifocal osteomyelitis, spine, treatment, bisphosphonates, tnf-inhibitors, Surgery, RD1-811
Abstract

Objective. To study clinical and laboratory features of spinal lesions associated with non-bacterial osteomyelitis (NBO), to define the role of surgery in its diagnosis and treatment, and to analyze the efficacy of different treatment regimens. Material and Methods. Retrospective two-center cohort of 54 children with NBO, including 18 patients with vertebral le- sions was studied. The level of evidence is 3. Results. Vertebral form of the non-bacterial osteomyelitis is characterized by high frequency of multifocal bone lesions. The features of clinical and X-ray manifestations of the vertebral form of NBO, its diagnosis and medical treatment are presented. First of all NBO should be differentiated from infectious (tuberculosis) and neoplastic lesions of the skeleton. Non-steroid anti-inflammatory drugs are not effective for the relief of pain in the NBO vertebral form, preference should be given to bisphosphonates and TNF-a inhibitors. Indications and volume of surgical techniques for diagnosis and treat- ment of this pathology are specified. Conclusion. Management of patients with the vertebral form of NBO should be interdisciplinary and carried out with the assistance of doctors of various specialties – pediatricians, rheumatologists, orthopedists, surgeons, phthisiatrician, etc.

Published
2016
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5. The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study

Author

Mikhail Kostik, Alexey S Maletin, Alexander Yu. Mushkin, and Olga L Kopchak

Subjects
Male, Sternum, Cohort Studies, 0302 clinical medicine, Immunology and Allergy, Medicine, Orthopedic Procedures, 030212 general & internal medicine, Family history, Child, Response rate (survey), Bone Density Conservation Agents, Diphosphonates, medicine.diagnostic_test, Osteomyelitis, Magnetic Resonance Imaging, Treatment Outcome, Antirheumatic Agents, Child, Preschool, Female, Joint Instability, medicine.medical_specialty, Adolescent, Immunology, Spinal Curvatures, 03 medical and health sciences, Sex Factors, Rheumatology, Internal medicine, Humans, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Foot Bones, Chronic recurrent multifocal osteomyelitis, Infant, Retrospective cohort study, Magnetic resonance imaging, medicine.disease, Radiography, Sulfasalazine, Methotrexate, Case-Control Studies, Concomitant, Tumor Necrosis Factor Inhibitors, Tomography, X-Ray Computed, business, Spondylitis
Abstract

Chronic non-bacterial osteomyelitis (CNO) is a group of immune-mediated diseases which appears in bone inflammation, destruction and some orthopaedic consequences, especially in the cases of spinal involvement. This study is to compare characteristics and treatment outcomes of CNO patients with spinal involvement. The retrospective cohort study included data from 91 pediatric patients with CNO. The diagnosis is based on Jannson's criteria with morphological confirmation (nonspecific chronic inflammation). Spine involvement detected by X-ray, computed tomography, magnetic resonance imaging, and bone scan in 29 (31.9%) patients. No differences in the family history, concomitant immune-mediated diseases between spinal (SpCNO) and peripheral (pCNO) forms of CNO have been revealed. Only 5 (10.2%) SpCNO patients (10.2%) had monofocal monovertebral involvement. The main risk factors of spinal involvement were female sex: RR = 2.0 (1.1; 3.9), sensitivity (Se) = 0.66, specificity (Sp) = 0.6; multifocal involvement: RR = 2.1 (0.9; 5.0), Se = 0.83, Sp = 0.37; no foot bones involvement: RR = 3.1 (1.3; 7.5), Se = 0.83, Sp = 0.5; sternum involvement RR = 2.3 (1.3; 4.1), Se = 0.24, Sp = 0.94. In the linear regression analysis only female sex (p = 0.005), multifocal involvement (p = 0.000001) and absence of foot bones involvement (p = 0.000001) were independent risk factors of spinal involvement (p = 0.000001). The response rate on bisphosphonates and tumor necrosis factor-a inhibitors was 90.9% and 66.7%, consequently. Only 4/29 (13.8%) SpCNO patients underwent surgery due to severe spinal instability or deformities. The spinal involvement is frequent in CNO and could be crucial for choosing a treatment strategy. Bisphosphonates and TNFa-inhibitors could be effective treatment options for severe SpCNO.

Published
2019
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6. Comparison of different treatment approaches of pediatric chronic non-bacterial osteomyelitis

Author

Olga L Kopchak, E. Isupova, Mikhail Kostik, Alexander Yu. Mushkin, and I.A. Chikova

Subjects
Male, medicine.medical_specialty, Adolescent, Immunology, Pamidronate, Disease, Gastroenterology, law.invention, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Randomized controlled trial, law, Sulfasalazine, Internal medicine, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', Child, 030203 arthritis & rheumatology, Bone Density Conservation Agents, business.industry, Osteomyelitis, Anti-Inflammatory Agents, Non-Steroidal, medicine.disease, Methotrexate, Treatment Outcome, Child, Preschool, Cohort, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Chronic non-bacterial osteomyelitis (CNO) is a chronic inflammatory bone disease which usually manifests in children and adolescents. There are a few data about pathogenesis and treatment. The aim of the study to compare the efficacy of different treatment approaches in pediatric CNO cohort patient. Fifty two children (25 boys and 27 girls) with CNO with average age at the onset of the disease 8.4 years (5.4; 11.0), number of foci − 3.0 (2.0; 6.0, incl. multifocal cases in 80.8%). Non-steroid anti-inflammatory drugs (NSAID) was the first-line treatment for non-vertebral cases, as well as pamidronate (PAM) for vertebral involvement. Second-line treatment includes sulfasalazine (SSZ), methotrexate (MTX), PAM and tumor necrosis factor-α inhibitors (TNFα-inh). We evaluated the dynamics of pain, patient’s and physician’s (MDVAS) assessment with visual-analog scale (VAS) and ability to each medication to achieve remission of CNO activity. According to the NSAID, MTX, SSZ, PAM and TNFα-inh groups the following data were registered: patient’s VAS: − 14.2% (p = 0.05), − 50.0% (p = 0.04), − 23.1 (p = 0.89), − 83.3% (p = 0.0001), − 73.6% (p = 0.0007); painVAS: − 21.9% (p = 0.01), − 18.6% (p = 0.13), + 36.4 (p = 0.89), − 79.7% (p = 0.00016), − 74.1%, (p = 0.0015); MDVAS: − 13.8% (p = 0.13); − 56.4% (p = 0.09), + 30.8% (p = 0.89), − 74.7%, (p = 0.0001), − 82.1 (p = 0.0015) respectively. The ability of each treatment strategy to achieve the CNO remission was 52.6%, 44.4%, 57,1%, 88.8% and 73.3%, respectively (log-rank test, p = 0.001). The efficacy of treatment approaches for CNO depended on the severity of the disease. NSAID, methotrexate, and sulfasalazine were effective in forms without spine involvement, but pamidronate and TNF-a inhibitors were useful in vertebral forms of CNO. Pamidronate and TNF-a inhibitors more extensively suppressed CNO activity. The randomized controlled trials for assessment of the efficacy and safety of these medications is mandatory to confirm these results.

Published
2018

7. AB0962 Clinical and laboratory characteristics of non-bacterial osteomyelitis: data analysis of 91 patients

Author

M. Kostik, Olga L Kopchak, and Alexander Yu. Mushkin

Subjects
medicine.medical_specialty, Pathology, medicine.diagnostic_test, business.industry, Osteomyelitis, medicine.disease, Gastroenterology, Bone scintigraphy, Concomitant, Internal medicine, Etiology, Medicine, Blood test, Femur, medicine.symptom, business, Prospective cohort study, Bone pain
Abstract

Background Non-bacterial Osteomyelitis (NBO) is a sterile inflammatory bone disorder of unknown etiology. It typically affects children and most commonly presents with bone pain and/or swelling. Objectives The aim of study is to evaluate clinical and laboratory features of non-bacterial osteomyelitis in children. Methods Our retrospective – prospective study was included 91 patients with NBO. A routine blood test (WBC, platelets, ESR, C-reactive protein (CRP) and hemoglobin levels), a radiological examination and a bone biopsy with evaluation bacteriological and morphological data were performed in all patients. Results The mean age of onset NBO was 7.3 years (2.5; 10.6). We did not reveal any gender peculiarities in our study. Family history of immune-mediated diseases is found in 5/75 (6.7%) in prospective group. Concomitant immune-mediated diseases were noted in 62/89 (68.1%). Diagnostic delay was 6.3 (2.0; 17.8) months. The radiological examination was performed in the following ratio: X-rays - 91 (100.0%), CT - 79 (86.8%), MRI - 66 (72.5), including MRI “whole body” with 15 pts, bone scintigraphy - 54 (59.3%). Monofocal form was registered in 1/3 cases. 2/3 cases was presented as a typical multifocal process with predominant involvement femur - 37 (40.7%), bone of foot - 36 (39.6%), tibia - 33 (36.3%), spine – 29 (31.9%). The number of foci is 3.0 (1.0; 6.0). We did not revealed any significant differences in quantity of WBC, platelets, hemoglobin level, ESR, CRP). Evidence confirming NBO was a negative bone biopsy in 100.0% cases. However, morphological data were as non-specific, as granulomatous inflammation. Conclusions NBO is determined as a primarily chronic multifocal process without specific clinical and laboratory peculiarities, associated with immune-mediated diseases. Diagnose must be established on morphological and bacteriological data bone biopsy. Disclosure of Interest None declared

Published
2017
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8. Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part two

Author

David Kern, Masato Yashiro, Gerd Horneff, Ana P. Sakamoto, Berent J. Prakken, Paula Vähäsalo, Juergen Brunner, Ezgi H. Baris, Helen McCarthy, Janet E. McDonagh, A. Grom, Adriana Albu, Lenka Linkova, I. Nikishina, Daniel Álvarez de la Sierra, Bruno Papia, Peggy Lee, Luisa Giannone, Tobias Schwarz, Mekibib Altaye, Margarita Onoufriou, Tatiana Sleptsova, N. Ruperto, O Thana, A. Baheti, Ilonka Orbán, Kai Lehmberg, F. Zulian, Helga Sanner, Karin Palmblad, Kousuke Shabana, Sebastiaan Vastert, Marta Rusmini, Olga Vougiouka, Dirk Holzinger, D. Shaikhani, Shouichi Ohga, Ismail Dursun Dursun, Claire T Deakin, Ingrid Herta Rotstein Grein, Maria Trachana, Ariane Klein, Eugenia Enriquez, Angelo Ravelli, Paul A. Brogan, L.S. Nazarova, Laila Al Shaqshi, Paulina Vele, Liana Guerra, Antonia Pascarella, Jelena Vojinovic, Juliana Molina, Kjell Tullus, S. Rodionovskaya, Chris Scott, A. N. Olivieri, Cliff Taggart, Clare Heard, Ricardo Pujol Borrell, Jens Klotsche, Grendel Burrell, Oriany L. Pereira, Silvia Giliani, Sandra Pereira, Jennifer Horonjeff, Beth A. Mueller, Lyudmyla M. Byelyaeva, Sergio Tufik, Carlo Agostoni, Valentina Muratore, Rostislav M. Filonovich, Fiona Hawke, Virginia Messia, Bo Magnusson, Kerry West, Sara Murias, Mustafa Doğan, Hafize Emine Sönmez, Annet van Royen-Kerkhof, K. Minden, Raquel Campanilho-Marques, Reem Abdawani, Maria Ceci, Maria Ekelund, Seza Ozen, Ratna Puri, Girolamo Luppino, Shannon Carr, Rita A. Amorim, K Kobrová, Rachael D. Wright, Chantal Job-Deslandre, Daniel J. Lovell, Jorge Kalil, Yi-jin Gao, Kubra Ozturk, Fulvio Parentin, Ursula Fearon, Frank Weller-Heinemann, Elizabeth Ang, Charles A Mebus, Andrea Superti-Furga, Alina Ferster, Rikard Wicksell, Mohammadreza Modaressi, F La Torre, Ela Tarakci, Wendy Thomson, Giorgia Malighetti, Antonio Eleuteri, Helena K. Khrustaleva, Alan Easton, Alexander Mushkin, Sara Marsal Barril, Erkan Demirkaya, Florence Kanakoudi-Tsakalidou, Diana Ekdawy, Lana Tambić Bukovac, Suvi Peltoniemi, Nur Arslan, Hermine I. Brunner, Tim Rapley, Donatella Vairo, Kirill Savostyanov, Fumiko Okazaki, Rachel Corkhill, Tufan Kutlu, MG Alpigiani, Fabio Fernandes Morato Castro, Juliana Farhat, Butsabong Lerkvaleekul, Scolozzi Paolo, Akihiko Saitoh, Jason Dare, Gustavo Rocha, Tatiana V. Viktorova, Riva Brik, Jason Palman, Fabrizia Corona, Susan Nielsen, Johannes Roth, Ma. Theresa M. Collante, Leonardo Oliveira Mendonça, D. Alexeev, Randy Q. Cron, Sriharsha Grevich, Andrea L. Jorgensen, Lúcia Maria de Arruda Campos, Kiran Nistala, Fernando Martins, R. Cimaz, Angela C. Mosquera, Ruy Carrasco, Reyhan Dedeoglu, Giovanni Filocamo, J. Dare, Paula Keskitalo, Ana J. D. F. C. Lichtenfels, Florence Uettwiller, Umberto Conte, Gecilmara Salviato Pileggi, Michal Uher, Mercedes Chan, Sarka Fingerhutova, Anne M. Stevens, Peter Bale, Mikel Alberdi-Saugstrup, Olga L Kopchak, Thomas A. Griffin, Constantin Ailioaie, Clifton Bingham, Ekaterina Alexeeva, Loshinidevi D Bathi, Jane Hurst, AnnaCarin Horne, Laura Muntean, Nermin Uncu, Mara Carraro, C Vargas, Lorenzo Quartulli, Ayşenur Paç Kısaarslan, Angela Mauro, F. Corona, Donato Rigante, Helen J. Lachmann, Ana Cordeiro, Ivan Foeldvari, Faysal Gok, Tatiana Gonzalez, S. S. M. Kamphuis, Hasret Ayyildiz-Civan, Claudia Pastorino, Gleice C. S. Russo, J. B. Kuemmerle-Deschner, Serena Pastore, Nigel Klein, M. Jorini, Tatjana Freye, Maria Tsolia, Philippe Jacqmin, Suzanne M M Verstappen, Syuji Takei, Khalid Hussain, Renzo Marcolongo, Yuichi Yamasaki, Sharmila Jandial, K. Leon, Maria Pia Sormani, T. A. Simon, Mohammed Muzaffer, Catalina Mosquera, Clovis Aa Silva, Zelal Ekinci, Zübeyde Gündüz, Bernd Denecke, Felicitas Bellutti Enders, Despina Eleftheriou, Ishbel MacGregor, Andrew Cant, Luisa Bonafé, Valda Staņēviča, Helen E. Foster, Alberto Tommasini, Nora Bartholomä, Nural Kiper, A. Kardolus, Eloisa Bonfa, Alessandro Consolaro, Lillemor Berntson, Umberto Garagiola, Richard K. Vehe, Vanessa Bugni Miotto e Silva, Chihaya Imai, Kathleen G. Lomax, Brian Best, Barbara Bonafini, M. Toth, D. Rigante, Eiman Abdalla, Leona Prochazkova, Lucy Wedderburn, Lovro Lamot, S. Verazza, Raffaella Carlomagno, Gillian I. Rice, Norm Ilowite, K. de Leeuw, Havva Evrengül, Jerold Jeyaratnam, Andrew Zeft, Andrea Taddio, R. Podda, Samuel Cassidy, Grant S. Schulert, Silvia Rosina, Marija Jelušić, Olivier Gilliaux, Rubén Burgos-Vargas, Mao Mizuta, Akihiro Yachie, Angel Phuti, Antonio Zea Mendoza, Emily Boulter, Zane Dāvidsone, Sofia Torreggiani, Marco Cattalini, Natali W. Gormezano, Fatma Dedeoglu, Hercília Guimarães, A. Insalaco, Andrea Coda, Viktor A. Malievsky, Thomas Zumbrunn, Agostino Nocerino, Ronald Pederson, Katarzyna Kobusinska, Anasuya Hazra, Ananadreia S. Lopes, Elena Campione, Toshiyuki Kitoh, Elena Tsitsami, Henny G. Hotten, Radka Kaneva, R. J. E. M. Dolhain, Ndate Fall, Francesco Licciardi, Deepti Suri, G. D’Angelo, Valentina Seraya, Elżbieta Smolewska, Anastasia Dropol, Ezgi Deniz Batu, Andreas Woerner, Christine Arango, Nadia E. Aikawa, Zoilo Morel, Megan Yuasa, Sandra Ammann, Erbil Unsal, Tomohiro Kubota, Toshitaka Kizawa, Fabrizio De Benedetti, Catherine Laing, Liudmila Rakovska, Yonatan Butbul Aviel, J-Peter Haas, Marta Minute, Christine Alvey, Vasiliko Dermentzoglou, Vania Schinzel, Isree Leelayuwattanakul, Ekim Taskiran, Gabriele Simonini, N. Martin, Nathalie Canham, Nicky Brice, Beatrice Vergara, Ika Birkić, Cengizhan Acikel, Johannes-Peter Haas, Ruth Fritsch, Alisa Vitebskaya, Fatih Yazici, Iva Brito, Nataša Toplak, Veronica Moshe, Gordon J Hendry, Nadia Luca, Deniz Doğru-Ersöz, Marco Matucci-Cerinic, Claudia Toppino, Zoë Johnson, Beatrice Goilav, Siyaram Didel, K. Marzan, Tamar B. Rubinstein, Angela Barnicoat, Peter Nourse, Thita Pacharapakornpong, Adele Civino, Inmaculada Calvo Penades, H. I. Brunner, Massimo Imazio, V. Gerloni, Ayla Kacar, Heinrike Schmeling, Marija Perica, Silvestre García de la Puente, Tadej Avcin, Filipa Oliveira-Ramos, S. Arsenyeva, Phillip J Hashkes, Sabrina Schuller, Adriana Rodriguez Vidal, Kathy de Graaf, Giedre Januskeviciute, M. Kaleda, Lee Dossetter, Jelena Basic, Elena Kaschenko, Erik Sundberg, Gizem Pamuk, Marek Zak, I. Foeldvari, Rachael Quarmby, Marc D. Natter, Antonarakis Gregory, P. A. Brogan, João Eurico Fonseca, Andrea Jorgensen, Ana F. Mourão, Gaurav Gulati, Yelda Bilginer, Banu Acar Celikel, Utako Kaneko, Karen L. Durrant, Alice Grossi, Maurizio Aricò, Ibrahim Al Zakwani, Yildirim Karslioglu, Takuji Murata, Monika Stoll, Maria Teresa Terreri, Ariana Kariminejad, Teresa A. Simon, Laura B Lewandowski, Marina Garcia Prat, Walter G. Ferlin, Albena Telcharova, Giovanni Maria Severini, Judith Wienke, Panagiota Nalbanti, Hakan Poyrazoglu, Athimalaipet V. Ramanan, Manisha Lamba, Z. Guo, J. Bohnsack, Norberto Guelbert, John F. Bohnsack, Lucy R. Wedderburn, Elvira Cannizzaro Schneider, Raul Gutiérrez Suárez, Debra Grech, Yonit Reis, Chris Pruunsild, Amit Rawat, Nienke M. ter Haar, Hiroshi Tamai, Alexander Pushkov, A. De Fanti, Valentina Marzetti, Sheila Weitzman, I. E. M. Bultink, Dilek Keskin, Sania Valieva, Klaus Tenbrock, Ana Luisa Rodriguez-Lozano, Lianne Kearsley-Fleet, Luca Messina, Chiara Gorio, Amra Adrovic, Stephanie J. W. Shoop, Davide Cumetti, Sana Al Zuhbi, Helena Khrustaleva, E. Zirkzee, Elio Castagnola, Clarissa Pilkington, Jingyao Leong, Vitor A. Teixeira, Reinhard Würzner, Sonia Melo Gomes, Orla Killeen, Antony C. Fisher, Sevket Erbil Unsal, Edward M. Behrens, Kristiina Aalto, Rebecca Nicolai, Thomas C. Stock, Luiz Cláudio Danzmann, Y. K. O. Teng, Stephen D. Marks, Fotios Papachristou, Valda Stanevicha, Richard Saffrey, Elizabeth Ralph, Johannes Peter Haas, Mary Slatter, Maria Tsinti, Mehmet Alikasifoglu, Mónica Martínez Gallo, Rayfel Schneider, Rosa Maria Rodrigues Pereira, Maria F. D. A. Giacomin, Alfésio Luís Ferreira Braga, Giulia Camilla Varnier, James McElnay, Jessica Foster, Ingrida Rumba-Rozenfelde, Francesca Minoia, Laurence Goffin, Roger C. Allen, Zehra S. Arıcı, Mette Nørgaard, Alberto Martini, Hofer Michaël, Andreas Eikelberg, Junko Yasumura, Maria José Santos, Tom Wolfs, Ada B. Sinoplu, Natalia Balera Ferreira Pinto, Michael Lang, Umberto Corpora, Hidenobu Kaneyasu, Fiorenzo Gaita, Olga Lomakina, Dimitrina Mihaylova, Gian Luca Erre, Fugen Cullu-Cokugras, Mesut Topdemir, Sriram Krishnaswami, Irina Nikishina, Noortje Groot, S. Pastore, Joke Dehoorne, Paula Estanqueiro, Shafe Fahoum, Francisca Aguiar, Mabel Ladino, Nico M Wulffraat, Jana Franova, Helena Erlandsson-Harris, Denise Pires Marafon, Adrian Liston, Edward H. Schuchman, Jaime C. Branco, Maria Teresa R. Terreri, Radoslava Saraeva, Ulrika Järpemo Nykvist, Maria Cristina Maggio, Kazuko Yamazaki, Lídia Teixeira, Hanquinet Sylviane, Ricardo Yepez, Susan Maillard, Tommy Gerschman, G. Horneff, Anne-Louise Ponsonby, Meredith Riebschleger, Alessandra Alongi, José Melo-Gomes, Iris Haug, Maria De Iorio, Ekaterina Alekseeva, Jan-Inge Henter, Elisa Pisaneschi, H. Kupper, Martina Niewerth, Berta López Montesinos, Shunji Hasegawa, Zahra Hadipour, R. M. Kuester, Silvia Maestroni, Pilar Guarnizo, Antonio Brucato, Tamaki Nakamura, Gustavo Antonio Moreira, Chaim Putterman, A. Hospach, Joost Frenkel, Svetlana O Salugina, A. Ravelli, Pavla Dolezalova, Gunnar L. Olsson, Eva González-Roca, Ellen Dalen Arnstad, Mohammad Alhemairi, Tina Hinnershitz, P. Quartier, Yildirim Karsioglu, Davinder Singh Grewal, Sergio Davì, Gökçen D. Tuğcu, Tomo Nozawa, Emily Robinson, M. C. Maggio, Maria Ballabio, Eleonora Bellucci, Alexei A. Grom, Rosa M. Pereira, Federica Vanoni, Shumpei Yokota, Justine A. Ellis, Helen Bristow, Mohammad-Hassan Moradinejad, Ricardo Russo, Harun Evrengül, Mario Abinun, Laura Carenini, Francesca Santarelli, C. Wallace, Maria Beatriz Fonseca, Timothy Beukelman, Saša Sršen, Véronique Hentgen, Sezgin Sahin, Silvia Zaffarano, Salvatore Albani, Valentin Brodszky, Clovis A. Silva, Graciela Espada, Jana Pachlopnik Schmid, Margaux Gerbaux, Stefano Stagi, Valentina Leone, Brian Leroux, Isabelle Koné-Paut, Gabriella Giancane, Soley Omarsdottir, Benedetta Schiappapietra, Alessandra Carobbio, Ricardo Menendez-Castro, Yoshifumi Kawano, Ozge Erdemli, Monia Lorini, Arjan Boltjes, Ellen Nordal, Carol A. Wallace, Mustafa Çakan, Reni Tzveova, Stefano Lanni, Salah Shokry, Kirsty McLellan, Qiong Wu, Nilay Arman, Adelina Tsakova, Michael W. Beresford, A. Consolaro, Francesca Bovis, Margarita Ganeva, Christoph Kessel, A. Martini, Taichi Kanetaka, Andre Schultz, Flora McErlane, Ronnie Wang, Mojca Zajc Avramovič, Thaschawee Arkachaisri, Boris Huegle, Funda Öztunç, Jane E Munro, Yanick J. Crow, Hiroyuki Wakiguchi, Rita Fonseca, Kim E. Nichols, Mia Glerup, Nils Venhoff, R. Filonovich, Erika Van Nieuwenhove, Nadia Rafiq, Elena Kamenets, Yasuo Nakagishi, Giampietro Farronato, Consuelo Modesto Caballero, Tulay Erkan, Jan Bonhoeffer, Jack Bukowski, Myrthes Toledo Barros, Gladys C. C. Esteves, Mirta Lamot, Rosa Alcobendas, Cláudia Moura, Florencia María Barbé-Tuana, Joo Guan Yeo, Mark Friswell, Yuko Sugita, Ari Shapiro, Nagla Abdelrahman, Phu-Quoc Lê, Kevin Murray, Susanne M Benseler, Anna Monica Bianco, J. Kalabic, Ana Catarina Duarte, Ivan Caiello, Joyce Davidson, Maria Isabel Gonzalez Fernandez, Larisa Zajtseva, Ebun Omoyinmi, Jaime de Inocencio, Dragana Lazarevic, Ritambhra Nada, Claudia Saad-Magalhães C, G. Conti, Andrew Gennery, Caroline Jones, Christophe Lelubre, Brian Rusted, Geneviève Lapeyre, Giulia Zani, Alina Boteanu, Maria T. Terreri, Nataliya Panko, Julia Albrecht, Federica Mongini, Lucio Giordano, Daniela Kaiser, Robert Nelson, Hans-Iko Huppertz, Gonca Keskindemirci, Karla Ištuk, Raffaele Strippoli, Dorota Rowczenio, Emma MacDermott, Roberta Caorsi, Emiliano Marasco, Sandra Sousa, Fatoş Yalçınkaya, Jaanika Ilisson, Yuki Kimura, Marco Turco, Nami Okamoto, Parveen Bhatti, Ekaterina M. Kuchinskaya, Stefano Volpi, Min Wang, Jeffrey M. Craig, M. Bijl, Giusi Prencipe, Fatemeh Tahghighi, W. van Dijk, Christiaan Scott, Masaki Shimizu, Alexey Maletin, Braydon Meyer, Joost F Swart, Sylvia Costa Lima Farhat, Anna Taparkou, R. Fritsch-Stork, Paolo Cressoni, Reiji Hirano, I. Chyzheuskaya, Stefania Simou, Kseniya Isayeva, Mariluz Gámir Gámir, Paivi Miettunen, Francesca Ricci, Ruta Šantere, George Lazaros, Madeleine Rooney, Stefan Stefanov, Huseyin Ozkan, Céline La, Boris Hügle, Vita Dolžan, P. Barone, R. Gallizzi, Aline L. de Oliveira, Silvia Federici, Lauren J. Lahey, Kimme L. Hyrich, Claudia Saad-Magalhães, Selçuk Yüksel, Valda Stanevica, Silvia De Pauli, Seid-Reza Raeeskarami, Calin Lazar, Sema Akman, Laurence Chatel, Kirsten Minden, Ismaiel A. Tekko, Philipp Henneke, E. Cortis, Elena Košková, Gil Amarilyo, Ana M. Marín Sánchez, Antonella Insalaco, Z. Birsin Ozcakar, Melissa Mariti Fraga, Lena Klevenvall, Luis Lira, Phoi-Ngoc Duong, Tatiana Bzarova, Neus Quilis, Wilco de Jager, Gary Sterba, Rina Denisova, Miroslav Harjacek, Eve M D Smith, N Ruperto, Gemma Lepri, Evgeniya Chistyakova, Rachel Kaufmann, Liliana Lourenço Jorge, Violeta Panaviene, Helena Canhão, Riccardo Belli, Grigoris Pardalos, Larisa I. Zajtseva, Nicolino Ruperto, Ezgi Batu, Paola Montesano, Alexander Solyom, Nicola Smith, Ales Janda, Sagar Bhattad, Liora Harel, Philip N. Hawkins, Gozde Yucel, François Willermain, Paolo Picco, Alessandro Rimini, Gordana Susic, Esi M. Morgan, Jessica Beckmann, Arina Lazareva, Agustin Remesal, Özge Altuğ Gücenmez, Troels Herlin, Andreas Groll, T. Yuraga, Ekaterina Zaharova, Adriana E. M. Sallum, Zeynep Birsin Özçakar, D. Milojevic, Can Kosukcu, Isabella Ceccherini, Sandrine Lacassagne, Tania M. Castro, R. Consolini, Klaus Müller, Dogan Simsek, Frank Rühle, Katia Kozu, Femke van Wijk, Yasin Sahin, Jonathan S. Hausmann, Gokalp Basbozkurt, M. Cattalini, Mª José Santos, Norman T. Ilowite, Adriana M. E. Sallum, Simona Rednic, Sirisucha Soponkanaporn, Giancarla Di Landro, Semanur Özdel, Timothy R. Radstake, Anastasia Wiener, Betül Sözeri, Estefania Quesada-Masachs, E. Zholobova, Joshua Newson, Ozgur Kasapcopur, Davide Montin, Terence Flood, Amir Mendelson, Manuela Pardeo, Flávia Heloísa dos Santos, Jamie Eaton, Vignesh Pandiarajan, Lyudmila Belyaeva, Edson Amaro Junior, Claudio Arnaldo Len, Tamás Constantin, Livia de Freitas Keppeke, Cristina Ferrari, Margarita Soloshenko, C. Rabinovich, David Popp, Jeremy Sokolove, Jaymi Taiani, Chiara Passarelli, de Min Cristina, José Costa, Stefanie Herresthal, Thomas Giner, Laure Caspers, Dilek Konukbay, Ulrich Salzer, Jorre S. Mertens, Marijan Frković, Yosef Uziel, Sabrina Chiesa, Luisa Bracci-Laudiero, Anders Fasth, Raul A. Chavez Valencia, Jordan T. Jones, Francesca Lancini, Alessandra Ferrari, Dana Nemcova, Mark Difrancesco, Ricardo Figueira, John Mitchell, Zohreh Nademi, E. Fedorov, Thomas Vogl, Carine Wouters, Mónica Eusébio, Hannah Leahey, Alessandra Pontillo, Marco Gattorno, Mandica Vidović, Lucas L. van den Hoogen, Mikhail Kostik, Giovanni Corsello, Gian Marco Moneta, Richard Mouy, Mariana Rodrigues, Veronica Medeghini, Gökçe Gür, Lucas Kich Grun, Stephan Ehl, Edi Paleka Bosak, Walter Ferlin, Hanna Lythgoe, Tsuyoshi Yamatou, Navdha R. Ramchurn, Carolina Furtado, Estefania Barral, Cecilia Lazea, Nikolay Tzaribachev, Vahid Ziaee, Fatemeh Hadipour, Alberto Sifuentes Giraldo, Kimberly Gilmour, Marite Rygg, Anna Valenti, María M Katsicas, Raju Khubchandani, Despoina Maritsi, Alessandra Tesser, R. M. Laxer, Clotilde Alizzi, Francisco Rivas-Larrauri, Aysen Tezcaner, Anne Dennos, Vasiliki Tzimouli, Vibeke Strand, Banu Acar, Fabio Candotti, Kseniia V. Danilko, Joachim Schultze, María Luz Gámir Gámir, Alessia Omenetti, Berit Flatø, Ruth Eraso, Bernard Lauwerys, Angela Pistorio, Andressa G. F. Alves, Gerd Ganser, Sara Signa, Ana Lopes, Emese Kiss, Charlene Foley, Sylvia Kamphuis, Maja Di Rocco, Kenan Barut, Ilaria Parissenti, Aida Koka, Nicholas Ng, Francis Corazza, Vinícius L. Braga, Laura E. Schanberg, Karin Beutel, Camila Hirotsu, Jonathan D Akikusa, Mihaela Sparchez, Karoline Ehlert, Jordi Anton, Adriana M. Sallum, Maria Cristina Castiglione, Surjit Singh, Julie Jones, Katya Temelkova, Tania S. Amin, Jasmin B Kuemmerle-Deschner, Samantha Bell, Sakda A.-O. Vallipakorn, Manuel Salgado, Filipa Ramos, Balahan Makay, Nadezhda Tsurikova, Gianmaria Viglizzo, Rosalba Ferraro, Sandra Hansmann, Nilgün Çakar, Ismail Dursun, Maria Stavrakidou, T. Bzarova, Sally Pino, Dhouib Amira, Salla Kangas, Antonella Meini, Dirk Foell, Dolunay Gürses, Dace Bērziņa, A. Speziale, Juan I. Arostegui Gorospe, Kelly L. Mieszkalski, Dawn M. Wahezi, S. Davì, Radoslav Srp, Daniel J. Kingsbury, Alexei A Grom, Falcini Fernanda, Peng Yin, Claire T. Deakin, Eva Hlavackova, Pavla Doležalová, Maria Mercedes Picarelli, Ezgi D. Batu, Alessandra Tricarico, Soamarat Vilaiyuk, Ivan Costa-Filho, A. Civino, Lukas Hackl, Pilar Gomez, Michael Hofer, M Manuela Costa, Zbigniew Zuber, Elena Ligostaeva, Carlos D. Rose, Jozef Hoza, Pranoot Tanpaiboon, Bonnie Vlahos, Sandra Garrote Corral, Martina Finetti, Giedre Grigelioniene, Susanne M. Benseler, X Wei, Pieter Van Dijkhuizen, Lee Nelson, Elettra Santori, David Martino, Anju Gupta, Nuray Aktay Ayaz, Noa Rabinowicz, Susan Shenoi, Rachel Chiaroni-Clarke, Claudia Bracaglia, Ruhan Düşünsel, M. Hofer, Rolando Cimaz, Juan I. Aróstegui, Ana Filipa Mourão, Ivonne Arroyo, Laura Damian, Marco F. C. D. Silva, D. J. Lovell, Marta Torcoletti, Clara Malagón, Luisa Klotz, Krisztina Sevcic, Douglas Veale, Belen Serrano Benavente, N. Groot, Polyxeni Pratsidou, Nicole Johnson, Karen Wynne, SR Rodionovskaya, Melania Saifridova, Kaara Tiewsoh, Ryan F. Donnelly, Fernanda Falcini, Valérie Badot, M. G. Alpigiani, L. Breda, Farida Abduragimova, Veronika Gjertsen Rypdal, Sophie Hambleton, E. Chalom, Anna Horne, Antonio Novelli, O. Kostareva, Panagiotis Tziavas, Yara Barrense-Dias, Cecilia Bava, Sarah Ringold, William H. Robinson, Sirirat Charuvanij, D. Kingsbury, Shuichi Ito, Luiz A. A. Pereira, Marcus Herbert Jones, S. I. Valieva, Flavio Sztajnbok, Florence Guilhot, Cristina de Min, Adriana Diaz-Maldonado, Simone A. Lotufo, Beril Talim, M. Heinrich, Paul Newland, and Laura Pagani

Subjects
030203 arthritis & rheumatology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Rheumatology, business.industry, 030220 oncology & carcinogenesis, Family medicine, Pediatrics, Perinatology and Child Health, medicine, Immunology and Allergy, business, Paediatric rheumatology
Published
2017
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9. SOPOSTAVITEL'NYY ANALIZ NEBAKTERIAL'NOGO I OSTROGO GEMATOGENNOGO OSTEOMIELITOV

Author

Olga L Kopchak, A.Yu. Mushkin, and M.M. Kostik

Subjects
Osteopathy, RZ301-397.5
Abstract

Небактериальный и острый гематогенный остеомиелиты (НБО и ОГО соответственно) - воспалительные заболевания опорно-двигательного аппарата, преимущественно встречающиеся у детей и подростков. Заболевания в ряде случаев могут иметь сходную клиническую картину, в связи, с чем требуют проведения дифференциальной диагностики, поскольку тактика терапии принципиально различная. Цель. Сравнить клинико-лабораторные особенности НБО и ОГО. Материал и методы. В исследование включены 52 пациента с НБО и 47 с ОГО в возрасте до 18 лет. Диагноз НБО устанавливали на основании клинической картины, лабораторных изменений, наличии очагов костной деструкции, выявленных при проведении лучевых методов исследования, биопсии кости, отрицательных бактериологических исследований биоптата. Диагноз ОГО устанавливали при наличии положительных результатов бактериологических исследований биоптата кости. Сопоставительный анализ проводился на основании оценки количества костных очагов, лабораторных данных - уровень гемоглобина, число лейкоцитов, тромбоцитов, СОЭ, СРБ, идентификации возбудителя и времени постановки диагноза. Результаты. Возраст дебюта заболевания у пациентов составил 8,4 (5,4; 11,0) и 11,0 (6,2; 12,9) с НБО и ОГО, соответственно (р=0,08). НБО с одинаковой частотой встречается как у мальчиков, так и у девочек, тогда как ОГО чаще встречался у мальчиков - 61,7% (р=0,17). Время от начала заболевания до постановки диагноза в сравниваемых группах значительно отличалось и составило 6,3 (2,0; 17,8) мес у пациентов с НБО и 0,1 (0,03; 0,17) мес у пациентов с ОГО (р=0,0000001). Не отмечено различий в уровне гемоглобина и тромбоцитов, выявлена тенденция более высокому уровню лейкоцитов при ОГО 12,6 х 109/л (8,4; 15,5), в сравнении - 7,8 х 109/л (6,7; 9,2) при НБО. Выявлены различия в показателях СОЭ - 39,5 (25,0; 58,0) мм/ч и 26,0 (11,0; 41,0, р=0,009), СРБ 65,0 мг/л (20,0; 146,0) и 8,2 мг/л (4,3; 34,0, р=0,01) у пациентов с ОГО и НБО, соответственно. У 29/43(67,4%) пациентов с ОГО из биоптата кости идентифицирован инфекционный возбудитель, тогда как при НБО в 100% случаев результаты бактериологического исследования пунктата кости были стерильны. Заболевание сопровождалось симптоматикой артрита в 69,2% (НБО) и 23,4% случаев (ОГО), (р=0,000005). Лихорадка отмечена у 43/47 (91,5%) и 20/52 (38,5%) пациентов с ОГО и НБО (р=0,0000001). Монофокальное поражение встречалось у всех пациентов с ОГО, тогда как при НБО в лишь у 10/52 (19,2%) больных (р=0,0000001). Выводы. Проведен анализ клинико-лабораторных особенностей НБО и ОГО. Выявлены достоверные различия между группами по активности заболевания, количеству очагов поражения, времени от дебюта до постановки диагноза.

Published
2016
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10. SAT0261 Different Treatment Strategies for Chronic Non-Bacterial Osteomyelitis: The Experince of 52 Patients

Author

E. Isupova, Alexander Yu. Mushkin, M. Dubko, V. Masalova, I.A. Chikova, L. Snegireva, Olga L Kopchak, Vyacheslav Chasnyk, Olga Kalashnikova, and M. Kostik

Subjects
medicine.medical_specialty, business.industry, Osteomyelitis, Immunology, medicine.disease, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Surgery, law.invention, Rheumatology, Randomized controlled trial, Sulfasalazine, law, Internal medicine, Concomitant, Cohort, medicine, Immunology and Allergy, Bacterial osteomyelitis, Treatment strategy, Methotrexate, business, medicine.drug
Abstract

Background Chronic non-bacterial osteomyelitis (CNO) is a heterogenous group of immune-mediated inflammatory bone diseases, often co-exist with other rheumatic diseases. There are no approved treatments for CNO except non-steroid anti-inflammatory drugs (NSAID). The efficacies of methotrexate (MTX), sulfasalazine, pamidronate (PAM), anti-IL1 and TNFα-inhibitors (TNFα-inh) were shown in different reports. Objectives The aim of study: to compare the efficacy of non-randomized different treatment approaches in pediatric patient CNO cohort. Methods 52 children (25 M and 27 F) with CNO has average age at the onset of disease 8.4 years (5.4÷11.0), the number of foci - 3.0 (2.0÷6.0, incl. multifocal cases in 80.8%), fever at the onset – 38.5%, spine involvement - 34.6%, positive family autoimmune diseases (AID) history - 7.7%, concomitant AID - 67.3%. NSAID was the first-line treatment for non-vertebral cases, as well as PAM for vertebral involvement. Second-line treatment includes MTX, PAM and TNFα-inh. Dynamics of pain, patient9s (PVAS) and physician9s (MDVAS) assessment and ability to each medication to achieve remission of CNO activity we evaluated. Results According to the NSAID, MTX, SSZ, PAM and TNFα-inh groups next data were registered: PVAS: -14.2% (p=0.05), -50.0% (p=0.04), -23.1 (p=0.89), -83.3% (p=0.0001), -73.6% (p=0.0007); pain: -21.9% (p=0.01), -18.6% (p=0.13), +36,4 (p=0.89), -79.7% (p=0.00016), -74.1%, (p=0.0015); MDVAS: -13.8% (p=0.13); -56.4% (p=0.09), +30.8% (p=0.89), -74.7%, (p=0.0001), -82.1 (p=0.0015) respectively. The ability of each treatment strategy to achieve the CNO remission was 52.6%, 44.4%, 57,1%, 88.8% and 73.3% respectively (log-rank test, p=0,001, figure). TNFα-inh usually used as second-third line treatment in cases where other options, especially PAM were fall. Conclusions The most effective treatment approaches for CNO were PAM and TNFα-inh. The randomized controlled trials for assessment efficacy and safety of these medications is mandatory to confirm these results. Disclosure of Interest None declared

Published
2016
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