The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases : insights after the first 5 years of the ERN ReCONNET

Funding Information: I. Bulina has received honoraria from Abbvie, Boehringer Ingelheim, Janssen and Pfizer. N. Costedoat-Chalumeau has received grants from UCB for a clinical research study. M. Matucci-Ce rinic has received grants from Janssen and MSD, and he is a member of speak ers bureau for Janssen, Sandoz, Bio gen, BI, Lilly and MSD. A. Meyer re ceived honoraria (<10,000 euros) from Lilly, LFB, Pfizer, Boehringer, Sanofi and research grants/support from CSL Behring, LFB, Sanofi, Fresenius Kabi and BMS. L. Mouthon received a grant from LFB. J.M. van Laar has received honoraria from Abbvie, Boehringer In-gelheim, Celltrion, Galapagos, Magenta, Roche, and grants from Astra Zeneca, Boehringer Ingelheim, Roche and Thermofischer. J.K. de Vries-Bouwstra received consulting fees from Abbvie, Janssen and Boehringer Ingelheim, and research grants from Roche, Galapagos and Janssen. The other authors have declared no competing interests. Publisher Copyright: © Copyright CliniCal and ExpErimEntal rhEumatology 2022.In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.publishersversionPeer reviewe

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study

Funding Information: This study was funded by the American College of Rheumatology and the European League Against Rheumatism. The views expressed herein are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the UK National Health Service, the NIHR, the UK Department of Health, or any other organisation. Patient research partners (KB and LN) were involved in the design, conduct, reporting and interpretation of the results of this study. Patient partners have participated in the development of this manuscript and are listed as coauthors. Funding Information: SES reports funding from a Vasculitis Clinical Research Consortium (VCRC)–Vasculitis Foundation Fellowship (the VCRC is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Science [NCATS], and is funded by a collaboration between NCATS and the National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS; U54 AR057319]). RC reports speaker's fees from Janssen, Roche, Sanofi, and Abbvie outside the submitted work. CH received funding under a sponsored research agreement from Vifor Pharmaceuticals, outside the submitted work. SLM has received consulting fees from AbbVie; consulting fees from AstraZeneca; other from Roche-Chugai; consulting fees from Sanofi; and non-financial support from Roche, all outside the submitted work; and is a patron of the patient charity PMRGCAuk. PM is a Medical Research Council-GlaxoSmithKline (MRC-GSK) EMINENT clinical training fellow, who has received project funding from this organisation, outside the submitted work; has received funding from the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre (UCLH BRC); reports grants from MRC-GSK; reports personal fees from Swedish Orphan Biovitrum and Lilly; and reports consultancy fees from Abbvie and Pfizer, all outside the submitted work. LN reports being a trustee of the charity PMR-GRA Scotland. JSA reports grants from the National Institute of Health (NIH) and NIAMS, the Rheumatology Research Foundation, the Brigham Research Institute, the R Bruce and Joan M Mickey Research Scholar Fund, and Amgen; grants and personal fees from Bristol-Myers Squibb; and personal fees from Gilead, Inova, Janssen, Optum, and Pfizer, all outside the submitted work. AD-G is supported by the US Centers for Disease Control and Prevention, the Rheumatology Research Foundation Scientist Development Award, the Robert D and Patricia E Kern Center for the Science of Health Care Delivery, and the Women's Health Career Enhancement Award outside the submitted work. KLH reports receiving speaker's fees from Abbvie; grant income from Bristol-Myers Squibb, UCB Pharma, and Pfizer, all outside the submitted work; and is supported by the NIHR Manchester Biomedical Research Centre outside the submitted work. RG reports non-financial support from Pfizer Australia and Janssen Australia; and personal fees from Pfizer Australia, Cornerstones, Janssen New Zealand, and Novartis, all outside the submitted work. UM-L is supported by grants from the German Ministry of Research and Education and the German Research Foundation outside the submitted work. MAG reports funding from the NIH and the NIAMS. PCR reports personal fees from Abbvie and Gilead; grants and personal fees from Janssen, Novartis, UCB Pharma, and Pfizer; non-financial support from Bristol-Myers Squibb and Pfizer; and personal fees from Lilly and Roche, all outside the submitted work. JY reports no competing interests related to this work; is supported by grants from NIH (K24 AR074534 and P30 AR070155); and reports consulting fees from Eli Lilly, Pfizer, Aurinia, and AstraZeneca, all outside the submitted work. PMM has received consulting or speaker's fees from Abbvie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB Pharma, all outside the submitted work (all <$10 000); and is supported by the NIHR UCLH BRC outside the submitted work. ES is a board member of the Canadian Arthritis Patient Alliance, which is a patient-run, volunteer-based organisation, whose activities are largely supported by independent grants from pharmaceutical companies. JWL reports grants from Pfizer, outside the submitted work. JSH reports no competing interests related to this work; is supported by grants from the Rheumatology Research Foundation; receives salary support from the Childhood Arthritis and Rheumatology Research Alliance; and reports consulting fees for Novartis, Swedish Orphan Biovitrum, and Biogen, all outside the submitted work (<$10 000). PS reports no competing interests related to this work, but reports receiving honorarium for editing social media for the American College of Rheumatology journals (<$10 000). SBh reports receiving non-branded consulting fees from AbbVie, Amgen, Horizon, Novartis, and Pfizer (<$10 000 from each)outside the submitted work. ZSW reports receiving grant support from Bristol-Myers Squibb and Principia-Sanofi; has consulted for Viela Bio and MedPace; and is supported by grants from the National Institutes of Health, all outside the submitted work. AS reports personal fees for lectures from AbbVie, Celltrion, Lilly, Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, and Pfizer outside the submitted work. EFM has received grants from Abbvie, Novartis, Lilly Portugal, Amgen Biofarmacêutica, Grünenthal SA, Merck Sharp & Dohme, Medac, and A Menarini Portugal-Farmacêutica SA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, all outside the submitted work. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, and Sanofi; consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB Pharma, all outside the submitted work. LC declares no competing interests related to this study, but her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España SA, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal, and UCB Pharma. NJP reports grants from NIH during the conduct of the study. MU-G reports grants from Pfizer and Janssen, outside the submitted work. SBa reports grants and personal fees from Alexion Pharma, outside the submitted work. RV reports grants from Novartis, Pfizer, and Bristol-Myers Squibb, outside the submitted work. All other authors declare no competing interests. Funding Information: This study was funded by the American College of Rheumatology and the European League Against Rheumatism. The views expressed herein are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the UK National Health Service, the NIHR, the UK Department of Health, or any other organisation. Patient research partners (KB and LN) were involved in the design, conduct, reporting and interpretation of the results of this study. Patient partners have participated in the development of this manuscript and are listed as coauthors. Publisher Copyright: © 2021 Elsevier LtdBackground: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding: American College of Rheumatology and the European Alliance of Associations for Rheumatology.publishersversionPeer reviewe

Interconversion of Anthozoa GFP-like fluorescent and non-fluorescent proteins by mutagenesis

BACKGROUND: Within the family of green fluorescent protein (GFP) homologs, one can mark two main groups, specifically, fluorescent proteins (FPs) and non-fluorescent or chromoproteins (CPs). Structural background of differences between FPs and CPs are poorly understood to date. RESULTS: Here, we applied site-directed and random mutagenesis in order to to transform CP into FP and vice versa. A purple chromoprotein asCP (asFP595) from Anemonia sulcata and a red fluorescent protein DsRed from Discosoma sp. were selected as representatives of CPs and FPs, respectively. For asCP, some substitutions at positions 148 and 165 (numbering in accordance to GFP) were found to dramatically increase quantum yield of red fluorescence. For DsRed, substitutions at positions 148, 165, 167, and 203 significantly decreased fluorescence intensity, so that the spectral characteristics of these mutants became more close to those of CPs. Finally, a practically non-fluorescent mutant DsRed-NF was generated. This mutant carried four amino acid substitutions, specifically, S148C, I165N, K167M, and S203A. DsRed-NF possessed a high extinction coefficient and an extremely low quantum yield (< 0.001). These spectral characteristics allow one to regard DsRed-NF as a true chromoprotein. CONCLUSIONS: We located a novel point in asCP sequence (position 165) mutations at which can result in red fluorescence appearance. Probably, this finding could be applied onto other CPs to generate red and far-red fluorescent mutants. A possibility to transform an FP into CP was demonstrated. Key role of residues adjacent to chromophore's phenolic ring in fluorescent/non-fluorescent states determination was revealed

Maturity model for assessing digitalization process of construction industry companies

The construction industry is on the verge of large–scale changes as Industry 4.0 is preparing industrial enterprises for serious challenges. Digital transformation can bring significant changes in all areas of enterprise activity. Maturity models are usually used to assess the current situation and measure the digital maturity of an organization. The authors’ four-stage model of digital maturity assessment for construction industry companies has been proposed. When developing the model, it had been decided to move away from general assessments and use specific changes that would occur at construction industry companies in the process of digital transformation as an assessment tool. The model contains fifteen assessment factors, changes of which at various stages are indicators of digital maturity. The proposed model contains a detailed description of the four stages of digital maturity, therefore it can serve not only to assess the digital maturity of industrial enterprises in the construction industry, but can also be used to indicate the goals planned to be achieved in the future as part of digital transformation, in strategies or business models of enterprises. A distinctive feature of the model is evaluation factors reflecting the degree of integration of the digital environment of industrial enterprises with BIM models of construction organizations

TUMOUR NECROSIS FACTOR alpha IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS IN BLOOD SERUM AND SYNOVIAL FLUID

publishersversionPeer reviewe

Synthesis of Nanocrystalline Magnesium and Aluminum Diborides

For obtaining MgB2 and AlB2 with nanometer size of coherent scattering area the technique based on the preliminary mechanical activation (MA) of initial reagents powder mixes and the subsequent reaction in the mode of the thermal explosion (TE) was used. The mentioned diborides are the promising compounds to use as a high-energy material in the ramjets and solid rocket motors because they possess very high mass- and volume-heat of combustion. Mostly, the diborides are produced under conditions of high temperatures and pressures. In this research a possibility has been explored of their producing by thermal explosion method when using preliminary mechanically activated components. The peculiarities of the technique to produce diborides are examined. Results of radiographic and electron microscope studies of the mixes of reagents after mechanical activation and of thermal explosion products are presented

Formation of TiC-Cu nanocomposites by a reaction between Ti25Cu75 melt-spun alloy and carbon

In this work, Ti25Cu75 melt-spun partially amorphous alloy was used as a source of Ti and Cu to synthesize in-situ TiC-Cu nanocomposites. The reaction between the alloy and carbon started during ball milling and continued during Spark Plasma Sintering. At the same time, during ball milling, the alloy experienced phase transformations: crystallization of the amorphous phase was followed by decomposition of TiCu3. Copper crystallites formed during the alloy transformations were the reason for the presence of copper regions 0.5–1 µm in size free from TiC nanoparticles in the sintered composites. The Ti-Cu intermetallics transformed into non-agglomerated TiC 10–20 nm in size distributed in the copper matrix. The hardness of the synthesized TiC-Cu nanocomposites exceeded that of composites obtained by conventional sintering of ball-milled Ti-C-Cu powders

data from the EULAR COVAX physician-reported registry

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND: There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs. OBJECTIVES: To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). METHODS: We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. RESULTS: A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20-30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. CONCLUSIONS: This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.publishersversionpublishe

Перинатальная ВИЧ-инфекция в Санкт-Петербурге и современная терапия сопутствующих вирусных инфекций

The study included 338 HIV-infected children (B-23) and 350 children with perinatal contact HIV infection (R-75), consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5%) diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS) amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis) — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP) — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic) SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment) regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI) in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.Под наблюдением находились 338 ВИЧ-инфицированных детей (В-23) и 350 детей с перинатальным контактом по ВИЧ-инфекции (R-75), состоящих на диспансерном учете в отделении материнства и детства Санкт-Петербургского городского центра СПИД. У 32 чел. (9,5%) диагностированы вторичные инфекции. В структуре оппортунистических инфекций вирусные (герпес-вирусные, ОРВИ) составили 39,8%, бактериальные (бронхит, ангина, пиодермия, туберкулез легких) — 34,8%, грибковые и паразитарные (кандидоз слизистой оболочки полости рта, пневмоцистная пневмония) — 25,4%. Комплексная терапия (этиотропная, патогенетическая, симптоматическая) ОРВИ у детей с В-23 и R-75 позволяет добиться в ранние сроки (6-е сут. лечения) регресса основных симптомов острых респираторных заболеваний. Современная терапия врожденной цитомегаловирусной инфекции (ВЦМВИ) у детей с В-23 и R-75 первого года жизни с применением антицитомегаловирусного иммуноглобулина и препарата человеческого рекомбинантного интерферона альфа-2b в виде ректальных суппозиториев — ВИФЕРОН®, обуславливает стойкую нормализацию клинико-лабораторных показателей

Опыт лечения хронического вирусного гепатита С у детей, рожденных ВИЧ-позитивными женщинами

The article presents information obtained from the analysis of the stories of 40 children up to 4 years old left without parental care and infected with hepatitis C through vertical transmission. Authors analyzed the results of integrated treatment of the disease with inclusion of combined antiviral immunomodulatory drug VIFERON®. The efficacy of VIFERON® in chronic viral hepatitis C in infants is confirmed.В статье представлены материалы ретроспективного исследования, в котором под наблюдением находились 40 оставшихся без попечения родителей детей в возрасте до 4-х лет, инфицированных вирусом гепатита С в результате вертикальной трансмиссии, в том числе рожденных ВИЧ-позитивными женщинами. Включение комбинированного противовирусного иммуномодулирующего препарата ВИФЕРОН® в комплексную терапию таких детей эффективно, безопасно и не вызывает побочных и нежелательных эффектов