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

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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

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients

Scoliosis and dental occlusion: a review of the literature

<p>Abstract</p> <p>Background</p> <p>Idiopathic scoliosis is a deformity without clear etiology. It is unclear wether there is an association between malocclusion and scoliosis. Several types of occlusion were described in subjects with scoliosis, mostly case-reports.</p> <p>Objectives</p> <p>The aim of this review was to evaluate the type of occluslins more prevalent in subjects with scoliosis</p> <p>Search strategy</p> <p>All randomised and controlled clinical trials identified from the Cochrane Oral Health Group Trials Register, a MEDLINE search using the Mesh term scoliosis, malocclusion, and relevant free text words, and the bibliographies of papers and review articles which reported the outcome of orthodontic treatment in subjects with scoliosis that were published as abstracts or papers between 1970 and 2010.</p> <p>Selection criteria</p> <p>All randomised and controlled clinical trials published as full papers or abstracts which reported quantitative data on the outcomes malocclusion in subjects with scoliosis.</p> <p>Data collection and analysis</p> <p>Data were extracted without blinding to the authors, age of patients or type of occlusion.</p> <p>Main results</p> <p>Using the search strategy eleven observational longitudinal studies were identified. No randomized clinical trials were recorded. Twenty-three cross-sectional studies were recorderd, and the others studies were reviews, editorials, case-reports, or opinions. The clinical trials were often not controlled and were about the cephalometric evaluation after treatment with the modified Milwuakee brace, followed by the orthodontic treatment of the class II relationship with a functional appliance. Clinical trials also included the study of the associations between scoliosis and unilateral crossbite, in children with asymmetry of the upper cervical spine. This association was also investigated in rats, pigs and rabbits in clinical trials. The other associations between scoliosis and occlusion seems to be based only on cross-sectional studies, case-reports, opinions.</p> <p>Authors' conclusions</p> <p>Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of unilateral Angle Class II malocclusions associated with scoliosis, and an increased risk of lateral crossbite, midline deviation in children affected by scoliosis. Also, documentation of associations between reduced range of lateral movements and scoliosis seem convincing. Data are also mentioned about the association between plagiocephaly and scoliosis.</p

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry

<p>Abstract</p> <p>Background</p> <p>This study aimed to quantify the active biological compounds in <it>C. officinalis </it>flowers. Based on the active principles and biological properties of marigolds flowers reported in the literature, we sought to obtain and characterize the molecular composition of extracts prepared using different solvents. The antioxidant capacities of extracts were assessed by using spectrophotometry to measure both absorbance of the colorimetric free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as the total antioxidant potential, using the ferric reducing power (FRAP) assay.</p> <p>Results</p> <p>Spectrophotometric assays in the ultraviolet-visible (UV-VIS) region enabled identification and characterization of the full range of phenolic and flavonoids acids, and high-performance liquid chromatography (HPLC) was used to identify and quantify phenolic compounds (depending on the method of extraction). Methanol ensured more efficient extraction of flavonoids than the other solvents tested.</p> <p>Antioxidant activity in methanolic extracts was correlated with the polyphenol content.</p> <p>Conclusions</p> <p>The UV-VIS spectra of assimilator pigments (e.g. chlorophylls), polyphenols and flavonoids extracted from the <it>C. officinalis </it>flowers consisted in quantitative evaluation of compounds which absorb to wavelengths broader than 360 nm.</p

SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease : Results from the COVID-19 Global Rheumatology Alliance provider registry

Funding Information: members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology (ACR), EULAR, the UK National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health or any other organisation. Competing interests KLH reports she has received non-personal speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this manuscript; KLH is supported by the NIHR Manchester Biomedical Research Centre. LG reports personal consultant fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, and grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi and Galapagos, all unrelated to this manuscript. AS reports research grants from a consortium of 14 companies (among them AbbVie, BMS, Celltrion, Fresenius Funding Information: Kabi, Gilead/Galapagos, Lilly, Mylan/Viatris, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis and UCB) supporting the German RABBIT register and personal fees from lectures for AbbVie, MSD, Roche, BMS, Lilly and Pfizer, all unrelated to this manuscript. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi-Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. EF-M reports personal consultant fees from Boehringer Ingelheim Portugal and that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharmakern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. IB reports personal consultant fees from AbbVie, Novartis, Pfizer and Janssen, all unrelated to this manuscript. JZ reports speaker fees from AbbVie, Novartis and Janssen/Johnson & Johnson, all unrelated to this manuscript. GR-C reports personal consultant fees from Eli Lilly and Novartis, all unrelated to this manuscript. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JS has received research support from Amgen and Bristol Myers Squibb and performed consultancy for Bristol Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. LW receives speaker’s bureau fees from Aurinia Pharma, unrelated to this manuscript. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon and Novartis (all <$10 000). MGM has no competing interests related to this work. She serves as a patient consultant for BMS, BI JNJ and Aurinia (all <$10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones and travel assistance from Pfizer (all <$10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<$10 000). ESi reports non-financial support from Canadian Arthritis Patient Alliance, outside the submitted work. PS reports personal fees from the American College of Rheumatology/Wiley Publishing, outside the submitted work. ZW reports grant support from Bristol Myers Squibb and Principia/Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this study. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work PCR reports personal fees from AbbVie, Atom Bioscience, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche and Pfizer; meeting attendance support from BMS, Pfizer and UCB; and grant funding from Janssen, Novartis, Pfizer and UCB Pharma (all <$10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Outside of this work, she has received research grants or performed consulting for Gilead, BMS Foundation, Pfizer, Aurinia and AstraZeneca. Funding Information: Twitter Jean Liew @rheum_cat, Loreto Carmona @carmona_loreto, Pedro M Machado @pedrommcmachado and Philip C Robinson @philipcrobinson Contributors All authors contributed to the study design, data collection, interpretation of results and review/approval of the final submitted manuscript. JL and MG are guarantors for this manuscript. Funding MG reports grants from the National Institutes of Health, NIAMS, outside the submitted work. KLH is supported by the NIHR Manchester Biomedical Research Centre. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JH is supported by grants from the Rheumatology Research Foundation. ZW is supported by grants from the National Institutes of Health. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Publisher Copyright: ©Objective. While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2.  Methods. We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. Results SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. Conclusion. More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.publishersversionPeer reviewe

Obstetric Outcomes in Women with Rheumatic Disease and COVID-19 in the Context of Vaccination Status

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi -square or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2%(n = 2). CONCLUSION: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy

Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.

International audienceObjectives To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).Methods Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.Results The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment.Conclusion I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination