Myo6 mediates osteoclast function and is essential for joint damage in collagen-induced arthritis.

OBJECTIVES: To explore the novel function of MYO6 on Osteoclast differentiation and its joint destruction capacity in Rheumatoid arthritis mice model. METHODS: We examined joint erosion in a collagen-induced arthritis (CIA) mouse model using micro-CT, with the mice having a MYO6 knockout background. Inflammatory cytokines were analyzed using an enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated the osteoclastogenesis ability of bone marrow-derived macrophages isolated from MYO6-/- mice and their littermate controls, examining both morphological and functional differences. Furthermore, we explored podosome formation and endosome maturation using immunofluorescence staining. RESULTS: We found that MYO6 deficiency attenuated arthritis development and bone destruction in CIA mice as well as impaired osteoclast differentiation by inhibiting NFATc1 induction. Our findings indicate that MYO6 is essential for the organization of podosomes by modulating the FAK/AKT and integrin-ß3/Src pathways. MYO6 also mediates endosome transportation by regulating the expression of Rab5 and GM130. This may impact the maintenance and functionality of the ruffled border, as well as the regulation of autophagy in osteoclasts. CONCLUSION: Our results demonstrated a critical function of MYO6 in osteoclast differentiation and its potential relevance in experimental arthritis.

The Potential Mechanisms of Qufeng Zhitong Capsule against Rheumatoid Arthritis Based on Network Pharmacology and In Vitro Experiments.

Qufeng Zhitong capsule (QFZTC) is a traditional Chinese herbal formula with potential therapeutic efficacy in rheumatoid arthritis (RA). This study seeks to clarify the potential effects and mechanisms of QFZTC against RA. Active compounds and targets of QFZTC were retrieved from the Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID) databases. RA-related targets were searched on GeneCards and DisGeNET databases. Protein-protein interaction (PPI) network was established using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were performed on hub targets. Molecular docking was conducted on hub targets and active compounds. High-performance liquid chromatography (HPLC) was applied to characterize the active compounds in QFZTC. RA-fibroblast like synoviocytes (RA-FLSs) were cultured and treated by QFZTC-containing serum, in which proinflammatory cytokines and hub targets were detected. Cell viability was determined by cell counting kit-8 (CCK-8) assay. A total of 360 active compounds and 445 potential targets are identified for QFZTC against RA. Protein-protein interaction (PPI) network determined five hub targets, interleukin 6 (IL6), IL1B, VEGFA, JUN, and tumor necrosis factor (TNF). GO and KEGG analyses revealed that the MAPK pathway may be a critical signaling in QFZTC treating RA. Molecular docking showed that luteolin, kaempferol, and myricetin has good affinity with TNF, and they were identified by HPLC. In vitro experiments confirmed that QFZTC restrained the cell viability and inflammation in RA. This study revealed the active compounds and molecular targets for QFZTC treating RA. QFZTC is a promising drug and ameliorates RA by inhibiting inflammatory response.

SIRT1 inhibitors within Qing-Luo-Yin alleviated white adipose tissues-mediated inflammation in antigen-induced arthritis mice.

BACKGROUND: White adipose tissues (WAT) release large amounts of inflammatory mediators, which are responsible for the pathology of rheumatoid arthritis (RA). PURPOSE: The current study investigated the involvement of WAT in the treatments of antigen-induced arthritis (AIA) mice with the herbal formula Qing-Luo-Yin (QLY). METHODS: Cytokines and biochemical/metabolic indicators were determined by ELISA and colorimetry methods, respectively. Monocytes were analyzed by flow cytometry. Tissues were subjected to PCR, western-blot and histological analyses. Pre-adipocytes were cultured in the different mouse serum from the in vivo experiment, and some of them were treated by certain compounds or/and lipopolysaccharide. Afterwards, the catalytic activity and thermostability of SIRT1 were tested. Gene/protein expression and cytokine production were investigated too. NAMPT and SIRT1 were silenced in some cells by siRNA. RESULTS: AIA mice suffered from inflammatory adipokines-mediated metabolism and immune disorders. Besides joint protective effects, QLY therapies favored adipocyte differentiation and suppressed inflammatory adipokines release. The up-regulation of fatty acid oxidation and inflammatory monocyte polarization was therefore inhibited in peripheral tissues. PPARγ expression was generally promoted by QLY. Whereas, SIRT1 activity was always impaired, indicated by the declined NAD+ levels and the increased ace-p65 expression. QLY effectively inhibited eNAMPT release in AIA mouse serum-cultured pre-adipocytes. This effect was antagonized by resveratrol (a SIRT1 agonist) and overshadowed by NAMPT silencing. QLY-related compounds berberine, dioscin and sophocarpine showed high binding affinities to SIRT1, stabilized this protein, and inhibited its deacetylation activity in vitro. Their effects on ace-p65 expression were weakened when SIRT1 was silenced. CONCLUSION: SIRT1 inhibitors in QLY reduced eNAMPT production and up-regulated PPARγ in AIA mice, leading to inflammation remission. These clues show that except for the well-known anti-inflammatory functions, SIRT1 participates in inflammatory reactions too and could be a potential anti-rheumatic target.

Water extracts of Tibetan medicine Wuweiganlu attenuates experimental arthritis via inducing macrophage polarization towards the M2 type.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuweiganlu (WGL) is a well-known formulation described in the "Four Medical Scriptures of Tibetan medicine", which is mainly used for the treatment of Rheumatoid Arthritis (RA) and other chronic ailments prescribed by Tibetan medicine. Nonetheless, the active constituents present in the water extracts of Wuweiganlu (WGLWE) specifically targeting arthritis treatment are largely unknown. AIM OF THE STUDY: The aim of this study is to explore the effects and underlying mechanisms of the active components in WGLWE on RA. MATERIALS AND METHODS: We utilized ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS) to identify the main chemical compositions of WGLWE. The polarization effect of WGLWE on bone marrow-derived macrophages (BMDM) was determined. A rat model of collagen-induced arthritis (CIA) was established by injecting an emulsion of bovine type II collagen mixed with an equal volume of incomplete Freund's adjuvant into the tail, paw and back of rats. A WGLWE-based ointment was topically applied to the legs and paws of the rats for 30 days. The rats' ankles were photographed to measure the degree of swelling. Micro-CT was used to image the knee joint and paw of rats, and the bone mineral density (BMD) and bone volume fraction (BV/TV) of knee joint in rats were analyzed. High-frequency ultrasound imaging of the rat knee joint was performed to observe knee joint effusion. Further, the serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-10, and arginine (Arg-1) in CIA rats were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) and immunofluorescence (IF) co-staining were employed to detect the expression levels of inflammatory factors in synovium. RESULTS: A total of 28 main components were identified in WGLWE, and these compounds can directly bind to the inflammatory pathway proteins such as JAK2, NFκB and STAT3. In vitro experiments demonstrated that WGLWE promoted the transformation of M1 macrophages into M2 macrophages and suppressed the release of proinflammatory cytokines TNF-α and IL-6. In vivo studies showed that WGLWE effectively reduced ankle swelling, alleviated knee joint effusion, and improved BV/TV while also reducing synovial inflammation levels. Furthermore, WGLWE compounds induced the transition of M1-type macrophages to M2-type macrophages in synovial tissue, resulting in decreased secretion of inflammatory factors TNF-α, WGLWE improved the synovial inflammatory state. CONCLUSION: Our results indicated that WGLWE alleviated joint inflammation in CIA rats and the underlying mechanism may be related to inducing the transformation of bone marrow-derived M1 macrophages to M2 macrophages, leading to an increase in the secretion of anti-inflammatory factors and a decrease in pro-inflammatory factors. Therefore, WGLWE may be used as a potential herbal preparation for the treatment of RA.

Study on toxicity/efficacy related substances and metabolic mechanism of Tripterygium wilfordii Hook. f based on O2LPS correlation analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f (TwHF) has been used as a traditional Chinese medicine for the treatment of rheumatoid arthritis and nephritis for hundreds of years. AIM OF THE STUDY: Although the efficacy of TwHF in the treatment of RA is definite, its serious side effects and toxicity have also received close attention from domestic and international researchers, so the clinical application of TwHF has been controversial. Most of the current TwHF toxicity studies have been conducted with animals in normal body states, but ignore the effects in pathological states. In this study, we aimed to find out the material basis and metabolic mechanism of the "toxicity/effectiveness" of TwHF on rat kidneys in different body states by using two-way orthogonal partial least squares (O2PLS) method. MATERIALS AND METHODS: In the present study, TwHF was extracted by reflux extraction method using ethanol as the extraction solvent. Firstly, the effects of TwHF on rat kidneys in different body states were first evaluated by detecting creatinine and urea nitrogen levels and morphological changes in kidney pathology identified the components of TwHF in rats in different body states using UPLC-Q-TOF/MS technique. Serum and urine metabolomics were used to search for biomarkers and metabolic pathways by which TwHF exerts renal injury and protection, and finally, O2PLS correlation analysis was used to correlate the components with renal protective and injury biomarkers. RESULTS: TwHF was found to have a protective effect on the kidney of RA rats and an injurious effect on the kidney of normal rats at a dose of 11.25 g/kg/d. The UPLC-Q-TOF/MS technique was used to identify 34 components in TwHF extracts; 23 components and 57 metabolites were identified in the administered rats. O2PLS screened three substances as both toxic and pharmacodynamic components of TwHF, namely 3,5-dimethoxyphenyl-2-propenl-ol, kaurane-16,19,20-triol, and demethylzeylasteral + O, and found that these three components may exert nephrotoxic effects via the nicotinic acid and nicotinamide metabolic pathways and nephroprotective effects via the tryptophan metabolic pathway. CONCLUSION: In this study, O2PLS analysis was used for the first time to combine biomarkers and components in vivo and found the material basis and metabolic mechanism of nephrotoxicity and efficacy of TwHF, which provided key clues for further study on the biological mechanism of toxicity and efficacy of TwHF.

The Giants of Rheumatology at Johns Hopkins: Lawrence E Shulman, MD, PhD and Mary Betty Stevens, MD.

Drs Lawrence E. Shulman and Mary Betty Stevens were the giants of rheumatology at Johns Hopkins during the latter half of the twentieth century. Together, they made immense contributions to our knowledge of systemic lupus erythematosus as well as other systemic autoimmune rheumatic diseases, provided excellent clinical care to thousands of patients with rheumatoid arthritis, systemic lupus erythematosus, and other systemic autoimmune rheumatic diseases, and trained almost 100 postdoctoral fellows, many of whom went on to highly successful careers in academic medicine, including the Directors of Divisions of Rheumatology and the Chairs of Departments of Medicine.

Targeting FGFR3 is a Useful Therapeutic Strategy for Rheumatoid Arthritis Treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory disease in which TNF-α plays an important role. Fibroblast growth factor receptor 3 (FGFR3) is reportedly involved in RA by regulating the expression of inflammatory cytokines. OBJECTIVE: This study examined the expression profile of FGFR3 in human synovial biopsy tissues and evaluated its gene-silencing effects on behaviors of synovial cells. METHODS: Immunohistochemical staining was used to measure FGFR3 expression in human RA joint tissues. Cell proliferation, migration, and apoptosis assays were used to monitor behavioral changes in cultured synovial SW-982 cells with siRNA-mediated FGFR3 gene silencing. Immunofluorescent staining and western blotting were used to detect molecular changes in the FGFR3 gene-silenced cells. RESULTS: FGFR3 up-regulation was noted in both cytoplasms and nuclei of synovial cells in human RA joints. FGFR3 siRNA delivery experiments corroborated that FGFR3 knockdown decreased proliferation and migration, and triggered apoptosis of synovial cells. The FGFR3 gene knockdown enhanced constitutive expression of epithelial marker E-cadherin and conversely suppressed expression of epithelial-mesenchymal transition (EMT) markers, including Snail, fibronectin, and vimentin. In addition, FGFR3 silencing significantly reduced the constitutive expressions of TNF-α, transcription factor NF-κΒ, and downstream COX-2 protein and collagenolytic enzyme MMP-9. MAPK inhibition markedly suppressed constitutive levels of NF-κΒ, COX-2, and MMP-9. CONCLUSION: Genetic interference of FGFR3 could modulate the expression of inflammatory mediators and EMT markers in the synovial cells. Targeting the FGFR3/MAPK signal axis may be considered a useful therapeutic strategy to ameliorate the development of RA.

A comprehensive quality evaluation for Huangqi Guizhi Wuwu decoction by integrating UPLC-DAD/MS chemical profile and pharmacodynamics combined with chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human "blood impediment" (a type of "Bi" syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA). AIM OF THE STUDY: The characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers. MATERIALS AND METHODS: First, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD. RESULTS: In total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples. CONCLUSION: Combining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

Nathan Zvaifler.

Nathan Zvaifler was one of the most original thinkers in the field of rheumatology contributing to modern understanding of the role of complement in mediating inflammation and the role of synoviocytes in the pathogenesis of the destructive changes of rheumatoid arthritis. His clinical acumen was unparalleled and his students are still in awe of the breadth of his knowledge.

Transdermal Delivery of Methotrexate Loaded in Chitosan Nanoparticles to Treat Rheumatoid Arthritis.

INTRODUCTION: Methotrexate shows high efficiency in the treatment of Rheumatoid arthritis, but its adverse effects cannot be tolerated by many patients. Additionally, Methotrexate suffers from rapid clearance from blood. Polymeric nanoparticles were used to solve these problems including chitosan. METHODS: Herein, a new nanoparticulate system to deliver Methotrexate (MTX) using chitosan nanoparticles (CS NPs) was developed to be used transdermally. CS NPs were prepared and characterized. The drug release was studied in vitro and ex vivo using rat skin. The drug performance in vivo was investigated on rats. Formulations were applied topically once a day on the paws and knee joints of arthritis rats for 6 weeks. Paw thickness was measured and synovial fluid samples were collected. RESULTS: The results showed that CS NPs were monodispersed, and spherical with a size of 279.9 nm and a charge above ± 30mV. Further, 88.02% of MTX was entrapped in the NPs. CS NPs prolonged MTX release and enhanced its permeation (apparent permeability ⁓35.00cm/h) and retention (retention capacity ⁓12.01%) through rats' skin. The transdermal delivery of MTX-CS NPs improves the progress of the disease compared to free MTX, as reflected by the lower arthritic index values, lower proinflammatory cytokines (TNF-α and IL-6), and higher anti-inflammatory cytokine (IL-10) in the synovial fluid. Further, the oxidative stress activities were significantly higher in the group treated with the MTX-CS NPs, as indicated by GSH. Finally, MTX-CS NPs were more effective in reducing lipid peroxidation in synovial fluid. CONCLUSION: In conclusion, loading Methotrexate in chitosan nanoparticles controlled its release and enhance its effectiveness against rheumatoid when applied dermally.

Calcium Folate for Reducing the Side Effects of Low-dose Methotrexate in Rheumatoid Arthritis: A Case Report.

INTRODUCTION: We reported a patient with rheumatoid arthritis who received chronic methotrexate (MTX) therapy and experienced several adverse reactions like hemocytopenia and renal impairment. Under the monitoring of the therapeutic drug concentration, calcium folate and other measures were used to accelerate methotrexate excretion and eliminate adverse reactions. CASE PRESENTATION: A 66-year-old man with rheumatoid arthritis received MTX and developed adverse effects of bone marrow suppression, like pancytopenia. He had a black stool, and he tested positive for occult blood, which was considered gastrointestinal bleeding. The blood MTX concentration reached 4.07 µmol/L, and leucovorin was administered to rescue the patient's life. Besides, hydration and alkaline urine were applied to quickly clear methotrexate inside the body. CONCLUSION: Low-dose MTX has fewer adverse reactions but may cause bone marrow suppression- related side effects. Blood concentration monitoring can be used to guide the rescue of MTX poisoning.

Recent developments in the synovial fibroblast pathobiology field in rheumatoid arthritis.

PURPOSE OF REVIEW: Synovial fibroblasts are the central cells of connective tissue homeostasis. In rheumatoid arthritis (RA) tissue, synovial fibroblasts are activated because of the proinflammatory environment very early in the disease. Epigenetic alterations in RASF result in a permanently activated stage, and activated RASF are involved in many processes of RA pathophysiology. Therefore, several recent findings of the last 18 months with focus on RASF activation and function are summarized. RECENT FINDINGS: RASF activation because of a profoundly altered epigenome leads to an invasive phenotype with increased migration, adhesion and invasion into cartilage, which was further characterized in several studies. RASF subtypes and subtype dynamics were evaluated using high-resolution techniques to better understand RASF pathophysiology. Many studies addressing interactions with immune or stromal cell types have been published showing that RASF interact with many different cell types contributing not only to their own activation and pro-inflammatory response but also to the activation of the other cells. SUMMARY: Highly interesting findings revealing mechanisms of RASF activation and altered functions have been published, RASF subsets further characterized, and interactions with cell types elucidated, which all contribute to a better understanding of the role of RASF in RA development and progression.

Ameliorative effect of Alangium chinense (Lour.) Harms on rheumatoid arthritis by reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Alangium chinense has been used as traditional folk medicine for centuries to treat rheumatoid arthritis (RA) by Guizhou Miao nationality with remarkable clinical effect. But the mechanism of its anti-RA is not fully clarified. AIM OF THE STUDY: To explore the effect and underlying mechanism of A. chinense against RA. MATERIAL AND METHODS: RA rats were induced by CII/IFA, and oral administrated with or without ethyl acetate extracts of Alangium chinense (ACEE) and tripterygium glycosides (GTW). Then arthritis scores, inflammatory factors in serum and histological evaluation were evaluated to assess the degree of joints disease. Proteomics were conducted via LC-MS/MS to clarify the mechanism of ACEE preliminarily, and further examined by immunohistochemistry, immunofluorescence, western botting, and molecular docking. RESULTS: ACEE decreased joints swelling, cell abscission and necrosis of joint tissues arthropathy of RA rats, and attenuated expression of TNF-α, IL-1ß, IL-6, PGE2, TGF-ß. Meanwhile, differentially expressed proteins in the ACEE treated groups were observed, which were involved in RA, spliceosome, cell adhesion molecules, phagosome and lysosome signaling pathways. Moreover, ACEE significantly ameliorated arthropathy, suppressed JAK-STAT pathway (JAK3, p-JAK3, STAT3, iNOS, RANKL), COX-2 pathway (COX-2, TNF-α, IL-6I, L-1ß, 5-LOX), and autophagic signaling pathway (LC3-Ⅰ, LC3-Ⅱ, p62, mTOR). But it showed little effect on the expression of COX-1, JAK1, JAK2, TyK2. CONCLUSION: It is the first evidence that A. chinense significantly ameliorates RA, and the underlying immune mechanism involves reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways.

A sensitive LC-MS/MS methotrexate assay capable of assessing adherence to methotrexate therapy in rheumatoid arthritis.

OBJECTIVES: To develop a sensitive liquid chromatography-tandem mass spectrometry method capable of measuring serum methotrexate in patients with rheumatoid arthritis to assess adherence to drug treatment. METHODS: Isotopically labelled internal standard and deionised water were added to sample prior to solid phase extraction using a Waters Oasis Max ion-exchange 96-well plate. Following extraction, samples were analysed by LC-MS/MS on a TQS-micro mass spectrometer. RESULTS: Mean recovery was 107 % for four different concentrations of methotrexate spiked into seven patient samples, whilst post extraction spiking gave a mean recovery of 100 %. Between-batch and within-batch CVs were ≤6 % at three different concentrations of methotrexate in fresh frozen plasma. Mean bias was <5 % for between-batch and within batch analysis at three different weighed in concentrations of methotrexate certified reference material. The lower limit of quantification of the assay was 0.1 nmol/L with linearity up to approximately 100 nmol/L. Dilution linearity studies were used to validate the dilution of patient samples prior to analysis. There was no significant interference in the method from lipaemia, haemolysis or icterus. CONCLUSIONS: A sensitive LC-MS/MS assay for methotrexate has been developed and validated. The method has been used to measure methotrexate adherence in patient samples from clinical trials and could be used in future research to assess the ability of the assay as a biofeedback intervention to improve adherence to methotrexate therapy.

Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

El valor predictivo de la autoeficacia en la evolución de la artritis reumatoide y su relación con el dolor y la función / The predictive value of self-efficacy in the evolution of rheumatoid arthritis and its relationship with pain and function

Antecedentes y objetivos: La artritis reumatoide (AR) cursa generalmente con una afectación mayor en el miembro superior, pudiendo ocasionar dificultades en el desempeño de actividades en el día a día. El objetivo principal de este estudio fue establecer la relación entre la autoeficacia, la intensidad del dolor y la duración de los síntomas en pacientes con AR, y analizar cómo y en qué medida cada uno de ellos influye en la discapacidad funcional, así como, conocer el valor predictivo de la autoeficacia sobre las demás variables. Métodos: Estudio transversal con una muestra de 117 mujeres con AR. Las variables de evaluación empleadas fueron la escala visual analógica (EVA), el cuestionario QuickDASH y la escala española de autoeficacia en enfermedades reumáticas. Resultados: Los resultados muestran que el modelo más significativo para la función (R2=0,35) incluye la variable función y dolor, por lo que, sí hay relación existente entre la autoeficacia, la intensidad del dolor y la funcionalidad del miembro superior, así como la asociación de las puntuaciones obtenidas en la EVA, QuickDASH y la escala española de autoeficacia en enfermedades reumáticas para su evaluación. Discusión y conclusiones: Nuestros resultados, concuerdan con estudios previos donde se establece la posible relación entre la autoeficacia y la discapacidad funcional, así como la autoeficacia y su relación con funciones físicas, demostrando que un bajo nivel de autoeficacia implica una disminución de la funcionalidad, pero sin que ninguna variable sea más predictora que otra.(AU)

Background and objectives: Rheumatoid arthritis (RA) primarily affects the upper limbs and can cause disturbances in the performance of daily activities. The main objective of this study was to establish the relationship between self-efficacy, pain intensity, and duration of symptoms in patients with RA and analyse how each influences functional disability, and to determine the predictive value of self-efficacy over the other variables. Methods: Cross-sectional study with a sample of 117 women diagnosed with RA. The endpoints were the visual analogue scale (VAS), Quick-DASH questionnaire and the Spanish scale of self-efficacy in rheumatic diseases. Results: The most significant model for function (R2=0.35) includes function and pain, therefore, there is a relationship between self-efficacy, pain intensity, and upper limb functionality. Discussion and conclusions: Our results agree with previous studies where a relationship between self-efficacy and functional disability is established, as well as self-efficacy and its relationship with physical functions, demonstrating that a low level of self-efficacy implies a decrease in functionality; however, no variable is more predictive than another.(AU)

Whole-hand and regional bone mineral density involvement in rheumatoid arthritis / Compromiso de la densidad mineral ósea de la mano completa y regional en la artritis reumatoide

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm2) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (−8.7%), dominant whole hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (−8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges.(AU)

La artritis reumatoide (AR) es una enfermedad autoinmune crónica caracterizada por poliartritis simétrica que puede provocar deformidad e incapacidad articular y osteoporosis. Nuestro objetivo fue evaluar la DMO de manos completa y por regiones en los pacientes con AR en comparación con los controles. Se incluyeron pacientes adultos de ambos sexos con AR, y sujetos controles de edad, sexo e IMC similar. La DMO se midió por DXA en columna lumbar (CL), manos completas y 3 regiones de interés: carpo, metacarpianos y falanges. Resultados: se incluyeron 44 sujetos control (49,5±11,8 años) y 60 con AR (52,7±12,7 años). Se encontró una DMO significativamente más baja en los pacientes con AR en CL (−8,7%), mano completa dominante (−9,5%) y mano completa no dominante (−8,7%) en comparación con los sujetos controles. Se encontró una correlación positiva significativa entre la CL y la DMO de la mano completa (dominante, r=0,63; no dominante, r=0,67). Finalmente, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante sin diferencias en la región de las falanges. En conclusión, la DMO de la mano fue significativamente menor en los pacientes con AR en comparación con los sujetos controles, y hubo una correlación significativa con la DMO de la CL. Demostramos que las mediciones de la DMO de toda la mano y diferentes ROI (carpo, huesos metacarpianos y falanges) por DXA serían una técnica fácilmente reproducible para evaluar la pérdida ósea. Además, la DMO de la mano completa, los huesos metacarpianos y el carpo fueron significativamente más altos en la mano dominante en comparación con la mano no dominante.(AU)

YouTube® as a source of information for Spanish-speaking patients with rheumatoid arthritis / YouTube® como fuente de información para pacientes hispanohablantes con artritis reumatoide

Introduction: Social media (SoMe) has reshaped access to health information, which may benefit patients with rheumatoid arthritis (RA), although an evaluation of the characteristics of contents for Spanish-speaking patients is lacking. We aimed to assess patient engagement, reliability, comprehensiveness, and quality of data uploaded to YouTube® for Spanish-speaking patients. Methods: We evaluated the videos uploaded to YouTube® in Spanish about RA. Information about video length, engagement (i.e., views, likes, popularity index), time online, and the source was retrieved; we appraised reliability (DISCERN), comprehensiveness (content score), and quality (Global Quality Score) using standardized scores. Results: We included 200 videos in the study and classified 67% of the videos as useful. These videos had a higher number of views (19,491 [10,132–61,162] vs. 11,208 [8183–20,538]), a longer time online (1156 [719–2254] vs. 832 [487–1708] days), and a shorter duration (6.3 [3.4–15.8] vs. 11.8 [7.4–20.3] min). Engagement parameters were similar between useful and misleading videos. Useful videos had higher reliability, comprehensiveness, and quality scores. Useful videos were mainly uploaded by independent users and government/news agencies; academic organizations offered only 15% of useful videos. Conclusions: Most of the information in YouTube® for Spanish-speaking patients with RA is useful; however, patient engagement is similar between useful and misleading content. More substantial involvement of academia in developing high-quality educational multimedia is warranted.(AU)

Introducción: Las redes sociales (ReSo) han redefinido el acceso a la información en salud, beneficiando a los pacientes con artritis reumatoide (AR). No se cuenta con una evaluación de las características de su contenido para pacientes hispanohablantes. Nuestro objetivo fue evaluar los parámetros de interacción, la confiabilidad, la exhaustividad y la calidad de la información disponible en YouTube® para pacientes hispanohablantes con AR. Métodos: Evaluamos los videos en español sobre AR disponibles en YouTube®. Se extrajo información sobre la duración del video, los parámetros de interacción (por ejemplo, vistas, likes, índice de popularidad), el tiempo en línea y la fuente generadora. Estimamos la confiabilidad (DISCERN), la exhaustividad (puntaje de contenido) y la calidad (Global Quality Score) utilizando puntajes estandarizados. Resultados: Incluimos 200 videos en el estudio y clasificamos a 67% como videos útiles. Estos videos tuvieron un mayor número de vistas (19.491 [10.132-61.162] vs. 11.208 [8.183-20.538]), un mayor tiempo en línea (1.156 [719-2.254] vs. 832 [487-1.708] días) y una menor duración (6,3 [3,4-15,8] vs. 11,8 [7,4-20,3] min). Los parámetros de interacción fueron similares entre los videos útiles y los no útiles. Los videos útiles presentaron puntajes mayores de confiabilidad, exhaustividad y calidad; en su mayoría fueron generados por usuarios independientes y por organizaciones gubernamentales/agencias de noticias. Las organizaciones académicas generaron únicamente 15% de los videos útiles. Conclusiones: La mayoría de la información en YouTube® para pacientes hispanohablantes con AR es útil. Sin embargo, los parámetros de interacción son similares entre los videos útiles y los no útiles. Se requiere una mayor participación de las organizaciones académicas en el desarrollo de multimedia educativo de alta calidad.(AU)

Emerging trends in nurse-led programs of care for management of patients with established rheumatoid arthritis: Systematic literature review / Tendencias emergentes en los programas de atención dirigidos por enfermeras para el manejo de pacientes con artritis reumatoide establecida: Revisión sistemática de la literatura

Introduction: In patients with rheumatoid arthritis (RA), nurses are considered as essential, not only to ensure pharmacological safety, but also in the promotion in self-care and decision-making, favouring the empowerment of patients. This systematic review aimed to summarize the available literature on the health education by the nurse in patients with RA. Material and methods: Following Cochrane Collaboration procedures, the PRISMA statement and PRISMA checklist, relevant quantitative studies published were retrieved from the CINAHL, Scopus, PubMed and Medic databases and then systematically reviewed. The search ended in August 2021. Nineteen studies were retained for inclusion and evaluated with the Scottish Intercollegiate Guidelines Network for Systematic Reviews. Results: We found statistically significant improvement in self-care (five studies), disease activity (three studies), quality of life (two studies), satisfaction (five studies) and adherence (one study) with the nursing-led management of patients with established rheumatoid arthritis. Discussion: Although there is solid evidence of improvement in satisfaction and self-care, there seems to be a trend also to improve other outcomes, such as DAS28, from the EULAR recommendations, the expansion of the therapeutic arsenal for rheumatoid arthritis and shared decision-making. In addition, recently and due to the implementation of new technologies, the role of the nurse has been evaluated through virtual consultations. The results of recent studies have shown that this an effective and well-accepted novel approach for the management of patients with stable rheumatoid arthritis. Conclusion: Our study suggests that nurse-led health education, in addition of improvement in satisfaction and self-care, improve activity disease scores in RA patients.(AU)

Introducción: En los pacientes con artritis reumatoide, las enfermeras se consideran esenciales, no solo para garantizar la seguridad farmacológica, sino también en la prestación de promoción en el autocuidado y la toma de decisiones, favoreciendo el empoderamiento de los pacientes. Esta revisión sistemática tuvo como objetivo resumir la literatura disponible sobre la educación sanitaria por parte de la enfermera en pacientes con artritis reumatoide. Material y métodos: Siguiendo los procedimientos de la Colaboración Cochrane, la declaración PRISMA y la lista de comprobación PRISMA, se recuperaron los estudios cuantitativos relevantes publicados en las bases de datos CINAHL, Scopus, PubMed y Medic y, a continuación, se revisaron sistemáticamente. La búsqueda finalizó en agosto de 2021. Diecinueve estudios fueron retenidos para su inclusión y evaluados con la Scottish Intercollegiate Guidelines Network for Systematic Reviews. ResultadosSe encontró una mejoría estadísticamente significativa en el autocuidado (cinco estudios), la actividad de la enfermedad (tres estudios), la calidad de vida (dos estudios), la satisfacción (cinco estudios) y la adherencia (un estudio) con el manejo dirigido por enfermería de pacientes con artritis reumatoide establecida. Discusión: Aunque siempre ha habido evidencias de mejora en la satisfacción y el autocuidado, parece haber una tendencia a mejorar también otros resultados, como el de Disease Activity Score in 28 Joints (DAS28), a partir de las recomendaciones de la European League Against Rheumatism (EULAR), la ampliación del arsenal terapéutico para la artritis reumatoide y la toma de decisiones compartida. Además, recientemente y debido a la implantación de las nuevas tecnologías, se ha evaluado el papel de la enfermera a través de las consultas virtuales. Los resultados de estudios recientes han demostrado que se trata de un nuevo enfoque...(AU)