Subluxación atlantoaxial en artritis reumatoidea. Resolución por odontoidectomía endonasal endoscópica y fusión e instrumentación por abordaje posterior. Reporte de caso

La subluxación atlantoaxial es la lesión más frecuente en la columna cervical causada por la artritis reumatoidea. Se manifiesta por rigidez de nuca, dolor cervical y déficit neurológico. El diagnóstico se realiza con tomografía computarizada e imágenes de resonancia magnética. El intervalo atlanto dental anterior mayor a 5mm indica inestabilidad atlantoaxial, el intervalo atlanto dental posterior menor a 14mm advierte riesgo neurológico. Las indicaciones más frecuentes de cirugía son: dolor cervical severo, inestabilidad y síntomas de mielopatía. Cuando existe compresión medular es necesaria la descompresión cervical alta sea por vía posterior o por vía anterior (odontoidectomía endonasal versus transoral). La línea rinopalatina nos indicará la factibilidad de una odontoidectomía endonasal endoscópica (OEE). El objetivo de la presentación del presente caso es compartir nuestra experiencia con la primera odontoidectomía endonasal endoscópica realizada en nuestro país y fomentar la utilización de la técnica. La cirugía fue realizada en un paciente con cuadriparesia espástica por subluxación atlantoaxial por artritis reumatoidea y que presentó excelente evolución pos operatoria, con recuperación casi completa. La OEE es una técnica operatoria mínimamente invasiva, ideal para pacientes con múltiples comorbilidades y que ofrece de buenos a excelentes resultados.

Atlantoaxial subluxation is the most common injury to the cervical spine caused by rheumatoid arthritis. It is manifested by neck stiffness, neck pain and neurological deficit. Diagnosis is made with computed tomography and magnetic resonance imaging. The anterior dental atlanto interval greater than 5mm indicates atlantoaxial instability, the posterior dental atlanto interval less than 14mm warns of neurological risk. The most frequent indications for surgery are: severe neck pain, instability and symptoms of myelopathy. When there is spinal cord compression, upper cervical decompression is necessary, either via a posterior or anterior approach (endonasal versus transoral odontoidectomy). The rhinopalatine line will indicate the feasibility of an endoscopic endonasal odontoidectomy (EEO). The objective of the presentation of this case is to share our experience with the first endoscopic endonasal odontoidectomy performed in our country and to promote the use of the technique. The surgery was performed on a patient with spastic quadriparesis due to atlantoaxial subluxation due to rheumatoid arthritis and who presented excellent postoperative evolution, with almost complete recovery. EEO is a minimally invasive surgical technique, ideal for patients with multiple comorbidities and offering good to excellent results.

Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Bone erosions and joint damage caused by chikungunya virus: a systematic review

ABSTRACT Background: Chikungunya fever is an emerging global infection transmitted by Aedes mosquitoes that manifests as an acute febrile illness with joint pain and can lead to chronic arthritis. The mechanism underlying chronic joint damage remains unclear; however, chronic chikungunya arthritis shares similarities with rheumatoid arthritis. Disease-modifying antirheumatic drugs have revolutionized rheumatoid arthritis treatment by preventing joint damage. However, the role of these therapies in chronic chikungunya arthritis has not been determined. We conducted a systematic review to evaluate the burden of joint structural damage in chronic chikungunya arthritis to help to define the role of disease-modifying therapy in this disease. Methods: This systematic review included retrospective and prospective studies, trials, and case reports evaluating joint damage caused by chikungunya virus. Various databases were searched without any date or language restrictions. Study selection was conducted independently by two researchers, and data were extracted from the articles selected. Results: A total of 108 studies were initially evaluated, with 8 meeting the inclusion criteria. Longitudinal studies have reported persistent joint pain from chikungunya infection and the progression of radiographic joint damage up to 13 years post-infection. Joint imaging revealed synovial inflammation, bone erosion, and cartilage destruction in patients with chronic chikungunya arthritis. Conclusions: Few studies have addressed chikungunya-induced joint damage, limiting our understanding of chronic chikungunya arthritis. Nevertheless, chronic chikungunya arthritis has similarities to rheumatoid arthritis. The success of early disease-modifying antirheumatic drug therapy in rheumatoid arthritis underscores the need for comprehensive research on its role in chikungunya arthritis.

Apport de l'échographie dans le diagnostic des hépatopathies chez les patients souffrant de la polyarthrite rhumatoïde à Cotonou / Hospital frequency and contribution of ultrasound in the diagnosis of hepatopathy in patients suffering from rheumatoid arthritis in Cotonou

Introduction L'échographie, modalité plus accessible dans notre pays constitue une alternative incontournable au diagnostic des hépatopathies sur polyarthrite rhumatoïde (PR). L'objectif de ce travail était de déterminer les caractéristiques de ces hépatopathies ainsi que l'apport de l'échographie dans leur diagnostic au CNHU-HKM. Méthode Etude transversale descriptive et analytique portant sur les patients suivis pour une PR, vus en consultation dans le service de rhumatologie du CNHU-HKM, ayant bénéficié d'une échographie abdominale, pendant la période d'étude allant du 15 Juillet 2020 au 15 Octobre 2020. La prévalence, les caractéristiques clinico-biologiques et échographiques des hépatopathies ont été étudiées. Résultats Ont été colligés 42 sujets. la fréquence hospitalière des hépatopathies était de 40,5%. La sex-ratio était de 0,8 et l'âge moyen de 50,9 ans. Sur le plan clinique, des douleurs de l'hypocondre droit (9,5%) , une hépatomégalie (14,3%) et un syndrome métabolique (38%) avaient été trouvées. Une cytolyse hépatique était notée chez 01 patient ; l'Ag HBs positif chez 02 patients. A l'échographie une hépatomégalie (26,1%), une stéatose hépatique (16,7%) et un kyste hépatique (2,4%) étaient retrouvés. Les étiologies principales évoquées étaient : hépatomégalie isolée (41,2%), métabolique (35,5%) et virale ( 11,4%). Conclusion Les hépatopathies sur PR sont fréquentes. Le profil clinique n'est pas spécifique. L'échographie dans notre contexte constitue un moyen fondamental d'aide au diagnostic chez ces patients.

Ultrasound, a more accessible modality in our country, is an essential alternative to the diagnosis of liver disease on rheumatoid arthritis (RA). The objective of this work was to determine the characteristics of these liver diseases as well as the contribution of ultrasound in their diagnosis in CNHU-HKM. Method Descriptive and analytical cross-sectional study of patients followed for RA, seen in consultation in the rheumatology department of the CNHU-HKM, who underwent an abdominal ultrasound, during the study period from July 15, 2020 to October 15, 2020. The prevalence, clinico-biological and ultrasound characteristics of liver disease were studied. Results A total of 42 subjects were collected. The hospital frequency of liver disease was 40.5%. The sex ratio was 0.8 and the mean age was 50.9 years. Clinically, right hypochondria pain (9.5%), hepatomegaly (14.3%) and metabolic syndrome (38%) were found. Hepatic cytolysis was noted in 01 patient; HBsAg positive in 02 patients. On ultrasound, hepatomegaly (26.1%), fatty liver disease (16.7%) and a liver cyst (2.4%) were found. The main etiologies were isolated hepatomegaly (41.2%), metabolic (35.5%) and viral (11.4%). Conclusion: Liver disease in RA patients is common. Ultrasound in our context is a fundamental means of aiding in the diagnosis of these patients

Mechanism of Traditional Chinese Medicine Intervening in Pyroptosis to Prevent and Treat Bone and Joint Related Diseases： A Review / 中国实验方剂学杂志

Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

Chinese Medicines Treat Rheumatoid Arthritis via Gut-joint Axis： A Review / 中国实验方剂学杂志

Rheumatoid arthritis （RA） is a systemic autoimmune disease with local joint pain as the main clinical manifestation. It is one of the diseases specifically responding to traditional Chinese medicine （TCM）. The occurrence of RA is not only related to innate factors like genetic disorder but also associated with environmental factors， such as diets and microbial infection. The intestine， a vital human organ with digestive and immune functions， is a place where microorganisms colonize and exert intestinal metabolism-improving， barrier-protecting， and immunomodulatory effects. As the research on the onset and treatment of RA is deepening， the potential relationship of intestinal structural and functional abnormalities with the pathogenesis and progression of RA has been revealed. As clinical and experimental studies indicated， joint inflammation coexists with the impaired barrier function， imbalanced immune cells， and disordered gut microbiota. The theory of the gut-joint axis in the pathogenesis， progression， and treatment of RA is highly consistent with the holistic view in TCM. The recent pharmacological studies have shown that Chinese medicine prescriptions and active components can inhibit inflammation， protect joints， and maintain the intestinal function. This article summarizes the basic connotation of the gut-joint axis in RA and the mechanism by which TCM protect the intestinal barrier and modulate the immunity by regulating the gut microbiota structure and improving microbial metabolism in the treatment of RA. This review gives insights into the future research on the gut-joint axis in RA.

Improvement effect and mechanism of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis model rats / 中国药房

OBJECTIVE To study the improvement effect of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis （RA） model rats and its potential mechanism. METHODS Female Wistar rats were randomly divided into normal control group， model group， aspirin group （positive control， 30 mg/kg）， low-dose and high-dose groups of total flavonoids from R. multiflora root （4.15， 8.30 g/kg， by crude drug）， with 10 rats in each group. Except for the normal control group， the RA model was induced in other groups by collagen induction and high-fat diet. After 14 days of modeling， they were given corresponding drug solution/0.5% sodium carboxymethyl cellulose solution intragastrically， once a day， for 36 consecutive days. The total body score， arthritis index （AI） and swollen joint count （SJC） of the rats were evaluated regularly. After the last medication， serum levels of interleukin-6 （IL-6）， intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule- 1 （VCAM-1） were determined. The pathological morphological changes in the vascular tissue of thoracic aorta were observed； the protein expression of Toll-like receptor 4 （TLR4） and the protein phosphorylation levels of Janus kinase 2 （JAK2） and signal transduction and activator of transcription 3 （STAT3） in vascular tissue of thoracic aorta were measured. RESULTS Compared with the normal control group， serum levels of IL-6， ICAM-1 and VCAM-1， protein expression of TLR4， and the protein phosphorylation levels of JAK2 and STAT3 in vascular tissue of thoracic aorta were increased significantly in model group （P＜ 0.01）. The atherosclerotic plaque （atheroma）， cholesterol crystal， lymphocyte infiltration and a small number of unbroken foam cell aggregation could be seen in the vascular tissue of thoracic aorta. Compared with the model group， total body score （except for the low-dose group）， AI and SJC were decreased significantly in groups of total flavonoids from R. multiflora root on the 28th day （P＜0.05 or P＜0.01）； total body score，AI and SJC were decreased significantly in low-dose group of total flavonoids from R. multiflora root on the 49th day （P＜0.05 or P＜0.01）； the other quantitative indicators in serum and vascular tissue were significantly reversed in groups of total flavonoids from R. multiflora root （P＜0.05 or P＜0.01）， and pathological damage of vascular tissue was significantly relieved. CONCLUSIONS Total flavonoids from R. multiflora root can significantly improve vascular injury in RA model rats， and its mechanism may be related to reducing the protein expression of TLR4 in vascular tissue and inhibiting the activation of IL-6/JAK2/ STAT3 signaling pathway.

Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis / 中国临床药理学与治疗学

AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.

Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment / 中国药理学通报

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats / 中国药理学通报

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Inhibition of Pannus Formation by Wutoutang in AIA Rats with Wind-cold-dampness Bi Syndrome Via Down-regulating HIF-1α/VEGFA/Ang Signaling Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg-1·d-1）， and indometacin group （10 mg·kg-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

Clinical observation of tofacitinib combined with hydroxychloroquine in the treatment of refractory rheumatoid arthritis / 中国药房

OBJECTIVE To observe the clinical efficacy and safety of tofacitinib combined with hydroxychloroquine in the treatment of refractory rheumatoid arthritis （RA）. METHODS From January 1， 2021 to January 1， 2022， 120 patients with refractory RA were selected as the study objects. According to the principle of random allocation， the patients were divided into group A， group B and group C， with 40 patients in each group. Group A was given Tofacitinib citrate tablet + Hydroxychloroquine sulfate tablet； group B was given Tofacitinib citrate tablet + Methotrexate tablet； group C was given Tofacitinib citrate tablet + Leflunomide tablet. Three groups were given relevant medicine for 6 months. Therapeutic efficacy and disease activity score 28 （DAS 28） of 3 groups as well as Sharp score， the levels of biochemical indicators [erythrocyte sedimentation rate （ESR）， C- reactive protein （CRP）]， immune indexes [rheumatoid factor （RF）， anti-cyclic peptide containing citrulline （anti-CCP） antibody]， serum cytokine indicators [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] before and after treatment were observed； the occurrence of adverse drug reactions during treatment was recorded. RESULTS After treatment， the proportions of ACR50 and ACR70 patients in group A were significantly higher than groups B and C （P＜0.05）； DAS28 score， Sharp score， biochemical indicators， immune indexes and serum cytokine indicators of 3 groups were significantly lower than before treatment （P＜0.05）， and gradually decreased with prolonged treatment time； after 6 months of treatment， DAS28 score， Sharp score， RF， anti-CCP antibody， the levels of IL-6 and TNF-α in group A were significantly lower than group B and C （P＜0.05）. There was no significant difference in the incidence of diarrhea， nausea and vomiting， leukopenia， rash， abnormal liver and kidney function， or dizziness among 3 groups （P＞0.05）. CONCLUSIONS Tofacitinib combined with hydroxychloroquine shows good efficacy and safety for refractory RA.

GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS-13/Brazil)

Abstract Background Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. Objectives This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. Methods The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). Results The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS-13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion The Brazilian Portuguese version of the RAKAS (RAKAS-13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Actividad y discapacidad en pacientes cubanos con artritis reumatoide como factores que influyen en la sexualidad / Activity and Disability in Cuban Patients with Rheumatoid Arthritis as Factors that Influence Sexuality

Introducción: La artritis reumatoide es una enfermedad autoinmune de carácter inflamatorio y crónico. La afectación en la esfera sexual es frecuente, compromete a ambos sexos y se relaciona con factores como el dolor, la discapacidad y el consumo de medicamentos. Esta afectación no ha sido suficientemente abordada en la literatura a pesar de su prevalencia, y en Cuba no se han reportado hasta el momento estudios relacionados sobre este tema de investigación. Objetivo: Determinar el impacto de la artritis reumatoide en la sexualidad y su relación en la actividad y la discapacidad. Métodos: Se realizó un estudio monocéntrico, transversal, descriptivo. Se incluyeron los pacientes con un diagnóstico de artritis reumatoide en el período comprendido de septiembre de 2019 a junio de 2021. Se utilizó el cuestionario Qualisex para evaluar el impacto de la artritis reumatoide en la sexualidad. Resultados: En el estudio doscientos veintiséis pacientes fueron incluidos, la media de edad fue de 53,38 años (DE ± 12,22) el 82,7 por ciento fueron mujeres. Al responder el autocuestionario Qualisex el 73,9 por ciento de los sujetos presentaron afectación en la sexualidad. No se estableció una relación significativa entre la afectación en la esfera sexual y el tiempo de evolución. A diferencia de los niveles altos de actividad y discapacidad. Conclusiones: En la población estudiada se presentó afectación en la sexualidad, no obstante, esta no se relacionó con el tiempo de evolución de la artritis reumatoide. Se encontró asociación entre la actividad de la enfermedad y la capacidad funcional con la afectación en la esfera sexual(AU)

Introduction: Rheumatoid arthritis is a chronic, inflammatory autoimmune disease. Disorders in the sexual sphere is frequent, it affects both sexes and it is related to factors such as pain, disability and medication consumption. This condition has not been sufficiently addressed in the literature despite its prevalence and in Cuba no studies related to the topic under study have been reported to date. Objective: To determine the impact of rheumatoid arthritis on sexuality and its relationship with activity and disability. Methods: A monocentric, cross-sectional and descriptive study was carried out on patients with a diagnosis of rheumatoid arthritis, from September 2019 to June 2021. The Qualisex questionnaire was used to evaluate the impact of rheumatoid arthritis on sexuality. Results: Two hundred twenty-six patients were included, the mean age was 53.38 years (SD ± 12.22) and 82.7percent were women. When answering the Qualisex self-questionnaire, 73.9percent of the subjects had effects in their sexuality. No significant relationship was established between the involvement in the sexual sphere and the time of evolution. Conclusions: The impact on sexuality in the studied population was not related to the duration of rheumatoid arthritis. On the other hand, an association was found between disease activity and functional capacity with effects in the sexual sphere(AU)

Análisis de la discapacidad por trastornos musculoesqueléticos en México de 1990 a 2021 / Analysis of musculoskeletal disorders-associated disability in Mexico from 1990 to 2021

Resumen Antecedentes: Los trastornos musculoesqueléticos (TME) afectan a 1710 millones de personas en todo el mundo y es la principal causa de discapacidad. Objetivo: Analizar los años vividos con discapacidad (AVD) por TME en México entre 1990 y 2021. Material y métodos: Con las estimaciones del estudio de la Carga Global de la Enfermedad 2021 se analizaron los AVD por TME y sus seis categorías: osteoartritis, artritis reumatoide, gota, dolor cervical, lumbalgia y otros TME. Se evaluaron patrones y tendencias del número, tasa cruda y tasa estandarizada por edad de los AVD a nivel nacional, estatal, por grupos de edad y sexo. Resultados: Los TME constituyeron la principal causa de AVD en México entre 1990 y 2021, con un incremento de 57.3 %; pasaron de 1458.4 a 2293.7 por 100 000 habitantes. La lumbalgia (840.6 AVD) destacó con la mayor tasa en 2021 y la osteoartritis, con el mayor incremento. Los TME se incrementaron con la edad y, con excepción de la gota, afectaron más a las mujeres. Conclusiones: De 1990 a 2021, los TME constituyeron la principal causa de AVD en México, con mayor impacto en adultos y mujeres. Los TME se evidencian desde edades tempranas, de ahí la necesidad de intervenciones continuas para preservar la calidad de vida.

Abstract Background: Musculoskeletal disorders (MSD) affect 1.71 billion people worldwide and are the leading cause of disability. Objective: To analyze the years lived with disability (YLD) attributed to MSD in Mexico between 1990 and 2021. Material and methods: With estimates from the Global Burden of Disease 2021 study, the YLDs due to MSD and their six categories were analyzed, including osteoarthritis, rheumatoid arthritis, gout, neck pain, low back pain, as well as other MSDs. Patterns and trends in the number, crude rate, and YLD age-standardized rate were evaluated at the national and state levels, as well as by age group and gender. Results: MSDs were the main cause of YLDs in Mexico between 1990 and 2021, with an increase of 57.3%, going from 1,458.4 to 2,293.7 per 100,000 population. Low back pain (840.6 YLD) showed the highest rate in 2021, while osteoarthritis had the largest increase. MSDs increased with age and, and except for gout, affected women more often. Conclusions: From 1990 to 2021, MSDs were the main cause of YLDs in Mexico, with a higher impact on adults and women. MSDs can appear early in life, hence the need for continuous interventions in order to preserve quality of life.

Relación de la enfermedad periodontal inflamatoria crónica con enfermedades sistémicas

Introducción: La enfermedad periodontal es una infección inmunoinflamatoria crónica de origen multifactorial. Puede avanzar a nivel sistémico por el paso de bacterias y sus productos al torrente sanguíneo, lo cual constituye un factor de riesgo para alteraciones sistémicas. La revisión bibliográfica se realizó de julio 2022 hasta febrero 2023. Se utilizaron las bases de datos PubMed, SciELO y Elsevier y el motor de búsqueda Google Académico. Objetivos: Describir la relación de la enfermedad periodontal inflamatoria crónica con enfermedades sistémicas. Desarrollo: La medicina periodontal estudia la relación que existe entre las periodontopatías y enfermedades sistémicas, como las cardiovasculares, cerebrovasculares, pulmonares, la renal crónica, la artritis reumatoide y el Alzheimer. Las bacterias provenientes de las bolsas periodontales pasan hacia la circulación sanguínea, producen infección metastásica y daño metastásico, mediante la producción de endotoxinas, lipopolisacáridos e inflamación metastásica. Conclusiones: La enfermedad periodontal crónica constituye un factor de riesgo para el desarrollo de enfermedades cardiovasculares, pulmonares, renales, trastornos cerebrovasculares, artritis reumatoide y el Alzheimer debido a reacciones inflamatorias producidas por microorganismos patogénicos; se establece una relación bidireccional entre estas enfermedades y las periodontopatías.

Introduction: Periodontal disease is a chronic immunoinflammatory infection of multifactorial origin. It can advance at a systemic level due to the passage of bacteria and their products into the bloodstream, which constitutes a risk factor for systemic alterations. The bibliographic review was carried out from July 2022 to February 2023. The PubMed, SciELO and Elsevier databases and the Google Scholar search engine were used. Objectives: Describe the relationship of chronic inflammatory periodontal disease with systemic diseases. Development: Periodontal medicine studies the relationship between periodontopathies and systemic diseases, such as cardiovascular, cerebrovascular, pulmonary, chronic kidney disease, rheumatoid arthritis and Alzheimer's. Bacteria from periodontal pockets pass into the blood circulation, producing metastatic infection and metastatic damage, through the production of endotoxins, lipopolysaccharides and metastatic inflammation. Conclusions: Chronic periodontal disease constitutes a risk factor for the development of cardiovascular, pulmonary, renal diseases, cerebrovascular disorders, rheumatoid arthritis and Alzheimer's due to inflammatory reactions produced by pathogenic microorganisms; A bidirectional relationship is established between these diseases and periodontopathies. The analysis of this relationship and the mechanisms by which it occurs guarantees the development of a more integrative care practice.