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ID PMID Title PublicationDate abstract
34484201 Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Mino 2021 Recent studies suggest that elevated CXCL13 serum levels in patients with primary Sjögren's syndrome (pSS) associate with minor salivary gland (MSG) histologic features, disease severity, as well as high-risk status for non-Hodgkin lymphoma (NHL) development and NHL itself. In contrast, limited discriminative value of CXCL13 saliva levels has been reported. Prompt by these reports, we sought to validate the clinical utility of CXCL13 by investigating potential correlations of serum and saliva levels with MSG histopathologic [including CXCL13+-cell number, severity of infiltrates and germinal center (GC) formation], serologic and clinical parameters, as well as NHL. CXCL13 levels were evaluated in paired serum and saliva specimens of 45 pSS patients (15 with NHL; pSS-associated NHL: SSL), 11 sicca-controls (sicca-complaining individuals with negative MSG biopsy and negative autoantibody profile), 10 healthy individuals (healthy-controls) and 6 non-SS-NHLs. CXCL13+-cells were measured in paired MSG-tissues of 22 of pSS patients studied (including 7 SSLs) and all sicca-controls. CXCL13 serum levels were significantly increased in pSS and SSL patients compared to sicca- and healthy-controls and were positively correlated with the CXCL13+-cell number and biopsy focus-score. Serum CXCL13 was significantly higher in pSS patients with GCs, rheumatoid factor, hypocomplementemia, high disease activity, NHL and in high-risk patients for NHL development. CXCL13 saliva levels were significantly increased in SSL patients (compared to non-SS-NHLs), patients with GCs and in high-risk for NHL patients. Univariate analysis revealed that CXCL13 serum, but not saliva, levels were associated with lymphoma, an association that did not survive multivariate analysis. Conclusively, our findings confirm that serum, but not saliva, levels of CXCL13 are associated with histologic, serologic and clinical features indicative of more severe pSS.
34060451 [Advances in autoantibodies and primary Sjogren's syndrome: An update]. 2021 Jun One of the hallmarks of primary Sjogren's syndrome (pSS) is the presence of various autoantibodies in patients' serum, including traditional autoantibodies for disease diagnosis and classification, autoantibodies associated with other autoimmune diseases, and the novel autoantibodies identified from mouse models. The autoantibodies are closely related to the diagnosis, prognosis, and clinical manifestations of pSS. There are significant differences in the prevalence and clinical correlations between anti-Ro60 antibody and anti-Ro52 antibody. Also, the novel autoantibodies play an important role in the diagnosis and classification of pSS. These advances further improve the accuracy of pSS diagnosis and provide references for basic and clinical research.
32430612 Combination value of biomarkers in discriminating adult onset Still's disease and sepsis. 2021 Feb BACKGROUND: Lymphocyte and plateletcrit (PCT) as proportions of routine complete blood count tests, have been studied as simple biomarkers for inflammatory diseases. The aim of our study was to investigate whether blood routine parameters, especially platelet parameters could be a useful tool to distinguish Adult onset Still's disease (AOSD) from sepsis. METHODS: We retrospectively reviewed 58 patients with AOSD and 55 sepsis patients diagnosed at the First Affiliated Hospital of Nanjing Medical University between January, 2015 to December 2018. Laboratory data including ferritin, blood routine parameters and C‑reactive protein (CRP) level were collected, and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) were calculated. RESULTS: The results showed that AOSD patients showed higher ferritin, lymphocyte and PCT (all P < 0.01) and these factors are independent risk factors for predicting AOSD. In receiver operating characteristic (ROC) curve analysis of LY, PCT and ferritin for distinguish of AOSD, the area under the curve (AUC) was 0.676 (0.576-0.777); 0.706 (95% CI = 0.596-0.816); 0.715 (0.617-0.814). Meanwhile, the AUC of the combination of lymphocyte, PCT and ferritin was 0.836 (0.737-0.909) with sensitivity 67.3, specificity 92.3, and the difference was significant. CONCLUSIONS: Thus we suggest that lymphocyte, PCT may be a useful tool to make a distinction between AOSD and sepsis, as supplementary biomarkers to ferritin.
33774640 Association between Hidradenitis Suppurativa and Inflammatory Arthritis: A Systematic Revi 2021 BACKGROUND: Several studies report a high prevalence of inflammatory arthritis among hidradenitis suppurativa (HS) patients. OBJECTIVES: To study the association between HS and inflammatory arthritis. METHODS: The systematic review and meta-analysis were performed according to the PRISMA guidelines to identify the association between HS and inflammatory arthritis, spondyloarthritis, ankylosing spondylitis (AS), and rheumatoid arthritis (RA). RESULTS: Seven studies were entered in the analysis, with 200,361 HS patients and 385,599 controls. Pooled analysis illustrated a significantly increased risk of inflammatory arthritis in HS patients compared to controls (odds ratio [OR] 3.44; 95% confidence interval [CI] 1.92-6.17). There was also a statistically significant association between HS and spondyloarthritis (OR 2.10; 95% CI 1.40-3.15), and between HS and AS (OR 1.89; 95% CI 1.14-3.12). Moreover, pooled analysis showed a statistically significant association between HS and RA (OR 1.96; 95% CI 1.28-2.98). CONCLUSIONS: Our findings show that HS patients have a 3-fold increased risk of developing inflammatory arthritis. HS patients are specifically at a higher risk for spondyloarthritis, its subtype AS, and RA.
34566640 Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumato 2021 Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1 β, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.
34535987 Importance of Shared Treatment Goal Discussions in Rheumatoid Arthritis-A Cross-Sectional 2021 Dec OBJECTIVE: Treat-to-target (T2T) and shared decision-making are valued features of current guidelines for rheumatoid arthritis (RA) management. Although T2T has demonstrated value for improving RA outcomes, implementation remains inconsistent and lacks standardization and procedures for including patient input. We sought to better understand the impact of shared decisions on T2T and how treatment goal discussions between patients and providers impact RA treatment improvement and satisfaction. METHODS: An anonymous, web-based questionnaire was presented to United States residents aged 18 years or older with a self-reported diagnosis of RA by a medical professional with 28 questions regarding socio-demographics, RA disease activity (DA), diagnosis, treatments, outcomes, and goals. Analyses included descriptive statistics with χ(2) and rank sum tests for comparisons. RESULTS: The questionnaire was completed by 907 people (mean age of 58 years; mean 11 years since diagnosis; 90% female). The majority (571; 63%) did not discuss RA treatment goals with providers. Patients engaging in treatment goal discussions with their providers were three times more likely to be satisfied with their treatment plans. Patients discussing treatment goals with their providers were more likely to have improved DA levels and 68% more likely to reach remission. CONCLUSION: A majority of patients with RA report having no treatment goal discussion with their providers; however, these discussions are associated with greater DA improvement and treatment satisfaction. Further research should seek understanding of how shared treatment goal discussions relate to successful RA management and explore the development of practical tools to implement them in regular clinic practice as part of a T2T regimen.
34366867 Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gu 2021 Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.
33644992 Discrepancy Between Multibiomarker Disease Activity and Clinical Disease Activity Scores i 2021 Feb 28 OBJECTIVE: Responsive assessment of disease activity in patients who have rheumatoid arthritis (RA) is necessary to evaluate therapeutic efficacy and guide treatment. We compared the utility of the multibiomarker disease activity (MBDA) score in the assessment of RA disease activity with that of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) score and the Clinical Disease Activity Index (CDAI) in a multicenter, randomized, placebo-controlled trial of repository corticotropin injection (RCI) in patients with persistently active RA. METHODS: Patients received 80 units of RCI twice weekly during a 12-week open-label period; those who experienced low disease activity at week 12 were randomly assigned to receive either 80 units of RCI or placebo twice weekly during a 12-week double-blind period. Changes in disease activity (measured by DAS28-ESR, CDAI, and MBDA scores) and correlations between MBDA scores and both DAS28-ESR and CDAI scores were assessed. RESULTS: Changes from baseline in DAS28-ESR and CDAI scores suggested that RCI therapy led to clinically meaningful improvements in disease activity, but improvements from baseline in MBDA scores were below the minimally important difference threshold. For the DAS28-ESR and CDAI, correlations with total MBDA and individual component scores were generally low (r ≤ 0.3) and occasionally moderate (r > 0.3 but r < 0.5). CONCLUSION: The results of the present study suggest overall MBDA scores are not sufficiently responsive for assessing RA disease activity after RCI therapy. These findings are consistent with those seen with other RA drugs and, although they are from a clinical trial, suggest the MBDA should not be a preferred disease activity measure in clinical practice.
34784873 Association of Serum and Crevicular Fluid Dickkopf-1 Levels with Disease Activity and Peri 2021 Nov 15 BACKGROUND: The aim of this study was to assess DKK-1 levels, in Gingival Crevicular Fluid (GCF) and serum, as a biomarker for bone loss and disease activity in periodontitis and early RA (eRA). METHODS: In this cross-sectional study, we obtained serum and GCF from 10 interproximal sites (Distal Buccal I/S, Mesio Buccal I/S, Distal Palatal/Lingual, Mesio Palatal/Lingual) according to the highest degree of inflammation by a patient for 240 sites from eRA patients. Patients received a periodontal assessment, a radiographic evaluation, tomography of interproximal sites, and DKK1 levels were determined by ELISA. Comparisons were performed by the Mann-Whitney U test and analysis by Chi2 test, and a logistic regression model was applied. RESULTS: The mean age was 46.33 ± 12.0 years, the Disease Activity Score (DAS-28-ESR) was 4.08 ± 1.4. Periodontitis was present in 65.2% of the patients, and 59.6% of these patients had bone loss in interproximal sites. Higher GCF-DKK1 levels were associated with serum-DKK1 (OR:2.41 IC95% 1.14-5.09, p=0.021) and were related with DAS28-ESR (p=0.001), Routine Assessment of Patient Index Data 3 (RAPID 3) (p=0.001), and tender joints (p=0.040). Foot bone erosion and juxta-articular osteopenia were associated with high levels of serum-DKK1 (p=0.009 and 0.001, respectively). Serum-DKK1 were associated with SDAI (OR: 2.38 IC95% 1.03-5.52, p=0.043), RAPID 3 (p=0.001), and rheumatoid factor (p=0.018). The GCF-DKK1 levels were associated with periodontal bone loss (p=0.011), periodontitis (p=0.070) and its severity (OR: 2.58 IC95% 2.28-7.28, p=0.001). Bone loss was more frequent in buccal sites (73.5%) and was associated with increased levels of DKK1 (p=0.033). CONCLUSION: In the early stages of the eRA disease, serum and GCF-DKK1 could be a biomarker for clinical disease activity and periodontal and articular bone erosion.
34303577 Subjective and Objective Outcomes of Surgery for Rheumatoid Forefoot Deformities Under the 2022 Jan We investigated the clinical outcomes of surgical procedures for the treatment of forefoot deformities in patients with rheumatoid arthritis. Twenty feet in 16 women (mean age 62.1 years) underwent corrective osteotomy of the first metatarsal bone with shortening oblique osteotomy of the lesser metatarsophalangeal joints (joint-preservation group), while 13 feet in 12 women (mean age 67.4 years) underwent arthrodesis of the first metatarsophalangeal joint with resection arthroplasty of the lesser metatarsophalangeal joints (joint-sacrifice group); mean follow-up for each group was 25.8 and 23.8 months, respectively. The mean total Japanese Society for Surgery of the Foot (JSSF) scale improved significantly from 64.2 to 89.2 in the joint-preservation group (p < .001), and from 54.2 to 74.2 in the joint-sacrifice group (p = .003). In the joint-preservation group, the postoperative range of motion (ROM) of the joint, walking ability, and activities of daily living scores of the JSSF scale were significantly higher than those in the joint-sacrifice group (p = .001, p = .001, and p = .019, respectively). There were no differences in the subscale scores of the self-administered foot evaluation questionnaire between 2 groups either pre- or postoperatively. No differences in the postoperative complications were found between 2 groups. Although the joint-sacrificing procedure resulted in lower objective outcomes than the joint-preserving procedure regarding the ROM of the joint, the walking ability, and the level of activities of daily living, both procedures resulted in similar treatment outcomes when evaluated by the subjective measures.
34876862 Analysis of Serum Immune Markers in Seropositive and Seronegative Rheumatoid Arthritis Amo 2021 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovial membrane. RA is classified as seropositive or seronegative, according to the absence or presence of primarily IgM RF, RF, and/or ACPA. The aim of this study is to identify the relationship between the serotype of rheumatoid arthritis and the level of ESR. METHODS AND MATERIALS: This is a descriptive, cross-sectional study done in Omdurman military hospital, Khartoum, Sudan. Conducted with 60 patients with RA, data were collected through a designated questionnaire which included demographic, age, gender, duration of the disease, laboratory finding. All the patients in the study were treated with conventional DMARDs and diagnosed according to the 2010 ACR/EULAR criteria; their disease activity status was assessed by DAS28/ESR. Data were analyzed using SPSS version 23. RESULTS: The study found that 91.7% of the patients were females, patients of age group between 36 and 50 years had the highest percentage at 38.3% followed by those between 51 and 70 years and the least age group between 20 and 35 years, 36.7% and 15%, respectively. Of all the patients 61.7% were found to be SPRA, while the remaining 38.3% were seronegative (SNRA). Altogether 55% of the patients had moderate disease activity, followed by 16.7% who had a remission, 15% had high disease activity and the remaining 13.3% had low disease activity. The metacarpophalangeal (MCP) joint was found to be the only joint that was significantly associated with DAS28 and its involvement was greater among seropositive patients. The most affected joints were found to be shoulders, knees, wrist, MCP, PIP and elbow, in that order. CONCLUSION: Females, middle-age group and shoulder joint were the most affected. Most RA was found to be SPRA, and the seropositive group was found to be more associated with high disease activity, while the seronegative group was associated with remission and low disease activity.
34803999 Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inh 2021 Clinical development of BTK kinase inhibitors for treating autoimmune diseases has lagged behind development of these drugs for treating cancers, due in part from concerns over the lack of selectivity and associated toxicity profiles of first generation drug candidates when used in the long term treatment of immune mediated diseases. Second generation BTK inhibitors have made great strides in limiting off-target activities for distantly related kinases, though they have had variable success at limiting cross-reactivity within the more closely related TEC family of kinases. We investigated the BTK specificity and toxicity profiles, drug properties, disease associated signaling pathways, clinical indications, and trial successes and failures for the 13 BTK inhibitor drug candidates tested in phase 2 or higher clinical trials representing 7 autoimmune and 2 inflammatory immune-mediated diseases. We focused on rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE) where the majority of BTK nonclinical and clinical studies have been reported, with additional information for pemphigus vulgaris (PV), Sjogren's disease (SJ), chronic spontaneous urticaria (CSU), graft versus host disease (GVHD), and asthma included where available. While improved BTK selectivity versus kinases outside the TEC family improved clinical toxicity profiles, less profile distinction was evident within the TEC family. Analysis of genetic associations of RA, MS, and SLE biomarkers with TEC family members revealed that BTK and TEC family members may not be drivers of disease. They are, however, mediators of signaling pathways associated with the pathophysiology of autoimmune diseases. BTK in particular may be associated with B cell and myeloid differentiation as well as autoantibody development implicated in immune mediated diseases. Successes in the clinic for treating RA, MS, PV, ITP, and GVHD, but not for SLE and SJ support the concept that BTK plays an important role in mediating pathogenic processes amenable to therapeutic intervention, depending on the disease. Based on the data collected in this study, we propose that current compound characteristics of BTK inhibitor drug candidates for the treatment of autoimmune diseases have achieved the selectivity, safety, and coverage requirements necessary to deliver therapeutic benefit.
33679400 Modeling and Simulation to Support Phase Ib/IIa Dose Selection for WBP216, A Long Half-Lif 2021 WBP216 is an innovative IL-6 antibody, presenting high affinity to IL-6 and a long half-life (40-60 days). To optimize the dosage regimen for future clinical trials, pharmacokinetics (PK) and pharmacodynamics (PD) of WBP216 would be firstly characterized in Chinese rheumatoid arthritis (RA) patients. PK, CRP and DAS28 data of WBP216 were collected from 26 RA patients in a single ascending dose study. Non-linear mixed effects modeling was used for a population PK/PD analysis. A two-compartment model with a sequential zero-first order absorption and a first order elimination best described PK behavior of WBP216. Apparent systemic clearance was 0.015 L/h, central volume was 8.04 L. CRP as the fast-decreasing endpoint and DAS28 as the slow-reacting endpoint were both fitted well through an indirect response model. The baseline of ALT and free IL-6 were found associated with PK/PD parameters during covariates exploration. Simulation results confirmed that a loading dose regimen either of administration at weeks 0, 2, and 6 or doubling the maintenance dose level, followed by maintenance dosing of 75-150 mg every 8 weeks, was expected to provide a best risk/benefit ratio in future clinical studies. We hope this first PK/PD study of WBP216 in Chinese RA patients will help in the clinical development of WBP216 in future and provide a reference to the dosage optimization of similar antibodies with long half-life. Clinical Trial Registration: CTR20170306.
34730058 MiR-144-3p induced by SP1 promotes IL-1β-induced pyroptosis in chondrocytes via PTEN/PINK 2022 Feb Rheumatoid arthritis (RA) often leads to functional disabilities and deformities. MiRNA plays a vital role in cell pyroptosis. Nevertheless, the function and underlying mechanism of miR-144-3p in pyroptosis during the progression of RA remains unclear. In this study, N1511 cells were stimulated with IL-1β to construct a RA model. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess the cell viability. Cell pyroptosis was detected by flow cytometry. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-18) were assessed by enzyme-linked immunosorbent assay (ELISA). The relationship among specific protein 1 (SP1), microRNA-144-3p (miR-144-3p), and phosphatase and tensin homolog (PTEN) was explored by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP), respectively. The level of miR-144-3p in N1511 cells was upregulated by IL-1β. MiR-144-3p knockdown inhibited IL-1β-induced pyroptosis in N1511 cells, and the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), Cleaved caspase-1, Gasdermin D (GSDMD), and Cleaved caspase-3 in IL-1β-stimulated N1511 cells were increased. The levels of inflammatory cytokines in N1511 cells were increased by IL-1β, which were restored by miR-144-3p knockdown. MiR-144-3p knockdown abolished IL-1β-induced inactivation of putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein (Parkin) signalling. Moreover, transcription factor SP1 could upregulate miR-144-3p expression and miR-144-3p negatively regulated PTEN expression. In summary, MiR-144-3p induced by SP1 could promote IL-1β-induced chondrocyte pyroptosis via inhibiting PTEN expression and suppressing the activation of PINK1/Parkin signalling, which provided a new strategy against RA.
35050146 Methotrexate Disposition, Anti-Folate Activity, and Metabolomic Profiling to Identify Mole 2021 Dec 28 Methotrexate (MTX) is widely used in the treatment of autoimmune arthritis but is limited by its unpredictable and variable response profile. Currently, no biomarkers exist to predict or monitor early therapeutic responses to MTX. Using a collagen-induced arthritis (CIA) mouse model, this study aimed to identify biochemical pathways and biomarkers associated with MTX efficacy in autoimmune arthritis. Following arthritis disease induction, DBA/1J mice were treated with subcutaneous MTX (20 mg/kg/week) and disease activity was assessed based on disease activity scores (DAS) and paw volume (PV) measurements. Red blood cell (RBC) and plasma samples were collected at the end of the study and were assessed for folate and MTX content. Plasma samples were analyzed by semitargeted global metabolomic profiling and analyzed by univariate and multivariate analysis. Treatment with MTX was associated with significant reductions in disease activity based on both DAS (p = 0.0006) and PV (p = 0.0006). MTX therapy resulted in significant reductions in 5-methyltetrahydrofolate (5mTHF) levels in plasma (p = 0.02) and RBCs (p = 0.001). Reductions in both RBC and plasma 5mTHF were associated with lower DAS (p = 0.0007, p = 0.01, respectively) and PV (p = 0.001, p = 0.005, respectively). Increases in RBC MTX were associated with lower DAS (p = 0.003) but not PV (p = 0.23). Metabolomic analysis identified N-methylisoleucine (NMI) and quinolone as metabolites significantly altered in disease mice, which were corrected towards healthy control levels in mice treated with MTX. Reductions in plasma NMI were associated with lower DAS (p = 0.0002) and PV (p = 9.5 × 10(-6)). Increases in plasma quinolone were associated with lower DAS (p = 0.02) and PV (p = 0.01). Receiver-operating characteristic curve analysis identified plasma NMI (AUC = 1.00, p = 2.4 × 10(-8)), RBC 5mTHF (AUC = 0.99, p = 2.4 × 10(-5)), and plasma quinolone (AUC = 0.89, p = 0.01) as top discriminating metabolites of MTX treatment. Our data support a relationship between MTX efficacy and its effect on circulating folates and identified 5mTHF, NMI, and quinolone as potential therapeutic biomarkers of disease activity and MTX response in the CIA mouse model of autoimmune arthritis.
34639000 Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence. 2021 Oct 1 Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40-60 ng/mL (100-150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.
34325117 CX3CL1/fractalkine regulates the differentiation of human peripheral blood monocytes and m 2021 Oct Osteoclast differentiation is promoted under inflammatory conditions and osteoclasts play a major role in bone destruction in rheumatoid arthritis (RA). Chemokine (C-X3-C motif) ligand 1 (CX3CL1), also known as fractalkine, functions as a chemoattractant and adhesion molecule, and is involved in the pathogenesis of RA. The blockade of CX3CL1 inhibits the migration of macrophages and osteoclast precursor cells into the inflamed synovium. In the present study, we investigated the direct stimulatory effects of CX3CL1 on osteoclast differentiation from human peripheral blood monocytes and monocyte-derived dendritic cells. A stimulation with CX3CL1 significantly promoted osteoclast differentiation from CD16(-) monocytes and also monocyte-derived dendritic cells induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). On the other hand, CD16(+) monocytes treated with M-CSF and RANKL did not differentiate into osteoclasts, even with CX3CL1. Calcium resorption was significantly increased by monocyte-derived osteoclasts, but not by dendritic cell-derived osteoclasts, following the addition of CX3CL1. The present results suggest that CX3CL1 directly regulates osteoclast differentiation. CX3CL1 may play important roles in the pathogenesis of RA, not only through the accumulation of inflammatory cells, but also through osteoclastogenesis.
33558062 Reverse total shoulder arthroplasty clinical and patient-reported outcomes and complicatio 2021 Apr OBJECTIVE: This systematic review aimed to investigate differences in clinical outcomes, patient-reported outcomes (PROs), and complication types and rates among preoperative diagnoses following reverse total shoulder arthroplasty (RTSA): rotator cuff tear arthropathy, primary osteoarthritis, massive irreparable rotator cuff tear, proximal humeral fracture, rheumatoid arthritis (RA), and revision of anatomic arthroplasty (Rev). LITERATURE SEARCH: Three electronic databases were searched from inception to January 2020. STUDY SELECTION CRITERIA: The inclusion criteria were (1) patients with a minimum age of 60 years who underwent RTSA for the stated preoperative diagnoses, (2) a minimum of 2 years' follow-up, and (3) preoperative and postoperative values for clinical outcomes and PROs. DATA SYNTHESIS: Risk of bias was determined by the Methodological Index for Non-randomized Studies tool and the modified Downs and Black tool. Weighted means for clinical outcomes and PROs were calculated for each preoperative diagnosis. RESULTS: A total of 53 studies were included, of which 36 (68%) were level IV retrospective case series. According to the Methodological Index for Non-randomized Studies tool, 33 studies (62%) showed a high risk of bias; the 3 randomized controlled trials showed a low risk of bias on the modified Downs and Black tool. RTSA improved clinical outcomes and PROs for all preoperative diagnoses. The Rev group had poorer final outcomes as noted by a lower American Shoulder and Elbow Surgeons score (69) and lower pain score (1.8) compared with the other preoperative diagnoses (78-82 and 0.4-1.4, respectively). The RA group showed the highest complication rate (28%), whereas the osteoarthritis group showed the lowest rate (1.4%). CONCLUSION: Studies in the RTSA literature predominantly showed a high risk of bias. All preoperative diagnoses showed improvements; Rev patients showed the worse clinical outcomes and PROs, and RA patients showed higher complication rates. The preoperative diagnosis in RTSA patients can impact outcomes and complications.
33569709 Medical overuse of therapies and diagnostics in rheumatology. 2021 May Medical overuse leads to a burden on healthcare costs and potentially is harmful to patients. We wanted to address medical overuse in musculoskeletal disease and rheumatology. We performed a systemic literature review from PubMed and Embase to study medical overuse. On the initial screen, 1499 studies were identified, 839 of them were related to medical overuse. Out of these, 52 were related to overuse in musculoskeletal diseases. Finally, 20 articles were chosen for this systemic review that reported overuse in rheumatology. The article identifies issues with overtesting, including the use of dual-energy X-ray absorptiometry to screen for osteoporosis in women younger than 65 years old and the use of magnetic resonance imaging to evaluate for osteoarthritis. Studies related to overtreatment reported over-prescription of vitamin D supplements resulting in vitamin D toxicity and increased risk of inappropriate prescriptions in patients with osteoarthritis and rheumatoid arthritis. Overtreating osteoporosis was reported after industry-sponsored education. Articles describing methods to reduce overuse included a study showing the reduction of unnecessary dual-energy X-ray absorptiometry scans after the introduction of the Choosing Wisely Campaign. Our findings suggest that there is some evidence that overtesting and overtreatment may be present in the field of rheumatology. This review aims to highlight this and help rheumatologists to be aware of overuse practices and provide appropriate evidence-based healthcare.
33557374 Molecular Imaging of Inflammatory Disease. 2021 Feb 4 Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.