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ID PMID Title PublicationDate abstract
31820726 Validation of new classification criteria of rheumatoid arthritis in an international mult 2020 Sep OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.
30229869 Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via the PI3K- 2019 Feb Our previous study revealed that Yin Yang 1(YY1) played an important part in promoting interleukin (IL)-6 production in rheumatoid arthritis (RA). However, whether YY1 has any role in regulation of IL-8 in RA remains unclear. YY1 and IL-8 expression in RA patients were analyzed by real-time polymerase chain reaction (PCR). Ingenuity pathway analysis (IPA) was used to analyze the signaling pathway involved in YY1-induced IL-8 production. The expression of YY1 and proteins involved in the pathway were detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Migration of neutrophils was performed by chemotaxis assay. In this study, we found that high expression of IL-8 was positively associated with YY1 expression in RA. Blocking YY1 expression by YY1-short hairpin (sh)RNA lentivirus reduced IL-8 production. Mechanistically, we showed YY1 activated IL-8 production via the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Further, using a co-culture system consisting of peripheral blood mononuclear cells (PBMC) and neutrophils, we found that migration of neutrophils would be inhibited by YY1 RNA interference. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the YY1-shRNA lentivirus led to reduction of IL-8 levels and attenuation of inflammation and neutrophil infiltration in vivo. Our results reveal a role of YY1 involved in neutrophil infiltration in RA via the PI3K/Akt/mTOR/IL-8 signaling pathway. YY1 may be a new therapeutic target for treatment of RA.
30643265 A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammator 2019 Feb Rheumatoid arthritis is characterized by progressive joint inflammation and affects ~1% of the human population. We noted single-nucleotide polymorphisms (SNPs) in the apoptotic cell-engulfment genes ELMO1, DOCK2, and RAC1 linked to rheumatoid arthritis. As ELMO1 promotes cytoskeletal reorganization during engulfment, we hypothesized that ELMO1 loss would worsen inflammatory arthritis. Surprisingly, Elmo1-deficient mice showed reduced joint inflammation in acute and chronic arthritis models. Genetic and cell-biology studies revealed that ELMO1 associates with receptors linked to neutrophil function in arthritis and regulates activation and early neutrophil recruitment to the joints, without general inhibition of inflammatory responses. Further, neutrophils from the peripheral blood of human donors that carry the SNP in ELMO1 associated with arthritis display increased migratory capacity, whereas ELMO1 knockdown reduces human neutrophil migration to chemokines linked to arthritis. These data identify 'noncanonical' roles for ELMO1 as an important cytoplasmic regulator of specific neutrophil receptors and promoter of arthritis.
31030723 [T follicular helper cells and their related molecules in rheumatoid arthritis: A review]. 2019 Mar Abnormal T follicular helper (Tfh) cells in patients with rheumatoid arthritis (RA) is related to the occurrence and development of RA. At present, the mechanism of Tfh cells regulating RA is still unclear. In addition, Tfh cell surface molecules C-X-C motif chemokine receptor 5 (CXCR5), inducible costimulatory molecule (ICOS) and programmed death factor 1 (PD-1) and its secreted interleukin 21 (IL-21), B-cell lymphoma 6 (BCL6) have been shown to be involved in the development of RA. We mainly reviewied the mechanism of RA regulation from the perspective of Tfh cell surface molecules and their secreted factors, analyzed the effects of various molecules related to Tfh cells on RA, and explored the significance of each molecule in the clinical diagnosis of RA and the potential ways of treating RA with each molecule as a target.
30947583 Comparison of median nerve stiffness with and without rheumatoid arthritis by ultrasound r 2020 May Objectives: This study aimed to compare median nerve stiffness measured by ultrasound real-time tissue elastography in patients with and without rheumatoid arthritis (RA and non-RA groups, respectively).Methods: Altogether, 402 hands of 201 RA group and 222 hands of 111 non-RA group were included in the study. Ultrasonography was performed to evaluate the circumference, cross-sectional area (CSA) and strain ratio as an elasticity of the median nerve at the inlet level of the carpal tunnel and the proximal portion of the carpal tunnel inlet. Using propensity score matching, the difference between RA and non-RA group were analyzed.Results: After propensity score matching, 135 hands in 104 RA group and 70 non-RA group were finally analyzed. There were no significant differences in the circumference and CSA of the median nerve between the two groups. The strain ratio of the median nerve was significantly higher in RA group than in non-RA group only at the inlet of the carpal tunnel level.Conclusions: The nerve stiffness in patients with RA measured by ultrasound real-time tissue elastography was higher than without RA. Inflammatory condition of the flexor tendon and wrist joint in patients with RA may generate fibrotic changes in the median nerve.Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000015314.
31025368 Periodontal status correlates with anti-citrullinated protein antibodies in first-degree r 2019 Jul AIM: To evaluate periodontal status in first-degree relatives of patients with rheumatoid arthritis (FDR-RA) and detect correlation with the presence of anti-citrullinated protein antibodies (ACPAs). MATERIALS AND METHODS: Rheumatologic status and periodontal status were evaluated in a nested case-control study of FDR-RA with no diagnosis of RA at enrolment. The following parameters were assessed in 34 ACPA-positive (ACPA+) and 65 ACPA-negative (ACPA-) subjects: gingival index (GI), plaque index (PI), probing depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). We compared the two groups using conditional logistic regression. RESULTS: In ACPA+ individuals, the mean, PD, BOP, CAL and number of sites per person with PD > 4 mm and BOP were significantly higher compared to the ACPA- group. All ACPA+ subjects had periodontitis: 44.1% presenting moderate and 47.1% severe periodontitis. ACPA- subjects had mainly mild (30.8%) and moderate (27%) periodontitis, differences being significantly different for both moderate periodontitis (p = 0.001) and severe periodontitis (p < 0.001). In multivariable analyses, ACPA status (p = 0.04) and age (p = 0.002) were significantly and independently associated with periodontal conditions. CONCLUSION: High prevalence and severity of periodontitis in FDR-RA was associated with seropositivity to ACPAs. This further strengthens the hypothesis that periodontitis may be a risk factor in the development of RA.
31402523 Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are associated with diseas 2019 Nov BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are indicators of systemic inflammation and are useful as markers in systemic rheumatic diseases. In this study, we compared the NLR, PLR, and MLR among patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), and explored possible associations with clinical features, disease activity, and prognosis in patients with PMR. METHODS: The study enrolled 94 patients with PMR and 242 patients with RA who were initially diagnosed at the rheumatology clinic of a university-based tertiary hospital. Symptoms, physical examination, and medical histories were collected with the results of laboratory tests. RESULTS: Neutrophil-to-lymphocyte ratio (4.5 ± 3.3 vs 2.8 ± 1.8), PLR (222.7 ± 115.5 vs 159.7 ± 78.1), and MLR (0.4 ± 0.3 vs 0.3 ± 0.2) were higher in patients with PMR compared with patients with RA (all P < .001). NLR, PLR, and MLR were correlated with specific laboratory values, including CRP and albumin, in patients with PMR. After disease activity resolved, NLR (2.95 ± 2.32, P < .001), PLR (137.5 ± 82.3, P < .001), and MLR (0.26 ± 0.16, P < .001) decreased significantly. By comparing patients according to the disease course, swollen joint counts were higher in the chronic course group compared with the remission group (P = .03), while the NLR, PLR, and MLR were similar. CONCLUSIONS: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio levels were associated with disease activity and specific clinical features, although they could not predict prognosis in patients with PMR.
30761562 Systematic review with meta-analysis: extrahepatic manifestations in chronic hepatitis C v 2019 Mar BACKGROUND: Although the prevalence of extrahepatic manifestations of chronic hepatitis C virus (HCV) infection has been reported from Western countries, their prevalence in East Asian countries is not well known. AIM: To perform a systematic review to quantify the prevalence of selected extrahepatic manifestations of HCV among patients from East Asia. METHODS: Medline, CINAHL, EMBASE, Cochrane and country-specific databases were reviewed according to standard guidelines for meta-analyses. Only articles with patients from East Asian countries were included. RESULTS: After review, 34 articles were selected (Japan = 9; China = 5, Korea = 3, Taiwan = 16, multiple countries = 1) with 646 228 subjects, 66 436 with HCV. Mean age for HCV-infected patients was 56 years (range 41-72 years), 50% were male (range 26%-73%). The pooled prevalence of type 2 diabetes in East Asian HCV patients was 19.0% (95% confidence interval 15.6%-22.9%) (n = 19 studies) with an increased risk when compared to non-HCV: odds ratio (OR) 1.58 (1.28-1.94). The prevalence of chronic kidney disease in HCV was 9.2% (5.0%-16.2%) (n = 7 studies), also with a significantly increased risk: OR=1.98 (1.41-2.77). Pooled prevalence of cardiovascular disease in HCV was 8.6% (3.5%-19.9%) (n = 6 studies), also with an increased risk: OR = 1.55 (1.21-1.98). The prevalence of lichen planus in HCV was 8.9% (3.6%-20.6%) (n = 6 studies) while the prevalence of rheumatoid arthritis was 4.5% (0.6%-25.7%) (n = 4 studies). CONCLUSIONS: These data show increased risk of developing extrahepatic manifestations in East Asian patients with HCV. Both hepatic and extrahepatic manifestations of the infection should be used to accurately determine the total burden of the disease in the region.
31214867 Association of radiographic findings in hand X-ray with clinical features and autoantibodi 2020 Jan Musculoskeletal involvement is one of the major causes of impairment in daily life of patients with systemic sclerosis (SSc). Several hand radiographic findings can be seen in SSc patients; however, their association with clinical features and autoantibodies remains unclear. Here, we analyzed 124 SSc patients with their hand X-rays and clinical and serological features. Abnormal findings in hand X-rays including acro-osteolysis, calcinosis, flexion contracture, erosive change, joint space narrowing, and subluxation were observed in 110 patients (68%). These X-ray findings were more prevalent in patients with longer disease duration and digital ischemic changes. The majority of erosions were typical for erosive hand osteoarthritis, which was seen in 19% of patients. Hand X-ray findings were associated with involved organs; acro-osteolysis with interstitial lung disease, calcinosis with pulmonary arterial hypertension and gastrointestinal tract involvement, and flexion contracture with gastrointestinal tract involvement. Those findings were also relevant to autoantibodies; acro-osteolysis was more common in SSc patients with anti-Scl70 antibody but less in patients with anticentromere antibody. Calcinosis was more prevalent in patient with anticentromere antibody. In our study, organ involvements and SSc-associated autoantibodies showed associations with hand radiographic abnormalities. Hand X-ray findings might reflect underlying pathogenesis and autoantibody profiles in SSc patients.Key Points• Hand X-ray abnormalities were observed in approximately two-thirds of patients with SSc.• Erosive osteoarthritis was more prevalent in SSc patients than general population.• Hand X-ray findings were associated with disease duration, organ involvements, and SSc-associated autoantibodies, reflecting underlying pathogenesis.
31594444 Endovascular preoperative embolization for temporomandibular joint replacement surgery. 2020 Feb BACKGROUND AND PURPOSE: This retrospective study evaluates the safety and effectiveness of preoperative endovascular embolization in patients who underwent temporomandibular joint (TMJ) replacement surgery. MATERIAL AND METHODS: We included all patients treated with preoperative embolization of the internal maxillary artery (IMAX) between June 2016 and January 2019. All patients were treated by the same surgeon using standard surgical approaches and procedures. Periprocedural adverse events, blood loss during surgery and clinical follow-up are reported. RESULTS: Fourteen patients (12 females, median age 32.5) were treated with 21 embolizations of the IMAX (bilateral embolizations in seven patients) prior to TMJ replacement surgery with prosthetic joints (TMJ Concepts prostheses). Seven patients presented with TMJ ankylosis/degenerative joint disease/post-trauma deformity, four patients with Idiopathic Condylar Resorption and resultant mandibular displacement/hypoplasia, two patients with rheumatoid arthritis-associated condylar degeneration and resultant loss of mandibular position, and 1 patient being re-reconstructed following management of a prosthetic joint infection. Seven patients underwent bilateral prosthetic joint replacement. Four patients underwent additional facial skeletal surgery as part of their treatment. The mean blood volume loss during TMJ surgery was approximately 370 cc (range 100-800 cc). Joint space-specific blood loss was not recorded, but, as per the surgical team, was significantly decreased when compared to non-embolized patients. There were no intra-procedural complications. The median clinical follow-up was 3.5 months (range 1-24 months). The modified Rankin scale (mRS) was 0 before the procedure and at last clinical follow-up in all patients. After TMJ surgery, three patients reported paresthesia of the trigeminal nerve likely related to the residual condyle resection and two patients had mild facial nerve weakness (Temporal and/or Marginal Mandibular branch) related to the surgical exposures. CONCLUSION: Endovascular preoperative embolization of the IMAX is feasible, safe and likely effective in reducing blood volume loss in complex TMJ replacement surgery.
31084537 Rheumatology Care Using Telemedicine. 2020 Mar Introduction: People living in many parts of the world have limited access to diagnostic studies and therapies for rheumatologic, musculoskeletal, and connective tissue diseases. The challenge has been particularly poignant for rural areas of low- and middle-income countries. Objectives: We report on the implementation of a telemedicine program in Iran for the evaluation and treatment of patients with rheumatologic and musculoskeletal diseases. More than 4,800 patients were seen remotely over a span of 5 years by a rheumatologist in the United States. The remote rheumatologist was aided by a general physician and a nurse at a local charity hospital in northeastern Iran that has a catchment area that includes rural regions extending to the border of Afghanistan. Seventy to 90 patients were evaluated online by the remote rheumatologist 3 days a week. A subset of patients was evaluated by the rheumatologist in person every 4 months. Materials and Methods: The population of rheumatology patients was evaluated using descriptive statistics. Information collected included demographic information consisting of age, gender, and primary rheumatologic diagnosis. Results: The average age of patients who were seen was 52 years and 89% of patients were women. Approximately 50% of patients were Afghan refugees. The most common disorders included osteoarthritis (1,149, 23.6%), rheumatoid arthritis (653, 13.4%), axial spondyloarthropathies (647, 13.3%), lumbar spinal stenosis (427, 8.8%), meniscal tear of the knee (326, 6.7%), and psoriatic arthritis (217, 4.5%). Certain conditions were lower than expected such as lupus (19, 0.4%) and fibromyalgia (169, 3.5%). Diagnostic tests included serologic tests (1,328, 27.3%), plain radiographs (946, 19.5%), magnetic resonance imaging (899, 18.5%), bone densitometry (147, 3.0%), and electromyography and nerve conduction study (132, 2.7%). The most common medications prescribed were non-steroidal anti-inflammatory drugs (791, 16.3%), methotrexate (764, 15.7%), pregabalin (234, 4.8%), duloxetine (230, 4.7%), sulfasalazine (177, 3.6%), etanercept (97, 2.0%), tofacitinib (64, 1.3%), adalimumab (18, 0.4%), and infliximab (9, 0.2%). Conclusions: Telemedicine is becoming more prevalent. We report the successful use of this service in evaluation and management of rheumatic diseases in a region with limited access to rheumatologic care. We have shown that patients can be seen, evaluated, and successfully treated with a variety of medications, including biologic agents.
30753461 Anti-receptor activator of nuclear factor κB ligand antibody treatment increases osteocla 2019 Apr 26 The receptor activator of nuclear factor κB ligand (RANKL) is an important factor for osteoclastogenesis and contributes to the pathology of rheumatoid arthritis (RA); thus, the anti-RANKL antibody (Ab) has been expected to protect joint destruction in RA patients. IL-8 also has osteoclastogenic activity; however, the role of IL-8 in the bone pathology of RA as well as the relation between IL-8 and RANKL remain unclear. In the present study, clinical observation revealed serum IL-8 levels of 611 pg ml-1 in RA patients with anti-RANKL Ab and 266 pg ml-1 in the same patients without anti-RANKL Ab. In vitro assay showed that anti-RANKL Ab induced production of IL-8 from pre-osteoclast-like cells (OCLs), and IL-8 promoted the formation of OCLs from peripheral monocytes even without RANKL activity. We further showed that treatment with FK506 (tacrolimus) possibly inhibits the increase in IL-8 levels in RA patients with anti-RANKL Ab, and in vitro assay confirmed that FK506 suppressed IL-8 production in pre-OCLs. These results suggest that inhibition of RANKL induces the change in osteoclastogenesis-promoting factor from RANKL to IL-8, and FK506 may be a valuable combination drug to support the use of anti-RANKL Ab in treatment of RA.
31372851 Validity of adopting a Health Assessment Questionnaire Disability Index less than 0.5 as a 2019 Dec OBJECTIVES: The effect of age on the Health Assessment Questionnaire Disability Index (HAQ-DI) scores of rheumatoid arthritis (RA) patients and the validity of adopting HAQ-DI < 0.5 as the target for functional remission and comprehensive disease control (CDC) under a treat-to-target (T2T) treatment strategy were investigated. METHOD: A total of 441 RA patients with > 3-year treatment under T2T were evaluated. The relationships between the HAQ-DI score at follow-up (HAQ) and 28-joint Disease Activity Score with C-reactive protein, Sharp/van der Heijde Score, age at follow-up, and HAQ-DI at baseline were statistically evaluated with best subset regression analysis in groups separated according to age and the EULAR response. CDC status was evaluated with a chi-square test. RESULTS: The HAQ score significantly correlated with all indices in the group ≥ 65 years old (G-O) and in the group with good or moderate EULAR responses (p < 0.01). No significant correlation was observed in the group < 65 years old (G-Y) or in the group with no EULAR response. The CDC ratio was not significantly different between the age groups, whereas the HAQ failure ratio was significantly greater in G-O than in G-Y (p < 0.01). No significant difference was found between the EULAR response groups. CONCLUSIONS: The HAQ score is influenced by age in patients > 65 years. T2T is appropriate for attaining good disease activity control but does not always lead to functional remission in these patients. The HAQ score < 0.5 is not an appropriate target for functional remission according to the CDC criteria for elderly patients.Key Points• ADL in elderly RA patient aged ≥ 65 years declines corresponding to his/her aging.• Functional remission for elderly RA patients is not the same as that for young RA patients.• The HAQ score < 0.5 in elderly RA patient is not an appropriate target for CDC.
30818333 Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inh 2019 Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
30468820 Influence of the TNFSF4 rs1234315 polymorphism in the susceptibility to systemic lupus ery 2019 Apr OBJECTIVES: The tumour necrosis factor superfamily 4 (TNFSF4) is a candidate gene for autoimmune diseases. We investigated the relationship of this gene with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Chinese Guangxi population. METHODS: A total of 294 patients with SLE, 210 with RA, and 282 healthy controls were genotyped for single nucleotide polymorphism (SNP) rs1234315 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The potential functional effects of the SNP were predicted by in silico analysis. RESULTS: Statistically significant associations with SLE and RA were detected at rs1234315, both by allele analysis (odds ratio 1.47, 95% confidence interval 1.17-1.86, p = 0.001; odds ratio 1.49, 95% confidence interval 1.15-1.92, p = 0.002; respectively), and genotype analysis (p = 0.003 and p = 7.000 × 10(-5), respectively). The Akaike's information criterion (AIC) values indicated that the recessive model may serve as the best-fit model for the SNP for SLE and RA. CONCLUSION: Our results provided support for TNFSF4 rsl234315 as a SLE and RA susceptibility locus in a Chinese Guangxi population.
29289700 Adherence to synthetic disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Resu 2019 Sep BACKGROUND: Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. PATIENTS AND METHODS: A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. RESULTS: The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. CONCLUSION: In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us.
30112581 A brief report on the clinical trial on neural mobilization exercise for joint pain in pa 2019 Jun BACKGROUND: In rheumatoid arthritis (RA) synovitis, activation of synoviocytes and infiltration of adaptive immune cells leads to synovial hyperplasia and joint swelling. Under the elevated extra-neural pressure, free nerve endings release neuropeptides, calcitonin gene-related peptide, and substance P, thus promoting neurogenic inflammation. OBJECTIVE: This study aimed to assess the effect of therapeutic neural mobilization (NM) exercises targeting the nervous system on disease impact in RA patients. METHODS: A total of 21 RA patients were randomized into NM (n = 11) and control (n = 10) groups. NM group patients performed NM exercises targeting the median, musculocutaneous, femoral, and saphenous nerve, as well as the entire nervous system twice daily for 4-8 weeks. Control RA patients performed gentle joint mobilization exercises targeting the same joints. Primary outcome was the change in pre-/post-treatment score in the validated Rheumatoid Arthritis Impact of Disease (RAID). Secondary outcome was erythrocyte sedimentation rate (ESR). RESULTS: There were no significant differences between the groups at baseline. No adverse events were observed and compliance was over 90%. Post-treatment, favorable changes were observed in the NM group RAID score: -5.1 vs. -0.8; weighted RAID score: -0.79 vs. -0.15. ESR was reduced in the NM group, albeit non-significantly. Regarding the RAID score domains, the NM group demonstrated significant improvements in pain and coping. CONCLUSION: The current data indicate a beneficial effect of NM exercises on pain and self-efficacy in our RA patients. Larger clinical studies are warranted to determine the clinical effectiveness of NM as a treatment for pain for RA patients and simultaneously address immune and neuropeptide modulation through NM.
31313080 Assessment of CD40 and CD40L expression in rheumatoid arthritis patients, association with 2019 Nov The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.
31056443 External Validity of a New Prediction Model for Patient Satisfaction After Total Knee Arth 2019 Aug BACKGROUND: The ability to identify patients at risk of dissatisfaction after total knee arthroplasty (TKA) remains elusive. This study's purpose was to determine the external validity of a recently published prediction model for patient satisfaction (PMPS) with the hypothesis that it would achieve similar predictive success in our study sample. METHODS: A 10-question PMPS statistically derived from 5 patient-reported outcome questionnaires was tested for external validity in this prospective cohort investigation. The PMPS incorporates gender, age, stiffness, noise, and pain catastrophizing, with a score of 20 or greater predictive of satisfaction. As in the original study, to determine satisfaction the 2011 Knee Society Score (KSS) satisfaction subscale was collected at 3 months postoperatively. Two hundred seventy-four patients were administered the PMPS preoperatively, and 145 patients completed the KSS at 3 months postoperatively (53.0% response rate; 59% female; age, 64.9; body mass index, 32.5). A Bland-Altman analysis to assess agreement was performed. RESULTS: One hundred thirty-three patients (91.7%) were satisfied and 12 (8.3%) were dissatisfied based on their postoperative KSS. The mean difference between the PMPS and KSS was 3.6 ± 8, but with a 95% prediction interval of -15.3 to 22.1 signifying almost no correlation. The PMPS did not predict any of the 12 dissatisfied patients postoperatively, and falsely predicted 5 patients to be dissatisfied of which 4 actually had a maximum postoperative KSS of 40. CONCLUSION: A previously published, internally validated 10-question PMPS was unable to predict satisfaction after TKA in our external study sample. This study emphasizes the difficulty of developing a simple, but robust questionnaire that consistently predicts patient satisfaction after TKA.
30205983 Treat to target strategy in early rheumatoid arthritis versus routine care - A comparative 2019 Apr OBJECTIVE: To assess the 2-year effect on disease activity and health-related quality of life (HRQoL) of implementing a clinical practice treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA). METHODS: Patients in the Norwegian Very Early Arthritis Cohort 2.0 (NOR-VEAC 2.0), included 2010-2015, were treated according to T2T principles with visits at baseline, 3, 6, 9, 12 months, then every 6 months plus monthly visits until DAS28 <2.6. These patients were compared to a pre-T2T cohort of patients included in the Norwegian Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) register 2006-2009. Both groups had a clinical diagnosis of RA (≤1 year) and were DMARD naïve. Disease activity and HRQoL outcomes were analysed, and the primary outcome was SDAI remission (≤3.3) at 2years. RESULTS: The T2T cohort included 293 patients (mean (SD) age 54 (13) years, 66% females, disease duration median (25,75 perc) 98 (57,164) days) and the routine care cohort 392 patients (age 54 (13) years, 68% females, 4 (0,30) days since diagnosis). At 2years, the proportion of patients achieving SDAI remission was 46% in the T2T cohort compared to 31% in the routine care cohort. EQ-5D was similar at baseline, but differed significantly between groups at 2years (median (25,75 perc) 0.77 (0.69, 0.85) vs 0.73 (0.59, 0.80), p < 0.001). Methotrexate monotherapy was the dominant DMARD regimen used to achieve SDAI remission in both cohorts. CONCLUSION: Higher remission rates and better HRQoL were achieved in patients following a T2T strategy in clinical practice compared to routine care.