Assessment of disease activity in patients with rheumatoid arthritis using plasma tumour M2-pyruvate kinase test.

Background: Pyruvate kinase M2 (PKM2) is an enzyme that regulates the final process of glycolysis and exists in tetrameric and dimeric forms. The dimeric form of PKM2, also known as tumour M2-PK, increases when aerobic glycolysis is augmented, a feature observed in rheumatoid arthritis (RA). We investigated whether plasma tumour M2-PK is elevated in patients with RA and whether its levels correlate with disease activity. Methods: Plasma levels of tumour M2-PK were measured for patients with RA (n=151), those with osteoarthritis (OA) (n=37), and controls (n=37). We evaluated the association between plasma tumour M2-PK and continuous variables using Pearson's correlation analysis, and multivariate logistic regression analysis to determine the association between plasma tumour M2-PK and disease activity status. Knee synovial tissue blocks from patients with RA and OA were subjected to real-time quantitative PCR (qPCR) using two different primers for PKM2 and tumour M2-PK immunohistochemical (IHC) staining. Results: The tumour M2-PK level significantly correlated with the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) (r=0.546, p<0.001) and DAS28-C-reactive protein (CRP) (r=0.589, p<0.001). Moreover, repeat testing of tumour M2-PK levels in 20 patients revealed a significant decline in tumour M2-PK levels after reduction in inflammation (p<0.001). Area under the receiver operating characteristic curve (AUROC) analysis demonstrated that upon incorporation of tumour M2-PK, ESR, and CRP, the area under the curve was 0.962 for distinguishing moderate/high from remission/low disease activity. Adjusted logistic regression also revealed that a tumour M2-PK >43.9 U/mL (OR 3.672, p=0.042) independently predicted moderate/high disease activity status. Furthermore, tumour M2-PK levels in patients with RA were significantly higher than in those with OA and controls (all p<0.001). However, no differences were found in PKM2 expression in RA and OA synovial tissues as assessed by qPCR, and IHC analysis revealed negligible tumour M2-PK expression in the synovial tissues. Conclusion: Circulating plasma tumour M2-PK levels may be a clinically useful indicator for evaluating disease activity and RA diagnosis.

Assessment of Intramuscular Fat and Correlation with Body Composition in Patients with Rheumatoid Arthritis and Spondyloarthritis: A Pilot Study.

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with changes in body composition. Ectopic intramuscular fat (IMAT) may alter muscle function and contribute to cardiometabolic disorders. In a pilot study, we analyzed IMAT in the calf with peripheral quantitative computed tomography (pQCT) and examined correlations between IMAT quantity and body composition parameters. In 20 patients with active RA and 23 with active SpA, IMAT was correlated with visceral fat (VAT; r = 0.5143 and 0.6314, respectively; p < 0.05) and total lean mass (r = 0.5414 and 0.8132, respectively; p < 0.05), but not with whole body fat mass. Total lean mass mediated 16% and 33% of the effects of VAT on IMAT in RA and SpA, respectively. In both RA and SpA, calf muscle area was correlated with total lean mass (r = 0.5940 and r = 0.8597, respectively; p < 0.05) and fat area was correlated with total body fat (r = 0.6767 and 0.5089, respectively; p < 0.05) and subcutaneous fat (r = 0.6526 and 0.5524, respectively; p < 0.05). Fat area was inversely correlated with handgrip and walking tests, and it was associated with disease activity and disability. We showed that ectopic IMAT, measured with pQCT, was correlated with VAT, but not with total body fat, in RA and SpA. This result suggests that metabolically active fat was specifically associated with IMAT.

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

The pharmacological assessment of resveratrol on preclinical models of rheumatoid arthritis through a systematic review and meta-analysis.

Resveratrol/RES (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in many food items and red wine, which exhibits pleiotropic biological effects. Several preclinical studies evaluating the efficacy of RES in animal models of rheumatoid arthritis (RA) have been conducted, but the diversity of the experimental conditions and of their outcomes preclude definitive conclusions about RES's efficacy. We, therefore, performed a meta-analysis to assess its efficacy in mitigating experimental RA. We searched three databases until January 2021 and used the random-effects model for drawing inferences. Eighteen studies involving 544 animals were used in this study. Pooled analysis showed that experimental RA causes paw swelling (Hedge's g = 9.823, p = 0.000), increases polyarthritis score and arthritis index, and RES administration reduces paw volume (Hedge's g = -2.550, p = 0.000), polyarthritis score, and arthritis index besides amelioration in the histopathological score and cartilage loss. RA is accompanied by increased oxidative stress due to high malondialdehyde (MDA) level (p < 0.001) and low superoxide dismutase (SOD) activity (p = 0.002), and RES reduced MDA level (p < 0.001) and increased SOD activity (p < 0.001). Experimental RA exhibited an increase in pro-inflammatory cytokines viz. tumor necrosis factor (TNF)-α (p < 0.001), interleukin (IL)-6 (p = 0.002), and IL-1 (p < 0.001); however, insufficient quantitative data precluded us from assessing changes in the anti-inflammatory cytokine, IL-10. In experimental RA, RES decreased TNF-α (p < 0.001), IL-6 (p < 0.001) and IL-1 (p = 0.001) and increased IL-10. This meta-analysis suggests that RES can be a clinically effective therapy for RA, pending clinical trials.

Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.

Advances in imaging technologies for the assessment of peripheral neuropathies in rheumatoid arthritis.

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis.

Severe joint deformity and patient global assessment of disease are associated with discrepancies between sonographic and clinical remission: A cross-sectional study of rheumatoid arthritis patients.

OBJECTIVE: Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. METHODS: In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2-5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. RESULTS: A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. CONCLUSIONS: While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.

Assessment of a dried blood spot C-reactive protein method to identify disease flares in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic 'flares' or inflammatory episodes-mostly occurring outside clinics-where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Matched venepuncture and finger lancet DBS samples were collected from n = 100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n = 30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland-Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between 'minimal' baseline and 6 week sample CRP data and the 'continuous' weekly CRP data. Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement - 14.24 to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of 'continuous' area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than 'minimal' AUC CRP data (54.5%). This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.Trial registration: The Remote Arthritis Disease Activity MonitoR (RADAR) study was registered on 22/06/2016 at ClinicalTrials.gov Identifier: NCT02809547. https://clinicaltrials.gov/ct2/show/NCT02809547 .

A modeling framework for the economic evaluation of baricitinib in moderate-to-severe rheumatoid arthritis.

Objectives: The approval in more than 50 countries of baricitinib, an oral Janus Kinase inhibitor for the treatment of Rheumatoid Arthritis (RA), warrants a framework for corresponding economic evaluations. To develop a comprehensive economic model assessing the cost-effectiveness of baricitinib for the treatment of moderately-to-severely active RA patients in comparison to other relevant treatments, considering the natural history of the disease, real world treatment patterns, and clinical evidence from the baricitinib trials.Methods: A systematic literature review of previously developed models in RA was conducted to inform the model structure, key modeling assumptions and data inputs. Consultations with rheumatologists were undertaken to validate the modeling approach and underlying assumptions.Results: A discrete event simulation model was developed to international best practices with flexibility to assess the cost-effectiveness of baricitinib over a lifetime in a variety of markets. The model incorporates treatment sequencing to adequately reflect treatment pathways in clinical practice. Outcomes assessed include cost and quality-adjusted life years, allowing for a full incremental analysis of cost-effectiveness of competing treatments and treatment sequences.Conclusion: The economic model developed provides a robust framework for future analyses assessing the cost-effectiveness of baricitinib for the treatment of RA in specific country settings.

Discordance between the patient's and physician's global assessment in rheumatoid arthritis: Data from the REAL study-Brazil.

BACKGROUND: Discordance between patient's global assessment (PtGA) and physician's global assessment (PhGA) has been described in rheumatoid arthritis (RA). Understanding the reasons for this discrepancy is important in the context of treat-to-target treatment strategy. OBJECTIVE: To assess the determinants of PtGA and PhGA and factors associated with discordance between them. METHODS: The REAL study included RA patients from Brazilian public health centers. Clinical, laboratory and outcomes measures were collected. PtGA and the PhGA were rated on a visual analog scale and analyzed. Three groups were defined: no discordance (difference between PtGA and PhGA within 3 cm), positive discordance (PtGA exceeding PhGA by >3 cm), and negative discordance (PtGA less than PhGA by >3 cm). Multivariate regression analysis was used to identify determinants of PtGA and PhGA and their discordance. RESULTS: 1115 patients (89,4% female, mean age 56.7y and median disease duration of 12.7y) were enrolled. Two factors were associated with PtGA in the final multivariate model: one point increase in the pain scale leads to an increase of 0.62 in PtGA; one point increase in HAQ increases by 9,25 points the PtGA. The factors associated with PhGA were pain scale, number of tender and swollen joints (NTJ and NSJ), positive RF, ESR, HAQ-DI and use of corticosteroids. Discordance between patient and physician was found in 30.52%: positive discordance in 24.6% and negative discordance in 5.92%. An increase of one point in the NSJ was associated with a 12% increase in the chance of negative discordance. The chance of positive discordance increased by 90% and 2% for each unit increased in HAQ-DI and pain scale respectively. Finally, the chance of positive discordance decreased by 3% for each point increased in NTJ and by 15% for each point increased in NSJ. CONCLUSION: In one-third of the assessments, there was disagreement between PtGA and PhGA (a positive discordance was found in 80% of them). Pain and function were determinants for patients to estimate disease activity, while swollen joints was the main factor related to a worse physician's evaluation. These data show how different can be the perspectives of patients and assistants.

Efficacy assessment of radiosynoviorthesis on the progression of radiological osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The study objective was to evaluate the long-term effect of radiosynoviorthesis (RSO) on the progression of radiological and nuclear-medical osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis. PATIENTS AND METHODS: The study included 89 hip joints of 81 patients, of which 48 had osteoarthritis (OA) and 33 had rheumatoid arthritis (RA). In terms of ankle joints, 64 patients were included of which 43 suffered from OA and 21 from RA. The mean follow-up time was 9.2 years for OA and 8.9 years for RA patients. Patients with RA were the active control group. Structural alterations of the hip joints were evaluated following Kellgren-Lawrence score and of ankle joint following Takakura score for both disease entities. For the evaluation of synovitis 2-phase bone scintigraphy was performed. RESULTS: RSO could prevent radiologic status deterioration among 70.6 % of hip osteoarthritic patients and 73.7 % among the hip RA patients. No structural progression was observed in 79.1 % of the treated ankle joints in patients with OA and in 85.7 % of the ankle joints in patients with RA.The scintigraphic response rate for the hip joints of OA patients was 68.6 %, 76.3 % for hip joints of RA patients, 83.1 %, ankle joints of OA patients, and 90.4 % ankle joints of RA patients.The radiographic and scintigraphic RSO response rates were not significantly higher for both joints in RA than OA patients. CONCLUSION: RSO can be a good alternative in the treatment of synovitis and prevention of deterioration of inflammatory and radiographic features even in patients suffering from osteoarthritis and rheumatoid arthritis. RSO may have also a long-term effect to stop or delay progression of both diseases.

Cost-utility analysis of de-escalating biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

OBJECTIVE: Recent guideline updates have suggested de-escalating DMARDs when patients with rheumatoid arthritis achieve remission or low disease activity. We aim to evaluate whether it is cost-effective to de-escalate the biological form of DMARDs (bDMARDs). METHODS: Using a Markov model, we performed a cost-utility analysis for RA patients on bDMARD treatment. We compared continuing treatment (standard care) to a tapering approach (i.e., an immediate 50% dose reduction), withdrawal (i.e., an immediate 100% dose reduction) and tapering followed by withdrawal of bDMARDs. The parametrization is based on a comprehensive literature review. Results were computed for 30 years with a cycle length of three months. We applied the payer's perspective for Germany and conducted deterministic and probabilistic sensitivity analyses. RESULTS: Tapering or withdrawing bDMARD treatment resulted in ICERs of €526,254 (incr. costs -78,845, incr. QALYs -0.1498) or €216,879 (incr. costs -€121,691, incr. QALYs -0.5611) compared to standard care. Tapering followed by withdrawal resulted in a loss of 0.4354 QALYs and savings of €107,969 per patient, with an ICER of €247,987. Deterministic sensitivity analysis revealed that our results remained largely unaffected by parameter changes. Probabilistic sensitivity analysis suggests that tapering, withdrawal and tapering followed by withdrawal were dominant in 39.8%, 28.2% and 29.0% of 10,000 iterations. CONCLUSION: Our findings suggest that de-escalating bDMARDs in patients with RA may result in high cost savings but also a decrease in quality of life compared to standard care. If decision makers choose to implement de-escalation in daily practice, our results suggest the tapering approach.

Relationship of callosities of the forefoot with foot deformity, Health Assessment Questionnaire Disability Index, and joint damage score in patients with rheumatoid arthritis.

Objectives: We aimed to investigate the relationship of callosities of the forefoot with foot deformity, the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified total Sharp score (TSS) in patients with rheumatoid arthritis (RA).Methods: A total of 202 patients and 404 feet were enrolled. We examined the prevalence of callosities. Clinical data included the HAQ-DI, TSS, hallux valgus angle (HVA), and calcaneal pitch angle (CPA). The analysis of factors associated with callosities of the forefoot was performed by comparing patients with and without callosities of the forefoot.Results: The prevalence of callosities was 31.2% of all patients and 24.0% of all feet. The patients with callosities of the forefoot had significantly higher TSS of the foot. The presence of callosities affected the HAQ-DI walking score. HVA and CPA were identified as being associated with callosities of the forefoot. Analyzing from the cutoff values, the odds ratios of HVA, CPA, and HVA and (combined) CPA were 4.64, 1.73, and 2.99, respectively.Conclusion: Hallux valgus and flatfoot were related to callosities of the forefoot in RA. This study suggested that to prevent callosities of the forefoot, early diagnosis and foot care for hallux valgus and flatfoot are needed in daily practice.

Assessment of nutritional status by dual X-Ray absorptiometry in women with rheumatoid arthritis: A case-control study.

Rheumatoid arthritis (RA) has been related to an impairment of the nutritional status. Body mass index (BMI) has been used but questions arise about how to properly evaluate nutritional status in RA patients. Few studies have evaluated it by dual-energy X-ray absorptiometry.In women with RA, to analyze:Case-control study including 89 women with RA. The control group was composed by 100 patients affected by non-inflammatory rheumatic disorders. Study variables included age, RA duration, history, activity and disability, and in relation to nutritional status: BMI, serum albumin (ALB), whole body DXA assessment, and skeletal muscle index (SMI).Mean age of patients was 62 ±â€Š8 years, mean duration of RA was 14 ±â€Š9 years, mean disease activity score (DAS28) was 3.7 ±â€Š1.4 and mean Health Assessment Questionnaire was 0.88 ±â€Š0.77. BMI was 27.43 ±â€Š5.16 Kg/m in patients and 27.78 ±â€Š3.98 Kg/m in controls (P: ns). ALB was within normal range in all patients.By whole body DXA, RA patients presented a statistically significant lower lean mass in all locations and lower fat mass in limbs than controls. Patients had a redistribution of fat mass to trunk. Lean mass directly correlated with fat mass.Neither BMI nor ALB correlated with DXA parameters.BMI, appendicular lean mass and SMI correlated inversely with disease duration. Trunk lean mass correlated inversely, and fat mass directly, with RA disability parameters.RA patients fulfilled criteria of sarcopenia in 44% of cases versus 19% of controls (P <.001). In RA patients, regarding SMI, BMI showed a high specificity to detect sarcopenia (94% of the patients with low BMI had sarcopenia) but low sensitivity (47% of the patients with normal BMI or overweight had sarcopenia).RA patients have an impairment of nutritional status associated to disease duration that looks like sarcopenia and that is not predicted by BMI.

Rheumatoid Arthritis: Atherosclerosis Imaging and Cardiovascular Risk Assessment Using Machine and Deep Learning-Based Tissue Characterization.

PURPOSE OF THE REVIEW: Rheumatoid arthritis (RA) is a chronic, autoimmune disease which may result in a higher risk of cardiovascular (CV) events and stroke. Tissue characterization and risk stratification of patients with rheumatoid arthritis are a challenging problem. Risk stratification of RA patients using traditional risk factor-based calculators either underestimates or overestimates the CV risk. Advancements in medical imaging have facilitated early and accurate CV risk stratification compared to conventional cardiovascular risk calculators. RECENT FINDING: In recent years, a link between carotid atherosclerosis and rheumatoid arthritis has been widely discussed by multiple studies. Imaging the carotid artery using 2-D ultrasound is a noninvasive, economic, and efficient imaging approach that provides an atherosclerotic plaque tissue-specific image. Such images can help to morphologically characterize the plaque type and accurately measure vital phenotypes such as media wall thickness and wall variability. Intelligence-based paradigms such as machine learning- and deep learning-based techniques not only automate the risk characterization process but also provide an accurate CV risk stratification for better management of RA patients. This review provides a brief understanding of the pathogenesis of RA and its association with carotid atherosclerosis imaged using the B-mode ultrasound technique. Lacunas in traditional risk scores and the role of machine learning-based tissue characterization algorithms are discussed and could facilitate cardiovascular risk assessment in RA patients. The key takeaway points from this review are the following: (i) inflammation is a common link between RA and atherosclerotic plaque buildup, (ii) carotid ultrasound is a better choice to characterize the atherosclerotic plaque tissues in RA patients, and (iii) intelligence-based paradigms are useful for accurate tissue characterization and risk stratification of RA patients.

Inter-observer agreement of standard joint count examination and disease global assessment in a cohort of Egyptian Rheumatoid Arthritis patients.

OBJECTIVES: To assess the inter-observer agreement of standard joint count between experienced Rheumatology professor (Prof) and young Rheumatology fellow (candidate), and to compare disease global assessment between professor, young candidate and patients. METHODS: This study included one hundred rheumatoid arthritis patients. For all patients independent clinical evaluation was done by two rheumatologists (professor and candidate) for detection of tenderness in 28 joints and swelling in 26 joints. The study also involved global assessment of disease activity by the provider (Prof and candidate) (EGA) as well as by the patient (PGA). The EGA was determined without previous knowledge of the patient's laboratory test results. RESULTS: A highly significant accordance (correlation) between professor and candidate was found in both the number of tender joints (p<0.001) (r=0.946), and the number of swollen joints (p<0.001) (r=0.797). Regarding swollen joints, the highest agreement was in right knee (0.929), while poor agreement was found in the right 5th MCP (0.049). Regarding tender joints, the highest analogy was in the right elbow (0.899), in contrast to the left 3rd PIP (0.462) which showed the least congruence. Agreement study using kappa measurement for disease global assessment showed: moderate agreement (between professor and candidate) (0.405), fair agreement between (professor and patient) (0.213), fair agreement between (candidate and patient) (0.367). CONCLUSION: Inter-observer reliability was better for TJCs than SJCs. Regarding SJCs agreement was better in large joints such as the knees compared to the small joints such as the MCPs. Disease global assessment may show discrepancy between patients and physicians.

Diagnostic accuracy of simplified ultrasound hand examination protocols for detection of inflammation and disease burden in patients with rheumatoid arthritis.

BACKGROUND: There is no consensus regarding the minimum number of joints that should be included in an ultrasound (US) scoring system to reliably assess for disease activity in rheumatoid arthritis (RA). PURPOSE: To assess whether simplified US protocols for hand examination are as informative as the examination of 22 joints in patients with RA, and to correlate the US parameters with disease activity (DAS-28). MATERIAL AND METHODS: This is a cross-sectional study of 224 RA patients stratified based on their DAS-28 scores and assessed using eight preselected US examination protocols, including 22, 18, 16, 14, ten, eight, and two different combinations of four joints, respectively. RESULTS: We found a significant difference between US hand scores regarding their ability to detect active inflammation and erosions. DAS-28 scores correlated very well with the power Doppler (PD) scores generated by all eight US examination protocols (r = 0.89-1, P < 0.05), irrespective of patients' disease activity. Simplified US scores missed information on presence of PD in 20.6-40.2% patients ( P < 0.05) and misdiagnosed non-erosive hand RA in 12-38.4% patients ( P < 0.05), depending on the number of joints excluded from US hand examination. CONCLUSION: Preselected simplified US scores are less reliable in appreciating the disease burden when compared with an extended protocol for 22 joint US examination, raising clinicians' awareness regarding the need to comprehensively assess multiple hand joints to reliably rule out subclinical inflammation.

[Clinical significance of detection of soluble interleukin 2 receptor alpha chain in the assessment of rheumatoid arthritis disease activity].

OBJECTIVE: To evaluate soluble interleukin-2 receptor alpha chain (sIL-2Rα, sCD25) in serum for the determination of rheumatoid arthritis (RA) activity. METHODS: Peripheral blood was collected from 108 patients with RA, 39 patients with osteoarthritis (OA) and 50 healthy control subjects, and synovial fluids were from 40 patients with RA. The sera from the patients with RA, the disease control group (osteoarthritis), the healthy control group, and the synovial fluids of the RA patients were detected by enzyme-linked immunosorbent assay (ELISA).The clinical manifestations and laboratory parameters of the patients with RA were recorded and the correlation with the serum sCD25 level was analyzed. RESULTS: The serum sCD25 concentration in RA group was (2 886±1 333) ng/L, the serum sCD25 concentration in OA group was (2 090±718) ng/L, and the serum sCD25 concentration in healthy group was (1 768±753) ng/L. The serum sCD25 level in the patients with RA was significantly higher than that in the disease controls and healthy controls (P<0.001). Sensitivity of serum sCD25 in the diagnosis of RA was 66.1% and specificity was 83.0%;serum sCD25 levels and erythrocyte sedimentation rate (r=0.321, P=0.001), C-reactive protein (r=0.446, P<0.001), DAS28 score (r=0.324, P<0.001), joint tenderness count (r=0.203, P=0.024), D-dimer levels (r=0.383, P<0.001), age (r=0.24, P=0.007), IgG (r=0.207, P=0.028), HRF-IgG (r=0.345, P=0.034) showed a significant positive correlation, and disease duration (r=-0.206, P=0.021) showed a negative correlation with sCD25;In patients with rheumatoid arthritis, the positive rates of serum ESR, CRP, and sCD25 were 14.3% (2 cases), 14.3% (2 cases), and 71.4% (10 cases) in the low disease activity group. The positive rates of serum ESR, CRP and sCD25 in the moderate disease activity group were 94.2% (49 cases), 82.7% (43 cases), and 86.5% (45 cases). The positive rates of serum ESR, CRP, and sCD25 in the high disease activity group were 100% (42 cases), 95.2% (40 cases), and 90.5% (38 cases);36 cases of ESR and/or CRP were negative (about 33.3%) in 108 patients, serum sCD5 levels of 17 cases in these 36 cases (about 47.2%)increased, of which 14 cases (about 82.4%) had a DAS28 score higher than 3.2. CONCLUSION: The serum sCD25 has a high specificity for diagnosis of RA and a poor sensitivity. The serum level is closely related to the activity of RA, indicating that sCD25 may be involved in the inflammatory process of RA and may become a new inflammatory marker of RA. It is more meaningful for detection of serum sCD25 when RA is active, but ESR and/or CRP is negative.

Performance of routine assessment of patient index data 3 (RAPID3) in monitoring disease activity of Chinese rheumatoid arthritis patients.

AIM: To explore the performance of routine assessment of patient index data 3 (RAPID3) in reflecting disease activity in Chinese rheumatoid arthritis (RA) patients. METHOD: The clinical data of 189 consecutive RA patients, including RAPID3 questionnaire, Disease Activity Score based on 28-joint count (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI), and ultrasonography of hand and wrist joints were collected. The consistency between RAPID3 and DAS28, CDAI, SDAI in RA patients with different disease activities was performed by Spearman's correlations, kappa and/or weighted kappa coefficients. RESULT: RAPID3 score was significantly associated with DAS28 and erythrocyte sedimentation rate (ESR), DAS28 with C-reactive protein (CRP), CDAI, SDAI (r = 0.797, 0.786, 0.784, and 0.760 respectively, P < 0.001 for all). RAPID3 was also significantly correlated with tender joint count, swollen joint count, ESR and CRP. The agreement of RAPID3 with DAS28 scoring systems was better in patients with moderate/high disease activity than those in remission/low disease activity. Ultrasonographic subclinical synovitis was presented in 42.3%-48.6% of patients in remission/low disease activity defined by various scoring criteria including RAPID3 with no significant difference observed (P = 0.22, >0.05). CONCLUSION: RAPID3 showed good correlation with DAS28 scoring systems, especially in patients with moderate/high disease activity. RAPID3 is a reliable and convenient tool to monitor disease activity.