Elevated DAS28-ESR in patients with rheumatoid arthritis who have comorbid fibromyalgia is associated more with tender joint counts than with patient global assessment or swollen joint counts: implications for assessment of inflammatory activity.

OBJECTIVES: More than 20% of rheumatoid arthritis (RA) patients have comorbid fibromyalgia (FM+), which may elevate DAS28-ESR (disease activity score 28-erythrocyte sedimentation rate) and other indices, resulting in challenges to assess inflammatory disease activity. Although several reports indicate that elevated patient global assessment (PATGL) may elevate DAS28 in the absence of inflammatory activity, less information is available concerning the other three components, tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR), to possibly elevate DAS28 in FM+ vs. FM- RA patients. METHODS: A PubMed search identified 14 reports which presented comparisons of DAS28-ESR and its four components in RA FM+ vs. FM- groups. Median DAS28, component arithmetic differences, pooled effect sizes and 95% confidence intervals were analysed in the FM+ vs. FM- groups. RESULTS: In FM+ vs. FM- groups, median DAS28 was 5.3 vs. 4.2, SJC 4.0 vs. 3.0, TJC 13.2 vs. 5.3, PATGL 61.6 vs. 39.9, ESR 26.3 vs. 26.5. DAS28-ESR was classified as "high" (>5.1) in 11/14 FM+ groups and "moderate" (3.2-5.1) in all 14 FM- groups. Effect sizes in FM+ vs. FM- groups for DAS28-ESR, SJC, TJC, PATGL, and ESR were large (≥0.8) in 10/14, 1/13, 12/13, 7/13, and 1/13 comparisons, respectively, and pooled effect sizes 0.84 (0.3, 1.4), 0.33 (-0.4, 1.0), 1.27 (0.01, 2.5), 0.91 (-0.6, 2.4), and 0.07 (-0.6, 0.7), respectively. CONCLUSIONS: DAS28-ESR is elevated significantly in FM+ vs. FM- RA patients; pooled effect sizes were highest for TJC, followed by PATGL, SJC and ESR. The findings appear relevant to response and remission criteria, treat-to-target, and general management of RA.

Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies - A longitudinal study.

AIM: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). METHODS: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. RESULTS: PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. CONCLUSION: Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.

[Methods for assessment of disease activity of polymyalgia rheumatica]. / Methoden zur Erfassung der Krankheitsaktivität der Polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is the second most frequent inflammatory rheumatic disease in old age. Remission and recurrence are frequently used as endpoints in clinical trials; however, there is as yet no international consensus on the definition of these states, which limits the comparability of published studies. The PMR activity score (PMR-AS) is the only composite score specifically developed for PMR, which together with remission is used to define low, middle and high disease activity. In recent studies the PMR-AS was often used and low disease activity was established as endpoint. The most important limitation of the PMR-AS is the potential influence of the individual variables by comorbidities. The value of C­reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are of restricted value in studies using drugs that influence the interleukin 6 (IL-6) axis. In these cases, calprotectin and osteopontin are promising alternative biomarkers, as they have already been shown to reflect disease activity independently of CRP in rheumatoid arthritis. Furthermore, imaging modalities including sonography, magnetic resonance imaging and fluorodeoxyglucose (FDG) positron emission tomography could also be helpful in monitoring disease activity; however, these techniques must first be validated in further studies. The PMR impact scale (PMR-IS) is a composite score to assess the impact of PMR on the patients; however, it has not yet been used in clinical studies. The development of additional patient reported outcomes (PRO) for PMR and the definition of standardized criteria for documentation of remission and recurrence are important questions in the future research agenda for PMR.

Platelet Indices and Erythrocyte Sedimentation Rate are useful Parameters in the Assessment of a Cohort of Nigerian Women with Preeclampsia.

BACKGROUND: The study compared some haematological parameters in normotensive pregnant women with those of women with pre-eclampsia (PE) to identify those parameters that may reinforce the occurrence and severity of PE. METHODS: The study was a case-control study involving 40 pre-eclamptic women as subjects and 40 normotensive pregnant women as controls. The subjects were classified into mild and severe based on their blood pressure of >140/90 mmHg and >169/100 mmHg, respectively. Full blood count (FBC) was done using a haematology autoanalyzer, D-dimer and fibrinogen were assessed by enzyme-linked immunosorbent assay (ELISA) method, while Prothrombin Time (PT) and activated plasma thromboplastin time (aPTT) were done manually. RESULTS: The mean PCV was higher while the mean WBC was lower in PE but the differences were not statistically significant. The ESR was significantly higher (50.48 ± 2.90mm/hr vs 41.05 ± 3.74mm/hr, p < 0.049). The mean neutrophil (59.38 ± 7.77% vs 64.95 ± 6.68%; p < 0.001) and lymphocyte (31.35±7.67% vs 7.63±7.47%, p = 0.031) counts were significantly lower and higher, respectively, in PE. Although the mean platelet count in PE was lower, the plateletcrit, mean platelet volume (MPV), and platelet distribution width (PDW) were significantly higher in PE (p = 0.01, 0.04, 0.001, respectively). The D-dimer was significantly higher in the women with PE (p < 0.001), while the PT, aPTT and fibrinogen concentrations were not statistically different between the two groups. CONCLUSION: It may be concluded that low platelet count, high MPV, PDW, PCT and ESR in PE women may reinforce the diagnosis while a high MPV may, in addition, discriminate between severe and mild Pre-eclampsia.

CONTEXTE: L'étude a comparé certains paramètres hématologiques chez des femmes enceintes normotendues à ceux de femmes atteintes de pré-éclampsie (PE) afin d'identifier les paramètres qui peuvent renforcer l'occurrence et la gravité de la PE. MÉTHODES: Il s'agissait d'une étude cas-témoins impliquant 40 femmes pré-éclamptiques comme sujets et 40 femmes enceintes normotendues comme témoins. Les sujets ont été classés en légers et sévères sur la base de leur pression artérielle de > 140/90 mmHg et >169/100 mmHg respectivement. La formule sanguine complète (FBC) a été réalisée à l'aide d'un auto-analyseur d'hématologie, les D-dimères et le fibrinogène ont été évalués par la méthode ELISA (enzymelinked immunosorbent assay), tandis que le temps de prothrombine (PT) et le temps de thromboplastine plasmatique activé (aPTT) ont été réalisés manuellement. RÉSULTATS: Le VPC moyen était plus élevé tandis que le nombre moyen de globules blancs était plus faible dans l'EP, mais les différences n'étaient pas statistiquement significatives. L'ESR était significativement plus élevé (50.48 ± 2.90mm/hr vs 41.05 ± 3.74mm/hr, p < 0.049). Les numérations moyennes des neutrophiles (59,38 ±7,77 % contre 64,95 ± 6,68 % ; p < 0,001) et des lymphocytes (31,35±7,67 % contre 27,63±7,47 %, p = 0,031) étaient respectivement plus faibles et plus élevées de manière statistiquement significative dans l'EP. Bien que la numération plaquettaire moyenne dans l'EP soit plus faible, le critère plaquettaire, le volume plaquettaire moyen (VPM) et la largeur de distribution plaquettaire (LDP) étaient significativement plus élevés dans l'EP (p = 0,01, 0,04, 0,001 respectivement). Le D-dimère était significativement plus élevé chez les femmes atteintes d'EP (p < 0,001), tandis que les concentrations de PT, aPTT et fibrinogène n'étaient pas statistiquement différentes entre les deux groupes. CONCLUSION: On peut conclure qu'une faible numération plaquettaire, un VPM élevé, un PDW, un PCT et un ESR chez les femmes atteintes d'EP peuvent renforcer le diagnostic, tandis qu'un VPM élevé peut, en outre, faire la distinction entre une pré-éclampsie grave et une pré-éclampsie légère. Mots clés: Prééclampsie, Numération plaquettaire, Indices plaquettaires, ESR, D-Dimères, Gravité.

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.

Performance of the Rheumatoid Arthritis Disease Activity Index in the Assessment of Disease Activity in Rheumatoid Arthritis-Findings From the REAL Study.

BACKGROUND/OBJECTIVE: Although telemedicine use has been under discussion for decades, this topic has gained unprecedented importance during the COVID-19 pandemic. The Rheumatoid Arthritis Disease Activity Index (RADAI) is a user-friendly tool, fully self-administered, to assess rheumatoid arthritis (RA) disease activity. The aim of this study was to compare the performance of RADAI with other disease activity indices, functional status, and inflammatory markers in a large cohort of RA patients. METHODS: We assessed the concurrent validity of RADAI against Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 Joints-C-reactive protein, Disease Activity Score in 28 Joints-erythrocyte sedimentation rate, Simplified Disease Activity Index, and physician assessment of disease activity and the correlation of RADAI with Health Assessment Questionnaire-Disability Index and inflammatory markers at the REAL Study baseline. We also evaluated the correlation of the change in RADAI and the change in CDAI over a 6-month follow-up. RESULTS: From the 1115 patients included in the REAL Study, 1113 had RADAI scores in the first assessment. At baseline, correlations between RADAI and other disease activity indices were strong, ranging from 0.64 (comparison with physician assessment) to 0.79 (comparison with CDAI). Correlation between the change in RADAI score over the 6 months of follow-up and the change in CDAI score over the same period was moderate/strong for the overall group and within the stratified analyses. CONCLUSION: The strong correlation of RADAI with other well-established tools for disease activity measurement reassures its use with RA patients' follow-up, especially in this new era of telemedicine.

Rheumatoid Arthritis disease activity assessment in routine care: performance of the most widely used composite disease activity indices and patient-reported outcome measures.

BACKGROUND AND AIM: To evaluate the convergent and discriminative validity of many continuous composite disease activity indices and patient-reported outcome measures (PROMs) in rheumatoid arthritis (RA). METHODS: In consecutive RA patients in moderate or high disease activity, according to the Simplified Disease Activity Index (SDAI) definition, were computed four additional composite disease activity indices, the 28-joint Disease Activity Score - erythrocyte sedimentation rate (DAS28-ESR), the Clinical Disease Activity Index (CDAI), the Chronic Arthritis Systemic Index (CASI), and the Mean Overall Index for RA (MOI-RA), and five PROMs, the Patients' Activity Scale (PAS), the Rheumatoid Arthritis Impact of Disease (RAID), the 5-item RA Disease Activity Index (RADAI-5), the Routine Assessment of Patient Index Data (RAPID3), and the Clinical Arthritis Activity (PRO-CLARA). Spearman's rho correlation coefficients were determined to assess their convergent validity, and discriminative performance was calculated by the area under the receiver-operating curve (AUC-ROC). The patients' opinion of their symptomatic status (PASS) was used as the external criterion. RESULTS: 246 RA patients with moderate (29.3%) or high disease activity (70.7%) have been assessed. The indices all showed a significant correlation (p <0.0001 for all). Among the composite disease activity indices, the CDAI was the one that showed the best discriminating ability compared to the PASS (AUC = 0.962), while among the PROMs the RAID was the most performing (AUC = 0.879). CONCLUSIONS: CDAI as composite index of disease activity, and RAID as PROM, are the two instruments with the best performances in relation to PASS. The use of validated disease activity measures can help in clinical practice to adopt treat-to-target strategies in RA patients. (www.actabiomedica.it).

Efficacy and Safety of Biosimilar and Originator Etanercept in Rheumatoid Arthritis Patients: Real-Life Data.

BACKGROUND: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound. OBJECTIVES: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals. METHODS: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment. RESULTS: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1. CONCLUSIONS: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings.

Trajectories of disease courses in the inception cohort of newly diagnosed patients with JIA (ICON-JIA): the potential of serum biomarkers at baseline.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging. METHODS: We analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later. RESULTS: Two-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months. CONCLUSION: Our data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.

Kawasaki Disease and Clinical Outcome Disparities Among Black Children.

OBJECTIVE: To determine whether Black children with Kawasaki disease exhibit disparities in prevalence, sequelae, and response to intravenous gamma globulin (IVIG) treatment. STUDY DESIGN: International Classification of Diseases codes were used to identify children with Kawasaki disease admitted to a tertiary center in the southeastern US. Subjects diagnosed and treated according to American Heart Association criteria were included. Demographic, laboratory, clinical, and echocardiographic data from the electronic medical record (2000-2015) were compared between Blacks and Whites. RESULTS: Data from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment, or coronary artery (CA) abnormalities during hospitalization were observed. Blacks showed lower IVIG response rates than Whites for patients administered IVIG within 10 days of fever onset (86.6% vs 95.6%; P = .007). Blacks received more ancillary drugs (9.6% vs 2.6%; P = .003), and endured longer hospitalizations (mean, 5 ± 3.9 days vs 3.4 ± 2.2 days; P = .001). Blacks presented with higher C-reactive protein level and erythrocyte sedimentation rate and lower hemoglobin, albumin, and sodium levels. Blacks had a higher proportion of persistent CA abnormalities than Whites at second follow-up echocardiogram (14.5% vs 6.3%; P = .03), and at third follow-up echocardiogram (21.2% vs 6.9%; P = .01). CONCLUSIONS: Compared with White children, Black children with Kawasaki disease had higher IVIG refractory prevalence, more severe inflammation, more ancillary treatments, and longer hospitalizations. Despite no racial differences in time to diagnosis or initial treatment, there was greater CA abnormality persistence among Black children at follow-up.

Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers.

OBJECTIVE: To test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters. STUDY DESIGN: We designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-year period (2002-2019) from a single clinical site and compared the cluster characteristics with those of 2 control groups of synthetic Kawasaki disease clusters. We defined a "true" Kawasaki disease cluster as at least 5 patients within a 7-day moving window. The observed and synthetic Kawasaki disease clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, rotated empirical orthogonal function analysis. RESULTS: In a univariate analysis, the median values for age, coronary artery z-score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true Kawasaki disease clusters exceeded the 95th percentile for the 2 synthetic clusters. REOF analyses revealed distinct patterns of demographic and clinical measures within clusters. CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensities of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of Kawasaki disease.

Assessment of Endocan Serum Level in Patients with Behçet Disease: Relation to Disease Activity and Carotid Intima Media Thickness.

Behçet disease (BD) is a form of vasculopathy that can influence blood vessels of variable diameters. Endocan is a biomarker of endothelial activation and it is secreted from endothelial cells as a soluble proteoglycan. The aim of the work was to assess endocan serum level in patients with BD and to examine its relationship with disease activity parameters and carotid intima media thickness (IMT). The study encompassed 42 patients with BD (25 males and 17 females) diagnosed according to the International Study Group Criteria of BD and 42 age and sex matched apparently healthy volunteers as controls. Human Endothelial cell-specific Molecule-1 (Endocan) was assessed using ELISA. Carotid mean IMT was calculated by Color Doppler ultrasonography. Thickness measurement more than 1 mm was considered abnormal:BD patients had significantly increased endocan serum levels (median, 249.5; IQR, 174 - 445 ng/l) compared to healthy controls (median, 190.5; IQR, 128 - 235 ng/l, P=0.002), endocan serum level was increased in BD patients with active disease (median, 434; IQR, 246 - 617.5 ng/l) compared to those with inactive disease (median, 195.5; IQR, 145 - 235 ng/l, P < 0.001) and healthy controls (P < 0.001). Endocan serum levels showed significant positive correlations with erythrocyte sedimentation rate (P=0.04), C-reactive protein (P < 0.001), BD Current Activity form (P < 0.001) and carotid IMT (P=0.008). In conclusion, Endocan can be used to monitor disease activity and endothelial dysfunction in BD.

Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials.

Importance: Large placebo responses in randomized clinical trials may keep effective medication from reaching the market. Primary outcome measures of clinical trials have shifted from patient-reported to objective outcomes, partly because response to randomized placebo treatment is thought to be greater in subjective compared with objective outcomes. However, a direct comparison of placebo response in subjective and objective outcomes in the same patient population is missing. Objective: To assess whether subjective patient-reported (pain severity) and objective inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]) outcomes differ in placebo response. Design, Setting, and Participants: The placebo arms of 5 double-blind, randomized, placebo-controlled clinical trials were included in this cross-sectional study. These trials were conducted internationally for 24 weeks or longer between 2005 and 2009. All patients with rheumatoid arthritis randomized to placebo (N = 788) were included. Analysis of data from these trials was conducted from March 27 to December 31, 2019. Intervention: Placebo injection. Main Outcomes and Measures: The difference (with 95% CIs) from baseline at week 12 and week 24 on a 0- to 100-mm visual analog scale to evaluate the severity of pain, CRP level, and ESR. Results: Of the 788 patients included in the analysis, 644 were women (82%); mean (SD) age was 51 (13) years. There was a statistically significant decrease in patient-reported pain intensity (week 12: -14 mm; 95% CI, -12 to -16 mm and week 24: -20 mm; 95% CI, -16 to -22 mm). Similarly, significant decreases were noted in the CRP level (week 12: -0.51 mg/dL; 95% CI, -0.47 to -0.56 mg/dL and week 24: -1.16 mg/dL; 95% CI, -1.03 to -1.30 mg/dL) and ESR (week 12: -11 mm/h; 95% CI, -10 to 12 mm/h and week 24: -25 mm/h; 95% CI, -12 to -26 mm/h) (all P < .001). Conclusions and Relevance: The findings of this study suggest that improvements in clinical outcomes among participants randomized to placebo were not limited to subjective outcomes. Even if these findings could largely demonstrate a regression to the mean, they should be considered for future trial design, as unexpected favorable placebo responses may result in a well-designed trial becoming underpowered to detect the treatment difference needed in clinical drug development.

The efficacy and safety of warming acupuncture and moxibustion on rheumatoid arthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA), as an autoimmune disease, can eventually lead to joint deformity and loss of function, seriously reduce the quality of life of patients and increase economic burden. As a traditional Chinese therapy, warming acupuncture and moxibustion is safe, economical, and has few side effects. At present, some studies have shown that warming acupuncture and moxibustion has a certain effect on RA, but there is no evidence of evidence-based medicine. The purpose of this study was to evaluate the efficacy and safety of warming acupuncture and moxibustion in the treatment of rheumatoid arthritis. METHOD: Randomized controlled trials of warming acupuncture and moxibustion treating RA will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and China biomedical literature database (CBM) from inception to July, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies independently. Statistical analysis is performed in RevMan 5.3 software. RESULTS: The primary outcome is symptom evaluation including morning stiffness, pain, and joint swelling. The number of joints affected by RA, Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), anti-cyclic peptide containing citrulline (A-CCP), and adverse effects, will be evaluated as secondary outcomes. CONCLUSIONS: This study will compare the efficacy and safety of warming acupuncture and moxibustion with common acupuncture in the treatment of RA, providing reliable evidence for clinical application. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/C8RY9.

Performance of the PET vascular activity score (PETVAS) for qualitative and quantitative assessment of inflammatory activity in Takayasu's arteritis patients.

PURPOSE: To assess the performance of PET vascular activity score (PETVAS) in comparison with SUVmax, inflammatory biomarkers and ITAS-2010 score in a cohort of TAK patients. METHODS: Sixty-four PET/CT scans acquired from 54 TAK patients were analyzed. The inflammatory activity was qualitatively determined by physician's global assessment and quantitatively determined by ITAS-2010 score. SUVmax and PETVAS were acquired by consensus review. Levels of the inflammatory biomarkers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and pentraxin-3 (PTX-3) were measured. Performance of the qualitative diagnoses and the quantitative correlation were, respectively, compared by receiver operating characteristic (ROC) curve and Spearman correlation coefficient. RESULTS: The biomarkers (CRP, ESR, PTX-3), PET uptake values (SUVmax, PETVAS), and ITAS-2010 scores were all significantly higher in active patients than in non-active ones. The area under the ROC curve and Youden Index of PETVAS and PTX-3 were higher than those of SUVmax, CRP, ESR, and ITAS-2010. PETVAS and PTX-3 resulted in a higher Spearman correlation coefficient with ITAS-2010 than other criteria, either among all patients or within the active group. Alteration trends of PETVAS and PTX-3 during follow-up showed a tighter correlation with clinical progression/remission assessment than other criteria. CONCLUSIONS: In TAK evaluation, PETVAS is superior for qualitative and quantitative assessment, compared with the regional SUVmax. Compared to CRP and ESR, inflammatory biomarker PTX-3 shows better qualitative performance and a higher correlation with PETVAS and ITAS-2010. These findings indicate that the use of PETVAS and PTX-3, instead of SUVmax and CRP/ESR, has potential advantages in the clinical evaluation of TAK.

Cost-effectiveness analysis of etanercept plus methotrexate vs triple therapy in treating Chinese rheumatoid arthritis patients.

OBJECTIVE: This study aimed to explore the cost-effectiveness of etanercept plus methotrexate (ETN+MTX) compared to triple disease-modifying anti-rheumatic drugs (DMARDs) in treating Chinese rheumatoid arthritis (RA) patients. METHODS: The 134 Chinese RA patients who were about to initiate ETN+MTX or triple DMARDs therapy based on treat-to-target strategy were consecutively recruited and categorized into ETN+MTX group (N = 49) or triple DMARDs group (N = 85). Treatment efficacy was assessed at month 3 (M3)/M6/M9/M12 after initiation of treatment. Also, 1-year treatment cost was evaluated, and cost-effectiveness analysis and sensitivity analysis were conducted. RESULTS: RA patients in ETN+MTX group exhibited similar disease activity and quality of life at each time point while elevated 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) change (M0-M12) and low disease activity rate compared with triple DMARDs group. For 1-year treatment cost, ETN+MTX required increased drug cost, decreased other medical cost, and finally elevated total cost compared with triple DMARDs. Meanwhile, compared to triple DMARDs, ETN+MTX produced an additional quality-adjusted life year (QALY) of 0.015, resulting in an incremental cost-effectiveness ratio (ICER) of ¥2,939,506.7 per QALY that was 53.1 folds of gross domestic product (GDP) per capita in China. More interestingly, sensitivity analysis revealed that the ETN price had to be reduced at least by 71.3% before ETN+MTX became cost-effectiveness compared to triple DMARDs. CONCLUSION: ETN+MTX is less cost-effective in treating Chinese RA patients compared with triple DMARDs.

A retrospective study of bone scintigraphy in the follow-up of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: is it useful to repeat bone scintigraphy for disease assessment?

OBJECTIVES: To investigate the value of repeated bone scintigraphy in the follow-up of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to characterize the changing pattern of osteoarticular lesions revealed by bone scintigraphy. METHOD: Twenty-four patients with SAPHO syndrome who had repetitively undergone bone scintigraphy and tests of inflammatory markers (erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)) were included in this retrospective study. The change in accumulation number was recorded as the difference in the number of accumulation sites between consecutive bone scintigraphy. The visual analog scale (VAS) for pain and medications prescribed were also reviewed. The relationships of the change in accumulation number with medication prescribed and change in ESR or CRP were analyzed. RESULTS: Twenty-four and 23 patients had follow-up tests of ESR and CRP, from which 30 and 28 follow-up data were obtained, containing the corresponding changes in ESR and CRP, respectively. A decrease in total accumulation number observed by bone scintigraphy was rarely observed, while decreases in ESR, CRP, and VAS were predominant. The accumulation number had significantly increased over time (follow-up with ESR: r = 0.389, p = 0.034; follow-up with CRP: r = 0.438, p = 0.020), in accordance with an "imprinting" pattern, while the inflammatory markers and VAS for pain predominantly decreased. There was no significant association between the change in accumulation number (local/total) and the change in ESR or CRP values (p > 0.05) or medications used for SAPHO (p > 0.05). CONCLUSIONS: This retrospective cohort study of 24 SAPHO patients demonstrated an "imprinting" pattern on bone scintigraphy, without a correlation to the decrease in inflammatory markers, patient disease assessment, or treatment type. Thus, repeated bone scintigraphy did not contribute an additional clinical value for the follow-up of patients with SAPHO.Key Points• In a cohort of 24 SAPHO patients, repeated bone scintigraphy revealed a continuous increase in tracer accumulation number, indicating an "imprinting" pattern.• The change in tracer accumulation number, defined as the difference in the number of accumulation sites between consecutive bone scintigraphy measurements, was inconsistent with the change in ESR, CRP, or VAS for pain.• The medications prescribed for SAPHO did not seem to contribute to a decrease in accumulation number.• Repeated bone scintigraphy did not seem to be useful for the assessment of disease activity in patients with SAPHO.

Utility of Tetrahydrobiopterin Pathway in the Assessment of Diabetic Foot Ulcer: Significant and Complex Interrelations.

OBJECTIVES: Tetrahydrobiopterin (BH4) pathway that included generation of neopterin (Neop), biopterin (Biop), and nitric oxide (NO) is altered in type 2 diabetes (T2D). The aim of this study was to assess the biomarkers of BH4 pathway in noninfected DFUs and to relate these levels to the variables of diabetes as well as to the hematological indices. METHODS: We performed a cross-sectional investigating study in a Kurdish people including 30 healthy subjects (group I), 66 T2D patients (group II), and 57 DFUs patients (group III). Hematological indices including red cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) were determined by Coulter hematological analysis. Serum BH4 markers including NO, Neop, and Biop were determined by using an enzyme-linked immunosorbent assay (ELISA) technology. The relationship between BH4 markers with glycemic and hematological indices was assessed by Spearman's correlation and multivariable regression analysis. RESULTS: Neop was significantly increased while PDW was significantly decreased in group III compared with group II patients. Nitric oxide was found to be inversely correlated with age (r = -0.382), duration of diabetes (r = -0.264), mean arterial blood pressure (r = -0.532), body mass index (r = -0.321), RDW (r = -0.322), and PDW (r = -0.284) in group III patients. Circulating Neop and Biop significantly correlated with RDW and erythrocyte sedimentation rate. Multivariable regression analysis revealed that serum Neop predicted the DFUs in 92.5% of group III patients. CONCLUSION: Tetrahydrobiopterin biomarkers are predictors of DFUs and the significant correlation of neopterin with red distribution width and erythrocyte sedimentation rate indicating the role of neopterin in the vascular and inflammation concerns of noninfected DFUs.

Prognostic factors for unfavourable outcomes of patients with spinal tuberculosis in a country with an intermediate tuberculosis burden: a multicentre cohort study.

AIMS: Spinal tuberculosis (TB) remains an important concern. Although spinal TB often has sequelae such as myelopathy after treatment, the predictive factors affecting such unfavourable outcomes are not yet established. We investigated the clinical manifestations and predictors of unfavourable treatment outcomes in patients with spinal TB. PATIENTS AND METHODS: We performed a multicentre retrospective cohort study of patients with spinal TB. Unfavourable outcome was defined according to previous studies. The prognostic factors for unfavourable outcomes as the primary outcome were determined using multivariable logistic regression analysis and a linear mixed model was used to compare time course of inflammatory markers during treatment. A total of 185 patients were included, of whom 59 patients had unfavourable outcomes. RESULTS: In multivariate regression analysis, the factors associated with unfavourable outcome were old age (odds ratio (OR) 2.51; 95% confidence interval (CI) 1.07 to 5.86; p = 0.034), acid-fast bacilli (AFB) smear positivity in specimens obtained through biopsy (OR 3.05; 95% CI 1.06 to 8.80; p = 0.039), and elevated erythrocyte sedimentation rate (ESR) at the end of treatment (OR 3.85; 95% CI 1.62 to 9.13; p = 0.002). Patients with unfavourable outcomes had a significant trend toward higher ESR during treatment compared with patients with favourable outcome (p = 0.009). Duration of anti-TB and surgical treatment did not affect prognosis. CONCLUSION: Elevated ESR at the end of treatment could be used as a marker to identify spinal TB patients with a poor prognosis. Patients whose ESR is not normalized during treatment, as well as those with old age and AFB smear positivity, should be aware of unfavourable outcomes. Cite this article: Bone Joint J 2019;101-B:1542-1549.

Assessment of subclinical atherosclerotic cardiovascular disease in patients with ankylosing spondylitis.

OBJECTIVE: The aim of the present study was to compare patients with ankylosing spondylitis (AS) with healthy controls with respect to subclinical atherosclerotic cardiovascular disease (CVD). METHODS: A total of 44 patients with AS with no history of CVD, diabetes mellitus, hypertension, chronic kidney disease, and lipid-lowering drug use were compared with 40 age- and sex-matched healthy controls with respect to carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), which are surrogate markers of subclinical atherosclerosis. Correlation analysis was also performed to examine the association between surrogate markers and disease activity with inflammation [Ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP)]. RESULTS: In addition to age and sex, both groups were comparable with respect to cigarette smoking, body mass index, and high-density lipoprotein cholesterol (p=0.425, p=0.325, and p=0.103, respectively). The level of total cholesterol was significantly lower in patients with AS (p=0.002). Nonsteroidal anti-inflammatory drug and tumor necrosis factor alpha inhibitor use ratios in patients with AS were 79.5% and 65.9%, respectively. There was no significant difference between both groups regarding PWV and CIMT (p=0.788 and p=0.253, respectively). In patients with AS, there was a significant correlation between ASDAS-CRP and CIMT (r=0.315, p=0.038), but the correlation between ASDAS-CRP and PWV was not significant (r=-0.183, p=0.234). CONCLUSION: The results of the present study could not provide sufficient evidence whether disease activity with inflammation caused subclinical atherosclerotic CVD in patients with AS without overt CVD. The increased atherosclerotic CVD risk is most probably multifactorial in patients with AS, but the extent of the contribution of disease activity with inflammation to increased atherosclerosis is controversial.