Datasets:

austin

/

rheum_abstracts

like 0

Follow

Austin Health 2

To define the diagnostic value of ultrasonographic (US) examination in comparison with magnetic resonance imaging (MRI) for the assessment of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). MRI and US examinations were performed in 33 patients (22 with RA and 11 with PsA). Alterations of the disc, alterations of the condyle and joint effusion were evaluated. Pathological changes of the TMJ were observed by MRI in 24 patients and by US in 31 patients. The sensitivity and specificity of US were calculated in comparison with MRI. The sensitivity was 72.2% and the specificity was 60% in the assessment of pathological changes of the TMJ. The sensitivity was 69.6% with specificity of 30.0% in the assessment of alterations of the disc; the sensitivity was 70.6% with specificity of 75.0% in the assessment of joint effusion. Significant concordance was not observed in the assessment of condylar alterations.

US imaging appears able to detect different pathological changes of the TMJ and may be considered an important diagnostic tool for clinical evaluation of the TMJ in RA and PsA.

To compare the correlation and specificity of the combined cortical thickness of the second metacarpal (CCT-MC) with Sharp's method (SM) for scoring joint erosions and joint space narrowing in rheumatoid arthritis (RA) and to compare the degree of interobserver agreement between the 2 methods. Hand microradiographs of 22 women with RA, functional classes III and IV, were scored independently by 3 rheumatologists using the CCT-MC and the CCT of the middle phalanx and SM. (1) There was a highly significant correlation between the total SM score and the CCT-MC for the 3 observers (r = 0.61, p = 0.0026), but not between the CCT of the middle phalanx and SM (r = 0.15, p = 0.53). There was a lower degree of agreement between the observers for SM erosion scores compared to the CCT-MC (intraclass correlation 0.88 for the CCT-MC and 0.63 for the SM); (2) Both joint space narrowing and erosion scores correlated highly with the CCT-MC (r = -0.60, p = 0.004; and r = -0.51, p = 0.014, respectively); (3) CCT-MC measurements are more closely related to the inner (d) as opposed to the outer (D) diameter of the 2nd metacarpal; (4) The mean time to obtain the CCT-MC score was 3.43 min (SD = 1.38) versus 9.83 min (SD = 3.20) for SM (p = 0.0001); (5) the derivative, (D2-d2)/D2, was significantly correlated with SM (r = -0.72, p = 0.0002) and its erosion and joint space narrowing components (r = -0.63, p = 0.0019; and r = -0.71, p = 0.0002, respectively).

The CCT-MC is a rapid, practical method with higher agreement among observers compared to SM and correlates highly with SM scores for joint damage in RA. CCT-MC appears to have a higher degree of specificity than other sites for CCT measurement. The CCT-MC is more closely related to the inner diameter than the outer diameter, which supports the notion that the principal site of accelerated bone loss due to RA in the hand occurs at the endosteal surface. The CCT-MC should be further assessed with respect to monitoring radiological progression in RA.

Increasing bone mineral density (BMD) has been found in several studies in patients with osteoarthritis (OA). Therefore, the simultaneous occurrence of osteoporosis (OP) and OA is denied by many clinicians. Because of our clinical impression, however, we suggest that we have to consider a common occurrence. In the present study we have examined the relationship between osteoathritis of the knee or the hip and osteoporosis. The BMD of the lumbar spine and the proximal femur of 117 OA patients (82 postmenopausal female patients aged 50-83 and 35 male patients aged 36-86 years) who subsequently required hip or knee replacements, but were otherwise healthy, was measured by dual-energy X-ray absorptiometry (DXA; Hologic QDR-2000). The results are given as required by the WHO and the new German guidelines of the DVO. The BMD was measured and categorised in a sex-related manner and the occurrence of disuse osteoporosis on the affected limb was examined. Furthermore, a comparison was made in the level of BMD between the OA of the involved hip or knee. There was a high occurrence of low BMD among the patients. 23.2 % of the women were affected by OP. This reflects the normal distribution of OP in the female population. 20 % of the male patients had occult OP. This is astonishingly high. Osteopenia was measured for 37.1 % of the male patients and 42.7 % of the female patients. Age proved to be a significant factor in the degree of BMD. Neither a disuse osteoporosis, nor a significance in the OA-affected joint to the degree of BMD, could be proven.

We cannot support the hypotheses that OA prevents OP. Moreover, the occurrence of OP in our study reflected the incidence of OP in the average female and was astonishingly high in the male population; this does not support the hypothesis that the two conditions are mutually exclusive. Also a lower risk of fractures among OA patients cannot be concluded. There is current open discussion whether a known BMD should influence the decision for a cemented or an uncemented prosthesis.

To clarify the molecular mechanisms of Sjögren's syndrome (SS), we analyzed the functional role of the STAT-1 gene, one of the interferon-gamma (IFNgamma)-inducible genes, in labial salivary glands (LSGs) from SS patients. The expression of STAT-1 messenger RNA (mRNA) was examined by real-time polymerase chain reaction (PCR) analysis, and the phosphorylation of STAT-1 protein (Tyr(701) and Ser(727) pSTAT-1) was investigated by Western blot and immunohistochemical analyses. The expression of IFNgamma-inducible 10-kd protein (IP-10), IFN regulatory factor 1 (IRF-1), and Fas was also examined by real-time PCR and immunohistochemical analyses. STAT-1alpha and STAT-1beta mRNA were highly expressed in LSGs from SS patients. The level of STAT-1alpha protein in SS LSGs was higher than that in 3 control LSGs, whereas STAT-1beta protein was not clearly detected by Western blot analysis. Moreover, Tyr(701) and Ser(727) pSTAT-1alpha proteins were specifically detected in SS LSGs. Immunohistochemical analysis showed localization of Tyr(701) pSTAT-1 in infiltrating lymphocytes and the adjacent ductal epithelium from SS patients. Ser(727) pSTAT-1 was localized only in the ductal epithelium of SS LSGs. The STAT-1-inducible genes IP-10 and IRF-1 and the Fas genes were highly expressed in SS LSGs and were colocalized with Ser(727) pSTAT-1-positive, but not Tyr(701) pSTAT-1-positive, cells.

We found evidence of the up-regulation of STAT-1alpha mRNA and protein in LSGs from SS patients, as well as the presence of pSTAT-1alpha in ductal epithelium from SS patients. Our findings suggest that STAT-1alpha, especially Ser(727) pSTAT-1, may function as a key molecule in the pathogenesis of SS.

To systematically review the literature to determine whether biomechanical factors, meniscal pathology, and physical activity are risk factors for bone marrow lesions (BMLs) at the knee identified from magnetic resonance imaging in pre-osteoarthritis and osteoarthritis populations. Electronic searches of MEDLINE and EMBASE were performed from January 1, 1996 to October 31, 2012 using the keywords of bone marrow lesion(s), bone marrow (o)edema, osteoarthritis, and knee. Studies examining biomechanical factors, meniscal pathology, or physical activity in relation to the presence, incidence, or change in BMLs at the knee were included. Two independent reviewers extracted the data and assessed the methodological quality of selected studies. Due to the heterogeneity of the studies, we performed a best evidence synthesis. Fifteen studies were included in this review, of which 9 were considered high quality. The study populations were heterogeneous in terms of the symptoms and radiographic knee osteoarthritis. There was strong evidence for relationships of mechanical knee alignment and meniscal pathology with BMLs in osteoarthritis populations. There was a paucity of evidence for a relationship between physical activity and BMLs.

Despite the heterogeneity of included studies, these data suggest that mechanical knee alignment and meniscal pathology are risk factors for BMLs in knee osteoarthritis. It suggests that BMLs in individuals with osteoarthritis are more susceptible to mechanical knee alignment. Given the role of BMLs in the pathogenesis of knee osteoarthritis, identifying strategies to modify these risk factors will be important in slowing the progression and reducing the burden of knee osteoarthritis.

Rheumatoid arthritis (RA) is the most common inflammatory disease involving the spine. It has a predilection for involving the craniocervical spine. Despite widespread involvement of the cervical spine with RA, few patients need surgery. The 3 major spinal manifestations of RA in the cervical spine are basilar invagination, atlantoaxial instability, and subaxial subluxations. Surgical management of RA involving the craniovertebral junction remains a challenge despite a decline in severe cases and an improvement in surgical techniques. We conducted an exhaustive review of English-language publications discussing RA involving the craniovertebral junction. We paid special attention to publications detailing modern surgical management of these conditions. In addition, we outline our own surgical experience with such patients. We discuss alternative surgical methods for treating basilar invagination, atlantoaxial instability, and concurrent subaxial subluxations. We detail our surgical technique for transoral odontoidectomy, occipital cervical fusion, and atlantoaxial fusion. We detail the use of spinal surgical navigation in both of these procedures.

Surgical management of RA remains a challenging field. There clearly has been a decrease in cases of mutilating RA involving the craniovertebral junction. Surgical techniques for managing these conditions have steadily improved.

Inflammation and anti-inflammatory treatments might influence the risk of diabetes. The objective of this study was to assess factors associated with incident diabetes in rheumatoid arthritis (RA). The study population consisted of RA patients from a multi-center cohort study, Corrona. To assess risk associated with disease modifying antirheumatic drug (DMARD) exposure, we assessed five mutually exclusive DMARD groups. Additionally, we assessed the risk associated with body mass index (BMI, <25, 25-30, >30 kg/m2) and glucocorticoid usage. Incident cases of diabetes were confirmed through adjudication, and Cox regression models were fit to estimate the risk of incident diabetes. We identified 21,775 DMARD treatment regimens, the mean (SD) age at the index visit was 58 (13) years, disease duration 10 (10) years, and 30% used oral glucocorticoids at the time. Eighty-four incident cases of diabetes were confirmed within the treatment exposure periods. The hazard ratio (HR, 95% confidence interval) for diabetes was significantly reduced in patients receiving TNF inhibitors, HR 0.35 (0.13, 0.91), compared to patients treated with non-biologic DMARDs other than hydroxychloroquine and methotrexate. Hydroxychloroquine, methotrexate and use of other biologic DMARDs had a numerically reduced risk compared to the same group. Patients prescribed ≥7.5 mg of glucocorticoids had a HR of 2.33 (1.68, 3.22) of incident diabetes compared with patients not prescribed oral glucocorticoids. RA patients with a BMI >30 had a HR of 6.27 (2.97, 13.25) compared to patients with BMI ≤25.

DMARDs, glucocorticoids and obesity influenced the risk of incident diabetes in a large cohort of RA patients. Monitoring for the occurrence of diabetes should be part of routine RA management with a focus on specific subgroups.

To clarify the significance of YKL-40, also called human cartilage glycoprotein-39, in the serum of patients with RA, we studied serum YKL-40 in relation to clinical and laboratory parameters. Seventy-two patients (16 men and 56 women) with RA and 40 age-matched healthy persons (14 men, 26 women) were included in this study. Serum levels of YKL-40, insulin-like growth factor-I (IGF-I) and interleukin-6 (IL-6) were measured by ELISA. Radiological changes reflecting joint destruction and the joint score for pain or swelling were assessed by taking into account the joint surface area. Serum CRP levels and the functional disability of patients were also determined. YKL-40 levels in the serum of patients with RA were significantly higher than those of controls (p < 0.0001), and showed positive correlations with serum levels of IL-6 (r = 0.301, p = 0.011) and CRP (r = 0.326, p = 0.006), but negative correlations with serum levels of IGF-I (r = -0.340, p = 0.004). The radiological score, but not joint pain, also correlated with YKL-40 levels (r = 0.364, p = 0.002). As the functional disability of patients became severe, the serum YKL levels increased.

Serum YKL-40 levels partially reflect the degree of inflammation and also reflect the joint destruction in patients with RA.

This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid arthritis-related interstitial lung disease (RA-ILD). PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively. Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI: 1.35-4.68; P = 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI: 0.17-0.62; P = 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD =  - 0.03; 95% CI: - 0.89-0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI: - 0.26-0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI: 2.19-3.71; P < 0.00001) and serum RF titer was significantly correlated with the risk of RA-ILD (SMD = 0.35; 95% CI: 0.23-0.46; P < 0.00001). However, for the analysis of RF dichotomous data, the funnel shape was asymmetric and the p value of egger test was less than 0.05, which indicated potential publication bias. • Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.

ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention.

To identify clinical and genetic risk factors for extra-articular manifestations of rheumatoid arthritis (ExRA). ExRA patients were identified retrospectively using predefined criteria in two hospital-based cohorts of RA patients, and compared to non-extraarticular RA controls from one of the cohorts, matched for disease duration. Forty-nine living and thirteen deceased cases of ExRA were identified. Extra-articular disease was predicted by the demonstration of antinuclear antibodies (Odds ratio (OR) 3.6; 95% CI: 1.4-9.1) and the presence of rheumatoid nodules within two years from RA diagnosis (OR 3.4; 95%, CI: 1.1-10.9) or at any time before ExRA onset (OR 2.8; 95% CI: 1.1-7.2). Male sex and rheumatoid factor did not affect the risk of ExRA. Although present in the majority of cases as well as controls, the disease associated HLA-DRB1 subtypes were not significant predictors of ExRA.

Extra-articular manifestations of rheumatoid arthritis in a hospital based population were predicted by antinuclear antibodies and rheumatoid nodules.

Surgical management options for bilateral knee osteoarthritis comprise staged or single-anaesthetic bilateral total knee replacements (SABTKRs). We examined the New Zealand Joint Registry hypothesizing there would be no difference between these practices compared to unilateral total knee replacement (TKR) examining 30-day mortality, all-cause revision rate and function. For this study, 84 946 primary TKRs were identified. We compared three groups: unilateral TKRs, all SABTKRs and all staged bilateral TKRs with intervals of 1 to 90 days, 91 days to 1 year and >1 year. Cumulative revision rates were calculated (Kaplan-Meier method). Mortality risks were compared to unilateral TKR and hazard ratios (HRs) calculated. Six-month Oxford scores were compared using analysis of variance. Thirty-day mortality for SABTKR was 0.219%: unilateral TKR 0.236% (HR 0.43; 95% confidence interval (CI) 0.38-0.48; P < 001). Staged TKR had lower mortality than unilateral TKR at three time interval groups unless performed within 90 days (adjusting for age and American Society of Anesthesiologists grade) TKR (<90 days HR 0.92; 95% CI 0.703-1.371; P = 0.915; 91-365 days HR 0.783; 95% CI 0.687-0.891; P < 0.001; >365 days HR 0.394; 95% CI 0.344-0.451; P < 0.001). Revision risk with SABTKR was lower at 0.43/100 component years (95% CI 0.37-0.49/100 component years) compared to unilateral 0.56/100 component years (95% CI 0.53-0.59; P < 0.05). Six-month Oxford scores were superior in SABTKR versus unilateral TKR (38.6 (95% CI 38.2-39) versus 36.9 (95% CI 36.8-37.1); P < 0.001).

SABTKR is at least as safe as unilateral TKR or staged bilateral TKR in appropriately selected cases. Surgeons should wait at least 90 days before the second procedure.

To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M). Samples from 3582 individuals from the Rotterdam Study, the Genetics osteoArthritis and Progression (GARP), the Chingford Study and the TwinsUK cohort were assayed using enzyme-linked immune sorbent assays. Log10 of concentration levels were correlated with risk of hip, hand and knee OA, hip and knee OA severity and incidence, and progression of knee OA, adjusting for age, gender and body mass index (BMI). Results were meta-analysed to assess overall significance. After adjusting for covariates, sCOMP was associated with knee OA and hip and knee OA incidence. Furthermore, sC2M was associated with knee OA incidence and progression. After adjustment for multiple tests (Bonferroni P < 0.002) only the association between sCOMP and knee OA remained significant (odds ratio (OR) = 3.26 (95%CI 1.63-10.1) P = 0.0008 for each standard deviation (SD) increase in biomarker levels). Levels of uCTX-II were significantly associated with risk of hand, hip and knee OA, progression and incidence of knee OA. A receiver operating characteristics (ROC) analysis showed a consistent improvement in prediction of knee OA progression from an average area under the curve (AUC) is 0.646 for age, sex and BMI alone to an AUC = 0.668 including uCTX-II for prediction.

uCTX-II is the most informative biochemical marker for prediction of OA. Both sCOMP and C2M showed some association with OA, thus indicating that they are descriptive of disease activity.

Sjögren's syndrome (SjS) causes malfunction of the salivary and lacrimal glands. Consequently, patients suffer from xerostomia and keratoconjunctivitis sicca. This can further affect the voice and swallowing function resulting in an impaired quality of life. Aim of this study is the systematic evaluation of the impact on voice and swallowing-related quality of life in patients with SjS. SjS patients were classified according to the American-European Consensus Group (AECG) criteria; antibodies to Ro (SS-A) or La (SS-B) antigens were detected, ESSPRI was completed. We used the following quality of life questionnaires: EORTC QLQ H&N 35, Anderson Dysphagia Inventory (ADI) and Voice Handicap Index (VHI). Patients additionally received a detailed phoniatric examination (auditory perception, videostroboscopy, acoustic analysis, Dysphonia Severity Index (DSI), aerodynamics measurements). Almost all the 54 patients (96.3%) had a limited quality of life due to their swallowing problems and 48% due to their voice problems. Both values correlated significantly with the degree of xerostomia. In the phoniatric examination, 77.8% had an increased DSI and two-thirds had abnormalities in videostroboscopy.

A reasonable impairment of quality of life in patients with SjS due to the limitations in voice and swallowing function was observed. As SjS does not limitate life expectancy, preservation of quality of life is important. Detection of voice and swallowing problems as potential reasons for quality of life impairment should be detected and, if diagnosed, treated accordingly.

To detect whether early growth response 1 (EGR1) in peripheral blood leucocytes (PBLs) indicates temporomandibular joint (TMJ) osteoarthritis (OA) lesions. Egr1 mRNA expression levels in PBLs were detected in eight malocclusion patients without temporomandibular disorder (TMD) signs and 16 malocclusion patients with clinical TMD signs with (eight) or without (eight) imaging signs of TMJ OA. Twelve 6-week-old rats were randomized to a control group and a unilateral anterior crossbite (UAC) group and were sampled at 4 weeks. The Egr1 mRNA expression levels in PBLs and protein expression levels in different orofacial tissues were measured. Patients with TMD signs with/without TMJ OA diagnosis showed lower Egr1 mRNA expression levels in PBLs than patients without TMD signs. The lower Egr1 mRNA expression was also found in the PBLs of UAC rats, which were induced to exhibit early histo-morphological signs of TMJ OA lesions. In subchondral bone of UAC rats, EGR1 protein expression was decreased, co-localization of EGR1 with osterix or dentin matrix protein-1 was identified, and the number of EGR1 and osterix double-positive cells was reduced (all p < .05).

Egr1 reduction in PBLs potentially indicates subchondral bone OA lesions at an early stage.

To determine if dendritic antigen-presenting cells (DC) are present in rheumatoid nodules, as has been reported in the synovial lesions of rheumatoid arthritis. Nodules (n = 14) were examined with monoclonal antibodies (Mab) recognizing the DC differentiation/activation markers CD83, CMRF44, and CMRF56 and an antibody recognizing the CD1a antigen present on epithelial tissue associated DC. Results. Cells expressing CMRF44 were common in rheumatoid nodules, comprising 22% of nucleated cells versus 13% in synovial membranes (n = 10). Cells positive for CD1a (5%) and CD83 (2%) were less common. A majority (86%) of CMRF44 positive cells were also positive for the macrophage marker CD14. This left a significant minority of putative DC that were single stained with CMRF44.

Cells bearing DC markers are as frequent in the rheumatoid nodule as in the synovial lesions. A majority are "indeterminate" cells that are CD14 positive but a proportion are single stained putative DC. The lack of lymphoid collections containing DC and T and B lymphocytes in the nodule suggests that local presentation of antigen may not occur in the rheumatoid nodule, as is thought to be the case in synovial membranes containing lymphoid follicles. This difference could potentially be explained by different states of activation, and differentiation of DC within the 2 lesions.

Before biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment, latent tuberculosis infection (LTBI) screening by tuberculin skin test (TST) or interferon gamma release assay (IGRA) is recommended. However, both tests have reduced reliability in immunosuppressed patients. We investigated whether dual LTBI screening with both tests could reduce the incidence of tuberculosis. Consecutive patients receiving b/tsDMARDs for rheumatic diseases in a regional hospital were recruited. All patients underwent either TST/IGRA or both. They were categorised into a single or dual testing group and were followed up for at least 6 months. Isoniazid was prescribed if any one test was positive. In total, 217 patients were included in this study; 121 underwent single LTBI testing and 96 underwent dual testing. Tuberculosis occurred in nine patients in the single testing group and one patient in the dual testing group (7.4% vs 1.0%, P=0.045). However, the difference was not statistically significant when follow-up duration was considered (log rank test). In total, 71 patients tested positive for LTBI with isoniazid treatment (28.9% in the single testing group and 45.8% in the dual testing group, P=0.007). Agreement between the IGRA and TST was 74.4% (Cohen's kappa=0.413); agreement was lower in patients receiving prednisolone. Infliximab use was independently associated with tuberculosis (P=0.032). Mild isoniazid-related side-effects occurred in seven patients.

Dual LTBI testing with both TST and IGRA is effective and safe. It might be useful for patients receiving prednisolone at the time of LTBI screening, or if infliximab therapy is anticipated.

The aims of the present rheumatoid arthritis (RA) study were (1) to examine the levels of serum 3-B-3 and 7-D-4 to find out whether they are different from controls, (2) to find out whether the concentrations of these epitopes change with disease duration in early RA and (3) whether the serum concentrations of 3-B-3 and 7-D-4 in early RA are prognostic for subsequent disease progression. The concentrations of 3-B-3 and 7-D-4 in sera were quantitated by immunoassays. The levels of 3-B-3 and 7-D-4 were significantly lower in RA than in controls (3- to 30-fold, P < 0.001). Changes in 3-B-3 and 7-D-4 were apparent with disease duration. At first presentation, the 3-B-3 concentration was lowest and increased at 12 months (3-fold, P < 0.001). This increase was transient since by 24 and 36 months the concentrations were not different to those at first presentation. The level of 7-D-4 was also lowest when the patients first presented at clinic and increased with time at 6 months (2-fold, P < 0.001). The increase was more prolonged for 7-D-4, remaining elevated at 12, 24 and 36 months. The lack of correlations of serum 3-B-3 and 7-D-4 with clinical measurements showed that these markers were not prognostic for disease severity.

The levels of 3-B-3 and 7-D-4 differed between RA and control sera, and changed with disease duration. These markers were not prognostic in predicting disease outcome.

To compare bone mass (BMD) in women with fibromyalgia (FM) with healthy females, and to evaluate whether self-reported pain and lack of functional capacity correlate to reduced BMD in FM patients. Thirty-one FM patients (20 pre- and 11 postmenopausal) and fourty-one healthy women (30 pre- and 10 postmenopausal) were enrolled in the study. BMD of the lumbar spine and the femoral neck was measured by a DEXA (Norland) scanner. Self reported pain was measured on a Visual Analog Scale (VAS). The Activity of Daily Living (ADL) component of the Fibromyalgia Impact Questionnaire (FIQ-ADL) was used as measure for physical capacity. BMD-lumbar spine and BMD-femoral neck did not differ significantly between FM patients and controls, though premenopausal FM patients tended to have lower BMD-femoral neck (p = 0.09). Self reported pain and FIQ-ADL among FM patients correlated with BMD-femoral neck (r(s) = -0.52, p = 0.003); (r(s) = -0.31, p = 0.09).

Premenopausal FM patients tended to have lower BMD of hip than controls. Self reported pain correlated negatively to BMD. Thus, the severity of FM might have a negative impact on bone mass.

Glucocorticoid (GC) therapy is frequently used to treat rheumatoid arthritis due to potent anti-inflammatory actions of GCs. Direct actions of GCs on immune cells were suggested to suppress inflammation. Define the role of the glucocorticoid receptor (GR) in stromal cells for suppression of inflammatory arthritis. Bone marrow chimeric mice lacking the GR in the hematopoietic or stromal compartment, respectively, and mice with impaired GR dimerisation (GR GR deficiency in immune cells did not impair GC-mediated suppression of STIA. In contrast, mice with GR-deficient or GR dimerisation-impaired stromal cells were resistant to GC treatment, despite efficient suppression of cytokines. Intriguingly, in mice with impaired GR function in the stromal compartment, GCs failed to stimulate non-classical, non-activated macrophages (Ly6C

We report a novel anti-inflammatory mechanism of GC action that involves GR dimerisation-dependent gene regulation in non-immune stromal cells, presumably FLS. FLS control non-classical, anti-inflammatory polarisation of macrophages that contributes to suppression of inflammation in arthritis.

To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy. Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks. Inadequate responders then entered the double blind phase and received a further 24 weeks' treatment with leflunomide (20 mg once daily) plus sulfasalazine (final dose 2 g once daily), or placebo plus sulfasalazine (dose as above). The primary efficacy variable was the DAS28 response rate, and secondary efficacy outcomes were ACR 20%, 50%, and 70% response rates. Adverse events, including standard laboratory tests, were recorded. 106 inadequate responders entered the double blind phase; 56 received leflunomide plus sulfasalazine, and 50 placebo plus sulfasalazine. In the intention to treat population, more patients receiving leflunomide plus sulfasalazine (25/56 (45%)) achieved a DAS28 response than those receiving placebo plus sulfasalazine (17/50 (34%)) (p = 0.179). In week 24 completers, more patients receiving leflunomide plus sulfasalazine (17/56 (30%)) were DAS28 responders than those receiving placebo plus sulfasalazine (10/50 (20%)) (p = 0.081). Comparable numbers in each group were ACR 20% responders; the ACR 50% response rate was significantly higher in the leflunomide plus sulfasalazine group (8.9%) than in the placebo plus sulfasalazine group (0%) (p = 0.038). The safety profiles of both groups were comparable.

Patient numbers are small and firm conclusions cannot be reached, but a non-significant benefit is indicated for combining leflunomide with sulfasalazine compared with switching to sulfasalazine alone in patients inadequately responding to leflunomide.

Systemic lupus erythematosus (SLE) is a chronic disease characterised by autoimmunity and increased susceptibility to infections. COVID-19 is a systemic viral disease currently spreading as a pandemic. Little is known about the impact of COVID-19 in patients with SLE. to acquire information on the impact of COVID-19 in SLE. A 26-item anonymous questionnaire investigating demographics, SLE clinical features, COVID-19 diagnoses and changes in treatments and daily habits was administered to patients with SLE from three referral centres through www.surveymonkey.com over 10 days. Data from the survey were compared to those from published estimates about the general population. Four-hundred-seventeen patients responded to the survey. More than 60% of subjects complained of symptoms that are also associated to COVID-19. Fourteen COVID-19 diagnoses (five confirmed by polymerase chain reaction) were reported, in contrast to a 0.73% prevalence of confirmed cases in Lombardy. One hospitalisation was reported. Fever, anosmia, dry cough, a self-reported history of neuropsychiatric SLE and a recent contact with confirmed COVID-19 cases were more strongly associated with COVID-19, as were symptoms and lower compliance to behavioural preventive measures in patients' contacts. No protective effect was seen in subjects on hydroxychloroquine.

COVID-19 morbidity might only moderately be increased in most patients with SLE, although limited information can be inferred on more severe cases. Hydroxychloroquine apparently seems not to confer protection to infection per se, although other beneficial roles cannot be excluded. Containment policies and behavioural preventive measures could have a major role in limiting the impact of COVID-19 in patients with SLE.

To evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission. GO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28-ESR remission was measured. 3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28-ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population.

Add-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.

Thymomas, benign or malignant, may be associated with autoimmune diseases. They are classically associated with myasthenia gravis, neuromyotonia, or pure red cell aplasia. We here report, to the best of our knowledge, the first description of an association between thymoma and Reynolds syndrome (systemic sclerosis associated with primary biliary cirrhosis) in an 80-year-old woman.

The suspected pathogenesis of this association could be a thymus escape of auto-reactive T lymphocytes and the consecutive development of an auto-immune disorder.

Double-button devices for endoscopic management of acute acromioclavicular joint dislocation (ACJD) provide satisfactory short-term functional and radiological results. However, little exists in the literature regarding the long- and medium-term results of these implants, especially regarding the evolution of the acromioclavicular joint (ACJ). Satisfactory and steady long- and medium-term outcomes can be achieved in patients with acute ACJD undergoing endoscopically assisted ACJ repair using a single double-button device. A retrospective single-center study was conducted in patients with acute Rockwood III and IV ACJD treated endoscopically with a single double-button device from October 2008 to October 2010, allowing a minimum 5-year follow-up. Functional evaluation used Constant and Quick-DASH scores. Clinical evidence of dislocation recurrence was combined with bilateral Zanca views to assess coracoclavicular distance. Acromioclavicular osteoarthritis was evaluated on the Paxinos test and Zanca views. Nineteen of the 25 operated patients were seen at a mean 76.9±8.5 months' follow-up. Mean age was 34.4±8.3 years. Mean Constant and Quick-DASH scores were 96.2±5.1 and 0.9±1.6 points, respectively. Four patients had a recurrence of their initial dislocation, 3 of whom had positive Paxinos test, whereas the 15 patients without recurrence had a negative test (p=0.004). Five patients had radiological evidence of ACJ osteoarthritis: all 4 patients with recurrence and 1 without (p=0.001). Therapeutic type IV-Retrospective case series.

Long- and medium-term radioclinical outcome of endoscopically assisted management of acute ACJD using a single double-button device seems to be satisfactory and steady over time. Recurrence of the initial dislocation appears to be related to onset of degenerative ACJ arthropathy.

To determine whether computed tomography (CT) or magnetic resonance imaging (MRI) is more suitable for the patient-specific instrumentation (PSI) systems for total knee arthroplasty (TKA). PubMed, Embase, and the Cochrane Library were searched from inception to June 2016 for prospective comparative trials that compared CT- versus MRI-based PSI systems for TKA. Our predefined primary outcome was the outliers incidence of coronal overall limb alignment. Six studies with a total of 336 knees meeting the eligibility criteria, and four trials were included in the meta-analysis. Compared with MRI-based PSI systems, CT-based PSI systems were associated with a higher outliers incidence of coronal overall limb alignment (risk ratio: 1.67; 95% confidence interval (CI): 1.03-2.72; P = 0.04), more angular errors of coronal overall limb alignment (mean difference (MD): 1.01°; 95% CI: 0.47-1.56; P = 0.0003), and longer operation time (MD: 5.02 min; 95% CI: 1.26-8.79; P = 0.009). While no significant differences in the coronal/sagittal alignment of the femoral/tibial component outliers, the angular errors of coronal overall limb alignment, the angular errors of the femoral/tibial component in coronal plane, or incidence of change of implant size of the femoral/tibial component were observed.

The current limited evidence suggests that MRI-based PSI systems exhibit higher accuracy for TKA regarding the coronal limb axis than CT-based PSI systems. However, well-designed studies comparing CT-versus MRI-based PSI systems for TKA are warrant to confirm these results before widespread use of this technique can be recommended.

To determine the pathological role of tumor necrosis factor alpha (TNF-alpha) in ocular surface disorder of patients with Sjögren syndrome (SS), TNF-alpha in the tears of patients with SS were analyzed. In addition, the relationship between TNF-alpha levels in the tear samples and the severity of the corneal epithelial disorder was evaluated. Tear samples were obtained from the 60 eyes of 30 patients with primary SS and the 60 eyes of 30 normal subjects. Tear samples were analyzed using a sandwich enzyme-linked immunosorbent assay to detect TNF-alpha. Corneal epithelial cell damage was examined with a slit-lamp biomicroscope and scored by the van Bijsterveld scoring system. TNF-alpha was detected in the tears of patients with SS at concentrations ranging from 8 to 1,500 pg/ml in 33 of the 60 eyes of the patients. In contrast, TNF-alpha was not detected in the tears of normal controls. The concentration of TNF-alpha was significantly higher in the tear samples from patients whose clinical scores were two or three points compared with patients whose scores were zero or one point (Mann-Whitney U test: p < 0.03).

TNF-alpha was detected in the tears of patients with SS, and tear TNF-alpha levels showed a significant correlation with the grade of corneal epithelial damage, suggesting that TNF-alpha is a potent mediator in keratoconjunctivitis sicca.

To determine whether systemic lupus erythematosus (SLE) can develop in the absence of BAFF in an SLE-prone host. Starting with C57BL/6 mice that express a human BCL2 transgene (Tg) in their B cells (thereby rendering B cell survival largely independent of BAFF-triggered signals), we introgressed this Tg into NZM 2328 mice genetically deficient in BAFF (NZM.Baff In comparison to their non-Tg NZM.Baff

The role of BAFF in the development of SLE-like disease may be dispensable as long as B cell survival is preserved via a BAFF-independent pathway. This may help explain the limited and variable clinical success with BAFF antagonists in human SLE. Thus, NZM.Baff

The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment. A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting, and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient-centered or disease-centered variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondyloarthritis, and knee osteoarthritis were then evaluated using the original OMERACT Filter and the newly proposed structure. Breakout groups critically reviewed the extent to which the candidate biomarkers complied with the proposed stepwise approach, as a way of examining the utility of the proposed 3-dimensional structure. Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials.

General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0.

To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years. Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded. Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1)).

BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy.

MRI slices of 1.5 mm thickness have been used in both cross sectional and longitudinal studies of osteoarthritis, but is difficult to apply to large studies as most techniques used in measuring knee cartilage volumes require substantial post-image processing. The aim of this study was to determine the optimal sampling of 1.5 mm thick slices of MRI scans to estimate knee cartilage volume in males and females for cross-sectional and longitudinal studies. A total of 150 subjects had a sagittal T1-weighted fat-suppressed MRI scan of the right knee at a partition thickness of 1.5 mm to determine their cartilage volume. Fifty subjects had both baseline and 2-year follow up MRI scans. Lateral, medial tibial and patellar cartilage volumes were calculated with different samples from 1.5 mm thick slices by extracting one in two, one in three, and one in four to compare to cartilage volume and its rate of change. Agreement was assessed by means of intraclass correlation coefficient (ICC) and Bland & Altman plots. Compared to the whole sample of 1.5 mm thick slices, measuring every second to fourth slice led to very little under or over estimation in cartilage volume and its annual change. At all sites and subgroups, measuring every second slice had less than 1% mean difference in cartilage volume and its annual rate of change with all ICCs > or = 0.98.

Sampling alternate 1.5 mm thick MRI slices is sufficient for knee cartilage volume measurement in cross-sectional and longitudinal epidemiological studies with little increase in measurement error. This approach will lead to a substantial decrease in post-scan processing time.

No studies have directly evaluated kinematic changes during squatting before and after bicruciate-stabilized total knee arthroplasty (BCS-TKA) with the dual cam-post mechanism and asymmetric surfaces. This study investigated the effect of BCS-TKA on changes to pre- and postoperative skeletal knee kinematics, to identify factors associated with postoperative skeletal kinematic parameters. Seventeen knees in 17 patients were prospectively recruited before primary TKA for advanced medial knee osteoarthritis. Subjects underwent BCS-TKA and were evaluated more than 1 year postoperatively. In vivo dynamic skeletal knee kinematics were evaluated using periodic radiographic images collected during squatting to quantify the tibiofemoral functional extension/flexion angle, anteroposterior (AP) translation, and axial rotation angle using image-matching techniques. Rotational alignments of femoral and tibial components were measured postoperatively using computed tomography images. The pre- and postoperative tibiofemoral functional extension/flexion angles during squatting were 12.2° ± 6.7°/100.1° ± 16.8° and 9.6° ± 8.6°/109.4° ± 16.8°, respectively, with a significant difference in flexion angle (p < .05). Total AP translation was significantly larger postoperatively than preoperatively (10.8 mm ± 3.7 mm vs. 14.4 mm ± 4.2 mm, respectively; p < .05). The pre- and postoperative total rotation angles were 6.6° ± 3.0° and 6.4° ± 3.7°, respectively, indicating no significant difference. The pre- and postoperative tibiofemoral functional flexion angles were significantly associated with each other (p = .0434, r = .49). The postoperative total rotation angle was significantly smaller when the total component rotational mismatch angle between the femoral and tibial components was above 5° vs. below 5° (4.6° ± 2.7° vs. 8.3° ± 3.9°, respectively; p < .05).

BCS-TKA significantly increased the tibiofemoral functional flexion angles, with larger AP translation postoperatively. Both preoperative skeletal kinematics and surgical techniques affected the skeletal kinematics of the replaced knee. A total component rotational mismatch angle greater than 5° significantly decreased postoperative total knee rotation during squatting.

Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA. 48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria. 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal.

US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.

Professionally-focussed behaviour change intervention (BCI) workshops were utilised in the Management of OsteoArthritis in Consultations (MOSAICS) trial investigating the feasibility of implementing the National Institute for Health and Care Excellence (NICE) Osteoarthritis (OA) Guideline in general practice. The workshops aimed to implement the general practitioner (GP) component of the trial intervention: an enhanced consultation for patients presenting with possible OA. This study presents an evaluation of the BCI workshops on GP competency in conducting these enhanced consultations. A before-and-after evaluation of the workshops, delivered to GPs participating in the intervention arm of the MOSAICS trial, using video-recorded GP consultations with simulated OA patients. GPs attended four workshops, which had been developed using an implementation framework. Videos were undertaken at three time-points (before workshops and at one- and five-months after) and were assessed by independent observers, blinded to time points, for GP competency in undertaking 14 predetermined consultation tasks. Videos of 15 GPs were assessed. GP competency increased from a median of seven consultation tasks undertaken by each GP at baseline to 11 at both time-points after the workshops. Specific tasks which were undertaken more frequently after the workshops related to explaining that OA is treatable and not inevitably progressive, eliciting and addressing patient expectations of the consultation, and providing written OA information. However, the use of the word "osteoarthritis" in giving the diagnosis of OA was not enhanced by the workshops.

BCI workshops can enhance GP competency in undertaking consultations for OA. Further initiatives to implement the NICE OA Guideline and enhance the care of people with OA in primary care can be informed by the content and delivery of the workshops evaluated in this study.

The purpose of this study was to determine the functional outcome and implant survivorship of mobile-bearing total ankle arthroplasty (TAA) performed by a single surgeon. We reviewed 205 consecutive patients (210 ankles) who had undergone mobile-bearing TAA (205 patients) for osteoarthritis of the ankle between January 2005 and December 2015. Their mean follow-up was 6.4 years (2.0 to 13.4). Functional outcome was assessed using the Ankle Osteoarthritis Scale, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, 36-Item Short-Form Health Survey (SF-36) score, visual analogue scale, and range of movement. Implant survivorship and complications were also evaluated. There were significant improvements in all functional outcome categories between the preoperative and final follow-up assessments (p < 0.001). Patients showed marked improvement in clinical outcomes in terms of pain, function, and quality of life. The overall implant survivorship was 91.7% at a mean follow-up of 6.4 years. In all, 33 major complications were identified with a 15.7% rate, resulting in 12 prosthesis failures (5.7%). Periprosthetic osteolysis (19 cases; 9.0%) was the most frequent complication.

Mobile-bearing TAA resulted in improved functional outcomes, a low major complication rate, and excellent implant survivorship at a mean follow-up of 6.4 years. Cite this article:

Conservative, nonsurgical therapies for basal joint osteoarthritis, such as thumb spica splinting and intra-articular corticosteroid injections, remain the mainstays for symptomatic treatment. This study compares intra-articular hylan, corticosteroid, and placebo injections with regard to pain relief, strength, symptom improvement, and metrics of manual function in a randomized, controlled, double-blinded study. Sixty patients with basal joint arthritis were randomized to receive 2 intra-articular hylan injections 1 week apart, 1 placebo injection followed by 1 corticosteroid injection 1 week later, or 2 placebo injections 1 week apart. Patients were evaluated at 2, 4, 12, and 26 weeks and assessed with Visual Analog Scale pain scores, strength measures, difference scores, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and range of motion measurements. All groups reported pain relief at 2 weeks. The steroid and placebo groups had significantly less pain at week 4 compared with baseline, but this effect disappeared by week 12. Only hylan injections continued to provide pain relief at 12 and 26 weeks compared with baseline. There were no significant differences in pain between groups at any time. At 12 and 26 weeks, the hylan group had improved grip strength compared with baseline, whereas the steroid and placebo groups were weaker. At 4 weeks, the steroid group reported in the difference score a greater improvement in symptoms (68%) compared with the hylan (44%) and placebo (50%) groups. Whereas at 26 weeks the hylan group reported the largest improvement in symptoms (68%), this was not statistically different from the placebo (47%) and steroid (58%) groups. There were no significant differences in Disabilities of the Arm, Shoulder, and Hand scores or range of motion among the groups. There were no complications from any injection. Therapeutic I.

There were no statistically significant differences among hylan, steroid, and placebo injections for most of the outcome measures at any of the follow-up time points. However, based on the durable relief of pain, improved grip strength, and the long-term improvement in symptoms compared with preinjection values, hylan injections should be considered in the management of basal joint arthritis of the thumb.

To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative. The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.

Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.

To compare unbiased estimates of short- vs long-term cartilage loss in osteoarthritic knees. 441 knees [216 Kellgren Lawrence (KL) grade 2, 225 KL grade 3] from participants of the Osteoarthritis Initiative were studied over a 4-year period. Femorotibial cartilage thickness was determined using 3 T double echo steady state magnetic resonance imaging, the readers being blinded to time points. Because common measurement time points bias correlations, short-term change (year-1 to year-2: Y1 → Y2) was compared with long-term change (baseline to year-4: BL → Y4), and initial (BL → Y1) with subsequent (Y2 → Y4) observation periods. The mean femorotibial cartilage thickness change (standardized response mean) was -1.2%/-0.8% (-0.42/-0.28) over 1 (BL → Y1/Y1 → Y2), -2.1%/-2.5% (-0.56/-0.55) over 2 (BL → Y2/Y2 → Y4), -3.3% (-0.63) over 3 (Y1 → Y4), and -4.5% (-0.78) over 4 years. Spearman correlations were 0.33 for Y1 → Y2 vs BL → Y4, and 0.17 for BL → Y1 vs Y2 → Y4 change. Percent agreement between knees showing progression during Y1 → Y2 vs BL → Y4 was 59%, and 64% for BL → Y1 vs Y2 → Y4. The area under the receiver operating characteristic curve was 0.66 for using Y1 → Y2 to predict BL → Y4, and 0.59 for using BL → Y1 to predict Y2 → Y4 change.

Weak to moderate correlations and agreement were observed between individual short- vs long-term cartilage loss, and between initial and subsequent observation periods. Hence, longer observation periods are recommended to achieve robust results on cartilage loss in individual knees. At cohort and subcohort level (e.g., KLG3 vs KLG2 knees), the mean cartilage loss increased almost linearly with the length of the observation period and was constant throughout the study.

To observe the effect of moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) on inflammatory factors and intestinal flora in the rats with adjuvant arthritis. A total of 36 Wistar rats were randomized into a normal group, a model group and a moxibustion group, 12 rats in each one. In the model group and the moxibustion group, the adjuvant arthritis model was established by a compound method, including the environmental factors, i.e. wind, cold and damp, and Freund's complete adjuvant. In the moxibustion group, moxibustion intervention was exerted at "Zusanli" (ST 36) and "Shenshu" (BL 23), for 20 min at each acupoint, once daily, consecutively for 21 days. The paw swelling degree and arthritis index (AI) score were observed before and after intervention in the rats of each group. Using real-time fluorescence quantitative PCR method (real-time PCR) and Western blot method, the mRNA and protein expressions of inflammatory factors of colon tissue, i.e. interleukin (IL) 1β, tumor necrosis factor-α (TNF-α), IL-6, were detected after intervention in the rats of each group. The intestinal flora was detected with 16SrRNA sequencing technology after intervention in the rats of each group. Compared with the normal group, the paw swelling degree and AI score were increased in the rats of the model group (

Moxibustion at "Zusanli" (ST 36) and "Shenshu" (BL 23) relieves the joint symptoms of adjuvant arthritis rats and inhibits the expressions of inflammatory factors, which is probably related to the regulation of the structure of intestinal flora.

In the European context of falling reimbursement rates for some osteoarthritis (OA) treatments, we performed a study to determine whether the cost covered by patients influenced the decisions of their physicians' prescriptions for medication. The study involved 106 general practitioners (GPs) and 82 rheumatologists. Preferences were elicited using a discrete choice experiment. Scenarios were generated including seven treatment attributes with associated different levels: pain relief, improvement in function, retardation of joint degradation, risk of moderate side effects, risk of serious side effects, cost borne by the patient and degree of patient acceptance of the treatment. OA treatment choices were significantly influenced by pain relief (β = 1.1533, P < 0.0001 for GPs and β = 0.5043, P = 0.0024 for rheumatologists), improvement in function (β = 1.2140 for GPs and β = 0.7192 for rheumatologists, P < 0.0001), annual cost to the patient (β = -0.0054 for GPs and β = -0.0038 for rheumatologists, P < 0.0001) and serious side effects (β = -0.5524 for GPs and β = -0.4268 for rheumatologists, P < 0.0001). The risk of moderate side effects only had an impact on GP decision making (β = 0.0282, P = 0.0028). All physicians were willing to make patients bear an extra annual cost of: (1) €225 among GPs and €189 among rheumatologists so that they could benefit from one unit improvement in function; and (2) €214 among GPs and €133 among rheumatologists so that they could benefit from a one unit improvement in pain relief.

When making decisions about which treatment to prescribe, physicians take into account the cost to patients. Changes in reimbursement rates for some OA treatments may lead to changes in prescribing practices.

Total knee replacement (TKR) operation is one of the most effective procedures, both clinically and in terms of cost. Because of increased volume and cost for this procedure during the past 3 decades, TKRs are often targeted for cost reduction. The purpose of this study was to evaluate the efficacy of two cost reducing methodologies, establishment of critical clinical pathways, and standardization of implant costs. Ninety patients (90 knees) were randomly selected from a population undergoing primary TKR during a 2-year period at a tertiary teaching hospital. Patients were assigned to three groups that corresponded to different strategies implemented during the evolution of the joint-replacement program. Medical records were reviewed for type of anesthesia, operative time, length of stay, and any perioperative complications. Financial information for each patient was compared among the three groups. Data analysis demonstrated that the institution of a critical pathway significantly shortened length of hospital stay and was effective in reducing the hospital costs by 18% (p < 0.05). In addition, standardization of surgical techniques under the care of a single surgeon substantially reduced the operative time. Selection of implants from a single vendor did not have any substantial effect in additionally reducing the costs.

Standardized postoperative management protocols and critical clinical pathways can reduce costs and operative time. Future efforts must focus on lowering the costs of the prostheses, particularly with competitive bidding or capitation of prostheses costs. Although a single-vendor approach was not effective in this study, it is possible that a cost reduction could have been realized if more TKRs were performed, because the pricing contract was based on projected volume of TKRs to be done by the hospital.

To confirm the association of a functional single-nucleotide polymorphism (SNP), C1858T (rs2476601), in the PTPN22 gene of British Caucasian rheumatoid arthritis (RA) patients and to evaluate its influence on the RA phenotype. A total of 686 RA patients and 566 healthy volunteers, all of British Caucasian origin, were genotyped for C1858T polymorphism by PCR-restriction fragment length polymorphism assay. Data were analysed using SPSS software and the chi 2 test as applicable. The PTPN22 1858T risk allele was more prevalent in the RA patients (13.9%) compared with the healthy controls (10.3%) (P = 0.008, odds ratio 1.4, 95% confidence interval 1.09-1.79). The association of the T allele was restricted to those with rheumatoid factor (RF)-positive disease (n = 524, 76.4%) (P = 0.004, odds ratio 1.5, 95% confidence interval 1.1-1.9). We found no association between PTPN22 and the presence of the HLA-DRB1 shared epitope or clinical characteristics.

We confirmed the previously reported association of PTPN22 with RF-positive RA, which was independent from the HLA-DRB1 genotype.

To compare the prevalence of diverse histopathologic features among patients with Sjögren's syndrome (SS) and controls, and to evaluate their relationship with age, a focus score (FS) ≥ 1 and some clinical and serological SS features. A blinded pathologist examined 63 SS and 11 control minor salivary gland biopsies. Focal lymphocytic sialadenitis (FLS) was defined as a focus score (FS) ≥ 1. We also evaluated lymphoepithelial lesions, germinal centers (GCs), epithelial metaplasia, dilatation and hyperplasia in the main secretory duct, perivascular cell infiltrate, adipose infiltration, acinar atrophy, interstitial fibrosis and lymphocytes/plasma cells remote from the FLS. We registered demographics, anti-Ro/La status and clinical features. We used Kendall's tau coefficients and logistic regression analysis. Sjögren's syndrome patients had a higher frequency of FS ≥ 1 (92% vs. 27%), acinar atrophy (78% vs. 18%), lymphocytes and plasma cells external to the FSL (92% vs. 64%) and stromal fibrosis (68% vs. 36%). A FS ≥ 1 correlated with the presence of GCs and acinar atrophy; whereas age correlated with duct dilation, duct epithelial hyperplasia, adipose infiltration and fibrosis. SS patients with hepatic involvement exhibited more frequent duct dilatation. After adjusting by age, anti-Ro/SSA (odds ratio [OR] 30.8, 95% CI 2.2-423.5, P = 0.01), a FS ≥ 1 (OR 54.3, 95% CI 4.8-612, P = 0.001) and fibrosis (OR 15.2, 95% CI 1.2-186.2, P = 0.03) were associated with SS.

Other histologic findings coexist with FLS, but only GC formation and acinar atrophy correlated with a FS ≥ 1. Age is mostly correlated with the remaining histological features. However, the clinical relevance of these findings is unknown.

To evaluate household and work place outcomes for patients with rheumatoid arthritis (RA) who were homemakers or employed workers, respectively, and who were treated with adalimumab plus methotrexate versus methotrexate monotherapy. We also determined baseline predictors of household and work place outcomes. Data were from a health economic companion study to PREMIER, a 2-year, randomized controlled trial of methotrexate-naive patients with early RA (<3 years) who received treatment with adalimumab plus methotrexate, adalimumab, or methotrexate. Absenteeism (number of days missed or unfit to work), presenteeism (self-judgment of the effects of RA on job or household performance), and employment status were collected from self-reports at baseline and varying time points during the study. Household and work place outcomes were generally similar for homemakers and employed workers. Over 2 years, patients who received combination therapy missed approximately half as many days as patients who received methotrexate (17.4 versus 36.9 days for employed workers; 7.9 versus 18.6 days for homemakers). Presenteeism was lower (reflecting better productivity) for combination therapy than methotrexate monotherapy. The likelihood of gaining/retaining employment over 2 years was greater for combination therapy than methotrexate monotherapy (odds ratio 1.530, 95% confidence interval 1.038-2.255; P = 0.0318). Baseline radiographic progression was an independent predictor for retaining/gaining employment at 2 years.

Compared with methotrexate monotherapy, combination therapy was associated with more positive work outcomes: less absenteeism, less presenteeism, and greater likelihood of gaining/retaining employment. Radiographic progression at baseline was predictive of the ability to retain or gain employment.

OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA). We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain). The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization.

Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.

Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion. We retrospectively reviewed the medical records of 101 patients who underwent TTC fusion at the same institution between 2011 and 2019. Risk ratios (RRs) associated with age, sex, diabetes, cardiovascular disease, smoking, preoperative ankle deformity, and the use of bone graft during surgery were related to the postoperative complications. We determined from these data which pre- and perioperative factors significantly affected the outcome. Out of the 101 patients included in the study, 29 (28.7%) had nonunion, five (4.9%) required below-knee amputation (BKA), 40 (39.6%) returned to the operating theatre, 16 (15.8%) had hardware failure, and 22 (21.8%) had a postoperative infection. Patients with a preoperative diagnosis of Charcot arthropathy and non-traumatic OA had significantly higher nonunion rates of 44.4% (12 patients) and 39.1% (18 patients) (p = 0.016) and infection rates of 29.6% (eight patients) and 37% (17 patients) compared to patients with traumatic arthritis, respectively (p = 0.002). There was a significantly increased rate of nonunion in diabetic patients (RR 2.22; p = 0.010). Patients with chronic kidney disease were 2.37-times more likely to have a nonunion (p = 0.006). Patients aged over 60 years had more than a three-fold increase in the rate of postoperative infection (RR 3.60; p = 0.006). The use of bone graft appeared to be significantly protective against postoperative infection (p = 0.019).

We were able to confirm, in the largest series of TTC ankle fusions currently in the literature, that there remains a high rate of complications following this procedure. We found that patients with a Charcot or non-traumatic arthropathy had an increased risk of nonunion and postoperative infection compared to individuals with traumatic arthritis. Those with diabetes, chronic kidney disease, or aged over 60 years had an increased risk of nonunion. These findings help to confirm those of previous studies. Additionally, our study adds to the literature by showing that autologous bone graft may help in decreasing infection rates. These data can be useful to surgeons and patients when considering, discussing and planning TTC fusion. It helps surgeons further understand which patients are at a higher risk for postoperative complications when undergoing TTC fusion. Cite this article:

To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA.

After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.

To define how the catabolic cytokines (Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFα)) affect the circadian clock mechanism and the expression of clock-controlled catabolic genes within cartilage, and to identify the downstream pathways linking the cytokines to the molecular clock within chondrocytes. Ex vivo cartilage explants were isolated from the Cry1-luc or PER2::LUC clock reporter mice. Clock gene dynamics were monitored in real-time by bioluminescence photon counting. Gene expression changes were studied by qRT-PCR. Functional luc assays were used to study the function of the core Clock/BMAL1 complex in SW-1353 cells. NFкB pathway inhibitor and fluorescence live-imaging of cartilage were performed to study the underlying mechanisms. Exposure to IL-1β severely disrupted circadian gene expression rhythms in cartilage. This effect was reversed by an anti-inflammatory drug dexamethasone, but not by other clock synchronizing agents. Circadian disruption mediated by IL-1β was accompanied by disregulated expression of endogenous clock genes and clock-controlled catabolic pathways. Mechanistically, NFкB signalling was involved in the effect of IL-1β on the cartilage clock in part through functional interference with the core Clock/BMAL1 complex. In contrast, TNFα had little impact on the circadian rhythm and clock gene expression in cartilage.

In our experimental system (young healthy mouse cartilage), we demonstrate that IL-1β (but not TNFα) abolishes circadian rhythms in Cry1-luc and PER2::LUC gene expression. These data implicate disruption of the chondrocyte clock as a novel aspect of the catabolic responses of cartilage to pro-inflammatory cytokines, and provide an additional mechanism for how chronic joint inflammation may contribute to osteoarthritis (OA).

The aim of this study was to investigate the frequency of CD4(+)CD25(+) regulatory T cells and their phenotypic expression in peripheral blood of children with active and non-active juvenile idiopathic arthritis (JIA) and healthy controls, to determine if their frequency or phenotypic expression is involved in the immunoregulation of this disease. From October 2004 to October 2005, 55 JIA patients and 55 age- and gender-matched healthy controls were enrolled in the study at National Taiwan University Hospital. Flow cytometry was used to determine the frequency of CD4(+)CD25(+) and CD4(+)CD25(hi) in CD4(+) T cells and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression on CD4(+)CD25(+) by tricolor staining. Basic profiles, medication history, clinical symptoms and laboratory data were obtained by chart review and outpatient department interviews. There was no significant difference in expression of CD4(+)CD25(+) T cells between patients with inactive JIA and normal controls (13.74+/-3.25% vs 12.85+/-3.68%, p>0.05). The expression of CD4(+)CD25(hi) T cells was significantly lower in inactive JIA patients than in normal controls (1.89+/-1.01% vs 2.76+/-1.28%, p<0.01). The expression of CTLA-4 on CD4(+)CD25(+) T cells was also significantly lower in inactive JIA patients compared with controls (4.37+/-2.02% vs 6.33+/-2.57%, p<0.001).

We speculate that a decreased frequency of CD4(+)CD25(hi) regulatory T cells and lower level of CTLA-4 expression on CD4(+)CD25(+) regulatory T cells might play a role in the immunoregulation of JIA.

The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography among elderly patients with low back or leg pain. To reveal the phenomenon of asymmetry regarding facet joint osteoarthritis (FJOA) in old patients and establish its relationships to spinal level, facet orientation, facet tropism and ligamentum flavum (LF) thickening. There were few reports regarding left-right asymmetry among severity of FJOA and its relationships to spinal level, facet orientation, facet tropism, and LF thickening remained unclear. The grade of bilateral FJOA was evaluated using 4-grade scale on computerized tomography images at the L3-4, L4-5, and L5-S1 levels of patients with age ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric FJOA group (FJOA I-II on both sides or FJOA III-IV on both sides) and asymmetric FJOA group (FJOA I-II on one side and FJOA III-IV on the other side). The relationships of FJOA to spinal level, facet orientation, facet tropism, and LF hypertrophy were evaluated. No association between asymmetric FJOA and spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference in facet orientation between 2 sides was observed at the L4-5 (P=0.018) and L5-S1 levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed significant difference in prevalence of facet tropism at the L5-S1 level (P<0.001). The LF showed significantly thicker on the side of FJOA III-IV than the side of FJOA I-II at each level in asymmetric FJOA group (P<0.05). However, no difference was found in thickness between 2 sides in symmetric FJOA group (P>0.05).

Asymmetric FJOA is associated with facet orientation and tropism, but not with spinal level. There is a close relationship between severity of FJOA and LF thickness.

To evaluate the efficacy and safety of etanercept (ETN) monotherapy compared with combination ETN and methotrexate (MTX) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.) Patients with active rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included in this 16 week, randomised, open-label study. Patients were randomly assigned to either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose of MTX or ETN monotherapy. 315 patients were randomised to ETN (n = 160) or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2 units, was achieved by 72.8% and 75.2% of patients treated with ETN and those treated with ETN plus MTX, respectively, with no significant difference (p = 0.658) between the two groups. The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0% of patients in the ETN group and by 82.4% of patients in the ETN plus MTX group. American College of Rheumatology 20%, 50% and 70% response rates achieved by both groups were also similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates of adverse and serious adverse events were similar between the treatment groups.

Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX resulted in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis.

MRI is the most sensitive imaging modality in juvenile idiopathic arthritis (JIA), but has practical limitations. Optimizing the scanning protocol is, therefore, necessary to increase feasibility and patient comfort. To determine the feasibility of bilateral non-contrast-enhanced open-bore MRI of knees and to assess the presence of literature-based MRI features in unsedated children with JIA. Children were classified into two clinical subgroups: active arthritis (group 1; n = 29) and inactive disease (group 2; n = 18). MRI features were evaluated using a literature-based score, comprising synovial hypertrophy, cartilage lesions, bone erosions, bone marrow changes, infrapatellar fat pad heterogeneity, effusion, tendinopathy and popliteal lymphadenopathy. The MRI examination was successfully completed in all 47 children. No scan was excluded due to poor image quality. Synovial hypertrophy was more frequent in group 1 (36.2%), but was also seen in 19.4% of the knees in group 2. Infrapatellar fat pad heterogeneity was more prevalent in group 2 (86.1%; P = 0.008). Reproducibility of the score was good (Cohen kappa, 0.49-0.96).

Bilateral non-contrast-enhanced open-bore knee MRI is feasible in the assessment of disease activity in unsedated children with JIA. Signs differing among children with active and inactive disease include infrapatellar fat pad heterogeneity and synovial hypertrophy.

Intravenous (IV) pulses of methylprednisolone (MEP) commonly are used to treat severe manifestations of systemic lupus erythematosus (SLE). However, despite wide use of this treatment the best dose, timing, and the situations in which this treatment should be used remain largely anecdotal. To review the mechanisms of action and evidence for clinical use of IV MEP in the treatment of SLE. The literature on MEP use in SLE from 1966 to 2002, using PubMed from the National Library of Medicine, was reviewed. As with other modes of corticosteroid administration, IV MEP has significant anti-inflammatory and immunosuppressive actions. These actions have been shown to be effective in treating SLE in clinical trials, for lupus nephritis. The studies are mainly uncontrolled and retrospective. Long-term observations from a few double-blind prospective trials suggest that monthly pulses of MEP, in addition to IV cyclophosphamide, may be useful. Pulse MEP is beneficial for several serious manifestations of SLE, such as neuro-psychiatric lupus, pulmonary hemorrhage, severe blood dyscrasias, cardiomyopathy, and vasculitis. However, significant side effects may occur, mostly infections, which are worse in patients with hypoalbuminemia.

IV pulses of MEP rapidly immunosuppress patients with organ and/or life-threatening manifestations of SLE. However, the gold standard 1 g/day for 3 consecutive days is associated with significant infectious complications and lower doses may be just as useful.

To explore the function of circular RNA IQ motif-containing GTPase-activating protein 1 (circ-IQGAP1) in interleukin (IL)-1β-induced osteoarthritis (OA) model and to explore whether circ-IQGAP1 can modulate microRNA-671-5p (miR-671-5p) and transcription factor 4 (TCF4) to regulate chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. The cartilage tissues were collected from 32 OA patients or normal subjects. Human chondrocyte CHON-001 cells were challenged via different doses of IL-1β for 24 hours. CHON-001 cells were transfected with circ-IQGAP1 overexpression vector, TCF4 overexpression vector, small interfering RNA (siRNA) for circ-IQGAP1, miR-671-5p mimic, miR-671-5p inhibitor or corresponding negative controls. Circ-IQGAP1, miR-671-5p and TCF4 abundances in cartilage tissues or CHON-001 cells were examined via quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell viability was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Cell apoptosis was measured by flow cytometry. The inflammatory injury was analyzed by the secretion levels of inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor-α [TNF-α]) by enzyme-linked immunosorbent assay (ELISA). The extracellular matrix degradation was evaluated by expression of aggrecan and matrix metalloproteinase 13 (MMP13) via western blot. The target relationship of miR-671-5p and circ-IQGAP1 or TCF4 was analyzed via dual-luciferase reporter and RNA immunoprecipitation (RIP) analyses. Circ-IQGAP1 abundance was enhanced in the cartilage tissues from OA patients compared with normal subjects (n = 32), and its expression was increased in CHON-001 cells after treatment of IL-1β in a dose-dependent pattern. MiR-671-5p expression was decreased in the cartilage tissues from OA patients (n = 32) and IL-1β-challenged CHON-001 cells. MiR-671-5p expression was negatively associated with circ-IQGAP1 level in OA patients. Circ-IQGAP1 silence mitigated IL-1β-caused chondrocyte viability reduction, apoptosis promotion, secretion of inflammatory cytokine (IL-6, IL-8 and TNF-α), and extracellular matrix degradation (reduction of aggrecan and increase of MMP13). MiR-671-5p was targeted and inhibited via circ-IQGAP1. MiR-671-5p knockdown attenuated the influence of circ-IQGAP1 interference on IL-1β-caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. TCF4 was targeted via miR-671-5p, and TCF4 expression was increased in the cartilage tissues from OA patients (n = 32) and IL-1β-challenged CHON-001 cells. TCF4 abundance in OA patients was negatively correlated with miR-671-5p expression. MiR-671-5p overexpression alleviated IL-1β-mediated chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation via decreasing TCF4 expression. Circ-IQGAP1 silence reduced TCF4 expression via regulating miR-671-5p in IL-1β-challenged CHON-001 cells.

Circ-IQGAP1 knockdown attenuated IL-1β-caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. Circ-IQGAP1 could regulate miR-671-5p/TCF4 axis to modulate IL-1β-caused chondrocyte damage. Circ-IQGAP1 might act as a new target for the treatment of OA.

Renal pathology and clinical outcomes in patients with primary Sjögren's syndrome (pSS) who underwent kidney biopsy (KB) because of renal impairment are reported. Twenty-four of 7276 patients with pSS underwent KB over 40 years. Patient cases were reviewed by a renal pathologist, nephrologist, and rheumatologist. Presentation, laboratory findings, renal pathology, initial treatment, and therapeutic response were noted. Seventeen patients (17 of 24; 71%) had acute or chronic tubulointerstitial nephritis (TIN) as the primary lesion, with chronic TIN (11 of 17; 65%) the most common presentation. Two had cryoglobulinemic GN. Two had focal segmental glomerulosclerosis. Twenty patients (83%) were initially treated with corticosteroids. In addition, three received rituximab during follow-up. Sixteen were followed after biopsy for more than 12 mo (median 76 mo; range 17 to 192), and 14 of 16 maintained or improved renal function through follow-up. Of the seven patients presenting in stage IV chronic kidney disease, none progressed to stage V with treatment.

This case series supports chronic TIN as the predominant KB finding in patients with renal involvement from pSS and illustrates diverse glomerular lesions. KB should be considered in the clinical evaluation of kidney dysfunction in pSS. Treatment with glucocorticoids or other immunosuppressive agents appears to slow progression of renal disease. Screening for renal involvement in pSS should include urinalysis, serum creatinine, and KB where indicated. KB with characteristic findings (TIN) should be considered as an additional supportive criterion to the classification criteria for pSS because it may affect management and renal outcome.

Patients with knee osteoarthritis have an increase in bone mass but no corresponding decrease in risk of fracture. This study describes the rates of hip fracture in subjects with knee osteoarthritis before and after having a total knee replacement (TKR), compared with matched controls. A population-based prospective cohort study was conducted. The study population included, from the General Practice Research Database (UK), patients 40 years and older, undergoing TKR between 1986 and end-2006 for knee osteoarthritis as 'cases' (n=20,033). Five disease-free controls (n=100,165) were randomly selected, and matched for age, gender and practice. Hip fractures were ascertained using READ codes, and yearly rates of hip fracture and rate differences were calculated for the 5 years before and after surgery, using Poisson regression. Stratified analyses were performed by age and history of fracture. Hip fracture rates were non-significantly reduced compared with controls before the operation. In the year after TKR, risk increased significantly (RR 1.58; 95% CI 1.14 to 2.19). Rates then declined to equal those of controls by 3 years, and continued decreasing until the end of follow-up; corresponding RR were not significant. The increased risk is greatest in younger ages and in those without previous fracture.

The association between knee osteoarthritis and fractures is time-dependent, which may explain the current controversy in the literature. The association is also modified by TKR: subjects have a higher rate of hip fracture than matched controls after TKR, although the rates may eventually decrease.

Acetylation polymorphism can alter therapeutic responses and toxicity to certain xenobiotics and may also be a factor that influences a patient's susceptibility to certain diseases. We investigated whether patients with rheumatoid arthritis (RA) differed from healthy individuals with regard to genotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). NAT2 polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction-restriction fragment length polymorphism methods with deoxyribonucleic acid extracted from peripheral blood. A statistically significant increase in the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was found among patients with RA in comparison with healthy subjects (52.5%; P <.0001). The risk of development of RA was almost 5-fold greater in slow acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval, 2.28-10.21). There was no correlation between NAT2 polymorphism and presence of rheumatoid factor, extra-articular manifestations, and age at first occurrence of disease symptoms.

NAT2 slow acetylation genotype may be a risk factor of individual susceptibility to RA.

To determine whether changes in health outcomes result from changes in domains of functioning and relevant environmental factors in musculoskeletal conditions. Longitudinal observational study on a convenience sample of 291 patients with low back pain, osteoarthritis, osteoporosis, rheumatoid arthritis and chronic widespread pain. The study was part of the MHADIE project. Data collection was performed at baseline, after 4 and 8 weeks using the ICF Core Sets for the corresponding musculoskeletal conditions. Multilevel models for change were used to determine which ICF categories explain the variability and change over time of the general, physical and mental health according to the SF-36. There are only small fluctuations in the health outcomes. These are related to functions of the locomotor apparatus, such as muscle power, and to activities and participation domains related to them, such as lifting and carrying objects. A large amount of baseline variance is explained with a relatively small number of ICF categories of functioning.

This study presents a list of functioning problems and environmental factors relevant to map out both the patterns and the variations in the experience of living with a chronic and painful condition. These are intervention targets common across MSC conditions.

Rheumatic diseases are frequently associated with interstitial lung disease. Since interstitial fibrosis is an irreversible process, understanding the mechanisms leading to fibrosis is necessary for the development of treatment strategies to prevent irreversible pulmonary damage. High-resolution Computed Tomography (HRCT) is superior to chest radiography in assessing the presence and extent of parenchymal abnormalities in diffuse infiltrative lung diseases and provides a sensitive and noninvasive method of quantifying global disease extent. The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. Eighty nonsmoking patients (24 patients with systemic sclerosis, 24 with primary Sjögren's syndrome, 20 with rheumatoid arthritis and 7 with dermatopolymyositis) were examined. No patient had any signs or symptoms of pulmonary disease. Thirty-three of 80 patients (41.2%) had abnormal HRCT findings, namely isolated septal/subpleural lines, irregular pleural margins and ground-glass appearance. Chest X-ray showed parenchymal abnormalities in only 15 patients (18.7%) who had evidence of fibrosis on HRCT. Abnormal differential cell counts (alveolitis) at bronchoalveolar lavage were found in 46 of 80 patients (57.5%). Three types of alveolitis were observed: pure lymphocyte alveolitis, pure neutrophil alveolitis, and neutrophil alveolitis associated with lymphocytosis (mixed alveolitis). The patients with neutrophil alveolitis had more extensive disease on HRCT than those with lymphocyte alveolitis or with normal cellular patterns at bronchoalveolar lavage. The extent of a reticular pattern on HRCT correlated with the neutrophil rate (p = 0.001) and total count (p = 0.003) on bronchoalveolar lavage. Eosinophil and lymphocyte rate and total count correlated (p < 0.05) with the extent of the ground-glass pattern on HRCT. Lung volumes were not significantly different among patients with ground-glass pattern and those with reticular patterns on HRCT, while the diffusing capacity for carbon monoxide was significantly lower (p < 0.05) in the latter.

HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease.

Dry needling (DN) in active myofascial trigger points (MTrPs) is effective to reduce pain, increase range of motion (ROM) and improve physical function in different musculoskeletal disorders. However, there is a lack of studies evaluating the effects of DN in active MTrPs in hip osteoarthritis (OA). To determine the short-term effects of DN on pain, hip ROM and physical function in patients with hip OA. Double-blind randomized controlled trial. Thirty patients with unilateral hip OA were randomized into two groups: DN group and sham group. Participants received three treatment sessions. The treatment was applied in active MTrPs of the iliopsoas, rectus femoris, tensor fasciae latae and gluteus minimus muscles. Pain intensity (visual analogic scale), passive hip ROM (universal goniometer and digital inclinometer) and physical function (30s chair-stand test and 20m walk test) were assessed at baseline and after the three treatment sessions. There was decreased pain intensity, increased hip ROM, and improved physical function following the DN treatment. These improvements were statistically significant (p < 0.05) compared to the sham group. The sham group had increased pain intensity and decreased hip ROM (p < 0.05).

Pain, hip ROM, and physical function improved after the application of DN in active MTrPs of the hip muscles in patients with hip OA.

Fibromyalgia is characterized by chronic widespread musculoskeletal pain and higher pain perception in specific anatomic sites called tender points. Fibromyalgia is frequently associated with psychiatric symptoms, like depression and anxiety; indeed some authors have argued about the possibility to classify this syndrome into affective spectrum disorder. Few studies have analyzed the impact of depressive symptoms on pain threshold. This research is aimed at evaluating the prevalence and the clinical correlates of depressive symptoms in fibromyalgic patients, and investigating their impact on pain perception and quality of life. Outpatients between 18 and 75 years with diagnosis of fibromyalgia according to the criteria of the American College of Rheumatology have been included. All subjects have been evaluated with the following rating scales: HAM-D; VAS (to quantify pain); a visual analogical scale to evaluate quality of life; and Paykel's List of Recent Life Events. Thirty subjects have been recruited. Most patients (83.3%) had clinically significant depressive symptoms as indicated by a HAM-D score >7. Depressive symptoms are associated with higher pain perception, worse quality of life and more severe life events.

The presence of depressive symptoms is associated with a great impairment in patients with fibromyalgia syndrome: indeed the psychiatric comorbidity lowers pain threshold and worsens the quality of life of our patients. Future studies should be conducted in order to identify the individual factors, e.g. stress or inflammatory processes, which drive the association between depression and higher severity of fibromyalgia syndrome.

The aim of this study is to measure retinal vessel density and thickness of the macula by optical coherence tomography angiography in patients with rheumatoid arthritis taking hydroxychloroquine. The study included 40 patients with rheumatoid arthritis taking hydroxychloroquine and 20 age-, gender-, and axial length-matched control subjects. Patients were divided into two groups according to the duration of hydroxychloroquine use. Twenty four of the patients were taking hydroxychloroquine for more than 5 years (Group 1), and the rest of 16 were taking hydroxychloroquine for less than 5 years (Group 2). A total of 20 age- and gender-matched volunteers with similar axial length were selected as Group 3. All of the patients underwent optical coherence tomography angiography, and 3 mm × 3 mm scanning mode was chosen for analyzing vascular density and morphological characteristics on the choriocapillaris layer. In addition, Humphrey visual field 10-2 was evaluated in each subject. The temporal deep vascular density was measured as 48.13% ± 8.5% in Group 1, 54.42% ± 10.3% in Group 2, and 60.35% ± 13.1% in Group 3. Deep temporal and deep hemi-inferior vascular density was significantly lower in Group 1 in comparison with Group 3 (p = 0.041 and p = 0.046, respectively). Visual field testing was normal in all patients.

The optical coherence tomography angiography findings showed that the parafoveal deep temporal and deep hemi-inferior vascular plexus density was reduced in patients taking hydroxychloroquine for more than 5 years despite having normal perimetry. This observation, which can be obtained only through optical coherence tomography angiography, may be relevant to the early findings of hydroxychloroquine toxicity.

To clarify the usefulness of measuring serum amyloid A (SAA) levels in patients with polymyalgia rheumatica (PMR), we compared this parameter to C-reactive protein (CRP). The study included 10 patients with PMR, who could be prospectively followed up from the start of prednisolone (PSL) treatment until the CRP level decreased to 1 mg/dl or less. When the CRP level decreased, the subjects were divided into the group in which the symptom persisted (n = 6) and those in which the symptom disappeared (n = 4). In the group in which the symptom persisted, both CRP and SAA levels were significantly higher. When the CRP level decreased, there was no significant difference in the CRP level between the two groups. However, the mean SAA level in the group in which the symptom persisted (137.8 micrograms/ml) was significantly higher than that in the group in which the symptom disappeared (21.8 micrograms/ml). On the initial consultation, there was a positive correlation between CRP and SAA (R = 0.77). The SAA level was more sensitive than the CRP level (y = 94.899 x -51.22). When the CRP level decreased, SAA was much more sensitive (y = 222.92 x +6.9121), suggesting the usefulness of SAA after the start of PSL treatment.

SAA may be a useful parameter of PMR activity.

Emerging evidence supports a crucial role of myeloid-derived suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their role in systemic lupus erythematosus (SLE) remains unknown. This study sought to address the role of MDSCs in the pathogenesis of SLE. MDSCs from (NZB × NZW)F1 lupus-prone mice were assessed for phenotype by flow cytometry, and the function of MDSCs was analyzed by in vitro T cell proliferation assay and real-time quantitative polymerase chain reaction. Extracellular trap (ET) formation was evaluated by immunofluorescence and confocal microscopy. The production of reactive oxygen species (ROS) by Ly-6G+ cells was determined by fluorescence-activated cell sorting analysis. Expansion of MDSCs was impaired and the function of MDSCs was defective in the lymphoid organs of (NZB × NZW)F1 lupus-prone mice with established disease, in which involvement of predominantly the granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the results showed that increased elimination of G-MDSCs, driven by the inflammatory milieu of lupus, could be attributed to ET formation, and that cytokines, such as interferon-α (IFNα), IFNγ, and interleukin-6, play a role in this process. Induction of ET release by G-MDSCs was mediated by the production of ROS, since inhibition of ROS generation significantly reduced ET release.

Collectively, the results of this study reveal that elimination of a crucial regulatory immune cell subset is a feature of the SLE microenvironment. These findings provide new insights into the pathogenetic mechanisms of the disease.

To study the prevalence of fibromyalgia (FM) in the general population according to a 2016 modification of the American College of Rheumatology criteria (FM 2016) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society pain taxonomy criteria (AAPT), and to compare diagnostic and clinical variables between the criteria sets. We studied 2,531 randomly selected subjects from the German general population in 2019. Pain regions from the Michigan Body Map were fitted to the FM 2016 and the AAPT criteria, and criteria symptom items were derived from validated questionnaires assessing somatic and psychological symptom burden and disability. We determined FM criteria prevalence and criteria-related scales including widespread and multisite pain (MSP) and symptom scales, and measured symptom burden and disability. According to the FM 2016 criteria, the prevalence of FM was 3.4% (n = 75 subjects; 95% confidence interval [95% CI] 2.7, 4.3) compared with 5.7% (n = 130 subjects; 95% CI 4.8, 6.8) for the AAPT criteria; κ = 0.65. Compared with AAPT-positive subjects, FM 2016-positive subjects had higher MSP, Widespread Pain Index score, Polysymptomatic Distress Scale scores, Symptom Severity Scores, and psychological symptom burden. Physician-diagnosed FM was reported by 1.1% of the subjects. Of these, 44.0% met the FM 2016 criteria, and 47.5% met the AAPT criteria.

The prevalence of FM in the German general population is 73% greater using the AAPT criteria than the FM 2016 criteria. The AAPT criteria select individuals with less symptom severity and fewer pain sites. The FM 2016 criteria, but not the AAPT criteria, provide a general severity measure for FM.

To assess the evolution of MR imaging findings in normal volunteers and subjects with hip osteoarthritis (OA) over 1.5 years described by the semi-quantitative Scoring Hip OA with MRI (SHOMRI) scoring system and their correlation with the evolution of clinical parameters. Hip MRI studies of 18 subjects with [Kellgren-Lawrence (KL) score = 2/3; mean age = 54.4 ± 11.2 years; 27.8% women] and 36 controls without radiographic OA [KL = 0/1; mean age = 43.7 ± 12.8 years; 50.0% women] were assessed at baseline and after 1.5 years by using SHOMRI, and their clinical status was evaluated by using Harris Hip Score and Hip Disability and Osteoarthritis Outcome Score (HOOS). Imaging and clinical parameters at baseline and their change over time were compared between groups using Mann-Whitney U and Fisher׳s exact tests. Spearman׳s rank correlations and generalized linear models adjusted for age, sex, BMI, and KL were used to assess associations between imaging and clinical findings. At baseline, OA subjects had significantly higher SHOMRI total scores than controls [median (IQR): 12.5 (6-19.5) vs. 7 (4-13.5); p = 0.024]. Over 1.5 years, only the progression rate of subchondral cysts was significantly higher in OA subjects than in controls (16.7% vs. 0.0%; p = 0.033), while no significant differences were found for any of the other SHOMRI subscales. Baseline bone-marrow edema pattern (BMEP) was significantly associated with worsening pain (HOOS subscale; p = 0.018) and hip-related quality of life (HOOS subscale; p = 0.044). Progression of subchondral cysts was significantly associated with worsening symptoms other than pain (HOOS subscale, p = 0.030). Baseline KL did not significantly correlate with worsening of any clinical symptoms (each, p > 0.05).

In this relatively young study population without or with mild to moderate radiographic hip OA, only minimal differences were found between groups regarding the progression of hip abnormalities as assessed by SHOMRI over 1.5 years. However, BMEP predicted clinical worsening and subchondral cyst progression was associated with worsening symptoms. Although longer follow-up periods are required, this suggests that SHOMRI is a useful tool to monitor hip abnormalities and their progression longitudinally.

Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases. To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome. Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5 years (52-464 weeks). Relapses, time (weeks) required to achieve a maintenance prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal were prospectively recorded. IL-17A mRNA was measured by real-time quantitative RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein expression was assessed by immunohistochemistry/immunofluorescence. IL-17A expression was significantly increased in temporal artery samples from GCA patients compared with controls (6.22±8.61 vs 2.50±3.9 relative units, p=0.016). Surprisingly, patients with strong IL-17A expression tended to experience less relapses, and required significantly shorter treatment periods (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no correlation between IL-17A and RORc or RORα expression suggesting that these transcription factors may not exclusively reflect Th17 differentiation, and that cells other than Th17 cells might contribute to IL-17 expression in active patients. Accordingly, FoxP3(+)IL-17A(+) cells were identified in lesions by confocal microscopy and were dramatically reduced in specimens from treated patients.

IL-17A expression is increased in GCA lesions, and is a predictor of response to glucocorticoid treatment. The contribution of FoxP3+ cells to IL-17A production in untreated patients suggests that induced-Tregs may facilitate disease remission when proinflammatory cytokine production is downregulated by glucocorticosteroids.

Despite lower socioeconomic status (SES) and higher disease burden, Hispanics in the US paradoxically display equal or lower mortality on average than non-Hispanic whites. Our objective was to determine if the "Hispanic paradox" occurs among patients with rheumatoid arthritis (RA). In a cohort of 706 RA patients, we compared differences in RA severity and comorbidity between Hispanic and non-Hispanic white ethnic groups at baseline. Cox proportional hazards models were used to estimate and compare mortality risk between Hispanics and non-Hispanic whites. We studied 706 patients with RA, of whom 434 were Hispanic and 272 were non-Hispanic white. Hispanics had significantly lower SES, greater inflammation, as well as higher tender and swollen joint counts. Patients were observed for 6,639 patient-years, during which time 229 deaths occurred by the censoring date (rate 3.4 per 100 person-years; 95% confidence interval 3.0, 3.9). Age- and sex-adjusted mortality was not significantly different between the 2 ethnic groups (hazard ratio [HR] 0.96). After adjustment for comorbidities, RA severity, and level of acculturation, mortality among Hispanics was lower (HR 0.56, P = 0.004).

Despite greater severity in most clinical manifestations and lower SES among Hispanics, paradoxically, their mortality was not increased. Further research is needed to understand the mechanisms underlying this survival paradox.

To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents. A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted. Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo.

Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.

Few large series of arthropathy related to anterior glenohumeral instability are available in the orthopaedic literature, preventing analysis of the incidence and the risk factors of preoperative and postoperative glenohumeral arthritis. Anterior stabilization surgery influences the risk factors of glenohumeral arthritis. Retrospective review. There were 570 patients who underwent an instability procedure. Clinical and radiographic preoperative data were collected for these patients. Arthritis was evaluated preoperatively and postoperatively with the Samilson classification. The mean age at surgery was 31.9 years. Follow-up averaged 6.5 years. The preoperative incidence of arthritis was 9.2%. Arthritic risk factors were older age at the initial dislocation and at surgery, increased length of time from the initial dislocation until surgery, and the presence of osseous glenoid rim lesions. Postoperative arthritis in patients without any preoperative arthritis occurred in 19.7% and was correlated with older age at the initial dislocation and at surgery, increased number of dislocations, and longer follow-up. Decreased external rotation at latest follow-up correlated with arthritis, although whether this was the cause or the effect was unclear.

Similar factors contribute to preoperative and postoperative arthritis in patients with anterior glenohumeral instability, suggesting that surgery does not influence the risk factors of arthritis. Although decreased external rotation with the arm at side statistically correlated with arthritis in this study, the authors were unable to establish this as an effectual relationship because nearly all patients with glenohumeral osteoarthritis, whether instability related or not, have decreased external rotation.

The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration. Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC). The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases.

eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases.

Multiplex analysis allows measurements of a large number of analytes simultaneously in each sample. On the basis of the Luminex multiplex technology (xMAP), kits for measuring multiple cytokines and chemokines (immunomodulators) are commercially available and are useful in investigations on inflammatory diseases. This study evaluated four multiplex kits (Bio-Plex, LINCOplex, Fluorokine, and Beadlyte) that contained 27, 29, 20, and 22 analytes each, respectively, for the analysis of immunomodulators in plasma of patients with rheumatoid arthritis (RA) who underwent treatment with antibody against CD20 (rituximab), a B-cell reductive therapy. Multiplex kits were tested on serial plasma samples obtained from six RA patients at baseline and multiple time points (3, 6, and 9 months) post-treatment with rituximab. The RA patients included in this study had previously failed therapy with disease modifying anti-arthritis drugs (DMARD) and treatment with anti-TNFalpha antibody (infliximab). Computer modeling and hierarchical cluster analysis of the multiplex data allowed a comparison of the performance of multiplex assay kits and revealed profiles of immunomodulators in the RA patients.

In plasma of RA patients who appeared to have benefited from the rituximab treatment, the profile of significantly elevated immunomodulators by at least two of the three kits (BioPlex, LINCOplex, Beadlyte) is as follows: IL-12p70, Eotaxin, IL-4, TNFalpha, Il-9, IL-1beta, IFNgamma, IL-10, IL-6, and IL-13. Immunomodulator profiling by multiplex analysis may provide useful plasma biomarkers for monitoring response to B-cell reductive therapy in RA patients.

Restoration of correct coronal alignment is one of the main goals of total knee arthroplasty (TKA). Traditionally, TKA has been considered successful when a neutral mechanical hip-knee-ankle (HKA) axis within 3° is achieved. Recent studies have reported no differences or improved clinical outcomes following a slight under-correction of the HKA axis for a varus knee. However, the influence of under-correction of a valgus knee has not been reported. This study investigated the influence of post-operative HKA alignment in TKA patients with valgus deformity on clinical outcomes. Ninety-three knees (93 patients) with pre-operative valgus alignment were evaluated with a mean follow-up period of 60 months. All patients were classified into three groups based on post-operative HKA alignment: neutral (0 ± 3°), mild valgus (3°-6°), and severe valgus (> 6°). These groups were compared using the Western Ontario and McMaster Universities osteoarthritis (WOMAC) index, the Knee Society (KS) knee score, KS function score, α-angle, β-angle, patella tilt angle, and the congruence angle. Sixty-nine knees were included in the neutral group, seventeen knees in the mild valgus group, and seven knees in the severe valgus group. In all cases, post-operative clinical and functional scores significantly improved compared to pre-operative scores. There were no differences between the three groups in post-operative clinical and functional scores. More post-operative patellar tilt angle outliers (> 10°) and congruence angle outliers (> 16°) were apparent in the severe valgus group (patellar tilt angle, 13 vs. 17 vs. 57.1%, p = 0.022; congruence angle, 32 vs. 47 vs. 71%, p = 0.035). III, Retrospective comparative study.

Slight under-correction following TKA for a valgus knee resulted in similar clinical outcomes. A residual valgus angle of more than 6° can induce patellar maltracking.

To investigate the clinical features and treatment in patients of marginal zone lymphoma (MZL)with monoclonal immunoglobulin (McIg). The clinical data of MZL patients with McIg, including 3 cases diagnosed and treated in Beijing Anzhen Hospital from Jan 2007 to Dec 2014 were retrospectively studied, meanwhile 36 patients searched from literatures were reviewed. Of a total of 39 patients, the ratio of male and female was 1.05∶1 with an average age of 65.1± 12.3 years old. 28 cases (71.8%)were with mucosa associated lymphoid tissue lymphomas (MALTL), 9 cases (23.1% )with nodal marginal zone lymphoma, and 2 cases (5.1%)with splenic marginal zone lymphoma. Nine cases (23.1% )were in the early stage, 30 cases (76.9%)in the advanced stage. The common initial symptom was non-mass lesions (65.5%), such as skin purpura, peripheral neuropathy; 13 patients (33.3% )were accompanied by autoimmune phenomenon, and most were with Sjogren's syndrome. Among MALTL patients, the common primary lesion was in non- gastrointestinal tract (17 cases, 60.7%). Most of patients with McIg were one with McIgM (82.0%); the others with McIgA, Mcκ-light chain, McIgG and double McIg. The level of plasma McIgM was (25.55±21.31)g/L, which was higher in advanced stage patients than in early stage ones [(29.85±20.60)g/Lvs (3.23±2.95)g/L,P= 0.008]. The complete remission (CR)rate was 56.0% and the overall response rate (ORR)92.0%, respectively in 30 patients treated by chemotherapy. At a median follow- up of 10 months, the 3- year progression free survival and the 3-year overall survival were 44.7% and 76.5%, respectively. The rates of ORR and CR in the patients received rituximab- included regimen were seemly better than those without rituximab one (100.0%vs 78.6%, 63.6%vs 50.0%;P>0.05), but no statistic differences were found. The CR rate in patients with McIgM was significantly higher than that with non- McIgM (P=0.026). The plasma McIgM level decreased after chemotherapy (P=0.002).

The MZL with McIg, perhaps a kind of unique subtype, usually occurred in 60 years or older patients. It was often diagnosed in patients of advanced stage and susceptible to autoimmune phenomenon. MALTL in non- gastrointestinal tract was more prone to find McIg. In MZL patients with McIg, McIgM was more common and other McIg rare. Rituximab-included regimen produced a better therapeutic response.

To illustrate different Larsen grades for CMC I. In the Heinola Follow-up Survey of Arthritis 103 seropositive patients with rheumatoid arthritis (RA) were followed prospectively over 20 years. Hand radiographs were taken at onset and at 1, 3, 8, 15, and 20 years from entry. One female patient was selected to demonstrate Larsen grades for CMC I, as she presented all the different grades of destruction during the progression of RA. Interobserver and intraobserver errors in grading of CMC I were tested. Radiographs of the different grades with schematic presentation are illustrated. Interobserver and intraobserver errors were in the Weighted Kappa test 0.75 and 0.82, respectively.

We emphasise the importance of following the destruction of CMC I separate from the entire carpus during the course of RA.

Osteoarthritis (OA) is the third most common diagnosis made by general practitioners in older patients. The aim of this study was to compare the function scores of different surgeries in the treatment of knee osteoarthritis (KOA). Cohort studies about different surgical treatments for KOA were included with a comprehensive search in PubMed, Cochrane Library, and Embase. The standard mean difference (SMD) value was evaluated and the surface under the cumulative ranking (SUCRA) curve was drawn with a combination of direct and indirect evidence. A total of 265 eligible patients were enrolled and served as the nonoperative treatment group, osteotomy group, unicompartmental knee arthroplasty (UKA) group, total knee arthroplasty (TKA) group, and arthroscopic surgery group. Before surgery, 6 months after surgery, 1 year after surgery and 5 years after surgery, the hospital for special surgery (HSS) knee score, Lysholm score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and American knee society score (KSS) were recorded. A total of 9 cohort studies including 954 patients with KOA were finally enrolled into the study. The network-meta analysis revealed that osteotomy and UKA treatments showed a better efficacy on improving the function score. Our cohort study further confirmed that, a higher HSS knee score after 1 year and higher Lysholm score after 6 months and 1 year were observed in the osteotomy and UKA groups, while better HSS knee score and KSS after 6 months and 1 year were showed in the osteotomy and TKA groups. In the TKA group, Lysholm score and KSS were higher and WOMAC score was lower after 5 years than other groups. WOMAC score was lowest in the UKA group after 6 months, 1 year and 5 years of surgery.

These results provide evidence that function scores of patients with KOA were improved by osteotomy, UKA, TKA, and arthroscopic surgery. And osteotomy and UKA showed better short-term efficacy, while TKA appeared better long-term efficacy.

Chronic musculoskeletal pain is often exacerbated by mental and social stress. The association between stress and musculoskeletal pain is potentially mediated by peripheral sympathetic nerves, either directly or indirectly through muscle activity. In the present study we wanted to determine whether sympathetic blockade could affect either the pain or the muscular activity experienced during mental stress in patients with chronic musculoskeletal pain. We performed a unilateral anaesthetic blockade of the lower cervical sympathetic ganglion (ganglion stellatum) in 18 patients with chronic musculoskeletal pain (10 with fibromyalgia and eight with chronic shoulder/neck pain). After the blockade the patients performed a 60-minute stressful task with low-grade mental stress that has induced pain and muscle activity in earlier experiments. Surface electromyography (SEMG) of the forehead, temples, neck, and shoulders, and heart rate and blood pressure were recorded together with ratings of pain. We did not find any side or sidextime effect for pain or muscular activity in any of the four muscle groups (p>0.12).

We investigated the potential involvement of peripheral sympathetic nerves in stress-related musculoskeletal pain. A peripheral sympathetic block did not affect pain and muscle responses to a stressful task. Other explanatory models should be implemented and tested experimentally to further investigate the clinical impression that mental stress exacerbates pain in patients with chronic musculoskeletal pain.

The role of subchondral bone in osteoarthritis (OA) development is well admitted. Cross-talk between subchondral bone and cartilage may be disrupted in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in bone remodeling control and could play a key role in OA progression. Our purpose of this study was to evaluate the preventive effect of interval-training exercise on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of experimental OA. At baseline, 48 male Wistar rats (8 weeks old) were separated into two groups: interval-training exercise or no exercise for 10 weeks. After this training period, each group was divided into two subgroups: MIA-injected knee (1 mg/100 μl saline) and saline-injected knee. Four weeks later, rats were sacrificed and carefully dissected. Evaluated parameters were: cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X-ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro-computed tomography (μCT), cortical subchondral bone lacunar osteocyte occupancy (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by epifluorescence). Our results showed deleterious effects of MIA on cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented by exercise. Exercise induced increase in full osteocyte lacunae surface and osteocyte occupancy (+60%) of cortical subchondral bone independently of OA. Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever the group at sacrifice.

Our results suggest that preliminary interval-training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our interval-training did not prevent MIA-induced cartilage degeneration.

Bone mineral density (BMD) of the lumbar spine, ultradistal radius, and calcaneus were significantly higher in the developmental dysplasia of the hip (DDH) patients than in the controls. Therefore, our data suggest that BMDs at different skeletal sites are greater in patients with DDH than in healthy women. DDH has been acknowledged as a potentially preosteoarthritic condition that results in the development of hip osteoarthritis. Patients with DDH have been reported to have abnormal morphology of the pelvis and spine. Additional research, including that of bone quality, needs to be conducted to elucidate the pathogenetic mechanism of this disease. We therefore sought to determine whether BMD differs between healthy women and women with DDH. We measured BMD in 40 women who were scheduled to undergo pelvic osteotomy for DDH (average age, 45.3 years) and in 31 healthy women used as age-matched controls (average age, 47.5 years). BMDs of the lumbar spine, radius, and calcaneus were measured. BMDs of the lumbar spine, ultradistal radius, and calcaneus were significantly higher in the DDH patients than in the controls.

Therefore, our data suggest that BMDs at different skeletal sites are greater in patients with DDH than in healthy women.

To assess the effects of intramuscular (im) neridronate (NE) on lumbar and femoral neck BMD and on markers of bone turnover in rheumatic patients under chronic low-dose glucocorticoids (GC) therapy. Sixty-nine osteopoenic and osteoporotic patients, affected by rheumatic diseases and gastric or esophageal conditions which contraindicated treatment with oral bisphosphonates (BPs), were randomly assigned to: Group A (23 patients) administered with daily calcium 1 g and vitamin D 800 UI; Group B (46 patients) receiving daily calcium 1 g, vitamin D 800 UI and im NE 25 mg monthly. After 12 months of therapy (M12) lumbar BMD was reduced of 2.97% in Group A, and improved of 3.34% (p=0.001) in Group B; at M12, femoral neck BMD was reduced of 2.40% in Group A and improved of 1.78% in Group B (p=0.010). After 6 (M6) and 12 months of therapy, the bone resorption markers were significantly reduced in Group B: OHPr-41.64% at M6 (p<0.001) and -37.91% at M12 (p<0.001); DPD-33.4% at M6 (p<0.001) and -33.18% (p<0.001) at M12: NTX -57.08% (p<0.001) at M6 and -55.95% (p<0.001) at M12; OC-11.62% (p=0.05) at M6 and -12.62% at M12 (p=0.06); B-ALP -13.95 % at M6 (p=0.04) and -0.85% at M12 (NS).

A twelve-month intramuscular NE treatment in rheumatic patients under GCs therapy improves lumbar and femoral BMD and mainly reduces the markers of bone resorption.

To determine the prevalence of substance use among adolescents with juvenile rheumatoid arthritis and to assess available opportunities for rheumatologists to identify high risk teens. Fifty-two teens (mean age 13.9 years, 86% female) completed questionnaires regarding substance use (alcohol, tobacco, marijuana, and other illicit substances), functional disability, and frequency of health care contacts. Alcohol use was reported by 30.7% of teens, including 23.5% of those for whom methotrexate was prescribed; 15.4% reported tobacco use in the last year, and 13.4% reported other illicit substance use in their lifetime, although most use was experimental. No teen reported marijuana use. The majority reported regular contact with their rheumatologist but only 26.9% were ever interviewed alone.

Many teens with juvenile rheumatoid arthritis, including those prescribed methotrexate, used substances, especially alcohol. When rheumatologists see adolescents, particularly in situations where methotrexate may be prescribed, a clinical setting conductive to confidentially, physician comfort in asking about sensitive topics such as substance abuse, and referral relationships with skilled adolescent health and substance abuse counseling providers are essential.

The HLA-DRB1 "shared epitope" (SE) genotypes are associated with rheumatoid arthritis (RA), but it remains controversial whether the association is with incidence, severity, or both, whether there are associations in seronegative patients, and whether different DRB1 alleles that contain the SE have similar effects on RA susceptibility and/or severity. The present study was undertaken to study these issues in a large cohort of patients with RA. White patients with RA of <6 months' duration (n = 793) were enrolled in an inception cohort. HLA-DRB1 typing was performed, and patients were categorized into 21 DRB1 genotype groups. The disability index of the Health Assessment Questionnaire was the primary outcome measure. DRB1 associations in seronegative RA patients closely resembled those in controls. Of seropositive patients, 21% had 2 copies of the epitope, 52% had 1 copy, and 27% had none. However, not all genotypes with 1 copy were associated with increased susceptibility; for example, frequencies of DRB1*0404/X and *01/X did not differ from those in controls. Absolute differences between seropositive RA patients and controls were greatest for DRB1*0401 homozygosity (3.8% versus 0.8%, respectively) and *0401/0404 heterozygosity (4.7% versus 1.0%). DRB1*0404 was increased in frequency in seropositive RA but, unlike *0401, an increased frequency was seen only with 2 epitope copies. The relatively rare DRB1*10 had an unexpected association with seropositive RA, being present in 1.7% of seropositive RA patients and 0.7% of controls, and also showed a trend toward association with greater disease severity. The presence of 2 epitope copies was associated with increased frequency of seropositivity and younger age at disease onset, not with disease severity. Treatment indication bias was substantial and may have accounted for some of these effects. HLA-DRB1*0401/0404 was found much more frequently in men and in patients with a lower age at disease onset, and there was a trend toward a higher frequency of *0404/0401 in women.

This large inception cohort study confirms previously identified major associations and provides additional insights. Only one dominant association was found: *0401, which differs from other SE alleles in a single Lys-for-Arg substitution. The association of the rare DRB1*10 allele has not previously been postulated. Sex associations were confirmed. Associations with seronegative RA were not seen. Not all genotypes containing an SE copy showed increased susceptibility to RA. The association of SE genotypes found in this study related to disease susceptibility rather than severity.

To investigate pregnancy related changes of rheumatoid factor (RF) isotypes and anti-citrullinated protein antibodies (ACPA) and their association with disease activity and therapy in patients with rheumatoid arthritis. In 22 rheumatoid arthritis patients disease activity (DAS28-CRP), therapy as well as the levels of rheumatoid factor isotypes (IgG, IgA, IgM) and ACPA were analysed longitudinally within 4 months before conception, once at each trimester and at 6,12 and 24 weeks postpartum. In addition, immunoglobulin isotypes (IgG, IgA, IgM) were measured in the pregnant rheumatoid arthritis patients as well as in 29 healthy pregnant women at the time points mentioned above. Our results showed that pregnancy significantly reduced systemic levels of the immunoglobulin isotypes IgG and IgA, but did not change the levels of IgG-RF, IgA-RF nor those of IgG-ACPA using assays with different antigen preparations. However, patients with active disease before and during pregnancy showed significantly higher levels of ACPA as compared to patients with low disease activity during pregnancy. Significantly more patients with low disease activity during pregnancy received pregnancy compatible disease modifying antirheumatic drugs or TNF-inhibitor therapy within four months before conception (P = 0.025).

Our results suggest that treatment should be adjusted to pregnancy compatible drugs preconceptionally and continued until conception and beyond to allow for stable inactive disease during gestation and control the levels of autoantibodies.

To establish (1) the efficacy of a six-week chronic disease management programme for knee osteoarthritis and (2) whether previous physiotherapy or being wait listed for surgery moderated the outcome of the programme. A pretest, posttest design with multivariate statistical modelling. One hundred and twenty-one people with severe osteoarthritis who were waiting, or being considered, for surgery. Western Ontario Osteoarthritis Index (WOMAC) scores, arthritis self-efficacy, distress and a patient-rated global indicator of response were collected at baseline, 6 and 12 weeks. History of previous physiotherapy, waiting list status, symptom duration, New Zealand disease severity score, radiographic changes and self-perceived need for surgery were recorded at baseline. There were moderate improvements in most outcomes; WOMAC function decreased by 0.29, WOMAC pain by 0.27, pain self-efficacy by 4.4, function self-efficacy by 5.6 and visual analogue scale (VAS) distress by 0.2 (effect sizes ranging from 0.3 to 0.5 at 12 weeks). Waiting list status was a significant modifier for function, pain, distress and self-related outcomes. Participants on the waiting list for surgery experienced lesser improvements. Previous physiotherapy was associated with greater improvements in WOMAC scores at six weeks, but not at 12 weeks.

The chronic disease management programme could be considered for people with severe knee osteoarthritis, but should be given prior to referral and placement on the waiting list for surgery. Previous physiotherapy should not preclude people from participating in a chronic disease management programme.

This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren's syndrome to facilitate the process in clinical routine. Patients with both CIDP and Sjögren's syndrome and CIDP without Sjögren's syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren's syndrome. The frequency of female patients was higher in patients with CIDP and Sjögren's syndrome (52%) versus CIDP patients without Sjögren's syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren's syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings.

In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren's syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.

Glucocorticoids are important drugs used to treat rheumatoid arthritis. We recommend glucocorticoid discontinuation as soon as possible given the associated side-effects, but many patients continue to take oral glucocorticoids long-term. The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating biological disease-modifying antirheumatic drugs (bDMARDs). Subjects were 564 patients from a Japanese multicenter registry who were administered glucocorticoids and methotrexate (MTX) followed by initiation of the first bDMARD. We examined the status of oral glucocorticoid use at 52 weeks after initiating the first bDMARD. By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariable analysis identified age, MTX dose, and glucocorticoid dose as factors independently associated with glucocorticoid discontinuation. After adjusting for baseline characteristics using propensity score matching, among patient groups administered MTX ≤ 8 mg/week and MTX > 8 mg/week, 105 pairs remained. A significantly higher rate of glucocorticoid discontinuation (41.0%) was noted for patients administered MTX > 8 mg/week.

Our findings suggest that glucocorticoids may be discontinued after initiating bDMARDs. Moreover, higher MTX doses (>8 mg/week) at the time of bDMARD initiation were associated with glucocorticoid discontinuation among patients treated with bDMARDs.

In the cranial humeral end, osteochondral injuries localize in a circular crown including part of the humeral head and part of the major and minor tuberosities. Since this region is easy to depict with US, we investigated the potentials of this technique in detecting osteochondral injuries. Seventy-five osteochondral injuries found at 492 US examinations performed in 12 months with a 7.5 MHz linear probe were retrospectively reviewed. Clinical history taking was focused on the following: a) previous trauma or b) luxation-instability and c) if the patient was a sportsman devoted to activities requiring forced abduction-external rotation or adduction-internal rotation. Since the site of the head's humeral injury is an important clue for diagnosis, we subdivided the humeral circle into four ideal quadrants by two perpendicular lines with the main line passing through the bicipital groove. Then, each injury was ascribed to a quadrant. All patients were also submitted to radiography (at least two films) and to MRI; CT was performed in 12 patients. Ten patients underwent surgery. We found 34 Hill-Sachs lesions, 15 traumas, 9 arthrotic lesions, 7 cases of anterointernal and 4 of posterosuperior impingement, 4 cases of infraspinatus enthesopathy and 2 erosions due to perihumeral calcifications. In our experience, US was an accurate tool in the identification of humeral head conditions, which were confirmed at CT and/or MRI in all patients (no false positives). As for the injury nature, US diagnosis was confirmed in all Hill-Sachs lesions (34/34 cases), traumas (15/15 cases) and 50% of the cases of posterosuperior impingement (2/4 cases). These conditions made up about 2/3 of the whole cases (51/75 cases). US failed to establish the injury nature in the 9 arthrotic lesions, 7 cases of anterointernal impingement, 4 cases of infraspinatus enthesopathy and 2 erosions due to perihumeral calcifications.

US can be suggested as the method of choice in the study of the osteochondral lining of the humeral head.

Rheumatoid arthritis (RA) has female preponderance and interferes with the ability to perform job roles. Household work has 2 dimensions, paid and unpaid. There is not a validated instrument that assesses the impact of RA on limitations to perform household work. We report the development and validation of a questionnaire that assesses such limitations, the HOWL-Q. The study was performed in 3 steps. Step-1 consisted on HOWL-Q conceptual model construction (literature review and semi-structured interviews to 20 RA outpatients and 20 controls, household workers, who integrated sample (S)-1). Step-2 consisted of instructions selection (by 25 outpatients integrating S-2), items generation and reduction (theory and key informant suggestions, modified natural semantic network technique, and pilot testing in 200 household workers outpatients conforming S-3), items scoring, and questionnaire feasibility (in S-3). Step-3 consisted of construct (exploratory factor analysis) and criterion validity (Spearman correlations), and HOWL-Q reliability (McDonald's Omega and test-retest), in 230 household work outpatients integrating S-4. Patients conforming the 4 samples were representative of typical RA outpatients. The initial conceptual model included 8 dimensions and 76 tasks/activities. The final version included 41 items distributed in 5 dimensions, was found feasible and resulted in 62.46% of the variance explained: McDonald's Omega = 0.959, intraclass-correlation-coefficient = 0.921 (95% CI = 0.851-0.957). Moderate-to-high correlations were found between the HOLW-Q, the HAQ, the Quick-DASH and the Lawton-Brody index. HOWL-Q score ranged from 0 to 10, with increasing scores translate into increase limitations.

The HOWL-Q showed adequate psychometric properties to evaluate household work limitations in women with RA.

To analyse the cardiovascular disease risk profile of women with fibromyalgia and compare it with control women; and to test whether physical activity is associated with the cardiovascular disease risk profile in this population. This cross-sectional study comprised 436 women with fibromyalgia (51.4±7.5 years old) and 217 controls (48.4±9.6 years old) from Andalusia, Spain. Clinical data, waist circumference, body fat percentage, resting heart rate, blood pressure and cardiorespiratory fitness were assessed. Moderate-to-vigorous physical activity was objectively assessed with accelerometry. A clustering of individual cardiovascular disease risk factors was represented by the number of cigarettes/day, adiposity, mean arterial pressure, resting heart rate and cardiorespiratory fitness. Women with fibromyalgia presented higher waist circumference and body fat percentage, greater number of cigarettes/day consumption and lower levels of cardiorespiratory fitness after controlling for age, marital status, educational level, occupational status, medication for cholesterol and monthly regular menstruation (all, p<.05). Women with fibromyalgia showed higher clustered cardiovascular disease risk than control women after controlling for the potential confounders described above (p<.001). Women with fibromyalgia who did not meet moderate-to-vigorous physical activity recommendations showed increased clustered cardiovascular disease risk after adjusting for the potential confounders described above (p<.001).

Women with fibromyalgia may present higher risk of cardiovascular disease than controls. Inadequate levels of moderate-to-vigorous physical activity may play a significant role as an additional predisposing factor for cardiovascular disease risk in this population.

Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA.

The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy.

Pain and depressive symptoms are common in patients with rheumatoid arthritis (RA). Information on the prevalence and treatment of both conditions in German RA patients is scarce. Using data from a nationwide statutory health insurance fund (BARMER GEK), 6193 RA patients aged 18 to 79 years were provided with a questionnaire covering a variety of items such as demographics, medical condition and quality of life in 2015. Pain caused by the joint disorder (11-point scale) was classified as none existent/mild, moderate or severe. Depressive symptoms were determined using the World Health Organization's five-item Well-being Index and categorized as none existent, mild or moderate/severe. Another item covered additional use of over-the-counter drugs. Data were linked to dispensation records. A total of 3140 RA patients were included. Median age was 66 years (79% female). About 70% of patients were classified as having moderate or severe pain. Depressive symptoms were found in 52% and were far more common among patients with higher pain levels. Analgesic treatment ranged from 45% to 76% (non-opioid analgesics) and from 6% to 33% (opioids) in patients with no/mild pain and those reporting severe pain, respectively. In patients reporting moderate or severe pain, substantially higher prevalences of opioid use were observed among those with depressive symptoms. Depending on depressive symptoms, antidepressant use ranged from 7% to 37%. Overall, over-the-counter drug use varied between 30% and 59%.

Pain and depressive symptoms are highly prevalent in German RA patients, often present together and influence each other's treatment. Copyright © 2017 John Wiley & Sons, Ltd.

To evaluate the measurement properties of a new osteoarthritis (OA) pain measure. The new tool, comprised of 12 questions on constant vs intermittent pain was administered by phone to 100 subjects aged 40+ years with hip or knee OA, followed by three global hip/knee questions, the Western Ontario and McMaster Universities (WOMAC) pain subscale, the symptom subscales of the Hip Disability and OA Outcome Score (HOOS) or Knee Injury and OA Outcome Score (KOOS), and the limitation dimension of the Late Life Function and Disability Instrument (LLFDI). Test-retest reliability was assessed by re-administration after 48-96h. Item response distributions, inter-item correlations, item-total correlations and Cronbach's alpha were assessed. Principle component analysis was performed and test-retest reliability was assessed by intra-class correlation coefficient (ICC). There was good distribution of response options across all items. The mean intensity was higher for intermittent vs constant pain, indicating subjects could distinguish the two concepts. Inter-item correlations ranged from 0.37 to 0.76 indicating no item redundancy. One item, predictability of pain, was removed from subsequent analyses as correlations with other items and item-total correlations were low. The 11-item scale had a corrected inter-item correlation range of 0.54-0.81 with Cronbach's alpha of 0.93 for the combined sample. Principle components analysis demonstrated factorial complexity. As such, scoring was based on the summing of individual items. Test-retest reliability was excellent (ICC 0.85). The measure was significantly correlated with each of the other measures [Spearman correlations -0.60 (KOOS symptoms) to 0.81 (WOMAC pain scale)], except the LLFDI, where correlations were low.

Preliminary psychometric testing suggests this OA pain measure is reliable and valid.

Gouty arthritis is increasing in prevalence in men and women, particularly in older age groups. A PubMed search was conducted to identify common comorbidities associated with gouty arthritis, their impact on quality of life, and strategies to manage gouty arthritis and its associated comorbidities. Gouty arthritis is associated with numerous comorbidities that are increasing in prevalence (chronic kidney disease [CKD], hypertension, obesity, diabetes, metabolic syndrome, and cardiovascular disease) and that negatively impact long-term prognosis and quality of life. Therefore, certain considerations and precautions are necessary when treating gouty arthritis in these patients. For example, nonsteroidal anti-inflammatory drugs can cause acute renal toxicity or worsen CKD and should be avoided in this population. Dosage adjustments are recommended when using colchicine and urate-lowering therapy in patients with CKD, which may limit efficacy. Febuxostat may be used in patients with mild to moderate renal impairment, but insufficient information is available for use in patients with creatinine clearance of less than 30 mL/min. Numerous drug-drug interactions in patients with gouty arthritis and comorbidities may alter serum uric acid levels. Several interleukin 1β inhibitors, which target the underlying inflammatory mechanism of gouty arthritis and many of its comorbidities, are in development and may provide an option for patients not adequately managed with other treatments.

Gouty arthritis is associated with renal, metabolic, and cardiovascular comorbidities that negatively impact overall health. The management of gouty arthritis in the presence of comorbidities is particularly challenging because of contraindications, the need for dosage adjustments, and polypharmacy.

This study analyzed the use of the one piece cervical device (OPCD) surgically inserted to treat atlanto-axial or subaxial subluxation. Operative results, techniques, and the enhanced correction mechanism were studied. The results were correlated to provide a rationale for posterior cervical spinal fusion. Wiring techniques were generally performed for posterior fusion. Recently, the Luque rod has been used on the cervical spine. One hundred eighty-seven patients were analyzed clinically and radiologically. The operative techniques were detailed and the corrective mechanism explained through biomechanical considerations. The patients were followed from 2 to 13 years. The results were 94% satisfactory. No poor or worsening cases were encountered.

Satisfactory operative results showed that the OPCD is safe, convenient, and reliable. It can be used in all areas of the cervical spine. The primary reason for these benefits is the enhanced correction mechanism of the OPCD.

A randomized, placebo-controlled, double-blind study was designed to investigate the effectiveness of ultrasound therapy in primary knee osteoarthritis. Ninety patients between 40 and 65 years of age having grade 2 and 3 bilateral knee osteoarthritis enrolled in the study were randomly assigned into 3 groups: continuous ultrasound, pulsed ultrasound, and placebo ultrasound. All patients were given a home exercise program. Patients were evaluated at baseline, at the end of the treatment, and at the second month after the treatment by a range of motion measurement, visual analog scale, Lequesne index for knee osteoarthritis, and Short Form-36 quality of life scale. The increase in the knee range of motion was similar in both ultrasound groups, while the change in the placebo group was not statistically significant. Visual analog scale scores and Lequesne scores of the placebo group at the second month were significantly greater than both ultrasound groups' scores (P < 0.01 and P < 0.05, respectively).

Significant improvements in terms of pain, function, and quality of life scales were noted in both ultrasound groups in comparison with the placebo group. No statistically significant difference was found in terms of efficacy between the continuous and pulsed ultrasound.

Individuals with systemic lupus erythematosus (SLE) are at high risk for infections and SLE- and medication-related complications. The present study was undertaken to define a set of SLE-specific adverse outcomes that could be prevented, or their complications minimized, if timely, effective ambulatory care had been received. We used a modified Delphi process beginning with a literature review and key informant interviews to select initial SLE-specific potentially preventable conditions. We assembled a panel of 16 nationally recognized US-based experts from 8 subspecialties. Guided by the RAND-UCLA Appropriateness Method, we held 2 survey rounds with controlled feedback and an interactive webinar to reach consensus regarding preventability and importance on a population level for a set of SLE-specific adverse conditions. In a final round, the panelists endorsed the potentially preventable conditions. Thirty-five potential conditions were initially proposed; 62 conditions were ultimately considered during the Delphi process. The response rate was 100% for both survey rounds, 88% for the webinar, and 94% for final approval. The 25 SLE-specific conditions meeting consensus as potentially preventable and important on a population level fell into 4 categories: vaccine-preventable illnesses (6 conditions), medication-related complications (8 conditions), reproductive health-related complications (6 conditions), and SLE-related complications (5 conditions).

We reached consensus on a diverse set of adverse outcomes relevant to SLE patients that may be preventable if patients receive high-quality ambulatory care. This set of outcomes may be studied at the health system level to determine how to best allocate resources and improve quality to reduce avoidable outcomes and disparities among those at highest risk.

Standard clinical and laboratory evaluations and novel laboratory techniques were used to identify patients with T-cell large granular lymphocyte leukemia (LGLL) and those with natural killer-cell variants of LGLL for comprehensive clinical evaluation. We used bone marrow histologic analysis, immunophenotypic markers of clonality, and T-cell-receptor gene rearrangement studies to identify patients. The study identified 44 patients with T-cell LGLL and 14 with natural killer-cell LGLL. The two disorders were similar in sex and age distribution of patients; peripheral blood lymphocyte, neutrophil, and platelet counts; and incidence of rheumatoid arthritis. Among the two groups, patients with the T-cell LGLL presented with significantly lower hemoglobin concentrations (P < 0.04) and a higher frequency of palpable splenomegaly (P < 0.01).

Overall disease progression and response to immunosuppressive therapy are similar between T-cell and natural killer-cell variants of LGLL.

Cytosolic phospholipase A2 (cPLA2) is a rate-limiting enzyme that plays a critical role in the biosynthesis of eicosanoids. The aim of this study was to investigate the mechanisms underlying interleukin-1β (IL-1β)-induced cPLA2 expression in human rheumatoid arthritis synovial fibroblasts (RASFs). Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. In a mouse model of IL-1β-mediated inflammatory arthritis, neutrophil infiltration, bone erosion, and cPLA2 expression in ankle synovium were analyzed by immunohistochemistry. IL-1β-induced cPLA2 expression was determined by Western blotting, real-time polymerase chain reaction, and gene promoter assay using pharmacologic inhibitors and transfection with short hairpin RNAs or small interfering RNAs. The recruitment of NF-κB and p300 to the cPLA2 promoter was determined by chromatin immunoprecipitation assay. Prostaglandin E2 (PGE2) biosynthesis was evaluated by enzyme-linked immunosorbent assay. IL-1β-induced cPLA2 expression and PGE2 release were mediated through a myeloid differentiation factor 88 (MyD88)/c-Src-dependent matrix metalloproteinase (MMP)/heparin-binding epidermal growth factor (HB-EGF) cascade linking to transactivation of the EGF receptor (EGFR)/phosphatidylinositol 3-kinase (PI 3-kinase)/Akt, p300, and NF-κB p65 pathways. IL-1β also stimulated Akt phosphorylation and nuclear translocation. Activation of Akt eventually led to the acetylation of histone residues by phosphorylation and recruitment of p300 and enhanced its histone acetyltransferase activity on the NF-κB elements of the cPLA2 promoter. IL-1β-induced NF-κB transcriptional activity was mediated through a PI 3-kinase/Akt-dependent cascade. Up-regulation of cPLA2 by IL-1β increased PGE(2) biosynthesis in RASFs.

IL-1β-induced cPLA2 expression is mediated through activation of the MyD88/c-Src, MMP/HB-EGF, EGFR/PI 3-kinase/Akt, p300, and NF-κB pathways. These results provide insights into the mechanisms underlying IL-1β-enhanced joint inflammatory responses in RA and may inspire new targeted therapeutic approaches.

The authors compared outcomes among persons with rheumatoid arthritis (RA) with a rheumatologist versus a non-rheumatologist as the main physician for this condition. A cohort of 1,025 persons with rheumatoid arthritis were followed for as long as 11 years. The principal measures were obtained from an annual structured telephone interview conducted by a trained survey worker. All persons with rheumatoid arthritis originally were selected from a random sample of community rheumatologists, but some subsequently had migrated to the practices of non-rheumatologists. The main outcome measures included the number of painful and swollen joints, extent of morning stiffness, a global pain rating, functional status, and a measure of global improvement. The persons with rheumatoid arthritis treated by rheumatologists reported significantly better functional status, fewer painful joints, and a lower overall pain rating, although the magnitude of these differences was small. A significantly greater proportion of the persons with rheumatoid arthritis treated by rheumatologists also reported improvement in a global measure of rheumatoid arthritis outcome and simultaneous improvement in all outcome measures. On all other outcome measures, the point estimate favored those with a rheumatologist as the main rheumatoid arthritis physician, although the differences did not reach statistical significance.

The evidence suggests an advantage for persons with a rheumatologist as the main rheumatoid arthritis physician, but on several of the measures of outcome, the magnitude of the advantage was small. Because the present study was an observational design, the possibility that the advantage among persons with a rheumatologist as the main rheumatoid arthritis physician is an artifact of selection bias cannot be ruled out.

Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose. Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.

mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

Medication decision-making poses a challenge for a significant proportion of patients. This is an even more challenging for patients who have complex, rare, immune conditions that affect them at a young age and are associated with the use of life-long treatment, perceived by some as having significant risk of side effects and toxicity. The aim of our study was to examine the perspectives of women with lupus nephritis on facilitators to medication decision-making. We used the nominal group technique (NGT), a structured formative process to elicit patient perspectives. An NGT expert moderated eight patient group meetings. Participants (n = 52) responded to the question "What sorts of things make it easier for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized facilitators to medication decisional processes. Fifty-two women with lupus nephritis participated in eight NGT meetings (27 African-American, 13 Hispanic, and 12 Caucasian). Average age was 40.6 years (standard deviation (SD) = 13.3), and disease duration was 11.8 years (SD = 8.3); 36.5 % obtained at least a college education, and 55.8 % had difficulty in reading health materials. Patients generated 280 decision-making facilitators (range of 26 to 42 per panel). Of these, 102 (36 %) facilitators were perceived by patients as having relatively more influence in decision-making processes than others. Prioritized facilitators included effective patient-physician communication regarding benefits/harms, patient desire to live a normal life and improve quality of life, concern for their dependents, experiencing benefits and few/infrequent/no harms with lupus medications, and their affordability. Relative to African-Americans, Caucasian and Hispanic patients endorsed a smaller percentage of facilitators as influential. Level of agreement with which patients within panels independently agreed in their selections of the three most influential facilitators ranged from 33 % to 60 %.

We identified facilitators to lupus medication decision-making. This information will be used to populate a decision aid for lupus nephritis.