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ID PMID Title PublicationDate abstract
29532734 Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who 2019 Mar OBJECTIVE: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy. METHODS: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed. Results 116/878 patients received sirukumab 50 mg/4 weeks (q4w, n = 35), 100 mg/2 weeks (q2w, n = 44) or placebo (n = 37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50 mg q4w:20 [57.1%]; p < .001, 100 mg q2w:24 [54.5%]; p = .001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50 mg q4w:29 [82.9%]; 100 mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs. CONCLUSION: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.
27927025 "Whenever I can I push myself to go to work": a qualitative study of experiences of sickne 2018 Feb PURPOSE: UK government policy emphasizes the importance of continuing to work for recovery from poor health, yet sickness presenteeism (going to work whilst ill) is commonly regarded as having negative consequences for organizations and individuals. Our study explores experiences of working after onset of rheumatoid arthritis (RA), a chronic musculoskeletal disorder characterized by high rates of work disability. MATERIALS AND METHODS: An exploratory qualitative study consisting of in-depth interviews and six-month follow-up with 11 men and women with RA employed at disease onset. RESULTS: We expand upon previous models of sickness presenteeism by distinguishing between presenteeism that occurs voluntarily (wanting to work despite illness) and involuntarily (feeling pressured to work when ill). RA onset affected participants' ability to work, yet motivation to remain working remained high. The implementation of workplace adjustments enabled participants to stay working and restore their work capacity. Conversely, managers' misinterpretation of organizational sickness absence policies could lead to involuntary presenteeism or delayed return to work, conflicting with the notion of work as an aid to recovery. CONCLUSION: Workplace adjustments can facilitate voluntary sickness presenteeism. To reduce work disability and sickness absence, organizational policies should be sufficiently flexible to accommodate the needs of workers with fluctuating conditions. Implications for rehabilitation Individuals with rheumatoid arthritis (RA) are at high risk of work disability. Individuals' motivation to remain in work following onset of RA remains high, yet sickness presenteeism (working while ill) has received largely negative attention. It is important to distinguish between voluntary and involuntary forms of sickness presenteeism. Workplace adjustments facilitate voluntary sickness presenteeism (wanting to work despite illness) and improve job retention and productivity among workers with RA. Involuntary presenteeism (feeling pressured to work while ill) may occur if organizational policies are not sufficiently flexible to accommodate the needs of workers with RA.
29518978 Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis. 2018 Mar 7 The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel(®)), infliximab (Remicade(®)), adalimumab (Humira(®)), certolizumab-pegol (Cimzia(®)), and golimumab (Simponi(®)), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα-TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.
28603283 TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibrobla 2018 Jul The upregulated expression of thioredoxin domain-containing protein 5 (TXNDC5) is associated with rheumatoid arthritis in patients and model mice. However, the underlying mechanism by which TXNDC5 influences the pathological activation of rheumatoid arthritis synovial fibroblasts (RASFs) remains unknown. In this study, we show that TXNDC5 expression in RASFs and their cytokine production are significantly upregulated in response to LPS, TNF-α and IL-6, but suppressed by transfection with TXNDC5-siRNA. TXNDC5 is further validated as the direct target of NF-κB signaling. Mechanistically, TXNDC5 directly interacts with heat shock cognate 70 protein (HSC70) to sequester it in the cytoplasm, and HSC70 silencing exerts the same effects as TXNDC5 on the biological activity of RASFs (for example, decreased cell viability, invasion and cytokine production). Furthermore, HSC70 activates NF-κB signaling by destabilizing IκBβ protein in the absence of LPS or facilitating its nuclear translocation in the presence of LPS. Importantly, TXNDC5 can also regulate the activity of NF-κB signaling in a HSC70-IκBβ-dependent manner. Taken together, by linking HSC70 and NF-κB signaling, TXNDC5 plays a pro-inflammatory role in RASFs, highlighting a potential approach to treat RA by blocking the TXNDC5/HSC70 interaction.
30318125 Keeping physically active with rheumatoid arthritis: semi-structured interviews to explore 2019 Sep BACKGROUND: Regular physical activity is safe and beneficial for people with rheumatoid arthritis (RA) but the majority of people with RA are less active than the general population and have a higher risk of co-morbidities. Exploring strategies used by physically active people with RA could inform effective methods to support those who are less active. OBJECTIVE: To explore the perspectives, experiences and strategies employed by people with RA who successfully engage with regular physical activity. DESIGN: Individual semi-structured interviews and thematic analysis. PARTICIPANTS: A purposive sample of physically active people with RA. RESULTS: Twelve females and three males participated (mean age 56, range 29 to 80; mean disease duration 13 years, range 10 months to 46 years). Analysis revealed eight constructs clustered into three themes. Theme 1: 'the individual' incorporated constructs of symptoms, feelings and role; theme 2: 'management' incorporated medical and self-management; theme 3: 'physical activity' incorporated constructs of type of physical activity, including barriers or facilitators. Participants reported a long history of physical activity prior to diagnosis and good support networks. All participants recognised that physical activity was key to their RA management, acknowledged the benefits from engaging in physical activity and were able to overcome barriers. Participants had strong beliefs that physical function would decline without regular physical activity. CONCLUSIONS: People with RA who successfully maintain physical activity are motivated by a desire to manage symptoms, resist functional decline and maintain health and independence. These findings should be explored with a wider range of people with RA.
27900440 Role of methotrexate chronotherapy in collagen-induced rheumatoid arthritis in rats. 2018 Apr AIM: To explore the circadian rhythm of serum interleukin (IL)-6 in collagen-induced arthritis (CIA) rats and compare the safety and effectiveness of methotrexate (MTX) administered traditionally and via chronotherapy. METHODS: CIA rat models were immunized with bovine type II collagen. Serum IL-6 levels in normal and CIA rats were measured at 2, 6, 10, 14, 18, or 22 h after the light was turned on (HALO). MTX was administered to 6 HALO/18 HALO experimental groups of Wistar rats once daily according to the IL-6 rhythm. The control groups (positive, negative, and normal) were given MTX or an equal volume of phosphate buffered saline (PBS) once a week simultaneously. Arthritis score, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP) levels in the serum were measured by enzyme-linked immunosorbent assay (ELISA). Histological changes in the ankle joint were analyzed. RESULTS: After 6 weeks of treatment, arthritis scores in the experimental group were lower than in the control group. The expression of TNF-α, IL-6, and CRP was lower in the 18 HALO group than in the control or 6 HALO groups. Histopathology scores in the experimental groups were lower than in the control group (p < 0.05). CONCLUSION: The plasma IL-6 levels in CIA rats were higher than in normal rats and showed significant circadian rhythm. Daily administration of MTX is more potent than weekly administration. The therapeutic index of rheumatoid arthritis (RA) may be improved with MTX therapy based on the IL-6 circadian rhythm.
29428471 Efficacy of constant long-term delivery of YM-58483 for the treatment of rheumatoid arthri 2018 Apr 5 The aim of this study was to investigate the efficacy and safety of YM-58483, a small molecular antagonist of Ca(2+) release-activated Ca(2+) (CRAC) channels, for the treatment of rheumatoid arthritis (RA), in vivo and ex vivo. YM-58483 was continuously injected subcutaneously in a collagen-induced arthritis (CIA) mouS.E.M.odel using an implanted osmotic pump. The severity of CIA was evaluated using the following parameters: body weight, hind paw volume, clinical score, histological analysis, cytokine levels, Ca(2+) influx, and specific IgG production. The efficacy of long-term application of YM-58483 was also verified ex vivo in RA patient-derived peripheral blood monocytes. Assessment of the clinical severity of CIA, cytokine profile in serum and joint protein extracts, and specific IgG production showed that continuous application of YM-58483 suppressed synovial inflammation by inhibiting immune cell activity. Chemical screening and hepatography indicated that long-term subcutaneous delivery of YM-58483 was safer than oral administration for systemic application. Moreover, constant preincubation with YM-58483 at an IC(50) of 0.1-1 nM altered proinflammatory cytokine production ex vivo in peripheral T cells derived from RA patients. Our findings suggest that continuous long-term application of appropriate CRAC inhibitors such as YM-58483 is a potential therapeutic strategy for global immunosuppression in RA.
29932210 Follistatin-like protein 1 induction of matrix metalloproteinase 1, 3 and 13 gene expressi 2018 Jan Elevated levels of follistatin-like protein 1 (FSTL1) have been found both in mouse models for human rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). In this study, we elucidated the potential mechanisms by which FSTL1 contributes to the pathogenesis of RA. Fibroblast-like synoviocytes (FLSs) were established from synovial tissues of RA patients and stimulated with human recombinant FSTL1. Protein and mRNA expression levels of select matrix metalloproteinases (i.e., MMP1, MMP3, MMP13) in FLS were measured by, respectively, real-time RT-qPCR and ELISA. Activation of MAPK and other pathways that affect MMPs were evaluated by Western blotting. We also compared concentrations of MMPs in plasma in RA patients versus healthy controls (HC). Expression levels of MMP1, MMP3, and MMP13 were clearly stimulated by FSTL1 in vitro. FSTL1 activated the inflammation-related NF-κB signaling pathway, as well as all three mitogen-activated protein kinase (MAPK) pathways and the JAK/STAT3 pathway. Moreover, select chemical inhibitors that target p38 (SB203580), Erk1/2 (SP600125), JNK (SCH772984), STAT3 (AG490), and NF-κB (BAY 11-7082) significantly attenuated MMP expression. Inhibition of Toll-like receptor 4 by compound TAK-242 significantly abolished those effects of FSTL1. Importantly, elevated plasma concentrations of MMP3 were found to correlate with plasma FSTL1 levels in RA patients. These findings suggest that FSTL1 accelerates RA progression by activating MAPK, JAK/STAT3, and NF-κB pathways to enhance secretion of different MMPs and this enhancement is via TLR4. Targeting FSTL1 may provide a promising pharmacological drug therapy to ameliorate RA symptoms and perhaps reverse disease progression.
30376836 Intensive therapy and remissions in rheumatoid arthritis: a systematic review. 2018 Oct 30 BACKGROUND: We systematically reviewed the effectiveness of intensive treatment strategies in achieving remission in patients with both early and established Rheumatoid Arthritis (RA). METHODS: A systematic literature review and meta-analysis evaluated trials and comparative studies reporting remission in RA patients treated intensively with disease modifying anti-rheumatic drugs (DMARDs), biologics and Janus Kinase (JAK) inhibitors. Analysis used RevMan 5.3 to report relative risks (RR) in random effects models with 95% confidence intervals (CI). RESULTS: We identified 928 publications: 53 studies were included (48 superiority studies; 6 head-to-head trials). In the superiority studies 3013/11259 patients achieved remission with intensive treatment compared with 1211/8493 of controls. Analysis of the 53 comparisons showed a significant benefit for intensive treatment (RR 2.23; 95% CI 1.90, 2.61). Intensive treatment increased remissions in both early RA (23 comparisons; RR 1.56; 1.38, 1.76) and established RA (29 comparisons RR 4.21, 2.92, 6.07). All intensive strategies (combination DMARDs, biologics, JAK inhibitors) increased remissions. In the 6 head-to-head trials 317/787 patients achieved remission with biologics compared with 229/671 of patients receiving combination DMARD therapies and there was no difference between treatment strategies (RR 1.06; 0.93. 1.21). There were differences in the frequency of remissions between early and established RA. In early RA the frequency of remissions with active treatment was 49% compared with 34% in controls. In established RA the frequency of remissions with active treatment was 19% compared with 6% in controls. CONCLUSIONS: Intensive treatment with combination DMARDs, biologics or JAK inhibitors increases the frequency of remission compared to control non-intensive strategies. The benefits are seen in both early and established RA.
30534652 Musculoskeletal ultrasound as a biomarker of remission - results from a one-year prospecti 2018 Dec 8 AIMS: To assess the role of musculoskeletal ultrasound (MSUS) as a biomarker of remission and to compare the rates of clinical and imaging remission in patients with rheumatoid arthritis (RA) on different types of treatment. MATERIAL AND METHODS: One hundred and forty-one patients underwent physical and ultrasound examination at 5 visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joints, and the second and fifth metatarsophalangeal joints was performed on gray scale ultrasound (GSUS) and on power Doppler ultrasound (PDUS) (German US7-score). The rate of imaging and clinical remission (DAS28, SDAI, CDAI, and Boolean) was established. The percentage of patients in clinical remission with persistent PD signal was assessed. RESULTS: In the sDMARDs group at month twelve, 43.6% of the patients achieved DAS28 remission, 5.1% - SDAI, 3.8% - CDAI, and 3.8% - Boolean remission. In the bDMARDs group 49.2% achieved DAS28 remission, 6.3% - SDAI, 4.8% - CDAI, and 4.8% - Boolean remission. Irrespective of which clinical index was applied, all patients in clinical remission had persistent synovial hypertrophy on GSUS. Synovial PD signal (PDUS score≥1) was detected in 77% and 71% of patients in DAS28 remission in the sDMARDs and bDMARDs group, respectively. Patients in SDAI, CDAI and Boolean remission in both treatment groups did not have а positive PD signal. CONCLUSIONS: There is persistence of synovitis both in patients on sDMARDs and bDMARDs in DAS28 clinical remission. This fact points to a discordance between DAS28 clinical remission and the imaging remission assessed by MSUS irrespective of the type of treatment. MSUS may be a feasible imaging method for the assessment of residual inflammation in daily rheumatology practice.
30173156 High Burden of Sexual Dysfunction in Female Patients with Rheumatoid Arthritis: Results of 2019 Jan OBJECTIVE: To evaluate the effect of rheumatoid arthritis (RA) on impairing women's sexuality regarding motivation, activity, and satisfaction, and to assess the correlation of disease-related physical impairment within sexual functioning. METHODS: An anonymous survey among women with RA and healthy controls (HC) using standardized questionnaires, predominantly the Changes in Sexual Functioning Questionnaire-short form (CSFQ-14). In addition, disease activity, depression, and disability were evaluated. RESULTS: There were 319 questionnaires distributed to patients and 306 to HC. Of these, 235 patient questionnaires (73.7%) and 180 HC questionnaires (58.8%) were returned, of which 203 and 169 were completed, respectively. Of the patients with RA, 47.8% had a total CSFQ-14 score of ≤ 41, indicating female sexual dysfunction (FSD), as compared to 14.2% of HC (p < 0.0001). The median CSFQ-14 score was lower in patients with RA [42 points, interquartile range (IQR) 36-48] than in HC (49 points, IQR 44-54; p < 0.0001), resulting in an OR of 5.53 (95% CI 3.19-9.57; p < 0.0001). After adjustment for confounders, given a higher mean age of patients (55.2 ± 11.3 yrs) than HC (47.4 ± 11.8 yrs; p < 0.0001), the OR for FSD in patients with RA was still 3.04 (95% CI 1.61-5.75; p = 0.001). Neither the Health Assessment Questionnaire-Disability Index nor the Clinical Disease Activity Index was associated with FSD after adjustment. CONCLUSION: FSD apparently is highly prevalent in female patients with RA, affects all subdomains of sexual function, and is most likely underestimated in daily clinical practice. Of note, FSD could not be linked to disability or RA disease activity.
29849918 Diet Quality and Its Relationship with Antioxidant Status in Patients with Rheumatoid Arth 2018 A direct contribution towards destructive, proliferative synovitis in rheumatoid arthritis (RA) has been attributed to reactive oxygen species action. Some nutrients are considered to be capable of improving the oxidant/antioxidant status in RA; however the impact of diet composition on the antioxidant capacity of serum has not yet been studied in this disease. The aim of the study was to assess the relationship between diet quality and antioxidant status in patients with RA and healthy controls. Nutritional assessment was performed, and antioxidant status in serum, without and with deproteinization (TAS and DSAS, resp.), was determined in 82 RA and 87 healthy subjects. The diet of the RA group was low-energy and imbalanced. TAS and DSAS were significantly lower in RA patients than in controls. Antioxidant status significantly correlated with the supply of foods and nutrients influencing antioxidant and anti-inflammatory defense in RA; however, in this group, TAS was more sensitive to diet than DSAS. In healthy subjects, the nonprotein pool of serum antioxidants was more tightly linked to diet. These outcomes indicate the need to monitor diet quality of patients with RA and the usefulness of TAS measurements in this monitoring.
29465363 Inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 on RANKL expression in fibrob 2018 Sep OBJECTIVES: To explore the inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 (l,25(OH)2D3) on receptor activator of nuclear factor-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLSs) and osteoclastogenesis induced by interleukin (IL)-22 in patients with rheumatoid arthritis (RA). METHODS: Fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLSs) were cultured and stimulated for RANKL expression with IL-22 in the absence or presence of various concentrations of l,25(OH)2D3, and JAK-2 inhibitor or p38 MAPK inhibitor at the optimised time point of IL-22 treatment. The level of RANKL messenger RNA (mRNA) or protein was measured using real-time polymerase chain reaction (RT-PCR) or western blot method. To assess the impact of l,25(OH)2D3 on osteoclastogenesis, isolated monocytes were activated by M-CSF and RANKL or cocultured with FLSs stimulated by IL-22 in the presence or absence of l,25(OH)2D3 and those inhibitors. TRAP-positive cells as differentiated osteoclasts were stained for alkaline phosphatase. RESULTS: FLSs stimulated with IL-22 for 72 hours were used in further experiment because of the highest expression of RANKL at this time point. The expression of RANKL mRNA and protein in IL-22-stimulated FLSs were significantly inhibited by 1 nM of 1,25(OH)2D3 (p<0.05). Interestingly, this inhibition was reversed by inhibitor of JAK-2/STAT-3 or p38 MAPK/NF-κB signalling. In monocytes cocultured with IL-22-stimulated FLSs in the presence of exogenous RANKL and M-CSF, 1,25(OH)2D3 could block the process of osteoclastogenesis by JAK-2/STAT-3 or p38 MAPK/NF-κB signalling. CONCLUSIONS: 1,25(OH)2D3 may exert inhibitory effect on osteoclastogenesis of RA-FLSs by down-regulating RANKL expression, which could be mediated by IL-22 through JAK-2/STAT-3 and p38 MAPK/NF-κB signalling.
29128424 The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rh 2018 Mar Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic. As a result, several assays for detection of ACPAs exist, which vary in sensitivity and specificity. In this study, we analyzed the reactivity of RA sera to selected peptides by solid-phase immunoassays in order to develop an ACPA assay with improved sensitivity and specificity. ACPA levels were determined with respect to sensitivity and specificity in 332 serum samples using the newly developed peptide panel, which was compared to the commercial assays CCPlus (Eurodiagnostica) and CCP3.1 (Inova Diagnostics). A primary panel (peptides 814, 33062 and 33156) was identified, which obtained a sensitivity of 71%, while the complete peptide panel reacted with 79% of RA sera screened. Total specificities of 89% and 80% were obtained for the primary peptide panel and the complete peptide panel. Sensitivities for the commercial assays ranged between 71% and 76% and specificities between 88% and 90%. These findings indicate that the generated peptide panel is optimal for ACPA detection and able to compete with commercial available assays. Collectively, this study may contribute to characterize autoimmunity towards citrullinated proteins and to the development of new and improved diagnostic assays for detection of ACPA and determination of RA.
30037875 Risk of rheumatoid arthritis in patients with hepatitis C virus infection receiving interf 2018 Jul 23 OBJECTIVES: To illuminate the association between interferon-based therapy (IBT) and the risk of rheumatoid arthritis (RA) in patients infected with hepatitis C virus (HCV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This retrospective cohort study used Taiwan's Longitudinal Health Insurance Database 2005 that included 18 971 patients with HCV infection between 1 January 1997 and 31 December 2012. We identified 1966 patients with HCV infection who received IBT (treated cohort) and used 1:4 propensity score-matching to select 7864 counterpart controls who did not receive IBT (untreated cohort). OUTCOME MEASURES: All study participants were followed until the end of 2012 to calculate the incidence rate and risk of incident RA. RESULTS: During the study period, 305 RA events (3.1%) occurred. The incidence rate of RA was significantly lower in the treated cohort than the untreated cohort (4.0 compared with 5.5 per 1000 person-years, p<0.018), and the adjusted HR remained significant at 0.63 (95% CI 0.43 to 0.94, p=0.023) in a Cox proportional hazards regression model. Multivariate stratified analyses revealed that the attenuation in RA risk was greater in men (0.35; 0.15 to 0.81, p=0.014) and men<60 years (0.29; 0.09 to 0.93, p=0.036). CONCLUSIONS: This study demonstrates that IBT may reduce the risk of RA and contributes to growing evidence that HCV infection may lead to development of RA.
30170401 Bone quality, and the combination and penetration of cement-bone interface: A comparative 2018 Aug To compare the microstructure, bone quality, and the combination and penetration of cement-bone interface in tissue specimens from patients with osteoarthritis (OA) and rheumatoid arthritis (RA).A total of 80 femoral condyle tissue specimens from 20 OA patients (40 condyles) and 20 RA patients (40 condyles) who underwent total knee arthroplasty at the Department of Orthopaedics in Tengzhou Central People's Hospital were collected between January 2017 and September 2017. According to the random number table method, 20 specimens from the OA group were defined as group A, and 20 specimens in the RA group were defined as group B. The bone quality parameters were measured by micro-CT. The remaining 20 specimens in the OA group and the remaining 20 specimens in the RA group were defined as group C and group D, the cement-bone interfaces were established by the self-made bone cement compression device, and were analyzed by micro-CT.Micro-CT measurement revealed that the bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) in group A were significantly higher than those in group B (all P < .05). The bone surface/bone volume (BS/BV), structure model index (SMI), trabecular separation (Tb.Sp), and degree of anisotropy (DA) in group A were significantly lower than those in group B (all P < .05). The penetration depth of bone cement in group D was significantly greater than those in group C via x-ray detection.The bone quality of OA patients is better than that of RA patients, but the combination and penetration of cement-bone interface of RA patients are better than that of OA patients. The findings advance our understanding of knee prosthesis and have important clinical implications, but they require validations in future studies with larger sample sizes.
30334419 Treatment mechanism of tolerogenic dendritic cells on rheumatoid arthritis. 2018 Sep This study aims to explore the possible mechanism of treatment of collagen-induced rheumatoid arthritis (RA) by tolerogenic dendritic cells (tDCs). Different methods were used to induce and cultivate tDCs, and suitable conditions for tDC cultivation were explored. The experimental RA induced by collagen in mouse was treated by the obtained tDCs, and the possible mechanism was explored. The serum concentration of TNF-α, IFN-β, IL-4 and anti-type II collagen antibody were detected by ELISA. The anti-type II collagen antibody of mice without treatment was higher than that without disease onset, while the Blank-DC group, VIP-DC group and Bay-D had no statistically significant differences (P>0.05). Compared to the group without disease onset, the TNF-α level of those without treatment was significantly higher, while INF-γ, IL-1β and IL-4 concentration showed no significant difference (P>0.05). Compared to the untreated group, the TNF-α and IL-1β concentration after VIP-DC treatment were significantly decreased, while IL-4 was increased (P less than0.05). In summary, VIP-DC and Bay-DC alleviate joint inflammation, synovitis and bone erosion by reducing the production of anti-type II collagen antibody, inhibiting proinflammatory factors and increasing inflammation inhibitors.
28464477 Smoking Behavior Changes in the Early Rheumatoid Arthritis Period and Risk of Mortality Du 2018 Jan OBJECTIVE: To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality. METHODS: We identified an incident RA cohort in the Nurses' Health Study (NHS; 1976-2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within 4 years of the RA/index date. We used Cox regression to obtain hazard ratios (HRs) for mortality, comparing sustained smoking cessation to continued smoking. RESULTS: Among 121,700 women in the NHS, we identified 938 with incident RA matched to 8,951 non-RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period, compared to 36.1% of comparators (odds ratio for sustained cessation 1.18 [95% confidence interval (95% CI) 0.88, 1.58]). There were 313 deaths (33.4%) in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58 [95% CI 0.33, 1.01]) and comparison (HR 0.47 [95% CI 0.39, 0.58]) cohorts. Women with RA had higher mortality for >5 post-RA pack-years (HR 3.67 [95% CI 2.80, 4.81]) than comparators with >5 post-index pack-years (HR 1.88 [95% CI 1.62, 2.17]; P < 0.001 for interaction; reference: ever-smoker non-RA women with 0 post-index pack-years). CONCLUSION: Sustained smoking cessation within 4 years of RA diagnosis reduced mortality risk, with a similar effect observed among non-RA comparators. Smoking >5 pack-years after RA diagnosis significantly increased mortality beyond the risk of non-RA comparators.
30069794 The Portuguese Rheumatoid Arthritis Impact of Disease (RAID) score and its measurement equ 2018 Nov PURPOSE: The Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven impact domains of interest for people with RA. This study aimed to test patients' understanding of the Portuguese RAID and evaluate its cross-cultural validity for use in Portugal. METHODS: This was a mixed methods study comprising two phases: (i) cognitive debriefing to determine patient's comprehension of the Portuguese RAID and (ii) cross-cultural validation using Rasch analysis. Construct validity was determined by fit to the model, invariance culture (compared with France and UK datasets) and evidence of convergent and divergent validity. RESULTS: Patients' input (n = 38) led to minor changes in the phrasing of two items to ensure conceptual equivalence between the Portuguese and the original RAID. In Rasch analysis (n = 288), two items 'Sleep' and 'Physical well-being' in the Portuguese dataset did not adequately fit the model specifications, suggesting multidimensionality (sleep-not necessarily associated with RA) and redundancy (physical well-being overlapping with functional disability). Despite the imperfections, the scale had high internal consistency, evidence of convergent and divergent validity and invariance to culture (compared to France n = 195 and UK n = 205 datasets). The scale was well targeted for patients with different levels of disease impact. CONCLUSIONS: The RAID has been successfully adapted into Portuguese and it can be used with confidence in clinical practice. Further research will be required to ensure it captures the full range of sleep problems in RA. Meanwhile, data across the three countries (Portugal, France and the UK) are comparable except for the two items (sleep and physical well-being).
30590949 IL-37 gene variant (rs3811047): A marker of disease activity in rheumatoid arthritis: A pi 2018 Dec BACKGROUND: Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Unraveling genetic determinants causing the disease would pave the road towards early detection and precise medicine. Interleukin 37 (IL-37), a natural inhibitor of innate immunity, was shown to be a key modulator in RA. Plasma levels were deregulated and correlated with disease activity. Therefore, we hypothesized the IL-37 gene variants could influence the clinical characteristics of RA patients. OBJECTIVE: This is a pilot study to assess the association of rs3811047 variant of IL-37 gene with RA development and disease activity in an Egyptian population. METHODS: A total of 100 individuals (50 RA patients and 50 healthy individuals) were enrolled in the study. Disease activity score of 28 joints (DAS28) was estimated for RA patients. Genotyping was performed using Real-Time PCR technology. RESULTS: There was no statistically significant association between genotype frequencies of rs3811047 and RA risk. However, there was a significant relationship between the studied single nucleotide polymorphism (SNP) and disease activity. Patients carrying the GG genotype had higher DAS28 score than patients with AA or AG genotypes (p = .041). CONCLUSION: IL-37 gene rs3811047 SNP was associated with more severe RA disease activity in the current population. Larger epidemiological study is warranted to validate our results.