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ID PMID Title PublicationDate abstract
35058618 Joint-on-chip platforms: entering a new era of in vitro models for arthritis. 2022 Apr Arthritis affects millions of people worldwide. With only a few disease-modifying drugs available for treatment of rheumatoid arthritis and none for osteoarthritis, a clear need exists for new treatment options. Current disease models used for drug screening and development suffer from several disadvantages and, most importantly, do not accurately emulate all facets of human joint diseases. A humanized joint-on-chip (JoC) model or platform could revolutionize research and drug development in rheumatic diseases. A JoC model is a multi-organ-on-chip platform that incorporates a range of engineered features to emulate essential aspects and functions of the human joint and faithfully recapitulates the joint's physiological responses. In this Review, we propose an architecture for such a JoC platform, discuss the status of the engineering of individual joint tissues and the efforts to combine them in a functional JoC model and identify unresolved issues and challenges in constructing an accurate, physiologically relevant system. The goal is to ultimately obtain a reliable and ready-to-use humanized model of the joint for studying the pathophysiology of rheumatic diseases and screening drugs for treatment of these conditions.
33890628 The sFlt-1 to PlGF ratio in pregnant women with rheumatoid arthritis: impact of disease ac 2022 Feb 2 OBJECTIVES: An elevated sFlt-1/PlGF ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with RA. We explored whether the sFlt-1/PlGFratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since SSZ has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether SSZ could affect sFlt-1 or PlGF levels. METHODS: Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21-42 years, were included, with a median gestational age of 30 + 3 weeks. RESULTS: No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (P = 0.07 and P = 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r = -0.01 and r = -0.05, respectively). Four (2%) women with a sFlt-1/PlGF ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. SSZ users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-SSZ users (n = 164, P = 0.91 and P = 0.11). CONCLUSION: Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, SSZ use did not affect sFlt-1 or PlGF levels in this population.
35084601 Association between depression, anxiety, chronic pain, or opioid use and tumor necrosis fa 2022 May INTRODUCTION: Depression, anxiety, and chronic pain are common comorbidities in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and may substantially impact patient outcomes. We aimed to determine whether these comorbidities were associated with earlier TNF-inhibitor (TNFi) discontinuation. METHODS: This retrospective cohort study using Optum's de-identified Clinformatics® Data Mart Database 2000-2014 identified patients with RA, PsA, and AS initiating a first TNFi. Depression/anxiety, chronic pain, and opioid use were identified using diagnosis codes and prescription fill data. Cox proportional hazards models were used to compare time to medication discontinuation in patients with or without each of these risk factors and to assess the additive effect of having multiple risk factors. RESULTS: Among 33,744 patients initiating a TNFi (23,888 RA, 6443 PsA, 3413 AS), depression/anxiety, chronic pain, and opioid use were common, with ≥ 1 risk factor in 48.1%, 42.5%, and 55.4% of patients with RA, PsA, and AS respectively. Each risk factor individually was associated with a 5-7-month lower median treatment persistence in each disease (all p < 0.001). Presence of multiple risk factors had an additive effect on time to discontinuation with HR (95% CI) 1.19 (1.14-1.24), 1.41 (1.33-1.49), and 1.47 (1.43-1.73) for 1, 2, or 3 risk factors respectively in RA. Findings were similar in PsA and AS. CONCLUSIONS: Depression, anxiety, chronic pain, and opioid use are common in inflammatory arthritis and associated with earlier TNFi discontinuation. Recognizing and managing these risk factors may improve treatment persistence, patient outcomes, and cost of care. Key Points • Depression, anxiety, chronic pain, and opioid use are common in patients with inflammatory arthritis. • In patients initiating treatment with a TNF-inhibitor, depression, anxiety, chronic pain, or recent opioid use are associated with sooner discontinuation of TNFi therapy. • Patients with multiple of these risk factors are even more likely to discontinue therapy sooner.
35163173 Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumato 2022 Jan 23 Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.
35140294 Impact of lifestyle and comorbidities on seropositive rheumatoid arthritis risk from Korea 2022 Feb 9 Rheumatoid arthritis (RA) is a systemic inflammatory arthritis in which primary prevention is key. However, the impact of lifestyle and comorbidities on RA development is unknown. Data from the Korean National Health Insurance Service (NHIS)-national sample cohort from 2002 to 2016 were used. At baseline, demographic characteristics, socioeconomic status, type of residential area, lifestyle behaviours (including exercise), and comorbidities (including the Charlson Comorbidity Index, CCI) were included. Cox regression analysis and Kaplan-Meier curves were used to evaluate the impact of lifestyle and comorbidities on seropositive RA occurrence. A total of 517,053 participants were included in the analysis for seropositive RA occurrence. Mean follow up duration was 71.5 and 142.3 person-month for seropositive RA occurrence group and non-occurrence group, respectively. Seropositive RA was diagnosed in 1,948 participants (0.37%) during follow-up. Cox regression analysis revealed that being aged between 40 and 79, a higher CCI, and hyperlipidemia resulted in elevated hazard ratios (HRs) for seropositive RA, whereas male gender, city residence, moderate alcohol consumption, high regular exercise and a BMI between 23 and 34.9 kg/m(2) resulted in lower HRs. Using Korean NHIS data, the present study demonstrates that high-intensity regular physical exercise and moderate alcohol consumption are negatively associated with seropositive RA occurrence, which are modifiable lifestyle habits that might aid the primary prevention of seropositive RA.
34782180 Systematic review of imaging tests to predict the development of rheumatoid arthritis in p 2022 Feb OBJECTIVE: To estimate and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and ultrasound, for the prediction of rheumatoid arthritis (RA) in unclassified arthritis (UA). METHODS: MEDLINE, Embase and BIOSIS were searched from 1987 to May 2019. Studies evaluating any imaging test in participants with UA were eligible. Reference standards were RA classification criteria or methotrexate initiation. Two authors independently extracted data and assessed validity using QUADAS-2. Sensitivities and specificities were calculated for each imaging characteristic and joint area. Summary estimates with 95% confidence intervals (CI) were estimated where possible. RESULTS: Nineteen studies were included; 13 evaluated MRI (n=1,143; 454 with RA) and 6 evaluated ultrasound (n=531; 205 with RA). Studies were limited by unclear recruitment procedures, inclusion of patients with RA at baseline, differential verification, lack of blinding and consensus grading. Study heterogeneity largely precluded meta-analysis, however summary sensitivity and specificity for MRI synovitis in at least one joint were 93% (95% CI 88%, 96%) and 25% (95% CI 13%, 41%) (3 studies). Specificities may be higher for other MRI characteristics but data are limited. Ultrasound results were difficult to synthesise due to different diagnostic thresholds and reference standards. CONCLUSION: The evidence for MRI or ultrasound as single tests for predicting RA in people with UA is heterogeneous and of variable methodological quality. Larger studies using consensus grading and consistently defined RA diagnosis are needed to identify whether combinations of imaging characteristics, either alone or in combination with other clinical findings, can better predict RA in this population.
35357093 The five major autoimmune diseases increase the risk of cancer: epidemiological data from 2022 May BACKGROUND: Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases (AIDs). This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese cohort. METHODS: A total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed-up for 38,726.55 patient-years, including those with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic scleroderma (SSc), and idiopathic inflammatory myositis (IIM). Demographic data, cancer incidence, predilecting sites and cancer onset time were recorded and compared among the five AIDs. RESULTS: Four hundred and thirty (5.3%) patients developed cancer. Their median age was 57.5 years and AID duration was 79.8 months. The estimated total standardized incidence ratio (SIR) of cancer in AIDs patients was 3.37, with the highest SIR observed in IIM (4.31), followed by RA (3.99), SSc (3.77), SS (2.88) and SLE (2.58). The increased SIR of cancers in AID patients showed a female predominance (female vs. male: 3.59 vs. 2.77) and younger patient involvement (age <50 vs. ≥50 years: 4.88 vs. 3.04). Patients with SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder, corpus uteri and cervix uteri. Patients with SS had a significantly high SIR for developing non-Hodgkin's lymphoma. Within 3 years of IIM diagnosis, 74.6% of the patients developed cancer and they had a high risk of ovarian cancer. RA was associated with a wide distribution of scancers, including non-Hodgkin's lymphoma, gynecologic, urinary tract, thyroid gland and lung cancers. SSc patients had increased SIRs for developing cervical uterine, lung, and breast cancers. CONCLUSION: Patients with five major AIDs in China had an increased risk of developing cancer, with a predominance in women and younger patients, although cancer incidence, predilection sites and cancer onset time may vary greatly in each AID entity.
35400371 Perioperative Management of Rheumatic Disease and Therapies. 2022 May Patients with rheumatic disease, including those with systemic lupus erythematous, rheumatoid arthritis, and spondyloarthritis, use total hip and knee arthroplasties at high rates. They represent a particularly vulnerable population in the perioperative setting because of their diseases and the immunosuppressant therapies used to treat them. Careful planning among internists, medical specialists, and the surgical team must therefore occur preoperatively to minimize risks in the postoperative period, particularly infection. Management of immunosuppressant medications, such as conventional synthetic disease-modifying antirheumatic drugs and targeted therapies including biologics, is one avenue by which this infectious risk can be mitigated.
35147259 Pathogenesis of follicular thymic hyperplasia associated with rheumatoid arthritis. 2022 Apr Lymphoproliferative disorders may occur in patients with rheumatoid arthritis (RA) who are treated with methotrexate. However, follicular thymic hyperplasia (FTH) associated with RA (FTH-RA) is generally not considered a lymphoproliferative disorder. To investigate the pathogenesis of FTH-RA, we examined 12 cases of FTH involving thymic enlargement, four of FTH involving RA and eight of FTH involving myasthenia gravis (MG). Increased numbers and larger germinal center (GC) size were observed in FTH-RA group. The percentage of distorted GCs was 13.3% in FTH-RA group and 3.25% in FTH associated with MG (FTH-MG) group. A greater meshwork of follicular dendritic cells was observed in the GCs of FTH-RA group. Positive indices of CD27(+) cells and PD-1(+) cells per GC in FTH-RA group were significantly higher than those in FTH-MG group, though positive indices of CD68(+) cells and CD163(+) cells were similar. Myoid cell proliferation, as evaluated by α-SMA, tenascin-C, and l-caldesmon expression, was significantly increased in the FTH-RA group compared with the FTH-MG group. These results suggest that FTH should be considered in patients with RA treated with methotrexate. The pathogenesis of FTH-RA includes GC expansion and increased numbers of memory B cells, follicular helper T cells, and myoid cells, indicating humoral immunity activation.
34370130 Real-world evaluation of effectiveness, persistence, and usage patterns of monotherapy and 2022 Jan OBJECTIVE: This study aimed to describe the real-world effectiveness and treatment persistence among patients with rheumatoid arthritis treated with monotherapy and combination therapy tofacitinib and biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This was a post hoc analysis of a retrospective, non-interventional study that extracted data for patients treated with tofacitinib or bDMARDs from the Australian OPAL dataset between March 2015 and September 2018. Monotherapy tofacitinib and bDMARDs and combination therapy tofactinib and bDMARDs were propensity score matched and treatment effectiveness and persistence of the groups were evaluated. RESULTS: In the bDMARD and tofacitinib monotherapy and combination therapy matched populations there were 1300 bDMARD initiators (n = 564 monotherapy) and 650 tofacitinib initiators (n = 282 monotherapy). In the bDMARD and tofacitinib monotherapy matched groups, 62.9% and 66.7% were in DAS-28 CRP disease remission after 18 months of treatment, respectively. In the combination therapy bDMARD and tofacitinib groups, 50% and 58.9% were in DAS-28 CRP disease remission after 18 months, respectively. The median treatment persistence was similar between the monotherapy bDMARD and tofacitinib treatment groups (36.7 months (95% CI 27.4 to "not reached') and 34.2 months (95%CI 30.3 to "not reached") respectively) as well as the combination therapy bDMARD and tofacitinib groups (32.2 months (95% CI 25.7 to 34.4) and 32.7 months (95%CI 28.7 to "not reached", respectively). CONCLUSIONS: Patients receiving combination therapy with tofacitinib or bDMARDs had higher disease activity scores at index than patients receiving monotherapy. Monotherapy with tofacitinib or bDMARDs, and combination therapy with tofacitinib or bDMARDs demonstrated similar treatment effectiveness and persistence, respectively. Key Points • This study provides real-world evidence regarding effectiveness, treatment persistence, and treatment patterns, among patients with rheumatoid arthritis (RA) treated with monotherapy or combination therapy tofacitinib. • The study suggests that monotherapy and combination therapy tofacitinib is an effective intervention in RA with persistence and effectiveness comparable to bDMARDs.
34505214 Sustainable positive effects of Ramadan intermittent fasting in rheumatoid arthritis. 2022 Feb The short-term positive effects of intermittent fasting during the month of Ramadan on rheumatic inflammatory diseases have been previously evaluated. The objective of this study was to assess the sustainability of these effects on rheumatoid arthritis (RA) activity. This prospective study included 35 patients with RA, who observed fasting during Ramadan 2019. The disease activity was assessed and compared between three time points: T1 (6 months before the beginning of Ramadan), T2 (during the month between the 7th day of fasting and the 7th day after Ramadan), and T3 (averagely 3.4 months after fasting). The disease activity score 28 (DAS28) was used to evaluate the disease activity. After a significant decrease of all disease activity parameters between T1 and T2, a gradual increase of clinical and biological outcomes was seen between T2 and T3. Except for CRP, which was significantly higher at T3 (p = 0.02), the changes of the other disease activity parameters were not statistically significant. By reference to baseline data (T1), the decrease of ESR, DAS28 CRP, and DAS28 ESR induced after Ramadan fast was maintained until T3, with statistically significant differences. We can therefore conclude that this study has been conducted at the beginning of the fading-out of the effects of Ramadan fast, and that the duration of 3 months may be the recommended interval between fasting periods to maintain the positive effects of intermittent fasting on RA activity. Key Points • Intermittent fasting can induce a rapid improvement of rheumatoid arthritis activity. • The positive effects of this model of fasting can last up to 3 months. • The recommended interval between fasting periods may be estimated at 3 months.
33617382 Patient satisfaction with total joint replacement surgery for rheumatoid arthritis: a ques 2022 Jan 5 OBJECTIVE: This study aimed to evaluate satisfaction with total joint replacement (TJR) surgery among patients with rheumatoid arthritis (RA). METHODS: We mailed questionnaires to randomly selected members of the Japan Rheumatism Friendship Association, stratified by age and prefecture, throughout Japan. The questionnaire collected demographic and clinical characteristics as well as patients' satisfaction with TJR and their current therapy. RESULTS: Of the 1156 patients who returned the questionnaire, 339 (29.3%) responded that they had had TJR of any type. The mean age was 66.6 years, and 94.4% were women. The mean time period from the hip and knee TJR was 14-15 years. Over half of the patients who had had TJR were satisfied with the results, especially those who had had hip (89.6%) and knee TJR (87.3%), who reported a high level of satisfaction. Multivariable linear regression analysis revealed that, in patients with knee TJR, satisfaction with current therapy was significantly related to whether they were satisfied with the results of the surgery. CONCLUSION: Most patients with RA who had undergone TJR were satisfied with the results even after a long period of time, and their level of satisfaction was associated with their satisfaction with current therapy.
34486098 Adaptation of a Shared Decision-Making Tool for Early Rheumatoid Arthritis Treatment Decis 2022 Mar BACKGROUND: Patient decision aids (PtDAs) enable shared decision-making between patients and healthcare providers. Adaptations to PtDAs for use with populations facing inequities in healthcare can improve the relevancy of information presented, incorporate appropriate cultural context, and address health literacy concerns. Our objective was to adapt the Early RA (rheumatoid arthritis) PtDA for use with Canadian Indigenous patients. METHODS: The Early RA PtDA was modified through an iterative process using data obtained from semi-structured interviews of two sequential cohorts of Indigenous patients with RA. Interview data were analyzed using thematic analysis. RESULTS: Seven participants provided initial feedback on the existing PtDA. The modifications they suggested were made and shared with another nine participants to confirm acceptability and provide further feedback. The first cohort suggested revisions to clarify medical and cost coverage information, include Indigenous traditional healing practice options, simplify text, and include Indigenous images and colors aligned with Canadian Indigenous community representation. Additional revisions were suggested by the second cohort to increase the legibility of the text, insert more Indigenous imagery, address formulary coverage for non-status First Nations patients, and include information about lifestyle factors in managing RA. CONCLUSION: Incorporating Indigenous-specific adaptations in the design of PtDAs may increase use and relevancy to support engagement in treatment decisions, thereby supporting health-equity oriented health service interventions. Indigenous patient-specific evidence and translation of key words into the end-users' Indigenous languages should be included for implementation of the PtDA.
35083555 Histone methyltransferase EZH2 in proliferation, invasion, and migration of fibroblast-lik 2022 Mar OBJECTIVE: Rheumatoid arthritis (RA) may lead to irreversible joint damage. The role of histone modifications in RA has been emphasized. This study investigated the effect of histone methyltransferase EZH2 on fibroblast-like synoviocytes (FLSs) in RA. MATERIALS AND METHODS: Synovial tissues were collected from RA patients and non-RA patients (NC). RA-FLSs and NC-FLSs were isolated and identified using flow cytometry. EZH2 expression in synovial tissues and FLSs was detected using RT-qPCR and Western blot. The proliferation, migration, and invasion of RA-FLSs and NC-FLSs were measured using MTT, EdU, and Transwell assays. The binding of EZH2, H3K27me3, and miR-22-3p was analyzed using ChIP assay. The targeting relationship between miR-22-3p and CYR61 was verified using dual-luciferase assay. miR-22-3p and CYR61 expressions were detected using RT-qPCR. CYR61 and H3K27me3 levels were detected using Western blot. Functional rescue experiments were performed to verify the effect of miR-22-3p or CYR61 on RA-FLSs. RESULTS: EZH2 was highly expressed in synovial tissues and FLSs from RA patients. The proliferation, migration, and invasion ability of RA-FLSs was stronger than that of NC-FLSs. Downregulation of EZH2 repressed proliferation, migration, and invasion of RA-FLSs. EZH2 inhibited miR-22-3p expression by binding to the miR-22-3p promoter and increasing H3K27me3 methylation level, and thereby upregulated CYR61 expression. Downregulation of miR-22-3p or overexpression of CYR61 annulled the inhibitory effect of EZH2 silencing on RA-FLS proliferation, migration, and invasion. CONCLUSION: EZH2 bound to the miR-22-3p promoter and inhibited miR-22-3p expression by upregulating H3K27me3 level, thereby promoting CYR61 expression and inducing the proliferation, migration, and invasion of RA-FLSs.
35443427 A Study of Pulmonary Function Tests in Patients with Rheumatoid Arthritis and its Associat 2022 Apr Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology marked by a symmetrical peripheral polyarthritis. Because it is a systemic disease RA may result in a variety of extra articular manifestations, Pulmonary involvement is a well known extra-articular manifestation of RA which can have myriad presentations and might be the second cause of death after infection. Pulmonary function test(PFTs) are widely used to provide objective measure of lung function for detecting and quantifying impairment of pulmonary function in patients with cardiopulmonary diseases. Although lung disease secondary to pulmonary infection and/or drug toxicity are frequent complications, lung disease directly associated with the underlying RA is more common. Lung involvement in RA carries a worse prognosis. The early recognition of changes in PFT may be used as early marker of pulmonary involvement and help in limiting the mortality and morbidity caused by the disease. Hence need for the study. MATERIAL: Descriptive cross sectional study conducted on 100 cases. INCLUSION CRITERIA: Patients Aged 18-60 years diagnosed with RA according to American college of Rheumatology-European league against rheumatism classification criteria. EXCLUSION CRITERIA: Known smokers, Presence of prior pulmonary disease, Known case of other Collagen vascular diseases and History of pulmonary infection in the last 3 months. Disease activity assessed by both DAS28 and CDAI score. OBSERVATION: Mean age of cases was 43.57 years with 21% males and 79% females. 96% cases had normal FEV1/ FVC ratio with mean DAS28 of 5.12±0.8 and 4% cases had mild obstruction with mean DAS28 in mild restriction being 6.2±0.588. There was statistically significant difference in DAS28 in cases having mild restriction compared to normal cases (P-value=0.0066). Here, we also found that as severity of restrictive pattern increases there was no significant effect on DAS score (P-value=0.3221). But duration of disease and duration of methotrexate use increases as severity of restrictive pattern increases (P-value <0.0001). CONCLUSION: we conclude from our study that there was predominant prevalence of restrictive pattern of PFT in the patients with RA, pulmonary involvement had significant association with duration of disease and duration of methotrexate use, on the contrary disease activity does not have much influence on pulmonary involvement in the diseased individual. Hence PFT alone can't be used as lone modality for early detection of pulmonary involvement in rheumatoid arthritis, additional implementation of DLCO along with spirometry can be tried to assess early involvement of respiratory membrane.
34382090 Prophylaxis against pneumocystis pneumonia in rheumatoid arthritis patients treated with b 2022 May 5 OBJECTIVES: The use of biologic and targeted synthetic (b/ts) DMARDs in the treatment of RA is increasing. Therefore, prevention of b/tsDMARDs-induced infection is important. Here we describe a prophylaxis protocol for preventing pneumocystis pneumonia (PCP) in RA patients treated with b/tsDMARDs. METHODS: The study subjects were 3787 RA patients from the FIRST registry. They were divided into cohort 1 (n = 807, requiring prophylaxis against PCP based on physicians' assessment at the point of new treatment with or switch to b/tsDMARDs) and cohort 2 (n = 2980, receiving strategic PCP prophylaxis). The incidence and risk factors for PCP were investigated. RESULTS: Twenty-six PCP cases were observed throughout the study. After the introduction of strategic PCP prophylaxis, PCP incidence diminished from 0.51/100 person-years (PYs) to 0.21/100 PYs (risk ratio = 0.42). Sulfamethoxazole and trimethoprim in combination (SMX-TMP) showed greater efficacy in the prevention of PCP than pentamidine inhalation (P <0.0001). The prophylaxis rate increased chronologically despite the falls in the average SMX-TMP dose and in the incidence of PCP. Subanalysis of the data for 929 patients from both groups who did not receive prophylaxis showed that old age, high BMI, coexisting lung diseases, low lymphocyte count, and low serum IgG levels increased the risk of PCP development. Development of PCP could be predicted (using an equation based on these variables) in patients not treated with glucocorticoids [area under the curve (AUC) = 0.910)], but less accurately in those on glucocorticoids (AUC = 0.746). CONCLUSIONS: Our study clarified the risk factors for PCP in RA patients on b/tsDMARDs treatment and highlighted and defined the criteria for effective prophylaxis against PCP.
34866331 Gene polymorphisms of SIRT1 in patients with rheumatoid arthritis. 2022 Feb AIM: Previous studies have shown that silent information regulator 1 (SIRT1) expression is elevated in rheumatoid arthritis (RA) patients. However, whether gene polymorphisms in SIRT1 gene associated with RA in a Chinese Han population remains to be discussed. METHOD: In this case-control study, 529 RA patients and 700 healthy controls were selected, and association of 11 SIRT1 gene polymorphisms (rs12415800, rs3740051, rs932658, rs3740053, rs7895833, rs10509291, rs33957861, rs7069102, rs2273773, rs3818292, rs1467568) with RA susceptibility was evaluated. RESULTS: Frequency of GA+GG genotype of rs3740051 in RA patients was significantly lower than that in healthy controls (P = .037). Frequencies of GC and GC+GG genotypes of rs7069102 were significantly lower than those in healthy controls (P = .036, P = .047). Frequencies of GA and GA+GG genotypes of rs1467568 were lower in RA patients as compared to those in healthy controls (P = .011, P = .013). For rs2273773, RA patients who carried the T allele had higher number of tender joints than patients who carried the C allele (P = .033). Other polymorphisms did not associate with RA risk. CONCLUSION: The findings suggest that rs3740051, rs7069102 and rs1467568 variants in SIRT1 gene are related to RA susceptibility in a Chinese Han population.
35356947 The effectiveness and safety of Wu tou decoction on rheumatoid arthritis: A protocol for s 2022 Mar 18 BACKGROUND: Rheumatoid arthritis (RA) is one of the common inflammatory diseases with arthritis due to a malfunction of the immune system. The treatments for RA include surgery, physiotherapy, occupational therapies, and medication. The representative treatment is medication and its usage has improved through several guidelines. However, it has some limitations and occurs adverse effects. Meanwhile, traditional Chinese medicine treatments have been used for RA treatment and Wu tou decoction (WTD) is one of them. Regardless of recent studies about WTD's efficacy on RA, there has been no systematic review on this issue. Therefore, this review will focus on the effectiveness and safety of WTD on RA. METHODS: The search for randomized controlled trial about WTD on RA will be performed using multiple electronic databases, manual searches, and the author's e-mail if necessary. According to predefined criteria, randomized controlled trials will be selected and summarization will be performed by the data on study participants, result measurements, interventions, adverse events, and risk of bias. Disease activity score including effective rate, swollen joint count, tender joint count, morning stiffness will be primary outcome measures while blood test about RA including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factors, and adverse events will be secondary outcome measures. We will perform meta-analysis by using Review Manager software, assess the risk of bias by Cochrane Collaboration "risk of bias" tool, and determine the quality of evidence by Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS: This study we will investigate the clinical evidence of the effectiveness and safety of WTD on RA. CONCLUSION: For the RA patients and clinicians, our study will be informative. It can be also a great help for the researchers and policy makers who concentrates on conservative management for RA. TRIAL REGISTRATION NUMBER: INPLASY; INPLASY202220099.
35152085 Low cumulative disease activity is associated with higher bone mineral density in a majori 2022 Apr OBJECTIVE: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. METHODS: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. RESULTS: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (β= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. CONCLUSION: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.
35421778 The multi-omics and analysis to reveal thermal processing enhanced anti-rheumatoid arthrit 2022 Jun 5 Radix Clematidis (RC) is the roots and rhizomes of Clematis chinensis Osbeck, which has potent effects for expelling wind and dispelling dampness. Processing RC with yellow wine is a traditional processing method. This study aimed to investigate thermal and yellow wine processing influences on potential effective components of RC and its anti-rheumatoid arthritis enhancement mechanisms. Different thermal and wine processing were adopted to get different RC samples. Scanning electron microscope and mercury intrusion porosimetry were used to measure fractal parameters of pore structure. Based on ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), main constituents were identified and quantified. Besides, the correlation between fractal parameters and main constituents was investigated. The anti-rheumatoid arthritis effect was researched in adjuvant-induced arthritis (AIA) rats. The levels of inflammatory cytokine were determined with ELISA kits. Non-targeted serum metabolomics was performed with UPLC-QTOF/MS. 35 compounds were identified in RC, mainly triterpenoid saponins, also including organic acids and lignanoids. The extraction yield of four active triterpenoid saponins significantly increased because looser tissue and wider pore size distribution. Fractal dimension and total surface area significantly increased while total porosity and total volume decreased. In AIA rats, thermal and wine processed RC could markedly inhibit inflammatory cytokines IL-6, IL-1β, TNF-α, and VEGF. Besides, tryptophan and lipid metabolism disorders were ameliorated. Thermal and yellow wine treatments engendered complex pore structure to increase the contents of four active triterpenoid saponins of RC, leading to greater anti-rheumatoid arthritis efficacy.