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32852109 Improvements in Fatigue Lag Behind Disease Remission in Early Rheumatoid Arthritis: Result 2021 Jan OBJECTIVE: To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA). METHODS: Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared. RESULTS: Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months. CONCLUSION: Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time.
34545450 Systemic inflammatory responses after orthopedic surgery in patients with rheumatoid arthr 2021 Dec OBJECTIVE: To investigate the acute phase response to surgical stress in patients with rheumatoid arthritis (RA) treated with tofacitinib, a Janus kinase (JAK) inhibitor. METHODS: A retrospective matched pair analysis of 34 patients treated with tofacitinib and 34 patients treated with conventional disease-modifying anti-rheumatic drugs (csDMARDs) was performed. Patients were matched for age, sex, and type of surgery; body temperature, C-reactive protein (CRP) level, and white blood cell (WBC) count, neutrophil count, and lymphocyte count were compared between the tofacitinib and csDMARDs groups within 2 weeks after orthopedic surgery. Postoperative complications within 90 days were also assessed. RESULTS: No surgical site infection or delayed wound healing was observed in the tofacitinib group; whereas, one case of superficial infection was noted in the csDMARDs group. A similar postoperative increase in body temperature and CRP level was observed in both the groups. Postoperatively, the tofacitinib group showed an increase in WBC and neutrophils counts and a decrease in lymphocyte count, unlike the csDMARDs group. In contrast to two patients (2.6%) in the csDMARDs group, seven patients (20.6%) in the tofacitinib group had lymphocyte counts below 500 cells/μL within 2 weeks postoperatively. CONCLUSION: Tofacitinib did not suppress postoperative increase in body temperature and CRP level. Because of the postoperative decrease in lymphocyte count in patients treated with tofacitinib, the timing for resuming tofacitinib treatment after surgery should be carefully considered. Key Points • This study is the first to report the complications and systemic inflammatory responses after orthopedic surgery in patients treated with tofacitinib in comparison with matched pairs treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) • While tofacitinib does not suppress postoperative increase in body temperature and CRP level, the postoperative decrease in lymphocyte count in patients treated with tofacitinib is significant compared with patients treated with csDMARDs • Attention should be paid to a reduced lymphocyte count when to resume tofacitinib after surgery.
33984273 A phingerprint for rheumatoid arthritis development? 2021 May 12 The human gut virome has become increasingly associated with health and disease. In this issue of Cell Host & Microbe, Mangalea et al. (2021) find differences in viromes of individuals at risk for rheumatoid arthritis (RA), suggesting that phages may play a role in RA and provide a path for biomarker development.
32058654 Defining Pain That Does Not Interfere With Activities Among Rheumatoid Arthritis Patients. 2021 May OBJECTIVE: The objectives of this study were to: 1) characterize the distribution of noninterfering pain (defined as the pain intensity level at which individuals can function without interference) across different aspects of life among patients with rheumatoid arthritis (RA), and 2) identify clinical characteristics associated with differing levels of noninterfering pain. METHODS: Patients with RA in FORWARD, The National Databank for Rheumatic Diseases completed 8 items from the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference item bank that asked about interference with activities. If subjects reported pain interference, they were asked, "At what level would pain no longer interfere with this activity?" on a scale of 0 to 10. Subjects were also asked, "At what level of pain would you be able to do everything you want to do?" Multiple linear regression analyses examined associations between clinical characteristics and noninterfering pain. RESULTS: A total of 3,949 patients with RA completed the questionnaires. Pain interference was most common for daily activities and least common for ability to concentrate. The mean ± SD level at which pain no longer interfered with activities ranged from 2.7 ± 2.1 for ability to fall/stay asleep to 3.1 ± 2.0 for social activities. Overall, the mean ± SD threshold for noninterfering pain was 2.8 ± 1.9. The mean ± SD level of pain at which patients could do everything they wanted to do was 2.3 ± 1.9. More severe pain intensity was associated with higher noninterfering pain. CONCLUSION: The mean pain level that did not interfere with activities was 3. High pain intensity was associated with high self-reported noninterfering pain.
34509462 Angiogenesis as a potential treatment strategy for rheumatoid arthritis. 2021 Nov 5 Angiogenesis is an early and key event in the pathogenesis of rheumatoid arthritis (RA) and is crucial for the proliferation of synovial tissue and the formation of pannus. This process is regulated by both angiogenesis-stimulating factors and angiogenesis inhibitors, the basis for the "on-off hypothesis of angiogenesis." In RA, inflammation, immune imbalance, and hypoxia can further turn on the switch for blood vessel formation and induce angiogenesis. The new vasculature can recruit white blood cells, induce immune imbalance, and aggravate inflammation. At the same time, it also can provide oxygen and nutrients for the proliferating synovial tissue, which can accelerate the process of RA. The current therapies for RA mainly target the inflammatory response of autoimmune activation. Although these therapies have been greatly improved, there are still many patients whose RA is difficult to treat or who do not fully respond to treatment. Therefore, new innovative therapies are still urgently needed. This review covers the mechanism of synovial angiogenesis in RA, including the detailed process of angiogenesis and the relationship between inflammation, immune imbalance, hypoxia, and synovial angiogenesis, respectively. At the same time, in the context of the development of angiogenesis inhibition therapy for cancer, we also discuss similar treatment strategies for RA, especially the combination of targeted angiogenesis inhibition therapy and immunotherapy.
34450504 Outcomes of COVID-19 in patients with rheumatoid arthritis: A multicenter research network 2021 Oct OBJECTIVES: To investigate outcomes of Coronavirus Disease-2019 (COVID-19) in patients with rheumatoid arthritis (RA) as compared to the general population. Additionally, outcomes were explored among RA patients stratified by sex, race, and medications use through sub-cohort analyses. METHODS: This comparative cohort study used a US multicenter research network (TriNetX) to extract data on all adult RA patients who were diagnosed with COVID-19, and adults without RA who were diagnosed with COVID-19 (comparative cohort) anytime from January 20, 2020 to April 11, 2021. COVID-19 outcomes were assessed within 30 days after its diagnosis. Baseline characteristics that included demographics and comorbidities were controlled in propensity score matching. RESULTS: A total of 9730 RA patients with COVID-19 and 656,979 non-RA with COVID-19 were identified. Before matching, the risk of all outcomes including mortality (RR: 2.11, 95%CI: 1.90 to 2.34), hospitalization (RR: 1.60, 1.55 to 1.66), intensive care unit-ICU admission (RR: 1.86, 1.71 to 2.05), mechanical ventilation (RR: 1.62, 1.44 to 1.82), severe COVID-19 (RR: 1.89, 1.74 to 2.06), acute kidney injury (RR: 2.13, 1.99 to 2.29), kidney replacement therapy/hemodialysis (RR: 1.40, 1.03 to 1.89), acute respiratory distress syndrome-ARDS (RR: 1.76, 1.53 to 2.02), ischemic stroke (RR: 2.62, 2.24 to 3.07), venous thromboembolism-VTE (RR: 2.30, 2.07 to 2.56), and sepsis (RR: 1.97, 1.81 to 2.13) was higher in RA compared to non-RA. After matching, the risks did not differ in both cohorts except for VTE (RR: 1.18, 1.01 to 1.38) and sepsis (RR: 1.27, 1.12 to 1.43), which were higher in the RA cohort. Male sex, black race, and glucocorticoid use increased the risk of adverse outcomes. The risk of hospitalization was higher in rituximab or interleukin 6 inhibitors (IL-6i) users compared to tumor necrosis factor inhibitors (TNFi) users, with no significant difference between Janus kinase inhibitors (JAKi) or abatacept users and TNFi users. CONCLUSION: This large cohort study of RA-COVID-19 found that the risk of all outcomes was higher in the RA compared to the non-RA cohort before matching, with no difference in the majority of outcomes after matching, implying the risk being attributed to adjusted factors. However, the risk of VTE and sepsis was higher in RA cohort even after matching, indicating RA as an independent risk factor. Male sex, black race, and glucocorticoid use were associated with adverse outcomes in RA with COVID-19. Rituximab or IL-6i users were associated with an increased risk of hospitalization compared to TNFi users.
34421923 PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies 2021 The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.
34462830 Circular RNA circ_0008360 Inhibits the Proliferation, Migration, and Inflammation and Prom 2022 Feb Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of many diseases, including rheumatoid arthritis (RA). However, the functions and molecular mechanism of circ_0008360 in RA remain unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0008360, microRNA-135b-5p (miR-135b-5p), and histone deacetylase 4 (HDAC4). Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to assess cell proliferation, migration, and apoptosis, respectively. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-135b-5p and circ_0008360 or HDAC4 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot assay was used to detect the protein expression of HDAC4 and proliferating cell nuclear antigen (PCNA). The expression of circ_0008360 was downregulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0008360 suppressed the proliferation, migration, and inflammation and promoted apoptosis of RA-FLSs, and circ_0008360 knockdown showed opposite effects. Moreover, miR-135b-5p was a direct target of circ_0008360, and miR-135b-5p could reverse the effects of circ_0008360 on proliferation, migration, inflammation, and apoptosis in RA-FLSs. Furthermore, HDAC4 was a downstream target of miR-135b-5p, and miR-135b-5p accelerated the proliferation, migration, and inflammation and suppressed apoptosis of RA-FLSs by targeting HDAC4. In addition, circ_0008360 positively regulated HDAC4 expression by sponging miR-135b-5p. Circ_0008360 inhibited the proliferation, migration, and inflammation and facilitated apoptosis of RA-FLSs by sponging miR-135b-5p and upregulating HDAC4, providing a potential target for prevention and treatment of RA.
33787418 Clinical management of patients with rheumatoid arthritis during the COVID-19 pandemic. 2021 Jun Introduction: Coronavirus disease 2019 (COVID-19) pandemic raises a great challenge in the management of patients with rheumatoid arthritis (RA), which are generally more susceptible to infection events because of the autoimmune condition itself and the treatment with immunomodulatory drugs. The use of disease-modifying anti-rheumatic drugs (DMARDs), including biologics and targeted-synthetic DMARDs, has aroused particular interest because of both their immunosuppressive effects and their hypothetical potential in COVID-19 treatment.Areas covered: For this narrative review, a literature search was conducted between December 2019 and February 2021 on PubMed including epidemiological studies, gathering the main evidence available to date about the impact of COVID-19 on RA patients and the influence of anti-rheumatic drugs on patients' susceptibility to this infection. We also summarize the recommendations from the international guidelines on the management of rheumatic diseases and treatments in this pandemic context, especially focused on RA.Expert opinion: About a year after the outbreak of the pandemic, we are able to answer some of the most relevant questions regarding patients with RA and their management in this pandemic context. Our efforts must now be directed toward consolidating the currently available data with more rigorous studies and facing new issues and challenges including, foremost, vaccination.
33408105 Disease-modifying antirheumatic drugs and organising pneumonia. 2021 Jan 6 Organising pneumonia (OP) in rheumatoid arthritis (RA) may be part of pulmonary manifestation (disease related) or disease-modifying antirheumatic drugs (DMARDs) related. We report a case series of RA patients with DMARDs related OP. A 65-year-old woman developed OP 3 weeks after initiation of methotrexate (MTX). High-resolution CT (HRCT) scan of the thorax revealed bilateral consolidations in the lung bases. She had complete radiological resolution 6 months after corticosteroid therapy with cessation of MTX. The second case was of a 60-year-old woman on MTX with recent addition of leflunomide due to flare of RA. She developed worsening cough 4 months later and HRCT scan revealed consolidation in the left upper lobe with biopsy proven OP. She responded within 6 months of corticosteroid therapy with clinical and radiological resolution. This case series highlights that OP may developed with low-dose MTX (as early as 3 weeks) and leflunomide and the diagnosis requires a high index of suspicion.
34702319 Increased radiographic progression of distal hand osteoarthritis occurring during biologic 2021 Oct 26 OBJECTIVES: A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. METHODS: Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. RESULTS: Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07-1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96-1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66-1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33-0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11-2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. CONCLUSIONS: These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.
33829452 JKAP correlates with lower disease risk and inflammation, and its increment during etanerc 2021 Mar OBJECTIVE: This study aimed to investigate the correlation of Jun N-terminal kinase pathway associated phosphatase (JKAP) with disease risk and inflammation, also to explore the association of its longitudinal change with etanercept (ETN) treatment efficiency in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: A total of 107 active RA patients about to receive ETN treatment and 60 healthy controls (HCs) were enrolled in this study. Serum JKAP level was measured by enzyme-linked immunosorbent assay in RA patients (at week 0 (W0), W6, W12, and W24) and HCs (at recruitment). RA patients were categorized into W24 response patients and W24 non-response patients, or W24 remission patients and W24 non-remission patients, respectively, according to clinical response status or remission status at W24. RESULTS: JKAP level was reduced in RA patients compared with HCs. In RA patients, decreased baseline JKAP was correlated with elevated C-reaction protein level and anti-citrullinated protein antibodies positive status. Moreover, JKAP level was increased during ETN treatment. Subgroup analyses revealed that JKAP level during ETN therapy was increased in W24 response patients, while no difference was discovered in JKAP level among different time points in W24 non-response patients. Meanwhile, JKAP level during ETN treatment was elevated in both W24 remission patients and W24 non-remission patients, however, its increment was more evident in W24 remission patients. CONCLUSIONS: JKAP correlates with reduced disease risk and inflammation, and its increment during ETN treatment associates with commendable treatment efficiency in RA patients.
34281633 Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparis 2021 Sep OBJECTIVE: The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab as monotherapy were assessed and compared with those of adalimumab in patients with rheumatoid arthritis (RA) who were intolerant to or responded inadequately to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab, and adalimumab in RA patients who are intolerant to or show an inadequate response to MTX. RESULTS: Three RCTs comprising 1,066 patients met the inclusion criteria. Tocilizumab 8 mg monotherapy was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ACR20 response rate. Compared with adalimumab, tocilizumab, and sarilumab as monotherapy showed significantly higher ACR20 response rates. Ranking probability based on SUCRA indicated that tocilizumab 8 mg had the highest probability of being the best choice for achieving ACR20 response rate, followed by sarilumab 200 mg, adalimumab 40 mg, and sirukumab 50 mg. Moreover, the ACR50 response rate showed a similar distribution pattern to that of ACR20. Regarding adverse events, the ranking probability based on SUCRA indicated that sarilumab 200 mg was possibly the safest, followed by adalimumab 40 mg, tocilizumab 8 mg, and sirukumab 50 mg. However, the number of patients who experienced serious adverse events did not differ significantly between these biologics. CONCLUSION: Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance.
33750008 Inclusion of Synovial Tissue-Derived Characteristics in a Nomogram for the Prediction of T 2021 Sep OBJECTIVE: This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients. METHODS: The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. RESULTS: The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28. CONCLUSION: The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.
34882373 Krebs von den Lungen-6, a promising marker in evaluating the severity of interstitial lung 2021 Oct Krebs von den Lungen-6 (KL-6) is one of the mucins associated with interstitial lung disease. We aimed to assess the value of KL-6 as a marker for detecting the presence of interstitial lung disease in Egyptian rheumatoid arthritis patients and to evaluate its ability to assess severity in different grades of interstitial lung disease. The study included 89 rheumatoid arthritis patients; 64 patients with interstitial lung disease and 25 patients without interstitial lung disease. Serum levels of KL-6 were assessed using enzyme linked immunosorbent assay. Levels of KL-6 were higher in patients with interstitial lung disease compared to patients without interstitial lung disease (P< 0.001). KL-6 levels were significantly higher in grade 4 patients than those in grades 1 and 2. Also, KL-6 levels were significantly higher in grade 3 patients than those in grades 1 and 2. Kl-6 levels were also higher in grade 2 patients compared to grade 1 patients. Finally, no difference was observed between grade 4 patients and grade 3 patients. KL-6 levels were significantly higher in usual interstitial pneumonia pattern compared other patterns (P=0.015). In conclusion, KL-6 is a potential circulating biomarker that may have a substantial role in detecting the presence and evaluating the severity of interstitial lung disease among rheumatoid arthritis patients.
34391020 Mutual-reinforcing sonodynamic therapy against Rheumatoid Arthritis based on sparfloxacin 2021 Sep Rheumatoid arthritis (RA) is an autoimmune disease associated with synovitis and cartilage destruction. Ultrasound (US)-driven sonodynamic therapy (SDT) possess a good application prospect in RA therapy because of its non-invasiveness and strong tissue penetration capabilities, which can kill activated synovial inflammatory cells. Nevertheless, the tiny accumulation of sonosensitizers in the joints and the hypoxic synovial microenvironment severely limit the therapeutic effect of SDT. Hence, we developed a sonosensitizer spafloxacin (SPX) doped and human serum albumin (HSA) loaded concave-cubic rhodium (Rh) nanozyme (Rh/SPX-HSA) to realize mutual-reinforcing SDT during ultrasonic activation. On the one hand, SPX would cause mitochondrial dysfunction by inducing excessive reactive oxygen species (ROS) production, thus suppressing fibroblast-like synoviocyte (FLS) under US conditions. On the other hand, concave-cubic rhodium was utilized as a nanozyme with endogenous peroxidase (POD) and catalase (CAT)-like enzyme activities, which not only relieved the hypoxia of the joint to resist angiogenesis, but also enormously ascended the SDT efficacy by rising (1)O(2) levels. Interestingly, the activity of nanozymes was also improved by the ultrasonic cavitation effect, thereby realizing mutual-reinforcing SDT. Overall, our strategy provided Rh-based to achieve effective SDT under hypoxic microenvironment, which offered a promising prospect for highly efficient treatment of RA.
32100969 "The Financial Impact Is Depressing and Anxiety Inducing": A Qualitative Exploration of th 2021 May OBJECTIVE: The financial experience faced by working-age people with arthritis includes living below the poverty line for many. Financial distress among people with arthritis is known to contribute to poorer health outcomes, including high psychological distress and more severe pain. Despite the demonstrated societal cost of arthritis care and management, the personal costs borne by the individual are not well understood. The aim of this study was to explore the perceived financial impacts of living with arthritis among younger adults (defined as those ages 18-50 years). METHODS: A qualitative descriptive study design was used. Participants with inflammatory arthritis or osteoarthritis were recruited from the community, including urban and rural settings. An interview schedule was developed, informed by existing literature, which was piloted prior to data collection. Deductive and inductive coding techniques were used to identify financial-related themes arising from the data. RESULTS: Semistructured interviews were conducted with 21 adults (90% female) with a mix of arthritis conditions, including rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. Four themes were identified: direct arthritis-attributable medical costs, indirect arthritis-attributable costs, insurance and pension costs, and broader financial impacts on the family. Nonsubsidized costs were frequently referenced by participants as burdensome and existed even within the publicly funded Australian health care system. CONCLUSION: Adults with arthritis experience significant arthritis-attributable financial burden and related distress. Financial concerns should be actively identified and considered within shared clinical decision-making to provide more patient-centered care for these individuals.
34846554 Participation in physical activity decreased more in people with rheumatoid arthritis than 2022 Feb The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.
34433518 The impact of medical therapies and factors related to treatment procedures in women with 2021 Dec OBJECTIVE: To examine whether medications used to treat rheumatoid arthritis (RA)/chronic inflammatory bowel disease (IBD), or factors related to the assisted reproductive technology (ART) procedures, impact the success of ART. In women with RA/IBD, initial studies have shown a reduced chance of a live-born child after ART. DESIGN: Cohort study. SETTING: Nationwide Danish health registries. PATIENTS: All Danish women with a fresh embryo transfer from January 1, 2006, through 2018. The cohorts comprised 1,824 embryo transfers in women with RA/IBD and 97,191 embryo transfers in women without RA/IBD. INTERVENTIONS: Observational, noninterventional study. MAIN OUTCOME MEASURE: Live birth per fresh embryo transfer. RESULTS: The chance of a live birth in women with RA/IBD receiving ART, compared with other women receiving ART, had an adjusted odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.68-0.91). Prescribed corticosteroids before embryo transfer were positively associated with a live-born child (adjusted OR, 1.21; 95% CI, 1.12-1.31), while the use of antiinflammatory/immunosuppressive agents did not have significant importance. Intracytoplasmic sperm injection was associated with a reduced chance (adjusted OR, 0.94; 95% CI, 0.90-0.97). Type of hormone treatment protocol did not have significant importance, and transfer at the blastocyst stage was positively associated with a live-born child (adjusted OR, 1.54; 95% CI, 1.46-1.62). CONCLUSIONS: In women with RA and/or IBD, prescribed corticosteroid before embryo transfer and embryo transfer at the blastocyst stage were associated with successful ART. Intracytoplasmic sperm injection was associated with a slightly reduced chance. Antiinflammatory/immunosuppressive agents and type of hormone protocols did not have significant importance.
34218340 Modification of Gut Microbiota in Inflammatory Arthritis: Highlights and Future Challenges 2021 Jul 3 PURPOSE OF REVIEW: This Review evaluates the available information on the modification of the microbiota by diet, prebiotics, probiotics, or drugs and its association with the severity of arthritis in animals and humans and highlights how this modulation could have therapeutic applications in RA. RECENT FINDINGS: The gut microbiota and microbiota-derived metabolites play a role in developing rheumatoid arthritis (RA) in animals and humans, making the intestinal microbiota an exciting novel approach to suppress autoimmunity. Studies in animal models of RA show that it is possible to modify the intestinal microbiota with drugs, natural products, diet, probiotics, and prebiotics. Furthermore, these changes showed beneficial effects on symptom relief in animal models of RA and that these effects were associated with modulation of the immune response. Therapies that modify the gut microbiota would significantly impact the preclinical stage of arthritis, based on the fact that dysbiosis occurs before clinical arthritis. The effects of interventions to modulate the microbiota could not reverse arthritis. Furthermore, the therapies modulating therapies in controlling symptoms were limited once arthritis developed. The results obtained in the study of acarbose, probiotics, and prebiotics suggest that these interventions may decrease the disease's incidence rather than treat or cure it.