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33385861 Statins and lower mortality in rheumatic diseases: An effect of immortal time bias? 2021 Feb OBJECTIVE: Randomized controlled trials of the effectiveness of statins on rheumatic disease outcomes have shown limited or no benefit. On the other hand, observational studies have reported remarkable effectiveness of statins at reducing mortality in patients with rheumatic diseases. We evaluated these observational studies for the presence of immortal time bias, which tends to exaggerate the effectiveness of drugs by creating a survival advantage for exposed patients. METHODS: We searched PubMed for observational studies investigating the impact of statins in patients with common rheumatic diseases, including rheumatoid arthritis, osteoarthritis, lupus, ankylosing spondylitis, gout and systemic autoimmune diseases. Studies were included if estimates for all-cause mortality among statin users compared to non-users were reported. We evaluated each study for the presence of immortal time bias and estimated the impact of the bias on the published results. RESULTS: We found eight observational studies investigating the impact of statins on mortality among patients with rheumatic diseases. Four studies were affected by the classical variant of immortal time bias, while the others introduced immortal time into the comparator via random-calendar date assignment. The studies with the classical form of immortal time bias, which tends to exaggerate drug effectiveness, reported protective effects of statins on mortality ranging from 13% to 57% reductions. In contrast, immortal time bias through random-calendar date assignment, which tends to play down the effectiveness by introducing immortal time in the comparator, reported 16% to 37% reductions in mortality. CONCLUSION: Bias in observational studies may explain the discrepancy in findings with randomized controlled trials on the effectiveness of statins in patients with rheumatic diseases. Future observational studies will need to rely on incident and prevalent new-user designs that emulate randomized trials and avoid immortal time bias.
33675969 Short-term outcomes of the Nexel total elbow arthroplasty. 2021 Sep BACKGROUND: Third-generation total elbow arthroplasties (TEAs) have shown better mechanical characteristics than older designs. However, these results remain purely mechanical and lack clinical evidence. The purpose of this study was to evaluate clinical and radiographic outcomes of the new-generation semiconstrained Nexel TEA performed at our center. MATERIALS AND METHODS: Between 2015 and 2017, 9 Nexel TEAs were implanted in 9 patients (mean age 61 years, range 38-71). Indication for further surgery, range of motion, mean Mayo Elbow Performance Score (MEPS), Subjective Elbow Value (SEV), radiolucency lines, outcome measures that included implant survival, complications, and revisions were assessed. RESULTS: The mean follow-up was 28 months (5-46 months). Average range of motion significantly improved from pre- to postoperation, with flexion from 120° (70°-140°) to 140° (130°-155°) and supination from 60° (0°-80°) to 80° (80°). Average MEPS improved from 33 (5-45) to 85 points (30-95). During the study period, 5 elbows (56%) experienced complications and 2 (22%) underwent revision. Aseptic humeral loosening was the main indication for revision. The survivorship rate without revision was 75% at 45 months. CONCLUSIONS: The short-term clinical results of the Nexel TEA are satisfactory. However, an unusually high rate of complications and revisions was observed, mainly at the humeral component. Further research with longer follow-up and more patients included are needed to validate this new prosthesis.
33575154 Evaluating Posterior Cruciate Ligament Integrity in Inflammatory Arthritis Patients Prescr 2021 Feb 5 Introduction Patients with inflammatory arthropathies present a significant challenge to the arthroplasty surgeon when they present with symptomatic degenerative changes of their knee joint. Debate is ongoing regarding the selection of implants for this cohort of patients. There is conflicting evidence for the use of posterior-stabilising (PS) over cruciate-retaining (CR) designs in this cohort. Biologics are licensed for use in moderate-to-severe disease that has not responded to conventional treatment. To our knowledge, there are no studies that have assessed the integrity of the posterior cruciate ligament (PCL) on magnetic resonance imaging (MRI) in these patients with more advanced disease prescribed biologic agents. Aim The aim of this study is to assess the integrity of the PCL on MRI in patients with inflammatory arthritis who are prescribed biologic agents. Methods A case-control study was performed, with cases identified through chart review to confirm prescription of biologic agents for inflammatory arthropathies, who also had contemporaneous MRI knee scans performed. Knee MRIs for age- and sex-matched controls with osteoarthritis (OA) and meniscal pathology were identified from the National Joint Registry and the Hospital In-Patient Enquiry (HIPE), respectively. The MRIs were reviewed by two musculoskeletal radiologists who were blinded to the clinical details. They were asked to assess the MRIs to determine PCL integrity, synovial Inflammation, and any associated pathology. Results No difference was noted in the rate of synovitis, PCL attenuation, or PCL tears between the OA and inflammatory arthropathy groups (p > 0.05). Conclusions The results of this study show no difference in the integrity and continuity of the PCL in those patients for age- and sex-matched controls on MRI. This finding lends support to the use of CR total knee arthroplasty in patients with inflammatory arthropathy on biologic agents.
34063326 Vaccination by Two DerG LEAPS Conjugates Incorporating Distinct Proteoglycan (PG, Aggrecan 2021 May 2 Rheumatoid arthritis (RA) can be initiated and driven by immune responses to multiple antigenic epitopes including those in cartilage proteoglycan (PG, aggrecan) and type II collagen. RA is driven by T helper 1 (Th1) or Th17 pro-inflammatory T cell responses. LEAPS (Ligand Epitope Antigen Presentation System) DerG peptide conjugate vaccines were prepared using epitopes from PG that elicit immune responses in RA patients: epitope PG70 (DerG-PG70, also designated CEL-4000) and the citrullinated form of another epitope (PG275Cit). The LEAPS peptides were administered alone or together in Seppic ISA51vg adjuvant to mice with PG G1 domain-induced arthritis (GIA), a mouse model of RA. Each of these LEAPS peptides and the combination modulated the inflammatory response and stopped the progression of arthritis in the GIA mouse model. Despite having a therapeutic effect, the DerG-PG275Cit vaccine did not elicit significant antibody responses, whereas DerG-PG70 (alone or with DerG-PG275Cit) induced both therapy and antibodies. Spleen T cells from GIA mice, vaccinated with the DerG LEAPS peptides, preferentially produced anti-inflammatory (IL-4 and IL-10) rather than pro-inflammatory (IFN-γ or IL-17) cytokines in culture. Similarly, cytokines secreted by CD4+ cells of unvaccinated GIA mice, differentiated in vitro to Th2 cells and treated with either or both DerG vaccine peptides, exhibited an anti-inflammatory (IL-4, IL-10) profile. These results suggest that the two peptides elicit different therapeutic immune responses by the immunomodulation of disease-promoting pro-inflammatory responses and that the combination of the two LEAPS conjugates may provide broader epitope coverage and, in some cases, greater efficacy than either conjugate alone.
34194234 Spermidine Inhibits Joints Inflammation and Macrophage Activation in Mice with Collagen-In 2021 PURPOSE: Spermidine (SPD) is a naturally occurring polyamine. In this study, we examined the role and possible mechanism of SPD in collagen-induced arthritis (CIA) mice. MATERIALS AND METHODS: CIA mice were intraperitoneally injected with SPD (2 and 50 mg/kg), dexamethasone (0.5 mg/kg), or saline daily for 21 days. The severity of the disease and inflammatory responses in the serum and joint tissue were assessed through macroscopic, immunohistochemical, and histological analyses. RESULTS: Macroscopic and histological results indicated that SPD protected against the development of CIA. SPD suppressed the levels of the pro-inflammatory cytokines IL-6 and IL-1β and increased the levels of the anti-inflammatory factor IL-10 in the serum. Immunohistochemical staining showed that 50 mg/kg SPD inhibited iNOS expression in synovial macrophages in the ankle joints of CIA mice. CONCLUSION: These results suggest that SPD may protect CIA mice by inhibiting the polarization of M1 macrophages in the synovial tissue, reducing pro-inflammatory cytokines, and promoting anti-inflammatory factor release.
34163211 Rheumatoid Arthritis Relapse and Remission - Advancing Our Predictive Capability Using Mod 2021 Clinical remission has become an achievable target for the majority of patients with rheumatoid arthritis, but subclinical inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) has been demonstrated to be frequent in patients in clinical remission. Subclinical synovitis has been shown to be linked to both subsequent structural damage progression and a risk of flare, demonstrating that subclinical synovitis represents incomplete suppression of inflammation and questions whether it is appropriate only to use clinical composite scores as treatment target in clinical practice. Maintaining a state of remission has proven important as sustained clinical remission impacts long-term outcome regarding joint damage progression, physical function and quality of life. Treating subclinical inflammation has been attempted and has led to more frequent strict clinical remission and better physical function, but also to more adverse events. Thus, an overall benefit of incorporating imaging goals in treat-to-target strategies has not been documented. However, in patients in clinical remission on biological disease-modifying anti-rheumatic drugs, both ultrasound and MRI may aid in the clinical decision regarding whether drug tapering or even discontinuation should be attempted.
34896652 An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases cl 2022 Mar Anti-Ro52 (or anti-TRIM21) antibodies are part of the family of anti-Ro/SSA antibodies, historically markers of Sjögren syndrome and systemic lupus erythematosus. Anti-Ro52 antibodies represent one the most frequently encountered autoantibodies in patients with connective tissue disease (primary Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies). Because of their lack of specificity and detection in patients with non-autoimmune disorders, the usefulness of anti-Ro52 testing in connective tissue diseases is still matter of debate among clinicians and immunologists. Autoantibodies are mainly diagnostic markers for autoimmune diseases but some of them can also be directly involved in the generation of tissue damage. Over the past decade several authors reported associations of anti-Ro52 antibodies with some clinical features - especially interstitial lung disease - and survival in patients with connective tissue diseases. There is also a growing evidence of the role of anti-Ro52 antibodies in the pathogenesis of connective tissue diseases. In this review, we comprehensively discuss the clinical associations of anti-Ro52 antibodies in the different connective tissue diseases and the recent advances on their potential role in the inflammatory response.
34251320 Untargeted serum metabolomics and potential biomarkers for Sjögren's syndrome. 2021 Nov OBJECTIVES: At present, the pathogenesis of Sjögren's syndrome (SS) remains unclear. This research aimed to identify differential metabolites that contribute to SS diagnosis and discover the disturbed metabolic pathways. METHODS: Recent advances in mass spectrometry have allowed the identification of hundreds of unique metabolic signatures and the exploration of altered metabolite profiles in disease. In this study, 505 candidates including healthy controls (HCs) and SS patients were recruited and the serum samples were collected. A non-targeted gas chromatography-mass spectrometry (GC-MS) serum metabolomics method was used to explore the changes in serum metabolites. RESULTS: We found SS patients and HCs can be distinguished by 21 significant metabolites. The levels of alanine, tryptophan, glycolic acid, pelargonic acid, cis-1-2-dihydro-1-2-naphthalenediol, diglycerol, capric acid, turanose, behenic acid, dehydroabietic acid, stearic acid, linoleic acid, heptadecanoic acid, valine, and lactic acid were increased in serum samples from SS patients, whereas levels of catechol, anabasine, 3-6-anhydro-D-galactose, beta-gentiobiose, 2-ketoisocaproic acid and ethanolamine were decreased. The significantly changed pathways included the following: Linoleic acid metabolism; unsaturated fatty acid biosynthesis; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; glycerolipid metabolism; selenocompound metabolism; galactose metabolism; alanine, aspartate and glutamate metabolism; glyoxylate and dicarboxylate metabolism; glycerophospholipid metabolism; and valine, leucine and isoleucine degradation. CONCLUSIONS: These findings enhance the informative capacity of biochemical analyses through the identification of serum biomarkers and the analysis of metabolic pathways and contribute to an improved understanding of the pathogenesis of SS.
34079231 Electronic Monitoring Feedback for Improving Medication Adherence and Clinical Outcomes in 2021 BACKGROUND: Non-adherence to medication (range 30-107%) is a major issue in patients with rheumatoid arthritis (RA). Previous research has shown that electronic monitoring feedback (EMF) might be an effective strategy to improve medication adherence in chronic conditions. Therefore, this study investigated the effectiveness of electronic monitoring feedback in patients with early RA to improve medication adherence and clinical outcomes compared to usual care. METHODS: An open-label randomized clinical trial was performed to compare EMF with standard care during a 12-month follow-up period on two sites of the Sint Maartenskliniek (Nijmegen and Boxmeer) in the Netherlands. Patients were eligible if they: (1) had a (working) diagnosis of early RA, (2) were currently using methotrexate, (3) were aged ≥18 years, and (4) had a life expectancy of ≥12 months. Primary outcome was the difference in proportion of non-adherent patients measured with the Compliance Questionnaire on Rheumatology after 12 months. Secondary outcomes were beliefs about medicines, medication adherence measured with the MMAS-8(®), patients' health status, prescription of biologic DMARDs, and disease activity after 12 months. RESULTS: Of the 367 initially-invited patients, 93 patients with early RA agreed to participate in this study. No significant difference was found in the proportion of non-adherent patients between the intervention arm and the usual care arm after 12 months follow-up (60.0% and 61.3%, p=0.93, respectively). Patients in the intervention arm tended to discontinue methotrexate earlier than patients in the usual care arm (median time in weeks: 15.7 (9.1-33.6) and 21.9 (19-28.4), respectively, p=0.31), whereas patients in the usual care arm tended to initiate biologic DMARDs earlier than those in the intervention arm (median time in weeks: 11.9 (5.7-22) and 17 (9.9-40.9), respectively, p=0.55). CONCLUSION: This study illustrates the challenge of targeting non-adherence with EMF in patients with early RA and shares important lessons learned about designing adherence intervention trials with respect to study attrition, accounting for drug survival, intervention fidelity, intervention uptake, and technical aspects.
33753012 [Immunity and tubular dysfunction in case of systemic disease]. 2021 Jun The immune renal tubular diseases are known since five decades, but their prevalence remains to be defined. They are caused by humoral and cellular effectors of innate and adaptative immunities on several targets of the renal tubule: protein channels, co or counter transporters, luminal or cytosolic enzymes, tight junctions. Genetic or epigenetic variations are also involved. Clinical manifestations are various and make the diagnosis difficult. They can precede the causal affection and they worsen the prognosis. The classical model consists in hypokalemic tubular distal acidosis observed in Sjögren's syndrome which illustrates the auto-immune epithelitis concept. Cellular immunity can act through other ways, like tertiary lymphoid neogenesis in systemic lupus. Humoral immunity through autoantibodies targets several membrane, cytosolic or nuclear proteins, causing specific tubular dysfonctions. It is also implied in the epithelial-mesenchymal transition of tubular cells. Innate immunity through cytokines may be involved. Treatment consists in electrolytic disorders correction and immunosupppressive medication: the choice should be guided at best by physiopathology.
34665704 Parotid salivary sodium levels of Sjögren's syndrome patients suggest B-cell mediated epi 2021 Nov Patients with primary Sjögren's syndrome (SS) suffer widely from lack of saliva production. Here we investigate potential mechanisms underpinning changes in SS patient saliva composition. Sodium concentration was significantly higher in all saliva samples collected: unstimulated submandibular/sublingual (SmSl) saliva (p<0.0001), stimulated SmSl saliva (p=0.002) and stimulated parotid (PG) (p<0.0001) saliva, compared to non-SS sicca controls. Chloride, phosphate and potassium ion concentrations, α-amylase activity and total protein content correlations were less consistently changed between SS and non-SS saliva types. Stimulated PG salivary sodium levels correlated with the degree of CD45+ lymphocytic cell infiltrate in the parotid glands (r=0.69, p<0.001), and even more strongly so with infiltrating CD20+ B cells (r=0.73, p<0.0001). CD3+ T cells were only moderately correlated with salivary sodium (r=0.23, p=0.015). In non-SS control or focus score (FS) negative SS PG tissue, the epithelial sodium channel (ENaC), responsible for sodium transport out of saliva, was localised to the apical membrane of luminal striated duct cells. In PG tissue from FS+ SS patients, apical ENaC expression appeared absent. We hypothesise that B cell-related proinflammatory cytokines in SS salivary glands may dysregulate sodium transport channels in SS.
34624052 Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy 2021 OBJECTIVES: To determine the diagnostic potential of simultaneous presence of serum anti-SSA/Ro and upregulated salivary protein biomarkers in patients with primary Sjögren's syndrome (pSS). METHODS: Previous proteomics data on the intensity of neutrophil elastase, calreticulin, tripartite motif containing protein 29 (TRIM29), clusterin and vitronectin provided basis for performing extended analysis. Protein data was obtained by liquid chromatography tandem mass spectrometry technique in whole saliva from 24 patients with pSS and 16 patients having symptoms of pSS, but not fulfilling the American College of Rheumatology/European League against Rheumatism classification criteria (non-pSS). Serum anti-SSA/Ro antibody was measured using enzyme-linked immunosorbent assays. Receiver operating characteristic curve (ROC) value was calculated for combined biomarkers. RESULTS: Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided the most optimal combination with an area under curve (AUC) of 0.995 (95% CI 0.98-1.00, p = 2.0E-7 and standard error 0.007) and combinations of sensitivity and specificity within the interval of 91-100%. ROC analysis showed that salivary levels of TRIM29 alone enabled differentiation between pSS and non-pSS with an area under curve (AUC) of 0.88 (95%CI 0.77-1.00). All patients with pSS and 3 non-pSS patients were serum anti-SSA/Ro positive. CONCLUSIONS: Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided a high diagnostic accuracy exceeding that of currently available tools used in pSS diagnostics. This biomarker combination represents a promising less invasive diagnostic tool for pSS. The clinical applicability of TRIM29 needs further testing in independent cohorts using relevant analytical techniques.
33358855 Triterpene saponins from Guo-gang-long attenuate collagen-induced arthritis via regulating 2021 Apr 6 ETHNOPHARMACOLOGICAL RELEVANCE: The stems of Entada phaseoloides (L.) Merr commonly named "Guo-gang-long", is a traditional Chinese folk medicine that has been used clinically in China for the treatment of arthritis. Our previous study described that triterpene saponins isolated from "Guo-gang-long" could inhibit the inflammatory response. However, the potential mechanism of "Guo-gang-long" on treatment of arthritis, and whether the triterpene saponins responsible for its anti-arthritic effect are unclear. AIM: To investigate the function and mechanisms of the triterpene saponins from E. phaseoloides (ES) in collagen-induced arthritis (CIA) rats. MATERIALS AND METHODS: The chemical components of ES were analyzed by HPLC. Anti-arthritic activity of ES was investigated in CIA rats, which was established by immunization with bovine type II collagen. Three doses of ES (25, 50 and 100 mg/kg) were administrated using oral gavage to CIA rats daily for 3 weeks. The anti-arthritic activity of ES was evaluated by clinical arthritis scoring, paw swelling and mechanical sensitivity, as well as histological changes in CIA rats. The impacts of ES on the regulation of the ubiquintin-editing enzyme A20 and MAPK signaling pathway, and production of pro-inflammatory cytokines in CIA rats were examined by Western blot, quantitative real-time PCR, ELISA, and immunohistochemical staining, respectively. RESULTS: ES treatment relieved the paw swelling, hyperalgesia and joint destruction, and prevented the progression of arthritis in CIA rats. Meanwhile, ES suppressed the excessive mRNA levels and protein expression of TNF-α and IL-17 in synovial tissues and hind paw joints, and reduced the production of IL-1β, TNF-α and IL-17 in serum. Furthermore, ES up-regulated A20 and suppressed the phosphorylation of p38 and ERK1/2 in hind paw joints, as well as inhibiting the activation of spinal p38 in CIA rats. CONCLUSION: ES could relieve rheumatic symptoms and prevent the development of rheumatoid arthritis. The effects of ES may be mediated by reducing proinflammatory cytokine levels, up-regulating A20 expression, reducing p38 and ERK1/2 activation in periphery, and inhibiting of phospho-p38 in spinal cord.
34603889 The Impact of Rheumatoid Arthritis on Bone Loss: Links to Osteoporosis and Osteopenia. 2021 Aug Rheumatoid arthritis (RA) is an autoimmune chronic connective tissue disease that produces persistent systemic inflammation, with joint inflammation leading to function loss and joint destruction. Low bone mass causes skeletal bone loss, commonly referred to as osteopenia or osteoporosis.  We conducted this literature review to examine the relationship between RA and osteoporosis and the variables contributing to this connection. We used articles from the US National Library of Medicine (PubMed), Google Scholar, Science Direct to access the required information. Eventually, our results concluded that RA could result in local periarticular and generalized bone loss. Many risk factors contribute to this association, such as chronic joints inflammation, glucocorticoid use, genetics, and estrogen hormone effects. Still, it is not clear yet whether this is due to a consequence of treatment, immobility, or the activity of the disease. There are many recommendations by the American College of Rheumatology for RA patients during the disease course to reduce the risk of osteoporosis development, which include early starts of disease-modifying anti-inflammatory drugs (DMARDs), doing a dual-energy x-ray (DXA) or quantitative ultrasound (QUS) for identifying a patient at risk of osteoporosis, taking vitamin D, calcium, and bisphosphonates. Further prospective studies and clinical trials are essential to provide a solid evidence-based recommendation that will help to prevent bone loss in RA patients.
34926082 Platelet-Rich Plasma for Rheumatoid Arthritis: A Case Series. 2021 Nov Rheumatoid Arthritis (RA) is a chronic disease characterized by severe inflammation that leads to degradation of articular cartilage and the formation of bony erosions. Currently, certain anesthesiologist-led pain management clinics have begun to take on a collaborative role in the treatment of patients with RA, as this progressive disease impairs work capacity due to chronic pain. We present three clinical cases in which platelet-rich plasma (PRP) was used for the treatment of RA in patients seeking a new therapy for pain control and improved range of motion, specifically in certain joints of the hand. The Patient Activity Scale II was employed as a standardized method to assess RA disease severity, recorded on the day of injection, at one month, at three months, and at six months. All of the included patients, ages 49, 60, and 63, had an established diagnosis of RA affecting the proximal interphalangeal and metacarpophalangeal joints of the hand. Over the course of six months, two out of three patients reported a 20% reduction in pain from the initial visit and a 30% improvement in overall well-being. The third patient noted a 50% decrease in pain from the initial visit and a 50% improvement in overall well-being. PRP treatment consistently resulted in functional improvement for each of the three patients treated, while also reducing long term pain and inflammation. Initial clinical and laboratory studies have shown that autologous plasma rich in platelets serves as a source of an abundance of growth factors once activated. The multitude of these growth factors injected into and around the diseased joints improves functionality in patients with RA indicating PRP may be a safe and beneficial therapy in patients with RA primarily affecting the joints of the hand.
34548823 A Comparison of Demographics, Disease Activity, Disability, and Treatment Among Rheumatoid 2021 INTRODUCTION: Osteoporosis (OP) is one of the most common comorbidities associated with rheumatoid arthritis (RA). Literatures reported that the risk for developing OP was strongly associated with duration and severity of RA. We aim to elaborate on the consequences of OP on disease activity and management plan in patients with RA. PATIENTS AND METHODS: A retrospective cohort study recruited 408 patients, including those with RA alone and with RA plus OP. The RA disease activity in the patients was assessed using disease activity score in 28 joints (DAS28-CRP). A statistical analysis was performed to compare data between the two groups of patients and determine any significant risk factor associated with the development of OP in RA patients. RESULTS: Of 408 patients who were included in this study, 353 patients (86.5%) had only RA, while 55 patients (13.5%) had RA with OP and showed significant difference (P = 0.04) concerning age categories. Patients diagnosed with RA and OP had RA duration longer than RA-only patients (independent t-test, P = 0.01). The two groups had almost similar disease activity at the three clinical visits, as well, had nearly similar disability at their first visit, whereas RA with OP patients had significant greater disability at their 2(nd) and 3(rd) visits (independent t-test, P = 0.001). Both groups were treated with the same biologic and non-biologic medication of similar frequency, although RA patients with OP received steroid more frequently than patients had RA only (61.7% vs. 41.7%, chi square test, P = 0.03). CONCLUSION: There was no significant difference in disease activity at both groups of patients. However, RA with OP group had longer duration of RA, were more frequently treated with steroids, and had greater disability. We recommend physicians focus on controlling RA disease activity, early screening for and treating of OP.
34199991 Long-Term Outcomes of Surgical Aortic Valve Replacement in Patients with Rheumatoid Arthri 2021 Jun 4 Background: Patients with rheumatoid arthritis (RA) have increased risk of developing cardiovascular disease and events. Little is, however, known about the influence of RA to the outcomes after surgical aortic valve replacement (SAVR). Methods: In a retrospective, nationwide, multicenter cohort study, RA patients (n = 109) were compared to patients without RA (n = 1090) treated with isolated SAVR for aortic valve stenosis. Propensity score-matching adjustment for baseline features was used to study the outcome differences in a median follow-up of 5.6 years. Results: Patients with RA had higher all-cause mortality (HR 1.76; CI 1.21-2.57; p = 0.003), higher incidence of major adverse cardiovascular events (HR 1.63; CI 1.06-2.49; p = 0.025), and they needed more often coronary artery revascularization for coronary artery disease (HR 3.96; CI 1.21-12.90; p = 0.027) in long-term follow-up after SAVR. As well, cardiovascular mortality rate was higher in patients with RA (35.7% vs. 23.4%, p = 0.023). There was no difference in 30-day mortality (2.8% vs. 1.8%, p = 0.518) or in the need for aortic valve reoperations (3.7% vs. 4.0%, p = 0.532). Conclusions: Patients with rheumatoid arthritis had impaired long-term results and increased cardiovascular mortality after SAVR for aortic valve stenosis. Special attention is needed to improve outcomes of aortic valve stenosis patients with RA after SAVR.
34675803 Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Art 2021 Arthritis is a disorder that is characterized by joint inflammation and other symptoms. Rheumatoid arthritis (RA), an autoimmune disease, is one of the most common arthritis in worldwide. Inflammation of the synovium is the main factor that triggers bone erosion in the joints in RA, but the pathogenesis of RA is not clearly understood. Kefir grain-fermented products have been demonstrated to enhance immune function and exhibit immune-modulating bioactivities. This study aims to explore the role of kefir peptides (KPs) on the regulation of dendritic cell, which are found in RA synovial fluid, and the protection effects of KPs on mice with collagen-induced arthritis (CIA). Immature mouse bone marrow-derived dendritic cells (BMDCs) were treated with KPs (2.2 and 4.4 mg/ml) and then exposed to lipopolysaccharide (LPS) to study the immune regulation function of KPs in dendritic cells. Mice with CIA (n = 5 per group) were orally administrated KPs (3.75 and 7.5 mg/day/kg) for 21 days and therapeutic effect of KPs on mice with arthritis were assessed. In this study, we found that KPs could inhibit surface molecule expression, reduce inflammatory cytokine release, and repress NF-κB and MAPK signaling in LPS-stimulated mouse BMDCs. In addition, a high dose of KPs (7.5 mg/kg) significantly alleviated arthritis symptoms, decreased inflammatory cytokine expression, suppressed splenic DC maturation and decrease the percentage of Th1 and Th17 in the spleens on mice with CIA. Our findings demonstrated that KPs ameliorate CIA in mice through the mechanism of suppressing DC maturation and inflammatory cytokine releases.
33246116 Tunisian Olea europaea L. leaf extract suppresses Freund's complete adjuvant-induced rheum 2021 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. (olive) is traditionally used as a folk remedy and functional food in Europe and Mediterranean countries to treat inflammatory diseases. O. europaea contains phenolic compounds and have been reported to prevent cartilage degradation. However, the function and mechanism of O. europaea in rheumatoid arthritis are not known. AIM OF THE STUDY: In this study, we aimed to examine anti-inflammatory and anti-arthritic effects of Tunisian O. europaea L. leaf ethanol extract (Oe-EE). MATERIALS AND METHODS: To do this, we employed an in vitro macrophage-like cell line and an in vivo Freund's complete adjuvant (AIA)-induced arthritis model. Levels of inflammatory genes and mediators were determined from in vivo samples. RESULTS: The Oe-EE clearly reduced the production of the lipopolysaccharide-mediated inflammatory mediators, nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in RAW264.7 cells. The results of HPLC showed that Oe-EE contained many active compounds such as oleuropein and flavonoids. In AIA-treated rats, swelling of paws, pain, and cartilage degeneration were alleviated by oral Oe-EE administration. Correlating with in vitro data, PGE(2) production was significantly reduced in paw samples. Furthermore, the molecular mechanism of Oe-EE was dissected, and Oe-EE regulated the gene expression of interleukin (IL)-6, inducible NO synthase (iNOS), and MMPs and inflammatory signaling activation. CONCLUSION: Consequently, Oe-EE possesses anti-inflammatory and anti-rheumatic effects and is a potential effective treatment for rheumatoid arthritis.
33832983 Differential characteristics and management of pseudoseptic arthritis following hyaluronic 2021 Mar IMPORTANCE: Acute pseudoseptic arthritis is a rare complication of hyaluronic acid (HA) injections that is not well documented in the literature. Practitioners initially suspect the symptoms of this complication to represent septic arthritis, cautiously prescribing antibiotics. This review identifies that time to presentation of symptoms postinjection, negative cell cultures and lack of crystallisation could be used as differentials to suspect pseudoseptic arthritis and to prescribe anti-inflammatory drugs while closely monitoring change of symptoms. OBJECTIVE: The purpose of this study was to describe the presentation, diagnosis and treatment of pseudoseptic arthritis. EVIDENCE REVIEW: A systematic review of the literature was conducted for studies reporting the use of HA injections for osteoarthritis resulting in pseudoseptic arthritis using the electronic databases MEDLINE, Embase and PubMed. Pertinent data were abstracted from the search yield. A unique case of a pseudoseptic reaction is also presented. FINDINGS: A total of 11 studies (28 cases), all of level IV and V evidence were included in this review. Reported cases of pseudoseptic arthritis in the literature present with severe joint pain (100%), effusion (100%), inability to weight-bear, functional impairment, and occasionally fever (22.2%). C reactive protein and erythrocyte sedimentation rate are generally elevated (71.4% and 85.7%, respectively), and leucocytosis above 10 000 was less common (50%). All reported cases in the literature identified aseptic growth on arthrocentesis, despite four cases (15.4%) reporting synovial leucocyte counts above 50 000. The presented case is the highest reported leucocyte count at 1 74 960 cells/mm(3). CONCLUSIONS AND RELEVANCE: Acute pseudoseptic arthritis is rare, but a number of cases have been reported in the literature. A high degree of suspicion for pseudoseptic arthritis may be maintained in patients who present under 72 hours following HA injection. Initial antibiotic treatment, along with anti-inflammatory medications until cultures are confirmed to be negative at 5 days, is a cautious approach. However, the strength of this conclusion is limited by the few reported cases. Ultimately, this review is intended to inform practitioners of the symptoms, diagnosis and treatment of this complication, such that it could be safely differentiated from septic arthritis. LEVEL OF EVIDENCE: IV.