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ID PMID Title PublicationDate abstract
35310712 Methotrexate-associated proliferative disorder in the lower esophagus extending to the gas 2022 Apr A 64-year-old woman was receiving oral methotrexate (MTX) for rheumatoid arthritis (RA) for 15 years. She underwent esophagogastroduodenoscopy because of discomfort in the chest. Endoscopic findings revealed an ulcer in the lower esophagus extending to the gastroesophageal junction (EGJ). The ulcer occupied half of the esophageal lumen and had a sharp and clear margin. Magnifying narrow-band imaging endoscopy revealed the deposition of white plaque, and there were few microvessels in the edge and bottom of the ulcer. Histologic examination of the biopsy specimens from the oral edge of the lesion revealed proliferation of atypical lymphoid cells (immunophenotype results: CD20 [+], CD3 [partially +], CD5 [-], and BCL-2 [-]]. The patient was diagnosed with methotrexate-associated lymphoproliferative disorder (MTX-LPD) and was advised to stop MTX intake. After 2 months of stopping MTX, the ulcer was found to be almost regressed and showed signs of healing. MTX-LPD in the lower esophagus extending to the EGJ is extremely rare. This case can help in expanding the understanding of esophageal MTX-LPD.
34900523 Pharmacological insights into autophagy modulation in autoimmune diseases. 2021 Nov As a cellular bulk degradation and survival mechanism, autophagy is implicated in diverse biological processes. Genome-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), indicating that autophagy dysregulation may be involved in the development of autoimmune diseases. A series of autophagy modulators have displayed protective effects on autoimmune disease models, highlighting the emerging role of autophagy modulators in treating autoimmune diseases. This review explores the roles of autophagy in the autoimmune diseases, with emphasis on four major autoimmune diseases [SLE, rheumatoid arthritis (RA), IBD, and experimental autoimmune encephalomyelitis (EAE)]. More importantly, the therapeutic potentials of small molecular autophagy modulators (including autophagy inducers and inhibitors) on autoimmune diseases are comprehensively analyzed.
34474646 Ultrasound efficacy of targeted-synthetic disease-modifying anti-rheumatic drug treatment 2021 Sep 2 OBJECTIVE: This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments. METHOD: This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups. RESULTS: All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders. CONCLUSION: Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.
34116007 Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphoryla 2021 Sep 15 The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. But, changes in the metabolism of normal synovial membranes or synovial cells during the early stages of inflammation remains unknown. Moreover, there are still many aspects of inflammatory signaling pathways altered by glycolysis inhibitors, that remain unclear. In this study we found that, in normal, non-pathological bovine synovial cells, most of ATP synthesis was generated by mitochondrial respiration. However, during the early of stages inflammation, initiated by lipopolysaccharide (LPS) exposure, synovial cells shifted to glycolysis for ATP production. The glycolysis inhibitor 2-deoxyglucose (2DG) reversed LPS induced increases in glycolysis for ATP production and suppressed the expression of inflammatory cytokines and proteolytic enzymes. 2DG suppressed the phosphorylation of the transcription factor cAMP response element binding protein (CREB) enhanced by LPS. Treatment with a CREB inhibitor reversed the expression of LPS-stimulated inflammatory cytokines and proteolytic enzymes. This study showed that changes in metabolism occur during the early stages of inflammation of synovial cells and can be reversed by 2DG and signaling pathways associated with CREB phosphorylation.
33916869 Analysis of the Associations between Arthritis and Fall Histories in Korean Adults. 2021 Apr 3 (1) Background: the purpose of the present study was to analyze the associations between arthritis and fall histories in Korean adults. (2) Methods: data from the 2015 and 2017 Korean Community Health Survey were analyzed. In total, 322,962 participants aged ≥40 years were included. The participants were divided into two different groups. First, the participants were divided into the 'arthritis (osteoarthritis or rheumatoid arthritis) for entire life' and 'nonarthritis for entire life (comparison I)' groups. Subsequently, the participants were divided into the 'current arthritis' and 'noncurrent arthritis (comparison II)' groups. Afterwards, we analyzed the prevalence odds ratios (pORs) of the fall histories of the participants using a logistic regression analysis with the 95% confidence interval (CI). The variables of income, education level, region of residence, smoking status, alcohol consumption, obesity, subjective health status, stress level, physical activity, and sleep hours were adjusted for as covariates. (3) Results: both the arthritis for entire life and current arthritis groups had higher prevalence rates of falls than the comparison I and comparison II groups, respectively (each p < 0.001). The pORs of falling ≥1 time and ≥2 times per year in the arthritis for the entire life group were 1.42 (95% CI = 1.38-1.46) and 1.69 (95% CI = 1.62-1.76), respectively. The adjusted pORs for falling ≥1 time and ≥2 times per year in the current arthritis group were 1.35 (95% CI = 1.31-1.39) and 1.56 (95% CI = 1.50-1.63), respectively. (4) Conclusions: previous arthritis has a significant impact on the risk of falling.
35024385 Usefulness of cortical thickness ratio of the third metacarpal bone for prediction of majo 2022 Jun OBJECTIVE: Patients with rheumatoid arthritis (RA) are at high risk for osteoporotic fractures. We developed an index called the third metacarpal cortical thickness ratio (CTR), which reflects bone mineral density (BMD) in RA patients. A longitudinal study was conducted to verify the usefulness of CTR during the follow-up period. METHODS: Patients with RA who underwent dual energy X-ray absorptiometry (DXA) and hand X-ray simultaneously were monitored for disease activity and activities of daily living at 3-month intervals, and BMD and CTR were measured at 1-year intervals. Mean CTR during follow-up was tested for correlation with mean BMD at both the lumbar spine (LS) and femoral neck (FN) during follow-up. Correlations were examined, including other variants potentially correlated with BMD. The risk ratio of accidental major osteoporotic fractures (MOF) in the variance including CTR and BMD was evaluated. RESULTS: A total of 300 patients, 40 men and 260 women, were enrolled. Mean follow-up length was 49.6 months. CTR was significantly associated with BMD in FN using a multivariate model of linear regression analysis (p < 0.0001), whereas CTR was significantly associated with BMD in LS using only a univariate model (p < 0.01). The only variant with a significantly higher risk ratio for incident MOF was the presence of prevalent MOF. CTR and BMD did not show a significantly higher risk ratio using Cox regression analysis. CONCLUSION: CTR correlated significantly with BMD even during follow-up, especially in FN. However, CTR and BMD were not risk factors for major MOF.
34768405 Association between Pulpal-Periapical Pathology and Autoimmune Diseases: A Systematic Revi 2021 Oct 23 Several studies have linked apical periodontitis and systemic diseases. The aim of this study is to present a systematic review of the available literature investigating whether there is an association between pulpal-periapical pathology and autoimmune disease. The review was conducted following the PRISMA statement. A literature search was performed in five databases. Studies involving patients with pulpal-periapical pathology and autoimmune diseases were included in the review. Based on the PICO model, the research question aimed to assess whether there is an increased risk of developing pulpal-periapical pathology in patients with autoimmune disease. Article selection, data extraction, and quality assessment were performed using an adapted version of the STROBE guidelines. A total of seven studies were included in our review. The types of articles were five case-control and two cross-sectional studies. Periapical pathologies were associated to three autoimmune diseases (diabetes mellitus I, rheumatoid arthritis, and inflammatory bowel disease). Among the included studies, four show a low risk of bias, while three present a moderate risk. There could be an association between apical periodontitis and autoimmune diseases, although most studies report statistically non-significant associations.
34626791 Lipid scavenging macrophages and inflammation. 2022 Jan Macrophages are professional phagocytes, indispensable for maintenance of tissue homeostasis and integrity. Depending on their resident tissue, macrophages are exposed to highly diverse metabolic environments. Adapted to their niche, they can contribute to local metabolic turnover through metabolite uptake, conversion, storage and release. Disturbances in tissue homeostasis caused by infection, inflammation or damage dramatically alter the local milieu, impacting macrophage activation status and metabolism. In the case of persisting stimuli, defective macrophage responses ensue, which can promote tissue damage and disease. Especially relevant herein are disbalances in lipid rich environments, where macrophages are crucially involved in lipid uptake and turnover, preventing lipotoxicity. Lipid uptake is to a large extent facilitated by macrophage expressed scavenger receptors that are dynamically regulated and important in many metabolic diseases. Here, we review the receptors mediating lipid uptake and summarize recent findings on their role in health and disease. We further highlight the underlying pathways driving macrophage lipid acquisition and their impact on myeloid metabolic remodelling.
31420237 Development of a risk indicator score for the identification of interstitial lung disease 2021 Apr BACKGROUND: Clinically evident interstitial lung disease (ILD) affects 10%-42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients. METHODS: Case-control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79-0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%. CONCLUSION: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.
34274242 Clinical Outcomes After First Metatarsophalangeal Joint Arthrodesis by Flat Cut Joint Prep 2022 Jan Sagittal misalignment is a major cause of patient dissatisfaction and re-operation after first metatarsophalangeal (MTP) joint arthrodesis. The stereotypical application of the fixed angle would be undesirable, especially in cases of flat or cavus foot. We retrospectively reviewed 31 cases (27 patients) in which first MTP joint arthrodesis was performed using the flat cut joint preparation technique with reference to the plantar clearance beneath the pulp of the toe while simulating weightbearing by pushing a board against the sole. The most common underlying cause of surgery was rheumatoid arthritis (22 cases [71%]). Clinical outcomes were evaluated by the Japanese of Surgery of the Foot (JSSF) hallux scale and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty-three cases were also examined by pedobarography to evaluate postoperative walking plantar pressure. At the most recent follow-up of a mean 19.6 months, the toe-to-floor distance of the hallux in static standing posture was a mean of 2.5 mm (range, 0-10 mm). All but 1 foot (97%) achieved bone union. There were no complications or revisions due to misalignment of the fused MTP joint. JSSF hallux scales improved significantly from 47 preoperatively to 82 postoperatively. All subscale scores except general health and well-being in the SAFE-Q improved significantly at final follow-up versus preoperative period. Plantar pressure under the hallux was correlated with the toe-to-floor distance but not radiographic parameter. In conclusion, first MTP joint arthrodesis achieved good clinical outcomes when using toe-to-floor distance and Kirschner wire template for flat cut joint preparation.
34021269 Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain 2021 Jul Tumor necrosis factor (TNF) inhibitors have improved a lot the treatment of numerous diseases, with the well-known example of rheumatoid arthritis (RA). In the early 2000s, postmarketing data quickly revealed an alarming number of severe tuberculosis (TB) under such treatment. These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization. The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma, with changes in cellular interactions, cytokine, and chemokine production. In addition to the role of TNF in granuloma, the interleukin (IL)-12/interferon (IFN)-γ pathway is required for an efficient host defense against TB. Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin (BCG) reaction or full TB. Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain. When TNF inhibitors are initiated, this transiently increases this risk of TB, through effects on cellular interactions in a latent TB granuloma. At a later stage, when a better control disease activity is obtained, the risk of TB is reduced but not abrogated. Given the clear benefit from TNF inhibition, latent TB infection screening at baseline is essential for an optimal safety.
33709226 Voxel-based mapping of five MR biomarkers in the wrist bone marrow. 2021 Oct OBJECTIVE: MRI is a reliable and accurate technique to characterize rheumatoid arthritis. The aim of this study was to provide voxel-by-voxel 3D maps of the proton density fat fraction (PDFF), the T(1) of water (T(1W)), the T(1) of fat (T(1F)), the T(2)* of water (T(2)*(W)), the T(2)* of fat (T(2)*(F)) in the wrist bone marrow. MATERIALS AND METHODS: The experiments were conducted on 14 healthy volunteers (mean age: 24 ± 4). The data were acquired at 1.5 T using two optimized four-echo 3D 1.2 × 1.2 × 1.2 mm(3)-isotropic spoiled gradient sequences. A repeatability study was carried out. The measurements were done using a homemade parametric viewer software. RESULTS: The inter-volunteer results were, on average: PDFF = 86 ± 3%, T(1W) = 441 ± 113 ms, T(1F) = 245 ± 19 ms, T(2)*(W) = 6 ± 1 ms and T(2)*(F) = 16 ± 3 ms. The coefficients of variation were for fat based biomarkers CV(PDFF) < 5%, CV(T1F) < 15% and CV(T2*F) < 10% in the repeatability study. DISCUSSION: The protocol and quantification tool proposed in this study provide high-resolution voxel-by-voxel 3D maps of five biomarkers in the wrist in less than 4 min of acquisition.
32918357 Interleukin-35 regulates the balance of Th17 and Treg responses during the pathogenesis of 2021 Jan Interleukin (IL)-35 belongs to the IL-12 cytokine family and is a heterodimer of the p35 and Epstein-Barr virus-induced gene 3 (EBI3) subunits. Functionally, IL-35 can promote the proliferation and activation of regulatory T cells (Tregs) and suppress the function of T helper 17 (Th17) cells and other inflammatory cells to inhibit immune responses. In recent years, an abnormal IL-35 expression causing a Th17/Treg imbalance has been associated with the development and progression of several connective tissue diseases (CTDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM)/polymyositis (PM), and primary Sjögren's syndrome (pSS). Here, we review the role of IL-35 in regulating the balance of Th17/Treg responses in different types of CTDs and provide new insights into the role of IL-35 in these diseases.
35056087 Molecular Modeling Insights into Upadacitinib Selectivity upon Binding to JAK Protein Fami 2021 Dec 25 Rheumatoid arthritis (RA) is a chronic disease characterized by bone joint damage and incapacitation. The mechanism underlying RA pathogenesis is autoimmunity in the connective tissue. Cytokines play an important role in the human immune system for signal transduction and in the development of inflammatory responses. Janus kinases (JAK) participate in the JAK/STAT pathway, which mediates cytokine effects, in particular interleukin 6 and IFNγ. The discovery of small molecule inhibitors of the JAK protein family has led to a revolution in RA therapy. The novel JAK inhibitor upadacitinib (Rinvoq(TM)) has a higher selectivity for JAK1 compared to JAK2 and JAK3 in vivo. Currently, details on the molecular recognition of JAK1 by upadacitinib are not available. We found that characteristics of hydrogen bond formation with the glycine loop and hinge in JAKs define the selectivity. Our molecular modeling study could provide insight into the drug action mechanism and pharmacophore model differences in JAK isoforms.
34159634 Surface AMP deaminase 2 as a novel regulator modifying extracellular adenine nucleotide me 2021 Jul Adenine nucleotides represent crucial immunomodulators in the extracellular environment. The ectonucleotidases CD39 and CD73 are responsible for the sequential catabolism of ATP to adenosine via AMP, thus promoting an anti-inflammatory milieu induced by the "adenosine halo". AMPD2 intracellularly mediates AMP deamination to IMP, thereby both enhancing the degradation of inflammatory ATP and reducing the formation of anti-inflammatory adenosine. Here, we show that this enzyme is expressed on the surface of human immune cells and its predominance may modify inflammatory states by altering the extracellular milieu. Surface AMPD2 (eAMPD2) expression on monocytes was verified by immunoblot, surface biotinylation, mass spectrometry, and immunofluorescence microscopy. Flow cytometry revealed enhanced monocytic eAMPD2 expression after TLR stimulation. PBMCs from patients with rheumatoid arthritis displayed significantly higher levels of eAMPD2 expression compared with healthy controls. Furthermore, the product of AMPD2-IMP-exerted anti-inflammatory effects, while the levels of extracellular adenosine were not impaired by an increased eAMPD2 expression. In summary, our study identifies eAMPD2 as a novel regulator of the extracellular ATP-adenosine balance adding to the immunomodulatory CD39-CD73 system.
33499333 Phenolic Compounds Impact on Rheumatoid Arthritis, Inflammatory Bowel Disease and Microbio 2021 Jan 22 Non-communicable chronic diseases (NCDs) are nowadays the principal cause of death, especially in most industrialized nations. These illnesses have increased exponentially with the consumption of diets very high in fat and sugar, not to mention stress and physical inactivity among other factors. The potential impact of suboptimal diets on NCDs' morbidity and mortality rates brings to the forefront the necessity for a new way of improving dietary habits. The literature provides extensive scientific work that presents evidence that phenolic compounds from diets have antioxidant, anti-inflammatory and antiproliferative activities that impact human health. Gut microbiota modulation by some phenolic compounds leads to favorable changes in abundance, diversity, and in the immune system. However, polyphenol's limited bioavailability needs to be overcome, highlighting their application in new delivery systems and providing their health benefits in well-established ways such as health maintenance, treatment or adjuvant to conventional pharmacological treatments. In this context, novel dietary approaches, including new food supplements, have emerged to prevent diseases and preserve health.
33470231 [Marked increase in high-sensitivity troponin I without evidence of acute coronary syndrom 2021 Feb Troponins measured by high-sensitivity methods (hs-cTn) are the current reference biomarkers to diagnose acute myocardial infarction. Conditions other than obstructive coronary heart disease may present an increase in hs-cTn. Heterophilic antibodies can interfere with the hs-cTn dosage. We report the case of a patient affected by rheumatoid arthritis, hospitalized for syncope and atypical chest pain. Serial blood samples documented high values of high-sensitivity troponin I and normal values of creatine kinase-MB and myoglobin. Echocardiogram, coronary angiography and electrophysiological study were normal. The use of heterophilic antibody blockers defined these values as false positive results. Therefore, to diagnose acute myocardial infarction, laboratory data should be integrated with clinical information and instrumental examinations. Marker release kinetics is crucial. Finally, there may be some possible causes of heterophilic antibodies (rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, mixed cryoglobulinemia, hepatitis C, infections, cancer, sarcoidosis) that could interfere with biomarker dosage.
33936655 Light chain Amyloidosis (AL) associated with multiple myeloma revealed by peripheral bilat 2021 Apr In chronic polyarthritis, the presence of macroglossia with absence of rheumatoid factor and anti-CCP antibodies may be suggestive of amyloid arthopathy. Clinical evaluation takes precedence over classification criteria.
33778476 Evaluation of the Structural Validity of the Work Instability Scale Using the Rasch Model. 2021 Mar OBJECTIVE: To use Rasch analysis to examine the measurement properties of the 23-item version of the Work Instability Scale (WIS-23) in a sample of worker compensation claimants with upper extremity disorders. DESIGN: Secondary data analysis on the data retrieved from a cross-sectional study. SETTING: Tertiary care hospital. PARTICIPANTS: Patients (N=392) attending a specialty clinic for workers with upper limb injuries at a tertiary hospital were prospectively enrolled. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: WIS-23. RESULTS: The study sample contained 392 participants between the ages of 19 and 73 years (mean, 47.0±10.5y). There were 148 (37.8%) women, 182 (46.4%) men, and 62 (15.8%) participants for whom sex identification was unavailable. The initial WIS data analysis showed significant misfit from the Rasch model (item-trait interaction: χ(2)=293.52; P<.0001). Item removal and splitting were performed to improve the model fit, resulting in a 20-item scale that met all assumptions (χ(2)=160.42; P=.008), including unidimensionality, local independence of items, and the absence of differential item function based on age, sex of respondents, employment type, and affected upper extremity area across all tested factors. CONCLUSION: With the application of Rasch analysis, we refined the WIS-23 to produce a 20-item WIS for work-related upper extremity disorders (WIS-WREUD). The 20-item WIS-WREUD demonstrated excellent item and person fit, unidimensionality, acceptable person separation index, and local independency. The WIS-20 may provide better measurement properties, although longitudinal psychometric evaluations are needed.
32404382 Medication persistence on biological therapies prescribed for the treatment of chronic inf 2021 Nov OBJECTIVES: Medication persistence, defined as the duration of time from its initiation to its discontinuation, is a surrogate for treatment effectiveness. The aim of the study was to evaluate persistence and causes of biological therapy (BT) suspension in patients with chronic inflammatory arthropathies: rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Single institution, descriptive, retrospective cohort study. Adult patients with chronic inflammatory arthropathies on BT between January 2009 and December 2016 were included. Persistence to BT was compared considering the type of pathology and treatment. The Kaplan-Meier test was used to analyse medication persistanence and factors associated with it. An analysis of reasons for therapy discontinuation was performed. RESULTS: Three hundred and sixty-two patients were included in the study, which comprised 478 BT lines. For all patients, the 12-month persistence rate was 71.3% (341 out of 478). At the end of the study, 45.2% of the patients continued on their initial BT. Median treatment persistence was 1489 days (CI 95% 1195 to 1783). Longer BT persistence was associated with naïve BT patients: 1945 days (95% CI 1523 to 2367; P<0.001) and ankylosing spondylitis diagnosis: 2402 days (95% CI 1604 to 3200; P=0.014). The most frequent causes of treatment discontinuation were therapeutic failure (47.6%) and adverse drug events (28.2%). CONCLUSIONS: We found good long-term persistence in patients with chronic inflammatory arthropathies treated with BT. Patients with rheumatoid arthritis had significantly shorter persistence compared with those with ankylosing spondylitis and psoriatic arthritis. Naïve BT was associated with longer persistence. Therapeutic failure was the main cause of BT withdrawal.