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ID PMID Title PublicationDate abstract
31504962 Secretory anti-citrullinated protein antibodies in serum associate with lung involvement i 2020 Apr 1 OBJECTIVE: A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. METHODS: One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. RESULTS: SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (σ = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (σ=0.20, P = 0.020). CONCLUSION: In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.
33243069 Detection of human cytomegalovirus in synovial neutrophils obtained from patients with rhe 2021 May Objectives: To examine whether signs of an active human cytomegalovirus (HCMV) infection are present in affected joints of patients with rheumatoid arthritis (RA).Method: Polymorphonuclear leucocytes (PMNLs) were obtained from synovial fluid (SF) of 17 RA patients and were analysed for HCMV-pp65 and HCMV-immediate early (IE) proteins using the antigenemia assay. Peripheral blood (PB) and SF obtained from these 17 patients and from 17 additional RA patients (n = 34) were tested for HCMV-IE and pp150 DNA with Taqman polymerase chain reaction. Plasma samples from the patients were analysed for HCMV-immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay and compared to 71 healthy gender-matched blood donors.Results: HCMV-pp65 protein was detected in 65% of synovial PMNL samples, but in only 18% of PMNLs from PB. In contrast, HCMV IE protein was not found in any of the analysed PMNL samples. On the DNA level, HCMV-IE and pp150 DNA was detected in SF of 13/32 (41%) and 14/23 (61%) of RA patients, respectively. HCMV-IE and pp150 DNA was also found in 24/33 (73%) and in 16/24 (67%) of PB samples obtained from RA patients, respectively. HCMV IgG seroprevalence was 76% in RA patients as well as in healthy controls, while only one RA patient was positive for specific IgM.Conclusions: HCMV pp65 antigen was found in PMNLs from SF of RA patients, indicating an active infection in the affected joint. Future studies are needed to determine whether HCMV infection can aggravate the inflammatory process in these patients.
32186765 lncRNA CASC2 downregulation participates in rheumatoid arthritis, and CASC2 overexpression 2020 May lncRNA cancer susceptibility candidate 2 (CASC2) is a recently identified oncogenic lncRNA in different types of cancers. Our preliminary microarray data showed that lncRNA CASC2 was downregulated in the plasma of patients with rheumatoid arthritis (RA), indicating the involvement of this lncRNA in RA. In the present study, lncRNA CASC2 and IL‑17 in plasma were detected by reverse transcription‑-quantitative PCR and ELISA, respectively. Diagnostic analyses were performed using receiver operating characteristic curves. Flow cytometry was performed to evaluate cell apoptosis. The effects of lncRNA CASC2 on IL‑17 expression were determined via western blotting. lncRNA CASC2 was found to be downregulated, while IL‑17 was upregulated in the plasma of RA patients when compared with these levels in the plasma of healthy controls. Plasma levels of lncRNA CASC2 and IL‑17 were significantly and inversely correlated in both RA patients and healthy controls. Altered plasma levels of lncRNA CASC2 and IL‑17 were able to differentiate RA patients from healthy controls. Overexpression of lncRNA CASC2 promoted, while treatment with IL‑17 inhibited the apoptosis of human fibroblast‑like synoviocytes (HFLSs) isolated from RA patients. Overexpression of lncRNA CASC2 inhibited IL‑17 expression in HFLS, while treatment with IL‑17 did not significantly affect the expression of lncRNA CASC2. Therefore, downregulation of lncRNA CASC2 is involved in RA and lncRNA CASC2 overexpression may promote the apoptosis of HFLS by downregulating IL‑17.
30947583 Comparison of median nerve stiffness with and without rheumatoid arthritis by ultrasound r 2020 May Objectives: This study aimed to compare median nerve stiffness measured by ultrasound real-time tissue elastography in patients with and without rheumatoid arthritis (RA and non-RA groups, respectively).Methods: Altogether, 402 hands of 201 RA group and 222 hands of 111 non-RA group were included in the study. Ultrasonography was performed to evaluate the circumference, cross-sectional area (CSA) and strain ratio as an elasticity of the median nerve at the inlet level of the carpal tunnel and the proximal portion of the carpal tunnel inlet. Using propensity score matching, the difference between RA and non-RA group were analyzed.Results: After propensity score matching, 135 hands in 104 RA group and 70 non-RA group were finally analyzed. There were no significant differences in the circumference and CSA of the median nerve between the two groups. The strain ratio of the median nerve was significantly higher in RA group than in non-RA group only at the inlet of the carpal tunnel level.Conclusions: The nerve stiffness in patients with RA measured by ultrasound real-time tissue elastography was higher than without RA. Inflammatory condition of the flexor tendon and wrist joint in patients with RA may generate fibrotic changes in the median nerve.Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000015314.
33374575 Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Age 2020 Dec 23 Topical anti-inflammatory and analgesic effect for the treatment of rheumatoid arthritis is of major interest because of their fewer side effects compared to oral therapy. The purpose of this study was to prepare different types of topical formulations (ointments and gels) containing synthetic and natural anti-inflammatory agents with different excipients (e.g.,: surfactants, gel-forming) for the treatment of rheumatoid arthritis. The combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), diclofenac sodium, a topical analgesic agent methyl salicylate, and a lyophilized extract of Calendula officinalis with antioxidant effect were used in our formulations. The aim was to select the appropriate excipients and dosage form for the formulation in order to enhance the diffusion of active substances and to certify the antioxidant, analgesic, and anti-inflammatory effects of these formulations. To characterize the physicochemical properties of the formulations, rheological studies, and texture profile analysis were carried out. Membrane diffusion and permeability studies were performed with Franz-diffusion method. The therapeutic properties of the formulations have been proven by an antioxidant assay and a randomized prospective study that was carried out on 115 patients with rheumatoid arthritis. The results showed that the treatment with the gel containing diclofenac sodium, methyl salicylate, and lyophilized Calendula officinalis as active ingredients, 2-propenoic acid homopolymer (Synthalen K) as gel-forming excipient, distilled water, triethanolamine, and glycerol had a beneficial analgesic and local anti-inflammatory effect.
32414425 Temporary interruption of baricitinib: characterization of interruptions and effect on cli 2020 May 15 BACKGROUND: In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. METHODS: During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. RESULTS: Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. CONCLUSIONS: Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01710358, NCT01711359, NCT01721057, NCT01721044.
33169172 Expression profile and diagnostic value of circRNAs in peripheral blood from patients with 2021 Jan Circular RNAs (circRNAs) have gained attention due to their performance in disease diagnosis. However, the characteristics of circRNAs in peripheral blood from patients with systemic lupus erythematosus (SLE) remain unknown. Therefore, the aim of the present study was to determine the expression profile and diagnostic potential of circRNAs in peripheral blood from patients with SLE. The global circRNA expression in the peripheral blood of patients with SLE and healthy controls (HCs) was detected using a circRNA microarray. Then, the expression levels of three upregulated circRNAs were selected for further validation by reverse transcription‑quantitative PCR (RT‑qPCR) in a training set. Moreover, the diagnostic value of these circRNAs was assessed by constructing a receiver operating characteristic curve, and then verified in a blind testing set. In total, 1,566 circRNAs were identified to be dysregulated between patients with SLE and HCs (≥2 fold change, P<0.05). Furthermore, the RT‑qPCR results were consistent with the microarray data, in that all three selected circRNAs, hsa_circ_0082688, hsa_circ_0082689 and hsa_circ_0008675, were significantly upregulated in patients with SLE (P<0.05). Results from the training set demonstrated that the combination of hsa_circ_0082688‑hsa_circ_0082689 may provide the most beneficial diagnostic potential. Moreover, the blind test results indicated that the combination model of hsa_circ_0082688‑hsa_circ_0082689 could effectively discriminate between patients with SLE from patients with rheumatoid arthritis and HCs, with a sensitivity of 91.30%, a specificity of 78.57% and an accuracy of 82.28%. Moreover, the combination model of hsa_circ_0082688‑hsa_circ_0082689 + anti‑dsDNA could more effectively discriminated the SLE group from the control groups, with a sensitivity of 95.65%, a specificity of 100.00% and an accuracy of 98.73%. In addition, correlation analysis results suggested that all three circRNAs in patients with SLE did not correlate with the SLE disease activity index. In conclusion, the expression levels of hsa_circ_0082688‑hsa_circ_0082689 may serve as potential biomarkers for SLE diagnosis.
33264346 Thermal characteristics of rheumatoid feet in remission: Baseline data. 2020 OBJECTIVES: Studies have shown conflicting characteristic thermographic patterns of the feet in patients with active rheumatoid arthritis (RA). However, to date no studies have compared thermographic patterns of patients with RA in remission and healthy controls. Thus this study aimed to investigate whether the thermal characteristics of the feet of RA patients, in clinical and radiological remission differ to those of healthy controls. METHODS: Using convenience sampling, RA patients were recruited upon confirmed absence of synovitis by clinical examination and musculoskeletal ultrasound. Thermal images of the feet were taken. Each foot was subdivided into medial, central, lateral, forefoot and heel regions. Subsequently, temperatures in the different regions were analyzed and compared to a cohort of healthy adults. RESULTS: Data from 32 RA patients were compared to that of 51 healthy controls. The Independent samples T-Test demonstrated a significant difference in temperatures in all the regions of the forefoot between RA participants versus healthy subjects (Table 1). Using the One-Way ANOVA test, no significant difference was found between all the forefoot regions (p = 0.189) of RA patients. Independent sample T-test found significant differences in all heel regions between the two groups (Table 2). One-Way ANOVA demonstrated no significant differences (p = 0.983) between the different foot regions (n = 192) of RA patients. CONCLUSION: These findings suggest that RA patients in clinical and radiological remission exhibit significantly different feet thermographic patterns compared to healthy controls. This data will provide the basis for future studies to assess whether thermographic patterns change with disease activity.
32503859 Applying cascaded convolutional neural network design further enhances automatic scoring o 2020 Sep OBJECTIVES: We have previously shown that neural network technology can be used for scoring arthritis disease activity in ultrasound images from rheumatoid arthritis (RA) patients, giving scores according to the EULAR-OMERACT grading system. We have now further developed the architecture of this neural network and can here present a new idea applying cascaded convolutional neural network (CNN) design with even better results. We evaluate the generalisability of this method on unseen data, comparing the CNN with an expert rheumatologist. METHODS: The images were graded by an expert rheumatologist according to the EULAR-OMERACT synovitis scoring system. CNNs were systematically trained to find the best configuration. The algorithms were evaluated on a separate test data set and compared with the gradings of an expert rheumatologist on a per-joint basis using a Kappa statistic, and on a per-patient basis using a Wilcoxon signed-rank test. RESULTS: With 1678 images available for training and 322 images for testing the model, it achieved an overall four-class accuracy of 83.9%. On a per-patient level, there was no significant difference between the classifications of the model and of a human expert (p=0.85). Our original CNN had a four-class accuracy of 75.0%. CONCLUSIONS: Using a new network architecture we have further enhanced the algorithm and have shown strong agreement with an expert rheumatologist on a per-joint basis and on a per-patient basis. This emphasises the potential of using CNNs with this architecture as a strong assistive tool for the objective assessment of disease activity of RA patients.
32711355 Adaptive weighted sum tests via LASSO method in multi-locus family-based association analy 2020 Oct Family based multi-locus tests integrate information from individual loci by weighted averaging of the marginal statistics, and have been proven to be more efficient and robust than the single-locus tests in genetic association studies. The power depends on how much information the weights can extract from data. The currently published weighted sum methods are only applicable to either common or rare variants and may suffer from substantial power loss especially for rare variants. In this paper, we propose a novel data-driven weight to improve the power under both common and rare variant circumstances. We use the l(1) regularization in Least Absolute Shrinkage and Selection Operator (LASSO) regression to construct the weight serving as a simultaneously adaptive marker selection process. Simulations for a dichotomous phenotype demonstrated that our LASSO-based approach outperformed the existing multi-locus methods in the sense of providing the highest statistical power while well controlled type I error rate under different scenarios. We also applied our methods to a real dataset for rheumatoid arthritis (GAW15 Problem 2). Two groups of alleles, in which individual SNPs had only modest and non-significant effects, were detected (P < 0.00001) using our proposed methods, whereas traditional multi-locus methods failed to identify them. In conclusion, the novel LASSO-based approach represents a superior weight-choosing strategy for multi-locus tests.
32550709 Vitamin D and disease activity in rheumatoid arthritis patients: a retrospective study in 2020 Jun 18 BACKGROUND: The relationship between the serum levels of Vitamin D and the severity of RA is a subject of great interest for the future therapeutic strategies. Although the evidence on the relationship between hypovitaminosis D and early RA is contradictory, preliminary data suggest that the serum levels of vitamin D are inversely associated with the disease activity. AIM: the main objectives of this study include: (1) to analyze the serum levels of vitamin D in patients with RA in comparison to healthy controls; (2) to investigatea possible correlation with disease activity. MATERIALS AND METHODS: This was a retrospective, comparative study conducted on 37 subjects suffering from RA and a group of 21 healthy matched controls. The following were determined in all studied subjects: erythrocyte sedimentation rate (ESR), white blood cells (WBC), hemoglobin (Hb), platelets (PLT), serum calcium (Ca), serum phosphorus (Phos), and serum 25 hydroxy-vitamin D. Moreover, in the RA group the IgM-Rhematoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) (immune-enzymatic method) were assessed. The Disease Activity Score of 28 joints (DAS28) was calculated for the RA patients. RESULTS: We observed that vitamin D deficiency is more common in RA patients than in healthy controls. No significant correlation between 25OHvitD and DAS28-ESR was found in our study cohort. CONCLUSIONS: There is no significant association of serum 25(OH)D with disease severity in a Western Romanian cohort with RA. However, this result could have implications for the disease management, as patients with RA could be supplemented with vitamin D even in the absence of disease activity.
33316402 Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic diseas 2021 Apr OBJECTIVES: Early in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ. METHODS: We conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ(2), and Student's t-tests. RESULTS: As of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200-400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86). CONCLUSIONS: HCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.
31214867 Association of radiographic findings in hand X-ray with clinical features and autoantibodi 2020 Jan Musculoskeletal involvement is one of the major causes of impairment in daily life of patients with systemic sclerosis (SSc). Several hand radiographic findings can be seen in SSc patients; however, their association with clinical features and autoantibodies remains unclear. Here, we analyzed 124 SSc patients with their hand X-rays and clinical and serological features. Abnormal findings in hand X-rays including acro-osteolysis, calcinosis, flexion contracture, erosive change, joint space narrowing, and subluxation were observed in 110 patients (68%). These X-ray findings were more prevalent in patients with longer disease duration and digital ischemic changes. The majority of erosions were typical for erosive hand osteoarthritis, which was seen in 19% of patients. Hand X-ray findings were associated with involved organs; acro-osteolysis with interstitial lung disease, calcinosis with pulmonary arterial hypertension and gastrointestinal tract involvement, and flexion contracture with gastrointestinal tract involvement. Those findings were also relevant to autoantibodies; acro-osteolysis was more common in SSc patients with anti-Scl70 antibody but less in patients with anticentromere antibody. Calcinosis was more prevalent in patient with anticentromere antibody. In our study, organ involvements and SSc-associated autoantibodies showed associations with hand radiographic abnormalities. Hand X-ray findings might reflect underlying pathogenesis and autoantibody profiles in SSc patients.Key Points• Hand X-ray abnormalities were observed in approximately two-thirds of patients with SSc.• Erosive osteoarthritis was more prevalent in SSc patients than general population.• Hand X-ray findings were associated with disease duration, organ involvements, and SSc-associated autoantibodies, reflecting underlying pathogenesis.
31594444 Endovascular preoperative embolization for temporomandibular joint replacement surgery. 2020 Feb BACKGROUND AND PURPOSE: This retrospective study evaluates the safety and effectiveness of preoperative endovascular embolization in patients who underwent temporomandibular joint (TMJ) replacement surgery. MATERIAL AND METHODS: We included all patients treated with preoperative embolization of the internal maxillary artery (IMAX) between June 2016 and January 2019. All patients were treated by the same surgeon using standard surgical approaches and procedures. Periprocedural adverse events, blood loss during surgery and clinical follow-up are reported. RESULTS: Fourteen patients (12 females, median age 32.5) were treated with 21 embolizations of the IMAX (bilateral embolizations in seven patients) prior to TMJ replacement surgery with prosthetic joints (TMJ Concepts prostheses). Seven patients presented with TMJ ankylosis/degenerative joint disease/post-trauma deformity, four patients with Idiopathic Condylar Resorption and resultant mandibular displacement/hypoplasia, two patients with rheumatoid arthritis-associated condylar degeneration and resultant loss of mandibular position, and 1 patient being re-reconstructed following management of a prosthetic joint infection. Seven patients underwent bilateral prosthetic joint replacement. Four patients underwent additional facial skeletal surgery as part of their treatment. The mean blood volume loss during TMJ surgery was approximately 370 cc (range 100-800 cc). Joint space-specific blood loss was not recorded, but, as per the surgical team, was significantly decreased when compared to non-embolized patients. There were no intra-procedural complications. The median clinical follow-up was 3.5 months (range 1-24 months). The modified Rankin scale (mRS) was 0 before the procedure and at last clinical follow-up in all patients. After TMJ surgery, three patients reported paresthesia of the trigeminal nerve likely related to the residual condyle resection and two patients had mild facial nerve weakness (Temporal and/or Marginal Mandibular branch) related to the surgical exposures. CONCLUSION: Endovascular preoperative embolization of the IMAX is feasible, safe and likely effective in reducing blood volume loss in complex TMJ replacement surgery.
31084537 Rheumatology Care Using Telemedicine. 2020 Mar Introduction: People living in many parts of the world have limited access to diagnostic studies and therapies for rheumatologic, musculoskeletal, and connective tissue diseases. The challenge has been particularly poignant for rural areas of low- and middle-income countries. Objectives: We report on the implementation of a telemedicine program in Iran for the evaluation and treatment of patients with rheumatologic and musculoskeletal diseases. More than 4,800 patients were seen remotely over a span of 5 years by a rheumatologist in the United States. The remote rheumatologist was aided by a general physician and a nurse at a local charity hospital in northeastern Iran that has a catchment area that includes rural regions extending to the border of Afghanistan. Seventy to 90 patients were evaluated online by the remote rheumatologist 3 days a week. A subset of patients was evaluated by the rheumatologist in person every 4 months. Materials and Methods: The population of rheumatology patients was evaluated using descriptive statistics. Information collected included demographic information consisting of age, gender, and primary rheumatologic diagnosis. Results: The average age of patients who were seen was 52 years and 89% of patients were women. Approximately 50% of patients were Afghan refugees. The most common disorders included osteoarthritis (1,149, 23.6%), rheumatoid arthritis (653, 13.4%), axial spondyloarthropathies (647, 13.3%), lumbar spinal stenosis (427, 8.8%), meniscal tear of the knee (326, 6.7%), and psoriatic arthritis (217, 4.5%). Certain conditions were lower than expected such as lupus (19, 0.4%) and fibromyalgia (169, 3.5%). Diagnostic tests included serologic tests (1,328, 27.3%), plain radiographs (946, 19.5%), magnetic resonance imaging (899, 18.5%), bone densitometry (147, 3.0%), and electromyography and nerve conduction study (132, 2.7%). The most common medications prescribed were non-steroidal anti-inflammatory drugs (791, 16.3%), methotrexate (764, 15.7%), pregabalin (234, 4.8%), duloxetine (230, 4.7%), sulfasalazine (177, 3.6%), etanercept (97, 2.0%), tofacitinib (64, 1.3%), adalimumab (18, 0.4%), and infliximab (9, 0.2%). Conclusions: Telemedicine is becoming more prevalent. We report the successful use of this service in evaluation and management of rheumatic diseases in a region with limited access to rheumatologic care. We have shown that patients can be seen, evaluated, and successfully treated with a variety of medications, including biologic agents.
32053981 Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases. 2020 Feb 11 The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H(2)S) were recently demonstrated in the context of different inflammatory diseases. In particular, H(2)S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H(2)S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H(2)S, more evidence is needed to understand the pathophysiology and the potential of H(2)S as a therapeutic agent. Within this review, we provide an overview on H(2)S biological effects, on its role in immune-mediated inflammatory diseases, on H(2)S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.
32920324 Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retro 2020 Oct OBJECTIVES: To assess the efficacy and tolerance profile of rituximab in rheumatoid arthritis (RA)-associated large granular lymphocyte leukemia (LGLL). METHODS: Multicenter retrospective case series. Inclusion criteria were RA defined by the ACR/EULAR 2010 criteria and LGLL defined by absolute LGL count ≥ 0.3 × 10(9)/L with evidence of an expanded clonal LGL population (flow cytometry, TCR-γ polymerase chain reaction, or Stat3 mutation). RESULTS: Fourteen patients (10 women, mean age 55.2 ± 14.2 years) included; 13 were seropositive for anti-cyclic citrullinated peptides (n = 11) or rheumatoid factor (n = 10). LGLL diagnosis was made 9.5 [IQR: 3.25;15.5] years after RA diagnosis. Thirteen patients had T-LGLL. Rituximab was the first-line therapy for LGLL for 4 patients. Previous treatment lines included methotrexate (n = 7), cyclophosphamide (n = 2), cyclosporin A (n = 1), or granulocyte colony-stimulating factor (n = 4). Rituximab was used in monotherapy (n = 8) or associated to methotrexate (n = 3), granulocyte colony-stimulating factor (n = 2), or alkylating agents (n = 1). The number of rituximab cycles ranged from 1 to 11 (median 6), with high heterogeneity in dosing regimens. Median duration response after rituximab initiation was 35 [IQR: 23.5;41] months. The overall response rate was 100%: 8 patients experienced complete response (normalization of blood count and LGL ≤ 0.3 × 10(9)/L) and 6 experienced partial responses (improvement in blood counts without complete normalization). The tolerance profile was good, with no infectious complications. CONCLUSION: rituximab appears as a valuable therapeutic option for RA-associated LGLL.
32959594 [Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway]. 2020 Sep 12 OBJECTIVE: To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1). METHODS: A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue. RESULTS: On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (P<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (P<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (P<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (P<0.01, P<0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (P<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (P<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (P<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (P<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (P<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (P<0.05). CONCLUSION: Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.
32591916 Therapeutic Options and Cost-Effectiveness for Rheumatoid Arthritis Treatment. 2020 Jun 26 PURPOSE OF REVIEW: During the last two decades, the therapeutic decisions and strategies for rheumatoid arthritis (RA) management have improved dramatically. Today, the therapeutic armamentarium is significantly augmented, and by using both old and new drugs, remission or low disease activity is a reasonable goal. The use of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) in combination with biologic (b) or targeted synthetic (ts) DMARDs has revolutionized RA treatment. Methotrexate administration is considered fundamental among other csDMARDs for the treatment of RA. It is recommended as the initial drug (monotherapy), or in combination with other csDMARDs, bDMARDs, and tsDMARDs in a step-up strategy. Furthermore, it can be used with other csDMARDs as initial combination-therapy. On the other hand, despite the fact that bDMARDs and ts DMARDs are highly efficacious and can also be used as monotherapy in certain cases, cost-effectiveness is still questionable when compared with csDMARDs. In this direction, the classic argument of utmost importance has to do with the most appropriate treatment strategy that shall be initially applied: csDMARD combination-therapy versus monotherapy, or step-up combinationtherapy with bDMARDs, especially tumor necrosis factor-α (TNFa) blockers. For this reason, a literature review of the most important csDMARDs combination and bDMARDs combination studies has been deployed. RECENT FINDINGS: The results showed that the triple csDMARDs therapy approach is more effective and less expensive. In addition, workers' productivity is higher than any other treatment options for RA. Triple-therapy constitutes a smart, efficacious, and significantly cheaper choice for RA therapeutic management.
32281474 Inflammatory myositis in systemic lupus erythematosus. 2020 Jun BACKGROUND: The coexistence of inflammatory myositis in systemic lupus erythematosus (SLE) has not been extensively studied. In this study, we describe the incidence, distinct types of inflammatory myositis, and risk factors for this finding in a cohort of pediatric and adult SLE patients. METHODS: We identified SLE patients with coexisting myositis followed between 2010 and 2019 at two pediatric hospitals and one adult hospital. Demographic, clinical, laboratory, and pathological features of myositis were collected, and descriptive statistics were applied. RESULTS: A total of 1718 individuals were identified as having SLE (451 pediatric and 1267 adult patients). Of these, 108 were also diagnosed with inflammatory myositis (6.3%). People of black race had a significantly higher prevalence of inflammatory myositis, as did those with childhood-onset SLE compared to adult-onset disease. In the majority of patients (68%), SLE and inflammatory myositis presented concurrently. Overlapping features of systemic sclerosis occurred in 48%, while dermatomyositis-specific rashes were present in a third. Arthralgias and inflammatory arthritis were seen in >90%. Thrombotic events and significant pregnancy-related morbidity were present in more than a third of patients. Lymphopenia, hypocomplementemia, and a positive RNP were the most common laboratory features noted. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were present in >40% of patients. A review of 28 muscle biopsy reports revealed a wide array of pathological features, including nonspecific changes, dermatomyositis, polymyositis, and necrotizing auto-immune myopathy. CONCLUSION: In our SLE patient population, 6.3% presented with concurrent inflammatory myositis. Dermatomyositis-specific rashes, clinical features of systemic sclerosis, arthralgias and arthritis, and cytopenias were common coexisting clinical manifestations. A high frequency of RNP, MSA, and MAA were found. People of black race and with childhood-onset disease had a higher prevalence of myositis. Our findings suggest that SLE patients of black race, with childhood-onset SLE, and who possess MSA or MAA should be routinely screened for myositis.