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ID PMID Title PublicationDate abstract
30358135 International Consortium for Health Outcome Measurement Set of Outcomes That Matter to Peo 2019 Dec OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.
31727971 Investigation of the curative effects of palm vitamin E tocotrienols on autoimmune arthrit 2019 Nov 14 The tocotrienol-rich fraction (TRF) from palm oil contains vitamin E, which possesses potent antioxidant and anti-inflammatory activities. Rheumatoid arthritis (RA) is a chronic joint inflammatory disease characterised by severe joint pain, cartilage destruction, and bone erosion owing to the effects of various pro-inflammatory mediators and cytokines. Here, we investigated the therapeutic effects of TRF in a rat model of collagen-induced arthritis (CIA). Arthritis was induced by a single intradermal injection of collagen type II in Dark Agouti (DA) rats. Rats were then treated with or without TRF by oral gavage from day 28 after the first collagen injection. Arthritic rats supplemented with TRF showed decreased articular index scores, ankle circumferences, paw volumes, and radiographic scores when compared with untreated rats. The untreated arthritic rats showed higher plasma C-reactive protein levels (p < 0.05) and production of pro-inflammatory cytokines than arthritic rats fed TRF. Moreover, there was a marked reduction in the severity of histopathological changes observed in arthritic rats treated with TRF compared with that in untreated arthritic rats. Overall, the results show that TRF had beneficial effects in this rat model of RA.
30906325 Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotr 2019 We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.
30674730 Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients. 2019 Jan 24 Osteoarthritis (OA) is a leading cause of disability, globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target inflammation therapeutically have had limited success. A better understanding of the cellular and molecular processes occurring in the OA synovium is needed to develop novel therapeutics. We investigated macrophage phenotype and gene expression in synovial tissue of OA and inflammatory-arthritis (IA) patients. Compared with IA, OA synovial tissue contained higher but variable proportions of macrophages (P < 0.001). These macrophages exhibited an activated phenotype, expressing folate receptor-2 and CD86, and displayed high phagocytic capacity. RNA sequencing of synovial macrophages revealed 2 OA subgroups. Inflammatory-like OA (iOA) macrophages are closely aligned to IA macrophages and are characterized by a cell proliferation signature. In contrast, classical OA (cOA) macrophages display cartilage remodeling features. Supporting these findings, when compared with cOA, iOA synovial tissue contained higher proportions of macrophages (P < 0.01), expressing higher levels of the proliferation marker Ki67 (P < 0.01). These data provide new insight into the heterogeneity of OA synovial tissue and suggest distinct roles of macrophages in pathogenesis. Our findings could lead to the stratification of OA patients for suitable disease-modifying treatments and the identification of novel therapeutic targets.
30268354 GANT61 alleviates arthritic symptoms by targeting fibroblast-like synoviocytes in CIA rats 2019 Mar BACKGROUND: Studies have identified that the fibroblast-like synoviocytes (FLS) exhibited tumor-like characteristics and was the key factor in the pathogenesis of Rheumatoid arthritis (RA). GANT61, an antagonist of the sonic hedgehog pathway, has been verified with inhibitory effect on many cancers. Here we investigated the effect of GANT61 on FLS and the development of collagen-induced arthritis (CIA). METHODS: 40 Sprague Dawley (SD) rats were randomly divided into four groups: normal, CIA, CIA+10 mg/kg GANT61 and CIA+20 mg/kg GANT61. CIA was induced in rat with collagen injecting. The GANT61 was administered by intraperitoneal injection every 2 days for 3 weeks. The CIA model was identified with the paw swelling, arthritis score and the pathologic changes in joint. The FLS of different group were primary cultured. The proliferative capacity of FLS was detecteded via Cell Counting Kit-8 (CCK-8) method, and the apoptosis was detecteded by flow cytometry. The Bcl-2, Bax, Caspases3 and cleaved Caspases3 in synovium and FLS were detecteded by Western Blot. RESULTS: The 20 mg/kg GANT61 treatment reduced the incidence of CIA and relieved the arthritis symptoms in CIA rats. The Bcl-2 was upregulated and the Bax was downregulated in the CIA rats synovium. The 10 mg/kg and 20 mg/kg GANT61 diminished the Bcl-2 expression, 20 mg/kg GANT61 increased the Bax and activated the Caspases3 in the CIA synovium. The proliferation of CIA-FLS was significantly higher and the apoptosis of the CIA-FLS was lower than that of the control group. The 10 mg/kg and 20 mg/kg GANT61 treatment can reduce cell proliferation and induce apoptosis by diminishing Bcl-2 and increasing the Bax in CIA-FLS. CONCLUSIONS: The GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA.
31601292 Methotrexate Central Nervous System Toxicity Identified in a Pharmacogenomics Pharmacist C 2019 Oct 1 OBJECTIVE: To report a possible pharmacogenomics (PGx)-related, cognitive dysfunction, adverse drug reaction from methotrexate (MTX) that may be multifactorial in origin. SUMMARY: The patient subject is a 76-year-old Caucasian female of Russian ancestry suffering from rheumatoid arthritis and treated with MTX who presented to the diagnostic and consultative physician service in a medical clinic with advancing cognitive dysfunction, manifesting as memory loss, dizziness, and confusion. Components of this possible adverse drug reaction (ADR) may include ancestry, pharmacogenomics (PGx) characteristics of the patient, and a change in route of administration, among others. The case demonstrates how patients referred to a pharmacist consult service for a suspected ADR with possible PGx implications may uncover other contributory factors to the ADR. CONCLUSION: PGx testing may increase clinical pharmacist referrals to identify a PGx etiology to an ADR. However, they may also identify other non-PGx contributory factors to an ADR.
30697106 Immune's-boosting agent: Immunomodulation potentials of propolis. 2019 Jan With a concomitant increase in immune-related diseases such as allergic diseases, Type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease and other immune-related responses such as immunodeficiency, various infectious, diseases, vaccines, and malignancies, it has become very important to have a well-balanced and properly functioning immune system for the maintenance of human health. Recent scientific research has strongly suggested propolis as one of the most promising immunomodulation agents. This review describes recent findings with respect to propolis and its ingredients that show potential in this respect and evaluate their potential mechanisms. The author believes that propolis or/and its ingredients alone and in combination could be promising in manipulating the immune response and inducing immunomodulation. Further exploratory studies are needed to support large clinical trials toward further development of propolis.
30684938 Odontoid cervical gout causing atlantoaxial instability: case report. 2019 Jan 25 The authors present a case report of a patient discovered to have a rotatory subluxation of the C1-2 joint and a large retroodontoid pannus with an enhancing lesion in the odontoid process eventually proving to be caused by gout. This patient represented a diagnostic conundrum as she had known prior diagnoses of not only gout but also sarcoidosis and possible rheumatoid arthritis, and was in the demographic range where concern for an oncological process cannot fully be ruled out. Because she presented with signs and symptoms of atlantoaxial instability, she required posterior stabilization to reduce the rotatory subluxation and to stabilize the C1-2 instability. However, despite the presence of a large retroodontoid pannus, she had no evidence of spinal cord compression on physical examination or imaging and did not require an anterior procedure to decompress the pannus. To confirm the diagnosis but avoid additional procedures and morbidity, the authors proceeded with the fusion as well as a posterior biopsy to the retroodontoid pannus and confirmed a diagnosis of gout.
31164168 Correction to: Use of daily electronic patient-reported outcome (PRO) diaries in randomize 2019 Jun 4 After publication of the original article [1], the authors have notified us of an error in language used in the text.
30928003 Non-Myasthenia Gravis Immune Syndromes and the Thymus: Is There a Role for Thymectomy? 2019 May Thymectomy has long been considered, performed, and discussed for many different nonmyasthenic immune syndromes. Thymectomy is now an established treatment for MG, and has been performed for other immune syndromes with varying degrees of improvement. Although numerous reports document immune syndromes' association with thymoma, few address the role of thymectomy in symptom resolution. This review assesses thymectomy in the various nonmyasthenic immune syndromes for which it has been tried. Based on this review, it seems appropriate to revisit a more active role for thymectomy in pure red cell aplasia, pemphigus, rheumatoid arthritis, autoimmune hemolytic anemia, and ulcerative colitis.
30572135 Th17 cells in renal inflammation and autoimmunity. 2019 Feb Th17 cells are a distinct lineage of T-cells. These T-cells express IL-17A and the lineage-defining transcription factor RORγt. Th17 cells have a pivotal, physiological role in host defense against pathogens. These pro-inflammatory T-cells are also key players in autoimmunity and a pathogenic role has been demonstrated in several diseases such as rheumatoid arthritis or psoriasis. Recently, there is evidence that Th17 cells may drive renal inflammation and renal autoimmunity in anti-neutrophil-cytoplasmic-antibody-(ANCA)-vasculitis and systemic lupus erythematosus. The aim of this review is to discuss the possible involvement of Th17 cells in renal autoimmunity and its value for future therapeutic approaches.
31394717 Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-In 2019 Aug 7 In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 μg/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of RORγt+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1β, IL-2, IL-6, IL-17, and tumor necrosis factor-α in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-κB ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions.
30925627 Elbow Arthroplasty: From Normal to Failure. 2019 Apr Total elbow arthroplasty is currently an established surgical treatment for several pathologies of the elbow. Although initially used primarily in the treatment of rheumatoid arthritis, indications for total elbow arthroplasty have expanded and now include trauma, primary and secondary osteoarthritis, fracture nonunion, and following neoplasm resection. Desired outcomes of elbow arthroplasty include decreasing patient pain, restoration of function and mobility, and prevention of or treatment for instability. In comparison with total elbow arthroplasty, radial head replacements are most commonly performed following trauma. An additional technique, capitellar resurfacing arthroplasty, was developed in an effort to prevent early-onset osteoarthritis secondary to altered elbow biomechanics following radial head replacement. Complications of these surgeries include loosening, fracture, instability and dissociation, bushing wear, and particle disease.
30929459 Surgical Treatment of Severe Hallux Abductovalgus With Dislocation of the First Metatarsop 2019 Jun Severe hallux abductovalgus deformity with dislocation and contracture at the first metatarsophalangeal joint is difficult to manage, especially in the presence of concomitant, long-standing rheumatoid arthritis. This article highlights a novel surgical technique that may be used to successfully address this challenging condition while minimizing the likelihood of complications. Levels of Evidence: Level IV.
30890732 Incidence of and Risk Factors for Complex Regional Pain Syndrome Type 1 after Surgery for 2019 Mar 19 This study aimed to evaluate the incidence rates of and risk factors for complex regional pain syndrome type 1 (CRPS-1) after surgery for distal radius fractures (DRFs). Using data from January 2007 to December 2014, we analysed the data from the Korean Health Insurance Review and Assessment (HIRA) service. After extracting the data of patients aged ≥18 years whose diagnostic and operation codes for DRFs were entered into the HIRA database, we analysed the incidence rates of and risk factors for CRPS-1. From 2007 to 2014, 172,194 DRFs were treated surgically. Within 1 year postoperatively, 1,103 CRPS-1 cases were diagnosed, with an incidence of 0.64%. On univariate and multivariate analyses, the risk factors that significantly correlated with the incidence of CRPS-1 included female sex, rheumatoid arthritis, open reduction, open fracture, and accompanying ulnar fracture, whereas old age, psychiatric disease, and external fixation were not statistically significant. The incidence of CRPS-1 after surgery for DRF was very low (0.64%) in South Korea. Careful monitoring is necessary for patients with complex fractures and rheumatoid arthritis who are at increased risk of developing CRPS-1.
30678091 Functional SNPs in the Human Autoimmunity-Associated Locus 17q12-21. 2019 Jan 23 Genome-wide association studies (GWASes) revealed several single-nucleotide polymorphisms (SNPs) in the human 17q12-21 locus associated with autoimmune diseases. However, follow-up studies are still needed to identify causative SNPs directly mediating autoimmune risk in the locus. We have chosen six SNPs in high linkage disequilibrium with the GWAS hits that showed the strongest evidence of causality according to association pattern and epigenetic data and assessed their functionality in a local genomic context using luciferase reporter system. We found that rs12946510, rs4795397, rs12709365, and rs8067378 influenced the reporter expression level in leukocytic cell lines. The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites.
30344019 Constrained Implant Arthroplasty for Distal Radioulnar Joint Arthrosis: Evaluation and Man 2019 Jul PURPOSE: Distal radioulnar joint (DRUJ) prostheses designed as semiconstrained devices aiming to replace the function of the ulnar head, sigmoid notch of the radius, and triangular fibrocartilage complex have demonstrated the capacity to restore the functional status of the DRUJ. However, soft tissue complications including tendons, nerves, and wounds, although documented, have not been the primary focus of prior reports. This study investigated short- to medium-term soft tissue complications after DRUJ semiconstrained implant arthroplasty. METHODS: We performed a retrospective review of patients undergoing semiconstrained DRUJ implant arthroplasty with clinical and radiological follow-up greater than 1 year. Data were reviewed with a focus on soft tissue complications after arthroplasty. RESULTS: Fifty DRUJ implant arthroplasties were performed over 10 years in 49 patients. Patients' average age was 47.8 years. Average duration of follow-up was 35.8 ± 3.7 months. A total of 46 patients underwent multiple operations before DRUJ arthroplasty. Postoperative pronosupination range of motion, grip strength, and visual analog scale pain scores were significantly improved after DRUJ arthroplasty. Wound-healing problems occurred in 11 arthroplasties; however, all wounds subsequently healed without operative intervention. Wound-related complications were significantly increased in patients with a history of rheumatoid arthritis or immunosuppression. Eighteen operations were required to address complications in 8 patients. Extensor tendinopathy was the most common indication for reoperation; 5 tenosynovectomy procedures were required in 4 wrists. A prominent screw requiring removal was identified in 3 cases of tenosynovitis. Periprosthetic fractures were identified in 3 wrists; 2 of these required reoperation for open treatment. Removal of hardware was required in 2 patients; these patients required 9 subsequent reoperations. CONCLUSIONS: Distal radioulnar joint arthrosis is a major problem and patients commonly undergo multiple reconstructive surgeries before DRUJ implant arthroplasty. No instances of wound-related complications or tendinopathy occurred in patients without previous surgeries, and wound-related complications occurred at a higher frequency with a history of rheumatoid arthritis or immunosuppression. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.
31301390 Rituximab as a trigger factor of medication-related osteonecrosis of the jaw. A case repor 2020 Jun Rituximab, an anti-CD20 monoclonal antibody, is an effective treatment for rheumatoid arthritis. Here we report the case of a patient with rheumatoid arthritis, having taken risedronate for 14 months to prevent corticosteroid-induced osteoporosis, more than 2 years ago, who presented osteonecrosis of jaw following herpetic gingivostomatitis two weeks after the beginning of a rituximab treatment associated with her usual anti-rheumatic drugs. Eight weeks later, no bone and/or gum healing was observed and a stage 2 medication-related osteonecrosis of the jaw (MRONJ) was diagnosed. A conservative approach was decided with antiseptic mouth washes, low-level laser treatment (LLLT) and systemic therapy with teriparatide. Complete mucosal coverage was obtained after more two years of follow-up. We suggest that rituximab as immunosuppressant might be a cause or a decompensating factor of MRONJ. Non-surgical periodontal treatment with LLLT and teriparatide are candidates for the treatment of MRONJ.
30886720 The potential usefulness of sputum cytology in the conclusive diagnosis of methotrexate-as 2019 BACKGROUND: Methotrexate has been used as an anchor drug for the treatment of rheumatoid arthritis and is considered to be a cause of methotrexate-associated lymphoproliferative disorder. Spontaneous regression can occur after withdrawal of methotrexate and may be associated with Epstein-Barr virus positivity and non-diffuse large B cell lymphoma histological type. Methotrexate-associated lymphoproliferative disorders are often diagnosed pathologically by lung biopsy. To the best of our knowledge, there have been no studies on the cytological diagnosis of methotrexate-associated lymphoproliferative disorder using sputum smears. CASE: A 70-year-old man, who was diagnosed with rheumatoid arthritis 13 years previously and who had been treated with methotrexate, presented shortness of breath and productive cough. Methotrexate-associated lymphoproliferative disorder was suspected as the sputum cytology showed many atypical lymphoid cells with hyperchromatic enlarged nuclei, foamy cytoplasm and distinct nucleoli. Chest computed tomography revealed multiple nodular shadows with interstitial pneumonia in the bilateral lower lung field. A lung biopsy specimen contained atypical lymphoid cells that were immunohistochemically positive for CD20 and MUM-1, and weakly positive for bcl-6, but negative for CD3 and CD10. There were no Epstein-Barr virus-infectious lymphoid cells by ISH-EBER. He was finally diagnosed with methotrexate-associated lymphoproliferative disorder (non-germinal center B-cell-like diffuse large B cell lymphoma histological type). Most of the nodules disappeared spontaneously following the withdrawal of methotrexate. DISCUSSION AND CONCLUSION: A cytologically conclusive diagnosis of methotrexate-associated lymphoproliferative disorder may be reached using sputum smears and clinical information.
29753087 Effects of salazosulfapyridine on the profile of cell surface proteins, revealed by biotin 2019 Jan OBJECTIVE: We investigated effects of salazosulfapyridine (SASP) on the protein profile of cell surface (CS)-proteins of SW982, a human synovial sarcoma cell line, using biotinylation of CS-proteins and 2-dimensional fluorescence difference gel electrophoresis (2D-DIGE). METHODS: SW982 cells were treated with SASP and its metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5ASA). Then the cells were treated with a membrane-impermeable biotinylating reagent. Biotinylated CS-proteins were isolated using NeutrAvidin-bound beads. CS-proteins affected by the drugs were detected by 2D-DIGE and subjected to mass spectrometry. RESULTS: By the 2D-DIGE analysis, in total 576 spots were detected, 29 out of which showed more than ±1.5-fold different intensity in the SASP-, SP-, and 5ASA-treated cells, compared to non-treated cells (p < 0.05). Interestingly, 7 out of the 29 spots changed their intensity only by SASP and 17 spots changed their intensity only by SP. We identified 9 protein from 15 out of the 29 spots, most of which were evidenced to exist on the cell surface by flow cytometry. CONCLUSION: We found novel effects of SASP and its metabolites on SW982 cells by the combination of biotinylation of cell surface proteins and 2D-DIGE analysis. These data would help understanding of anti-rheumatic actions of SASP. Furthermore, the combination would be a useful method for the analysis of CS-proteins in various conditions.