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ID PMID Title PublicationDate abstract
33331306 [Significance of anti-tubulin-α-1C autoantibody in systemic sclerosis]. 2020 Dec 18 OBJECTIVE: To detect the serum level of a novel autoantibody, anti-tubulin-α-1C, in patients with systemic sclerosis (SSc) and to investigate its clinical significance. METHODS: Anti-tubulin-α-1C antibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 62 patients with SSc, 38 systemic lupus erythematosus (SLE), 24 primary Sjögren's syndrome (pSS) patients, and 30 healthy controls (HCs). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin A(IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), C3, C4, rheumatoid factor (RF), antinuclear antibody(ANA), anti-centromere antibodies(ACA), anticardiolipin (aCL), anti-dsDNA antibody, anti-Sm antibody, anti-RNP antibody, anti-Scl-70 antibody, anti-Ro52 antibody, anti-SSA antibody, anti-SSB antibody, centromere protein A(CENP-A), centromere protein B (CENP-B) were measured by standard laboratory techniques. Raynaud's phenomenon and modified Rodnan skin score(MRSS) were recorded to evaluate the disease status of SSc. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman rank correlation were used for statistical analyses. RESULTS: The serum anti-tubulin-α-1C antibody concentration in SSc group was 81.24±34.38, the serum anti-tubulin-α-1C antibody concentration in SLE group was 87.84±38.52, the serum anti-tubulin-α-1C antibody concentration in pSS group was 59.79±25.24, and the serum anti-tubulin-α-1C antibody concentration in healthy group was 39.37±18.7. Multivariate analysis revealed that anti-tubulin-α-1C antibody levels were significantly increased in the SSc and SLE patients. The expression level of anti-tubulin-α-1C antibody in SSc was higher compared with the pSS group and the health control group (P < 0.01). Further analysis demonstrated that the elevated anti-tubulin-α-1C antibody were correlated with the SSc inflammation and disease activity markers ESR(r=0.313, P=0.019), The levels of anti-tubulin-α-1C antibody were also significantly correlated with MRSS(r=0.636, P < 0.01). The best cut-off value for the diagnose of SSc was 76.77 as mean+2SD value. The proportion of Raynaud's phenomenon was higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than that in anti-tubulin-α-1C autoantibody negative group(71.4% vs. 37.5%, P=0.039). The proportions of anti-Scl-70 antibody, anti-CENP antibody and anti-cardiolipin antibody were higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than in the anti-tubulin-α-1C autoantibody negative group (37.9% vs. 15.2%, 34.5% vs. 12.1%, 13.8 vs. 0, respectively, all P < 0.05). CONCLUSION: Based on this explorative stu-dy, the level of anti-tubulin-α-1C antibody increased in the serum of the patients with SSc. There were correlations between anti-tubulin-α-1C autoantibody and clinical and laboratory indicators of the SSc patients. It may become a novel biomarker indicative of active SSc and could be applied in future clinical practice.
31914604 A bispecific soluble receptor fusion protein that targets TNF-α and IL-21 for synergistic 2020 Jan This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL-17-producing T (Th17) cell-polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL-17 and vascular endothelial growth factor but increased the production of IL-10 in CD4(+) T cells, as well as directly suppressed osteoclastogenesis. Collagen-induced arthritis (CIA) and IL-1R antagonist (IL-1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours. Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL-1Ra knockout mice by reducing the numbers of inflammatory cytokine-expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL-17 and TNF-α, in murine splenic CD4(+) T cells. These findings suggest that BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, may be an effective treatment to overcome the limitations of anti-TNF therapy for patients with rheumatoid arthritis.
32274768 Ortho-vanillin nanoparticle-doped glucan microspheres exacerbate the anti-arthritic effec 2020 Jun BACKGROUND: Methotrexate (MTX) commonly used in rheumatoid arthritis (RA) has severe adverse effects. Ortho-vanillin, an inhibitor of Toll-like receptors (TLR), can prevent inflammation. Glucan is a cereal fiber recognized by dectin-1 or β-glucan receptors of phagocytic macrophages. The purpose of the current project was to study the effect of co-administration of MTX and vanillin by targeted delivery to macrophages using β-glucan microspheres to reduce inflammation of RA. METHODS: MTX and vanillin nanoparticles in bovine serum albumin (BSA) or gelatin were doped in glucan particles (GPs) and characterized for their physical properties. Twenty-four hours after induction of RA in paw of rats, they received normal saline (1 mg/kg, ip), MTX (2 mg/kg/week, ip), β-glucan (1 mg/kg/week, ip), GPs-MTX (2 mg/kg/week, ip), GPs-vanillin (200 mg/kg/day, po), and GPs-MTX (2 mg/kg/week, ip) plus GPs-vanillin (200 mg/kg/day, po). The last group received free MTX ip and vanillin po for 14 days. Then, joint diameters, TNF-α and IL-6, were evaluated in rats. RESULTS: The particle size of the GPs was 5.3 µm. MTX loading efficiency in glucan microspheres was 64.5% and vanillin 44.2%. The microspheres released 88.7% of MTX and 95.1% of vanillin over 24 h. The results of in vivo studies showed a significant reduction in paw volume, TNF-α and IL-6 (p < 0.05) in animals treated with combination of MTX and vanillin-doped glucan microspheres compared to the mixture of the two drugs in free form or each drug alone. CONCLUSIONS: Co-administration of MTX and vanillin-doped GPs may be more effective than MTX alone in RA.
33521573 Disease Activity, Functional Ability and Nutritional Status in Patients with Rheumatoid Ar 2020 Dec AIM: The aim of the present pilot study was to assess differences in the nutritional status, Mediterranean diet (MD) adherence, and functional ability among patients with rheumatoid arthritis (RA), according to disease activity. METHODS: A total of 48 patients with RA, outpatients of a hospital in Athens, Greece were recruited. Disease activity was evaluated with DAS28, functional status with the Health Assessment Questionnaire (HAQ), MD adherence with the MedDietScore and malnutrition with the patient-generated subjective global assessment (PG-SGA). RESULTS: A relationship was noted between DAS28 and HAQ, indicating a reduced functional status with increased RA activity. Although MD adherence differed between DAS28 categories, no specific differences were noted in the PG-SGA or the MedDietScore in the post-hoc analyses. According to the PG-SGA, no need for nutritional intervention was noted among participants. CONCLUSIONS: The origin of the participants might have reduced the differences between MD adherence and DAS28. In parallel, the PG-SGA does not appear sensitive in detecting muscle-related malnutrition among patients with RA.
33296441 Correction: Effect of methotrexate use on the development of type 2 diabetes in rheumatoid 2020 [This corrects the article DOI: 10.1371/journal.pone.0235637.].
30887278 Vascular Arginase Is a Relevant Target to Improve Cerebrovascular Endothelial Dysfunction 2020 Feb Emerging data revealed that rheumatoid arthritis (RA) is associated with higher risk of cerebrovascular diseases. Whereas cerebral endothelial dysfunction is acknowledged as a critical aspect of cerebrovascular diseases, its presence in RA and the mechanisms involved are currently unknown. By using the model of rat adjuvant-induced arthritis (AIA), the present study investigated cerebrovascular reactivity in pressurized middle cerebral arteries (MCA) on day 33 post-immunization. The results revealed that arthritis induced a dramatic decrease in the vasodilatory response to acetylcholine (ACh), ADP, and bradykinin (n = 7-9 arteries, p < 0.0001). By using nor-NOHA, L-NAME, BH(4), and Tempol, the results showed that the reduced response to ACh relied on arginase overactivation (n = 8), low NOS activity (n = 8), BH(4) deficiency (n = 9), and excessive superoxide production (n = 9). Immunohistological analysis revealed an endothelial upregulation of arginase 2 (p < 0.05, n = 5-6) and NADPH oxidase (p < 0.05, n = 5-7) while eNOS expression was unchanged in AIA (n = 6). To assess whether arginase inhibition may be a relevant therapeutic, AIA rats were treated with an arginase inhibitor (nor-NOHA, 40 mg/kg/day, i.p., n = 20 rats) daily from day 10 to day 33 post-immunization. The treatment alleviated the impaired response of MCA to endothelium-dependent agonists, through an increase in NOS signaling and a suppression of BH(4) deficiency and superoxide overproduction. By contrast, it did not change the course of arthritis. In conclusion, arthritis induced a cerebrovascular endothelial dysfunction involving an imbalance in the arginase/NOS pathway. Arginase inhibition appears as a promising therapy beyond anti-rheumatic drugs for reducing the risk of cerebrovascular diseases in RA.
33246116 Tunisian Olea europaea L. leaf extract suppresses Freund's complete adjuvant-induced rheum 2021 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. (olive) is traditionally used as a folk remedy and functional food in Europe and Mediterranean countries to treat inflammatory diseases. O. europaea contains phenolic compounds and have been reported to prevent cartilage degradation. However, the function and mechanism of O. europaea in rheumatoid arthritis are not known. AIM OF THE STUDY: In this study, we aimed to examine anti-inflammatory and anti-arthritic effects of Tunisian O. europaea L. leaf ethanol extract (Oe-EE). MATERIALS AND METHODS: To do this, we employed an in vitro macrophage-like cell line and an in vivo Freund's complete adjuvant (AIA)-induced arthritis model. Levels of inflammatory genes and mediators were determined from in vivo samples. RESULTS: The Oe-EE clearly reduced the production of the lipopolysaccharide-mediated inflammatory mediators, nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in RAW264.7 cells. The results of HPLC showed that Oe-EE contained many active compounds such as oleuropein and flavonoids. In AIA-treated rats, swelling of paws, pain, and cartilage degeneration were alleviated by oral Oe-EE administration. Correlating with in vitro data, PGE(2) production was significantly reduced in paw samples. Furthermore, the molecular mechanism of Oe-EE was dissected, and Oe-EE regulated the gene expression of interleukin (IL)-6, inducible NO synthase (iNOS), and MMPs and inflammatory signaling activation. CONCLUSION: Consequently, Oe-EE possesses anti-inflammatory and anti-rheumatic effects and is a potential effective treatment for rheumatoid arthritis.
32445658 Structural optimization of HPMA copolymer-based dexamethasone prodrug for improved treatme 2020 Aug 10 Despite their notorious adverse effects, glucocorticoids (GC, potent anti-inflammatory drugs) are used extensively in clinical management of rheumatoid arthritis (RA) and other chronic inflammatory diseases. To achieve a sustained therapeutic efficacy and reduced toxicities, macromolecular GC prodrugs have been developed with promising outcomes for the treatment of RA. Fine-tuning the activation kinetics of these prodrugs may further improve their therapeutic efficacy and minimize the off-target adverse effects. To assess the feasibility of this strategy, five different dexamethasone (Dex, a potent GC)-containing monomers with distinctively different linker chemistries were designed, synthesized, and copolymerized with N-(2-hydroxypropyl) methacrylamide (HPMA) to obtain 5 macromolecular Dex prodrugs. Their Dex releasing rates were analyzed in vitro and shown to display a wide spectrum of activation kinetics. Their therapeutic efficacy and preliminary toxicology profiles were assessed and compared in vivo in an adjuvant-induced arthritis (AA) rat model in order to identify the ideal prodrug design for the most effective and safe treatment of inflammatory arthritis. The in vivo data demonstrated that the C3 hydrazone linker-containing prodrug design was the most effective in preserving joint structural integrity. The results from this study suggest that the design and screening of different activation mechanisms may help to identify macromolecular prodrugs with the most potent therapeutic efficacy and safety for the management of inflammatory arthritis.
32190423 Rheumatoid meningitis: A case report and review of the literature. 2020 Feb PURPOSE OF REVIEW: Rheumatoid arthritis is a systemic inflammatory disorder, which can involve many organs; among which, CNS involvement, as in rheumatoid meningitis (RM), is rare and difficult to recognize. Our goal is to present collective data of RM cases to better characterize this disease process and to start new discussions about pathophysiology, diagnosis, and treatment. RECENT FINDINGS: Since Kato et al., 39 cases of RM have been reported. Approximately 59% were women, presenting with neurologic deficits (56%) and diagnosed by MRI findings, leptomeningeal enhancement (69%), after CSF analysis. Seventy-four percent were treated with corticosteroids, 64% as maintenance therapy, with 46% experiencing improvement or resolution in symptoms without relapse. SUMMARY: Diagnosis and prognosis of RM has drastically changed since the year 2000. Early detection with CSF and MRI or biopsy findings, coupled with early treatment using corticosteroids and immunologic therapy, has reduced mortality in this population.
33832983 Differential characteristics and management of pseudoseptic arthritis following hyaluronic 2021 Mar IMPORTANCE: Acute pseudoseptic arthritis is a rare complication of hyaluronic acid (HA) injections that is not well documented in the literature. Practitioners initially suspect the symptoms of this complication to represent septic arthritis, cautiously prescribing antibiotics. This review identifies that time to presentation of symptoms postinjection, negative cell cultures and lack of crystallisation could be used as differentials to suspect pseudoseptic arthritis and to prescribe anti-inflammatory drugs while closely monitoring change of symptoms. OBJECTIVE: The purpose of this study was to describe the presentation, diagnosis and treatment of pseudoseptic arthritis. EVIDENCE REVIEW: A systematic review of the literature was conducted for studies reporting the use of HA injections for osteoarthritis resulting in pseudoseptic arthritis using the electronic databases MEDLINE, Embase and PubMed. Pertinent data were abstracted from the search yield. A unique case of a pseudoseptic reaction is also presented. FINDINGS: A total of 11 studies (28 cases), all of level IV and V evidence were included in this review. Reported cases of pseudoseptic arthritis in the literature present with severe joint pain (100%), effusion (100%), inability to weight-bear, functional impairment, and occasionally fever (22.2%). C reactive protein and erythrocyte sedimentation rate are generally elevated (71.4% and 85.7%, respectively), and leucocytosis above 10 000 was less common (50%). All reported cases in the literature identified aseptic growth on arthrocentesis, despite four cases (15.4%) reporting synovial leucocyte counts above 50 000. The presented case is the highest reported leucocyte count at 1 74 960 cells/mm(3). CONCLUSIONS AND RELEVANCE: Acute pseudoseptic arthritis is rare, but a number of cases have been reported in the literature. A high degree of suspicion for pseudoseptic arthritis may be maintained in patients who present under 72 hours following HA injection. Initial antibiotic treatment, along with anti-inflammatory medications until cultures are confirmed to be negative at 5 days, is a cautious approach. However, the strength of this conclusion is limited by the few reported cases. Ultimately, this review is intended to inform practitioners of the symptoms, diagnosis and treatment of this complication, such that it could be safely differentiated from septic arthritis. LEVEL OF EVIDENCE: IV.
33081099 Therapeutic Maintenance of Baricitinib and Tofacitinib in Real Life. 2020 Oct 16 BACKGROUND: Janus kinase inhibitors (JAKis) represent a new alternative to treat rheumatoid arthritis (RA). The objective of this study was to evaluate the effectiveness, tolerance profile, and maintenance of these treatments (tofacitinib and baricitinib) in real life. METHODS: All patients in the rheumatology department of Amiens University Hospital treated by JAKis for RA were included from 1 October 2017 to 20 May 2020. Clinical and biological data were provided retrospectively in this observational and single-center study. We aimed to study the JAKi maintenance rate at 12 months and their clinical and biological safety profiles. RESULTS: Fifty-five patients were included. Drug maintenance at 12 months was 67.6%. Factors associated with poorer maintenance were a higher Charlson comorbidity index (HR 1.311 (1.089-1.579); p = 0.0042), a higher age (HR 1.055 (1.015-1.096); p = 0.0067), and corticosteroids therapy at initiation (HR 2.722 (1.006-7.365); p = 0.0487). The clinical and biological safety profile was generally good. CONCLUSIONS: Our study found that a higher Charlson index, age, and corticosteroids appeared to be associated with the earlier discontinuation of treatment. JAKis had a response and tolerance profile in real life at least equivalent to that of biological disease-modifying antirheumatic drugs (bDMARDs).
32884875 A Study on the Relevance of Glucose-6-Phosphate Dehydrogenase Level Screening in Patients 2020 Aug 2 Objective Drug-induced hemolytic anemia can occur in patients with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The practice of G6PD-deficiency screening in the rheumatology field has been inconsistent. This study aimed to determine the utility of screening prior to the initiation of hydroxychloroquine and/or sulfasalazine in rheumatology patients in the ambulatory clinics at Stony Brook University Hospital, New York. Methods We conducted a retrospective chart review of cases of rheumatic diseases that were screened for G6PD deficiency at Stony Brook University Hospital ambulatory clinics. Demographic details and relevant clinical and laboratory data of the patients were collected. The data from similar studies in the literature were searched for and reviewed. Results This study consisted of 228 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome. Among those patients, 94.7% received hydroxychloroquine, sulfasalazine, or dapsone; 41% (89/228) of patients were screened for G6PD deficiency, and the majority of them were on treatment with hydroxychloroquine. Of those patients, 7.9% (five Caucasians and two African Americans) were found to have G6PD deficiency, and two of the G6PD-deficient patients received hydroxychloroquine. There was no incidence of hemolytic anemia documented in any of the seven patients with G6PD deficiency. We reviewed the literature and found three similar studies of patients receiving hydroxychloroquine with no reported hemolytic anemia from different medical centers in the US, and the frequency of G6PD deficiency reported in these studies was 1.4%, 4.0%, and 4.2%, respectively. Conclusions Our study suggests that the frequency of G6PD deficiency in our rheumatic population is similar to that of the general population, and the risk of hemolytic anemia in G6PD deficiency associated with hydroxychloroquine is extremely rare. Hence, G6PD screening may not be recommended prior to starting treatment with hydroxychloroquine.
32448639 Microbes, helminths, and rheumatic diseases. 2020 Aug There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.
32831850 Serum Peptidomic Profile as a Novel Biomarker for Rheumatoid Arthritis. 2020 Over the last decades, there has been an increasing need to discover new diagnostic RA biomarkers, other than the current serologic biomarkers, which can assist early diagnosis and response to treatment. The purpose of this study was to analyze the serum peptidomic profile in patients with rheumatoid arthritis (RA) by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The study included 35 patients with rheumatoid arthritis (RA), 35 patients with primary osteoarthritis (OA) as the disease control (DC), and 35 healthy controls (HC). All participants were subjected to serum peptidomic profile analysis using magnetic bead (MB) separation (MALDI-TOF-MS). The trial showed 113 peaks that discriminated RA from OA and 101 peaks that discriminated RA from HC. Moreover, 95 peaks were identified and discriminated OA from HC; 38 were significant (p < 0.05) and 57 nonsignificant. The genetic algorithm (GA) model showed the best sensitivity and specificity in the three trials (RA versus HC, OA versus HC, and RA versus OA). The present data suggested that the peptidomic pattern is of value for differentiating individuals with RA from OA and healthy controls. We concluded that MALDI-TOF-MS combined with MB is an effective technique to identify novel serum protein biomarkers related to RA.
32141956 Lyme disease: diagnosis and treatment. 2020 May PURPOSE OF REVIEW: Lyme disease is an important, vector-borne infection found throughout the temperate Northern hemisphere. The disease causes rash, acute systemic illness, and in some untreated patients, inflammatory arthritis. This review examines the emergence, clinical features and management of early Lyme disease and Lyme arthritis. RECENT FINDINGS: There has been continuing progress in characterizing the clinical manifestations, diagnostic testing and treatment of Lyme disease. Almost all patients with early Lyme disease can be cured with antibiotic treatment. In most cases, Lyme arthritis also responds to antibiotics, but some patients require additional treatment approaches. SUMMARY: The diagnosis of Lyme disease is based on clinical manifestations and adjunctive laboratory testing. For the rheumatologist, Lyme arthritis should be recognized by a pattern of attacks of asymmetric, oligo-arthritis, recognizable by clinical manifestations in the same way that other rheumatic diseases, such as gout or rheumatoid arthritis, are diagnosed.
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.
32914050 Use of biologic or targeted-synthetic disease-modifying anti-rheumatic drugs and risk of d 2020 OBJECTIVES: Given that RA treatment might affect the severity of diabetes mellitus (DM), we compared the risk of DM treatment intensification in patients with both RA and DM newly initiating a biologic DMARD or tofacitinib. METHODS: Using claims data from the IBM MarketScan database (2005-2016), we identified patients aged ≥18 years with RA who initiated abatacept, a TNF inhibitor (TNFi), rituximab, tocilizumab or tofacitinib. Patients were required to have type 1 or type 2 DM and to use at least one antidiabetic drug at baseline. We assessed DM treatment intensification (i.e. addition of a new insulin or non-insulin antidiabetic medication). We also assessed non-insulin antidiabetic medication switching events. RESULTS: We included 10 019 patients with RA and DM initiating a biologic DMARD or tofacitinib. Baseline insulin use was the highest in rituximab initiators (44%) and lowest in tofacitinib initiators (35%). The incidence rate per 1000 person-years for DM treatment intensification ranged from 148.2 (tofacitinib) to 198.0 (rituximab). The risk of DM treatment intensification was similar between abatacept and TNFi [hazard ratio (HR) 0.97, 95% CI: 0.82, 1.15], rituximab (HR 0.99, 95% CI: 0.79, 1.23) and tocilizumab (HR 0.94, 95% CI: 0.74, 1.19), but lower for tofacitinib compared with abatacept (HR 0.67, 95% CI: 0.50, 0.90). The risk of non-insulin DM treatment switching was not different between abatacept and other biologic DMARDs. CONCLUSION: In patients with both RA and DM, we found no difference in the risk of DM treatment switching or intensification after initiating abatacept vs TNFi, rituximab and tocilizumab, whereas the risk appeared to be lower for tofacitinib.
32402735 Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case repor 2020 Aug Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.
32873150 TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases 2020 Sep Aberrant tumour necrosis factor (TNF) signalling is a hallmark of many inflammatory diseases including rheumatoid arthritis (RA), irritable bowel disease and lupus. Maladaptive TNF signalling can lead to hyper active downstream nuclear factor (NF)-κβ signalling in turn amplifying a cell's inflammatory response and exacerbating disease. Within the TNF intracellular inflammatory signalling cascade, transforming growth factor-β-activated kinase 1 (TAK1) has been shown to play a critical role in mediating signal transduction and downstream NF-κβ activation. Owing to its role in TNF inflammatory signalling, TAK1 has become a potential therapeutic target for the treatment of inflammatory diseases such as RA. This review highlights the current development of targeting the TNF-TAK1 signalling axis as a novel therapeutic strategy for the treatment of inflammatory diseases.
32704614 Two parallel short forms to measure disease- and treatment-associated knowledge in rheumat 2020 OBJECTIVE: The aim was to develop two disease- and treatment-related knowledge about RA (DataK-RA) short forms using item response theory-based linear optimal test design. METHODS: We used the open source Excel add-in solver to program a linear optimization algorithm to develop two short forms from the DataK-RA item bank. The algorithm was instructed to optimize precision (i.e. reliability) of the scores for both short forms, subject to a number of constraints that served to ensure that each short form would include unique items and that the short forms would have similar psychometric properties. Agreement among item response theory scores obtained from the different short forms was assessed using the Bland-Altman method and Student's paired t-test. Construct validity and relative efficiency of the short forms was evaluated by relating the score to age, sex and educational attainment. RESULTS: Two short forms were derived from the DataK-RA item bank that satisfied all content constraints. Both short forms included 15 unique items and yielded reliable scores (r > 0.70), with low ceiling and floor effects. The short forms yielded statistically indistinguishable mean scores according to Student's paired t-test and Bland-Altman analysis. Scores on short forms 1 and 2 were associated with age, sex and educational attainment to a similar extent. CONCLUSION: In this study, we developed two DataK-RA short forms with unique items, yet similar psychometric properties, that can be used to assess patients pre- and post-test interventions aimed at improving disease-related knowledge in RA patients.