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ID PMID Title PublicationDate abstract
32921004 Posttraumatic Stress Disorder, Depression, Anxiety, and Persistence of Methotrexate and TN 2020 Oct OBJECTIVE: To examine the relationship of posttraumatic stress disorder (PTSD) with earlier treatment discontinuation and medication adherence in US veterans with rheumatoid arthritis (RA). METHODS: Veterans Affairs (VA) administrative data (2005-2014) were used to define unique dispensing episodes of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) for veterans with RA. Diagnosis codes were used to categorize patients into mutually exclusive groups: PTSD (with/without depression/anxiety), depression/anxiety without PTSD, and neither psychiatric diagnosis. Multivariable Cox proportional hazards models were used to evaluate associations between psychiatric diagnoses and time to disease-modifying antirheumatic drug discontinuation (lapse in refill >90 days). Multivariable logistic regression was used to examine associations of diagnoses with medication nonadherence (proportion of days covered <0.8). RESULTS: There were 15 081 dispensing episodes of MTX and 8412 dispensing episodes of TNFi. PTSD was independently associated with a greater likelihood of earlier discontinuation of both MTX (hazard ratio [HR] 1.15 [1.10-1.21]) and TNFi (HR 1.20 [1.13-1.28]). Depression/anxiety had a comparable risk of discontinuation for both MTX (HR 1.14 [1.10-1.19]) and TNFi (HR 1.16 [1.10-1.22]). Depression/anxiety, but not PTSD, was associated with higher odds of MTX (odds ratio [OR] 1.12 [1.03-1.22]) and TNFi (OR 1.14 [1.02-1.27]) nonadherence. CONCLUSION: Veterans with RA and comorbid PTSD, depression, or anxiety had poor persistence of MTX and TNFi therapies. These results suggest that earlier discontinuation and low adherence to therapy among patients with RA with these psychiatric comorbidities may contribute to worse disease outcomes. Mechanisms by which these comorbidities contribute to lower adherence deserve further investigation and may lead to targeted interventions to improve disease outcomes.
31416922 Evaluation of the Economic Burden of Psoriatic Arthritis and the Relationship Between Func 2020 May 1 OBJECTIVE: This analysis aimed to evaluate the economic burden of patients with psoriatic arthritis (PsA) on the UK healthcare system and estimate the relationship between functional status and direct healthcare costs. METHODS: Functional status [measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI)], demographics, disease history, and healthcare resource use data were extracted from a cohort of patients at the Royal National Hospital for Rheumatic Diseases, Bath, UK. Each resource use item per patient was then allocated a unit cost. Linear regression models were used to predict costs as a function of HAQ-DI. Medication costs were not included in the primary analysis, which was carried out from the UK National Health Service perspective. RESULTS: Data were available for 101 patients. Mean HAQ-DI score was 0.84 (SD 0.75) and mean age at HAQ-DI measurement was 57.8 (SD 10.7). Total annual healthcare costs per patient, excluding medication costs, ranged between £174 and £8854, with a mean of £1586 (SD £1639). A 1-point increase in HAQ-DI score was associated with an increase in total costs of £547.49 (standard error £224), with secondary care consultations appearing to be the primary factor. Subgroup analyses suggested higher cost increases in patients with HAQ-DI scores of 2-3 and with a disease duration > 10 years. CONCLUSION: Patients with PsA place a significant economic burden on the healthcare system. Functional status is highly correlated with costs and appears to be driven mainly by the cost of secondary care consultations. Results were similar to previous studies in rheumatoid arthritis populations.
32714994 Clinical Characteristics of Peripheral Neuropathy in Eosinophilic Granulomatosis with Poly 2020 OBJECTIVE: To investigate clinical features, independent associated factors, treatment, and outcome of patients with peripheral neuropathy (PN) in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We retrospectively analyzed clinical data of 110 EGPA patients from 2007 to 2019 in Peking Union Medical College Hospital. The independent factors associated with PN in EGPA were analyzed with univariate and multivariate logistic regressions. RESULTS: In EGPA with PN, paresthesia and muscle weakness were observed in 82% and 33% of patients, respectively. Both the upper and lower limbs were involved in 51% of patients. 30% of EGPA patients had symmetrical multiple peripheral neuropathy, whereas only 16.4% presented with mononeuritis multiplex. Compared to patients without PN, patients with PN had a higher erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Birmingham vasculitis activity score (BVAS), and positivity of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). Regarding manifestations, patients with PN tended to develop weight loss and arthritis or joint pain. Notably, ANCA positivity, arthritis or joint pain, and higher BVAS were found to be independent associated factors for PN in EGPA. Patients with PN more frequently need glucocorticoid pulses and intravenous infusion of cyclophosphamide. With the longest follow-up of 11.0 years, we found that age and cardiac involvement were risk factors for survival, and female was the protective factor. CONCLUSION: PN in EGPA frequently displays with symmetrical multiple peripheral neuropathy in China. Positive ANCA, arthritis or joint pain, and higher BVAS are the independent associated factors of PN in EGPA. Glucocorticoids with immunosuppressants are vital therapeutic strategy.
32089932 Tuberculous Arthritis of the Knee with Rice Body Formation: A Report of a Rare Case. 2020 In this report, we present the case of a 53-year-old man with rice body formation in the right knee caused by tuberculous arthritis (TB arthritis). The patient visited our hospital in January 2018 with a seven-month history of swelling and pain in the right knee. He had no previous history of tuberculosis, and the results of the routine laboratory tests were within normal limits; he also tested negative for rheumatoid factor. Magnetic resonance (MR) imaging revealed multiple rice bodies in the right knee, measuring 5-8 mm. He underwent an arthroscopic operation in the right knee in January 2018 and received antituberculosis polytherapy for 6 months. He was followed-up for more than 01 year. The patient regained good function of the operated knee with no evidence of recurrence during the last follow-up in February 2019. Conclusion. The biggest challenge in diagnosing tuberculosis arthritis is the consideration of its possibility in the differential diagnosis, not only in endemic countries where tuberculosis is frequent. A high level of suspicion for TB should be maintained for every infection of the knee joint, particularly in the case of intra-articular rice bodies.
32506699 Incidence of COVID-19 in Patients With Rheumatic Diseases Treated With Targeted Immunosupp 2020 Oct OBJECTIVE: To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. METHODS: Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab. RESULTS: The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. CONCLUSION: Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region.
31852583 An increased disease burden of autoimmune inflammatory rheumatic diseases in Korea. 2020 Jun OBJECTIVES: To estimate the prevalence, medical utilization, and recent changes in the economic burden of autoimmune rheumatic diseases (AIRDs) in Korea. METHODS: Using a nationwide claims database that includes all medical claims made by approximately 50 million Korean residents, the prevalences of seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and others between 2012 and 2016 were calculated. Changes in medical utilization and the direct medical costs of each AIRD from 2012 to 2016 were also evaluated. RESULTS: Based on the data for 2016, seropositive RA was the most common AIRD in Korea with 96,330 cases (188.5/100,000 population), followed by AS (30,006, 58.7/100,000 population), SLE (19,441, 38.0/100,000 population), Behçet's disease (BD, 14,943, 29.2/100,000 population), primary Sjögren syndrome (pSS, 12,018, 23.5/100,000 population), and systemic sclerosis (SSc, 3606, 7.1/100,000 population). In terms of medical utilization, patients with eosinophilic granulomatosis with polyangiitis visited outpatient clinics the most frequently (9.8 times/year/patient), while hospitalization was most frequent in microscopic polyangiitis patients (1.0 time/year/patient). Total medical costs for all AIRDs increased from $154,348,011 in 2012 to $262,481,974 in 2016. The annual medical cost per patient in 2016 was the highest in microscopic polyangiitis ($6223/year), followed by psoriatic arthritis ($3,362/year), and granulomatosis with polyangiitis ($2823/year). CONCLUSIONS: In Korea, the most prevalent AIRD is seropositive RA, followed by AS, SLE, BD, pSS, and SSc. The economic burden of AIRDs has risen substantially in the last 5 years due not only to an increase in their prevalence but also to an increase in medical costs per patient.
33087256 Natural Killer Cell Transcript 4 promotes the development of Sjӧgren's syndrome via activ 2021 Jan Autoimmune disorders are the third most common diseases in the United States, and affect the daily lives of millions of people. In this study, we analyzed patient samples, utilized a transgenic mouse model and human B cells to reveal Natural Killer Cell Transcript 4 (NK4) as a novel regulator that promotes the development of autoimmune disorders. NK4 was significantly elevated in samples from patients with Sjӧgren's Syndrome (SS). SS patients show elevated NK4 levels. There is a strong and positive correlation between the increased levels of NK4 and the duration of SS. Interestingly, transgenic expression of NK4 in a mouse model led to the development of autoantibodies and lymphocytic infiltration in salivary glands similar to those in SS patients. Those phenotypes were associated with increased B1a cells in the peritoneum, plasma cells in the spleen, and increased IgM, IgA, and IgG2a in serum of the NK4 transgenic mice. The autoimmune phenotypes became more severe in older mice. Moreover, after NK4 transfection, human naïve B cells were activated and memory B cells differentiation into IgG and IgA-plasmablasts, resulting in an increased production of autoantibodies.NK4 regulated the differentiation and activation of B cells through activating Rap1 activity. NK4 also promoted B cell migration in a paracrine fashion through an induction of CXCL13 in endothelial cells. Collectively, these findings identify NK4 as a promoter of the development of autoimmune disorders through its roles on B cells. Therefore, NK4 may be a novel therapeutic target for the treatment of autoimmune diseases.
32299307 Diagnosis and treatment of primary biliary cholangitis. 2020 Jul Primary biliary cholangitis is a cholestatic, chronic autoimmune liver disease with a wide individual variation in disease progression. The diagnosis is predominantly based on chronic elevation of alkaline phosphatase and the presence of anti-mitochondrial antibodies or other specific antinuclear antibodies (i.e. anti-gp210 and anti-sp100). Even in early-stage disease, health-related quality of life can be severely impaired by symptoms such as pruritus, fatigue, and sicca syndrome and metabolic bone disease should be assessed and treated. The prognosis of the disease is, however, largely determined by the development of cirrhosis and its complications. Ursodeoxycholic acid is associated with an improved prognosis and should be initiated and continued in all patients. Clinical outcome is related to the biochemical response to ursodeoxycholic acid, but the prognosis of those with an incomplete response is still better than those who remain untreated. Obeticholic acid was recently approved as second-line treatment and bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Preliminary data suggest an additive effect of triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate, whereas other promising drugs are being evaluated in clinical trials.
33268076 Factors predictive for union of basal fracture of the ulnar styloid process after distal r 2021 Mar BACKGROUND: Some basal ulnar styloid fractures (USFs) achieve union without surgical fixation when accompanying distal radius fractures (DRFs) are treated via placement of volar locking plates (VLPs). The purpose of this study was to seek factors predictive of such healing through the retrospective case-control study. METHODS: We evaluated 203 patients who received VLPs to treat DRFs in our institute from March 2010 to February 2018; Group 1 contained "union" patients and Group 2 contained "nonunion" patients. Basic demographic, radiological, and operative variables were compared. At the final follow-up (at least 2 years postoperatively), pain was scored using a visual analog scale (VAS). Scores on the Disabilities of the Arm, Shoulder, and Hand (DASH) instrument; grip strengths; and demerit points of the Gartland and Werley system were compared between groups. RESULTS: Group 1 consisted of 58 patients and Group 2 consisted of 147 patients. Univariate analysis showed that age, bone mineral density (BMD), and Gaulke USF classification significantly differed between groups (all p < 0.05). Multivariate analysis showed that BMD (p < 0.001, odds ratio [OR] = 0.214, 95% confidence interval [95% CI] = 0.126-0.363) and Gaulke classification (p < .001, OR = 0.092, 95% CI = 0.034-0.250) were significantly associated with USF union, which was significantly higher in patients with mean BMD ≥ -0.12 (the cutoff value) and type IIC USFs. However, postoperative clinical outcomes at the final follow-up did not differ significantly between groups (all p > 0.05). CONCLUSIONS: Approximately 30% (58/205) of basal USFs associated with DRFs united after VLPs alone were placed to treat the DRFs. BMD ≥ -0.12 independently predicted union. Type IIC USFs exhibited more union than other fracture types. Additional surgical fixation of a basal USF accompanied by a DRF treated via VLP placement may be unnecessary, especially if BMD is good and fracture type is IIC. LEVEL OF EVIDENCE: Level III, Case-control study.
33319166 Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19. 2021 Jan 22 Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood but is not associated with severity of COVID-19 disease, length of stay, or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo, aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
32545788 Focus on the Role of NLRP3 Inflammasome in Diseases. 2020 Jun 13 Inflammation is a protective reaction activated in response to detrimental stimuli, such as dead cells, irritants or pathogens, by the evolutionarily conserved immune system and is regulated by the host. The inflammasomes are recognized as innate immune system sensors and receptors that manage the activation of caspase-1 and stimulate inflammation response. They have been associated with several inflammatory disorders. The NLRP3 inflammasome is the most well characterized. It is so called because NLRP3 belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent evidence has greatly improved our understanding of the mechanisms by which the NLRP3 inflammasome is activated. Additionally, increasing data in animal models, supported by human studies, strongly implicate the involvement of the inflammasome in the initiation or progression of disorders with a high impact on public health, such as metabolic pathologies (obesity, type 2 diabetes, atherosclerosis), cardiovascular diseases (ischemic and non-ischemic heart disease), inflammatory issues (liver diseases, inflammatory bowel diseases, gut microbiome, rheumatoid arthritis) and neurologic disorders (Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis and other neurological disorders), compared to other molecular platforms. This review will provide a focus on the available knowledge about the NLRP3 inflammasome role in these pathologies and describe the balance between the activation of the harmful and beneficial inflammasome so that new therapies can be created for patients with these diseases.
32190609 Inhibitory Effect of Rosae Multiflorae Fructus Extracts on the Receptor Activator of NF-κ 2020 Feb BACKGROUND: Rosae Multiflorae fructus (RMF), known to have anti-inflammatory and antioxidant properties, has been used as a traditional remedy for inflammatory diseases such as arthritis in Eastern Asia. However, its effect on osteoclasts, which play a crucial role in resorptive inflammatory bone diseases, is yet to be elucidated. METHODS: The effect of extract of RMF (RMF-E) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis was examined by tartrate-resistant acid phosphatase (TRAP) staining, real-time polymerase chain reaction and western blot analysis. In addition, RANKL-induced Ca(2+)-oscillation was also investigated. RESULTS: RMF-E remarkably inhibited TRAP(+)-osteoclast and resorptive pit formation in a dose-dependent manner. In addition, the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic, known as pivotal transcription factors for osteoclast formation in vitro and in vivo, and that of the osteoclast differentiation markers such as Acp5, Oscar, CtsK, Atp6v0d2, Tm7sf4, and Nfatc1 were significantly decreased by RMF-E treatment during osteoclastogenesis. The inhibitory effect of RMF-E on RANKL-induced osteoclastogenesis was caused by the suppression of p38 mitogen-activated protein kinase activation, and RANKL-induced Ca(2+)-oscillation removal via inactivation of Bruton's tyrosine kinase (BTK), and subsequently phospholipase C-γ2. CONCLUSIONS: RMF-E negatively regulates osteoclast differentiation and formation. These findings suggest the possibility of RMF-E as a traditional therapeutic agent against osteoclast-related bone disorders such as osteoporosis, rheumatoid arthritis, and periodontitis.
33208344 Anti-centromere antibodies target centromere-kinetochore macrocomplex: a comprehensive aut 2021 May OBJECTIVES: Anti-centromere antibodies (ACAs) are detected in patients with various autoimmune diseases such as Sjögren's syndrome (SS), systemic sclerosis (SSc) and primary biliary cholangitis (PBC). However, the targeted antigens of ACAs are not fully elucidated despite the accumulating understanding of the molecular structure of the centromere. The aim of this study was to comprehensively reveal the autoantigenicity of centromere proteins. METHODS: A centromere antigen library including 16 principal subcomplexes composed of 41 centromere proteins was constructed. Centromere protein/complex binding beads were used to detect serum ACAs in patients with SS, SSc and PBC. ACA-secreting cells in salivary glands obtained from patients with SS were detected with green fluorescent protein-fusion centromere antigens and semiquantified with confocal microscopy. RESULTS: A total of 241 individuals with SS, SSc or PBC and healthy controls were recruited for serum ACA profiling. A broad spectrum of serum autoantibodies was observed, and some of them had comparative frequency as anti-CENP-B antibody, which is the known major ACA. The prevalence of each antibody was shared across the three diseases. Immunostaining of SS salivary glands showed the accumulation of antibody-secreting cells (ASCs) specific for kinetochore, which is a part of the centromere, whereas little reactivity against CENP-B was seen. CONCLUSIONS: We demonstrated that serum autoantibodies target the centromere-kinetochore macrocomplex in patients with SS, SSc and PBC. The specificity of ASCs in SS salivary glands suggests kinetochore complex-driven autoantibody selection, providing insight into the underlying mechanism of ACA acquisition.
31993047 Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Mod 2019 Toll-like receptors (TLRs) are important mediators of chronic inflammation in numerous autoimmune diseases, although the role of these receptors in primary Sjögren's syndrome (pSS) remains incompletely understood. Previous studies in our laboratory established Myd88 as a crucial mediator of pSS, although the disease-relevant ligands and the upstream signaling events that culminate in Myd88 activation have yet to be established. The objective of this study was to identify specific Myd88-dependent TLR-related pathways that are dysregulated both locally and systemically in a mouse model of pSS [NOD.B10Sn-H2 (b) /J (NOD.B10)]. We performed RNA-sequencing on spleens derived from NOD.B10 mice. We then harvested salivary tissue and spleens from Myd88-sufficient and deficient C57BL/10 (BL/10) and NOD.B10 mice and performed flow cytometry to determine expression of Myd88-dependent TLRs. We cultured splenocytes with TLR2 and TLR4 agonists and measured production of inflammatory mediators by ELISA. Next, we evaluated spontaneous and TLR4-mediated inflammatory cytokine secretion in NOD.B10 salivary tissue. Finally, we assessed spontaneous Myd88-dependent cytokine secretion by NOD.B10 salivary cells. We identified dysregulation of numerous TLR-related networks in pSS splenocytes, particularly those employed by TLR2 and TLR4. We found upregulation of TLRs in both the splenic and salivary tissue from pSS mice. In NOD.B10 splenic tissue, robust expression of B cell TLR1 and TLR2 required Myd88. Splenocytes from NOD.B10 mice were hyper-responsive to TLR2 ligation and the endogenous molecule decorin modulated inflammation via TLR4. Finally, we observed spontaneous secretion of numerous inflammatory cytokines and this was enhanced following TLR4 ligation in female NOD.B10 salivary tissue as compared to males. The spontaneous production of salivary IL-6, MCP-1 and TNFα required Myd88 in pSS salivary tissue. Thus, our data demonstrate that Myd88-dependent TLR pathways contribute to the inflammatory landscape in pSS, and inhibition of such will likely have therapeutic utility.
33323531 Improving Pneumococcal Vaccination Rates in Rheumatology Patients by Using Best Practice A 2021 Sep OBJECTIVE: To improve pneumococcal vaccination (PV) rates among rheumatology clinic patients on immunosuppressive therapy in the outpatient settings. METHODS: This quality improvement project was based on the pre-post intervention design. Phase I of the project targeted patients with rheumatoid arthritis from 13 rheumatology clinics (January 2013-July 2015) on immunosuppressive therapy to receive the pneumococcal polysaccharide vaccine (PPSV23). In the Phase II study (January 2016-October 2017), all patients on immunosuppressive medications regardless of diagnosis were targeted to receive PPSV23 and the pneumococcal conjugate vaccine (PCV13). The best practice alerts (BPAs) for both PVs were developed based on the Centers for Disease Control and Prevention guidelines, which appeared on electronic medical records for eligible patients at the time of assessment by the medical assistant. The BPA was designed to inform the vaccination status and enable the physician to order the PV, or to document refusal or deferral reasons. Education regarding vaccine guidelines, BPAs, vaccination process, and regular feedback of results were important project interventions. The vaccination rates during pre-post intervention for each study phase were compared using chi-square test. RESULTS: During phase I, PPSV23 vaccination rates improved from a 28% preintervention rate to 61.5% (P < 0.0001). During phase II, 77.4% of patients had received either PPSV23, PCV13, or both, compared to 49.6% of patients in the preintervention period (P < 0.0001). The documentation rates (vaccine received, ordered, patient refusal and deferral reasons) increased significantly in both phases. CONCLUSION: Electronic identification of vaccine eligibility and implementation of BPAs with capabilities to order and document resulted in significantly improved PV rates. The process has potential for self-sustainability and generalizability.
33197589 Does preoperative diagnosis impact patient outcomes following reverse total shoulder arthr 2021 Jun BACKGROUND: The indications for reverse total shoulder arthroplasty (rTSA) have expanded to include the treatment of a wide variety of shoulder pathologies, and there may be significant differences in patient outcomes based on preoperative diagnosis. METHODS: A systematic review of the orthopedic literature contained in the PubMed, Cochrane, and Embase databases was performed on November 14, 2019. Studies investigating rTSA indicated for 7 distinct preoperative diagnoses (massive rotator cuff tear [MCT] without glenohumeral osteoarthritis [GHOA], MCT with GHOA or cuff tear arthropathy, primary GHOA, inflammatory arthritis with MCT, failed shoulder arthroplasty, proximal humeral fracture [PHF], and sequelae following PHF) were included. The main outcomes of interest included functional outcomes (abduction, external rotation, and forward flexion) and patient-reported outcome measures (American Shoulder and Elbow Surgeons shoulder score and Constant-Murley score). Because of significant variation in measurement and reporting, data on internal rotation were not extracted. In addition, radiographic outcomes and complication rates were extracted and recorded for each of the included studies. RESULTS: In total, 47 studies, comprising 2280 patients, met the inclusion criteria. Significant improvements in functional outcomes and patient-reported outcome measures were found across the preoperative diagnostic groups. There were no significant differences between the diagnostic groups regarding improvement between preoperative and postoperative values for the outcomes of interest, with the exception that the inflammatory arthropathy group had significantly less improvement in the Constant-Murley score than the primary GHOA and revision arthroplasty groups. Although there were few differences in improvement between groups, there were significant differences regarding the level of postoperative functional performance, which was not as consistent in the context of trauma or revision operations (ie, complex PHF, fracture sequela, and revision arthroplasty groups). CONCLUSION: Reverse total shoulder arthroplasty can provide reliable improvement in clinical outcomes regardless of preoperative diagnosis, with few differences across diagnostic groups regarding preoperative to postoperative improvement. The groups with primary GHOA and MCTs with or without GHOA demonstrated the most reliable postoperative functional outcomes of the examined diagnostic groups. Postoperative outcomes were not as consistent in the context of trauma or revision operations, and these groups may benefit from a variety of modern advancements in rTSA, although further research into these modalities for these groups is needed. Finally, rTSA remains an important treatment option in the context of rheumatoid arthritis, with similar outcomes and complication rates compared with the 6 other operative indications.
33327271 CD74 auto-antibodies display little clinical value in Chinese Han population with axial sp 2020 Dec 11 The European cohort study has indicated about CD74 IgG-autoantibodies as potential marker for axial spondyloarthritis (axSpA) diagnosis. However, multiple studies have questioned the diagnostic value of various disease-specific autoantibodies in different ethnic groups. Here, we have tried to assess the diagnostic value of anti-CD74 IgG and IgA autoantibodies in axSpA patients from Chinese Han population.The anti-CD74 IgG and IgA autoantibodies were analyzed using ELISA assay in a cohort of 97 axSpA patients, including 47 treatment-naïve axSpA patients never treated with steroids or immunosuppressants and 50 treated axSpA patients. The rheumatic disease control (RDC) group consisted of 40 rheumatoid arthritis, 25 systemic lupus erythematosus, 18 psoriatic arthritis patients, and 60 healthy controls (HC).Our data demonstrated the presence of anti-CD74 IgA auto-antibodies in 25.8% of the axSpA patients, 30.1% of the RDC group patients and none in HC. Similarly, anti-CD74 IgG autoantibodies were observed in 23.7% of the axSpA patients, 18.1% of the RDC patients and 18.3% of the HC. The sensitivity, specificity, and accuracy of IgA autoantibodies were 21.3%, 82.5%, & 67.4%, respectively, while for IgG, it was 27.7%, 81.8%, and 68.4%, in treatment-naïve axSpA patients. Furthermore, weak positive relationship between anti-CD74 IgA autoantibodies and bath ankylosing spondylitis disease activity index ( r = 0.253, P = .012) and functional index (bath ankylosing spondylitis functional index; r = 0.257, P = .011) was observed.Overall, our study demonstrated little clinical and predictive value of CD74 autoantibodies in the diagnosis of axSpA and its related manifestations, among Chinese Han population.
33299992 Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19. 2020 Dec 3 Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood, but is not associated with severity of COVID-19 disease, length of stay or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo , aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
31562704 Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significa 2020 Mar Autoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen- or damage-associated molecular patterns via pattern-recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions, including infectious, metabolic, autoinflammatory, and autoimmune diseases. The inflammasome generally comprises a PRR, procaspase 1, and an adaptor molecule connecting the PRR and procaspase 1. Upon inflammasome activation, procaspase 1 becomes active caspase 1 that converts pro-interleukin-1β (proIL-1β) and proIL-18 into mature and active IL-1β and IL-18, respectively. The cytokines IL-1β and IL-18 have multipotent effects on immune and nonimmune cells and induce and promote systemic and local inflammatory responses. Human studies have shown increased levels of these cytokines, altered activation of inflammasome-related molecules, and/or the presence of inflammasome activators in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, crystal-induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs, such as the kidneys, joints, and salivary glands, as well as in the cardiovascular system. In animal models of rheumatic diseases, inflammation and tissue damage improve upon genetic or pharmacologic targeting of the inflammasome, supporting its pathogenic role. Herein, we review the clinicopathologic significance and therapeutic targeting of inflammasome activation in rheumatic diseases and related conditions based on recent findings.
32132215 A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without 2020 Mar 4 On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense peptides (CDPs) that rapidly accumulate in cartilage of the knees, ankles, hips, shoulders, and intervertebral discs after systemic administration. These CDPs could be used to concentrate arthritis drugs in joints. A cartilage-accumulating peptide, CDP-11R, reached peak concentration in cartilage within 30 min after administration and remained detectable for more than 4 days. Structural analysis of the peptides by crystallography revealed that the distribution of positive charge may be a distinguishing feature of joint-accumulating CDPs. In addition, quantitative whole-body autoradiography showed that the disulfide-bonded tertiary structure is critical for cartilage accumulation and retention. CDP-11R distributed to joints while carrying a fluorophore imaging agent or one of two different steroid payloads, dexamethasone (dex) and triamcinolone acetonide (TAA). Of the two payloads, the dex conjugate did not advance because the free drug released into circulation was sufficient to cause on-target toxicity. In contrast, the CDP-11R-TAA conjugate alleviated joint inflammation in the rat collagen-induced model of rheumatoid arthritis while avoiding toxicities that occurred with nontargeted steroid treatment at the same molar dose. This conjugate shows promise for clinical development and establishes proof of concept for multijoint targeting of disease-modifying therapeutic payloads.