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ID PMID Title PublicationDate abstract
32843324 Salivary gland epithelial cells from patients with Sjögren's syndrome induce B-lymphocyte 2020 Nov OBJECTIVE: Primary Sjögren's syndrome (pSS) is characterised by chronic hyperactivation of B lymphocytes. Salivary gland epithelial cells (SGECs) could play a role in promoting B-lymphocyte activation within the target tissue. We aimed to study the interactions between SGECs from patients with pSS or controls and B lymphocytes. METHODS: Patients had pSS according to 2016 European League Against Rheumatism/American College of Rheumatology criteria. Gene expression analysis of SGECs and B lymphocytes from pSS and controls isolated from salivary gland biopsies and blood was performed by RNA-seq. SGECs from pSS and controls were cocultured with B-lymphocytes sorted from healthy donor blood and were stimulated. Transwell and inhibition experiments were performed. RESULTS: Gene expression analysis of SGECs identified an upregulation of interferon signalling pathway and genes involved in immune responses (HLA-DRA, IL-7 and B-cell activating factor receptor) in pSS. Activation genes CD40 and CD48 were upregulated in salivary gland sorted B lymphocytes from patients with pSS. SGECs induced an increase in B-lymphocyte survival, which was higher for SGECs from patients with pSS than controls. Moreover, when stimulated with poly(I:C), SGECs from patients with pSS induced higher activation of B-lymphocytes than those from controls. This effect depended on soluble factors. Inhibition with anti-B-cell activating factor, anti-A proliferation-inducing ligand, anti-interleukin-6-R antibodies, JAK1/3 inhibitor or hydroxychloroquine had no effect, conversely to leflunomide, Bruton's tyrosine kinase (BTK) or phosphatidyl-inositol 3-kinase (PI3K) inhibitors. CONCLUSIONS: SGECs from patients with pSS had better ability than those from controls to induce survival and activation of B lymphocytes. Targeting a single cytokine did not inhibit this effect, whereas leflunomide, BTK or PI3K inhibitors partially decreased B-lymphocyte viability in this model. This gives indications for future therapeutic options in pSS.
32039403 Liver fibrosis and CD206(+) macrophage accumulation are suppressed by anti-GM-CSF therapy. 2020 Feb BACKGROUND & AIMS: Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206(+) macrophages, which may participate in maintaining chronic liver disease in a GM-CSF-dependent manner. We aimed to elucidate the exact role of GM-CSF in the development and progression of chronic liver disease. METHODS: Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206(+) monocyte/macrophages, fibrosis and GM-CSF. This was followed by functional validations in vitro and in vivo in humanised mice. RESULTS: Using multiplex immunofluorescence and histo-cytometry, we show that highly fibrotic livers had a greater density of CD206(+) macrophages that produced more TNFα and GM-CSF in the non-tumour liver regions of patients with hepatocellular carcinoma (n = 47), independent of aetiology. In addition, the absolute number of CD206(+) macrophages strongly correlated with the absolute number of GM-CSF-producing macrophages. In non-HCC chronic HCV(+) patients (n = 40), circulating GM-CSF levels were also increased in proportion to the degree of liver fibrosis and serum viral titres. We then demonstrated in vitro that monocytes converted to TNFα-producing CD206(+) macrophage-like cells in response to bacterial products (lipopolysaccharide) in a GM-CSF-dependent manner, confirming the in vivo normalisation of serum GM-CSF concentration following oral antibiotic treatment observed in HBV-infected humanised mice. Finally, anti-GM-CSF neutralising antibody treatment reduced intrahepatic CD206(+) macrophage accumulation and abolished liver fibrosis in HBV-infected humanised mice. CONCLUSIONS: While the direct involvement of CD206(+) macrophages in liver fibrosis remains to be demonstrated, these findings show that GM-CSF may play a central role in liver fibrosis and could guide the development of anti-GM-CSF antibody-based therapy for the management of patients with chronic liver disease. LAY SUMMARY: Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.
32673730 Small molecule antagonist of C-C chemokine receptor 1 (CCR1) reduces disc inflammation in 2020 Dec BACKGROUND CONTEXT: Targeting chemokines or chemokine receptors is a promising treatment strategy for diseases with chronic inflammation such as rheumatoid arthritis and discogenic pain. Identifying specific molecules and determining their effectiveness in animal models are the first steps in developing these treatments. Macrophage markers have been detected in the intervertebral disc tissues of patients with disc degenerative disease and discogenic pain and in different animal models. Macrophage recruitment into the disc may play a role in initiation of inflammation and if unresolved may lead to chronic inflammation and subsequent back pain. PURPOSE: The objectives of these studies are to (1) identify chemokine receptor antagonists that can block macrophage migration induced by disc cells in vitro and (2) determine if intradiscal treatment with these antagonists can reduce disc inflammation and degeneration in vivo. STUDY DESIGN: In vitro migration assays were used to test effectiveness of chemokine receptor antagonists to block macrophage migration induced by disc cells. The rabbit annular puncture model was used to test for anti-inflammatory and regenerative effects of chemokine receptor antagonist treatment in vivo. METHODS: In vitro - THP-1 human monocytic cell line and freshly isolated rabbit primary splenocytes were assayed for migration using 3 µm Corning Transwell inserts with conditioned media of interleukin (IL)-1β treated human or rabbit disc cells. Inhibition of macrophage migration was evaluated using different concentrations of small molecule antagonists of C-C chemokine receptor (CCR)1 and CCR2. In vivo - New Zealand White rabbits (n=40) underwent disc puncture and intradiscal treatment with saline, CCR1 or CCR2 antagonists within the same procedure. X-ray and magnetic resonance (MR) images and serum samples were taken for disc height, MRI grade and IL-8 serum level analyses. Intervertebral discs were isolated for RNA analysis of inflammatory and disc phenotypic markers and for immunohistochemical analysis of macrophage marker, RAM11. The outcome measures were compared between the three treatment groups. These studies were funded by a research grant from AO Foundation, Switzerland (Project no S-14-86A; 120000 CHF). CCR1 and CCR2 antagonists were kindly provided by ChemoCentryx (Mountain View, CA). RESULTS: In vitro migration assays showed that THP-1 migration induced by disc cells was blocked by CCR2 antagonist more effectively than CCR1 antagonist, while rabbit splenocyte migration was inhibited by CCR1 antagonist and not the other. In the rabbit annular puncture model, rabbit discs treated with CCR1 antagonist had significantly better MRI grades than those treated with CCR2 antagonist at 6 weeks post-treatment. Gene expression studies demonstrate that discs treated with CCR1 or CCR2 antagonists expressed less inflammatory markers than saline-treated discs at 3 weeks post-treatment. Although CCR2 antagonist treatment did not reduce inflammatory marker expression at 6 weeks, discs treated with CCR1 antagonist expressed less inflammatory markers and also a higher ratio of collagen type 2 to collagen type 1 genes indicating favorable disc matrix production. There were no significant differences between all three treatment groups in regards to disc height indexes, IL-8 serum levels or macrophage marker detection. CONCLUSIONS: These studies have identified that small molecule antagonists against CCR2 and CCR1 were respectively effective in blocking THP-1 and rabbit splenocyte migration induced by disc cells in vitro. Further, both CCR2 and CCR1 antagonist intradiscal treatments were effective in reducing disc inflammation at an early time point of 3 weeks. Lastly, only CCR1 antagonist demonstrated anti-inflammatory effects and better MRI grades at 6 weeks. CLINICAL SIGNIFICANCE: Our preclinical studies demonstrate that CCR1 and CCR2 antagonist delivery through intradiscal injection is sufficient to reduce disc inflammation at early time points, whereas CCR1 antagonists had longer term anti-inflammatory effects. Clinical studies have found that CCR1 antagonist was safe, tolerable and clinically active in reducing inflammation in rheumatoid arthritis patients. These studies suggest that CCR1 antagonist may be a promising biological treatment to reduce disc inflammation that translates to back pain relief.
32340707 The Future of Axial Spondyloathritis Treatment. 2020 May Axial spondyloathritis (axSpA) treatment with biologic DMARDs was previously focused around anti-TNF agents. Significant advances in research have led to new therapeutic options, such as secukinumab, an IL-17 inhibitor, which has been approved for the treatment of axSpA. Two other biologic agents that are already licensed for rheumatoid and psoriatic arthritis, tofacitinib and ixekizumab, have demonstrated improved outcomes in axSpA. Several newer agents have been developed to inhibit IL-17, IL-23, and JAK. Early trials are promising; however, further research is needed. Rapid expansion of therapies available to treat axSpA could lead to improved disease control and decreased disease burden.
33130935 Repair integrity and functional outcomes of arthroscopic repair in chronic anterior should 2022 Jan INTRODUCTION: This study compared the clinical outcome and repair integrity of single-loaded and double-loaded single-row arthroscopic repair of chronic anterior shoulder instability. MATERIALS AND METHODS: Fifty consecutive chronic anterior shoulder instability cases treated by arthroscopic labral repair were included. A single-loaded single-row technique was used in the first 25 consecutive shoulders, and a double-loaded single-row technique was used in the next 25 consecutive shoulders. The number of suture anchors was 4 in the shoulders that underwent single-loaded repair and 3 in the shoulders that underwent double-loaded repair. 42 shoulders (84.0%) followed up clinical outcomes were evaluated a minimum 2 years (mean 28.5 months; range 24-46) postoperatively. The postoperative labral repair integrity was evaluated by MDCT-arthrogram at a minimum 6 months postoperatively. RESULTS: At the final follow-up, the average UCLA, ASES, Constant, Rowe score, VAS pain score, and VAS for instability scores improved significantly, to 33.05, 92.33, 89.05, 94.86, 0.90 and 0.52, respectively, in the single-loaded group and to 32.19, 90.10, 89.05, 94.52, 0.90, and 0.86, respectively, in the double-loaded group. The clinical scores improved in both groups postoperatively (all P < 0.05); however, there was no significant difference between the two groups at final follow-up (P = 0.414, 0.508, 1.000, 0.917, 1.000, and 0.470, respectively). The re-tear rate was 2 (9.5%) in the shoulders that underwent single-loaded repair and 3 (14.3%) in the shoulders that underwent double-loaded repair; this difference was statistically not significant (P = 0.634). CONCLUSION: The double-loaded single-row technique resulted in comparable clinical outcomes, and re-tear rate compared with the single-loaded single-row technique in chronic anterior shoulder instability at short-term follow-up. Number of used suture anchor in double-loaded single-row technique was fewer than that of single-loaded single-row technique. LEVEL OF EVIDENCE: Comparative retrospective study, level III.
32770355 Inevitable nonunion after ulnar shortening osteotomy in patients with ulnar impaction synd 2020 Oct BACKGROUND: Nonunion after ulnar shortening osteotomy (USO) was observed at a high rate in patients undergoing long-term bisphosphonate (BP) maintenance treatment after breast cancer surgery. Here, we report the unique features of these nonunions. METHODS: In total, 485 patients who had undergone USO between March 2008 and September 2017 were screened for inclusion based on the following criteria: (1) definitive nonunion after USO; (2) prior history of or ongoing BP therapy after the diagnosis of breast cancer; and (3) no evidence of metastasis in the ulna treated with USO, as determined based on the radiological evaluation. RESULTS: Five patients with histories of breast cancer and subsequent BP treatment were identified; all (100%) of these patients showed definitive nonunion after USO. The mean age was 56.2 years, and all ulnae were on the contralateral side to that of the original breast cancer. Intravenous Ibandronate(®) and Zolendronate(®) were administrated to one and four patients, respectively. The mean period of administration was 67.8 months. Three patients exhibited suspicious lesions impending atypical fracture on their femurs, and the other two patients were treated by intramedullary nailing after the occurrence of atypical fractures. Radiological evaluation revealed no evidence of a metastatic lesion, including in the musculoskeletal system, in any patient. Osteosynthesis was performed with cancellous iliac bone graft and mean of 4.3 months after osteosynthesis, union in all cases was achieved. CONCLUSIONS: Problems associated with BP treatment are well known. Even in cases in which the agent is essential for preventing bony metastasis of breast cancer, the normal bony physiology, including bone turnover and healing, is likely to be compromised. In addition to atypical fractures of the femur and ulna, procedures such as USO are likely to be affected by BP. Furthermore, not only a primary iliac bone graft but also other method (oblique osteotomy) should be needed to avoid nonunion during plating in USO. LEVEL OF EVIDENCE: IV, Retrospective case series.
31497844 Unique Sjögren's syndrome patient subsets defined by molecular features. 2020 Apr 1 OBJECTIVE: To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes. METHODS: pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200. RESULTS: Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell-attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1α, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters. CONCLUSION: Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.
34543559 Still's disease: a rare condition, in a patient of unusual age. 2020 INTRODUCCIÓN: Cuando inicia en el adulto, la enfermedad de Still es de mayor prevalencia en caucásicos y entre los 16 y 35 años. De etiología desconocida, se asocia a HLA-II, DR2, 4 y 7, y Bw35. El comienzo de los síntomas es agudo, con fiebre en agujas, asociada a exantema en las extremidades y el tronco, maculopapular, eritematoso y evanescente, pruriginoso, con fenómeno de Koebner. Presenta artralgias y artritis con un patrón poliarticular, simétrico y migratorio, mialgias y adenopatías. El 90% de los pacientes presentan anemia, leucocitosis con neutrofilia y trombocitosis asociada a la actividad, así como elevación de transaminasas y ferritina > 2000. El factor reumatoide y los anticuerpos antinucleares son negativos. El objetivo del presente trabajo es presentar un caso de enfermedad de Still que se sale del patrón habitual de manifestación. CASO CLÍNICO: Mujer de 56 años, inicia con exantema -maculopapular, eritematoso, pruriginoso, en zona periorbitaria -bilateral, tórax anterior, región glútea bilateral y zonas de extensión de codos y rodillas, que respetan el abdomen. Fiebre vespertina de 39 °C, con artralgias de codos, muñecas y rodillas, y mialgias, con faringe hiperémica. Después de descartar procesos infecciosos, neoplásicos y autoinmunitarios, y de acuerdo con los criterios de Yamaguchi y Fautrel, se diagnosticó enfermedad de Still. CONCLUSIONES: Este caso se presenta por la baja prevalencia de la enfermedad de Still y porque en el grupo etario de nuestra paciente no es habitual su presentación. Los -antecedentes familiares y el cuadro clínico sugestivo obligaron a descartar la presencia de otros procesos mórbidos, toda vez que el diagnóstico de enfermedad de Still es de exclusión. BACKGROUND: Adult-onset on Still’s disease is common in Caucasians, between 16 and 35 years. Its cause is unknown, but it is associated with HLA-II, DR2, 4, 7 and Bw35. First symptoms are acute; fever in needles associated with exanthema in extremities and maculopapular trunk, erythematous and evanescent, pruritic with Koebner phenomenon. Patients present arthralgias and arthritis with a polyarticular, symmetrical and migratory pattern; myalgias and adenopathies. 90% of patients have anemia, leukocytosis with neutrophilia and thrombocytosis associated with the activity. Elevation of transaminases and ferritin greater than 2000. The rheumatoid factor and antinuclear antibodies are negative. The aim of this article is to present a case report of Still’s Disease whose pattern of appearance is uncommon. CASE REPORT: A 56-year-old woman presented papular macular, erythematous, pruritic exanthema, in the bilateral peri-orbital area, anterior thorax, bilateral gluteal region, and elbow and knee extensions, while respecting abdomen. In addition, evening fever of 39 °C with arthralgias in elbows, wrists, and knees, myalgias, and hyperemic pharynx were manifested. According to the criteria of Yamaguchi and Fautrel, and after ruling out infectious, neoplastic, autoimmune processes, Still’s disease was concluded. CONCLUSIONS: This case is presented due to the low prevalence of Still’s disease and its presentation is not usual in the age group of our patient. The family history and very ­indicative clinical pictures forced us to rule out the presence of other morbid processes, while reinforcing the diagnosis of Still’s disease, since it is by exclusion.
33260891 Aqueous Extract of Kan-Lu-Hsiao-Tu-Tan Ameliorates Collagen-Induced Arthritis in Mice by I 2020 Nov 27 BACKGROUND: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. METHODS: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund's adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H(2)O(2)) were measured using ELISA, thiobarbituric acid reactive substances, and a hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. RESULTS: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1β, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H(2)O(2) in paw tissues. CONCLUSIONS: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.
33070255 Public interest in rheumatic diseases and rheumatologist in the United States during the C 2021 Feb To evaluate the public interest in rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. Google Trends was queried to analyze search trends in the United States for numerous rheumatic diseases and also the interest in a rheumatologist. Three 8-week periods in 2020 ((March 15-May 9), (May 10-July 4), and (July 5-August 29)) were compared to similar periods of the prior 4 years (2016-2019). Compared to a similar time period between 2016 and 2019, a significant decrease was found in the relative search volume for more than half of the search terms during the initial March 15-May 9, 2020 period. However, this trend appeared to reverse during the July 5-August 29, 2020 period where the relative volume for nearly half of the search terms were not statistically significant compared to similar periods of the prior 4 years. In addition, this period showed a significant increase in relative volume for the terms: Axial spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, antiphospholipid syndrome, scleroderma, Kawasaki disease, Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis, and rheumatologist. There was a significant decrease in relative search volume for many rheumatic diseases between March 15 and May 9, 2020 when compared to similar periods during the prior 4 years. However, the trends reversed after the initial period ended. There was an increase in relative search for the term "rheumatologist" between July and August 2020 suggesting the need for rheumatologists during the COVID-19 pandemic. Policymakers and healthcare providers should address the informational demands on rheumatic diseases and needs for rheumatologists by the general public during pandemics like COVID-19.
32995474 Non-traditional risk factors and the risk of myocardial infarction in the young in the US 2020 Oct Although most prevalent in elderly, myocardial infarction (MI) also affects younger adults. We sought to investigate baseline characteristics in young patients (<55 years) with MI using the National Inpatient Sample (NIS) database between 2004 and 2015. Multivariable logistic regression models were used to assess factors associated with acute myocardial infarction (AMI) in young patients. After multivariable analyses adjusted for age, sex, race, family history of atherosclerosis, body mass index (BMI), diabetes, hypertension, hyperlipidemia, chronic kidney disease, and current cigarette smoking; novel risk factors such as human immunodeficiency virus (HIV), systemic lupus erythematosus (SLE), and obstructive sleep apnea (OSA) were associated with a higher risk of developing an AMI in the young (adjusted OR for HIV 4.06; 95 CI 3.48-4.71, p < 0.001), (adjusted OR for SLE 2.12; 95 CI 1.89-2.39, p 0.04), and (adjusted OR for OSA 1.16; 95 CI 1.12-1.20, p < 0.001), respectively. Rheumatoid arthritis was associated with a lower risk of AMI (adjusted OR 0.83; 95 CI 0.76-0.89, p < 0.001). After multivariable analyses, cigarette smoking (adjusted OR 1.98; 95 CI 1.95-2.02, p < 0.001), obesity (adjusted OR 1.37; 95 CI 1.33-1.41, p = 0.003), hyperlipidemia (adjusted OR 1.07; 95 CI 1.04-1.08, p < 0.001) and a family history of CAD (adjusted OR 1.35; 95 CI 1.3-1.4, p < 0.001) were also associated with a higher risk of developing an AMI in the young. In conclusion, young patients with AMI have both traditional risk factors and non-traditional risk factors. In addition to traditional risk factors, close attention should be paid to emerging risk factors such as SLE, HIV and OSA.
32929074 Chitinase-3 like-protein-1 function and its role in diseases. 2020 Sep 14 Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4(+) T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.
32931643 Incidence and case fatality rate of COVID-19 in patients with inflammatory articular disea 2021 Apr OBJECTIVE: To describe the incidence and fatality of coronavirus disease 2019 (COVID-19) and identify risk factors to fatality in patients with inflammatory articular diseases (IAD). METHODS: This is a cross-sectional observational study of IAD patients and COVID-19 with controls matched for age, sex, and RT-PCR. A control group was used to compare the cumulative incidence (CI) and case fatality rate (CFR). The main outcomes of the study were CI and CFR. Other variables included comorbidities, treatments, and characteristics of the COVID-19. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with IAD. RESULTS: Of the 1537 patients who fulfilled the inclusion criteria, 23/1537 (1.49%) had IAD 13 (0.8%) had rheumatoid arthritis (RA), 5 psoriatic arthritis (PsA) (0.3%) and 5 axial spondyloarthritis (0.3%). There were no significant differences in CI of COVID-19 and CFR in patients with IAD compared with COVID-19 patients without IAD. In RT-PCR positive patients, the CI of COVID-19 in PsA and AS was higher. Of the 23 IAD patients, 2 RA patients (8.6%) died. The patients did no show characteristics of the COVID-19 disease different from the population. In multivariate analysis, the factor associated with fatality in patients with IAD was older age (OR [95% CI], 1.1 [1.0-1.2]). CONCLUSION: COVID-19 CI, fatality rate and other features do not seem to be increased in IAD patients. Older age was associated with fatality in patients with IAD.
32165034 Sexual function and reproduction can be impaired in men with rheumatic diseases: A systema 2020 Jun BACKGROUND: Information about the possible effect of rheumatic diseases on male sexual function and reproduction (sexual health) is scarce and difficult to summarize. Factors known to impair sexual health, such as inflammation, medication use and hypogonadism can be present in a significant proportion of male patients with rheumatic diseases. OBJECTIVES: The objective of our study was to systematically review the literature for the influence of paternal rheumatic disease on sexual health, such as sexual function, reproductive hormones, male fertility, pregnancy and offspring outcomes. DATA SOURCES: English language articles identified through Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar and the Clinical trial registries of Europe and the USA published until February 2019. STUDY APPRAISAL AND SYNTHESIS METHODS: Literature was synthesized in narrative form and in summary tables. Outcomes were categorized as: sexual function, reproductive hormones, fertility and pregnancy and offspring outcomes. Results are presented per category and per disease. RESULTS: 9735 articles were identified with our search strategy. After removal of duplicates, excluding articles by screening titles and abstracts and assessing eligibility by reading 289 fulltext articles, 87 articles fulfilled the eligibility criteria. All included studies enrolled patients diagnosed with a rheumatic disease and had results at least on one of the outcome categories. Sexual function was the most common category, followed by reproductive hormones, fertility and pregnancy and offspring outcomes. Sexual function is impaired in a high proportion of patients with rheumatic diseases. This was statistically significant in most of the studies where a control group was available. Clinically relevant abnormalities in reproductive hormones were mainly identified in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and a positive correlation with disease activity were reported. Semen quality in men with rheumatic diseases can be impaired in patients with SLE, SpA, sarcoidosis, BD and MWS. Sperm count and motility were the most common semen quality parameters affected. No negative effect of paternal RA and vasculitis on pregnancy outcomes were reported in 3 studies. No studies reporting the effect of paternal disease on offspring outcomes were identified. LIMITATIONS: Most of the studies included in this review suffer from an inconsistent methodological quality, definitions of outcomes varied in several studies, a wide variety of screening questionnaires and/or diagnostic tools were used and results might only apply to the specific populations that were studied. CONCLUSIONS: This systematic review suggests that sexual health is impaired in men with rheumatic diseases. The degree and extent of sexual health impairment vary per disease. More research is needed to fully understand the link between rheumatic diseases and impaired male sexual health. Meanwhile, rheumatologists should be aware of this association and discuss it with their patients. IMPLICATIONS OF KEY FINDINGS: Sexual health of men with rheumatic diseases can be impaired by the disease itself. Especially in men trying to conceive, information on sexual function, reproductive hormones and sperm quality are needed to identify these problems. Treatment resulting in lower disease activity can improve overall sexual health in man with rheumatic diseases and facilitate their journey to fatherhood. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2018 CRD42018099845.
33758812 Outcomes and Risk Factors of Systolic Pulmonary Artery Pressure Progression in Patients wi 2020 Dec OBJECTIVES: This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases. PATIENTS AND METHODS: A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up. RESULTS: The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p<0.001). In patients with systemic sclerosis, the majority of patients remained static within their pressure group or rose progressively: the patients with markedly elevated sPAP at follow-up were higher than those at baseline (32% versus 15%, p<0.01). In patients with mixed connective tissue disease (MCTD) or rheumatoid arthritis (RA), the majority of patients remained static within their pressure group or gradually improved: the patients with markedly elevated sPAP at follow-up were lower than those at baseline (RA=14% versus 29%, MCTD=5% versus 16%, p<0.05). CONCLUSION: Persistently high sPAP or increase of sPAP over 60 mmHg at follow-up was associated with increased mortality. There were some differences in the progression of sPAP according to the underlying rheumatic diseases.
33584521 Optic Perineuritis and Its Association With Autoimmune Diseases. 2020 Background: Optic perineuritis (OPN) is a special optic neuropathy that has a distinct etiology from neuromyelitis optica spectrum disorders (NMOSDs) or multiple sclerosis (MS)-related optic neuritis (ON). The mechanisms of how this inflammation developed and invaded the nerve sheath remain unknown. This study is aimed to analyze the etiology and different clinical characteristics of OPN in a Chinese patient population. Methods: Neuro-ophthalmological examination, orbit magnetic resonance imaging (MRI) and a series of blood samples were used in this retrospective observational cohort study to compare characteristics of OPN with idiopathic demyelination optic neuritis (IDON). Results: Forty-four OPN cases (74 eyes) and 61 IDON cases (78 eyes) were analyzed. OPN cases included 33 cases (59 eyes) were associated with specific autoimmune diseases, 10 cases (13 eyes) were associated with infection diseases, 1 case was idiopathic disease. The causes of OPN with CTD were Graves' disease, Immunoglobulin G4-related disease (IgG-4 RD), granulomatosis with polyangiitis (GAP), systemic lupus erythematosus (SLE), Sarcoidosis, Rheumatoid arthritis, scleroderma, Behcet's disease, and gout. All patients received orbital MRI. Overall, 33 cases showed orbit fat infiltration. Specifically, nine cases with IgG-4 RD showed trigeminal nerve branch involvement, 12 cases with Graves' disease showed extraocular muscle belly enlargement, and 4 cases with GAP showed pterygopalatine fossa pseudotumor. Compared to IDON patients, OPN patients were older (p = 0.004) and more likely bilateral involvement 26 (78.79%) patients had bilateral involvement in OPN group vs. 17 (27.87%) in the IDON group (p < 0.001). Visual acuity scores using LogMAR testing was better in OPN patients compared to those with IDON, 0.55 ± 0.91 vs. 1.19 ± 1.24 (p < 0.001). Other ophthalmologic findings unique to the OPN group include 11 (33.33%) cases of ptosis, nine (27.27%) cases of diplopia, and 10 (30.30%) cases of exophthalmos, compared to zero cases of these conditions in the IDON group. Eight (13.11%) IDON patients also had multiple sclerosis (MS) and 7 (11.48%) patients had neuromyelitis which was significantly more than the zero patients in OPN group (p = 0.04). Conclusions: OPN had distinct etiologies and clinical characteristics from IDON and is more often associated with autoimmune diseases. Using OPN characteristics to diagnose autoimmune diseases should prove useful for clinicians when presented with patients that have multiorgan dysfunction that include ophthalmologic findings.
33352479 When symptoms become side effects: Development of the side effect attribution scale (SEAS) 2021 Feb OBJECTIVES: Symptom misattribution is a central process in the nocebo effect but it is not accurately assessed in current side effect measures. We have developed a new measure, the Side Effect Attribution Scale (SEAS), which examines the degree to which people believe their symptoms are treatment side effects. METHODS: The SEAS was tested in three New Zealand studies: a vaccination sample (n = 225), patients with gout or rheumatoid arthritis (n = 102), and patients switching to a generic medicine (n = 69). The internal reliability of the scale was examined using Cronbach's alpha. To assess validity, the Side Effect Attribution Total Score and Side Effect Attribution Binary Score were related to a number of psychological measures associated with side effect reporting. RESULTS: The scale showed good internal reliability across the three studies, with Cronbach alphas ranging from 0.840 to 0.943. Analysis of the effect sizes showed that the Attribution Total Score was generally more strongly associated with nocebo responding than Attribution Binary Score. Participants had greater Side Effect Attribution Total Scores if they had higher expectations for vaccination side effects (r = 0.18, p = .028), more worry about future vaccine effects (r = 0.16, p = .046), a higher perceived sensitivity to medicines (r = 0.50, p < .001), greater anxiety (r = 0.25, p = .016), greater intentional non-adherence (r = 0.30, p = .003), greater medicine information seeking (r = 0.26, p = .010), lower trust in pharmaceutical agencies (r = -0.29, p = .026), and lower medicine efficacy beliefs (r = -0.46, p < .001). CONCLUSIONS: The SEAS provides a more nuanced assessment of symptom attribution beliefs. It appears to be more sensitive measure than just a side effect total, as it is associated with a greater number of relevant psychological variables. Future research should examine the scale in other populations and settings.
33349545 Occupational ionizing radiation-induced skin injury among orthopedic surgeons: A clinical 2022 Jan BACKGROUND: This study aimed to assess orthopedic surgeons' attitudes and behaviors toward occupational radiation exposure and investigate the prevalence of occupational radiation-induced skin injury among orthopedic surgeons. Similarly, risk factors for the presence of radiation-induced skin injury were investigated. METHODS: Overall, 108 orthopedic surgeons were administered self-reported questionnaires about occupational radiation exposure, and their hands were then photographed. Their fields of expertise were classified into spine, arthroplasty, sports medicine, hand, oncology, rheumatoid arthritis, pediatric orthopedic, and resident. Dermatologists evaluated the surgeons' skin conditions and classified into 3 grades of injury: grade 0, no clinical symptoms; grade 1, careful observation required; and grade 2, detailed examination required. Logistic regression analysis was performed to investigate the factors related to the presence of radiation-induced skin injury. Crude and adjusted logistic regression analysis using the backward stepwise selection method was similarly conducted. Receiver operating characteristic curve (ROC) analysis was performed to estimate the predictive power of exposure time, occupational period, and accumulated annual exposure time for radiation-induced skin injury. RESULTS: In total, 93.5% of the surgeons were careful about occupational radiation exposure, of which 76.8% used a dosimeter. Skin changes in the hands were self-reported by 42.5% of the surgeons, and radiation-induced skin injury was diagnosed in 31.4%. The accuracy of the self-reported skin changes was 100% for grade 2 and 61.5% for grade 1. Adjusted regression analysis showed that dermatologists' diagnosis-related factors were self-reported skin changes (odds ratio [OR] 3.1) and spine surgeons (OR 3.2). ROC analysis demonstrated that an occupational period >21 years and an accumulated exposure time >6696 min were considered risk factors, with ORs of 4.07 and 5.99, respectively. CONCLUSIONS: Orthopedic surgeons, particularly spine surgeons, should be regularly examined by dermatologists early in their careers for early detection of radiation-induced skin injury on the hands.
33276950 In vitro display evolution of the PURE system-expressed TNFα-binding unnatural cyclic pe 2021 Jan 1 Tumor necrosis factor-alpha (TNFα) is a multifunctional cytokine associated with inflammation, immune responses, and autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. In the present study, we performed in vitro selection, systematic evolution of ligands by exponential enrichment (SELEX) against human TNFα from mRNA-displayed peptide library prepared with Escherichia coli-reconstituted cell-free transcription/translation system (PURE system) and cyclized by N-chloroacetyl-N-methyl-d-phenylalanine incorporated by genetic code expansion (sense suppression). We identified a novel TNFα-binding thioether-cyclized peptide that contains an N-methyl-d-phenylalanine. Since cyclic structure and presence of an N-methyl-d-amino acid can increase proteolytic stability, the TNFα binding peptide has potential to be used for therapeutic, research and diagnostic applications.
33174109 Incidence of COVID-19 in patients with rheumatic disease: is prior health education more i 2021 Apr The COVID-19 pandemic has led to major changes in clinical practice on a global scale in order to protect patients. This includes the identification of vulnerable patients who should "shield" in order to reduce the likelihood of contracting SARS-CoV2. We used national specialty guidance and an adapted screening tool to risk stratify patients identified from our prescribing and monitoring databases, and identify those needing to shield (score ≥ 3) using information from departmental letters, online general practice records and recent laboratory investigations. We collated underlying rheumatological conditions and risk factors. Two months into the shielding process, we examined the COVID-19 status of these patients using hospital laboratory records and compared to population level data. Of 887 patients assessed, 248 (28%) scored ≥ 3 and were sent a standard shielding letter. The most common risk factor in the shielding letter group was age ≥ 70 years and/or presence of a listed co-morbidity (199 patients). The most common rheumatology conditions were rheumatoid arthritis (69.4%), polymyalgia rheumatica (8.5%) and giant cell arteritis (8.5%). Coronavirus incidence rates were similar in the shielding letter group (0.403%) and in the UK population (0.397%). However, we found a trend towards lower incidence (0.113%) in our whole cohort (RR 0.28, 95%CI 0.04-2.01 for the whole cohort compared to UK population). The trend towards lower incidence in this cohort could be because of prior education regarding general infection risk and response to public health messages. While risk stratification and shielding could be effective, prior education regarding general infection risk and public health messages to enhance health protection behaviours during a pandemic may have equal or more important roles. Key Points • Patients on treatment for rheumatic disorders showed a trend for lower incidence of COVID-19 transmission irrespective of shielding letter status • This could potentially be because of prior education regarding infection risk received when starting on disease-modifying medication • Health education influencing health protection behaviours may be of equal or more importance than shielding information in reducing transmission of SARS-CoV-2.