Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35200081 Dietary supplementation of hemp oil in teddy dogs: Effect on apparent nutrient digestibili 2022 Mar Present study aimed to evaluate the influence of distinct concentration of dietary supplements hemp oil on apparent nutrient digestibility, blood biochemical parameters and metabolomics of teddy dogs. A total of 25 healthy teddy dogs were selected and divided into five treatments according to diet supplements hemp oil at a rate of 0% (A), 0.5% (B), 1% (C), 2% (D), and 4% (E). Appropriate added hemp oil improved apparent nutrient digestibility of dry matter, crude protein and crude fat (86.32-88.08%, 86.87-88.87% and 96.76-97.43%). The hemp oil significantly increased blood biochemical of utilization related total protein, albumin and globulin (61.33-69.54, 35.08-40.38 and 26.53-31.63 g/L), immunity capacity related immunoglobulin E and γ-interferon (203-347kU/L and 23.04-25.78ng/L), energy-related thyroxine and triiodothyronine (27.11-36.75 and 0.94-1.67 nmol/L). In addition, hemp oil improved superoxide dismutation (26.47-33.02 U/ml) and reduced malondialdehyde (5.30-3.28 nmol/ml). The differential metabolites mainly included nucleotides and metabolites of oxidized lipids, bile and other fatty acids, coenzymes and vitamins. The main metabolic pathways included purine and arachidonic acid metabolism, bile and unsaturated fatty acid biosynthesis, cell oxidative phosphorylation and rheumatoid arthritis. Overall, appropriate dietary supplements hemp oil positively to nutrient digestibility and blood metabolism, immunity and antioxidant capacity, 1% to 2% hemp oil supplements was recommended for teddy dog diet.
35127323 A case of Epstein-Barr virus-positive mucocutaneous ulcer of the hypopharynx: a mimicker o 2022 Jan Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a new disease, described by the World Health Organization in 2017. It has been recognized as a specific type of immunodeficiency-associated lymphoproliferative disorder. Since patients with EBVMCU present with only cutaneous or mucosal ulcers, it is difficult to clinically distinguish them from carcinoma. A 72-year-old man, who took methotrexate (MTX) (12 mg/week) for rheumatoid arthritis, was referred to our hospital because endoscopy revealed an ulcerated mass in the left pyriform sinus, suggesting hypopharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography and magnetic resonance imaging revealed an ill-defined mass in the left pyriform sinus without lymphadenopathy in the head and neck region. A biopsy of the ulcerative lesion in the hypopharynx was performed, and lymphoproliferative disease was suspected, based on the histopathological findings. Two weeks after MTX withdrawal, the lesions in the hypopharynx disappeared. The patient was diagnosed with EBVMCU, based on the clinical and histopathological findings. This is the first case report of EBVMCU of the hypopharynx. EBVMCU should be considered as a differential diagnosis in immunocompromised patients with hypopharyngeal mucosal ulcers without lymph node or organ involvement.
35099279 A Comprehensive Review of Yoga Research in 2020. 2022 Feb Objectives: Accumulated evidence garnered in the last few decades has highlighted the role of yoga in health and disease. The overwhelming mortality and morbidity mediated by noncommunicable epidemics such as heart disease and cancer have fostered a search for mechanisms to attenuate them. Despite overwhelming success in acute care, the efficacy of modern medicines has been limited on this front. Yoga is one of the integrative therapies that has come to light as having a substantial role in preventing and mitigating such disorders. It thus seems trite to analyze and discuss the research advancements in yoga for 2020. The present review attempts to distill recent research highlights from voluminous literature generated in 2020. Methods: This review was conducted on the articles published or assigned to an issue in 2020. The authors searched the PubMed database for clinical studies published in the English language, using yoga (including meditation) as the intervention, and having an adequate description of the intervention. Then, they extracted data from each study into a standardized Google sheet. Results: A total of 1149 citations were retrieved in the initial search. Of these, 46 studies met eligibility criteria and were finally included. The studies were predominantly on mental health and neuropsychology, addressing various issues such as anxiety, postural balance, migraine, academic performance, and childhood neglect. Anxiety, stress, and depression were other common denominators. Eight studies were on cardiorespiratory systems, including exercise capacity, cardiac rehabilitation, myocardial infarction, and hypertension. Three studies were on diabetes, evaluating the effect of yoga. Five studies focused on cognition, health status, and autonomic regulation and few others included cancers, infertility, ulcerative colitis, urinary incontinence, restless leg syndrome, rheumatoid arthritis, chronic pain, and metabolic syndrome. Finally, most studies were on noncommunicable diseases with one exception, human immunodeficiency virus; two randomized controlled trials were dedicated to it. Conclusions: Yoga has been studied under a wide variety of clinicopathological conditions in the year 2020. This landscape review intends to provide an idea of the role of yoga in various clinical conditions and its future therapeutic implications.
34971804 Inflammatory muscle involvement in systemic vasculitis: A systematic review. 2022 Mar Vasculitis are severe systemic autoimmune diseases which may involve different organs and systems. Conversely, muscles do not represent an organ commonly involved by systemic vasculitis and myositis is not include among any classification or diagnostic criterion of vasculitis. In this regard, we aimed to review the literature in order to report all the available evidence concerning the inflammatory involvement of muscle in patients affected by systemic vasculitis. We collected a total of 108 papers, for a sum of 395 patients affected by muscle vasculitis. Most of them suffered from medium and small vessels vasculitis (mainly polyarteritis nodosa and ANCA-associated vasculitis) or from vasculitis secondary to rheumatoid arthritis. Conversely, muscle involvement in case of large vessel vasculitis occurred seldom, while only few papers reported such occurrence in Kawasaki or Behçet's disease. Histological findings may differ, but the most common ones displayed a necrotizing vasculitis of perimysium vessels, while granulomatous vasculitis was assessed only in case of ANCA-associated vasculitis patients. Creatine kinase were usually within normal range, seldom elevated, while imaging findings were generally undistinguishable from the ones found in idiopathic inflammatory myopathies: magnetic resonance imaging displays signal hyperintensity in T2 and STIR scans, while few data exist for positron emission tomography. The presentation of the disease may be fearsome and severe, sometimes life-threatening, but an overall good response to conventional immunosuppressants and/or glucocorticoids has been reported.
29939664 Morvan Syndrome. 2022 Jan Morvan syndrome or Morvan’s fibrillary chorea (MFC) is a rare constellation of neurological symptoms, consisting of peripheral nerve hyperexcitability, autonomic instability, and encephalopathy often associated with autoantibodies to voltage-gated potassium channel complexes (VGKCs). On 12 April 1890, the French physician, Dr. Augustine Marie Morvan first published a novel description of this neurological syndrome in La Gazette Hebdomadaire de Medecine et de Chirurgie.  He called it “la choree fibrillaire,” which we now know as Morvan syndrome. There have been approximately 60 cases published in the French and other literature but only a few in English literature since then. See table 1 in media section at the end of this script for a review and comparison of the varied clinical features and clinical outcomes in 20 such cases reported in English literature.                                                                                                                                    As per table 1, Morvan syndrome is predominantly a male-dominant entity with a male to female ratio of 19 to 1. The only female case was a rheumatoid arthritis patient on gold therapy who developed mild Morvan syndrome features, and whose condition reverted once treatment was discontinued. Insomnia, hyperhidrosis, dysautonomia, and myokymia were consistent findings noted in 100% (all 20) of the patients. Whereas, hallucinations were seen in 75% (15) of the patients and anti-voltage-gated potassium channel antibodies (VGKC) were observed in 45% (9) of the patients. Another very consistent finding was the conspicuous absence of seizures in 100% (all 20) of the cases and benign findings on MRI in 100% (all 20) in contrast to Limbic encephalitis where seizures and temporal lobe structural abnormalities on MRI are classic findings. Myokymia was seen in 100% (all 20) of the patients, and it was confirmed in most 80%(16) cases with EMG studies which showed spontaneous, either repetitive or continuous muscle activity in the form of fasciculations which were a combination doublet, triplet, multiplet, or neuromyotonic discharges. Other sporadic findings were elevated manganese levels in 5% (1), oligoclonal bands in cerebrospinal fluid (CSF) in 15% (3), thymoma in 40% (8), Acetylcholine receptor (AchR) antibodies in 30% (6) of patients. However, AchR antibodies in association with myasthenic features were seen in only 10% (2) of the patients. Twenty percent (4) of the patients had AchR antibodies without myasthenic features. Treatment modalities tried with varied effectiveness were thymectomy in 25% (5), anticonvulsant therapy in 45% (9), immunosuppression in 50% (10), and IVIG in 20% (4) of the patients. The most effective treatment was plasma exchange which was tried in 55% (11) of the patients, all of whom except one patient showed dramatic improvement. Treatment effectiveness was even more significant when immunosuppression and plasma exchange was tried together. Death was the outcome in only 20% (4) of the patients.
35655424 Protective effect of dexpanthenol against methotrexate-induced liver oxidative toxicity in 2022 Jun 2 Methotrexate is a familiar chemotherapeutic preferred in a wide range of clinical fields such as leukemia, psoriasis, rheumatoid arthritis, neoplastic and autoimmune disorders. However, methotrexate therapy has limitations as it causes severe side effects from which liver damage is the most important one. Several antioxidant compounds have been studied against methotrexate related liver toxicity, but dexpanthenol has not been experienced. Vitamin B5-derived dexpanthenol is a usual therapeutic having a potent anti-inflammatory and antioxidant effect. In this study, we aimed to evaluate the ameliorating effect of dexpanthenol against methotrexate-induced hepatotoxicity. We performed our experiments on Wistar albino rats divided randomly into four groups involving control, dexphantenol, dexpanthenol + methotrexate and methotrexate applied animals. After this experimental work on rats, for the first time, we showed dexpanthenol improvement effect on ROS-caused hepatotoxicity initiated by methotrexate administration in terms of liver tissue antioxidant/oxidant enzymes, liver function tests, and histological changes. We suggest that dexpanthenol might be applied during methotrexate treatment in order to reduce the liver toxicity. However, further studies are needed to find out the optimal dose regimen and to understand the mechanism of action.
35383056 Rheumatoid interstitial lung disease in Canterbury New Zealand: prevalence, risk factors a 2022 Apr 5 INTRODUCTION: Rheumatoid arthritis (RA) affects approximately 0.5%-1% of the general population. Clinically significant interstitial lung diseases (ILD) develops in just under 10% of people with RA, and subclinical disease is more common. Little is known about RA-ILD in New Zealand (NZ), or the number of persons with RA in Canterbury, NZ. This study aims to determine: (1) incidence and prevalence of RA, (2) incidence and prevalence of RA-ILD, (3) clinical characteristics and risk factors for the development of RA-ILD, (4) long-term outcomes of RA-ILD, in the population resident within the Canterbury District Health Board (CDHB) catchment area. METHODS AND ANALYSIS: Persons aged 18 years of age and older, and resident in the region covered by the CDHB with RA as well as RA-ILD will be identified by retrospective review of medical records. Prevalent as well as incident cases of RA between 1 January 2006 and 31 December 2008 and between 1 January 2011 and 31 December 2013 will be identified, and followed until 30 June 2019. Existing as well as incident cases of RA-ILD during this time will be identified. The association between the development of ILD and clinical characteristics and environmental exposures will be examined using Cox-proportional hazard models. Kaplan-Meier methods will be used to estimate survival rates for patients with RA-ILD. Mortality for people with RA and RA-ILD will also be compared with the general population of the CDHB. ETHICS AND DISSEMINATION: Data will be obtained by retrospective review of medical records. Deidentified patient data will be stored in a secure online database. Data on individual patients will not be released, and all results will only be published in aggregate. Ethical approval has been obtained from the University of Otago Human Research Ethics Committee (REF HD18/079). Results will be published in peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12619001310156; Pre-results.
35110331 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal 2022 Jun OBJECTIVE: To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). METHODS: Following European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion. RESULTS: Four overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering. CONCLUSION: These recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.
35144926 Proteogenomic analysis of the autoreactive B cell repertoire in blood and tissues of patie 2022 May OBJECTIVE: To comparatively analyse the aberrant affinity maturation of the antinuclear and rheumatoid factor (RF) B cell repertoires in blood and tissues of patients with Sjögren's syndrome (SjS) using an integrated omics workflow. METHODS: Peptide sequencing of anti-Ro60, anti-Ro52, anti-La and RF was combined with B cell repertoire analysis at the DNA, RNA and single cell level in blood B cell subsets, affected salivary gland and extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) of patients with SjS. RESULTS: Affected tissues contained anti-Ro60, anti-Ro52, anti-La and RF clones as a small part of a polyclonal infiltrate. Anti-Ro60, anti-La and anti-Ro52 clones outnumbered RF clones. MALT lymphoma tissues contained monoclonal RF expansions. Autoreactive clones were not selected from a restricted repertoire in a circulating B cell subset. The antinuclear antibody (ANA) repertoires displayed similar antigen-dependent and immunoglobulin (Ig) G1-directed affinity maturation. RF clones displayed antigen-dependent, IgM-directed and more B cell receptor integrity-dependent affinity maturation. This coincided with extensive intra-clonal diversification in RF-derived lymphomas. Regeneration of clinical disease manifestations after rituximab coincided with large RF clones, which not necessarily belonged to the lymphoma clone, that displayed continuous affinity maturation and intra-clonal diversification. CONCLUSION: The ANA and RF repertoires in patients with SjS display tissue-restricted, antigen-dependent and divergent affinity maturation. Affinity maturation of RF clones deviates further during RF clone derived lymphomagenesis and during regeneration of the autoreactive repertoire after temporary disruption by rituximab. These data give insight into the molecular mechanisms of autoreactive inflammation in SjS, assist MALT lymphoma diagnosis and allow tracking its response to rituximab.
35012368 Immunoregulatory effects of dental mesenchymal stem cells on T and B lymphocyte responses 2022 Mar Background: In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is an autoimmune disease resulting from keratoconjunctivitis sicca and xerostomia. Methods: Mononuclear cells isolated from pSS patients cultured with or without dental MSCs and analyzed for lymphocyte responses via flow cytometry. Results: Dental-follicle (DF)- and dental-pulp (DP)-MSCs downregulated CD4(+) T lymphocyte proliferation by increasing Fas-ligand expression on T lymphocytes and FoxP3 expressing Tregs, and decreasing intracellular IFN-γ and IL-17 secretion in pSS patients. DF-MSCs decreased the plasma B cell ratio in the favor of naive B cell population in pSS patients' mononuclear cells. Conclusion: DF- and DP-MSCs can be the new cellular therapeutic candidates for the regulation of immune responses in pSS.
35468261 Associations of Socioeconomic Status with Disease Progression in African Americans with Ea 2022 Apr 25 OBJECTIVE: In prior cross-sectional analyses of African Americans (AA) with RA, measures of socioeconomic status (SES) were associated with clinical joint damage and poorer patient-reported outcome (PRO) scores. The purpose of this study is to determine whether SES measures are associated with disease progression in a cohort of AA patients with early RA (<2 years duration). METHODS: We analyzed baseline SES and change in 60-month clinical radiographs and PRO data (n=101 and 177, respectively) in individuals with early RA. SES measures were educational attainment, occupation, homeownership, household income, and block group poverty (BGP). Outcomes were based on radiographs (total erosion and joint space narrowing [JSN] scores on hands and feet) and PROs (pain, fatigue, disability, and learned helplessness). We used logistic regression with mixed effects accounting for study site to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Both low education and occupation status were associated with worsening pain (aOR=5.86, 95% CI=3.05-11.3 and aOR=2.55, 95% CI=1.54-4.21). Patients without a high-school diploma were more likely to have worsened reports of learned helplessness (OR=1.92, 95% CI=1.37-2.67). Community measures of SES were also significantly associated with PRO score changes. Patients living in areas of BGP >20% were twice as likely to experience increased disability scores over 60 months of disease duration (OR=1.95, 95% CI=1.17-3.25). We found no association between SES measures and erosion or JSN score progression. CONCLUSION: Low educational attainment and non-professional occupation status were associated with increased worsening of PROs. However, there were no corresponding increases in radiographically assessed erosion or JSN score progression.
35125053 Impact of switching to infliximab biosimilars on treatment patterns among US veterans rece 2022 Apr OBJECTIVE: To compare treatment patterns of United States (US) veterans stable on innovator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on innovator IFX (continuers). METHODS: US Veterans Healthcare Administration data (01/2012-12/2019) were used to identify adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis (AS), or Crohn's disease and ulcerative colitis (i.e. inflammatory bowel disease [IBD]), treated with innovator or biosimilar IFX. Index date was the first IFX biosimilar administration for switchers or a random innovator IFX administration for continuers. Patients were required to have ≥5 innovator IFX administrations during the 12 months pre-index (prevalent population). Patients with ≥12 months of observation prior to the first innovator IFX administration were analyzed as the primary population (incident population), and data were assessed from start of innovator IFX. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Treatment patterns were evaluated post-index; continuers were censored before switching to IFX biosimilar. Discontinuation was defined as switching to another biologic (including innovator IFX) or having ≥120 days between 2 consecutive index treatment records. RESULTS: In the incident population, mean [median] duration of follow-up was 737 [796] days among switchers (N = 838) and 479 [337] days among continuers (N = 849). Compared to continuers, switchers were 2.88-times more likely to discontinue index therapy (hazard ratio [HR] = 2.88, p < .001) and 4.99-times more likely to switch to another innovator biologic (HR = 4.99, p < .001). Of 653 switchers switching to another innovator biologic, 594 (91.0%) switched back to innovator IFX. Results were similar among the prevalent population and RA and IBD subgroups. CONCLUSION: Patients switching from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (notably back to innovator IFX) than those remaining on innovator IFX; however, reasons for discontinuation and switching are unknown.
35123541 Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation an 2022 Feb 5 BACKGROUND: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn't been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. METHODS: LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. RESULTS: We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. CONCLUSIONS: These results showed that TOD can be adopted as a potential therapeutic agent for OA.
35089649 Differences in the Association Between Oral Glucocorticoids and Risk of Preterm Birth by D 2022 Jan 28 OBJECTIVE: To investigate causes of discrepancies in the association between early pregnancy oral glucocorticoid (OGC) use and preterm birth risk among women with rheumatoid arthritis (RA) in health care utilization data from California Medicaid (Medi-Cal) and the prospective cohort MotherToBaby Pregnancy Studies. METHODS: Separately, we estimated risk ratios (RRs) between OGC exposure before gestational day 140 and preterm birth risk in data from Medi-Cal (2007-2013; n = 844) and MotherToBaby (2003-2014; n = 528). We explored differences in socioeconomic status, OGC dose distribution, exposure misclassification, and confounding by RA severity across the data sources. RESULTS: Preterm birth risk in women without OGC was 17.3% in Medi-Cal and was 9.7% in MotherToBaby. There was no association between OGC and preterm birth in Medi-Cal (adjusted RR 1.00 [95% confidence interval (95% CI) 0.71, 1.42]), and a 1.85-fold (95% CI 1.20, 2.84) increased preterm birth risk in MotherToBaby. When restricting each sample to women with a high-school diploma or less, preterm birth risk following no OGC exposure was 15.9% in Medi-Cal and 16.7% in MotherToBaby; adjusted RRs were 1.16 (95% CI 0.74, 1.80) in Medi-Cal and 0.81 (95% CI 0.25, 2.64) in MotherToBaby. Cumulative OGC dose was higher in MotherToBaby (median 684 mg) than in Medi-Cal (median 300 mg). An OGC dose of ≤300 mg was not associated with increased preterm birth risk. Exposure misclassification and confounding by RA severity were unlikely explanations of differences. CONCLUSION: Higher baseline preterm birth risk and lower OGC dose distribution in Medi-Cal may explain the discrepancies. Studies are needed to understand the effects of autoimmune disease severity and undertreatment on preterm birth risk in low-income populations.
34732389 Characterising risk of non-steroidal anti-inflammatory drug-related acute kidney injury: a 2022 Mar BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.
35418287 COVID-19 Mortality in Patients with Rheumatic Diseases: A Real Concern. 2022 Apr 12 BACKGROUND: Coronavirus disease 2019 (COVID 19) is a worldwide pandemic that has devastated the world in a way that has not been witnessed since the Spanish Flu in 1918. In this study, we aim to investigate the outcomes of patients with rheumatic diseases infected with COVID19 in Oman. METHODS: A multi-center retrospective cohort study included patients with underlying rheumatological conditions and COVID-19 infection. Data was collected through the electronic record system and by interviewing the patients with a standard questionnaire. RESULTS: 113 patients with different rheumatic diseases were included with the following rheumatological diagnoses: rheumatoid Arthritis (40.7%), systemic lupus erythematosus (23.1%), psoriatic arthritis (8%), Behcet's disease (7%), ankylosing spondylitis (6.2%), other vasculitides including Kawasaki disease (4.4%) and 10.6% other diagnoses. The mean (SD) age of patients was 43 (14) years, and 82.3% were female. The diagnosis of COVID-19 was confirmed by PCR test in (84.1%) of the patients. The most common symptoms at the time of presentation were fever in 86%, cough (81%), headache (65%), and myalgia (60%). Hospitalization due to COVID-19 infection was reported in 24.1% of the patients, and 52.2 % of these patients had received some form of treatment. In this cohort, the intake of immunosuppressive and immunomodulating medications was reported in 91.1% of the patients. During the COVID-19 infection, 68% of the patients continued taking their medications. Comorbidities were present in 39.8% of the patients. Pregnancy was reported in 2% of the patients. The 30 days mortality rate was found to be 3.5%. Diabetes, obesity, and interstitial lung diseases (ILD) were the strongest risk factor for mortality (p-value 0.000, 0.000, and 0.001), respectively. Rituximab was given in 3.8 % of the patients, and it was significantly associated with increased mortality among our patients (P-value <0.001). CONCLUSION: COVID-19 infection in patients with rheumatic diseases have an increased mortality rate in comparison to the general population, with diabetes, morbid obesity, chronic kidney diseases, interstitial lung disease, cardiovascular disease, obstructive lung disease, and liver diseases as comorbidities being the most risk factors associated with death. Greater care should be provided to this population, including the prompt need for vaccination.
35172900 Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells fr 2022 Feb 16 BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE. METHODS: Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56(bright), CD56(dim)CD57(-), and CD56(dim)CD57(+)), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochondrial reactive oxygen species (mtROS) and total ROS levels were detected with MitoSOX Red and DCFH-DA staining respectively. Published data (GSE63829 and GSE23695) from Gene Expression Omnibus (GEO) was analyzed by Gene Set Enrichment Analysis (GSEA). RESULTS: Total peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56(dim)CD57(+) NK cell proportion, which was negatively associated with disease activity and positively correlated with levels of complement(C)3 and C4. Compared with HCs, peripheral CD56(dim)CD57(+) NK cells from SLE patients exhibited altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addition, when treated with hydrogen peroxide (H(2)O(2)), peripheral CD56(dim)CD57(+) NK cell subset was more prone to undergo apoptosis than CD56(dim)CD57(-) NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4(+) T cells in vitro. CONCLUSION: Our study demonstrated a selective loss of mature CD56(dim)CD57(+) NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. The attenuated in vitro cytotoxicity of CD56(dim)CD57(+) NK cells may contribute to the impaired ability of eliminating pathogenic CD4(+) T cells in SLE.
34741435 TNFi Cycling Versus Changing Mechanism of Action in TNFi-Experienced Patients: Result of t 2022 Jan OBJECTIVE: Comparative effectiveness research can inform treatment decisions regarding the choice of biologics for rheumatoid arthritis (RA). The objective of this study is to compare the efficacy of tumor necrosis factor inhibitors (TNFis) and non-TNFis (nTNFis) in real-world patients with RA and past TNFi experience. METHODS: Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) was nested within the United States Corrona registry. Adult patients with RA with moderate to high disease activity (Clinical Disease Activity Index [CDAI] >10) with exposure to one or more prior TNFis who were switching to a new TNFi or nTNFi (choice of therapy per physician choice) were enrolled. The primary outcome was the achievement of low disease activity (LDA) at 12 months (CDAI ≤10; disease activity score in 28 joints based on C-reactive protein [DAS28-CRP] <2.67). Propensity score modeling probability of treatment with nTNFi versus TNFi adjusted for imbalanced factors. The response rate was modeled using mixed-effect logistic regression models, adjusting for a priori and imbalanced baseline factors and accounting for the practice-related treatment patterns. RESULTS: After applying inclusion criteria, 939 biologic initiations were analyzed, 505 (53.7%) nTNFis and 434 (46.3%) TNFis. Patients who started nTNFis were significantly more likely to have longer disease duration, more prior TNFi use, and higher patient fatigue scores and were more likely to have government insurance. At 12 months, 28% of nTNFi and 24% of TNFi initiators were in LDA by CDAI, and 22% of nTNFi and 19% of TNFi initiators were in LDA by DAS28-CRP. After multivariable adjustment and controlling for the influence of site-related confounding, there were no significant differences in the likelihood to reach LDA by CDAI (adjusted odds ratio [aOR] = 1.12; 95% confidence interval [CI], 0.78-1.62) or DAS28-CRP (aOR = 1.16; 95% CI, 0.77-1.75). CONCLUSION: In this large, real-world study enrolling patients with RA with prior TNFi exposure, switching to an nTNFi biologic was comparable in its clinical effectiveness with switching to another TNFi.
35644031 Longitudinal immune cell profiling in early systemic lupus erythematosus. 2022 May 29 OBJECTIVE: To investigate the immune cell profiling and their longitudinal changes in systemic lupus erythematosus (SLE). METHODS: We employed mass cytometry with three different 38-39 marker panels (Immunophenotyping, T cell/monocyte, and B cell) in cryopreserved peripheral blood mononuclear cells (PBMCs) from nine patients with early SLE, 15 patients with established SLE, and 14 non-inflammatory controls. We used machine learning-driven clustering, FlowSOM (Flow Self-Organizing Maps) and dimensional reduction with tSNE (t-distributed Stochastic Neighbor Embedding) to identify unique cell populations in early and established SLE. For the nine early SLE patients, longitudinal mass cytometry analysis was applied to PBMCs at enrollment, six months post-enrollment, and one year post-enrollment. Serum samples were also assayed for 65 cytokines by Luminex multiplex assay, and associations between cell types and cytokines/chemokines assessed. RESULTS: T peripheral helper cells (Tph cells), T follicular helper cells (Tfh cells) and several Ki67(+) proliferating subsets (ICOS(+) Ki67(+) CD8 T cells, Ki67(+) regulatory T cells, CD19(int) Ki67(hi) plasmablasts, and Ki67(hi) PU.1(hi) monocytes) were increased in early SLE patients, with more prominent alterations than were seen in early rheumatoid arthritis (RA) patients. Longitudinal mass cytometry and multiplex serum cytokine assays of samples from early SLE patients revealed that Tfh cells and CXCL10 decreased at one year post-enrollment. CXCL13 correlated positively with several of the expanded cell populations in early SLE. CONCLUSIONS: Two major helper T cell subsets and unique Ki67(+) proliferating immune cell subsets were expanded in the early phase of SLE, and the immunologic features characteristic of early SLE evolved over time.
35546332 A real-life analysis of patients with rheumatologic diseases on biological treatments: Dat 2022 Apr OBJECTIVE: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. METHODS: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. RESULTS: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. CONCLUSION: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.