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ID PMID Title PublicationDate abstract
32224441 Immunogenic and inflammatory responses to citrullinated proteins are enhanced following mo 2020 Jun BACKGROUND/OBJECTIVE: Malondialdehyde-acetaldehyde adducts (MAA) act as potent immune adjuvants and co-localize with citrullinated antigens in tissues effected by rheumatoid arthritis (RA). We sought to examine the role of MAA-adducts in promoting RA-related autoimmunity and inflammation. METHODS: DBA/J1 mice were immunized with human serum albumin (HSA), HSA-MAA, citrullinated HSA (HSA-Cit), or HSA-MAA-Cit with subsequent measurement of serum anti-citrullinated protein antibody (ACPA) and anti-Cit T cell responses. Cellular binding of the same antigens was examined using THP-1 monocytes and Chinese Hamster Ovary (CHO) cells transfected with specific scavenger receptors (SRs: TLR4, SR-B2, SREC-1). The effects of these antigens on THP-1 activation were then examined by quantifying plate adherence, pro-inflammatory (TNFα, IL-1β, IL-10) cytokine release, and SR (CD14, SR-B2)/co-stimulatory molecule (CD80, HLA-DR) expression. Comparisons were completed using one-way ANOVA with Tukey's post-hoc test. RESULTS: Mice immunized with co-modified HSA produced significantly higher ACPA concentrations than all other groups whereas T cell responses to citrullinated proteins were highest following immunization with HSA-MAA. Both transfected CHO and THP-1 cells demonstrated significantly higher binding of HSA-MAA-Cit vs. HSA or HSA-Cit. THP-1 cells exposed to HSA-MAA-Cit expressed significantly higher concentrations of TNFα, IL-1β, and IL-10 vs. all other groups. Furthermore, THP-1 cells demonstrated significantly increased plate adherence and higher expression of CD14, SR-B2, and HLA-DR following incubation with HSA-MAA-Cit vs. HSA or HSA-Cit. CONCLUSION: These studies demonstrate that MAA-adduction of citrullinated antigen greatly enhances immune and cellular responses, potentially acting as a key co-factor in RA pathogenesis.
32757291 Are there any clinical differences between ankylosing spondylitis patients and familial Me 2021 Jan OBJECTIVE: Familial Mediterranean Fever (FMF) is an autoinflammatory disease that is commonly present with recurrent episodes of fever, peritonitis, pleuritis or arthritis. Enthesitis and sacroilitis can also be seen in FMF. Spondylitis is a less common manifestation of joint involvement in FMF and there are controversial publications about whether this involvement is FMF-related or coincidentally. The aim of this study was to provide a comparison between ankylosing spondylitis (AS) patients and FMF patients with AS. METHODS: A total of 404 patients who 360 of them was AS and 44 was FMF patients with AS (in accordance with Tel Hashomer) patients with AS (in accordance with modified New York criteria) were included in this study. All cases were evaluated retrospectively and patient's demographic and clinical data were recorded. RESULTS: The mean age was 34.5 ± 8.6 years and 61.4% of patients were female in FMF group. In AS group, the mean age was 41.2 ± 10.8 years and 67.8% of patients were male. In AS group, 92% of patients had inflammatory back pain, 51% had hip pain, 30% had heel pain, 14% had peripheral arthritis and 11% had uveitis. In FMF group, 98% of patients had inflammatory back pain, 59% had hip pain, 48% had heel pain, 43% had peripheral arthritis and 4.5% had uveitis. Syndesmophyte and enthesitis on X-ray were seen in 18% and 22% of AS patients, and 7% and 41% of FMF patients with AS, respectively. There were significant differences between AS patients and FMF patients with AS in terms of heel pain (P: .017), peripheral arthritis (P: .000) and enthesitis (P: .006). CONCLUSION: Peripheral arthritis and enthesitis were more frequent, and uveitis and syndesmophyte were less frequent in FMF patients with spondylitis than AS patients. When we look at gender differences, clinical and genetic features, it seems to be different condition from AS.
32945153 Pharmacokinetics, Safety, and Tolerability of Single- and Multiple-Dose Once-Daily Baricit 2020 Nov The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once-daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1 hour (median). Plasma concentrations declined rapidly following the attainment of peak concentrations, with a mean terminal half-life of 5.7 to 7.3 hours. Steady-state plasma concentrations of baricitinib were achieved after the second day of once-daily dosing, with minimal accumulation of baricitinib in plasma (up to 10% increase in area under the plasma concentration-time curve). Single- and multiple-dose mean values for area under the plasma concentration-time curve from time zero to infinity and maximum plasma concentration appeared to increase in an approximately dose-proportional manner across the dose range. Single and multiple oral doses of once-daily baricitinib up to 10 mg were well tolerated by healthy Chinese subjects.
32726514 Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizuma 2021 Jan We assessed pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD relationships of interleukin-6 (IL-6), soluble IL-6 receptor, and C-reactive protein (CRP) in serum, and absolute neutrophil count (ANC) in blood following single doses of subcutaneous sarilumab versus intravenous tocilizumab (NCT02097524) from patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) and on a stable dose of MTX. Patients with RA randomized (1:1:1:1) to single-dose sarilumab (150 or 200 mg subcutaneously) or tocilizumab (4 or 8 mg/kg intravenously) were included (n = 101), and PK, PD, and PK/PD relationships and safety were assessed over 6 weeks postdose. PK profiles for both drugs are described by parallel linear and nonlinear target-mediated clearance pathways. PD markers showed similar onset of effect during the first week postdose, regardless of dose or route of administration. CRP and ANC decreased, with median postdose nadirs at 7-15 days for CRP and 3-5 days for ANC. Both drugs at low and high doses achieved the same nadir for ANC and a similar return toward baseline within 2 weeks postdose, suggesting a saturation of effect. Safety profiles of sarilumab and tocilizumab were generally similar. In conclusion, despite differences in PK, the onset of the decrease in CRP (efficacy) and ANC (safety) after a single dose were similar for subcutaneous sarilumab and intravenous tocilizumab. PD effects and safety were consistent with previous studies.
32271055 A randomized-controlled pilot trial of an online compassionate mind training intervention 2020 Nov Problematic use of prescribed and over-the-counter analgesics is widespread and increasing among people with chronic pain, but the availability of preventative and treatment services is limited. We evaluated a 21-day online intervention based on compassionate mind training in a prospective, randomized-controlled trial. The participants were 73 adults with concerns about their use of analgesics for chronic pain conditions. Participants completed measures of analgesic use, misuse and dependence, plus self-criticism and self-reassurance (self-inadequacy, self-reassurance, and self-hate), cognitive impulsivity (negative urgency, lack of perseverance, lack of premeditation, sensation-seeking, and positive urgency) and behavioral impulsivity (delay discounting) at baseline, postintervention, and 1-week postintervention follow-up. Following baseline assessment, participants were randomized to compassionate mind training (CMT; n = 38) or relaxation music (n = 35), both delivered online. No adverse events or safety issues were reported and high participant retention and exercise completion rates showed that the intervention was acceptable to participants. Repeated measures analysis of variance showed that by comparison with relaxation music, the CMT group had reduced prescription analgesic use, F = 6.123, p = .015, analgesic dependence, F = 14.322, p < .001, self-hate, F = 12.218, p < .001, negative urgency, F = 7.323, p = .006, and lack of perseverance, F = 7.453, p = .001, from baseline to postintervention, and those improvements were maintained at follow-up. The results show that exercises based on CMT principles and techniques and delivered online can reduce analgesic use, risk of analgesic dependence, and some aspects of self-criticism and impulsivity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
32052313 Pharmacokinetic Similarity and Comparative Pharmacodynamics, Safety, Efficacy, and Immunog 2020 Apr OBJECTIVES: The aims were to demonstrate pharmacokinetic (PK) similarity between DRL_RI, a proposed rituximab biosimilar, and two reference innovator products (Rituxan(®) [RTX-US] and MabThera(®) [RTX-EU]) and compare their pharmacodynamics (PD), efficacy, safety, and immunogenicity in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX)-based therapy and no prior biologic administration. METHODS: In this randomized, double-blind, parallel-group study, 276 patients with moderate-to-severe active RA were randomized to receive DRL_RI, RTX-US, or RTX-EU on days 1 and 15. The primary PK end points included area under the concentration-time curve from time 0 to 336 h after first infusion (AUC(0-14 days, first infusion)), AUC from day 1 through week 16 (AUC(0-∞, entire course)), and AUC from time 0 to time of last quantifiable concentration after the second dose (AUC(0-t, second infusion)). Secondary end points included other PK parameters, such as maximum concentration (C(max)), time to C(max) after each infusion, terminal half-life, systemic clearance, and volume of distribution after the second infusion; PD parameters and efficacy until week 24; safety and immunogenicity at week 24 and 52; and B cell recovery until week 52. AUC from time 0 to time of last quantifiable concentration after the first dose and over the entire course from day 1 through week 16 (AUC(0-t, entire course)) was analyzed as an exploratory end point. RESULTS: The 91% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the primary end point of AUC(0-∞, entire course) were within the bioequivalence limits of 80-125% for all comparisons: DRL_RI versus RTX-US 100.37% (92.30-109.14), DRL_RI versus RTX-EU 93.58% (85.98-101.85), and RTX-US versus RTX-EU 93.24% (85.62-101.54). PD outcomes (peripheral blood B-cell depletion and mean change in Disease Activity Score [28 joints]-C-reactive protein), efficacy, safety, and immunogenicity were also comparable between DRL_RI and the reference products. CONCLUSION: DRL_RI, a proposed biosimilar, demonstrated three-way PK similarity with RTX-EU and RTX-US, the reference innovator products, with comparable efficacy, PD, safety, and immunogenicity. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02296775.
32499126 Efficacy and Safety of Tofacitinib, Baricitinib, and Upadacitinib for Rheumatoid Arthritis 2020 Jul OBJECTIVE: To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis (RA). METHODS: Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire-Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated. RESULTS: Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire-Disability Index scores (mean differences, -0.31; 95% CI, -0.34 to -0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92). CONCLUSION: Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
32209192 [Recommendations of diagnosis and treatment of primary Sjögren's syndrome in China]. 2020 Apr 1 Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In China, standardized diagnosis and treatment for Sjögren's syndrome lags behind other common rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Based on the evidence and guidelines from China and other countries, Chinese Sjögren's Syndrome Collaborative Research Group together with stomatologist and ophthalmologist developed Standardization of diagnosis and treatment of primary Sjögren's syndrome. The purposes are: (1) to standardize the detection and interpretation of key indicators for the diagnosis of Sjögren's syndrome, including serum anti SSA antibody and labial gland pathology; (2) to suggest using widely accepted disease activity index in evaluation of the disease; (3) to standardize rational management for Sjögren's syndrome patients with topical and systemic diseases.
32578580 Ultrasound-guided core biopsy of the parotid gland: the procedure from the Rheumatology po 2020 Jan Ultrasound-guided core biopsy is a minimally invasive technique able to identify lymphoma accompanying Sjögren syndrome, neoplasms or infiltrative diseases, with less complications compared to open biopsy. With these images, we aim to describe the ultrasound-guided core biopsy procedure, in a female patient with rheumatoid arthritis who presented evident inhomogeneity of the parotid gland. The procedure was performed by rheumatologists, trained in ultrasonography of the salivary glands, demonstrating that ultrasound-guided core biopsy is an easy and safe method to obtain salivary gland tissue.
32531798 Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years f 2021 Apr BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis. METHODS: Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY). RESULTS: Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time. CONCLUSIONS: No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.
32062606 Neurophysiological Features of Peripheral Nervous System Involvement and Immunological Pro 2020 Nov 1 OBJECTIVE: The aim of this study was to evaluate the prevalence, type of neuropathy, and the relationship between the presence of autoantibodies and neuropathy development in patients with primary Sjögren syndrome (pSS). METHODS: Sixty-one patients with pSS underwent a complete neurological and electrophysiological examination as well as immunological tests including rheumatoid factor (RF) and autoantibodies such as antinuclear antibodies (ANA), anti-Ro/SSa, and anti-La/SSB antibodies. RESULTS: The axonal loss or demyelination were found in 39 patients (63.9%). Twenty-nine (47.5%) subjects fulfilled both clinical and electrophysiological criteria of peripheral neuropathy of predominantly axonal type. Seropositivity to both anti-Ro and anti-La antibodies was more frequently found in patients with normal nerve conduction study. Seropositivity to anti-Ro alone was present in the majority of patients with axonal neuropathy (P < 0.05). The presence of RF was associated with several electrodiagnostic signs of demyelination (P < 0.01). The ANA titer showed no independent association with neuropathy. CONCLUSION: Peripheral neuropathy is a frequent complication in patients with pSS. Seropositivity limited to anti-Ro is associated with increased risk of axonal neuropathy in comparison to seropositivity to both anti-Ro and anti-La antibodies. Seropositivity to RF may contribute to demyelination.
32873554 EULAR/eumusc.net standards of care for rheumatoid arthritis: cross-sectional analyses of i 2020 Nov OBJECTIVE: As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. METHODS: Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. RESULTS: Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. CONCLUSIONS: Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.
32973091 Synergy between 15-lipoxygenase and secreted PLA(2) promotes inflammation by formation of 2020 Oct 13 Damage-associated endogenous molecules induce innate immune response, thus making sterile inflammation medically relevant. Stress-derived extracellular vesicles (stressEVs) released during oxidative stress conditions were previously found to activate Toll-like receptor 4 (TLR4), resulting in expression of a different pattern of immune response proteins in comparison to lipopolysaccharide (LPS), underlying the differences between pathogen-induced and sterile inflammation. Here we report that synergistic activities of 15-lipoxygenase (15-LO) and secreted phospholipase A(2) (sPLA(2)) are needed for the formation of TLR4 agonists, which were identified as lysophospholipids (lysoPLs) with oxidized unsaturated acyl chain. Hydroxy, hydroperoxy, and keto products of 2-arachidonoyl-lysoPI oxidation by 15-LO were identified by mass spectrometry (MS), and they activated the same gene pattern as stressEVs. Extracellular PLA(2) activity was detected in the synovial fluid from rheumatoid arthritis and gout patients. Furthermore, injection of sPLA(2) promoted K/BxN serum-induced arthritis in mice, whereby ankle swelling was partially TLR4 dependent. Results confirm the role of oxidized lysoPL of stressEVs in sterile inflammation that promotes chronic diseases. Both 15-LO and sPLA(2) enzymes are induced during inflammation, which opens the opportunity for therapy without compromising innate immunity against pathogens.
31927702 Electrophysiological and SD-OCT findings in patients receiving chloroquine therapy in rela 2020 Aug PURPOSE: Assessment of multifocal ERG (mfERG) changes in patients treated with chloroquine and their correlation with morphological abnormalities, detected by spectral-domain optical coherence tomography in relation to cumulative dosage. METHODS: Data from 37 eyes of 20 patients were retrospectively collected, and one randomly selected eye per patient was considered for statistical analysis. Eyes were divided into three groups according to mfERG and visual acuity findings: normal, early and advanced maculopathy. Functional measures of the first three mfERG rings were compared with retinal thickness measures of the corresponding OCT ETDRS circles. Data on cumulative dose and duration of therapy were also evaluated. RESULTS: The mean mfERG values progressively decreased according to the stage of the disease. In particular in the early maculopathy group, amplitudes were significantly reduced in all the three central rings. The mean ring ratio R1/R2 was abnormal only in the early maculopathy group. OCT thickness measures were significantly lower in all the three ETDRS circles in the advanced maculopathy group, and in the paracentral circle in the early maculopathy group. Considering all the eyes, there was a statistically significant correlation between functional and morphological values (p < 0.001). High chloroquine cumulative dosages were always associated with retinal toxic effects, whereas lower cumulative dosages generated different levels of toxicity. CONCLUSIONS: This study shows a strong association between mfERG ring values and the corresponding OCT thickness measures; however, mfERG may enhance early detection of functional changes in patients treated with chloroquine, especially in ambiguous cases. At low chloroquine cumulative dosages, different subjects might have different susceptibilities to the drug.
33291545 Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patient 2020 Dec 4 Pro-inflammatory CD4(+)CD28(-) T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4(+)CD28(-) T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4(+)CD28(-) T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4(+)CD28(-) T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4(+)CD28(-) T cells showed higher expression of VPAC(2) and lower of VPAC(1), VPAC(2) showing a significant increased expression in EA cells. Sorted CD4(+)CD28(-) T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis.
32605558 Prevalence and risk factors for bone loss in Southern Chinese with rheumatic diseases. 2020 Jun 30 BACKGROUD: This study is to explore the prevalence of different stages of bone loss and the potential risk factors in rheumatic patients. METHOD: A cross-sectional study recruits 1398 rheumatic patients and 302 healthy subjects. Demographic data, blood, and bone mineral density (BMD) tests are collected. Risk factors for bone loss in rheumatic patients are analyzed by logistic regression. RESULTS: (1) Rheumatic patients are consisted of 40.0% rheumatoid arthritis (RA), 14.7% systemic lupus erythematosus (SLE), 14.2% osteoarthritis (OA), 9.2% ankylosing spondylosis (AS), 7.9% gout, 7.0% primary Sjogren syndrome (pSS), 3.8% systemic sclerosis (SSc), and 3.2% mixed connective tissue disease (MCTD). (2) In male patients aged under 50 and premenopausal female patients, the bone mineral density score of AS (53.9%, P < 0.001) and SLE (39.6%, P = 0.034) patients is lower than the healthy controls (18.2%). (3) Osteopenia and osteoporosis are more prevailing in male patients aged or older than 50 and postmenopausal female patients with RA (P < 0.001), OA (P = 0.02) and SLE (P = 0.011) than healthy counterparts. (4) Those with SLE, RA and AS gain the highest odd ratio of 'score below the expected range for age', osteopenia and osteoporosis, respectively. (5) Age, female, low BMI and hypovitaminosis D are found negatively associated with bone loss. Dyslipidemia and hyperuricemia could be protective factors. CONCLUSION: Young patients with AS and SLE have a significant higher occurrence of bone loss, and older patients with RA, OA and SLE had higher prevalence than healthy counterparts. SLE, RA, SSc and AS were founded significant higher risks to develop into bone loss after adjustment. Age, BMI and gender were commonly-associated with bone loss in all age-stratified rheumatic patients. These findings were not markedly different from those of previous studies.
32157251 The evolving role of TonEBP as an immunometabolic stress protein. 2020 Jun Tonicity-responsive enhancer-binding protein (TonEBP), which is also known as nuclear factor of activated T cells 5 (NFAT5), was discovered 20 years ago as a transcriptional regulator of the cellular response to hypertonic (hyperosmotic salinity) stress in the renal medulla. Numerous studies since then have revealed that TonEBP is a pleiotropic stress protein that is involved in a range of immunometabolic diseases. Some of the single-nucleotide polymorphisms (SNPs) in TONEBP introns are cis-expression quantitative trait loci that affect TONEBP transcription. These SNPs are associated with increased risk of type 2 diabetes mellitus, diabetic nephropathy, inflammation, high blood pressure and abnormal plasma osmolality, indicating that variation in TONEBP expression might contribute to these phenotypes. In addition, functional studies have shown that TonEBP is involved in the pathogenesis of rheumatoid arthritis, atherosclerosis, diabetic nephropathy, acute kidney injury, hyperlipidaemia and insulin resistance, autoimmune diseases (including type 1 diabetes mellitus and multiple sclerosis), salt-sensitive hypertension and hepatocellular carcinoma. These pathological activities of TonEBP are in contrast to the protective actions of TonEBP in response to hypertonicity, bacterial infection and DNA damage induced by genotoxins. An emerging theme is that TonEBP is a stress protein that mediates the cellular response to a range of pathological insults, including excess caloric intake, inflammation and oxidative stress.
31977037 Immunohistochemical Assessment of the Diagnostic Utility of PD-L1 (Clone SP142) for Methot 2020 Apr 15 OBJECTIVES: We describe results of programmed death ligand 1 (PD-L1) immunohistochemical assessment in methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) and highlight the characteristics of classic Hodgkin lymphoma (CHL) type MTX-LPD. METHODS: Fifty cases of MTX-LPD, including CHL type (n = 9), diffuse large B-cell lymphoma type (n = 15), and polymorphic B-cell LPD (n = 21), were investigated. RESULTS: Staining with anti-PD-L1 clone SP142 was exclusively found in CHL type (89%) but not in the others. Cases of CHL type MTX-LPD involved nodal disease and were associated with Epstein-Barr virus. They were histopathologically characterized by a vaguely nodular pattern, predominance of mononuclear cells, and strong expression of at least one pan-B-cell marker. Their clinical course was variable, with spontaneous regression in 5 patients, relapse in 2, and a fatal course in 1. CONCLUSIONS: The PD-L1 (clone SP142) workup aids the diagnostic approach to patients with MTX-LPD. CHL type MTX-LPD appears to represent a unique morphologic variant of CHL.
32767527 Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Stud 2021 Jan OBJECTIVE: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. METHODS: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94-1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66-1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56-1.23]). None of the differences were significant. CONCLUSION: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.
32202190 Effects of naringenin on the pharmacokinetics of tofacitinib in rats. 2020 Dec Context: Naringenin and tofacitinib are often used together for treatment of rheumatoid arthritis in Chinese clinics.Objective: This experiment investigates the effect of naringenin on the pharmacokinetics of tofacitinib in rats.Materials and methods: Twelve Sprague-Dawley rats were randomly divided into two groups (experimental group and control group). The experimental group was pre-treated with naringenin (150 mg/kg/day) for two weeks before dosing tofacitinib, and equal amounts of CMC-Na solution in the control group. After a single oral administration of 5 mg/kg of tofacitinib, 50 μL blood samples were directly collected into 1.5 mL heparinized tubes via the caudal vein at 0.083, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. The plasma concentration of tofacitinib was quantified by UPLC/MS-MS.Results: Results indicated that naringenin could significantly affect the pharmacokinetics of tofacitinib. The AUC(0-24) of tofacitinib was increased from 1222.81 ± 222.07 to 2016.27 ± 481.62 ng/mL/h, and the difference was significant (p < 0.05). Compared with the control group, the T(max) was increased from 0.75 ± 0.29 to 3.00 ± 0.00 h (p < 0.05), and the MRT((0-24)) was increased from 4.90 ± 0.51 to 6.57 ± 0.66 h (p < 0.05), but the clearance was obviously decreased from 4.10 ± 0.72 to 2.42 ± 0.70 L/h/kg (p < 0.05) in experimental group. Although the C(max) and t(1/2) of tofacitinib were increased, there were no significant differences (p > 0.05).Conclusions: This research demonstrated a drug-drug interaction between naringenin and tofacitinib possibly when preadministered with naringenin; thus, we should pay attention to this possibility in the clinic.