Browse

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

ID PMID Title PublicationDate abstract
32162133 Photobiomodulation with 630-nm LED radiation inhibits the proliferation of human synoviocy 2020 Dec Phototherapy has been used to treat postoperative pain and inflammatory response in rheumatoid arthritis. Confidence in this approach, however, is impaired by lack of understanding of the light-triggered cellular and molecular mechanisms. The purpose of this study was to characterize the response of human synoviocyte MH7A cells to visible LED red light in an attempt to elucidate the associated action mechanism. Human synoviocyte MH7A cells were treated with 630-nm LED light after stimulation of tumor necrosis factor-α (TNF-α). The effects of light radiation on cell proliferation and migration were detected by MTT assay and scratch test. The expressions of inflammatory cytokines were measured using RT-qPCR. This was followed by detection of the levels of extracellular proteins IL-6 and IL-8 after differential radiation. Furthermore, the expression levels and activation of proteins on PI3K/AKT/mTOR signaling pathway were examined with Western blot. In terms of the proliferation and migration, repeated radiation with LED red light (630 nm, 26 and 39 J/cm(2)) exerted an inhibitory effect on synoviocyte MH7A cells. Expression of inflammatory factors (IL-6, IL-1β, IL-8, and MMP-3) was reduced; meanwhile, the expression of anti-inflammatory factor IL-10 was promoted. At the protein level, treatment with 39 J/cm(2) of LED red light could decrease the level of extracellular protein (IL-6 and IL-8) and affect the expression and phosphorylation of proteins on TRPV4/PI3K/AKT/mTOR signaling pathway induced by TNF-α. These results demonstrated that LED red light (630 nm) inhibits proliferation and migration of MH7A cells. The growth-inhibiting effects of LED red light on human synoviocyte MH7A cells appear to be associated with regulation of the TRPV4/PI3K/AKT/mTOR signaling pathway.
31694743 Long-term survival of lung transplantation for interstitial lung disease associated with c 2020 Jul OBJECTIVES: Interstitial lung disease (ILD) is a leading cause of mortality in patients with connective tissue diseases (CTD). Lung transplantation has become a viable option for patients with end-stage CTD-ILD. However, patients with CTD are often considered suboptimal candidates for lung transplantation because of concerns of worse outcomes. We assessed post-transplant survival of patients with CTD-ILD compared to patients with idiopathic pulmonary fibrosis (IPF). METHODS: Medical records of patients who underwent lung transplantation for CTD-ILD at a single referral centre for lung transplantation in Northern Spain between 1998 and 2018 were reviewed. This cohort was compared with patients with IPF (group-matched for age ±3.3 years, transplant year and use of basiliximab induction previous to transplant). Cumulative survival rates after transplantation were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: We studied 26 patients with CTD-ILD and 26 patients with IPF. The underlying diseases of CTD-ILD patients were rheumatoid arthritis (n=9), scleroderma (n=6), Sjögren's syndrome (n=4), ANCA-associated vasculitis (n=3), anti-synthetase syndrome (n=2), and dermatomyositis, systemic lupus erythematosus (1 each). Baseline characteristics were similar in both groups. CTD-ILD patients experienced acute graft rejection less commonly than those with IPF (32.0% vs. 62.5%; p=0.032). However, a non-statistically significant increased frequency of chronic graft rejection was observed in CTD-ILD patients (20.0% vs. 8.3%; p=0.417). In this regard, the 5-year cumulative survival rates after transplantation was reduced in CTD-ILD (42.4% vs. 65.8%) but the difference did not achieve statistical significance (p=0.075). CONCLUSIONS: Long-term post-transplant survival in Northern Spanish patients with CTD-ILD is reduced compared with IPF.
33339187 Eudebeiolide B Inhibits Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by R 2020 Dec 16 Eudebeiolide B is a eudesmane-type sesquiterpenoid compound isolated from Salvia plebeia R. Br., and little is known about its biological activity. In this study, we investigated the effects of eudebeiolide B on osteoblast differentiation, receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. Eudebeiolide B induced the expression of alkaline phosphatase (ALP) and calcium accumulation during MC3T3-E1 osteoblast differentiation. In mouse bone marrow macrophages (BMMs), eudebeiolide B suppressed RANKL-induced osteoclast differentiation of BMMs and bone resorption. Eudebeiolide B downregulated the expression of nuclear factor of activated T-cells 1 (NFATc1) and c-fos, transcription factors induced by RANKL. Moreover, eudebeiolide B attenuated the RANKL-induced expression of osteoclastogenesis-related genes, including cathepsin K (Ctsk), matrix metalloproteinase 9 (MMP9) and dendrocyte expressed seven transmembrane protein (DC-STAMP). Regarding the molecular mechanism, eudebeiolide B inhibited the phosphorylation of Akt and NF-κB p65. In addition, it downregulated the expression of cAMP response element-binding protein (CREB), Bruton's tyrosine kinase (Btk) and phospholipase Cγ2 (PLCγ2) in RANKL-induced calcium signaling. In an ovariectomized (OVX) mouse model, intragastric injection of eudebeiolide B prevented OVX-induced bone loss, as shown by bone mineral density and contents, microarchitecture parameters and serum levels of bone turnover markers. Eudebeiolide B not only promoted osteoblast differentiation but inhibited RANKL-induced osteoclastogenesis through calcium signaling and prevented OVX-induced bone loss. Therefore, eudebeiolide B may be a new therapeutic agent for osteoclast-related diseases, including osteoporosis, rheumatoid arthritis and periodontitis.
35097407 Comorbidities Associated With Poor Outcomes Following Operative Hammertoe Correction in a 2020 Oct BACKGROUND: Although complications following hammertoe correction surgery are rare, older patients with comorbid conditions are often considered poorer operative candidates compared with younger, healthier patients because of a suspected increased risk of adverse outcomes. The aim of this study was to determine if the presence of multiple comorbidities was associated with increased complications or unsuccessful patient-reported outcomes following operative hammertoe correction in geriatric patients. METHODS: Prospectively collected data was reviewed on 78 patients aged 60 years or older who underwent operative correction of hammertoe deformity. Patient demographics, comorbidities, and postoperative complications were recorded. Patient-reported outcomes were assessed using preoperative and postoperative visual analog scale for pain and Short Form Health Survey Physical and Mental Component Summary with 1 year of follow-up. Patients were divided into 2 groups based on number of comorbidities (0 or 1 vs > 2) and then compared. The average age of patients was 69.4 years and the prevalence of comorbidities in the study population was as follows: 11.5% smokers, 25.6% on blood thinners, 15.4% with rheumatoid arthritis, 7.7% with diabetes mellitus, 2.6% with peripheral arterial disease, 6.4% with chronic obstructive pulmonary disease, 11.5% with coronary artery disease, and 23.1% with osteoporosis. RESULTS: Fifty-three patients (67.9%) had 0 or 1 comorbidity and 25 (32.1%) had 2 or more comorbidities. Compared to the 0 or 1 comorbidity group, the presence of multiple comorbidities was associated with an adjusted odds ratio (OR) for superficial wound infection of 4.18 (P = .045) and deformity recurrence requiring surgery OR of 23.15 (P = .032). Patient-reported outcomes were similar between comorbidity groups. CONCLUSIONS: This study further informs foot and ankle specialists to maintain increased surveillance for postoperative complications and unsuccessful outcomes in patients with multiple comorbidities. Although geriatric patients still report significant improvements in both pain and function, patients with underlying medical conditions should be counseled about their increased risks when pursuing operative hammertoe correction. LEVEL OF EVIDENCE: Level III, retrospective comparative series.
32354165 The Role of Crosstalk between AR3 and E2F1 in Drug Resistance in Prostate Cancer Cells. 2020 Apr 28 BACKGROUND: Drug resistance is one of the most prevalent causes of death in advanced prostate cancer patients. Combination therapies that target cancer cells via different mechanisms to overcome resistance have gained increased attention in recent years. However, the optimal drug combinations and the underlying mechanisms are yet to be fully explored. AIM AND METHODS: The aim of this study is to investigate drug combinations that inhibit the growth of drug-resistant cells and determine the underlying mechanisms of their actions. In addition, we also established cell lines that are resistant to combination treatments and tested new compounds to overcome the phenomenon of double drug-resistance. RESULTS: Our results show that the combination of enzalutamide (ENZ) and docetaxel (DTX) effectively inhibit the growth of prostate cancer cells that are resistant to either drug alone. The downregulation of transcription factor E2F1 plays a crucial role in cellular inhibition in response to the combined therapy. Notably, we found that the androgen receptor (AR) variant AR3 (a.k.a. AR-V7), but not AR full length (AR-FL), positively regulates E2F1 expression in these cells. E2F1 in turn regulates AR3 and forms a positive regulatory feedforward loop. We also established double drug-resistant cell lines that are resistant to ENZ+DTX combination therapy and found that the expression of both AR3 and E2F1 was restored in these cells. Furthermore, we identified that auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, overcame drug resistance and inhibited the growth of drug-resistant prostate cancer cells both in vitro and in vivo. CONCLUSION AND SIGNIFICANCE: This proof-of-principle study demonstrates that targeting the E2F1/AR3 feedforward loop via a combination therapy or a multi-targeting drug could circumvent castration resistance in prostate cancer.
31654585 Promotion of a quality standard for Porana sinensis Hemsl. based on the efficacy-oriented 2020 Feb Multicompound determination for the quality control of traditional Chinese medicine (TCM) may often be inadequate, since these compounds may not be associated with, or fully represent, the clinical effects of TCM. Moreover, the individual contributions of each constituent to the pharmacological effect are often not considered. In China, Porana sinensis is widely used as a substitute for Erycibe sources to treat joint pain and rheumatoid arthritis. The existing quality control methods for P. sinensis neither consider the individual contributions of various compounds nor control the actual quality associated with different clinical efficacies. In the present study, a novel efficacy-oriented approach, named the effect-constituent index (ECI), was established for P. sinensis. Analyses of the spectrum-effect relationship and components in rat plasma were conducted to systematically and scientifically select quality markers. Quantitative analysis of multicomponents via a single marker method was introduced to enhance the practical application value of the established ECI. The established ECI shows a good ability to distinguish and predict the bioeffect-based quality of P. sinensis. The present study also provides a reference for the establishment and application of ECI as a quality control method for TCMs.
33229070 Influence of Intraoperative Medial Collateral Ligament Bony Avulsion Injury on the Outcome 2021 Apr BACKGROUND: The purpose of this study is (1) to find the clinical and radiological outcome of intraoperative bony avulsion of medial collateral ligament (MCL) treated with screw and washer construct and (2) to predict the preoperative factors which may contribute to the avulsion-type MCL injury during primary total knee arthroplasty (TKA). METHODS: Intraoperative MCL avulsion injury occurred in 46 (0.8%) of the 4916 consecutive primary TKA from January 2011 to December 2015. After exclusion, the 41 knees were matched 1:2 with controls without MCL injury and compared for the various clinical, radiological, and functional parameters. The clinical parameters analyzed were age, gender, body mass index, preoperative diagnosis like osteoarthritis or rheumatoid arthritis, range of motion, sagittal deformity, and vitamin D levels. The radiological parameters calculated were coronal deformity, proximal tibial varus angle, distal femur valgus angle, joint line congruence angle, posterior tibial slope, "cup and saucer" morphology, presence or absence of knee subluxation, tibia vara, and femoral bowing. The preoperative and postoperative Knee Society Score and Knee Society Functional Score were analyzed. Complications or revisions, if any, were noted during the follow-up. Multivariate logistic regression analysis was used to predict the preoperative risk factors for MCL avulsion injury. RESULTS: At a mean follow-up of 58.4 ± 19.3 months, there were no radiological or physical examination findings of instability. Compared to the preoperative disability, there was a statistically significant improvement in clinical scores (Knee Society Score and Knee Society Functional Score) in the final follow-up (P < .001) in both cases and the control group. The mean preoperative coronal deformity was 170.6 ± 6.96 in the study group and 167.7 ± 4.3 in the control group (P = .021). The mean preoperative tibial slope was 10.5 ± 4.9 in the study group and 7.91 ± 4.15 in the control group (P = .003). The preoperative knee subluxation was present in 48.8% knees (P < .001) and "cup and saucer" morphology in 68.3 knees (P < .001) in the study group. The adjusted odds of MCL avulsion injury were greater for severe varus deformity (odds ratio [OR] 1.462, 95% confidence interval [CI] 1.15-1.86), knee subluxation (OR 39.78, 95% CI 3.78-418.86), and "cup and saucer" morphology (OR 33.11, 95% CI 5.69-192.66). CONCLUSION: Intraoperative MCL bony avulsion injury can be managed successfully with screw and washer construct without the need for increased prosthetic constraint in primary TKA. The presence of severe varus deformity, knee subluxation, and "cup and saucer" morphology tend to have an increased chance of MCL avulsion injury.
33199235 Agrimophol suppresses RANKL-mediated osteoclastogenesis through Blimp1-Bcl6 axis and preve 2021 Jan Excessive activity of osteoclasts causes many bone-related diseases, such as rheumatoid arthritis and osteoporosis. Agrimophol (AGR), a phenolic compound, originated from Agrimonia pilosa Ledeb. In prior studies, AGR is reported to possess schistosomicidal and mycobactericidal activities. However, no reports covered its anti-osteoclastogenesis characteristic. In this study, we found that AGR inhibited RANKL-induced osteoclastogenesis, bone-resorption, F-actin ring formation, and the mRNA expression of osteoclast-associated genes such as CTSK, TRAP, MMP-9, and ATP6v0d2 in vitro. In addition, AGR suppressed RANKL-induced expression of c-Fos and NFATc1. However, AGR treatment did not affect NF-κB activation and MAPKs phosphorylation in RANKL-stimulated BMMs, which implicated that AGR might not influence the initial expression of NFATc1 mediated by NF-κB and MAPKs signaling. Our results further indicated that AGR did not alter phosphorylation levels of GSK3β and the expression of calcineurin, which implicated that AGR treatment might not interfere with phosphorylation and de-phosphorylation of NFATc1 mediated by GSK3β and calcineurin, respectively. B-lymphocyte-induced maturation protein-1 (Blimp1), which was regarded as a transcriptional repressor of negative regulators of osteoclastogenesis, was markedly attenuated in the presence of AGR, leading to the enhanced expression of B-cell lymphoma 6 (Bcl-6). Meanwhile, Blimp1 knockdown in BMMs by siRNA strongly enhanced the expression of Bcl6 and reduced NFATc1 induction by RANKL. These findings suggested that AGR inhibited RANKL-induced osteoclast differentiation through Blimp1-Bcl-6 signaling mediated modulation of NFATc1 and its target genes. Consistent with these in vitro results, AGR exhibited a protective influence in an in vivo mouse model of LPS-induced bone loss by suppressing excessive osteoclast activity and attenuating LPS-induced bone destruction. Hence, these results identified that AGR could be considered as a potential therapeutic agent against bone lysis disease.
33122743 Chronic rhinosinusitis and premorbid autoimmune diseases: a population-based case-control 2020 Oct 29 Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case-control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28-1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34-1.67], 3.47 [1.12-10.8], 1.22 [1.04-1.43], 1.60 [1.31-1.96], 2.10 [1.63-2.72], and 1.69 [1.26-2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14-1.58] and 1.50 [1.38-1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72-2.49] and 1.39 [1.28-1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.
33119380 Relationship of medical comorbidities to psychological health at 2 and 5 years following t 2021 May Objective: To examine the relationship between medical comorbidities and psychological health outcomes at 2 and 5 years following traumatic brain injury (TBI). Method: Veterans Affairs (VA) TBI Model System participants who completed a 2-year (n = 225) and/or 5-year (n = 283) follow-up with a comorbidities interview were included in the current study. Psychological health outcomes were assessed using the Patient Global Impression of Change (PGIC), Patient Health Questionnaire-9 (PHQ-9), and Satisfaction with Life Scale (SWLS). While controlling for known predictors of outcome, the relationship of overall comorbidity burden to psychological outcomes was examined cross-sectionally using generalized linear regression at 2 and 5 years post-TBI. Lasso regularization was used to examine relationships of specific comorbid conditions to outcome. Results: Greater comorbidity burden was significantly associated with lower satisfaction with life at 2 and 5 years post-TBI and was associated with greater depressive symptomatology at 5 years post-TBI. Chronic pain was associated with lower satisfaction with life and greater depressive symptoms at both 2- and 5-year follow-up. Sleep apnea was associated with lower satisfaction with life and greater depressive symptoms at 5-year follow-up. Rheumatoid arthritis was associated with lower satisfaction with life and lower levels of perceived improvement in health and well-being at the 5-year follow-up. Implications: Results suggest that medical comorbidities may have a cumulative impact on adverse psychological health outcomes in chronic stages of TBI. This study further highlights the complexity of patients with TBI and the importance of identifying medical comorbidities as they provide potential targets for intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
33107286 [Evaluation of Patients Diagnosed with COVID-19 in Terms of Risk Factors]. 2020 Oct Coronaviruses are RNA viruses that can cause disease in the upper and lower respiratory tract in humans and animals. Lately, a new coronavirus causing pneumonia cases was detected in Wuhan, China in December 2019. Soon after, the name of the virus was identified as the "severe acute respiratory syndrome coronavirus-2", and the World Health Organization named the disease coronavirus disease-2019 (COVID-19). In our country, the first cases began to appear in the second week of March. In this study, we aimed to investigate the demographic characteristics and risk factors of patients with the diagnosis of COVID-19. A total of 100 patients (53 female and 47 male) were included in our study. The patients included in the study were randomly selected from the registration system and their information was evaluated retrospectively. The mean age of the patients was 54.42 (Age range= 20-90). When the risk factors for catching the disease were evaluated; it was determined that there was at least one risk factor in 46 patients; 30 patients had close contact with the COVID-19 patient in the social environment (30%) and 16 patients had a travel history outside the city in the last 14 days (16%). The most common symptoms in our patients were; cough (93%), fever (42%), dyspnea (22%), weakness (8%), sore throat (7%), diarrhea (6%), headache (5%) and sputum (2%). The most common comorbid conditions in our patients were detected as hypertension (42%), diabetes mellitus (DM) (21%), congestive heart failure (10%), allergic asthma (7%), chronic obstructive pulmonary disease (6%), rheumatoid arthritis (3%), coronary artery disease (2%), solid organ tumour (2%), depression (1%) and epilepsy (1%). The mean age of our 15 patients who were monitored in intensive care unit was 65 y (± 11.46), the mean age of 85 patients followed in the service was 52.55 (± 16.35) and this difference was statistically significant (p= 0.006). When these two groups were compared in terms of comorbid diseases, the presence of DM was 40% higher (n= 6) in intensive care patients, and this difference was statistically significant (p= 0.05). In addition, the majority [11 patients (73%)] of the patients hospitalized in the intensive care unit were male (p= 0.03). When smoking was evaluated as a risk factor for serious illness, 4 of 11 patients (26%) in intensive care unit had a smoking history, while none of the patients who have died due to COVID-19 had a smoking history. These findings suggested to us that smoking does not increase the severity of COVID-19 disease. As a result, knowledge about the disease should be increased rapidly by sharing the studies on risk factors, transmission routes and clinical features of COVID-19 infection, which affects the whole world.
33101286 Priming Is Dispensable for NLRP3 Inflammasome Activation in Human Monocytes In Vitro. 2020 Interleukin (IL)-18 and IL-1β are potent pro-inflammatory cytokines that contribute to inflammatory conditions such as rheumatoid arthritis and Alzheimer's disease. They are produced as inactive precursors that are activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. NLRP3 inflammasome activation is regarded to require a priming step that causes NLRP3 and IL-1β gene upregulation, and also NLRP3 post-translational licencing. A subsequent activation step leads to the assembly of the complex and the cleavage of pro-IL-18 and pro-IL-1β by caspase-1 into their mature forms, allowing their release. Here we show that human monocytes, but not monocyte derived macrophages, are able to form canonical NLRP3 inflammasomes in the absence of priming. NLRP3 activator nigericin caused the processing and release of constitutively expressed IL-18 in an unprimed setting. This was mediated by the canonical NLRP3 inflammasome that was dependent on K(+) and Cl(-) efflux and led to ASC oligomerization, caspase-1 and Gasdermin-D (GSDMD) cleavage. IL-18 release was impaired by the NLRP3 inhibitor MCC950 and by the absence of NLRP3, but also by deficiency of GSDMD, suggesting that pyroptosis is the mechanism of release. This work highlights the readiness of the NLRP3 inflammasome to assemble in the absence of priming in human monocytes and hence contribute to the very early stages of the inflammatory response when IL-1β has not yet been produced. It is important to consider the unprimed setting when researching the mechanisms of NLRP3 activation, as to not overshadow the pathways that occur in the absence of priming stimuli, which might only enhance this response.
33049473 Investigations of adsorption behavior and anti-inflammatory activity of glycine functional 2021 Feb 5 The adsorption behavior of the amino acid, glycine (Gly), via the carboxyl, hydroxyl, and amino groups onto the surfaces of Al(12)N(12) and Al(16)N(16) fullerene-like cages were computationally evaluated by the combination of density functional theory (DFT) and molecular docking studies. It was found that Gly can chemically bond with the Al(12)N(12) and Al(16)N(16) fullerene-like cages as its amino group being more favorable to interact with the aluminum atoms of the adsorbents compared to carboxyl and hydroxyl groups. Oxygen and carbon doping were reported to reduce steric hindrance for Glycine interaction at Al site of Al(12)ON(11)/Gly and Al(12)CN(11)/Gly complexes. Interaction was further enhanced by oxygen doping due to its greater electron withdrawing effect. Herein, the Al(12)ON(11)/Gly complex where two carbonyl groups of Gly are bonded to the aluminum atoms of the Al(12)N(12) fullerene-like cage is the most stable interaction configuration showing ∆(ads)H and ∆(ads)G values of -81.74 kcal/mol and -66.21 kcal/mol, respectively. Computational studies also revealed the frequency shifts that occurred due to the interaction process. Molecular docking analysis revealed that the Al(12)N(12)/Gly (-11.7 kcal/mol) and the Al(12)ON(11)/Gly (-9.2 kcal/mol) complexes have a good binding affinity with protein tumor necrosis factor alpha (TNF-α). TNF-α was implicated as a key cytokine in various diseases, and it has been a validated therapeutic target for the treatment of rheumatoid arthritis. These results suggest that the Al(12)N(12)/Gly complex in comparison with the Al(16)N(16)/Gly, Al(12)ON(11)/Gly, and the Al(12)CN(11)/Gly complexes could be efficient inhibitors of TNF-α.
33012087 Risk of autoimmune diseases in recurrent aphthous ulcer patients: A nationwide population 2021 Sep OBJECTIVE: To estimate the risk of developing autoimmune disease in patients diagnosed having recurrent aphthous stomatitis (RAS) through a nationwide population-based cohort study. METHODS: This study included two group of patients who had three or more episodes with aphthae diagnosed from their physician (RAS group) and a similar matched group of patients without aphthae (control group). Both groups were collected within the period of 2005-2007 from the Korean National Health Insurances claims database. Non-RAS cohort was matched after frequency matching. The final enrolled subjects were observed during a follow-up period from 2008 to 2015 and those who received autoimmune diseases diagnoses during follow-up were identified. The hazard ratio (HR) for developing autoimmune diseases was estimated. RESULTS: A total of 4,637 patients with RAS and 4,637 controls were included. The risk of overall autoimmune diseases was significantly increased in the RAS group (adjusted HR [aHR)], 1.19). With regard to each disease entity, patients with RAS showed an increased risk of Behcet's disease (31.16), systemic lupus erythematous (SLE) (1.74), ankylosing spondylitis (AS) (1.47), gout (1.47), Hashimoto thyroiditis (1.42), Graves' disease (1.37), and rheumatoid arthritis (RA) (1.19). CONCLUSION: RAS-like lesion may be an early sign of systemic autoimmune disease, as it was associated with an increased risk of Graves' disease, Hashimoto thyroiditis, SLE, AS, gout, RA, and Behcet's disease from real-world data.
32984847 Long-term hydroxychloroquine use in patients with rheumatic conditions and development of 2020 Nov BACKGROUND: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. FINDINGS: Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52-1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55-0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51-1·42). INTERPRETATION: Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. FUNDING: None.
32846192 The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharma 2021 Jan 30 ETHNOPHARMACOLOGICAL RELEVANCE: Herba Patriniae has been used for thousands of years in China as a traditional Chinese medicine with heat-clearing and detoxicating effects. It is applied widly for the treatment of rheumatoid arthritis, diarrhea, acute hepatitis, pelvic inflammatory disease and ulcerative colitis in clinic. Two species, namely Patrinia scabiosaefolia Fisch. (PS) and Patrinia villosa Juss. (PV) from the Caprifoliaceae family, are considered as Herba Patriniae in the pharmaceutical industry. AIM OF THE REVIEW: This paper aims to comprehensively outline the traditional uses, botanical description, phytochemistry, pharmacology, toxicology, quality control, pharmacokinetics and patents of Herba Patriniae, and elaborate the same/different characteristics between PS and PV. MATERIALS AND METHODS: Detailed information of Herba Patriniae was collected from various online databases (Pubmed, Web of Science, Google Schola, China National Knowledge Infrastructure Database, National Intellectual Property Administration, PRC National Medical Products Administration), and those published resources (M.Sc. Thesis and books). RESULTS: A total of 233 compounds have been identified in Herba Patriniae, including triterpenoid saponins, flavonoids, organic acids, iridoids, and volatiles. A very distinct difference was observed, that PS is rich in triterpenoid saponins and volatiles, while PV contains more flavonoids. Two source species of Herba Patriniae gave similar pharmacological effects on anti-cancer, anti-inflammatory, antioxidant, antimicrobial, sedative and hypnotic effects. But there were no reports were on antipruritic, proangiogenic and anti-diarrheal effects for PS, and no studies on anti-diabetic effects for PV. Generally, Herba Patriniae showed non-toxic in the clinical dose, but mild side effects, such as temporary leukopenia, dizziness and nausea, could be found when large and excessive dosage is used. A variety of compounds have been quantified for the quality control of PS and PV. The variety, growth environment, growth time, and harvest time not only affected the contents but also the pharmacological activities of the bioactive compounds. In the past year, patents for compositions containing PV and PS have been filed, mainly involving human health, hygiene, agriculture, and animal husbandry. Unfortunately, the research on pharmacokinetics is insufficient. Only the prototype components and metabolites were repored after intragastric administration of total flavonoids extract from PV in rats. CONCLUSION: Herba Patriniae has displayed a significant medicinal value in clinic, but the differences in phytochemistry, pharmacological effects and the content of compounds have been found between two official recorded species. About side effects and pharmacokinetic characteristics, the differences between two species have not been well studied. For a better clinical use of Herba Patriniae, it is urgent to establish systematic pharmacology, quality control, pharmacokinetics, and clinical researches on the same/different characteristics between PS and PV.
32807193 Reproductive health needs of adolescent and young adult women with pediatric rheumatic dis 2020 Aug 17 BACKGROUND: The purpose of this study was to identify reproductive health knowledge gaps and topics that concern adolescent and young adult (AYA) women with pediatric rheumatic diseases and their parents. METHODS: Data collection occurred in two cohorts. In the first cohort, young women (15-20 years old) with pediatric-onset rheumatic conditions and their parents were recruited from a single, academic pediatric rheumatology center. In the second cohort, young women (18-25 years old) with pediatric-onset rheumatic conditions were recruited from a national conference for families with pediatric rheumatic diseases. This resulted in 20 adolescents and young adults (18.3 ± 2.4 years old), and 7 parent focus group participants. Focus group leaders facilitated discussions centered on reproductive health topics that participants identified as important, their sources of knowledge, and preferences for patient education and ongoing follow-up. Data were summarized independently by 4 researchers to reduce potential bias and subsequently analyzed using rapid qualitative analysis. RESULTS: All participants, regardless of diagnosis, medication, current sexual activity, or current intention to have children, expressed concern about the effect of their rheumatic condition and medications on fertility, risks to mother and child during and after pregnancy, and obtaining safe and effective contraception. Additionally, some participants discussed the burden of disease and its potential impact on motherhood. Finally, participants raised concern around the effect of disease and medication on routine reproductive health care, such as menstrual cycles, feminine self-care, and preventive exams. Three themes emerged: 1) participants had been advised to avoid unplanned pregnancy, however reported receiving inadequate explanation to support this instruction, 2) participants conceptualized reproductive health as tied to rheumatic disease management and thus suggested ways to include family members in discussion, and 3) rheumatology practitioners were not considered a resource of reproductive health information. CONCLUSIONS: Young women and their parents reported dissatisfaction with the availability, quantity, and quality of reproductive health information they received, particularly when related to their pediatric-onset rheumatic disease. These findings provide an initial step in understanding the patient perspective of reproductive health in rheumatology, and how to address these concerns in the care of young women with rheumatic diseases.
32673703 Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders. 2020 Oct Phosphodiesterases (PDE) are a diverse family of enzymes (11 isoforms so far identified) responsible for the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are involved in several cellular and biochemical functions. Phosphodiesterase 4 (PDE4) is the major isoform within this group and is highly expressed in the mammalian brain. An inverse association between PDE4 and cAMP levels is the key mechanism in various pathophysiological conditions like airway inflammatory diseases-chronic obstruction pulmonary disease (COPD), asthma, psoriasis, rheumatoid arthritis, and neurological disorders etc. In 2011, roflumilast, a PDE4 inhibitor (PDE4I) was approved for the treatment of COPD. Subsequently, other PDE4 inhibitors (PDE4Is) like apremilast and crisaborole were approved by the Food and Drug Administration (FDA) for psoriasis, atopic dermatitis etc. Due to the adverse effects like unbearable nausea and vomiting, dose intolerance and diarrhoea, PDE4 inhibitors have very less clinical compliance. Efforts are being made to develop allosteric modulation with high specificity to PDE4 isoforms having better efficacy and lesser adverse effects. Interestingly, repositioning PDE4Is towards neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and sleep disorders, is gaining attention. This review is an attempt to summarize the data on the effects of PDE4 overexpression in neurological disorders and the use of PDE4Is and newer allosteric modulators as therapeutic options. We have also compiled a list of on-going clinical trials on PDE4 inhibitors in neurological disorders.
32632509 Blindness increases the risk for hip fracture and vertebral fracture but not the risk for 2020 Dec The risks for hip fracture and vertebral fracture, but not the risk for distal radius fracture, were significantly higher in the blindness group than in the control group with a maximum 12-year follow-up. PURPOSE: To evaluate the influence of visual impairment on the risk for osteoporotic fractures at common sites: hip, thoracic/lumbar vertebra, and distal radius. METHODS: This longitudinal follow-up study used a database of a national sample cohort from 2002 to 2013 provided by the Korean National Health Insurance Service. Of a total of 1,125,691 subjects, 3918 patients with visual impairment and age ≥ 50 years were enrolled in a 1:4 ratio; 15,672 control participants were matched for age, sex, income, and region of residence. Stratified Cox proportional-hazards models were used to evaluate the crude and adjusted (for steroid medication, rheumatoid arthritis, depression, osteoporosis, diabetes mellitus, and stroke history) hazard ratios (HRs) for each fracture site. Fracture diagnoses were based on the ICD-10 codes: hip fracture (S720, S721, S722), vertebral fracture (S220, S320), and distal radius fracture (S525). RESULTS: The HRs for hip and vertebral fracture were significantly higher in the blindness group (adjusted HR = 2.46, p < 0.001 for hip fracture; adjusted HR = 1.42, p = 0.020 for thoracic/lumbar vertebral fracture) than in the matched control group. However, the HR for distal radius fracture was not higher in the blindness group. The HRs for all three fracture sites were not significantly higher in the non-blindness visual impairment group after adjustment. CONCLUSION: The risks for hip fracture and vertebral fracture were significantly higher in the blindness group. However, the risk for distal radius fracture was not related to visual impairment including blindness.
32619724 Effect of statin use on cardiovascular events and all-cause mortality in immune-mediated i 2020 Oct BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of premature cardiovascular disease and all-cause mortality. Given lipid-lowering and anti-inflammatory properties, statins theoretically provide greater survival benefits for patients with IMIDs. OBJECTIVE: We aimed to evaluate the impact of statin on all-cause mortality and cardiovascular risk in patients with IMIDs, and examine whether the effect varies between primary prevention and secondary prevention. METHODS: We systematically searched PubMed, EMBASE and Cochrane Library to identify eligible studies evaluating the association between statin use and all-cause mortality or cardiovascular events in IMIDs. Data were pooled using fixed-effects or random-effects meta-analysis according to I(2) and pooled hazard ratios (HRs) and 95 % confidence intervals (CIs) were used as summary statistic. RESULTS: Our meta-analysis included 12 studies that comprised 148,722 patients with IMIDs (57,670 statin users, 91,052 statin non-users) contributing more than 840,113 patient-years. In pooled analysis, statin initiation was associated with 28 % decreased risk of all-cause mortality (random-effects: meta-HR 0.72, 95 % CI 0.65-0.80), 23 % decreased risk of major adverse cardiovascular events (fixed-effects: meta-HR 0.72, 95 % CI 0.62-0.83). Subgroup analysis of patients with rheumatoid arthritis showed similar results (fixed-effects: meta-HR 0.77, 95 % CI 0.67-0.89 for all-cause mortality; meta-HR 0.75, 95 % CI 0.63-0.88 for major adverse cardiovascular events). Furthermore, the protective role of statin in decreasing mortality was stronger in patients receiving statin for primary prevention of cardiovascular diseases than that for secondary prevention (fixed-effects: meta-HR 0.64, 95 % CI 0.59-0.70; meta-HR 0.84, 95 % CI 0.80-0.89, respectively), although both were statistically significant. Additional analysis yielded similar benefit from statin usage between females and males regarding mortality. CONCLUSION: Statin use was associated with lower risks of mortality and cardiovascular events, with greater benefits for primary prevention in those IMIDs patients without prior cardiovascular disease.