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To investigate cardiovascular risk among diabetic patients with Sjögren syndrome.This study was a nationwide population-based case-control study from 1997 to 2013, in which the association between autoimmune diseases and diabetes was investigated. The study population consisted of individuals with newly diagnosed type 2 diabetes with macrovascular or microvascular complications with at least two outpatient visits or one hospitalization as the outcome variables, and the exposure variables included traditional risk factors, medications, and autoimmune diseases. The odds ratio of cardiovascular events among each prevalent autoimmune disease and hydroxychloroquine's effect on cardiovascular risk were analyzed.The study included a total of 7026 individuals with diabetes with microvascular and macrovascular complications and the same number of patients in the control group. Sjögren syndrome was significantly higher in the diabetes complication group than in the non-complication group (0.8% vs 0.5%, P = 0.036). By using multivariate analysis, we found hypertension, hyperlipidemia, and Sjögren syndrome to be three independent risk factors for diabetes vascular complications (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.82-2.10; OR 1.53, 95% CI 1.42-1.64; and OR 1.67, 95% CI 1.06-2.65; respectively, all P 0.05). Treatment with traditional statins and aspirin might be able to overcome the increased risk of developing cardiovascular events while comparing between diabetes patients with and without Sjögren syndrome.Sjögren syndrome is an unrecognized independent risk factor for cardiovascular events among diabetes patients, which indicates that patients with diabetes combined with Sjögren syndrome require closer follow up regarding cardiovascular complications in clinical settings. Treatment with hydroxychloroquine might not be enough to lower the cardiovascular risk significantly in diabetes patients with Sjögren syndrome.

Background: Moderate to severe atopic dermatitis (AD) is difficult to treat. There are rare reports on the treatment of moderate to severe AD by lowering serum IgE with a combination of methotrexate (MTX) and azathioprine (AZA) and hence improving symptoms. Objective: This study aimed to improve AD symptoms by lowering serum IgE with a combination therapy of MTX and AZA. Design: Retrospective cohort study of patients treated during 2013 and 2019. Setting: Patients recruited from a tertiary care university hospital in Taiwan. Participants: Sixty-five (case group) and 36 (control group) patients with moderate to severe AD, aged between 10 and 77 years. Measurements: Patients in the case group received a combination of MTX (15 mg weekly) and AZA (150 mg daily) for 1 to 5 years. Patients in the control group received any therapies other than this combination. Serum total IgE levels were checked periodically in both groups. Results: Serum total IgE was markedly reduced in the case group. For example, the cumulative success rates of a 50% IgE reduction in the case group in year 1 and year 5 were 69.2% and 98.5%, respectively, compared to 10.0% and 18.2% in the control group (hazard ratio 14.8; p < 0.001). At the end of year 4, the cumulative success rate of IgE reduction to below the normal range was 41.1% in the case group and 3.4% in the control group (hazard ratio 6.71; p = 0.033). Regarding adverse events, the rates of abnormal white blood cell counts, hemoglobin, platelet counts, and alanine aminotransferase were not increased in the case group compared to the control group. Conclusion: Combination therapy with MTX and AZA was effective in treating patients with intractable AD by reducing their serum total IgE levels.

We aimed to compare the long-term persistence between different tumor necrosis factor-alpha inhibitors (TNFis) with immune-mediated rheumatic diseases (IMRD). This study can potentially provide insights into the real-world evidence regarding safety and effectiveness of TNFi treatment in a Chinese population.We enrolled newly diagnosed IMRD patients in this active comparator, retrospective cohort study by using National Taiwan insurance claim datasets. The drug survivals of first-line TNFi agents, including etanercept, golimumab, and adalimumab were compared. Propensity score matching was conducted to control the confounding effect from the observed covariates. The cumulative proportion of discontinuation was calculated over 5 years. The multiple-variable regression and propensity score analysis was used for confounding adjustment.After propensity score matching, there were 2267 patients identified in each etanercept, golimumab, and adalimumab group. We observed the 5-year cumulative proportion of discontinuation was 52.80%, 45.85%, and 56.86% in etanercept, golimumab, and adalimumab, respectively. Compared with golimumab, increase of 31% (95% CI: 20-43) and 38% (95% CI: 26-50) risk of discontinuation were observed in etanercept and adalimumab. The factors including female gender, increasing age, long hospital stays, without co-medication with nonsteroidal anti-inflammatory drugs or methotrexate were associated were discontinuation of first-line TNFi treatment.Golimumab had better drug survival than etanercept or adalimumab over 5 years of observation in Asian IMRD patients. Gender, age, longer hospital stays, concomitant use of disease-modifying antirheumatic drugs were associated with survival with TNFis.

We conducted a large, retrospective cohort study using data from Taiwan’s National Health Insurance Research Database to evaluate whether the risk of developing osteoporosis is associated with sepsis. Our study found that adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis. There have been limited studies regarding the osteoporosis risk associated with sepsis. Our purpose is to evaluate whether the risk of developing osteoporosis is associated with sepsis. We conducted a large, retrospective cohort study using data from Taiwan’s National Health Insurance Research Database. From the insurance claims data, a total of 13,178 patients diagnosed with sepsis from 2000 to 2012 were included in the sepsis cohort, and a propensity score-matched cohort included 13,178 individuals without sepsis. To calculate the incidence of osteoporosis, both groups were followed until 2013. Cox regression analysis was performed to obtain the hazard ratios (HRs) to assess the risk of developing osteoporosis. The Kaplan–Meier method was used to estimate the cumulative incidence of osteoporosis. The overall incidences of osteoporosis (per 1,000 person-years) in the sepsis and non-sepsis groups were 10.2 and 10.7, respectively. The risk of osteoporosis significantly increased in the presence of sepsis (adjusted HR = 1.17, 95% confidence interval (CI) = 1.04–1.31). The risk of osteoporosis in the sepsis group was significantly higher than that in the non-sepsis group for young patients aged 20–49 years and patients aged 50–64 years (adjusted HR = 1.93, 95% CI = 1.08–3.44; adjusted HR = 2.01, 95% CI = 1.52–2.65, respectively). The Kaplan–Meier curves of cumulative probability also showed a significantly increased risk of osteoporosis in patients aged 20–49 years and aged 50–64 years with sepsis compared with non-sepsis (P = 0.025; P < 0.001, respectively). Adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.

Cardiac arrhythmias have a strong association with pneumonia due to the cardiovascular response to infection. Electrocardiographic (ECG) changes in patients with pneumonia are associated with greater disease severity. Atrial fibrillation (AF) is the most common type of cardiac arrhythmia.This population-based cohort study investigated the incidence of AF among Taiwanese adults with pneumonia using data from the National Health Insurance Research Database in Taiwan.A total of 34,883 patients with pneumonia and an equal number of individuals without pneumonia were eligible after excluding those with a previous diagnosis of AF and matching 1:1 by age, sex, and comorbidities. The Cox proportional hazards model was used to estimate hazard ratios for AF in both groups.Patients were more likely to develop AF throughout the 1-year follow-up period after the diagnosis of pneumonia. The incidence of AF was 1.2 (414/334,746) per 1000 person-months. Patients with pneumonia had a 4.08-fold (95% confidence interval 3.37-4.95) increased risk for AF compared to patients without pneumonia.Patients with pneumonia exhibited an increased risk for AF, especially in the early period after diagnosis of pneumonia.

Burns can cause cell death and irreversible tissue damage. We examined the pathway of human dermis fibroblasts cell death caused by skin burns and the roles of chloroquine in human skin keratinocytes HaCaT wound healing. Western blot assays were performed to assess expression of proteins associated with autophagy, apoptosis, and endoplasmic reticulum stress in skin cells following burns. Changes in apoptosis-related proteins were assessed using flow cytometry, and wound cell migration was examined using wound healing assays. The burn animal model was used to test whether chloroquine would promote wound healing. In human burned fibroblasts, expression of LC3B-II and Cleave-caspase-7 was increased, whereas expression of Beclin-1, p62, and Grp78 was decreased. Severe burn induced ER stress and ERK phosphorylation, but PD98059 or necrostatin-1 treatment cells did not affect expression of autophagy LC3B-II protein and can induce apoptosis. Even though added with TGF-β and FGF did not repair autophagy caused by burns. Suggesting that autophagy and apoptosis were involved in heat-injured mechanism. Recombinant Wnt3a protein can help restore expression of β-catenin which reduced following burns in keratinocytes. Wnt3a protein can promote migration of keratinocytes after burns. Interesting, chloroquine increased expression of LC3B-II protein and restored cell migration activity after 24 h of burns. Consistently, surgical dressing containing chloroquine promoted wound healing in a burn animal mode. Autophagy and Wnt/β-catenin is two signalling pathways that participate in cell repair and wound healing in human fibroblasts, keratinocytes. Surgical dressing containing chloroquine can recover wound healing in burned rats.

Obsessive-compulsive disorder (OCD) includes a wide range of symptoms and is often associated with comorbidities. Although psychiatric involvement may be an early manifestation of Sjögren’s syndrome (SS), only a few studies have demonstrated the relationship between OCD and SS. This is a nationwide cohort study identifying the risk of SS in OCD patients. We studied a longitudinal health insurance database for the period from 1999 to 2013. The study group was OCD patients with at least three outpatient visits or one hospitalization. The comparison cohort was matched by age and sex, as well as comorbidities. We calculated the risk of Sjögren’s syndrome using Cox proportional hazard regression models. We performed a propensity score match for confounders and effect modifiers between the two groups. The propensity score probability was estimated through logistic regression. Primary outcome was the incidental SS. A total of 1678 patients with OCD (49% women, mean age: 35.6 years) and 3356 controls were followed up, resulting in 13,077 and 25,856 person-years, respectively. The hazard ratio for developing SS was 3.31 (95% C.I.: 1.74–6.28) in patients with OCD, compared to those without OCD after adjusting for age, sex, and comorbidities. Furthermore, the risk of SS significantly increased over the 2-year follow-up period after OCD diagnosis. We concluded that risk of SS is significantly increased in patients with OCD compared to those without OCD. Clinically, Sjögren’s symptoms in OCD patients should be regularly assessed.

The purpose of this study is to evaluate the relationship between hydroxychloroquine (HCQ) and diabetic retinopathy (DR) via the national health insurance research database (NHIRD) of Taiwan. All patients with newly diagnosed type 2 diabetes (n = 47,353) in the NHIRD (2000–2012) were enrolled in the study. The case group consists of participants with diabetic ophthalmic complications, 1:1 matching by age (±1 year old), sex, and diagnosis year of diabetes was used to provide an index date for the control group that corresponded to the case group (n = 5550). Chi-square test for categorical variables and Student’s t-test for continuous variables were used. Conditional logistic regression was performed to estimate the adjusted odds ratio (aOR) of DR. The total number of HCQ user was 99 patients (1.8%) in the case group and 93 patients (1.7%) in the control group. Patients with hypertension (aOR = 1.21, 95% CI = 1.11–1.31) and hyperlipidemia (aOR = 1.65, 95% CI = 1.52–1.79) significantly increased the risk of diabetic ophthalmic complications (p &lt, 0.001). Conversely, the use of HCQ and the presence of rheumatoid diseases did not show any significance in increased risk of DR. HCQ prescription can improve systemic glycemic profile, but it does not decrease the risk of diabetic ophthalmic complications.

Background In terms of melanoma, recent advances have been made in target therapies and immune checkpoint inhibitors, but durable remission is rare. Ganoderma immunomodulatory proteins (GMI) induce a cytotoxic effect in cancer cells via autophagy. However, the role of GMI in melanoma is not clear. Purpose The aims of this study are to investigate the inhibiting effects of GMI combined with chidamide on survival and metastases of melanoma cells via integrin-related signaling pathway and to propose strategies for combining GMI and chidamide using animal model. Methods Cell viability was measured by cell CCK-8. The activities of apoptosis- and migration-related proteins were detected on Western blot. Flow cytometry was used to analyze cell cycle distribution and sub-G1 fraction in treated melanoma cells. To evaluate the activity of combination GMI and chidamide treatment, an in vivo anti-tumor metastasis study was performed. Results GMI combined with chidamide additively induced apoptosis. GMI inhibited the expressions of Integrin α5, αV, β1, and β3. The level of p-FAK was inhibited by GMI. Combination treatment of GMI and chidamide decreased survivin and increased cleaved caspase-7 and LC3 II/I. Integrin-αV overexpression activated p-FAK pathways in A375.S2 cells. GMI significantly inhibited cell growth and migration of A375.S2 cells on wound healing assay. In vivo, GMI combined with chidamide suppressed distal tumor metastasis. Conclusion GMI inhibits the migration and growth of melanoma cells via integrin-related signaling pathway. GMI and chidamide induces apoptosis. In vivo, GMI and chidamide additively reduce distant metastases. GMI and chidamide are potential immunotherapeutic adjuvant for metastatic melanoma.

To examine the association between endometriosis and the risk of systemic lupus erythematosus (SLE), this nationwide, population-based, retrospective cohort study was conducted based on National Health Insurance Research Database in Taiwan. Endometriosis (N = 16,758) and non-endometriosis (N = 16,758) groups were identified by matching baseline characteristics and comorbidities. Student’s t-tests and the Kaplan–Meier estimator were utilized to estimate the hazard ratio (HR) and cumulative probability of SLE in the two groups. The endometriosis group showed a significantly higher incidence density rate (0.3 vs. 0.1 per 1000 person-years) and hazard ratio in SLE group (adjusted HR [aHR], 2.37; 95% confidence interval [CI] 1.35–4.14) compared to the non-endometriosis group. Subgroup analysis revealed that patients with endometriosis between 30 and 45 years of age, or were non-steroidal anti-inflammatory drug users, or were hormonal medications-free participants, had higher risks of SLE. For patients with endometriosis, surgical intervention did not significantly impact on the risk of SLE. Our results demonstrated an increased risk of SLE in patients with endometriosis. Clinicians should be aware of this association when managing patients with endometriosis or SLE.

To the Editor: We have read with great interest in the article by Wang, et al on the higher incidence of non-Hodgkin lymphoma (NHL) in patients with primary Sjogren syndrome (pSS) and the higher incidence of pSS in patients with NHL1. Thank you for the discovery of the bilateral relationship between pSS and NHL in this nationwide population-based study1. However, we have some questions and findings that we would like to discuss. First, although the pSS cohort excluded patients diagnosed with other specific autoimmune diseases before the … Address correspondence to Dr. J.C. Wei, Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan. Email: jccwei{at}gmail.com.

To investigate the effects of hydroxychloroquine, sulfasalazine and methotrexate on ischemic stroke in patients with rheumatoid arthritis (RA).This population-based retrospective cohort study included 7904 RA patients and 15 808 non-RA patients between 2000 and 2010. All of the participants were sampled from the National Health Insurance Research Database (NHIRD) of Taiwan. Using univariate analyses, these two groups of patients were compared to evaluate the differences in disease-modifying anti-rheumatic drugs usage and demographic variables. Cox proportional hazard models and Schoenfeld residuals test were performed to estimate the hazard ratios for ischemic stroke and proportional hazard assumptions of these drugs, respectively.The mean age of participants was about 53 years old, and about 70% of RA patients were women. The hazard ratio for ischemic stroke was 1.21 (95% CI: 1.10-1.34; P0.01) in the case group compared with the control group, and this significant difference persisted throughout the 10-year period. With respect to RA patients, while hydroxychloroquine showed an insignificant protective effect on ischemic stroke, sulfasalazine and methotrexate were found out to have inconsistent effects during these 10 years. The proportional hazard assumption test of methotrexate at0.5 defined daily dose (8.75 mg/week) was violated at a significant level after adjustment (P = 0.0002).At a dosage of0.5 defined daily dose, short-term methotrexate might decrease ischemic stroke risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.

Aim To assess the effects of celecoxib and sulfasalazine on cardiovascular risk in patients with ankylosing spondylitis (AS). Methods We performed a 10-year population-based retrospective cohort study. A total of 1208 AS patients and 19 328 non-AS patients were sampled from the Taiwan National Health Insurance (NHI) database. We compared these two groups of patients to identify the differences in the exposure of non-steroidal anti-inflammatory drugs and sulfasalazine and their effects on cardiovascular risk. Univariate analyses were performed using Chi-squared tests for dichotomous variables and t-tests for continuous variables. Cox proportional hazard models were conducted to investigate the risk of developing cardiovascular diseases (CVD). Results AS patients had an adjusted hazard ratio (HR) of 1.72 (CI = 1.46–2.02, P < 0.01) for CVD compared with non-AS controls. The risk increased significantly with the progression of the disease. The use of celecoxib and sulfasalazine provided protective effects against CVD in both groups of patients. Both drugs at high cumulative defined daily doses (DDD) and celecoxib alone at high cumulative DDD showed significant protective effects against CVD in AS patients and the control group, respectively. Sulfasalazine at ≥ 0.5 DDD (1000 mg/day) reduced CVD risk in patients with AS (HR = 0.65, CI = 0.43–0.998, P < 0.05). Conclusions In this population-based retrospective cohort study, sulfasalazine at its optimal dose reduced CVD risk in patients with AS. Celecoxib was neutral regarding CVD risk in AS patients.

Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease associated with a high prevalence of cardiovascular disease (CVD). Hydroxychloroquine (HCQ) is commonly used to control disease activity in patients with SLE. We evaluated its potential additional therapeutic effect for reducing CVD in SLE patients. We conducted a retrospective cohort study, in which one million participants were sampled from 23 million beneficiaries and data were collected from 2000 to 2013. In total, 826 SLE patients receiving HCQ medication were included after exclusion for previous CVD. The total number of SLE patients was 795 after follow-up for more than one year. After adjusting for chronic comorbidity, a significantly decreased hazard ratio (HR) for coronary artery disease (CAD) was found among SLE patients with a high usage of HCQ for at least 318 days (HR = 0.31, 95% confidence interval, CI: 0.12&ndash, 0.76). A low HR for CAD was observed in SLE patients with a high cumulative dose of at least 100,267 mg HCQ (HR = 0.25, 95% CI: 0.09&ndash, 0.66). However, there was no significant lowering of the HR for stroke. Long-term HCQ therapy decreases the HR of CVD in SLE patients. The cardiovascular protective effect of HCQ therapy was associated with decrease in CAD, but not stroke.

Ketoconazole, an antifungal agent, has been used to inhibit hormone synthesis in types of prostate and breast cancer. Immunomodulatory proteins of Ganoderma microsporum (GMI) inhibit the tumor necrosis factor-α- and epidermal growth factor-induced metastatic ability of lung cancer cells. Cutaneous malignant melanoma is a highly invasive and metastatic skin cancer. However, to the best of our knowledge, there is limited understanding regarding the effects of ketoconazole and GMI on melanoma. The current study aimed to investigate the inhibitory effects of GMI combined with ketoconazole on melanoma survival and metastasis. The effects of GMI combined with ketoconazole on the viability, migration and protein expression of melanoma cells were determined by MTT assay, Boyden chamber assay and western blot analysis, respectively. The expression of monocyte chemoattractant protein-1 (MCP-1) was investigated by enzyme-linked immunoabsorbent assay. The present results indicate that ketoconazole enhances the GMI-induced decrease in proliferation and migration of A375.S2 melanoma cells in a concentration-dependent manner. Ketoconazole was identified to reduce the level of GMI-induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK)-α and autophagy; however, ketoconazole did not affect p-AMPK-β levels in A375.S2 cells. In addition, ketoconazole and dorsomorphin dihydrochloride, an AMPK inhibitor, were revealed to reduce MCP-1 secretion in A375.S2 cells. In summary, the present study revealed that ketoconazole enhances GMI-inhibited proliferation and migration of A375.S2 melanoma cancer cells, and inhibits the secretion of MCP-1.

We read with great interest the article by Pappas et al 1 who evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) such as adalimumab, etanercept, certolizumab pegol, golimumab or infliximab versus a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) as the first-line treatment in patients with rheumatoid arthritis (RA). The authors concluded that there were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for the outcomes assessed, including the Clinical Disease Activity Index (CDAI), the 28-Joint Modified Disease Activity Score, the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, morning stiffness and fatigue. In this observational study, data collected from 1 October 2001 to 31 January 2018 within a large US healthcare registry were evaluated, and 4816 patients who had a non-remission CDAI score …

We read with great interest the article by Micheroli et al 1 for comparison of effectiveness between secukinumab (SEC) and tumour necrosis factor inhibitor (TNFi) in axial spondylitis (axSpA), with evidence conform to the current recommendation in a Swiss real-world setting. According to current guidelines,2 ,3 ,4interleukin-17 inhibitor (IL-17i) or alternative TNFi are both recommended as the switch option of biological disease-modifying antirheumatic drug in patients with previous TNFi failure. Although head-to-head comparison clinical trials between IL-17 inhibition and TNF blockade have been conducted in psoriatic arthritis recently5 6 and is ongoing in axSpA, we appreciated Micheroli et al 1 for their new information in this real-world indirect comparison study. However, some issues can be further discussed. First, regarding the study design, it was not mentioned whether treatment adjustment was due to drug inefficacy or intolerability and the types of TNFi, receptor fusion protein or monoclonal antibody …

Introduction Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied. Methods Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect TG2 expression in synovial fluid mononuclear cells (SFMCs) and synovial tissue from patients with gouty arthritis. MSU crystal-exposed RAW264.7 mouse macrophages were analyzed for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and TG2 expression by RT-PCR and enzyme-linked immunosorbent assay (ELISA). TG2 small interfering (si)-RNA-mediated silencing and overexpression in RAW264.7 cells were used to evaluate the involvement of TG2 in resolving MSU crystal-induced inflammation. The role of metastatic tumor antigen 1 (MTA1), a master chromatin modifier, was investigated by MTA1 si-RNA-mediated knockdown. In addition, the inflammatory responses were followed in wild type and TG2 null mice after being challenged with MSU crystals in an in vivo peritonitis model. Results TG2 expression was up-regulated in the synovium tissue and SFMCs from patients with gouty arthritis. The levels of MTA1, TG2, TGF-β1, IL-1β and TNF-α mRNAs were consistently increased in MSU crystal-stimulated RAW264.7 cells. si-MTA1 impaired the basal, as well as the MSU crystal-induced expression of TG2 and TGF-β1, but increased that of IL-1β and TNF-α. TG2 overexpression dramatically suppressed MSU crystal-induced IL-1β and TNF-α, but significantly enhanced the TGF-β1 production. Neutralizing TGF-β antibodies or inhibition of the crosslinking activity of TG2 attenuated these effects. On the contrary, loss of TG2 resulted in a reduced TGF-β, but in an increased IL-1β and TNF-α production in MSU crystal-stimulated RAW264.7 cells and mouse embryonic fibroblasts (MEFs). MSU crystal-stimulated IL-1β production was Janus kinase 2 (JAK2)-signaling dependent and TG2-induced TGF-β suppressed the activity of it. Finally, TG2-deficient mice exhibited hyper inflammatory responses after being challenged with MSU crystals in an in vivo peritonitis model. Conclusions These findings reveal an inherent regulatory role of the MTA1-TG2 pathway in the self-limitation of MSU crystal-induced inflammation via positively regulating the levels of active TGF-β1 in macrophages that opposes the MSU crystal-induced JAK2-dependent pro-inflammatory cytokine formation. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0592-7) contains supplementary material, which is available to authorized users.

The aim of the study is to assess the effects of celecoxib and sulfasalazine on the risk of coronary artery disease (CAD) in patients with ankylosing spondylitis (AS). Using the claims data of Taiwan National Health Insurance (NHI) database, a nationally representative data that contain the medical records of 23 million Taiwan residents, we randomly selected 1 million cohort from the database, and then we enrolled only patients who were newly diagnosed with AS (n = 4829) between year 2001 and 2010, excluding patients who had CAD (ICD-9- CM codes: 410–414) before the diagnosis of AS (n = 4112). According to propensity score matched 1:2 on age, gender, AS duration, Charlson comorbidity index, hypertension, and hyperlipidemia, 236 and 472 patients were included in the case (AS with CAD) and control (AS without CAD) groups, respectively. We used the WHO defined daily dose (DDD) as a tool to assess the dosage of sulfasalazine and celecoxib exposure. Conditional logistic regression was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) for the risk of CAD associated with use of sulfasalazine and celecoxib. Among 4112 AS patients, 8.4% (346/4112) developed CAD. CAD in AS patients were positively associated with age of 35 to 65, Charlson comorbidities index (CCI), hypertension, and hyperlipidemia. There was no gender difference between case and control groups. After adjustment for age, gender, CCI, hypertension, and hyperlipidemia, sulfasalazine users with an average daily dose ≥ 0.5 DDD (0.5 gm/day) had negative association with CAD events as compared to sulfasalazine nonusers (OR 0.63; 95% CI, 0.40–0.99, P 1.5 DDD, were negatively associated with CAD events, compared to celecoxib nonusers (OR 0.34; 95% CI, 0.13–0.89; P

Abstract Introduction: Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied. Conclusions: These findings reveal an inherent regulatory role of the MTA1-TG2 pathway in the self-limitation of MSU crystal-induced inflammation via positively regulating the levels of active TGF-b in macrophages that opposes the MSU crystal- induced JAK2 -dependent pro-inflammatory cytokine formation.