HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

Reduced risk of dementia in patients with type 2 diabetes mellitus using Chinese herbal medicine: A nested case-control study.

BACKGROUND: Dementia is a prevalent condition in type 2 diabetes mellitus (T2DM) patients. While Chinese herbal medicine (CHM) is often employed as complementary therapy for glycemic control, its effect in controlling likelihood of dementia has not yet been fully elucidated. AIM: To compare the risk of dementia between T2DM patients with and without CHM treatment. METHODS: We undertook a nested case-control study and obtained data on patients 20-70 years of age who received medical care for T2DM between 2001 and 2010 from the National Health Insurance Research database in Taiwan. Cases, defined as those with dementia that occurred at least one year after the diagnosis of T2DM, were randomly matched to controls without dementia from the study cohort at a 1:1 ratio. We applied conditional logistic regression to explore the associations between CHM treatment and dementia. RESULTS: A total of 11699 dementia cases were matched to 11699 non-dementia controls. We found that adding CHM to conventional care was related to a lower risk of dementia [adjusted odds ratio (OR) = 0.51], and high-intensity CHM treatment was associated with an adjusted OR of 0.22. CONCLUSION: This study shows that the cumulative CHM exposure was inversely associated with dementia risk in an exposure-response manner, implying that CHM treatment may be embraced as a disease management approach for diabetic patients to prevent dementia.

Performance of a New Instrument for the Measurement of Systemic Lupus Erythematosus Disease Activity: The SLE-DAS.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects multiple organ systems and manifests in a relapsing-remitting pattern. Consequently, it is paramount for rheumatologists to assess disease activity, identify flare-ups, and establish treatment goals for patients with SLE. In 2019, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) was introduced as a novel tool for measuring disease activity. This tool refines the parameters of the established SLE Disease Activity Index 2000 (SLEDAI-2K) to enhance the assessment process. This review aims to provide an introduction to the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and summarizes research on its development, its comparison with existing disease activity measures, and its performance in clinical settings. Literature searches on PubMed using the keyword "SLE-DAS" were conducted, covering publications from March 2019 to September 2023. Studies that compared SLE-DAS with other SLE disease activity measurement tools were reviewed. Findings indicated that SLE-DAS consistently performs on par with, and sometimes better than, traditional measures in assessing clinically meaningful changes, patient improvement, disease activity, health-related quality of life, hospitalization rates, and disease flare-ups. The association between SLE-DAS and mortality rates among patients with SLE, however, remains to be further explored. Although SLE-DAS is a promising and potentially effective tool for measuring SLE disease activity, additional research is needed to confirm its effectiveness and broaden its clinical use.

Integrating Chinese Herbal Medicine into Conventional Care Was Related to Lower Risk of Sarcopenia Among Rheumatid Arthritis Patients: A Retrospective, Population-Based Study.

Objective: Sarcopenia is a frequently observed comorbidity of rheumatoid arthritis (RA) due to the chronic activation of the innate immune system. Accumulating evidence has indicated that Chinese herbal medicine (CHM) safely suppresses proinflammatory pathways and controls inflammation-associated disease, but its effect in reducing the risk of developing sarcopenia among RA subjects has not been established. We conducted a population-level cohort study to compare the sarcopenia risk in patients with RA who use or do not use CHM. Methods: Using claims from a nationwide insurance database, we recruited patients with newly diagnosed RA and without sarcopenia between 2002 and 2010. Propensity score matching was applied to randomly select sets of CHM users and non-CHM users to compare the sarcopenia risk until the end of 2013. The risk of new-onset sarcopenia was assessed using the Cox proportional hazards model. Results: As compared to non-CHM users, those receiving CHM treatment had a lower incidence of sarcopenia (7.69 vs 9.83 per 1000 person-years). CHM was correlated with a decreased chance of sarcopenia after controlling for potential covariates. Notably, use of CHM for more than two years may diminish the risk of getting sarcopenia by about 47% when taken as prescribed. Prescriptions of several herbal formulae may benefit the reduction of sarcopenia risk, such as Yan-Hu-Suo, Bei-Mu, Da-Huang, Huang Qin, Ping-Wei-San (PWS), Shu-Jing-Huo-Xue-Tang (SJHXT) and Chuan-Xiong-Cha-Tiao-San (CXCTS). Conclusion: This study produced new evidence as it is the first to show that the longer duration of CHM use was correlated to reduced risk of sarcopenia in a dose-dependent manner, implying that CHM treatment could be embraced as a routine care strategy for preventing sarcopenia.

Rheumatic Diseases: New Progress in Clinical Research and Pathogenesis.

Rheumatic diseases encompass a group of disorders that primarily target the musculoskeletal system, including joints, bones, muscles, and connective tissue [...].

Increased Expression of Long Noncoding RNA LOC100506314 in T cells from Patients with Nonsegmental Vitiligo and Its Contribution to Vitiligo Pathogenesis.

This study aimed to identify the abnormal expression of long noncoding RNAs (lncRNAs) in T cells from patients with vitiligo and to investigate their functional roles in the immune system. Using microarray analysis, the expression levels of RNA transcripts in T cells from patients with vitiligo and controls were compared. We identified several genes and validated their expression levels in T cells from 41 vitiligo patients and 41 controls. The biological functions of the lncRNAs were studied in a transfection study using an RNA pull-down assay, followed by proteomic analysis and western blotting. The expression levels of 134 genes were significantly increased, and those of 142 genes were significantly decreased in T cells from vitiligo patients. After validation, six genes had increased expression, and three genes had decreased expression in T cells from patients with vitiligo. T-cell expression of LOC100506314 was increased in vitiligo, especially CD4+, but not CD8+ T cells. The expression levels of LOC100506314 in CD4+ T cells was positively and significantly associated with the severity of vitiligo. LOC100506314 was bound to the signal transducer and activator of transcription 3 (STAT3) and macrophage migration inhibitory factor (MIF). Enhanced expression of LOC100506314 inhibited the phosphorylation of STAT3, protein kinase B (AKT), and extracellular signal-regulated protein kinases (ERK), as well as the levels of nuclear protein of p65 and the expression of IL-6 and IL-17 in Jurkat cells and T cells from patients with vitiligo. In conclusion, this study showed that the expression of LOC100506314 was elevated in CD4+ T cells from patients with vitiligo and associated the severity of vitiligo. LOC100506314 interacted with STAT3 and MIF and inhibited IL-6 and IL-17 expression by suppressing the STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), AKT, and ERK pathways. Enhanced expression of LOC100506314 in T cells may be a potential treatment strategy for vitiligo.

Use of Chinese Herbal Medicine Was Related to Lower Risk of Osteoporotic Fracture in Sarcopenia Patients: Evidence from Population-Based Health Claims.

Introduction: With population aging, sarcopenia and its accompanying risk of osteoporotic fracture has drawn increased attention. Nowadays, while Chinese herbal medicine (CHM) is often used as complementary therapy for many medical conditions, its effect against likelihood of osteoporotic fracture among sarcopenia subjects was not fully elucidated yet. We therefore conducted a population-level study to compare osteoporotic fracture risk for sarcopenia persons with or without CHM use. Methods: Using the patient record from a nationwide insurance database, we recruited persons with newly diagnosed sarcopenia and simultaneously free of osteoporotic fracture between 2000 and 2010. Propensity score matching was then applied to randomly select sets of CHM users and non-CHM users. All of them were tracked until end of 2013 to measure the incidence and adjusted hazard ratios (HRs) for new new-onset fracture in multivariable Cox proportional hazards model. Results: Compared to non-CHM users, the CHM users indeed had a lower incidence of osteoporotic fracture (121.22 vs 156.61 per 1000 person-years). Use of CHM correlated significantly with a lower fracture likelihood after adjusting for potential covariates, and those receiving CHM treatment for more than two years experienced a remarkably lower risk by 73%. Uses of several herbal formulae were correlated to reduced risk of osteoporotic fracture, such as Caulis Spatholobi, Xuduan, Duzhong, Danshen, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang, Shao-Yao-Gan-Cao-Tang, and Shen-Tong-Zhu-Yu -Tang. Conclusion: Our study depicted that cumulative CHM exposure was inversely associated with osteoporotic fracture risk in a duration-dependent manner, implying that CHM treatment may be embraced as routine care in preventing incident osteoporotic fracture.

Effects of a walking exercise programme on disease activity, sleep quality, and quality of life in systemic lupus erythematosus patients.

AIM: This quasi-experimental study aimed to explore effects of walking exercise on disease activity, sleep quality, and quality of life among individuals with systemic lupus erythematosus. METHODS: After recruiting people with systemic lupus erythematosus from a hospital in Taiwan between October 2020 and June 2021, participants were free to opt to receive one walking exercise programme plus standard care for 3 months or to membership of a control group receiving routine care. Primary outcomes included Systemic Lupus Erythematosus Disease Activity Score, the Pittsburgh Sleep Quality Scale, and a quality-of-life scale for patients with systemic lupus erythematosus, namely, LupusQoL. These scales were administered first, at baseline and later, within 1 week following completion of the intervention. Between-group effects were compared using generalized estimating equations with adjustment for baseline variables. RESULTS: The experimental and control groups each included 40 participants. Multivariate analysis indicated that adding the walking exercise programme into routine care elevated sleep quality and LupusQoL (the latter in the subscales of physical health, planning, and intimate relationships), except for disease activity. CONCLUSION: Findings of this study supported the addition of walking exercise as part of routine care for people with systemic lupus erythematosus and may be a reference in the provision of adequate care for these patients.

Increased Risk of Developing Systemic Lupus Erythematosus and Rheumatoid Arthritis in Patients with Primary Sjögren's Syndrome-A Secondary Cohort Analysis of Nationwide, Population-Based Claims Data.

BACKGROUND: This retrospective cohort study aimed to examine the risk of developing systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in patients with primary Sjögren's syndrome (pSS) compared to controls using data from a nationwide health claims database. METHODS: Four distinct cohorts of patients with newly diagnosed pSS were established using Taiwan's National Health Insurance Research Database. Cohorts I and II were created to evaluate the risk of developing SLE and RA, respectively. Cohorts III and IV were assembled similarly to Cohorts I and II but employed a stricter definition, based on catastrophic illness certificate (CIC) status, for identifying patients with pSS. Comparison cohorts of patients without pSS were formed by frequency matching for sex, 5-year age interval, and index year. Incident rate ratios (IRR) for SLE or RA development were determined using Poisson regression models. RESULTS: Patients with pSS, selected from just outpatient visits or with additional CIC status showed a significantly higher risk of developing SLE or RA compared with the controls. When stratified by age group or sex, the risk of developing SLE was notably higher in the young age group (adjusted IRR 47.24, p = 0.002) and women (adjusted IRR 7.63, p = 0.003) among patients with pSS. In addition, both men and women with pSS, irrespective of age, showed a significantly elevated risk of developing RA. CONCLUSIONS: Patients with pSS exhibited an elevated risk of developing SLE and RA. Rheumatologists should carefully monitor patients with pSS for potential SLE and RA development.

Integration of Chinese Herbal Medicine into Routine Care Was Related to Lower Risk of Chronic Kidney Disease in Patients with Rheumatoid Arthritis: A Population-Based Nested Case-Control Study in Taiwan.

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as the first-line agents for the symptomatic relief of rheumatoid arthritis (RA), but it may insidiously provoke the onset of renal diseases, especially chronic kidney disease (CKD). While Chinese herbal medicine (CHM) has become an increasingly popular adjunctive therapy among RA groups, there are currently no available data on the effect of CHM use towards risk of CKD. This study aimed to explore on a population-level whether CHM use decreases sequent CKD risk among them. Methods: In this nested case-control study retrieved from the nationwide insurance database of Taiwan from 2000 to 2012, we looked at the association between CHM use and the likelihood of developing CKD, with a focus on usage intensity. Cases with CKD claims were defined and matched to one randomly selected control case. Conditional logistic regression was then applied to estimate odds ratio (OR) of CKD from CHM treatment measured before the index date. For each OR, we calculated a 95% confidence interval for CHM use relative to the matched control. Results: This nested case-control study included 5464 patients with RA, where after matching comprised 2712 cases and 2712 controls. Among them, there were 706 and 1199 cases that ever received CHM treatment, respectively. After the adjustment, CHM use in RA individuals was related to a lower likelihood of CKD, with an adjusted OR of 0.49 (95% CI: 0.44-0.56). Additionally, a dose-dependent, reverse association was found between the cumulative duration of CHM use and risk of CKD. Conclusion: Integrating CHM into conventional therapy may reduce the likelihood of developing CKD, which could be a reference in instituting novel preventive strategies to improve treatment outcomes and reduce related fatalities for RA subjects.

Increased frequency of hospital admissions with active systemic lupus erythematosus disease activity defined by two different disease activity indices: A cohort study.

The objective of this cohort study was to evaluate the association between the frequency of hospital admissions and disease activity, as defined by two different disease activity measurements: the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), in adult patients with systemic lupus erythematosus (SLEs). Patients with SLE were recruited from the rheumatology outpatient department of a regional hospital in southern Taiwan. SLE-DAS and SLEDAI-2K were used to define SLE disease activity and the cause of hospital admissions was identified by a rheumatologist based on medical records. A generalized linear model (GLM) with gamma distribution and log-linked function was used to analyze variables associated with the frequency of admission. The mean frequency of hospitalization was 0.34 times per year for all-cause and 0.21 times per year for SLE-related admission. Multivariate GLM analysis showed that moderate/severe SLE disease activity defined by SLE-DAS was associated with an increased frequency of all-cause and SLE-related hospital admissions while adjusting for other covariates. Moderate/severe SLE disease activity defined by SLEDAI-2K was only significantly associated with an increased frequency of all-cause hospitalization. When steroid dosage was included in the model, moderate/severe SLE disease activity defined by the SLE-DAS remained significantly associated with SLE-related hospital admissions (p = 0.032). In conclusion, disease activity defined by the SLE-DAS, but not SLEDAI-2K was associated with an increased frequency of SLE-related hospitalization. Steroid dosage, a lower educational level, and smoking were associated with an increased frequency of hospital admissions, whereas underweight and alcohol use were associated with a decreased frequency of hospital admissions. Rheumatologists should promptly control SLE disease activity of their patients, provide them with adequate health education, and maintain steroid doses to as low as possible to reduce the risk of hospital admissions.

Relationship between Chinese Herbal Medicine Use and Risk of Sjögren's Syndrome in Patients with Rheumatoid Arthritis: A Retrospective, Population-Based, Nested Case-Control Study.

Background and Objectives: Sjögren's Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against the SS onset. This study aimed to compare risk of SS for RA patients with and without use of CHM. Materials and Methods: Data obtained for this nested case-control study were retrieved from Taiwanese nationwide insurance database from 2000-2013. Cases with SS claims were defined and matched to two randomly selected controls without SS from the recruited RA cohorts. Risk of SS in relation to CHM use was estimated by fitting multiple conditional logistic regression. Results: Patients aged between 20 and 80 years were included and 916 patients with incident SS were matched to 1832 non-SS controls by age, sex and index year. Among them, 28.1% and 48.4% cases ever received CHM therapy, respectively. After adjusting for baseline characteristics, CHM use was found to be related to a lower risk of SS among them (adjusted odds ratio = 0.40, 95% confidence interval: 0.34-0.47). A dose-dependent, reverse association, was further detected between the cumulative duration of CHM use and SS risk. Those receiving CHM therapy for more than 730 days showed a significantly reduced risk of SS by 83%. Conclusions: Findings of this study indicated that the add-on CHM formula, as part of RA care, may be a beneficial treatment for prevention against the incident SS.

Increased risk of hospital admissions in patients with active systemic lupus erythematosus (SLE) classified according to two different SLE disease activity indices: a prospective cohort study.

OBJECTIVES: The aim of this prospective cohort study was to investigate the risk of hospital admissions within one year in patients with active systemic lupus erythematosus (SLE), classified according to the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) or the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). METHODS: This study was conducted in adult patients with SLE recruited from the rheumatology outpatient department in a regional hospital in southern Taiwan. SLE disease activity was measured with SLE-DAS and SLEDAI-2K. The computerised patient record database was accessed to identify patients' hospital admissions. Cox regression analyses were used to estimate the hazard ratio (HR) for all-cause and SLE-related hospital admission in SLE patients classified by SLE-DAS and SLEDAI-2K. RESULTS: A total of 326 adult patients with SLE completed this study. All-cause and SLE-related hospital admissions within one year occurred in 17.5% and 12.6% of the patients, respectively. Results of the Cox regression analysis indicated that SLE patients with moderate/severe disease activity classified by the SLE-DAS (HR=2.43, p=0.005) but not moderate/severe disease activity classified by the SLEDAI-2K (HR=1.84, p=0.057) was significantly associated with the risk of SLE-related admissions. However, only moderate/severe disease activity classified by the SLE-DAS was significantly associated with the risk of all-cause admissions (HR=1.94, p=0.016). When steroid dosage was considered, only the steroid dosage was significantly associated all-cause and SLE-related admissions. CONCLUSIONS: In this study, SLE disease activity classified by SLE-DAS was significantly associated with an increased risk for both all-cause and SLE-related hospital admissions. Rheumatologists should be vigilant for increased risk of hospital admissions in patients with moderate/high SLE disease activity as classified by SLE-DAS.

Increased dental visits in patients with rheumatoid arthritis: a secondary cohort analysis of population based claims data.

OBJECTIVE: To study the utilization of dental care in patients with rheumatoid arthritis (RA) and compare the incidence of common dental disorders in patients with and without RA. METHODS: This data used in this study was from the population-based Taiwan's National Health Insurance Research Database. We identified 1337 patients with newly diagnosed RA between January 2000 and December 2012. We also identified 13,370 individual without a diagnosis of RA using frequency matching on 5-year age intervals, sex, and index year. Patients with a diagnosis of primary Sjögren's syndrome were excluded. Dental disorders were identified using respective ICD-9-CM codes confirmed by dentists. The incidence and incidence rate ratio [IRR] of each dental disorders were calculated using Poisson regression. RESULTS: Compared with the comparison cohort, the prevalence of dentist visits in the RA cohort were significantly higher (70.3% vs. 66.7%, p = 0.008) and the frequency of dentist visits in the RA cohort were also significantly higher (median 2.67 vs. 1.78 per year, p < 0.001). In addition, the incidence of visits for dental caries (adjusted IRR 1.16, p < 0.001), pulpitis (adjusted IRR 1.12, p = 0.044), gingivitis (adjusted IRR 1.13, p = 0.027), periodontitis (adjusted IRR 1.13, p = 0.004), and oral ulcer (adjusted IRR 1.24, p = 0.003) were higher in patients with RA. CONCLUSIONS: An elevated prevalence and frequency of dental visits were associated with patients with RA. In addition, elevated incidence of dental disorders, including dental caries, pulpitis, gingivitis, periodontitis, and oral ulceration, were observed. Oral health should be accessed regularly in patients with RA.

Increased Risk of Common Orthopedic Surgeries for Patients with Rheumatic Diseases in Taiwan.

Background and Objectives: Rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, and systemic lupus erythematosus (SLE), are characterized by chronic arthritis or spondyloarthritis, which can lead to joint and spine destruction. Our previous studies showed that the risk of common orthopedic surgeries, including total knee replacement (TKR), total hip replacement (THR), or spine surgery, was increased in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE. The aim of this review was to summarize the risk of TKR, THR, cervical spine, and lumbar spine surgery on the basis of studies conducted using data from Taiwan's National Health Insurance Research Database (NHIRD). Materials and Methods: The risk of TKR, THR, cervical spine surgery, and lumbar spine surgery in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE was summarized from the results of our previous studies and unpublished findings based on NHIRD data. Results: Patients with rheumatoid arthritis and psoriasis and men with ankylosing spondylitis showed an increased risk of TKR. Patients with rheumatoid arthritis, ankylosing spondylitis, and women with SLE showed an increased risk of receiving THR. Only patients with ankylosing spondylitis had an increased risk of cervical spine surgery, and patients with rheumatoid arthritis or ankylosing spondylitis showed an increased risk of lumbar spine surgery. Although the risk of THR, TKR, or spine surgery in these patients has declined in the era of biologics use, direct evidence for the effects of biologics agents is not yet available. Conclusions: There was an increased risk of common orthopedic surgery in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and SLE. Clinicians should be vigilant to reduce the increased risk of TKR and THR in young and middle-aged patients with rheumatoid arthritis, THR in young patients with ankylosing spondylitis, and young female patients with SLE, as well as cervical spine surgery in young patients with ankylosing spondylitis.

The Prescription of Chinese Herbal Medicine and Risk of Endometriosis in Women with Rheumatoid Arthritis: A Population-Based Cohort Study.

Purpose: The systemic inflammation is believed to provide an outline of the association between rheumatoid arthritis (RA) and endometriosis. This retrospective cohort study aimed to explore the association of Chinese herbal medicine (CHM) use with the prevention of endometriosis onset in women diagnosed with RA. Methods: We utilized the claims data from the National Health Insurance of Taiwan from 2000 to 2009 and excluded individuals diagnosed with endometriosis before being diagnosed with RA, using age at clinical diagnosis. After selection and propensity-score matching, a total of 5992 females aged ≧20 years old and with newly diagnosed RA but without endometriosis at baseline were included, which contained 2996 CHM users and 2996 non-CHM users. All of them were followed until the end of 2013 to measure the incidence of endometriosis. Results: During the study period, we noticed that CHM users had a substantially lower incidence of endometriosis compared to non-CHM users (2.54 vs 5.19 per 1000 person-years). Use of CHM correlated significantly with a lower endometriosis likelihood even after adjusting for potential covariates, with the adjusted hazard ratio of 0.47 (95% confidence interval, 0.35-0.65). A longer duration of CHM use was associated with a reduction in endometriosis risk, especially in those using CHM for more than 730 days. Uses of several herbal products may be associated with a lower risk of endometriosis, like Ge-Gen, Da-Huang, Huang-Qin, Ye-Jiao-Teng, Chuan-Niu-Xi, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, Ping-Wei-San, Gan-Lu-Yin, and Dang-Gui-Nian-Tong-Tang. Conclusion: Taken together, adding CHM to conventional therapy may reduce the incidence of endometriosis in women with RA. The therapeutic mechanisms and safety of these natural products may be a direction for future clinical studies.

HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K/AKT Signaling.

Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-α and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS.

Patterns of Outpatient Phecodes Predating the Diagnosis of Systemic Lupus Erythematosus in Taiwanese Women.

Shortening the time to diagnosis and initiating early treatment are imperative to improve outcomes in patients with systemic lupus erythematosus (SLE). The aim of this case-control study, based on the data from the Taiwan's National Health Insurance Research Database (NHIRD), was to investigate the patterns of diagnoses of disease phenotypes in female patients with SLE up to eight years prior to its definitive diagnosis. The 547 cases were selected from the 2000-2012 NHIRD catastrophic illness datafile and frequency-matched with 2188 controls. The primary diagnosis based on the first ICD-9-CM code for each outpatient visit was converted to Phecodes. Separate regression models, based on least absolute shrinkage and selection operator (lasso) regularization, with seven different lag periods from 1-2 to 7-8 years, were conducted. Results showed that SLE was associated with 46 disease phenotypes in a lag period of 2-3 years, but fewer in other lag periods. A number of SLE-associated disease phenotypes, such as primary thrombocytopenia, thyroid diseases, Raynaud's syndrome, renal disease, and several infectious diseases, occurred mainly in the first few years prior to SLE diagnosis. In conclusion, SLE should be suspected when the disease phenotypes identified in the present study occurred concomitantly.

Association of Chinese herbal medicine use with the depression risk among the long-term breast cancer survivors: A longitudinal follow-up study.

Background: Breast cancer patients are at elevated risk of depression during treatment, thus provoking the chance of poor clinical outcomes. This retrospective cohort study aimed to investigate whether integrating Chinese herbal medicines citation(CHM) into conventional cancer therapy could decrease the risk of depression in the long-term breast cancer survivors. Methods: A cohort of patients aged 20-70 years and with newly diagnosed breast cancer during 2000-2008 was identified from a nationwide claims database. In this study, we focused solely on survivors of breast cancer at least1 year after diagnosis. After one-to-one matching for age, sex, and baseline comorbidities, breast cancer patients who received (n = 1,450) and did not receive (n = 1,450) CHM treatment were enrolled. The incidence rate and hazard ratio citation(HR) for depression between the two groups was estimated at the end of 2012. A Cox proportional hazard model was constructed to examine the impact of the CHM use on the risk of depression. Results: During the study period, the incidence rate of depression was significantly lower in the treated cohort than in the untreated cohort [8.57 compared with 11.01 per 1,000 person-years citation(PYs)], and the adjusted HR remained significant at 0.74 (95% CI 0.58-0.94) in a Cox proportional hazards regression model. The corresponding risk further decreasing to 43% among those using CHM for more than 1 year. Conclusion: Finding from this investigation indicated that the lower risk of depression observed in breast cancer patients treated with CHM, suggesting that CHM treatment should be considered for disease management toward breast cancer. Yet, the optimal administered dose should be determined in further clinical trials.