Traditional Chinese medicine in the treatment of patients with hyperuricemia: A randomized placebo-controlled double-blinded clinical trial.

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.

Is low-dose tumor necrosis factor inhibitor effective and safe in patients with ankylosing spondylitis flare-up after renal transplantation? A case report and literature review.

Rheumatic diseases, the immunosuppressant drugs used after solid organ transplantation to prevent graft rejection, and the biologics used for controlling rheumatic disease, especially tumor necrosis factor inhibitors (TNFi)-all of these could increase the risk of malignancy. The roles of biologics for disease control in rheumatic disease patients after kidney transplantation (KT) are not well established because only a few cases are reported, and the possibility of increasing infection and malignancy rates. Here, we present the first case of ankylosing spondylitis (AS) successfully treated with low-dose TNFi for disease activity flare-up 5 months after KT and review the literature to see whether the use of biologics, especially TNFi, in AS patients with disease activity flare-ups after receiving KT is effective and safe.

Case Report: Successful treatment with methotrexate in a 10-year-old boy with co-occurrence of generalized psoriasis and vitiligo.

The co-occurrence of psoriasis (PsO) and vitiligo is rare in Asian countries, especially in children. This case report presents the first-ever occurrence of PsO combined with vitiligo in an Asian boy under 6 years of age, in whom symptom improvement was observed after the use of methotrexate (MTX) as the sole treatment. Although previous studies have indicated that there is a close correlation between the two diseases, methotrexate (MTX), which is a commonly used treatment for PsO, is not a standard treatment for vitiligo. Even with advanced progress in biologics and Janus kinase inhibitor (JAKi), the biologics and JAKi used in vitiligo are still inconsistent. In our case report, the successful use of MTX indicated that there are shared immune pathways between PsO and vitiligo. Further exploration is needed to optimize the treatment options for this co-occurrence of PsO and vitiligo.

Case report of new-onset ulcerative colitis after MVC-COVI1901 vaccine injection for SARS-CoV-2.

A 23-year-old man suffered from diarrhea after receiving the MVC-COVI1901 vaccine. The patient then presented to our emergency department due to swelling and pain in his right knee. Synovial effusion studies of the right knee revealed inflammation. Gram and acid-fast stains reported negative results and no crystals were found under a polarized light microscope. During his hospitalization, the patient underwent a colonoscopy and computed tomography (CT) due to bloody stool. Pancolitis was suspected under colonoscopy and an abdominal CT scan supported our diagnosis showing wall thickening and mucosal enhancement. Pathology showed distorted crypt architecture and acute cryptitis with abscesses. After excluding other causes of ulcerative colitis (UC), the patient was diagnosed with MVC-COV1901 vaccine-related UC and inflammatory bowel disease arthropathy. Subsequent presentation of UC and inflammatory bowel disease-related arthropathy after receiving the MVC-COVI1901 vaccine has not previously been reported. We speculate that the pathogenesis could be correlated to the vaccine's components (spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide) through the combination of 2 effects: the activation of Toll-like receptor (TLR) 4 by S-2P, and the activation of TLR9 and expression of interleukin-13 by CpG-1018 adjuvant. In conclusion, it is remarkable that the MVC-COVI1901 vaccine may lead to the incidence of autoinflammatory diseases such as UC.

Case report: Successful treatment with tofacitinib and colchicine in a patient with Schnitzler syndrome.

We report a case of late-onset Schnitzler syndrome successfully treated with Janus-activated kinase (JAK) inhibitors and colchicine. Schnitzler syndrome should be considered for recurrent chronic urticaria when accompanied by fever, fatigue, rapid weight loss, and poor response to antihistamine treatment. Skin biopsy, bone marrow biopsy, and electrophoresis help confirm the diagnosis. Early diagnosis and treatment can lead to complete resolution of symptoms. Besides interleukin (IL)-1 and IL-6 inhibitors, JAK inhibitors and colchicine may be considered as other choices of treatment.

The long-term persistence of tumor necrosis factor inhibitors in patients with moderate to severe immune-mediated rheumatic diseases: A nation-wide, population-based real-world study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Chloroquine alleviates the heat-induced to injure via autophagy and apoptosis mechanisms in skin cell and mouse models.

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-ß 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 ß-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/ß-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.

Increased risk of being diagnosed with endometriosis in patients with Systemic lupus erythematosus: a population-based cohort study in Taiwan.

Epidemiological study shows inconsistent results in the association between endometriosis and Systemic lupus erythematosus (SLE). We conducted a nationwide retrospective cohort study and analyzed data from the Taiwan Longitudinal Health Insurance Research Database 2000 (n = 958,349) over a 13-year follow-up period (2000-2013). After matching 1930 SLE women with 7720 non-SLE women in a 1:4 ratio by age, we used Cox proportional hazard regression to calculate the adjusted hazard ratio (aHR) for endometriosis diagnosed after SLE. We also used a diagnosis of endometriosis with previous gynecologic surgery codes as secondary outcomes and performed sensitivity analyses using a landmark analysis. After adjustment for age, urbanization, income, length of hospital stay, and comorbidities in the age-matched group, women with SLE had a higher risk of endometriosis than women without SLE (aHR 1.32, 95% CI 1.02-1.70). When we defined endometriosis as patients with an ICD-9 endometriosis code after undergoing gynecologic surgery, the increased risk of endometriosis in patients with SLE was not significant. Our findings suggest that the risk of endometriosis was significantly elevated in the cohort of women with SLE compared with the age-matched general cohort of women. The burden of endometriosis in SLE patients requires special attention.

Sjögren syndrome is a hidden contributor of macrovascular and microvascular complications in patients with type 2 diabetes.

OBJECTIVE: To investigate cardiovascular risk among diabetic patients with Sjögren syndrome. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Risk of Major Adverse Cardiovascular Events in Ankylosing Spondylitis Patients With a History of Acute Anterior Uveitis: A Nationwide, Population Based Cohort Study.

Background: To investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS). Methods: We identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed. Results: There were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57-1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25-5.25). Conclusion: This cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.

Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities. METHODS: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities. RESULTS: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities. CONCLUSIONS: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.

Risk of atrial fibrillation in patients with pneumonia.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Patients with pneumonia exhibited an increased risk for AF, especially in the early period after diagnosis of pneumonia.

Influenza Vaccination Is Associated With Lower Incidental Asthma Risk in Patients With Atopic Dermatitis: A Nationwide Cohort Study.

Background: Atopic march refers to the natural history of atopic dermatitis (AD) in infancy followed by subsequent allergic rhinitis and asthma in later life. Respiratory viruses interact with allergic sensitization to promote recurrent wheezing and the development of asthma. We aimed to evaluate whether influenza vaccination reduces asthma risk in people with AD. Methods: This cohort study was conducted retrospectively from 2000 to 2013 by the National Health Insurance Research Database (NHIRD). Patients with newly diagnosed AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 691) were enrolled as the AD cohort. We matched each vaccinated patient with one non-vaccinated patient according to age and sex. We observed each participant until their first asthma event, or the end of the study on December 31, 2013, whichever came first. Results: Our analyses included 4,414 people with a mean age of 53 years. Of these, 43.8 were male. The incidence density of asthma was 12.6 per 1,000 person-years for vaccinated patients, and 15.1 per 1000 person-years for non-vaccinated patients. The adjusted hazard ratio (aHR) of asthma in the vaccinated cohort relative to the non-vaccinated cohort was 0.69 (95% CI = 0.55-0.87). Vaccinated patients had a lower cumulative incidence of asthma than unvaccinated patients. Vaccinated participants in all age and sex groups trended toward a lower risk of asthma. People will reduce more asthma risk when taking shots every year. Conclusion: Influenza vaccination was associated with lower asthma risk in patients with AD.

Relationship of Hydroxychloroquine and Ophthalmic Complications in Patients with Type 2 Diabetes in Taiwan.

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 < 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.