Circulating leptin and its correlation with rheumatoid arthritis activity: a meta-analysis

Objective@#The aim of the study was to investigate the association between the levels of leptin in the circulating of individuals with rheumatoid arthritis (RA) and the severity of the disease. @*Methods@#We looked through the databases of Embase, Medline, and the Cochrane Library. We conducted a meta-analysis on the correlations between circulating leptin and the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and Creactive protein (CRP) levels in RA patients, as well as a meta-analysis of circulating or circulating leptin levels in RA patients. @*Results@#This meta-analysis study analyzed 42 different comparisons from 37 different publications, including a total of 2,350 patients with RA and 1,815 controls. The RA group had substantially higher leptin levels than the control group (standardized mean difference [SMD]=0.507, 95% confidence interval [CI]=0.309~0.704, p<0.001). The finding that RA patients had higher leptin levels was unaffected by sample size. The correlation between circulating leptin levels and DAS28 is statistically significant (correlation coefficient=0.247, 95% CI=0.087~0.396, p=0.003). Leptin levels are also correlated with CRP levels (correlation coefficient=0.203, 95% CI=0.048~0.349, p=0.010). @*Conclusion@#This comprehensive meta-analysis demonstrates that the circulating leptin levels of RA patients are elevated, and provides compelling evidence of the significant relationship between leptin levels and the activity of RA. The findings of this research suggest that leptin plays a significant role in the pathophysiology of this disease.

Mendelian Randomization Research on the Relationship Between Rheumatoid Arthritis and Systemic Lupus Erythematosus and the Risk of Autistic Spectrum Disorder

Objective@#The purpose of this study was to examine whether there is a causal link between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and autism spectrum disorder (ASD). @*Methods@#We used inverse variance weighted (IVW), weighted median, and MR-Egger regression methods to perform two-sample Mendelian randomization (MR) study using publicly available summary statistics datasets. In addition, we employed genome-wide association studies (GWASs) for RA and SLE as exposure and an ASD GWAS as an outcome. @*Results@#Thirty-three and 28 single-nucleotide polymorphisms from RA and SLE GWASs were selected as instrumental variables for ASD. The IVW method revealed no evidence supporting a causal association between RA and SLE and risk for ASD (beta=−0.077, standard error [SE]=0.041, p=0.062; beta=0.014, SE=0.021, p=0.493). The weighted median approach yielded no evidence of any causal association between RA and SLE and risk for ASD (beta=−0.071, SE=0.058, p=0.223; beta=0.045, SE=0.030, p=0.130). MR-Egger analysis demonstrated no causal association between RA and SLE and risk for ASD (beta=−0.062, SE=0.079, p=0.434; beta=0.048, SE=0.043, p=0.273). The MR results calculated using IVW, the median weighted and the MR-Egger regression approaches were consistent. @*Conclusion@#The findings of the MR analysis did not support a causal relationship between RA or SLE and the risk of ASD.

The Gut Microbiome and Osteoarthritis: A Two-Sample Mendelian Randomization Study

Objective@#The aim of this study was to examine if the intestinal microbiome is causally correlated with osteoarthritis (OA) incidence. @*Methods@#A two-sample Mendelian randomization (MR) study was conducted using inverse variance weighting (IVW), weighted median, and MR-Egger regression techniques. Publicly accessible summary statistics dataset of intestinal microbiomes of European descent from genome-wide association studies (GWASs) (a total with 3,326 individuals) was used as an exposure. As an outcome, summary data from the GWAS include 3,498 patients with OA of the knee and hip from the arcOGEN sample and 11,009 controls of European descent. @*Results@#We identified 29 single-nucleotide polymorphisms from GWAS of intestinal microbiomes as instrumental variables. The IVW approach found no evidence to suggest a causal relationship between the intestinal microbiota and OA (beta=−0.001, standard error [SE]=0.004, p=0.748). The regression test of MR-Egger showed that the directional pleiotropy was unlikely to be a bias (intercept=0.002, SE=0.007, p=0.697) and the MR-Egger study showed no causal relation between the intestinal microbiota and the OA (beta=−0.002, SE=0.005, p=0.630). The weighted median analysis also did not have indications of a causal relationship between the intestinal microbiota and OA (beta=−0.002, SE=0.005, p=0.630). The MR results calculated using IVW, the median weighted and the MR-Egger regression approaches were consistent. @*Conclusion@#The findings of the MR analysis did not support a causal relationship between intestinal microbiome and OA risk.

Association Between Signal Transducers and Activators of Transcription 4 rs7574865 Polymorphism and Systemic Lupus Erythematosus: A Meta-analysis

. The purpose of this study was to determine whether the rs7574865 polymorphism of signal transducers and transcription 4 activators (STAT4) in multiple ethnic populations is associated with susceptibility to systemic lupus erythematosus (SLE). Methods. A meta-analysis on the STAT4 T allele rs7574865 polymorphism was performed in all subjects of study as well as in each ethnic population. Results. It included twenty-four manuscripts with 36 comparative studies of 22,898 SLE patients and 24,838 controls. The mean frequency of the STAT4 rs7574865 T allele was 28.5%, ranging from 14.3% to 35.7%, among the controls. T allele rates were 14.3%, 22.8%, 31.9%, 32.4%, and 35.7%, respectively in African American, European, Arab, Asian, and Latin American populations. Meta-analysis revealed a substantial correlation in all subjects between STAT4rs7574865 and SLE (odds ratio=1.549, 95% confidence interval=1.459∼1.644, p＜0.001). Analysis after stratification of race showed a strong association between the STAT4 rs7574865 T allele and SLE in Europeans, Asians, Latin Americans, African Americans, and Arabs. Conclusion. This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism in different ethnic groups was correlated with SLE susceptibility, and that its prevalence depended on ethnicity.

Circulating Interleukin-37 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus and Their Correlations With Disease Activity: A Meta-analysis

Objective@#. To assess the circulating levels of interleukin (IL)-37 in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and determine a correlation between plasma/serum IL-37 levels and disease activity. @*Methods@#. We performed a meta-analysis comparing plasma/serum IL-37 level between patients with RA or SLE and controls, and examined correlation coefficients between circulating IL-37 levels and disease activity. @*Results@#. A total of 14 publications included 711 patients with RA and 394 controls, 522 patients with SLE and 259 controls. In the RA group, the IL-37 level was significantly higher than in the control group (standardized mean difference [SMD]=1.222, 95% confidence interval [CI]=0.722∼1.711, p＜0.001). Subgroup analysis by sample size showed a significantly higher IL-37 level in RA group of large (n＞90) and small sample numbers (n≤90) (SMD=0.994, 95% CI=0.323∼1.666, p＜0.001; SMD=1.617, 95% CI=1.328∼1.906, p＜0.001). In addition, IL-37 level in SLE group was significantly higher than in control group (SMD=1.096, 95% CI=0.635∼1.558, p＜0.001). A strong association between circulating IL-37-level and RA activity based on Disease activity Score 28 was shown (correlation coefficients=0.547, 95% CI=0.355∼0.695, p＜0.001). Meta-analysis of the coefficients for correlation indicated a positive correlation between the circulating level of IL-37 and SLE activity based on Systemic Lupus Erythematosus Disease Activity Index (coefficients for correlation＜0.588, 95 % CI=0.270∼0.806, p=0.003). @*Conclusion@#. Our meta-analysis showed that circulating IL-37 levels are higher in RA and SLE patients, and there is a positive correlation between IL-37 and disease activity in RA and SLE.

The Uric Acid and Gout have No Direct Causality With Osteoarthritis: A Mendelian Randomization Study

OBJECTIVE: To examine whether uric acid level or gout is causally associated with the risk of osteoarthritis.METHODS: We performed a two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods. We used the publicly available summary statistics datasets of uric acid level or gout genome-wide association studies (GWASs) as the exposure, and a GWAS in 3,498 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as the outcome.RESULTS: Six single nucleotide polymorphisms (SNPs) from the GWAS data on uric acid level and 12 SNPs from the GWAS data on gout were selected as instrumental variables (IVs). The IVW analysis did not support a causal association between uric acid level or gout and risk of osteoarthritis (beta=−0.026, standard error [SE]=0.096, p=0.789; beta=−0.018, SE=0.025, p=0.482). MR-Egger regression revealed no causal association between uric acid level or gout and risk of osteoarthritis (beta=0.028, SE=0.142, p=0.852; beta=−0.056, SE=0.090, p=0.548). Similarly, no evidence of a casual association was provided by the weighted median approach (beta=0.004, SE=0.064, p=0.946; beta=−0.005, SE=0.025, p=0.843).CONCLUSION: The results of MR analysis demonstrates that uric acid level and gout may be not causally associated with the increased risk of osteoarthritis. Considering MR study is not susceptible to bias from unmeasured confounders or reverse causation, the epidemiological evidence for an association between uric acid level or gout and a higher risk of osteoarthritis may be due to residual confounding or reverse causation rather than direct causality.

Circulating Interleukin-18 Level in Systemic Lupus Erythematosus

OBJECTIVE: This study aimed to evaluate the relationship between circulating interleukin (IL)-18 levels and systemic lupus erythematosus (SLE) and establish a correlation between plasma/serum IL-18 levels and SLE activity.METHODS: We performed a meta-analysis comparing plasma/serum IL-18 levels in patients with SLE to controls by using fixed or random effects model based on the heterogeneity.RESULTS: Sixteen studies with 659 SLE patients and 502 controls were included in this meta-analysis. Meta-analysis showed that IL-18 levels were significantly higher in the SLE group (standardized mean difference=1.556, 95% confidence interval=1.087~2.024, p<0.001). Stratifying by ethnicity showed that IL-18 levels were significantly elevated in the SLE groups of European, Asian, and Arab populations. Stratification by adjustment for age and/or sex revealed a significantly higher IL-18 level in the SLE group, independently of the adjustment. Subgroup analysis by sample size showed significantly higher IL-18 levels in the SLE group for both large sample (n≥50) and small sample (n<50) subgroups. Subgroup analysis by data type showed significantly higher IL-18 levels in the SLE group for both original and calculated data populations.CONCLUSION: This meta-analysis demonstrated that circulating IL-18 levels are higher in patients with SLE.

Associations Between Circulating Interleukin-17 Levels and Systemic Lupus Erythematosus and Between Interleukin-17 Gene Polymorphisms and Disease Susceptibility: A Meta-analysis

OBJECTIVE: To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and systemic lupus erythematosus (SLE) and associations between polymorphisms in IL17 genes and SLE susceptibility.METHODS: We performed a meta-analysis of serum/plasma IL-17 levels in patients with SLE and controls and evaluated the associations between the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms and IL17F copy number variations (CNVs) and risk of SLE.RESULTS: Thirteen studies focusing on 2,096 patients with SLE and 2,587 controls were included. Our meta-analysis revealed that IL-17 levels were significantly higher in the SLE group than the control group (standardized mean difference=1.045, 95% confidence interval [95% CI]=0.521~1.568, p < 0.001). Subgroup analysis using sample size showed increased IL-17 levels in samples from large (n>100) but not small (n < 90) SLE groups. We found no evidence of associations between SLE and the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms. However, a significant association was found between SLE and IL17F CNVs in a pooled cohort of affected individuals compared to that in pooled controls (odd ratio=3.663, 95% CI=2.466~5.221, p < 0.001).CONCLUSION: This meta-analysis revealed significantly higher circulating IL-17 levels in patients with SLE and showed evidence of associations between IL17F CNVs and SLE.

YKL-40 Levels in Rheumatoid Arthritis and Their Correlation with Disease Activity: A Meta-analysis

OBJECTIVE: To examine the relationship of serum/plasma YKL-40 levels with rheumatoid arthritis (RA) and their correlation with RA activity and rheumatoid factor (RF) level. METHODS: We performed a meta-analysis comparing the serum/plasma YKL-40 levels between patients with RA and controls and examined the correlation coefficients of the circulating YKL-40 level with the RF level and RA activity based on the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. RESULTS: Nine studies (707 patients with RA and 1,041 controls) were included in the meta-analysis. The YKL-40 levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD]=1.071, 95% confidence interval [CI]=0.726~1.417, p100) populations. Meta-analysis of correlation coefficients showed a significant positive correlation between the YKL-40 levels and DAS28, ESR, CRP level, and RF level (DAS28: correlation coefficient=0.381, 95% CI=0.044~0.640, p=0.028; RF level: correlation coefficient=0.341, 95% CI=0.176~0.487, p<0.001). CONCLUSION: The circulating YKL-40 levels are high in patients with RA and positively correlate with RA activity and RF level.

Causal Association between Bone Mineral Density and Osteoarthritis: A Mendelian Randomization Study

OBJECTIVE: To examine whether bone mineral density (BMD) is causally associated with osteoarthritis (OA). METHODS: We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods. We used publicly available summary statistics datasets of a genome-wide association study (GWAS) on femur neck (FN) BMD of individuals of European ancestry as the exposure and a GWAS for non-cancer illness code self-reported: OA from the individuals included in the UK Biobank as the outcome. RESULTS: We selected 21 independent single-nucleotide polymorphisms with genome-wide significance (p<5.00E-08) from GWAS on FN BMD as the instrumental variables. The IVW method (beta=0.010, standard error [SE]=0.003, p=0.002) and the weighted median approach (beta=0.011, SE=0.004, p=0.006) yielded evidence of a causal association between FN BMD and OA. However, the MR-Egger analysis showed no causal association between FN BMD and OA (beta=0.005, SE=0.017, p=0.753). Since MR-Egger regression suffers from a lack of power and a susceptibility to weak instrument bias, the MR analysis results may support a causal association between FN BMD and OA. CONCLUSION: The results of MR analysis by IVW and weighted median, but not MR-Egger regression indicate that FN BMD is likely to be causally associated with an increased risk of OA incidence The current findings may provide an opportunity to elucidate the underlying mechanisms of the effects of BMD on the OA incidence.

Causal Association between Rheumatoid Arthritis with the Increased Risk of Type 2 Diabetes: A Mendelian Randomization Analysis

OBJECTIVE: This study aimed to examine whether rheumatoid arthritis (RA) is causally associated with type 2 diabetes (T2D). METHODS: We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We used the publicly available summary statistics datasets from a genome-wide association studies (GWAS) meta-analysis of 5,539 autoantibody-positive individuals with RA and 20,169 controls of European descent, and a GWAS dataset of 10,247 individuals with T2D and 53,924 controls, overwhelmingly of European descent as outcomes. RESULTS: We selected 10 single-nucleotide polymorphisms from GWAS data on RA as instrumental variables to improve the inference. The IVW method supported a causal association between RA and T2D (β=0.044, standard error [SE]=0.022, p=0.047). The MR-Egger analysis showed a causal association between RA and T2D (β=0.093, SE=0.033, p=0.023). In addition, the weighted median approach supported a causal association between RA and T2D (β=0.056, SE=0.025, p=0.028). The association between RA and T2D was consistently observed using IVW, MR Egger, and weighted median methods. Cochran's Q test indicated no evidence of heterogeneity between instrumental variable estimates based on individual variants and MR-Egger regression revealed that directional pleiotropy was unlikely to have biased the results (intercept=−0.030; p=0.101). CONCLUSION: MR analysis supports that RA may be causally associated with an increased risk of T2D.

Overall and Sex-specific Mortality in Psoriatic Arthritis and Ankylosing Spondylitis: A Meta-analysis

OBJECTIVE: This study examined the all-cause and sex-specific standardized mortality ratios (SMRs) in patients with spondyloarthropathy. METHODS: Studies examining the all-cause and/or cause-specific SMRs in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) compared to the general population were surveyed using MEDLINE, EMBASE, and Cochrane databases and manual searches. A meta-analysis of the all-cause and sex-specific SMRs in patients with rheumatic diseases was then performed. RESULTS: In total, 7 comparisons (5 PsA and 2 AS) from 6 reports met the inclusion criteria. Disease-specific meta-analysis showed that the pooled SMR was 1.299 (95% confidence interval [CI] 1.092–1.605, p=0.015) for PsA and 1.784 (95% CI 1.576–2.020, p < 0.001) for AS. Meta-analysis showed that the SMRs of PsA and AS were significantly higher (1.299 to 1.784 times) than those in the general population. The age- and sex-adjusted SMR was highest for AS (1.784), followed by PsA (1.299). Moreover, sex-specific meta-analysis showed that the all-cause SMRs were increased in female and male patients with PsA. On the other hand, mortality increased in male patients with AS (SMR 1.834), whereas there was no significant increase in female patients with AS. CONCLUSION: All-cause mortality is higher in patients with PsA and AS compared to the general population. On the other hand, the mortality was higher in males with AS but not in females.

Metabolic syndrome: prevalence and risk factors in Korean gout patients

BACKGROUND/AIMS: We performed this study to investigate associations between metabolic syndrome, chronic kidney disease (CKD), and gout. METHODS: We reviewed the medical records of 151 patients with gout at the Department of Rheumatology in Korea University Ansan Hospital. The following measures were examined: waist circumference, blood pressure, alcohol consumption, and levels of triglyceride, high density lipoprotein cholesterol, fasting serum glucose, serum uric acid (SUA), creatinine, insulin, and C-peptide. We assessed metabolic syndrome by the homeostasis model assessment of insulin resistance (HOMA-IR) index and renal function by the Modification of Diet in Renal Disease equation; patients were classified according to World Health Organization Asia-Pacific obesity criteria. RESULTS: The prevalence of metabolic syndrome in gout patients (50.8%) was higher than in non-gout patients. The mean SUA level was significantly higher in gout patients with metabolic syndrome (9.13 ± 3.15 mg/dL) than in gout patients without metabolic syndrome (8.14 ± 2.07 mg/dL). The mean SUA level was also significantly higher in patients with gout and CKD (9.55 ± 2.86 mg/dL) than in patients with gout but no CKD (7.74 ± 2.27 mg/dL). In gout patients, HOMA-IR was positively correlated with waist circumference (r = 0.409, p = 0.001). CONCLUSIONS: The prevalence of metabolic syndrome in patients with gout was 50.8%, which is higher than the prevalence in the general Korean population. Hyperuricemia in gout patients was correlated with metabolic syndrome and CKD. Insulin resistance may provide clues to better understand the relationship between metabolic syndrome, CKD, and gout.

Association between Circulating Adiponectin Levels and Osteoarthritis: A Meta-analysis

OBJECTIVE: The aim of this study was to analyze the relationship between the circulating adiponectin levels and osteoarthritis (OA). METHODS: Meta-analysis was conducted on the serum/plasma adiponectin levels in patients with OA and controls, and subgroup analysis was performed based on ethnicity, sex, OA site, and adjustment for age, sex, and/or body mass index (BMI). RESULTS: Seven studies with eleven comparisons including 538 patients with OA and 366 controls were selected, which showed that the adiponectin levels were significantly higher in the OA group than in controls (standardized mean difference [SMD]=0.745, 95% confidence interval [CI]=0.316~1.174, p=0.001). Stratification according to ethnicity showed significantly elevated adiponectin levels in Caucasian individuals with OA (SMD=0.769, 95% CI=0.218~1.319, p=0.006). Stratification according to sex revealed significantly higher adiponectin levels in women with OA, but not in men (SMD=0.861, 95% CI=0.099~1.623, p=0.027; SMD=1.177, 95% CI=−0.911~3.316, p=0.281). Stratification by an adjustment for age, sex, or BMI showed significantly higher adiponectin levels in the OA group (SMD=0.837, 95% CI=0.326~ 1.349, p=0.001). Stratification according to the OA site showed significantly higher adiponectin levels in patients with knee OA (SMD=0.938, 95% CI=0.456~1.419, p < 0.001). CONCLUSION: The significantly higher levels of circulating adiponectin in patients with OA than in healthy controls indicates that adiponectin likely plays a role in the pathogenesis of OA.

Baseline extent of damage predicts spinal radiographic progression in Korean patients with ankylosing spondylitis treated with golimumab

BACKGROUND/AIMS: For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population. METHODS: Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study. RESULTS: Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p 10 and less common (13.0%) with baseline mSASSS = 0. CONCLUSIONS: In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.

Productivity Loss of Rheumatoid Arthritis Patients according to the Their Stages of the Disease Activity Score

OBJECTIVE: Productivity loss was compared by 3-stage of disease activity and associations between higher disease activity and high productivity loss were identified. METHODS: Data were extracted from Rheumatoid Arthritis (RA) Patient-reported Outcomes Research, which enrolled 2,000 RA patients (>20-year) on disease-modifying-antirheumatic-drugs (DMARDs) (≥6-month) from December 2012 to June 2013. This included 1,457 RA patients with the disease activity score (DAS-28-ESR) in their medical charts. Productivity loss in time and indirect cost was estimated using The World Health Organization Health and Work Performance Questionnaire (HPQ). Baseline characteristics and productivity loss outcomes were compared according to DAS-28-ESR groups. RESULTS: 84.4% were females, 54.2% had low DAS-28-ESR ( 5.1). Patients with moderate to high DAS-28-ESR had higher lost productivity time (LPT) and monthly costs of LPT than those with low DAS-28-ESR (time in hours: 110.0±58.4 vs. 132.4±57.2 vs. 71.5±52.0, p < 0.0001; monthly costs of LPT in 1,000 Korean won: 1,097±607 vs. 1,302±554 vs. 741±531, p < 0.0001). Multiple regression analyses revealed significant associations with high LPT in high (adjusted odds ratio [OR]=3.87, 95% confidence interval [CI]: 2.18∼6.87) and moderate DAS-28-ESR (adjusted OR=1.88, 95% CI: 1.41∼2.52) compared to low DAS-28-ESR. In addition, positive associations with high monthly costs of LPT were observed in high (adjusted OR=3.45, 95% CI: 1.98∼5.99) and moderate DAS-28-ESR (adjusted OR=1.93, 95% CI: 1.43∼2.54) compared to low DAS-28-ESR. CONCLUSION: Timely therapeutic strategies should be taken into consideration given that the RA patients with moderate to high DAS-28-ESR showed strong associations with high productivity loss for effective management of RA.

Clinical Outcomes of Standard Triple Therapy Plus Probiotics or Concomitant Therapy for Helicobacter pylori Infection

BACKGROUND/AIMS: The efficacy of standard triple therapy (STT) in treating Helicobacter pylori infection has decreased. Many investigators have attempted to increase the eradication rate. We investigated the outcomes of concomitant therapy (CT) and STT combined with probiotics (STP) as a first-line treatment for H. pylori infection. METHODS: We reviewed the medical records of 361 patients who received either STP (n=286) or CT (n=75). The STP group received STT combined with a probiotic preparation for 1 week. The CT group received STT and metronidazole for 1 week. RESULTS: The intention-to-treat and per-protocol eradication rates were 83.6% (95% confidence interval [CI], 79.0 to 87.7) and 87.1% (95% CI, 81.2 to 89.7) in the STP group and 86.7% (95% CI, 78.7 to 93.3) and 91.4% (95% CI, 83.6 to 97.1) in the CT group (p=0.512 and p=0.324), respectively. The frequency of adverse effects was higher in the CT group (28.2%) than in the STP group (12.8%) (p=0.002). CONCLUSIONS: STP and CT are encouragingly efficacious as first-line treatments for H. pylori infection. Therefore, adding probiotics to STT may be a feasible option to avoid side effects.

Association of Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Mean Platelet Volume with Systemic Lupus Erythematosus Disease Activity: A Meta-analysis

OBJECTIVE: A series of common blood tests neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV) could provide a measure of systemic lupus erythematosus (SLE) activity. METHODS: We searched the Medline, Embase, and Cochrane databases and performed a meta-analysis comparing NLR, PLR, and MPV in patients with SLE to controls, and examined correlation coefficients between NLR, PLR, and MPV and SLE activity based on SLE Disease Activity Index (SLEDAI) using random-effects models. RESULTS: Nine studies were included in this meta-analysis. Meta-analysis revealed that NLR was significantly higher in the SLE group than in the control group (standard mean difference [SMD]=2.747, 95% confidence interval [CI]=1.241∼4.254, p<0.001). PLR was also significantly higher in the SLE group (SMD=1.564, 95% CI=0.122∼3.006, p=0.034). Meta-analysis of correlation coefficients showed that both NLR and PLR were positively associated with SLEDAI (correlation coefficient=0.404, 95% CI=0.299∼0.500, p<0.001; correlation coefficient=0.378, 95% CI=0.234∼0.505, p<0.001). The pooled sensitivity and specificity of NLR for diagnosis of lupus nephritis were 75.1% (95% CI, 68.5∼81.0) and 72.9% (95% CI, 64.9∼80.0), respectively. The area under the curve of NLR were 0.794. However, meta-analysis indicated no elevated MPV in the SLE group and no correlation between MPV and SLE activity. CONCLUSION: This meta-analysis demonstrated that both NLR and PLR are higher in patients with SLE, a significantly positive correlation exists between NLR/PLR and SLE activity.

Urinary Tumor Necrosis Factor-like Weak Inducer of Apoptosis as a Biomarker for Lupus Nephritis: A Meta-analysis

OBJECTIVE: This study evaluates serum or urinary tumor necrosis factor-like weak inducer of apoptosis (TWEAK) as a biomarker for lupus nephritis (LN). METHODS: We conducted a meta-analysis examining serum or urinary TWEAK levels in patients with systemic lupus erythematosus (SLE), patients with LN (active or inactive), and healthy controls. We tabulated correlation coefficients between urinary TWEAK level and total or renal SLE Disease Activity Index (tSLEDAI or rSLEDAI). RESULTS: Eight studies were included in this meta-analysis. The meta-analysis revealed that serum TWEAK levels tended to be higher in patients with SLE than in controls (standard mean difference [SMD]=0.850, 95% confidence interval [CI]=−0.067∼1.767, p=0.069). Urinary TWEAK was significantly higher in patients with active LN than in those with inactive LN (SMD=2.865, 95% CI= −0.831∼4.898, p=0.006). In addition, urinary TWEAK was positively associated with tSLEDAI and rSLEDAI (correlation coefficient= 0.436, 95% CI=0.204∼0.622, p=4.3×10⁻⁴; correlation coefficient=0.483, 95% CI=0.108∼0.738, p=0.014). Pooled sensitivity and specificity of urinary TWEAK for diagnosis of LN were 81.3% (95% CI, 73.3∼87.8) and 76.0% (95% CI, 66.3∼84.2), indicating good diagnostic accuracy. CONCLUSION: The meta-analysis demonstrated that urinary TWEAK was significantly higher in patients with active LN than in those with inactive LN, and that urinary TWEAK levels were positively correlated with renal disease activity.

Meta-analysis of Circulating Adiponectin, Visfatin, and Ghrelin Levels in Patients with Systemic Lupus Erythematosus

OBJECTIVE: To evaluate the association between circulating adiponectin, visfatin, and ghrelin levels and systemic lupus erythematosus (SLE). METHODS: We conducted a meta-analysis to compare serum/plasma adiponectin, visfatin, and ghrelin levels in patients with SLE to those of healthy controls. RESULTS: Eleven articles (822 patients with SLE and 676 controls) were included in the meta-analysis. The meta-analysis showed that the adiponectin level was significantly higher in the SLE group than in the control group (standardized mean difference [SMD]=0.360, 95% confidence interval [CI]=0.025∼0.695, p=0.035). Stratification according to region showed that high adiponectin levels were associated with SLE in the Western population (SMD=0.225, 95% CI=0.024∼0.426, p=0.028), but not in the South American population. A subgroup analysis that adiponectin level is significantly higher in the SLE group than in the control after adjustment for age, sex, body mass index, large sample size (n>100); and mean age>40 years (SMD=0.492, 95% CI=0.065∼0.920, p=0.024; SMD=0.492, 95% CI=0.065∼0.920, p=0.024; SMD=0.429, 95% CI=0.124∼0.733, p=0.006, respectively). Stratification by region showed significantly increased visfatin and ghrelin levels in the SLE group in Western and South American populations. CONCLUSION: Our meta-analysis demonstrated that circulating adiponectin, visfatin, and ghrelin levels are significantly higher in SLE.