RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

Association between the functional <Emphasis Type="Italic">MHC2TA</Emphasis> −168 A/G polymorphism and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the functional major histocompatibility complex II transactivator (MHC2TA) ?168 A/G polymorphism is associated with susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted to estimate the association between the MHC2TA?168 A/G polymorphism and RA. A total of 15 comparative studies, which included 14,158 patients and 13,642 controls, were included in the meta-analysis. Based on the meta-analysis, there was no association between RA and the MHC2TA ?168 G allele in the study subjects (OR?=?1.046, 95 % CI?=?0.987–1.108, p?=?0.130) or Caucasians (OR?=?1.027, 95 % CI?=?0.986–1.070, p?=?0.193). However, the country-specific meta-analysis revealed an association between the MHC2TA ?168 G allele and RA in the Swedish population (OR?=?1.131, 95 % CI?=?1.023–1.250, p?=?0.016). A direct comparison between rheumatoid factor (RF)-positive and RF-negative patients revealed that the frequency of the G allele was significantly lower in RF-positive patients (OR?=?0.783, 95 % CI?=?0.628–0.975, p?=?0.029) than in RF-negative patients. This meta-analysis demonstrated that the MHC2TA ?168 A/G polymorphism is not associated with susceptibility to RA in Caucasians.     

Association between susceptibility to rheumatoid arthritis and <Emphasis Type="Italic">PADI4</Emphasis> polymorphisms: a meta-analysis

The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]?=?1.155, 95 % confidence interval [CI]?=?1.069–1.249, p?=?2.7?×?10^?5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR?=?1.273, 95 % CI?=?1.193–1.359, p?<?1.0?×?10^?9), but not in Caucasians (OR?=?1.024, 95 % CI?=?0.973–1.078, p?=?0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR?=?2.311, 95 % CI?=?1.1.858–2.875, p?<?1.0?×?10^?9) and Caucasians (OR?=?1.523, 95 % CI?=?1.157–2.004, p?=?0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR?=?1.547, 95 % CI?=?1.247–1.919, p?=?7.1?×?10^?6) and Caucasians (OR?=?1.096, 95 % CI?=?1.025–1.172, p?=?0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR?=?1.263, 95 % CI?=?1.153–1.384, p?=?5.8?×?10^?8), but not in Caucasians (OR?=?1.123, 95 % CI?=?0.980–1.287, p?=?0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.     

The functional <Emphasis Type="Italic">PTPN22</Emphasis> C1858T polymorphism confers risk for rheumatoid arthritis in patients from Central Mexico

Rheumatoid arthritis (RA) is a complex genetic disease. Human leukocyte antigen (HLA) and non-HLA genes are reportedly associated with an increased risk of RA. The protein tyrosine phosphatase non-receptor 22 gene (PTPN22), which encodes the lymphoid tyrosine phosphatase (LYP) protein, is one of the best examples of a non-HLA gene associated with a risk for RA in several populations. The functional PTPN22 C1858T (R620W) non-synonymous polymorphism is widely associated with an increased risk for RA in Europeans and non-Europeans. The aim of this study was to determine if the PTPN22 C1858T polymorphism confers susceptibility to RA in a sample of patients from Mexico. This study included 364 RA patients and 387 non-related controls from Central Mexico. Genotyping of the PTPN22 C1858T (rs2476601) polymorphism was performed using allelic discrimination assays with TaqMan probes. The functional PTPN22 C1858T polymorphism was associated with an increased risk for RA in our study population. The CC vs CT genotype in RA patients versus healthy controls had an odds ratio (OR) of 4.17 (95 % CI 1.79–9.74, p?=?0.00036), while T allele had an OR of 4.06 (95 % CI 1.75–9.41, p?=?0.00043). PTPN22 is a genetic risk factor for developing RA in the Mexican population.     

The association between 10-year fracture risk by FRAX and osteoporotic fractures with disease activity in patients with rheumatoid arthritis

As rheumatoid arthritis (RA) is an independent risk factor for osteoporotic fractures, the severity of disease activity may correlate with fracture risk. Our objectives were to determine the prevalence of major osteoporotic and hip fractures in patients with RA and to identify the factors related to their 10-year probabilities. This study enrolled 232 patients with RA, aged 40–90 years, who participated in the Siriraj RA Cohort in 2016 and 2017. Demographic data, disease activity scores 28 (DAS28), and health assessment questionnaires (HAQ) were collected. All participants were evaluated for asymptomatic vertebral fractures by thoracolumbar spine radiography. The osteoporotic fracture risks were determined using the fracture risk assessment tool (FRAX). Most subjects were postmenopausal women in their sixth decade; the median disease duration was 12.95 years. Forty-six percent of patients had osteoporotic fractures, and most (87%) were vertebral fractures. Eighty-one patients had asymptomatic vertebral compression fractures. Of those, 57%, 25%, and 18% had low, moderate, and high 10-year probabilities of major osteoporotic fractures, respectively, while 51%, 34%, and 15% had low, moderate, and high 10-year probabilities of hip fractures, respectively. Factors significantly associated with the 10-year probabilities of major osteoporotic and hip fractures were disease duration (p 0.017, 0.009), menopause duration (p?<?0.001 both), cumulative disease activity (DAS28; p 0.004, 0.029), and cumulative functional disability (HAQ; p?<?0.001 both). Moderate to high 10-year probabilities of major osteoporotic and hip fractures are common in RA. Cumulative disease severity is a high risk for osteoporotic fractures.     

The psychosocial status of the family members of rheumatoid arthritis patients in Korea

To investigate the psychosocial aspect of the family members of the patients with rheumatoid arthritis (RA), we conducted a population-based analysis to examine the psychosocial characteristics of family members of RA patients in comparison with the general population. From the Fifth Korea National Health and Nutrition Examination Survey dataset (KNHANES V) (2010–2012), we identified 363 RA patients and selected family members of these patients who were aged 20 years or older (n = 367). The control group was randomly sampled from members of families without RA patients and matched for sex and age (n = 1101). We compared the psychosocial characteristics of family members of RA patients with the control group. Additionally, serial conditional logistic regression models were performed to evaluate the factors that affect psychosocial status of the RA family members, after adjusting for covariates. No significant differences were found in socioeconomic status between the two groups. For psychological factors, stress (85.8 vs 74.7 %, p < 0.001) and depression (7.9 vs 3.3 %, p < 0.001) were more common in the family members of RA patients. The presence of a RA patient in the family showed a positive association with stress [odds ratio (OR) 2.07; 95 % confidence interval (CI) 1.48–2.88, p < 0.001] and depression (OR 2.59, CI 1.55–4.32, p < 0.001), after adjusting for socioeconomic status. Our data show that the family members of RA patients have an increased prevalence of stress and depression. Physicians who treat RA patients should also consider the needs and the burden of family members.     

Interleukin 12B gene polymorphisms and susceptibility to rheumatoid arthritis: a data synthesis

The aim of this study was to investigate the association of two common interleukin 12B (IL-12B) polymorphisms (rs3212227 and rs6887695) with rheumatoid arthritis (RA) susceptibility through meta-analyses. A systematic literature search of PubMed, Web of Science, Cochrane Library, and Embase databases was conducted on articles published before 28 February 2016. Then odds ratio (OR) with 95 % confidence interval (CI) was used to quantify the strength of association for homozygote, heterozygote, dominant, and recessive genetic models. Nine articles with a total of 17 case–control studies (12 for IL-12B rs3212227 polymorphism and 5 for IL-12B rs6887695 polymorphism) met our inclusion criteria. The pooled results demonstrated that IL-12B rs3212227 (homozygote model: OR?=?0.96, 95 % CI?=?0.81–1.15; heterozygote model: OR?=?1.07, 95 % CI?=?0.93–1.23; dominant model: OR?=?1.05, 95 % CI?=?0.91–1.20; recessive model: OR?=?0.93, 95 % CI?=?0.79–1.10) and rs6887695 (homozygote model: OR?=?1.01, 95 % CI?=?0.84-1.21; heterozygote model: OR?=?1.14, 95 % CI?=?0.86–1.51; dominant model: OR?=?1.14, 95 % CI?=?0.87–1.48; recessive model: OR?=?1.01, 95 % CI?=?0.85–1.21) polymorphisms may not be associated with RA risk. Our meta-analyses demonstrated that IL-12B rs3212227 and rs6887695 polymorphisms do not confer susceptibility to RA.     

Baricitinib,a Janus kinase inhibitor,in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication. We used RevMan 5.3 to perform meta-analysis between groups on baricitinib (2 and 4 mg daily) and placebo using random effect model calculating odds ratio (OR) as well as 95% confidence interval (CI). Compared to placebo, 2 mg of baricitinib was more effective in achieving ACR20 [54 vs. 36.6%; OR 2.09; 95% CI 1.60–2.71; p?<?0.00001; I² 0%], ACR50 [31.6 vs. 10.3%; OR 2.3; 95% CI 1.68–3.15; p?<?0.00001; I² 0%], and ACR70 responses [18.7 vs. 5.1%; OR 4.05; 95% CI 2.54–6.44; p?<?0.00001; I² 0%]. Similarly, 4 mg of baricitinib daily was more effective than placebo. Baricitinib 2 mg once daily did not increase any adverse events [65.3 vs. 62.4%; OR 1.03; 95% CI 0.80–1.34; p?=?0.8; I² 0%], serious adverse events [3.5 vs. 5%; OR 0.68; 95% CI 0.37–1.27; p?=?0.22; I² 0%], and herpes zoster [1.2 vs. 0.4%; OR 2.34; 95% CI 0.27–20.47; p?=?0.44; I² 37%] as compared to placebo. Similarly, 4 mg of baricitinib did not increase the risk of serious adverse events but increased herpes zoster infection [OR 3.88; 95% CI 1.36–11.06; p?=?0.01; I² 0%] when compared to placebo. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment.     

Fostamatinib,an oral spleen tyrosine kinase inhibitor,in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32–2.62, P = 0.0004, I ² 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93–3.23, P < 0.00001, I ² 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99–4.51, P < 0.00001, I ² 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33–5.87, P < 0.00001, I ² 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2–2.11; P = 0.001; I ² 0 %), diarrhea (OR 3.54; 95 % CI 2.43–5.16; P < 0.00001; I ² 2 %), hypertension (OR 2.55, 95 % CI 1.54–4.22, P = 0.0003; I ² 42 %) and neutropenia (OR 5.68, 95 % CI 1.97–16.42, P = 0.001, I ² 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99–3.13; P = 0.05; I ² 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.     

Risk factors associated with the occurrence of proximal humerus fractures in patients with rheumatoid arthritis: a custom strategy for preventing proximal humerus fractures

To our knowledge, no prior report focused on the risk factors for proximal humerus fractures in patients with rheumatoid arthritis. The purpose of this study was to evaluate the association between potential risk factors and the occurrence of proximal humerus fractures in patients with rheumatoid arthritis. A total of 11,907 patients with rheumatoid arthritis were enrolled in our observational cohort rheumatoid arthritis study between 2000 and 2012. Self-reported proximal humerus fractures were verified using the patients’ medical records. Cox proportional hazard models were used to analyze the independent contribution of risk factors to the occurrence of proximal humerus fractures. During follow-up (mean 5.6 years), 92 proximal humerus fractures were verified in 91 patients. Multivariate Cox regression analyses estimated that the hazard ratios of sustaining a proximal humerus fracture were 1.37 for every 10-year increase in age [95 % confidence interval (CI) 1.10–1.70; P < 0.01], 1.95 for increases in serum C-reactive protein levels (mg/100 mL; 95 % CI 1.15–3.34; P < 0.05), 2.13 for a history of fractures (95 % CI 1.34–3.40; P < 0.01), 1.07 for the daily prednisolone dose (per mg; 95 % CI 1.01–1.13; P < 0.05), and 1.97 for oral bisphosphonate use (95 % CI 1.20–3.23; P < 0.01). Better control of rheumatoid arthritis with a smaller daily prednisolone dose in elderly patients with a history of fractures may be important for preventing proximal humerus fractures.     

Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis

The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029–2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876–1.649, p = 0.255; OR 2.132, 95 % CI 0.764–5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316–25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212–4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.     

Heel quantitative ultrasound in HIV-infected patients: a cross-sectional study

Purpose

HIV infection has been associated with increased risk of osteoporosis and fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the reference standard to assess bone mineral density (BMD); however, it is not easily accessible in several settings. Heel Quantitative ultrasound (QUS) is a radiation-free, easy-to-perform technique, which may help reducing the need for DXA.

Methods

In this cross-sectional study, we used heel QUS (Hologic Sahara^®) to assess bone status in a cohort of HIV-infected patients. A QUS stiffness index (QUI) threshold >83 was used to identify patients with a low likelihood of osteoporosis. Moreover, we compared QUS results with those of 36 sex- and age-matched HIV-negative controls.

Results

244 HIV-positive patients were enrolled. Median heel QUI value was 83 (73–96) vs. 93 (IQR 84–104) in the control group (p = 0.04). 110 patients (45 %) had a QUI value ≤83. Risk factors for low QUI values were age (OR 1.04 per year, 95 % CI 1.01–1.07, p = 0.004), current use of protease inhibitors (OR 1.85, CI 1.03–3.35, p = 0.039), current use of tenofovir (OR 2.28, CI 1.22–4.27, p = 0.009) and the number of risk factors for secondary osteoporosis (OR 1.46, CI 1.09–1.95, p = 0.01). Of note, QUI values were significantly correlated with FRAX score (r = ?0.22, p = 0.004). According to EACS guidelines, 45 % of patients had risk factors for osteoporosis which make them eligible for DXA. By using QUS, we may avoid DXA in around half of them.

Conclusions

As HIV-positive patients are living longer, the prevalence of osteoporosis is expected to increase over time. Appropriate screening, prevention and treatment are crucial to preserve bone health in this population. The use of screening techniques, such as heel QUS, may help reducing the need for DXA. Further studies are needed to define the diagnostic accuracy of this promising technique in the setting of HIV.

     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.     

Characteristics of rheumatoid arthritis patients undergoing reverse shoulder arthroplasty

The risks and complication profile of reverse total shoulder arthroplasty (RSA) in rheumatoid arthritis (RA) patients has yet to be clearly defined as most studies have small cohorts. Using a large inpatient database, the purpose on our study was to determine the overall demographics, hospitalization characteristics, and early complication rates in rheumatoid patients and compared these to rotator-cuff arthropathy patients without RA undergoing RSA. Utilizing United States Nationwide Inpatient Sample from 2010 to 2013, we evaluated a total of 919 RA RSA and compared them to 8097 patients without RA undergoing RSA. The outcomes included demographic characteristics like age, race, sex, Deyo comorbidity score, perioperative complications, and mean length-of-stay. The RA cohort had 81% females versus 60% in the comparison cohort. This cohort was younger (p = 0.006) and had longer hospitalization time (p = 0.001), but the total inpatient costs were not significantly different (p = 0.15). In regards to Deyo index, rheumatoid patients had significantly higher scores (p < 0.001). The inpatient complication rates for infection (p = 0.9), nerve injury (p = 0.9), and instability (p = 0.19) were similar, but the RA cohort had more prosthetic-related (p = 0.001) and greater tuberosity-related (p = 0.008) complications. The mortality rates were also similar (p = 0.625). In RSA for RA patients, surgeons should be mindful of preoperative risk factors and demographic characteristics that may influence their outcomes. Caution should specifically be paid to the possibility of longer hospitalization time and increased incidence of certain complications, including intraoperative fracture, when compared to non-rheumatoid patients. Close collaboration between rheumatologists, surgeons, and primary care physicians is a must for optimizing and managing these patients.     

Aortic aneurysm associated with rheumatoid arthritis: a population-based cross-sectional study

There is substantial evidence that aortic aneurysm (AA) may be a manifestation of several systemic rheumatic disorders. However, only several studies have assessed the association between rheumatoid arthritis (RA) and AA. The aim of this study was to evaluate the incidence of AA in RA patients in a case-control study. A retrospective case-control study was performed utilizing the database of Clalit Health Services (CHS), a large healthcare provider organization in Israel. Data available from the CHS database included age, sex, socioeconomic status (SES), and diagnoses of chronic diseases, including AA. Patients over the age of 20 years who were diagnosed with RA (“cases”) were compared with a sample of age- and gender-matched enrollees without RA (“controls”) regarding the prevalence of AA. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 11,782 RA patients and 57,973 age- and gender-matched controls. The proportion of AA was significantly higher in RA patients (0.72 %) compared to the control group 0.49 % (odds ratio (OR) 1.48, 95 %; confidence interval (CI) 1.15–1.88; p = 0.002). A multivariate analysis that evaluated covariates associated with AA revealed an independent association of AA and RA after adjustment for different factors including age, gender, SES, and smoking status (OR 1.406, 95 %; CI 1.094–1.789; p = 0.006). Our study has demonstrated that AA is more prevalent in patients with RA in comparison with general population. Future large randomized studies are important to identify cardiovascular- and disease-related risk factors for AA formation in RA patients.     

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0–3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist–MCP–ankle–MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist–hand–ankle–MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.     

Association between self-reported snoring and arterial stiffness: data from the Brisighella Heart Study

The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with cardiovascular risk is well known, but its investigation is complex and not suitable for studying large cohorts of subjects. Thus, we prospectively evaluated 1476 non-pharmacologically treated subjects selected from the last survey of the Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the subjects if they were aware of snoring during the night, and if this was associated with episodes of apnoea. A full set of clinical and laboratory parameters were evaluated, while augmentation index (AIx), and pulse wave velocity (PWV) were recorded with the Vicorder^® apparatus. A logistic regression analysis identifies as main independent predictors of AIx age (OR 1.058, 95 % CI 1.043–1.065, p < 0.001), Body Mass Index (OR 1.046, 95 % CI 1.014–1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95 % CI 1.004–1.023, p = 0.001). The main independent predictors of PWV are snoring (OR 1.215, 95 % CI 1.083–1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95 % CI 1.135–1.598, p = 0.014), age (OR 1.078, 95 % CI 1.052–1.089, p < 0.001), serum uric acid [SUA] (OR 1.093, 95 % CI 1.026–1.151, p < 0.001) and mean arterial pressure (OR 1.042, 95 % CI 1.024–1.056, p < 0.001). In conclusion, in our cohort of overall healthy subjects, self-reported snoring and sleep apnoea are independently associated with a higher PVW, and AIx is statistically significantly higher in snorers with or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B are associated with AIx, while SUA and mean arterial pressure are related to PWV.     

A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer

Purpose

The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC.

Methods

A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines.

Results

Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320–8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425–2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735–0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782–1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929–1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776–1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890–1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414–2.949; p = 0.842).

Conclusions

In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.

     

Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I ² 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I ² 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I ² 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I ² = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I ² = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.     

Multiple behavioral factors are associated with occurrence of large,flat colorectal polyps

Purpose

The prevalence of advanced dysplasia and synchronous lesions is particularly high in patients with large, flat colorectal polyps. However, the impact of lifestyle on the development of such polyps is poorly investigated. Hence, this study aims to identify associations between behavioral factors and the occurrence of large, flat colorectal polyps.

Methods

Behavioral factors were retrospectively analyzed in patients with large, flat polyps and control patients with at most one diminutive polyp. Information on lifestyle factors, comorbidities, and demographic parameters were determined by a structured, self-administered questionnaire.

Results

Questionnaires of 350 patients with large, flat polyps and 489 control patients were included in the analysis. Most large, flat colorectal polyps contained adenoma with low-grade neoplasia and were located in the right colon. Multivariate analysis showed that advanced age (per 1-year increase—OR 1.09, CI 1.07–1.11, p < 0.0001), frequent cigarette smoking (OR 2.04, CI 1.25–3.32, p = 0.0041), daily consumption of red meat (OR 3.61, CI 1.00–12.96, p = 0.0492), and frequent bowel movements (OR 1.62, CI 1.13–2.33, p = 0.0093) were independent risk factors for occurrence of large, flat colorectal polyps. In contrast, frequent intake of cereals (OR 0.62, CI 0.44–0.88, p = 0.0074) was associated with a reduced risk.

Conclusion

Multiple behavioral factors modulate the risk for developing large, flat colorectal polyps. This knowledge can be used to improve prevention of colorectal cancer.