Impact of Concomitant Immunomodulator Use on Long-Term Outcomes in Patients Receiving Scheduled Maintenance Infliximab

The long-term benefits of combining scheduled infliximab with concomitant immunomodulators [azathioprine or 6-mercaptopurine (6-MP)] in patients with Crohn’s disease are unclear. Historical cohort followed for 5 years after initiation of infliximab for active Crohn’s disease. Data were available on 123 patients who received scheduled maintenance infliximab infusions, for up to 5 years after initiation of infliximab. Clinical remission rates in the entire cohort were 73% (82/113) at 1 year, 65% (65/100) at 2 years, and 58% (21/36) at 5 years. Remission rates with maintenance infliximab were significantly improved in those receiving concomitant immunomodulators at 1 year (86% versus 68%, P = 0.03), but not at 2 years (80% versus 72%, P = 0.4). In a multivariate logistic regression model, concomitant immunomodulator use was not associated with a significantly improved odds ratio of remission in patients on maintenance infliximab [odds ratio (OR) 1.1, 95% confidence intervals (CI) 0.9–1.2, P = 0.9]. The risk of surgery was significantly reduced in those receiving immunomodulators at the commencement of maintenance infliximab (OR 0.3, 95% CI 0.1–0.7, P = 0.01), but not in patients who continued maintenance concomitant therapy (OR 0.4, 95% CI 0.1–1.5, P = 0.1). The combination of maintenance infliximab and an immunomodulator produced modest improvements in outcomes beyond maintenance infliximab alone in this cohort.     

Lack of association between promoter polymorphisms of <Emphasis Type="Italic">HLA</Emphasis>-<Emphasis Type="Italic">G g</Emphasis>ene and rheumatoid arthritis in Korean population

The aim of this study was to determine whether the HLA-G gene was associated with susceptibility to rheumatoid arthritis (RA). Major histocompatibility complex, class I, G (HLA-G) is involved in immunoregulatory processes and particularly in pathogenesis of inflammatory disorders. To investigate possible association between HLA-G and RA, 296 RA patients and 468 healthy controls were enrolled in this study. Two-promoter single-nucleotide polymorphisms (SNPs) (rs1736936, -1202T/C and rs2735022, -586C/T) in HLA-G gene were analyzed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). For analysis of data, Helixtree software, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used. Multiple logistic regression models (codominant, dominant, and recessive) were performed for odds ratio (OR), 95% confidence interval (CI), and P value. There were no significant differences in distributions of genotypes and haplotypes between RA patients and control subjects. In clinical features of RA, we found differences between C-reactive protein levels (≥0.5 or <0.5 mg/dL) and two-promoter SNPs. Rs1736936 was significant in codominant (P = 0.028, OR = 0.66, 95% CI = 0.45–0.96) and dominant (P = 0.046, OR = 0.58, 95% CI = 0.34–0.99) models. Also, rs2735022 was significant in codominant (P = 0.038, OR = 0.67, 95% CI = 0.46–0.98) and dominant (P = 0.03, OR = 0.55, 95% CI = 0.33–0.94) models. However, these significant associations disappear after Bonferroni correction. Our results suggest that HLA-G promoter polymorphisms may be not associated with the development of RA in Korean population.     

The status of serum vitamin D in patients with rheumatoid arthritis and undifferentiated inflammatory arthritis compared with controls

Inadequate vitamin D may be involved in the pathogenesis and or progression of several disorders, including connective tissue diseases. To determine the status of vitamin D in different stages of inflammatory arthritis, the levels of vitamin D in established rheumatoid arthritis (RA) and undifferentiated inflammatory arthritis (UIA) were compared with controls. Patients with RA and UIA entered the study. Serum 25-hydroxyvitamin D (25-OHD) was measured by ELISA method, and concentrations less than 20 ng/ml were considered as deficient levels. In statistical analysis, the Mann–Whitney U test was used for comparing differences between groups and logistic regression analysis with calculation of adjusted odds ratio (OR) was used to determine the association between serum 25-OHD deficiency and disease condition. A total of 108 RA, 39 UIA, and 239 controls were studied. There were no significant differences in mean serum 25-OHD level and frequency of serum 25-OHD deficiency between RA and controls (37 ± 37.7 vs. 33.2 ± 28.6 ng/ml, P = 0.96). But the mean serum 25-OHD level in UIA was significantly lower than in the controls (25.1 ± 23.9 vs. 33.2 ± 28.6 ng ml, P = 0.04). A significant positive association was observed between serum 25-OHD deficiency and UIA (56.4% vs. 35.5%, OR = 2.34, 95% CI, 1.18–4.65, P = 0.021) which remained significant after adjustment for sex and age (adjusted OR = 2.24, 95% CI, 1.01–4.55, P = 0.026). Whereas the association between serum 25-OHD deficiency and RA did not reach statistical significance (40.7% vs. 35.5%, OR = 1.24, 95% CI, 0.78–1.99). These findings indicate higher serum vitamin D deficiency in patients with ongoing arthritis rather than established arthritis. Respecting to deleterious effects of vitamin D deficiency on immune system and progressive nature of UIA, a significant proportion of high risk UIA can be recognized by serum 25-OHD determination.     

Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthritis in South Asians and Caucasians of East Midlands in the United Kingdom

Genetic associations of TNFR2, VDR (Bsm I and Fok I), A2M, GSTT₁, GSTM₁ and ACE in South Asian and Caucasian patients with rheumatoid arthritis (RA) were assessed in this study. DNA samples from South Asians (134 cases, 149 controls) and Caucasians (137 cases, 150 controls) from the East Midlands of the United Kingdom were genotyped for seven polymorphisms. All cases were rheumatoid-factor positive. Significant genetic associations were observed with TNFR2 R–R (OR = 3.16, CI 1.20–9.26, P < 0.05), A2M 1–1 (OR = 2.09, CI 1.21–3.64, P < 0.05) and GST T₁null (OR = 1.97, CI 1.07–3.68, P < 0.05) among Caucasian patients. In South Asians, VDR Bsm I B–B genotype (OR = 2.08, CI 1.23–3.52, P < 0.05), A2M 2–2 genotype (OR = 3.99, CI 1.19–17.18, P < 0.05), and GST T₁null genotype (OR = 2.81, CI 1.40–5.77, P < 0.002) genotypes were associated with RA. In the majority of cases, recessive and multiplicative modes of inheritance explained the observed associations. This study demonstrates that ethnicity affects the genetic associations in RA.     

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients

Objective: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery.

Methods: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables.

Results: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256–7.986; p?=?0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436–11.389; p?=?0.008) and disease duration (OR, 1.004; 95% CI, 1.000–1.007; p?=?0.029) were associated with an increased risk of DWH.

Conclusions: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.     

Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low systemic inflammatory activity

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457–961%) vs 797% (95% CI, 556–1,037%), P = 0.59 and 37% (95% CI, 26–47%) vs 41% (95% CI, 31–50%), P = 0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease.     

Risk factors for mortality–morbidity after emergency–urgent colorectal surgery

Background  The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. Materials and methods  All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. Results  The median age of patients was 73 (range 17–98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm³ (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63–6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score ≥3 (OR = 2.9, 95% CI 1.9–4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4–7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4–3.4, p = 0.0003). Conclusions  The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients’ ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.     

A Surveillance Report of HIV Status and High Risk Behaviors Among Rapid Testing Participants in Tallinn,Estonia

Estonia has the second highest adult HIV prevalence in Europe of 1.3%. The primary transmission is among injecting drug users (IDU), who account for 56–90% of HIV infections (Report on the Global AIDS Epidemic: UNAIDS/WHO, July 2008 and Platt et al. AIDS 20(16):2120–2123, 2006). Of those persons newly diagnosed, 50.4% reported injecting drugs in the last 12 months, 16.3% of these reported IDU as the sole risk factor and 31.2% reported IDU among other risk factors. In this sample (n = 790) 170 persons reported a high risk behavior and 51 persons received a positive result through rapid testing. The largest proportion (35.29%) was among persons reporting high risk heterosexual intercourse and second (33.33%) among persons sharing injecting equipment. Covariates in a logistic regression model indicate that male sex (OR = 2.57, 95% CI 1.00–6.59), non-Estonian ethnicity (OR = 2.68, 95% CI 1.46–4.93), higher education (OR = 0.56, 95% CI 0.40–0.80), and high risk heterosexual intercourse (OR = 2.68, 95% CI 1.19–6.02) are statistically significant in predicting a positive HIV status.     

A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulation of eukaryotic gene expression. Aberrant expression and structural alternation of miRNAs are considered to participate in tumorigenesis and cancer development. Recently, different genotypes of miR-196a polymorphisms (SNP, rs11614913) were found to be associated with the survival of patients with lung cancer and increased risk of breast cancer. To further investigate whether this polymorphism may influence glioma risk or not, we examined the SNP allele frequency in Chinese population. Our data shows the genotype CC of miR-196a (rs11614913) polymorphism is associated with decreased risk of glioma in the Chinese population (OR = 0.74, 95% CI:0.56–0.98). Furthermore, a significant association was observed between this genotype and glioma risk in the subgroups of adult glioma (OR = 0.73, 95% CI:0.55–0.98), male glioma (OR = 0.69, 95% CI:0.48–0.99) and patients with glioblastoma (OR = 0.58, 95% CI:0.37–0.91). This was the first study investigating the association between the miR-196a rs11614913 and glioma risk. Compared with the results from previous studies in lung cancer and breast cancer, our data suggest a different genotype association in glioma. This may be related to the diversity on the tissue origin, tumor type, tumorigenesis, and developing process.     

Interleukin-18 promoter polymorphisms in Japanese patients with rheumatoid arthritis: protective effect of the T allele and T/T genotype at rs360722

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a strong genetic contribution to its pathogenesis. Among numerous candidate genes, cytokine gene polymorphisms have been implicated. Interleukin-18 (IL-18) induces production of tumor necrosis factor-α and promotes T helper (Th)1-type immune responses. This study investigates the association between IL-18 promoter polymorphisms and RA susceptibility. A total of 2471 Japanese case–control samples (1493 RA patients and 978 healthy controls) were examined. Three haplotype tag single-nucleotide polymorphisms, rs1946518A/C, rs360718T/G, and rs360722T/C, spanning from the 5′UTR to intron 1 were genotyped using allelic discrimination with the use of specific TaqMan probes, and three haplotypes (A–T–T, C–T–C, and A–G–C) were determined. Among these polymorphisms, the frequency of the T allele at rs360722, which tags the A–T–T haplotype, was significantly lower in the RA patient group compared with the normal subjects [0.46 versus 0.49, P = 0.0061, Fisher’s exact probability test, odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.75–0.95]. Having the T/T genotype further increased the significance (0.20 versus 0.27, P = 0.0006, OR = 0.72, 95% CI = 0.58–0.86). Therefore, presence of the T allele and T/T genotype at rs360722 reduces the susceptibility of Japanese people to RA.     

Outcome of patients with seronegative spondyloarthritis continuing sulphasalazine and methotrexate after a short course of infliximab therapy—experience from a tertiary care teaching hospital in South India

The objective of the study is to evaluate the outcome of patients with seronegative spondyloarthritis continuing on sulphasalazine (SSZ) and methotrexate (MTX) after a short course of infliximab. Patients with seronegative spondyloarthritis on MTX and SSZ were given short course of infliximab therapy at 0, 2, 6 and 14 weeks. Outcome of these patients while continuing on MTX and SSZ was assessed. Clinical features, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were noted at baseline (pre-infliximab), 1 month, 3 months and last follow-up after last dose of infliximab infusion. Twenty-four patients were included in this study. The mean duration of follow-up was 9.1 months. Statistically significant reduction in tender and swollen joint count was noted at all the three visits as compared to baseline. Fall in ESR and CRP was statistically significant at 1 and 3 months, but not at last follow-up. Mean reduction in BASDAI at 1 month ,3 month and last follow-up after last infliximab dose were 3.907 (95% CI 2.98–4.83; p < 0.001), 4.53 (95% CI 3.56–5.49; p < 0.001) and 2.48 (95% CI 1.12–3.84; p = 0.002), respectively. Mean reduction in BASFI at 1 month, 3 months and last follow-up after last infliximab dose were 4.13 (95% CI 3.23–5.04; p < 0.001), 4.34 (95% CI 2.8–5.88; p < 0.001) and 2.38 (95% CI 0.86–3.90; p = 0.005), respectively. Continuing SSZ and MTX after short course of infliximab results in sustained improvement in our patients with seronegative spondyloarthritis in India.     

The skinny on sexual risk: the effects of BMI on STI incidence and risk

Few studies examine the influence of body mass index (BMI) on sexual risk. The purpose of this study was to determine whether BMI among 704 young mothers (ages 14–25) related to STI incidence and sexual risk. We examined the effect of BMI groups (normal weight, overweight, and obese) at 6 months postpartum on STI incidence and risky sex (e.g., unprotected sex, multiple partners, risky and casual partner) at 12 months postpartum. At 6 months postpartum, 31% of participants were overweight and 40% were obese. Overweight women were more likely to have an STI (OR = 1.79, 95% CI = 1.11–2.89, P < .05) and a risky partner (OR = 1.64, 95% CI = 1.01–2.08, P < .05) at 12 months postpartum compared to normal weight women. However, obese women were less likely to have an STI than normal weight women (OR = .57, 95% CI = .34–.96, P < .01). BMI related to STI incidence and sexual risk behavior. Integrated approaches to weight loss and sexual risk prevention should be explored.     

Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis

This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83–8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45–30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28–6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23–32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68–0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.     

Infliximab in Ulcerative Colitis is Associated with an Increased Risk of Postoperative Complications After Restorative Proctocolectomy

Purpose  Little data exist regarding infliximab use in surgical decision making and postoperative complications in ulcerative colitis. Our goals were to determine the rate of postoperative complications in infliximab-treated ulcerative colitis patients undergoing restorative proctocolectomy and to determine whether three-stage procedures are more often necessary. Methods  We studied a group of infliximab-treated patients and matched control subjects who underwent two-stage restorative proctocolectomy between 2000 and 2006. Postoperative complications were compared. In addition, the rate of three-stage procedures was compared between all infliximab- and noninfliximab-treated patients. Results  A total of 523 restorative proctocolectomies were performed. In the infliximab group, there were 46 two-stage and 39 three-stage procedures. Covariate-adjusted odds of early complication for the inflixmab group was 3.54 times that of controls (P = 0.004; 95 percent confidence interval (CI), 1.51–8.31). The odds of sepsis were 13.8 times greater (P = 0.011; 95 percent CI, 1.82–105) and the odds of late complication were 2.19 times greater (P = 0.08; 95 percent CI, 0.91–5.28) for infliximab. The odds of requirement for three-stage procedures was 2.07 times greater in the infliximab group (P = 0.011; 95 percent CI, 1.18–3.63). Conclusions  Infliximab increases the risk of postoperative complications after restorative proctocolectomy and has altered the surgical approach to ulcerative colitis. Potential benefits of infliximab should be balanced against these risks. Dr. Sandborn is a consultant (fees paid to Mayo Clinic) to Centocor, Abbott Laboratories, and UCB Pharma; research support for Centocor, Abbott Laboratories, and UCB Pharma. Dr. Pardi is a consultant to Abbott, Salix, Lonza, Elan, and Biobalance; research support for Salix, Proctor & Gamble, Astra Zeneca, Genzyme, Ocera, Optimer Pharmaceuticals, and Massachusetts Biologic Laboratories. Supported by the Edward and Josephine Story Cleveland Clinic Ileal Pouch Database Fund. Read at the meeting of The American Society Colon and Rectal Surgery, St. Louis, Missouri, June 2 to 7, 2007.     

Alcohol Use, Intimate Partner Violence, Sexual Coercion and HIV among Women Aged 15–24 in Rakai, Uganda

Disinhibition due to alcohol may induce intimate partner violence and sexual coercion and increased risk of HIV infection. In a sample of 3,422 women aged 15–24 from the Rakai cohort, Uganda, we examined the association between self-reported alcohol use before sex, physical violence/sexual coercion in the past and prevalent HIV, using adjusted odds ratios (Adj OR) and 95% confidence intervals (95% CI). During the previous year, physical violence (26.9%) and sexual coercion (13.4%) were common, and alcohol use before sex was associated with a higher risk of physical violence/sexual coercion. HIV prevalence was significantly higher with alcohol consumption before sex (Adj OR = 1.45, 95% CI: 1.06–1.98) and especially when women reported both prior sexual coercion and alcohol use before sex (Adj OR = 1.79, 95% CI: 1.25–2.56). Alcohol use before sex was associated with physical violence and sexual coercion, and both are jointly associated with HIV infection risk in young women.     

Hyperhomocysteinemia in ankylosing spondylitis: prevalence and association with clinical variables

We evaluated the prevalence and characteristics associated with hyperhomocysteinemia in ankylosing spondylitis (AS). Ninety-seven patients with AS were compared with 97 controls. The assessment included clinical characteristics, disease activity (BASDAI), functioning (BASFI), history of drugs, and erythrocyte sedimentation rate (ESR). Total serum homocysteine (tHcy) was determined by fluorescence polarization immunoassay. A higher frequency of hyperhomocysteinemia (>15 μmol/L) was observed in AS (12 vs. 1%, P = 0.002). In the multivariate analysis the risk for hyperhomocysteinemia was increased in patients with higher score of HAQ-S (OR = 5.27, 95% CI: 1.29–21.44) and higher ESR (OR = 1.09, 95% CI: 1.02–1.18). No statistical associations was observed between hyperhomocysteinemia with other variables including methotrexate or sulfasalazine utilization. In conclusion, this study found a significant prevalence of hyperhomocysteinemia in Mexican patients with AS mainly associated to a worst functional impairment. Further follow-up studies are required to evaluate the risk of cardiovascular disease in these patients.     

Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients

Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR–RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ²-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65–16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19–3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67–5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.     

Response variability to aspirin and one-year prediction of vascular events in patients with stable coronary artery disease

The aim of this study was to assess the association between “aspirin non responsiveness” in patients with coronary artery diseases (CAD) and the risk of major adverse cardiovascular events (MACE). 204 patients with CAD receiving aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI-CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the patients aspirin responsiveness. The clinical primary endpoint was the occurrence of MACE including: cardiovascular death, MI, stroke or transient ischemic attack. The secondary endpoint was the occurrence of Recurrent Acute Vascular Event (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%; P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7–2.4; P = 0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2–32.2; P = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated with an increased risk of either MACE or RAVE. Our results, reinforce the importance of being able to diagnose laboratory “aspirin non responsiveness”, and extend the evidence that aspirin non responsiveness may explain in part the occurrence of RAVE.