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Abstract Background Women with rheumatoid arthritis (RA) have increased morbidity and mortality due to coronary heart disease. Chronic systemic inflammation is known to accelerate atherosclerosis and increase arterial stiffness in patients, but other mechanisms may also be involved. Biomarkers of oxidant stress, inflammation, insulinaemia and endothelial dysfunction were measured in blood and urine from 46 RA patients and 48 age-matched controls. Plaque formation and intima-medial thickness (IMT) were measured using B-mode carotid Doppler scan. Findings The prevalence of plaque was increased (p = 0.042) in RA patients between 50–59 years old compared to the same age group in controls. 8-isoprostane (p = 0.004), C-reactive protein (p < 0.001), interleukin-6 (p < 0.001), insulin (p = 0.035), adiponectin (p = 0.012), vascular cell adhesion molecule (VCAM) (p = 0.029) and E-selectin (p < 0.001) were all increased while selenium (p = 0.003) and LDL-cholesterol (p = 0.025) were both decreased in all RA patients. 8-isoprostane correlated with 10 year cardiac risk (r = 0.55, p < 0.001), VCAM with IMT (r = 0.37, p = 0.012) and E-selectin with rheumatoid factor titre (r = 0.43, p = 0.003) in RA patients. In the control group, age, carotid IMT, VCAM, systolic blood pressure and smoking status were all associated with plaque development whereas in RA patients only age was associated with plaque. Conclusion The burden of atherosclerosis is particularly increased in middle-aged women with RA. Patients with RA have increased levels of oxidant stress, inflammation, insulin and soluble adhesion molecules. As the association between classical risk factors was much weaker in RA patients compared to controls, these additional factors may be more important in the accelerated development of atheroma in RA.

Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery‐induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III–IV obesity (body mass index ≥40 and ≥50 kg/m2, respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months' follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki‐67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy‐two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was −32.7 and −62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki‐67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA‐IR) and inflammation (hsCRP, IL‐6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down‐regulation of PI3K‐AKT–mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease. What's new? Obesity is a major risk factor for endometrial cancer (EC). In this study, the authors found that, in obese women, bariatric surgery‐induced weight loss resulted in significant, beneficial changes in circulating biomarkers of insulin resistance, inflammation, and reproductive hormones, in endometrial morphology, and in molecular pathways that are implicated in endometrial carcinogenesis. The latter included changes in Ki‐67 expression and activation of the PI3K‐AKT‐mTOR oncogenic signaling pathway, including PTEN and pAKT. These results may have important implications for screening, prevention and treatment of EC. [ABSTRACT FROM AUTHOR]

Objectives: In systemic lupus erythematosus (SLE) patients, glomerular filtration rate (GFR) is usually estimated using the modified Cockcroft-Gault (mCG) and Modification of Diet in Renal Disease (MDRD) equations. We aimed to study cystatin C (sCysC) in SLE to assess its agreement with standard renal indices and investigate factors affecting sCysC in SLE., Methods: SLE patients (≥4 ACR criteria) and healthy women from Greater Manchester were recruited and clinical assessments were undertaken. SCysC was measured using R & D Systems' ELISA. Agreement between renal measures was assessed using Deming plots and factors associated with sCysC in SLE were examined by multiple linear regression analyses., Results: 178 patients and 68 controls had median (IQR) ages of 53 (46-61) and 50 (39-60) years, respectively. In an age-adjusted analysis, SLE patients had higher sCysC (1.16 [0.98-1.36] vs. 0.950 [0.73-1.13] mg/l; p<0.0001) and within SLE those with a history of lupus nephritis had higher sCysC (1.31 [1.10-1.66] vs. 1.11 [0.95-1.29] mg/l; p<0.005). SCysC correlated positively with serum creatinine, and inversely to renal measures (r=-0.530; p<0.0001 [mCG], and r=-0.620; p<0.0001 [MDRD]). There was closer agreement between the two eGFR measures than between either eGFR measures and sCysC. In addition to age and serum creatinine, a multivariate analysis (β, p) found that high-sensitivity C-reactive protein (hs-CRP) (0.03, 0.026) was also independently associated with sCysC in SLE., Conclusions: In SLE, sCysC may be influenced by low grade inflammation as well as by renal dysfunction. Therefore, SCysC should not supplant current assessment of renal dysfunction in SLE.