Abstract-Aortic stiffness and chronic kidney disease are closely linked by shared risk factors and associated increased cardiovascular mortality. At lower levels of renal function, aortic stiffness is independently associated with glomerular filtration rate. However, the longitudinal impact of aortic stiffness on renal function has not been reported previously. A cohort of 133 patients with chronic kidney disease stages 3 and 4 (estimated glomerular filtration rate: 15 to 59 mL/min per 1.73 m 2 ) underwent prospective measurement of arterial stiffness parameters and monitoring of renal function. Aortic pulse wave velocity measurement was performed in 120 patients. The mean age was 69Ϯ12 years (meanϮSD; 103 men, 30 women, and 23.3% diabetic). Mean systolic blood pressure was 155Ϯ21 mm Hg, and mean diastolic blood pressure was 83Ϯ11 mm Hg. The mean Modification of Diet in Renal Disease estimated glomerular filtration rate was 32Ϯ11 mL/min per 1.73 m 2 . Change in renal function was measured using reciprocal creatinine plots and the dichotomous combined end point of Ն25% decline in renal function or start of renal replacement therapy. After stepwise multivariate analysis, aortic pulse wave velocity was independently associated with gradient of reciprocal creatinine plot (rϭ0.46; Pϭ0.014). In multivariate analysis of the end point of Ն25% decline in renal function or start of renal replacement therapy, independent predictors were aortic pulse wave velocity (rϭ0.48; Pϭ0.002), systolic blood pressure (rϭ0.17; Pϭ0.039), and urine protein:creatinine ratio (rϭ0.20; Pϭ0.021). We, therefore, conclude that aortic stiffening is independently associated with rate of change in renal function in patients with chronic kidney disease stages 3 and 4. (Hypertension. 2010;55:1110-1115.) Key Words: aorta Ⅲ pulse pressure Ⅲ microvessels Ⅲ kidney Ⅲ creatinine Ⅲ pulse pressure Ⅲ renal insufficiency C hronic kidney disease (CKD) is a common condition, affecting 10% to 13% of the population of the United States, 1 associated with a dramatically increased cardiovascular (CV) mortality, which increases with severity of renal impairment. This excess CV risk is in part attributed to an increase of traditional risk factors among people with CKD 2 but may also relate to the complex metabolic and vascular changes of CKD, including arterial stiffening. Aortic stiffness increases progressively as renal function declines 3 and has been independently associated with CV mortality in patients with renal failure. 4,5 Although much research has investigated the role of aortic stiffening in the causation of CV disease in patients with CKD, less attention has been paid to its potential etiologic role in the causation and progression of renal impairment. Aortic stiffening causes increased systolic blood pressure (BP; SBP) and widened pulse pressure (PP), both factors associated in longitudinal studies with increased rate of decline of renal function. 6,7 In addition, aortic stiffening results in loss of the dampening of ventricular ejection and could lead ...

The structural, chemical and electronic changes of ceria as a function of decreasing particle size have been studied: at sizes below 5 nm the total amount of reducible oxygen dramatically increases due to superoxide formation on the ceria surface, a result indicative of a size dependent oxygen buffering capacity.

Background Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis [UC]. We sought to define the effectiveness and adverse effects of tofacitinib in a real-world cohort. Methods We conducted a retrospective observational cohort study of 134 patients with UC [64% male; median age 37 years [range 16–81]; 83% of patients had previously received at least one biologic] treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index [SCCAI] or partial Mayo score [PMS], depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3and SCCAI ≤2 or a PMS ≤1, respectively. Results Overall, 74% (88/119; 95 confidence interval [CI] 65–81%] patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% [47/108; 95% CI 3453%] patients at Week 26. Primary non-response was independently associated with younger age [p = 0.014] and higher C-reactive protein [CRP] levels at baseline [p = 0.004]. Only 23% [3/13] of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% [27/134; 95% CI 1428%] of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred. Conclusions In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.