Randomized Phase 2b Trial of Tofacitinib (CP‐690,550) in De Novo Kidney Transplant Patients: Efficacy, Renal Function and Safety at 1 Year

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93568/1/j.1600-6143.2012.04127.x.pd

Expansions of cytotoxic CD4+CD28− T-cells drive excess cardiovascular mortality in rheumatoid arthritis and other chronic inflammatory conditions and are triggered by CMV infection

A large proportion of cardiovascular pathology results from immune-mediated damage, including systemic inflammation and cellular proliferation, which cause a narrowing of the blood vessels. Expansions of cytotoxic CD4+ T-cells characterized by loss of CD28 (‘CD4+CD28− T-cells’ or ‘CD4+CD28null cells’) are closely associated with cardiovascular disease (CVD), in particular coronary artery damage. Direct involvement of these cells in damaging the vasculature has been demonstrated repeatedly. Moreover, CD4+CD28− T-cells are significantly increased in rheumatoid arthritis (RA) and other autoimmune conditions. It is striking that expansions of this subset beyond 1-2% occur exclusively in CMV-infected people. CMV infection itself is known to increase the severity of autoimmune diseases, in particular RA and has also been linked to increased vascular pathology. A review of the recent literature on immunological changes in cardiovascular disease, RA, and CMV infection provides strong evidence that expansions of cytotoxic CD4+CD28− T-cells in RA and other chronic inflammatory conditions are limited to CMV-infected patients and driven by CMV-infection. They are likely to be responsible for the excess cardiovascular mortality observed in these situations. The CD4+CD28− phenotype convincingly links CMV infection to cardiovascular mortality based on a direct cellular-pathological mechanism rather than epidemiological association

Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/- 13 years, 57% male, 21% diabetics, mean eGFR 51 +/- 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients

Plasma 25-Hydroxyvitamin D Concentration and Metabolic Syndrome Among Middle-Aged and Elderly Chinese Individuals

OBJECTIVE—To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome in the Chinese population. RESEARCH DESIGN AND METHODS—Plasma 25(OH)D was measured in a cross-sectional sample of 1,443 men and 1,819 women aged 50–70 years from Beijing and Shanghai. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Fasting plasma glucose, insulin, lipid profile, A1C, and inflammatory markers were measured. RESULTS—The geometric mean of plasma 25(OH)D was 40.4 nmol/l, and percentages of vitamin D deficiency [25(OH)D <50 nmol/l] and insufficiency [50 ≤ 25(OH)D <75 nmol/l] were 69.2 and 24.4%, respectively. Compared with the highest 25(OH)D quintile (≥57.7 nmol/l), the odds ratio for metabolic syndrome in the lowest quintile (≤28.7 nmol/l) was 1.52 (95% CI 1.17–1.98, $P_{trend} = 0.0002$) after multiple adjustment. Significant inverse associations also existed between 25(OH)D and individual metabolic syndrome components plus A1C. Moreover, we observed significant inverse associations of 25(OH)D with fasting insulin and the insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) in overweight and obese individuals (BMI ≥24 kg/m2) but not in their normal-weight counterparts (test for interaction: $P = 0.0363$ and $0.0187$ for insulin and HOMA-IR, respectively). CONCLUSIONS—Vitamin D deficiency is common in the middle-aged and elderly Chinese population, and a low 25(OH)D level is significantly associated with an increased risk of having metabolic syndrome and insulin resistance. Prospective studies and randomized clinical trials are warranted to determine the role of 25(OH)D in the development of metabolic syndrome and related metabolic diseases

The effect of tobacco smoking and treatment strategy on the one-year mortality of patients with acute non-ST-segment elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate whether a previously shown survival benefit resulting from routine early invasive management of unselected patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) may differ according to smoking status and age.</p> <p>Methods</p> <p>Post-hoc analysis of a prospective observational cohort study of consecutive patients admitted for NSTEMI in 2003 (conservative strategy cohort [CS]; n = 185) and 2006 (invasive strategy cohort [IS]; n = 200). A strategy for transfer to a high-volume invasive center and routine early invasive management was implemented in 2005. Patients were subdivided into current smokers and non-smokers (including ex-smokers) on admission.</p> <p>Results</p> <p>The one-year mortality rate of smokers was reduced from 37% in the CS to 6% in the IS (p < 0.001), and from 30% to 23% for non-smokers (p = 0.18). Non-smokers were considerably older than smokers (median age 80 vs. 63 years, p < 0.001). The percentage of smokers who underwent revascularization (angioplasty or coronary artery bypass grafting) within 7 days increased from 9% in the CS to 53% in the IS (p < 0.001). The corresponding numbers for non-smokers were 5% and 27% (p < 0.001). There was no interaction between strategy and age (p = 0.25), as opposed to a significant interaction between strategy and smoking status (p = 0.024). Current smoking was an independent predictor of one-year mortality (hazard ratio 2.61, 95% confidence interval 1.43-4.79, p = 0.002).</p> <p>Conclusions</p> <p>The treatment effect of an early invasive strategy in unselected patients with NSTEMI was more pronounced among smokers than non-smokers. The benefit for smokers was not entirely explained by differences in baseline confounders, such as their younger age.</p

Association of Serum 25-Hydroxyvitamin D Levels with Markers for Metabolic Syndrome in the Elderly: A Repeated Measure Analysis

The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects

Transplantation in Diabetic Kidney Failure Patients: Modalities, Outcomes, and Clinical Management

Diabetes mellitus (DM) is a common and devastating disease, affecting up to 19.3 million Americans. It is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States. Diabetic patients with ESRD have a high incidence of cardiovascular disease and death. For those kidney transplant patients with no history of DM prior to transplantation, the development of new onset diabetes after transplantation (NODAT) also poses a serious threat to both graft and patient survival. Kidney transplantation is the best renal replacement option for diabetic ESRD and has the potential to halt the progression of cardiovascular diseases. Early referral for transplant evaluation is essential for pre-emptive or early kidney transplantation in this cohort of patients. In type 1 DM patients with ESRD, simultaneous pancreas and kidney transplantation (SPK) should be encouraged; and in patients facing prolonged waiting time for SPK transplantation but with an available living donor, living donor kidney transplantation followed by pancreas after kidney transplantation (PAK) is a suitable alternative. Islet transplantation in type 1 diabetics is deemed experimental by Medicare, and easy access to this modality remains restricted to qualified patients enrolled in clinical trials or with private insurance. The optimal management of kidney transplant patients with pre-existent DM or NODAT involves a multi-pronged approach consisting of pharmacological and nonpharmacological intervention to address all potential cardiovascular risk factors such as glycemic and lipid control, blood pressure control, weight loss, and smoking cessation. Finally, re-transplantation should be recommended in suitable kidney transplant patients when the kidney allograft demonstrates continuous and progressive decline in function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79210/1/j.1525-139X.2010.00708.x.pd