Citations

ABSTRACTBackgroundThe objective of this study was to investigate cardiovascular disease risk factor (cvRF) profiles and compare their trends over 17 years in patients with and without acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).HypothesisTime trends of cvRF are different between ACS and non‐ACS patients.MethodsThis study was a time‐trend analysis from 1994 to 2010 within the Mayo Clinic PCI registry. Outcome measures were incidence and prevalence of cvRF, including the Framingham Risk Score (FRS), at the time of admission for PCI.ResultsAge of non‐ACS patients was higher than that of ACS patients, and age distribution slightly shifted toward older age in both groups (P for trend <0.001). There was no difference in FRS between the 2 groups; however, 10‐year cardiovascular disease risk (%) remained higher in non‐ACS than in ACS patients, decreasing over time. Diastolic blood pressure and high‐density lipoprotein cholesterol were higher in non‐ACS patients, but total cholesterol and low‐density lipoprotein cholesterol were higher in ACS patients, with an improving trend over time. Prevalence of diabetes mellitus, hypertension, and history of hypercholesterolemia were higher in non‐ACS patients, increasing over time. Smoking did not change over time. Use of most medications increased over time in both groups.ConclusionsMost cvRFs and their time trends exhibited statistically significant differences between ACS and non‐ACS patients, except systolic blood pressure, body mass index, and history of myocardial infarction. A new risk‐factor profile assessment may be needed for stratification of PCI patients according to ACS and non‐ACS status. Clinical and public‐health interventions should consider different approaches to ACS and non‐ACS patients.

Diabetes-induced cognitive decline has been recognized in human patients of type 2 diabetes mellitus and mouse model of obesity, but the underlying mechanisms or therapeutic targets are not clearly identified. We investigated the effect of caloric restriction on diabetes-induced memory deficits and searched a molecular mechanism of caloric restriction-mediated neuroprotection. C57BL/6 mice were fed a high-fat diet for 40 weeks and RNA-seq analysis was performed in the hippocampus of high-fat diet-fed mice. To investigate caloric restriction effect on differential expression of genes, mice were fed high-fat diet for 20 weeks and continued on high-fat diet or subjected to caloric restriction (2 g/day) for 12 weeks. High-fat diet-fed mice exhibited insulin resistance, glial activation, blood–brain barrier leakage, and memory deficits, in that we identified neurogranin, a down-regulated gene in high-fat diet-fed mice using RNA-seq analysis; neurogranin regulates Ca 2+ /calmodulin-dependent synaptic function. Caloric restriction increased insulin sensitivity, reduced high-fat diet-induced blood–brain barrier leakage and glial activation, and improved memory deficit. Furthermore, caloric restriction reversed high-fat diet-induced expression of neurogranin and the activation of Ca 2+ /calmodulin-dependent protein kinase II and calpain as well as the downstream effectors. Our results suggest that neurogranin is an important factor of high-fat diet-induced memory deficits on which caloric restriction has a therapeutic effect by regulating neurogranin-associated calcium signaling.

Abstract Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%–43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%–44%) randomized to rituximab. Six (17%; 95% CI, 7%–34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%–29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Clin Cancer Res; 22(2); 319–27. ©2015 AACR.