Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas

Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas, and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine (5hmC) and higher 5-methylcytosine (5mC) levels, as well as increased dimethylation of histone H3K79. Mutations in IDH1 or IDH2 were associated with longer overall survival (p = 0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (p = 0.021). IDH1 and IDH2 mutations are significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2,309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors

Managing cardiovascular disease risk in patients treated with antipsychotics: a multidisciplinary approach

BACKGROUND: The use of antipsychotic medication in the United States and throughout the world has greatly increased over the last fifteen years. These drugs have significant side effect burdens, many of them relating to cardiovascular health. OBJECTIVE: To review the available evidence on the major cardiovascular issues that arise in patients taking antipsychotic medication. METHOD: A PubMed literature review was performed to identify recent meta-analyses, review articles, and large studies. Further articles were identified through cited papers and based on expert consultation when necessary. RESULTS: CLINICAL GUIDANCE ON THE FOLLOWING ADVERSE EFFECTS AND ANTIPSYCHOTICS WAS REVIEWED: electrocardiogram (ECG) changes, (specifically, prolonged QT and risk of torsades de pointes), weight gain, dyslipidemia, metabolic syndrome, and myocarditis. Specific attention was paid to monitoring guidelines and treatment options in the event of adverse events, including dose change, medication switch, or adjuvant therapy

The Implications of Fruit and Vegetable Consumption in Patients with Diabetes

It is widely accepted that the management of diabetes should include both pharmacologic and lifestyle modifications. However, these recommendations are not readily or consistently incorporated into clinical practice. Current guideline recommendations encourage an emphasis on nutrient-dense foods, which include those foods that tend to be high in flavonoids such as fruits and vegetables. Polyphenolic compounds in fruits and vegetables have been shown to affect the same biological processes as certain classes of pharmacological therapy used in the treatment of diabetes. A better understanding of the benefits of these compounds may help healthcare professionals, including pharmacists, communicate dietary recommendations to patients