Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience.

IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4-128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.

Effect of stress on clinical reasoning during simulated ambulatory consultations.

BACKGROUND: The goal of this study was to examine the impact of subjective and physiological stress responses on medical students' diagnostic reasoning and communication skills. METHOD: A prospective randomized quantitative study was undertaken, looking at ambulatory consultations in internal medicine. On the first day (baseline day), volunteer year 6 students (n = 41) participated in a simulated ambulatory consultation with standardized patients (SPs). On the second day (study day), one week later, they were randomly assigned to two groups: a low stress (n = 20) and a high stress (n = 21) simulated ambulatory consultation. Stress was measured using validated questionnaires and salivary cortisol. The SPs assessed the students' reasoning and communication. The students completed assessments of their clinical reasoning after the consultations. RESULTS: Although stress measures were all significantly higher in the high-stress condition (all p < 0.05), no differences were found in diagnostic accuracy and justification scores. However, correlational analyses revealed a negative correlation between multiple-stress measures and the students' ability to generate arguments for differential diagnoses. CONCLUSION: Stress was associated with impairments in clinical reasoning, of a nature typically suggestive of premature closure.

Indicators of iron status are correlated with adiponectin expression in adipose tissue of patients with morbid obesity.

AIM: The aim of this study was to assess interactions between glucose and iron homoeostasis in the adipose tissue (AT) of obese subjects. METHODS: A total of 46 obese patients eligible for bariatric surgery were recruited into the study. Anthropometric and biochemical characteristics were assessed, and biopsies of subcutaneous (SCAT) and visceral adipose tissue (VAT) performed. The mRNA levels of genes involved in iron and glucose homoeostasis were measured in their AT and compared with a pool of control samples. RESULTS: Gene expression of hepcidin (HAMP) was significantly increased in the SCAT and VAT of obese patients, while transferrin receptor (TFRC) expression was reduced, compared with non-obese controls, suggesting a higher iron load in obese patients. Also, mRNA levels of adiponectin (ADIPOQ) were decreased in both SCAT and VAT in obese patients, and correlated negatively with hepcidin expression, while adiponectin expression was positively correlated with TFRC expression in both SCAT and VAT. Interestingly, TFRC expression in VAT correlated negatively with several metabolic parameters, such as fasting blood glucose and LDL cholesterol. CONCLUSION: Iron content appears to be increased in the SCAT and VAT of obese patients, and negatively correlated with adiponectin expression, which could be contributing to insulin resistance and the metabolic complications of obesity.