KRAS Mutations Are Associated with Shortened Survival in Patients with Epithelioid Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural surface that includes three major histologic subtypes, epitheliod, sarcomatoid and biphasic. Epithelioid mesothelioma is usually associated with better prognosis. The genetic mechanisms driving MPM, the possible target mutations and the correlation with overall survival remain largely unsettled. We performed target exome sequencing in 29 cases of MPM aimed at identifying somatic mutations and, eventually, their correlation with phenotypic traits and prognostic significance. We found that KRAS mutations, occurring in 13.7% of cases, were associated with shortened median survival (7.6 versus 32.6 months in KRAS wild-type; p = 0.005), as it was the occurrence of any ≥3 mutations (7.6 versus 37.6 months; p = 0.049). Conversely, the presence of KDR single nucleotide polymorphism p.V297I (rs2305948) resulted in a favorable variable for survival (NR versus 23.4 months; p = 0.026). With the intrinsic limitations of a small number of cases and patient heterogeneity, results of this study contribute to the characterization of the mutation profile of MPM and the impact of selected somatic mutations, and possibly KDR polymorphism, on prognosis.

Multicenter Evaluation of the Idylla NRAS-BRAF Mutation Test in Metastatic Colorectal Cancer.

Treatment of colorectal cancer (CRC) with monoclonal antibodies against epidermal growth factor receptor requires the assessment of the mutational status of exons 2, 3, and 4 of the NRAS and KRAS oncogenes. Moreover, the mutational status of exon 15 of the BRAF oncogene is a marker of poor prognosis in CRC. The Idylla NRAS-BRAF Mutation Test is a reliable, simple (<2 minutes hands-on time), and quick (<2 hours turnaround time) sample-to-result solution, enabling the detection of clinically relevant mutations in NRAS (18 mutations) and BRAF (5 mutations). A multicenter study was conducted in 14 centers using the Idylla NRAS-BRAF Mutation Test to assess the NRAS and BRAF mutational status of 418 formalin-fixed, paraffin-embedded tissue samples from CRC patients. Results were compared with those obtained earlier by routine reference methods, including next-generation sequencing, pyrosequencing, mass spectrometry-based assays, PCR-based assays, and Sanger sequencing. In case of discordance, additional tests were performed by digital droplet PCR. Overall, after testing confirmation and excluding invalids/errors by design, concordances between the Idylla NRAS-BRAF Mutation Test and the reference test results were found in almost perfect agreement. In conclusion, the Idylla NRAS-BRAF Mutation Test enables the routine detection of all NRAS and BRAF mutations deemed clinically relevant according to the latest clinical guidelines, without necessitating molecular expertise or infrastructure.

Professional oral hygiene procedures do not influence plasma glucose levels in systemically healthy individuals: a short-term, randomised, controlled trial.

PURPOSE: The treatment of gingival inflammation is associated with improved glycaemic control in diabetic patients. The goal of this parallel-randomised controlled trial (RCT) was to test the shortterm effects of professional oral hygiene procedures on plasma glucose levels in systemically healthy individuals. MATERIALS AND METHODS: Systemically healthy individuals with gingivitis and no sign of periodontitis were enrolled at a private practice in Italy. Patients were randomised to either a 1 hour (h) session of professional oral hygiene procedures or to 1 h in the waiting room. Not fasting blood glucose levels were assessed by a blind examiner at baseline (T0), 1 h (T1) and 2 h (T2) after procedures and finally 1 week after (T3). Oral hygiene procedures were then performed also in the control group. RESULTS: Twenty patients were randomly allocated to each group. There were no drop-outs. Blood glucose levels at T0 (P = 0.0001) and time of measurement (P = 0.0001) were statistically significant, while oral hygiene procedures were not (mean difference between groups 0.77 mg/dl, 95%CI -2.64 mg/dl; 4.18 mg/dl, P = 0.6581). Mean blood glucose levels decreased between T0 and T1, were stable between T1 and T2 and showed similar levels to baseline after 1 week (T3) for both groups. CONCLUSION: This short-term RCT showed that professional oral hygiene procedures were not able to influence plasma glucose levels in individuals with gingivitis, but otherwise systemically healthy.