Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948)

New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9–79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7–66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5–91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6–93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP

Molecular epidemiology of Candida albicans and Candida glabrata strains isolated from intensive care unit patients in Poland

Over the last decades, Candida spp have been responsible for an increasing number of infections, especially in patients requiring intensive care. Knowledge of local epidemiology and analysis of the spread of these pathogens is important in understanding and controlling their transmission. The aim of this study was to evaluate the genetic diversity of 31 Candida albicans and 17 Candida glabrata isolates recovered from intensive care unit patients from the tertiary hospital in Krakow between 2011-2012. The strains were typed by random amplified polymorphic DNA (RAPD) polymerase chain reaction using five primers (CD16AS, HP1247, ERIC-2, OPE-3 and OPE-18). The results of the present investigation revealed a high degree of genetic diversity among the isolates. No clonal relationship was found among the C. albicans strains, whereas two C. glabrata isolates were identical. The source of Candida infection appeared to be mostly endogenous; however, the presence of two clonal C. glabrata strains suggested the possibility of cross-transmission of these pathogens. Our study confirmed the high discriminatory power of the RAPD technique in the molecular typing of Candida clinical isolates. This method may be applied to the evaluation of transmission routes of pathogenic fungi on a local level

Conformation-Related Reaction Efficiency of Glutarimides with Phenyllithium. Structures of 3,3,5,5-Tetramethylglutarimide and 2-Hydroxy-2-phenyl-3,3,5,5-tetramethyl-6-piperidone. X-ray and Theoretical Study

Crystal structures of 3,3,5,5-tetramethylglutarimide [3,3,5,5-tetramethylazacyclohexane-2,6-dione] (8) and the product of its reaction with phenyllithium, 2-hydroxy-2-phenyl-3,3,5,5-tetramethyl-6-piperidone (9), have been determined by X-ray structural methods [(8), monoclinic, P21/c, a = 7.715 (2), b = 11.136 (2), c = 11.707 (2) Å, \beta = 105.63 (3)°; (9), triclinic, P\overline 1, a = 6.1685 (6), b = 11.1475 (10), c = 11.526 (2) Å, \alpha = 117.100 (10), \beta = 103.390(10), \gamma = 91.288 (7)°]. Molecular structures of three different glutarimides are discussed. Their energy optimal structures were determined with the use of ab initio calculations. The results of crystallographic and theoretical studies show that the conformational changes in glutarimide introduced by substitution with methyl groups resulted in electron-charge distribution changes. These differences in charge distribution are the reason for the observed variation in yields of the reaction of glutarimides with phenyllithium.</jats:p