Intramural and subserosal echogenic foci on US in large-bowel intussusceptions: prognostic indicator for reducibility?

BACKGROUND: In large-bowel intussusceptions, several US signs are known to indicate a lower likelihood of reducibility by enema. US can demonstrate echogenic dots or lines (foci) in the bowel wall, which might indicate an ischemic bowel. OBJECTIVE: To determine the presence of echogenic intramural and subserosal foci in large-bowel intussusceptions and to evaluate the degree of correlation with reducibility. MATERIALS AND METHODS: Between 2001 and 2008, 74 consecutive US examinations were retrospectively evaluated by two pediatric radiologists for intramural and subserosal echogenic foci, or trapped gas, in the intussusception. The degree of correlation between the sonographic findings and reducibility was evaluated. RESULTS: Of 73 intussusceptions examined by US, 56 (76%) were reducible and 17 (23%) were not reducible. Out of 10 intussusceptions with intramural gas, 11 with subserosal gas, and 14 with intramural and subserosal gas, 8 (80%), 6 (56%), 9 (64%), respectively, were not reducible. The presence of intramural gas or subserosal gas or both predicted a lower chance of reduction, but with regard to the effect of these findings together, intramural gas was the only significant predictor. CONCLUSION: Having intramural gas in large-bowel intussusception significantly decreases the chance of reduction.

Management of infusion reactions in clinical trials and beyond: the US and EU perspectives

Monoclonal antibodies have expanded our cancer-fighting armamentarium in both the United States and Europe. While in general, monoclonal antibodies are well tolerated and do not have significant overlapping side effects with traditional cytotoxic agents, severe infusion reactions (IRs)--sometimes severe enough to be life threatening--have been reported. The pathophysiology of severe infusion reactions associated with monoclonal antibodies is poorly understood, but mechanisms are beginning to be elucidated. Geographic differences in the incidence of IRs have become apparent. Understanding the risk, recognizing the signs and symptoms, and being ready to promptly manage severe IRs are key for the clinician to avoid unnecessarily discontinuing these effective anticancer agents and prevent potentially tragic consequences for their patients. To date, clinical trials have incorporated monoclonal antibodies into combinations with standard cytotoxic regimens; it is expected that in time clinical trials will be testing promising new combinations utilizing multiple targeted agents, resulting in improved toxicity profiles and efficacy for cancer patients.

Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics

PURPOSE To explore whether population-related pharmacogenomics contribute to differences in patient outcomes between clinical trials performed in Japan and the United States, given similar study designs, eligibility criteria, staging, and treatment regimens. METHODS We prospectively designed and conducted three phase III trials (Four-Arm Cooperative Study, LC00-03, and S0003) in advanced-stage, non-small-cell lung cancer, each with a common arm of paclitaxel plus carboplatin. Genomic DNA was collected from patients in LC00-03 and S0003 who received paclitaxel (225 mg/m(2)) and carboplatin (area under the concentration-time curve, 6). Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism. Results were assessed by Cox model for survival and by logistic regression for response and toxicity. Results Clinical results were similar in the two Japanese trials, and were significantly different from the US trial, for survival, neutropenia, febrile neutropenia, and anemia. There was a significant difference between Japanese and US patients in genotypic distribution for CYP3A4*1B (P = .01), CYP3A5*3C (P = .03), ERCC1 118 (P < .0001), ERCC2 K751Q (P < .001), and CYP2C8 R139K (P = .01). Genotypic associations were observed between CYP3A4*1B for progression-free survival (hazard ratio [HR], 0.36; 95% CI, 0.14 to 0.94; P = .04) and ERCC2 K751Q for response (HR, 0.33; 95% CI, 0.13 to 0.83; P = .02). For grade 4 neutropenia, the HR for ABCB1 3425C-->T was 1.84 (95% CI, 0.77 to 4.48; P = .19). CONCLUSION Differences in allelic distribution for genes involved in paclitaxel disposition or DNA repair were observed between Japanese and US patients. In an exploratory analysis, genotype-related associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. This common-arm approach facilitates the prospective study of population-related pharmacogenomics in which ethnic differences in antineoplastic drug disposition are anticipated.

Expected and Unexpected Consequences of the Educational Expansion in Europe and the US. Theoretical approaches and empirical findings in comparative perspective

A main mechanism behind the change in European and North American societies in the second half of the 20th century is the educational expansion, i.e. the increase in educational opportunities and the higher demand for education. Whereas other abstract social processes like modernization have been widely theorized in social science literature, the educational expansion and its consequences in particular have not been well studied. Therefore the main aim of this compilation is to deal with the question of whether the demands of the educational reforms have been fulfilled and which other consequences the educational expansion has had. This book will focus on consequences of the educational expansion for individuals and their life courses as well as for the social structure and other societal areas such as culture and politics. Aspects that will be analysed in the light of educational expansion include participation in education, educational inequalities, labour market outcomes, educational returns, and gender differences as well as crime, life expectancy, and lifestyles. Countries analysed in the book include West European countries like Germany, France, Italy and Spain, East European countries (Hungary, Poland, and the Czech Republic) as well as the US.