Sichere Lagekontrolle von Magensonden: ein oft unterschätztes Thema zur Vermeidung potenziell schwerwiegender Komplikationen

Die Anaesthesiologie - Die Anlage einer Magensonde im OP oder auf einer Intensivstation (ITS) stellt eine alltäglich durchgeführte Prozedur dar. Obwohl die Sonde häufig durch...     

Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

The Venom of Philippine Tarantula (Theraphosidae) Contains Peptides with Pro-Oxidative and Nitrosative-Dependent Cytotoxic Activities against Breast Cancer Cells (MCF-7) In Vitro

Background: Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease. Methods: Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels. Results: The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2−) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation. Conclusion: These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy.