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The fragility index (FI) is a sensitivity analysis of the statistically significant result of a clinical study. It is the number of hypothetical changes in the primary event of one of the two cohorts in a 1-to-1 comparative trial to render the statistically significant result non-significant (ie, to alter the P-value from ≤0.05 to >0.05). The FI can be compared with the patient drop-out rates and protocol violations, which, if much higher than the FI, may arguably suggest less robustness/stability of the trial's results. To illustrate the concept, we have chosen the Term Breech Trial (TBT) as a case study. The TBT results favor planned cesarean birth, as opposed to planned vaginal delivery, in the term singleton fetus with breech presentation. Our analysis shows that the FI of the TBT is 21, which is small in comparison to the number (hundreds) of protocol violations present. Some experts have suggested the inclusion of the FI in data analysis and subsequent discussion of clinical trial data. Routine use of such a metric may be valuable in encouraging readers to maintain a healthy degree of skepticism, especially when interpreting trial results which may directly influence clinical practice., (© 2022 Wiley Periodicals LLC.)

The phytochemical sulforaphane (SF) has gained interest for its apparent association with reduced cancer risk and other cytoprotective properties, at least some of which are attributed to activation of the transcription factor Nrf2. Repair of bulky DNA adducts is important for mitigating carcinogenesis from exogenous DNA damaging agents, but it is unknown whether in vivo treatment with SF affects adduct repair. At 12 h following a single oral dose of 100 mg/kg SF, an almost doubling in activity for repair of pyridyloxobutylated DNA was observed in CD-1 mouse liver nuclear extracts, but not in lung extracts. This change at 12 h in repair activity was preceded by the induction of Nrf2-regulated genes but not accompanied by changes in levels of the specific nucleotide excision repair (NER) proteins XPC, XPA, XPB and p53 or in binding of hepatic XPC, XPA and XPB to damaged DNA. SF also did not significantly alter histone deacetylase activity as measured by acetylated histone H3 levels, or stimulate formation of γ-H2A.X, a marker of DNA damage. A significant reduction in oxidative DNA damage, as measured by 8-OHdG (a biomarker of oxidative DNA damage), was observed only in DNA from the lungs of SF-treated mice 3 h post-dosing. These results suggest that the ability of SF to increase bulky adduct repair activity is organ-selective and is consistent with activation of the Nrf2 signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)