Spin and fragility in randomised controlled trials in the anaesthesia literature: a systematic review.

BACKGROUND: Given variable frequency of misleading reports and the potential for spin (a way of describing results that can mislead readers) to influence interpretation of randomised controlled trials (RCTs), we have undertaken a spin reassessment. We evaluated the quality of recent literature in anaesthesia journals by assessing the presence of spin and calculating the fragility index. METHODS: This systematic review of randomised trials was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched via PubMed® from January 1, 2019 to January 1, 2021 to identify all RCTs published in one of the 20 anaesthesia journals with the highest journal impact factors during this time. Four pairs of reviewers assessed articles independently for eligibility using a piloted electronic data extraction form. They assessed the presence of spin in statistically negative RCTs and calculated the fragility index for statistically positive RCTs. RESULTS: Of the 802 screened records, 162 (20%) articles were analysed for spin, and 65 (8%) trials were analysed for fragility index. For the statistically negative studies, 66 articles (40%) presented spin; 89% of these occurrences of spin were described in the conclusion of the abstract. The primary type of spin was the highlight of secondary outcomes (67%). For statistically positive trials, the median fragility index was 4 [1-8]. CONCLUSIONS: This systematic review showed that 40% of statistically negative trials in high-impact anaesthesia journals could mislead readers. For statistically positive RCTs, the results relied on few subjects, with a median fragility index of 4 [1-8]. Efforts must be continued to reduce spin and fragility in the medical literature.

Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice.

The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.