Tumor and serum levels of per- and polyfluoroalkyl (PFAS) in hepatobiliary and gastrointestinal malignancy.

BACKGROUND: There has been significant controversy over the carcinogenic potential of per- and polyfluoroalkyl substances (PFAS). STUDY DESIGN: A total of 37 serum and tumor samples from patients with hepatobiliary and gastrointestinal malignancy were tested for 24 analytes of PFAS. RESULTS: At least one PFAS analyte was found in 97% (36/37) of the serum samples and 41% (15/37) of the tumor samples. The serum Perfluorooctanesulfonic acid (PFOS) levels were significantly higher than the national levels (6.77 ng/mL vs. 5.20 ng/mL; p = 0.038). Patients with PFOS in tumor samples had significantly higher levels in serum when compared to tumor samples without PFOS (9.4 ng/mL vs 5.5 ng/mL; p = 0.015). CONCLUSIONS: Patients were found to have significantly higher levels of PFOS when compared to the reported national levels. Additionally, the patients with higher serum levels of PFOS also had tumor positive samples.

Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2020: A Systematic Review.

BACKGROUND: Termination of a clinical trial before the maximum planned sample size is accrued can occur for multiple valid reasons but has implications for the interpretation of results. We undertook a systematic review of contemporary acute stroke trials to document the prevalence of and reasons for early termination. METHODS: We searched MEDLINE for randomized controlled trials of acute stroke therapies published between 2013 and 2020 in 9 major clinical journals. Manuscripts describing the primary results of phase 2 and phase 3 trials of acute stroke care were included. Data on study characteristics and adherence to CONSORT reporting guidelines were abstracted and summarized using descriptive statistics. Where feasible, we compared treatment effect sizes between trials terminated early and those not terminated early. RESULTS: Of 96 randomized controlled trials, 39 (41%) were terminated early, 84 (88%) had a data and safety monitoring board, and 57 (59%) reported a prespecified statistical stopping rule. Among the 39 trials terminated early, 10 were discontinued for benefit, 10 due to logistical issues, 8 for futility, 6 because of newly available evidence, 1 for harm, and 4 for other or a combination of reasons. The median percentage of the maximum planned sample size accrued among trials terminated early was 63% (range, 8%-89%). Only 55% of trials (53 of 96) reported whether interim efficacy analyses were conducted, as recommended by the CONSORT guidelines. When 10 endovascular therapy trials were compared according to early termination status, the effect sizes of trials terminated early for benefit were only modestly larger than those not terminated early. CONCLUSIONS: The high prevalence of early termination in combination with the wide variety of reasons underscores the necessity of meticulous trial planning and adherence to methodological and reporting guidelines for early termination. Registration: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42019128727.