Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Preliminary study on the effects of treatment for breast cancer: immunological markers as they relate to quality of life and neuropsychological performance.

BACKGROUND: Immunological biomarkers were related to quality of life and neuropsychological performance in women recently diagnosed with breast cancer through the first six months of treatment. A comparison group of breast cancer survivors in remission were also evaluated. METHOD: Twenty women newly diagnosed with breast cancer and 26 breast cancer survivors at least a year after treatment were evaluated four times over a course of six to 8 months. The assessments included quality-of-life, emotional and spiritual well-being, sleep quality, computerized neuropsychological performance, and cytokine immunology biomarkers using flow cytometry. The principal immunological markers examined were the CD4+, CD8+, and CD16+ counts. RESULTS: Although equivalent at enrollment, active treatment women reported higher anxiety, depression, poorer quality-of-life, and poorer processing speed and accuracy on memory, logical processes, and coding neuropsychological tasks. They also had significantly higher CD8+ and CD16+ cell count levels during treatment over the next six to eight months than comparison group women in remission. Women undergoing chemotherapy as well during treatment phase also had a significant decline in CD4+ counts. Higher percent CD8+ levels during treatment was associated with poorer quality of life and more depression, while higher CD4+ and CD8+ were associated with poorer neuropsychological memory and processing speed performance. CONCLUSION: Significant increases in CD8+ is a sensitive biomarker of a broad range of poorer quality-of-life and neurocognitive functioning outcomes during breast cancer treatment, especially in women undergoing chemotherapy. Quality of life should be monitored in breast cancer patients and psychosocial support made available as a standard of care.

Do Solvated Electrons (e(aq)⁻) Reduce DNA Bases? A Gaussian 4 and Density Functional Theory-Molecular Dynamics Study.

The solvated electron (e(aq)⁻) is a primary intermediate after an ionization event that produces reductive DNA damage. Accurate standard redox potentials (E(o)) of nucleobases and of e(aq)⁻ determine the extent of reaction of e(aq)⁻ with nucleobases. In this work, E(o) values of e(aq)⁻ and of nucleobases have been calculated employing the accurate ab initio Gaussian 4 theory including the polarizable continuum model (PCM). The Gaussian 4-calculated E(o) of e(aq)⁻ (-2.86 V) is in excellent agreement with the experimental one (-2.87 V). The Gaussian 4-calculated E(o) of nucleobases in dimethylformamide (DMF) lie in the range (-2.36 V to -2.86 V); they are in reasonable agreement with the experimental E(o) in DMF and have a mean unsigned error (MUE) = 0.22 V. However, inclusion of specific water molecules reduces this error significantly (MUE = 0.07). With the use of a model of e(aq)⁻ nucleobase complex with six water molecules, the reaction of e(aq)⁻ with the adjacent nucleobase is investigated using approximate ab initio molecular dynamics (MD) simulations including PCM. Our MD simulations show that e(aq)⁻ transfers to uracil, thymine, cytosine, and adenine, within 10 to 120 fs and e(aq)⁻ reacts with guanine only when a water molecule forms a hydrogen bond to O6 of guanine which stabilizes the anion radical.