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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.
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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.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Trastornos del Conocimiento/epidemiología , Citocinas/sangre , Calidad de Vida/psicología , Adulto , Biomarcadores/sangre , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/psicología , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Resultado del TratamientoRESUMEN
The solvated electron (e(aq)â») 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)â» determine the extent of reaction of e(aq)â» with nucleobases. In this work, E(o) values of e(aq)â» 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)â» (-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)â» nucleobase complex with six water molecules, the reaction of e(aq)â» with the adjacent nucleobase is investigated using approximate ab initio molecular dynamics (MD) simulations including PCM. Our MD simulations show that e(aq)â» transfers to uracil, thymine, cytosine, and adenine, within 10 to 120 fs and e(aq)â» reacts with guanine only when a water molecule forms a hydrogen bond to O6 of guanine which stabilizes the anion radical.