Multicenter analysis to assess risk of major adverse cardiac events in patients undergoing high-sensitivity troponin testing in the emergency department.

Study hypothesis: Our objective was to evaluate 30-day major adverse cardiac events (MACE) in emergency department (ED) patients with normal high-sensitivity troponins (hs-trop). We hypothesized that MACE rates would be <1% in patients with (1) two normal troponins regardless of change in troponin (delta) and (2) index hs-trop below the limit of quantitation (LOQ) regardless of the institution modified HEART score. Methods: This was a multicenter, retrospective, cohort study of adult patients who presented to 1 of 18 EDs between July 2020 and April 2021 with acute coronary syndrome as defined by an institutional-modified HEART score completed by their treating physician or midlevel, no evidence of ST-elevation myocardial infarction, and an index or serial gender-adjusted hs-trop within normal limits. The primary outcome was MACE within 30 days of index ED encounter. A detailed case review was then performed for those patients experiencing a MACE. Results: Of the 9084 patients who had single or serial normal troponins, 31 (0.34%; confidence interval [CI] 0.23%-0.48%) experienced MACE. Of the 6140 patients with 2 normal hs-trop and a delta (change in troponin) <4, 27 patients (0.44%; CI 0.29%-0.64%) experienced MACE. Only 1 of the 69 patients with 2 normal hs-trop results but delta (change in troponin) ≥ 4 (1.45%; CI 0.04%-7.81%) suffered MACE. This patient was classified as non-low risk by our institutional HEART score. Of 7498 patients with an index hs-trop 

Discrepancies in Physician and Coroner Findings in Cases of Fatal Suspected Physical Child Abuse.

OBJECTIVES: As mandated reporters of suspected abuse, physicians must consider abuse when a child dies unexpectedly. Subsequently, a coroner or medical examiner determines the manner of death (MOD) and cause of death (COD). Accurate diagnoses and determinations are important for social safety and justice. This study described discrepancies between physicians' and coroners' findings in cases of fatal suspected physical child abuse. METHODS: This study was a single-institution, retrospective review. All children 6 years or younger who died in a pediatric emergency department from October 2006 to January 2013 with a coroner report were included in this study. Coroner reports, MODs, and CODs were reviewed. Skeletal survey results were compared with coroners' findings. RESULTS: One hundred twenty-nine children were included. The MODs included the following: undetermined, 63 (49%); accident, 32 (25%); natural, 31 (24%); and homicide, 3 (2%). Thirty-three (26%) of the 129 patients had abuse suspected at the time of death in the emergency department; in this subset, MODs were as follows: undetermined, 16 (48%); accident, 8 (24%); natural, 6 (18%); and homicide, 3 (9%). Sudden infant death syndrome or sudden unexpected death was the most common COD in all children (68, 55%). Skeletal surveys were positive in 12 children with 29 fractures identified; 8 (28%) of the 29 fractures were corroborated on autopsy findings. Of the 12 children with positive skeletal survey findings, only 1 was ruled a homicide. CONCLUSIONS: We found discrepancies between coroner determination of homicide and abuse suspected by physicians, especially among children with fractures. Improved communication between agencies in cases of fatal child abuse is needed.

Variants in an Hdac9 intronic enhancer plasmid impact Twist1 expression in vitro.

Skin tumor susceptibility 5 (Skts5) was previously mapped to mouse chromosome 12 through linkage analysis of skin tumor susceptible Mus musculus (NIH/Ola-S) and skin tumor resistant outbred Mus spretus (SPRET/Out-R) mice. Hdac9 was identified as a potential candidate for Skts5 based on conserved non-synonymous sequence variants and expression analyses. Studies by others identified an enhancer in human HDAC9 that correlated with TWIST1 expression. We identified 45 sequence variants between NIH/Ola-S and SPRET/Out-R mice from the orthologous region of the human HDAC9 enhancer. Variants mapping to intron 18 differentially affected luciferase expression in vitro. NIH/Ola-S clones showed an approximate 1.7-fold increased luciferase expression relative to vector alone or the equivalent clones from SPRET/Out-R-R. Furthermore, cells transfected with a portion of the NIH/Ola-S intron induced 2.2-fold increases in Twist1 expression, but the same region from SPRET/Out-R mice resulted in no up-regulation of Twist1. In silico transcription factor analyses identified multiple transcription factors predicted to differentially bind NIH/Ola-S and SPRET/Out-R polymorphic sites. Chromatin immunoprecipitation studies of two transcription factors, Gata3 and Oct1, demonstrated differential binding between NIH/Ola-S and SPRET/Out-R plasmids that corroborated the in silico predictions. Together these studies provide evidence that the murine orthologous region to a human HDAC9 enhancer also acts as a transcriptional enhancer for mouse Twist1. As ectopic sequence variants between NIH/Ola-S and SPRET/Out-R differentially impacted luciferase expression, correlated with Twist1 expression in vitro, and affected Gata3 and Oct1 binding, these variants may explain part of the observed differences in skin tumor susceptibility at Skts5 between NIH/Ola-S and SPRET/Out-R.