Challenges and Successes in Introducing Coronary CT Angiography in an Emergency Medicine-Run Observation Unit.

This study was designed to analyze the departmental changes in transitioning the Emergency Department (ED)-run Observation Medicine Unit's routine noninvasive cardiac evaluation from the traditional standard-of-care procedures to coronary computed tomography angiography (CCTA).  While the routine use of CCTA for the evaluation of chest pain has been deemed feasible and safe, provider confidence appears apprehensive, and ordering patterns appear reluctant to change.  We conducted a retrospective analysis of data from two risk-matched cohorts of ED patients who presented with symptoms suggestive of acute coronary syndrome (ACS) but without ischemic electrocardiogram (ECG) changes or positive troponin. Endpoints included length of stay, major adverse cardiovascular event (MACE) rates at 28 days, recidivism rate, and downstream findings on coronary catheterization.  The adoption of CCTA led to a significant reduction in the length of stay for patients in the ED-run Observation Medicine Unit. Provider and nursing education initiatives were crucial in overcoming initial resistance and improving the implementation of CCTA. Post-education, there was a marked increase in the volume of CCTA performed and a decrease in the length of stay, enhancing overall departmental throughput.  The results suggest that CCTA offers a reliable and efficient diagnostic alternative to traditional noninvasive tests, with high diagnostic accuracy contributing to faster decision-making and reduced need for invasive procedures. Continuous education for providers and nursing staff was essential to ensure adherence to the new protocol and improve clinical outcomes.  Transitioning to CCTA for routine noninvasive cardiac evaluation in the ED-run Observation Medicine Unit demonstrated significant efficiency and diagnostic accuracy benefits. Successful implementation requires targeted educational efforts to ensure competency and confidence among healthcare providers. The findings support the integration of CCTA into standard clinical practice for the evaluation of chest pain in the emergency setting, with future research needed to validate these results in broader patient populations and assess long-term outcomes.

Nuclear Smooth Muscle α-actin in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout ACTA2, encoding smooth muscle α-actin (αSMA), predispose to adult onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by childhood-onset diverse vascular diseases. Our data indicate that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors, and the ACTA2 p.R179 variant decreases nuclear localization of αSMA. SMCs explanted from a SMC-specific conditional knockin mouse model, Acta2SMC-R179/+, are less differentiated than WT SMCs, both in vitro and in vivo, and have global changes in chromatin accessibility. Induced pluripotent stem cells from patients with ACTA2 p.R179 variants fail to fully differentiate from neural crest cells to SMCs, and single cell transcriptomic analyses of an ACTA2 p.R179H patient's aortic tissue shows increased SMC plasticity. Thus, nuclear αSMA participates in SMC differentiation and loss of this nuclear activity occurs with ACTA2 p.R179 pathogenic variants.

Nuclear Smooth Muscle α-actin Participates in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout ACTA2, encoding smooth muscle α-actin (αSMA), predispose to adult-onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by diverse childhood-onset vascular diseases. Here we show that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors. The ACTA2 p.R179 αSMA variant shows decreased nuclear localization. Primary SMCs from Acta2 SMC-R179C/+ mice are less differentiated than WT SMCs in vitro and in vivo and have global changes in chromatin accessibility. Induced pluripotent stem cells from patients with ACTA2 p.R179 variants fail to fully differentiate from neuroectodermal progenitor cells to SMCs, and single-cell transcriptomic analyses of an ACTA2 p.R179H patient's aortic tissue show increased SMC plasticity. Thus, nuclear αSMA participates in SMC differentiation, and loss of this nuclear activity occurs with ACTA2 p.R179 pathogenic variants.

Clinicopathologic Aspects of Vocal Fold Leukoplakia in Smokers and Nonsmokers.

BACKGROUND: We aimed to investigate possible causes of leukoplakia and squamous cell carcinoma. We particularly sought to characterize the effect of smoking history because leukoplakia has been observed in nonsmokers. METHODS: We retrospectively identified patients with a diagnosis of leukoplakia who were treated at Mayo Clinic (Jacksonville, Florida), in the Department of Otorhinolaryngology, from 1/1/2006 through 8/31/2019. Each patient was age- and sex-matched (1:2 ratio) to control patients without leukoplakia. Information about possible risk factors, chief symptoms, and social history with smoking and alcohol use was obtained from health records. Nine risk factors were analyzed independently with multivariate analysis. Continuous risk factors were compared between cases and controls with the Wilcoxon rank sum test; categorical variables were compared with the χ2 test. RESULTS: The final cohort consisted of 72 patients with leukoplakia (mean [SD] age, 66 [11] years; 61 men [85%]) and 144 age- and sex-matched controls. Compared with the control group, significantly more cases were current smokers (26% vs. 5%) and fewer were never-smokers. (17% vs. 51%) (P < 0.001). Cases also had a significantly longer duration of smoking history compared with controls (median, 30 vs. 0 years; P < 0.001). Alcohol consumption was not significantly different between cases and controls (53% vs. 54%; P > 0.99). When assessing never-smokers and those who had not smoked for more than 25 years, a history of smoking (P = 0.002) and the number of years smoked (P = 0.002) were significantly different for cases and controls. CONCLUSION: Most vocal fold leukoplakia lesions have a low risk of malignancy. It is important to evaluate the characteristics of the lesion and assess the patient's risk factors. Follow-up is a key factor in patient management, but for patients with recurrent leukoplakia, the duration and frequency of surveillance is still controversial and varies among medical centers. Future prospective studies with advanced analyses are warranted because they may strengthen the ability to identify clinical factors that influence the development of squamous cell carcinoma.