Risk of Delayed Percutaneous Coronary Intervention for STEMI in the Southeast United States.

Background: Emergent reperfusion by percutaneous coronary intervention (PCI) within 90 minutes of first medical contact (FMC) is indicated in patients with ST-segment elevation myocardial infarction (STEMI). However, long transport times in rural areas in the Southeast US make meeting this goal difficult. The objective of this study was to determine the number of Southeast US residents with prolonged transport times to the nearest 24/7 primary PCI (PPCI) center. Methods: A cross-sectional study of residents in the Southeastern US was conducted based on geographical and 2022 5-Year American Community Survey data. The geographic information system (GIS) ArcGIS Pro was used to estimate Emergency Medical Services (EMS) transport times for Southeast US residents to the nearest PPCI center. All 24/7 PPCI centers in North Carolina, South Carolina, Georgia, Florida, Mississippi, Alabama, and Tennessee were included in the analysis, as well as nearby PPCI centers in surrounding states. To identify those at risk of delayed FMC-to-device time, the primary outcome was defined as a >30-minute transport time, beyond which most patients would not have PCI within 90 minutes. A secondary outcome was defined as transport >60 minutes, the point at which FMC-to-device time would be >120 minutes most of the time. These cutoffs are based on national median EMS scene times and door-to-device times. Results: Within the Southeast US, we identified 62,880,528 residents and 350 PPCI centers. Nearly 11 million people living in the Southeast US reside greater than 30 minutes from a PPCI center (17.3%, 10,866,710, +/- 58,143), with 2% (1,271,522 +/- 51,858) living greater than 60 minutes from a PPCI hospital. However, most patients reside in short transport zones; 82.7% (52,013,818 +/- 98,741). Within the Southeast region, 8.4% (52/616) of counties have more than 50% of their population in a long transport zone and 42.3% (22/52) of those have more than 90% of their population in long transport areas. Conclusions: Nearly 11 million people in the Southeast US do not have access to timely PCI for STEMI care. This disparity may contribute to increased morbidity and mortality.

Thermal stability and kinetic constants for 129 variants of a family 1 glycoside hydrolase reveal that enzyme activity and stability can be separately designed.

Accurate modeling of enzyme activity and stability is an important goal of the protein engineering community. However, studies seeking to evaluate current progress are limited by small data sets of quantitative kinetic constants and thermal stability measurements. Here, we report quantitative measurements of soluble protein expression in E. coli, thermal stability, and Michaelis-Menten constants (kcat, KM, and kcat/KM) for 129 designed mutants of a glycoside hydrolase. Statistical analyses reveal that functional Tm is independent of kcat, KM, and kcat/KM in this system, illustrating that an individual mutation can modulate these functional parameters independently. In addition, this data set is used to evaluate computational predictions of protein stability using the established Rosetta and FoldX algorithms. Predictions for both are found to correlate only weakly with experimental measurements, suggesting improvements are needed in the underlying algorithms.