The effect of geographic origin and destination on congenital heart disease outcomes: a retrospective cohort study.

BACKGROUND: Congenital heart disease (CHD) is a common and significant birth defect, frequently requiring surgical intervention. For beneficiaries of the Department of Defense, a new diagnosis of CHD may occur while living at rural duty stations. Choice of tertiary care center becomes a function of geography, referring provider recommendations, and patient preference. METHODS: Using billing data from the Military Health System over a 5-year period, outcomes for beneficiaries age < 10 years undergoing CHD surgery were compared by patient origin (rural versus urban residence) and the distance to treatment (patient's home and the treating tertiary care center). These beneficiaries include children of active duty, activated reserves, and federally activated National Guard service members. Analysis of the outcomes were adjusted for procedure complexity risk. Treatment centers were further stratified by annual case volume and whether they publicly reported results in the society of thoracic surgery (STS) outcomes database. RESULTS: While increasing distance was associated with the cost of admission, there was no associated risk of inpatient mortality, one year mortality, or increased length of stay. Likewise, rural origination was not significantly associated with target outcomes. Patients traveled farther for STS-reporting centers (STS-pr), particularly high-volume centers. Such high-volume centers (> 50 high complexity cases annually) demonstrated decreased one year mortality, but increased cost and length of stay. CONCLUSIONS: Together, these findings contribute to the national conversation of rural community medicine versus regionalized subspecialty care; separation of patients between rural areas and more urban locations for initial CHD surgical care does not increase their mortality risk. In fact, traveling to high volume centers may have an associated mortality benefit.

The axon degeneration gene SARM1 is evolutionarily distinct from other TIR domain-containing proteins.

Many forms of neurodegenerative disease are characterized by Wallerian degeneration, an active program of axonal destruction. Recently, the important player which enacts Wallerian degeneration was discovered, the multidomain protein SARM1. Since the SARM1 protein has classically been thought of as an innate immune molecule, its role in Wallerian degeneration has raised questions on the evolutionary forces acting on it. Here, we synthesize a picture of SARM1's evolution through various organisms by examining the molecular and genetic changes of SARM1 and the genes around it. Using proteins that possess domains homologous to SARM1, we established distances and Ka/Ks values through 5671 pairwise species-species comparisons. We demonstrate that SARM1 diverged across species in a pattern similar to other SAM domain-containing proteins. This is surprising, because it was expected that SARM1 would behave more like its TIR domain relatives. Going along with this divorce from TIR, we also noted that SARM1's TIR is under stronger purifying selection than the rest of the TIR domain-containing proteins (remaining highly conserved). In addition, SARM1's synteny analysis reveals that the surrounding gene cluster is highly conserved, functioning as a potential nexus of gene functionality across species. Taken together, SARM1 demonstrates a unique evolutionary pattern, separate from the TIR domain protein family.