Race-based disparities in access to surgical palliation for hypoplastic left heart syndrome.

BACKGROUND: Racial disparities in outcomes have been shown to persist in many operative specialties, including the management of congenital heart disease. Using a demographic-adjusted methodology, we examined whether patient race influenced access to high-performing centers for the operative management of hypoplastic left heart syndrome. METHODS: The 2005-2017 National Inpatient Sample was queried to identify all pediatric (≤5 years) hospitalizations with an operation for hypoplastic left heart syndrome. A racial disparity index was generated for each hospital and defined as the proportion of White patients receiving operative management for hypoplastic left heart syndrome divided by the proportion of White patients admitted for respiratory failure. This methodology quantified hospital-level racial variation while adjusting for the local racial makeup of each center. RESULTS: Of the 17,275 patients who met inclusion criteria, 64.1% were managed at high-volume centers. Patients at high-volume centers had a similar distribution of operative type, age, and burden of comorbidities. The mean racial disparity index steadily grew from 1.06 at the lowest volume decile of operative volume to 1.51 at the highest, indicating an increasing proportion of White patients as volume increased. Using risk-adjusted analysis, each decile increase in hospital volume was associated with a 14% relative reduction in odds of mortality and a 0.06 increase in predicted racial disparity index. Increasing volume was further associated with reduced odds of non-home discharge but did not alter resource utilization. CONCLUSION: We demonstrate that high-volume centers disproportionally serve White patients and have superior clinical outcomes compared to low-volume centers. This study highlights the critical importance of equitable access to expert care for high-risk conditions such as hypoplastic left heart syndrome.

Amyloid-beta(1-42) rapidly forms protofibrils and oligomers by distinct pathways in low concentrations of sodium dodecylsulfate.

Alzheimer's disease (AD) is characterized by large numbers of senile plaques in the brain that consist of fibrillar aggregates of 40- and 42-residue amyloid-beta (Abeta) peptides. However, the degree of dementia in AD correlates better with the concentration of soluble Abeta species assayed biochemically than with histologically determined plaque counts, and several investigators now propose that soluble aggregates of Abeta are the neurotoxic agents that cause memory deficits and neuronal loss. These endogenous aggregates are minor components in brain extracts from AD patients and transgenic mice that express human Abeta, but several species have been detected by gel electrophoresis in sodium dodecylsulfate (SDS) and isolated by size exclusion chromatography (SEC). Endogenous Abeta aggregation is stimulated at cellular interfaces rich in lipid rafts, and anionic micelles that promote Abeta aggregation in vitro may be good models of these interfaces. We previously found that micelles formed in dilute SDS (2 mM) promote Abeta(1-40) fiber formation by supporting peptide interaction on the surface of a single micelle complex. In contrast, here we report that monomeric Abeta(1-42) undergoes an immediate conversion to a predominant beta-structured conformation in 2 mM SDS which does not proceed to amyloid fibrils. The conformational change is instead rapidly followed by the near quantitative conversion of the 4 kDa monomer SDS gel band to 8-14 kDa bands consistent with dimers through tetramers. Removal of SDS by dialysis gave a shift in the predominant SDS gel bands to 30-60 kDa. While these oligomers resemble the endogenous aggregates, they are less stable. In particular, they do not elute as discrete species on SEC, and they are completed disaggregated by boiling in 1% SDS. It appears that endogenous oligomeric Abeta aggregates are stabilized by undefined processes that have not yet been incorporated into in vitro Abeta aggregation procedures.