Racial/Ethnic and Socioeconomic Disparities in Total Knee Arthroplasty 30- and 90-Day Readmissions: A Multi-Payer and Multistate Analysis, 2007-2014.

Previous studies have addressed racial/ethnic and socioeconomic disparities in total knee arthroplasty (TKA) within the Medicare population. However, there is limited research examining these disparities across racial/ethnic and socioeconomic groups in the general population. This study used administrative data from the State Inpatient Databases from the Healthcare Cost and Utilization Project for the years 2007-2014 from California (2007-2011 only), Florida, New York, and Maryland (2012-2014 only). In all, 739,857 TKA readmission-eligible patients aged ≥8 years were included in the analysis. Black patients and patients with Medicaid had a higher likelihood of 30- and 90-day readmissions compared to white patients and patients with private insurance, respectively. Patients living in higher median income areas and patients treated at higher volume hospitals had lower likelihoods of 30- and 90-day readmissions compared to patients in the lowest median income quartile and patients treated at the lowest volume hospitals, respectively. These results confirmed racial/ethnic and socioeconomic disparities in TKA readmissions across 4 geographically diverse states, identified public insurance status as the salient factor across subpopulations, and raise awareness of the existence of these disparities outside of the Medicare population.

Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity.

During exercise, defects in calcium (Ca2+) release have been proposed to impair muscle function. Here, we show that during exercise in mice and humans, the major Ca2+ release channel required for excitation-contraction coupling (ECC) in skeletal muscle, the ryanodine receptor (RyR1), is progressively PKA-hyperphosphorylated, S-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in "leaky" channels that cause decreased exercise tolerance in mice. Mice with skeletal muscle-specific calstabin1 deletion or PDE4D deficiency exhibited significantly impaired exercise capacity. A small molecule (S107) that prevents depletion of calstabin1 from the RyR1 complex improved force generation and exercise capacity, reduced Ca2+-dependent neutral protease calpain activity and plasma creatine kinase levels. Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity.