Impact of Racial and Socioeconomic Disparities on Access to Interspinous Spacer for Treatment of Lumbar Spinal Stenosis: A Nationwide Medicare Analysis.

BACKGROUND: In mild to moderate lumbar spinal stenosis (LSS) where conservative care treatments fail, minimally invasive treatments, such as interspinous spacers without decompression or fusion (ISD), may be appropriate. While previous studies have demonstrated racial and socioeconomic disparities in the surgical treatment of LSS, there are limited data on how those factors impact accessibility to these procedures. This study explored demographic, socioeconomic, and geographic differences in the use of ISD. METHODS: Using the Medicare 100% files from 2017 through 2022, this retrospective claims analysis identified when and if patients diagnosed with LSS received ISD implantation. Cox proportional hazards regression was used to examine the association between racial and socioeconomic characteristics and the rate of ISD implantation, stratified by geographic region. RESULTS: A total of 1,316,622 individuals met the inclusion criteria; 4730 (0.4%) underwent ISD implantation, with a mean (standard deviation) time to treatment of 11.9 (13.2) months after diagnosis. The likelihood of ISD implantation was higher for older patients (except for the oldest group), males, those with lower disease burden, and White patients. Cox regression revealed that the associations of racial and socioeconomic factors with ISD implantation varied by U.S. region. In the Midwest and Northeast, lower median household income was associated with a decreased likelihood of ISD implantation regardless of race, while in the South, Black patients were less likely to undergo ISD implantation regardless of income. CONCLUSIONS: The observed disparities in access to ISD implantation mirror existing trends in surgical interventions for LSS, suggesting further study and interventions are needed to address inequities.

In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.

Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.

Apoptotic histone modification inhibits nuclear transport by regulating RCC1.

A number of signalling pathways have been identified that regulate apoptosis, but the mechanism that initiates apoptosis remains incompletely understood. We have found that the nuclear RanGTP level is diminished during the early stages of apoptosis, which correlates with immobilization of RCC1 on the chromosomes. Furthermore, the expression of phosphomimetic histone H2B or caspase-activated Mst1 immobilizes RCC1 and causes reduction of nuclear RanGTP levels, which leads to inactivation of the nuclear transport machinery. As a consequence, nuclear localization signal (NLS)-containing proteins, including NF-kappaB-p65, remain bound to importins alpha and beta in the cytoplasm. Knocking down Mst1 allows resumption of nuclear transport and the nuclear entry of NF-kappaB-p65, which have important roles in rescuing cells from apoptosis. Therefore, we propose that RCC1 reads the histone code created by caspase-activated Mst1 to initiate apoptosis by reducing the level of RanGTP in the nucleus.