Tissue homeostasis and the prevention of neoplasia require regulatory co‐ordination between cellular proliferation and apoptosis. Several cellular proteins, including c‐myc and E2F, as well as viral proteins such as E1A, have dual functions as positive regulators of apoptosis and proliferation. The product of the retinoblastoma tumor suppressor gene, pRb, binds these proteins and is known to function in growth suppression. To examine whether pRb may function as a negative regulator of both proliferation and apoptosis, we analyzed apoptosis induced in transfected derivatives of the human osteosarcoma cell line SAOS‐2. Ionizing radiation induced apoptosis in a time‐ and dose‐dependent manner in SAOS‐2 cells, which lack pRb expression. In both a transient and stable transfection assay, SAOS‐2 derivatives expressing wild‐type (wt) pRb exhibited increased viability and decreased apoptosis following treatment at a variety of radiation doses. Expression in SAOS‐2 of a mutant pRb that fails to complex with several known binding partners of pRb, including E1A and E2F, did not protect SAOS‐2 cells from apoptosis. Radiation exposure induced a G2 arrest in SAOS‐2 and in derivatives expressing pRb. Inhibition of DNA synthesis and cell cycle progression by aphidicolin treatment failed to protect SAOS‐2 cells or pRb‐expressing isolates from undergoing apoptosis. Our data document a novel function for pRb in suppressing apoptosis and suggest that several proteins shown to induce apoptosis, including E1A, E2F and c‐myc, may do so by interfering with the protective function of pRb.

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key WorDS • injury • nerve • repair • sciatic • sural • peripheral nerve • anatomyAbbreviations used in this paper: AGC = axon guidance channel; CSA = cross-sectional area; EHL = extensor hallucis longus.

OBJECTIVE With an increasing number of disease-modifying drugs available to manage rheumatoid arthritis (RA), spine surgeons have anecdotally noted decreased rates of cervical spine surgical procedures in this population. Although these medications have been shown to mitigate RA progression and its systemic effects on joint destruction, there are currently no large-scale studies of RA patients that suggest the use of these disease-modifying drugs has truly coincided with a decline in cervical spine surgery. METHODS Patients with RA who underwent cervical spinal fusion from 1998 to 2021 performed by the senior author were retrospectively reviewed. The cohort was stratified into 3 categories based on procedure level: 1) occipitocervical, 2) atlantoaxial, and 3) subaxial. The number of surgical procedures per year in each subgroup was evaluated to determine treatment trends over time. National (Nationwide) Inpatient Sample (NIS) data on both RA and non-RA patients who underwent cervical fusion were analyzed to assess for surgical trends over time and for differences in likelihood of surgical intervention between RA and non-RA patients over the epoch. RESULTS From 1998 to 2021, the number of overall cervical fusions performed in RA patients significantly declined (–0.13 procedures/year, p = 0.01) in this cohort, despite an overall significant increase in cervical fusions in non-RA patients over the same period. NIS analysis of cervical fusions across all patients similarly demonstrated a significant increase in cervical fusions over the same epoch (19,278 cases/year, p < 0.0001). When normalized for changes in population size, the incidence of new surgical procedures was lower in patients with RA regardless of surgical technique. Anterior cervical fusion was the most common approach used over the epoch in both RA and non-RA patients; correspondingly, RA patients were significantly less likely to undergo anterior cervical fusion (OR 0.655, 95% CI −0.4504 to −0.3972, p < 0.0001). CONCLUSIONS At the authors’ institution, there was a clear decline in the number of cervical fusions performed to treat the 3 most common forms of cervical spine pathology in RA patients (basilar impression, atlantoaxial instability, and subaxial cervical deformity). Although national trends suggest an increase in total cervical fusions in both RA and non-RA patients, the incidence of new procedures in patients with RA was significantly lower than in patients without RA, which supports the anecdotal results of spine surgeons nationally.

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