Prediction of 2-year clinical outcome trajectories in patients undergoing anterior cervical discectomy and fusion for spondylotic radiculopathy.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is often described as the gold standard surgical technique for cervical spondylotic radiculopathy. Although outcomes are considered favorable, there is little prognostic evidence to guide patient selection for ACDF. This study aimed to 1) describe the 24-month postoperative trajectories of arm pain, neck pain, and pain-related disability; and 2) identify perioperative prognostic factors that predict trajectories representing poor clinical outcomes. METHODS: In this retrospective cohort study, patients with cervical spondylotic radiculopathy who underwent ACDF at 1 of 12 orthopedic or neurological surgery centers were recruited. Potential outcome predictors included demographic, health, clinical, and surgery-related prognostic factors. Surgical outcomes were classified by trajectories of arm pain intensity, neck pain intensity (numeric pain rating scales), and pain-related disability (Neck Disability Index) from before surgery to 24 months postsurgery. Trajectories of postoperative pain and disability were estimated with latent class growth analysis, and prognostic factors associated with poor outcome trajectory were identified with robust Poisson models. RESULTS: The authors included data from 352 patients (mean age 50.9 [SD 9.5] years; 43.8% female). The models estimated that 15.5%-23.5% of patients followed a trajectory consistent with a poor clinical outcome. Lower physical and mental health-related quality of life, moderate to severe risk of depression, and longer surgical wait time and procedure time predicted poor postoperative trajectories for all outcomes. Receiving compensation and smoking additionally predicted a poor neck pain outcome. Regular exercise, physiotherapy, and spinal injections before surgery were associated with a lower risk of poor disability outcome. Patients who used daily opioids, those with worse general health, or those who reported predominant neck pain or a history of depression were at greater risk of poor disability outcome. CONCLUSIONS: Patients who undergo ACDF for cervical spondylotic radiculopathy experience heterogeneous postoperative trajectories of pain and disability, with 15.5%-23.5% of patients experiencing poor outcomes. Demographic, health, clinical, and surgery-related prognostic factors can predict ACDF outcomes. This information may further assist surgeons with patient selection and with setting realistic expectations. Future studies are needed to replicate and validate these findings prior to confident clinical implementation.

Predictors of home discharge after scheduled surgery for degenerative cervical myelopathy.

OBJECTIVE: Degenerative cervical myelopathy (DCM) is an important public health issue. Surgery is the mainstay of treatment for moderate and severe DCM. Delayed discharge of patients after DCM surgery is associated with increased healthcare costs. There is a paucity of data regarding predictive factors for discharge destination after scheduled surgery for patients with DCM. The purpose of this study was to identify factors predictive of home versus nonhome discharge after DCM surgery. METHODS: Patients undergoing scheduled DCM surgery who had been enrolled in a prospective DCM substudy of the Canadian Spine Outcomes and Research Network registry between January 2015 and October 2020 were included in this retrospective analysis. Patient data were evaluated to identify potential factors predictive of home discharge after surgery. Logistic regression was used to identify independent factors predictive of home discharge. A multivariable model was then used as a final model. RESULTS: Overall, 639 patients were included in the initial analysis, 543 (85%) of whom were discharged home. The mean age of the entire cohort was 60 years (SD 11.8 years), with a BMI of 28.9 (SD 5.7). Overall, 61.7% of the patients were female. The mean length of stay was 2.72 days (SD 1.7 days). The final internally validated bootstrapped multivariable model revealed that younger age, higher 9-Item Patient Health Questionnaire score, lower Neck Disability Index scores, fewer operated levels, mJOA scores indicating mild disease, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects were predictive of home discharge. CONCLUSIONS: Younger age, less neck-related disability, fewer operated levels, more significant depression, less severe myelopathy, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects are predictive of home discharge after surgery for DCM. These factors can help to guide clinical decision-making and optimize postoperative care pathways.

Seizure-induced thoracolumbar burst fractures - Not to be missed.

While rare, post-ictal thoracolumbar burst fractures are commonly missed due to confounding factors, resulting in delayed treatment and the potential for serious neurological deficits. This paper serves as a call for a high-degree of clinical suspicion when treating post-ictal patients to ensure they undergo a focused neurological examination of the lower extremities. If unresponsive/uncooperative, spinal precautions should be maintained until the spine can be cleared clinically or radiographically. In all events, if the patient is complaining of musculoskeletal pain possibly originating from the spine, radiographic evaluations are warranted to prevent possible deficits caused by a missed thoracolumbar fracture.

Raloxifene prevents stress granule dissolution, impairs translational control and promotes cell death during hypoxia in glioblastoma cells.

Glioblastoma (GBM) is the most common primary malignant brain tumor, and it has a uniformly poor prognosis. Hypoxia is a feature of the GBM microenvironment, and previous work has shown that cancer cells residing in hypoxic regions resist treatment. Hypoxia can trigger the formation of stress granules (SGs), sites of mRNA triage that promote cell survival. A screen of 1120 FDA-approved drugs identified 129 candidates that delayed the dissolution of hypoxia-induced SGs following a return to normoxia. Amongst these candidates, the selective estrogen receptor modulator (SERM) raloxifene delayed SG dissolution in a dose-dependent manner. SG dissolution typically occurs by 15 min post-hypoxia, however pre-treatment of immortalized U251 and U3024 primary GBM cells with raloxifene prevented SG dissolution for up to 2 h. During this raloxifene-induced delay in SG dissolution, translational silencing was sustained, eIF2α remained phosphorylated and mTOR remained inactive. Despite its well-described role as a SERM, raloxifene-mediated delay in SG dissolution was unaffected by co-administration of ß-estradiol, nor did ß-estradiol alone have any effect on SGs. Importantly, the combination of raloxifene and hypoxia resulted in increased numbers of late apoptotic/necrotic cells. Raloxifene and hypoxia also demonstrated a block in late autophagy similar to the known autophagy inhibitor chloroquine (CQ). Genetic disruption of the SG-nucleating proteins G3BP1 and G3BP2 revealed that G3BP1 is required to sustain the raloxifene-mediated delay in SG dissolution. Together, these findings indicate that modulating the stress response can be used to exploit the hypoxic niche of GBM tumors, causing cell death by disrupting pro-survival stress responses and control of protein synthesis.