Immune checkpoint inhibitors have been successful across several tumor types; however, their efficacy has been uncommon and unpredictable in glioblastomas (GBM), where <10% of patients show long-term responses. To understand the molecular determinants of immunotherapeutic response in GBM, we longitudinally profiled 66 patients, including 17 long-term responders, during standard therapy and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations associated with immunosuppressive expression signatures in non-responders, and an enrichment of MAPK pathway alterations (PTPN11, BRAF) in responders. Responsive tumors were also associated with branched patterns of evolution from the elimination of neoepitopes, as well as differences in T cell clonal diversity and tumor microenvironment profiles. Our study shows that clinical response to anti-PD-1 immunotherapy in GBM is associated with specific molecular alterations, immune expression signatures, and immune infiltration that reflect the tumor’s clonal evolution during treatment.

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Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to benefit from cytoreductive surgery, ie, those with favorable RPA and RC.

Cervical spondylotic myelopathy (CSM) is among the most common spinal cord disorders of the elderly. Muscle fat infiltration (MFI), a potential pathological sign of muscle adiposity, may contribute to or be associated with pain/disability/impairments in patients with CSM. We examined the relationship between MFI and CSM's clinical manifestations by enrolling nine CSM patients and five aged-matched controls to undergo MRI imaging of the cervical spine with MFI. A blinded investigator calculated MFI for each of the bilateral multifidii muscles from C3 to C7 on the MRI images. Nurick scores, Neck Disability Index, and modified Japanese Orthopedic Association scores were collected for all patients. CSM patients and controls were equivalent with respect to age, height, weight, gender, race, smoking status, and employment status. MFI was higher in patients with CSM than in controls (31.7% v. 24.6%, respectively, p = 0.0178). Higher MFI was associated with increased disability on the Nurick scale (p = 0.0371). MJOA scores correlated linearly with MFI (R = 0.542, p = 0.0453), but not NDI (p = 0.3125). Increased MFI of the multifidus muscles is associated with cervical myelopathy and a clinically significant decline in sensorimotor function as measured by mJOA and Nurick scores. Spinal injury in CSM may lead to secondary muscle loss and muscle fat infiltration.

OBJECTIVEVenous thromboembolism (VTE) after spinal surgery is a major cause of morbidity, but chemoprophylactic anticoagulation can prevent it. However, there is variability in the timing and use of chemoprophylactic anticoagulation after spine surgery, particularly given surgeons’ concerns for spinal epidural hematomas. The goal of this study was to provide insight into the safety, efficacy, and timing of anticoagulation therapy after spinal surgery.METHODSThe authors retrospectively examined records from 6869 consecutive spinal surgeries performed in their departments at Northwestern University. Data on patient demographics, surgery, hospital course, timing of chemoprophylaxis, and complications, including deep venous thrombosis (DVT), pulmonary embolism (PE), and spinal epidural hematomas requiring evacuation, were collected. Data from the patients who received chemoprophylaxis (n = 1904) were compared with those of patients who did not (n = 4965). The timing of chemoprophylaxis, the rate of VTEs, and the incidence of spinal epidural hematomas were analyzed.RESULTSThe chemoprophylaxis group had more risk factors, including greater age (59.70 vs 51.86 years, respectively; p < 0.001), longer surgery (278.59 vs 145.66 minutes, respectively; p < 0.001), higher estimated blood loss (995 vs 448 ml, respectively; p < 0.001), more comorbid diagnoses (2.69 vs 1.89, respectively; p < 0.001), history of VTE (5.8% vs 2.1%, respectively; p < 0.001), and a higher number were undergoing fusion surgery (46.1% vs 24.7%, respectively; p < 0.001). The prevalence of VTE was higher in the chemoprophylaxis group (3.62% vs 2.03%, respectively; p < 0.001). The median time to VTE occurrence was shorter in the nonchemoprophylaxis group (3.6 vs 6.8 days, respectively; p = 0.0003, log-rank test; hazard ratio 0.685 [0.505–0.926]), and the peak prevalence of VTE occurred in the first 3 postoperative days in the nonchemoprophylaxis group. The average time of initiation of chemoprophylaxis was 1.46 days after surgery. The rates of epidural hematoma were 0.20% (n = 4) in the chemoprophylaxis group and 0.18% (n = 9) in the nonchemoprophylaxis group (p = 0.622).CONCLUSIONSThe risks of spinal epidural hematoma among patients who receive chemoprophylaxis and those who do not are low and equivalent. Administering anticoagulation therapy from 1 day before to 3 days after surgery is safe for patients at high risk for VTE.

In this pilot study, we demonstrate the feasibility of measuring the resectability of glioblastoma through crowdsourcing. This tool could be used to quantify resectability, a potential confounder in neuro-oncology clinical trials.

CrossFit is a popular, high-intensity style workout with the potential to injure its participants. Spine injuries were the most common type of injury observed and frequently required surgical intervention.

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