ImportanceGlioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.ObjectiveTo investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.Design, Setting, and ParticipantsThis phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021.InterventionsThe active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies.Main Outcomes and MeasuresThe primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials.ResultsA total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03).Conclusions and RelevanceIn this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone.Trial RegistrationClinicalTrials.gov Identifier: NCT00045968
Conventional valve shunting for treatment of hydrocephalus has a high rate of long-term complications. Endoscopic ventriculostomy by fenestration of the third ventricular floor, a minimally-invasive technique, avoids many of the drawbacks of extracranial shunting. Endoscopy was performed in 12 hydrocephalic patients with MRI-diagnosed aqueductal stenosis and neurological signs. Intraoperative ultrasound guidance allowed aiming the tip of the rigid endoscope to the foramen of Monro, and direct entering of the enlarged third ventricle. This technique is as exact as stereotaxy but is faster and easier. No complications were seen due to the surgical procedure. Nine patients were cured from their complaints, in 3 cases there was a subjective improvement of neurology. Long-term patency of the third ventriculostomy was confirmed by movement-sensitive MRI.
The results of this study demonstrate that transplantation of autograft bone material harvested during the ACC integrated well in the cage and in the adjacent vertebral bodies. Thus, complications associated with explantation of autograft material from other donor sites, e.g., the iliac crest, could be avoided. The early postoperative and midterm follow-up periods provided no evidence of morphological or functional instability of the operated cervical segments when this autograft technique was used in combination with cervical instrumentation.
Previous studies with animal models of supratentorial ICP elevation have demonstrated a pressure gradient between the supratentorial and the infratentorial compartments. The present study was designed to investigate the possible presence of such a gradient in the case of infratentorial ICP elevation. An inflatable infratentorial balloon catheter was implanted in seven domestic pigs. The infratentorial ICP (ICPi) was measured in the left cerebellar hemisphere, and the supratentorial ICP (ICPs) was measured in the left cerebral hemisphere. The corresponding pulse amplitudes (ICPi-PA, ICPs-PA) were recorded in both compartments, and the cerebral perfusion pressure (CPP) was calculated. ICPi and ICPs values prior to balloon inflation were 4.4 (SD 2.2) and 4.1 (SD 2.3) mm Hg, respectively, and increased to 63.1 (SD 32.6) and 62.3 (SD 28.1) mmHg after balloon inflation. ICPi-PA rose from 3.1 (SD 0.43) to 12.8 (SD 8.0) mmHg, and ICPs-PA rose from 3.2 (SD 0.63) to 13.0 (SD 7.1) mmHg. CPP decreased from 86.1 (SD 12.0) to 55.4 (SD 14.6) mm Hg. The paired difference between ICPi and ICPs values was 0.44 (SD 1.96) mmHg, and the paired difference of ICP amplitudes was 0.03 (SD 1.19) mmHg. All these differences in infratentorial and supratentorial values were statistically not significant. In conclusion, infratentorial ICP elevation in the presented pig model leads to a uniform ICP elevation in the intracranial space without development of a considerable pressure gradient below and above the tentorium. In the low pressure part of the ICP curve, cerebrospinal fluid connects the compartments and contributes to the pressure equilibrium. The early obstruction of the foramen magnum by intruding cerebellar tissue seems to isolate the infratentorial from the spinal compartment. In the high-pressure part of the curve, the upwards cerebellar transtentorial herniation takes over the pressure transfer, and the whole intracranial space can be considered as a single compartment in the pig.
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