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The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow. Editor's summary: Patients with high grade gliomas (HGG) and particularly glioblastoma (GBM) have poor overall survival and lack predictive biomarkers to guide therapeutic treatment. To overcome this, Peruzzi et al. have developed intratumoral microdevices (IMD) to be inserted and removed during surgery that release drugs, resected tissue can then be evaluated for efficacy that reflects systemic treatment efficacy. This was tested in six patients (NCT04135807) and found to be safe, and tissue was usable for downstream analysis with implications to replicating responses to temozolomide. This device requires additional testing in patients but represents a promising strategy to help guide treatment of HGG and improve treatment outcomes. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Objectives  Cerebrospinal fluid (CSF) leaks are a possible complication in patients with skull base fractures (SBFs). The widely cited incidence of CSF leaks is 10 to 30% in SBF patients; however, this estimate is based only on a few outdated studies. A recent report found CSF leaks in <2% SBF patients, suggesting the incidence may be lower now. To investigate this, we report here our institutional series. Design  This study is a retrospective chart review. Setting  The study was conducted at two major academic medical centers (2000–2018). Participants  Adult patients with SBF were included in this study. Main Outcome Measures  Variables included age, gender, CSF leak within 90 days, management regimen, meningitis within 90 days, and 1-year mortality. Results  Among 4,944 patients with SBF, 199 (4%) developed a CSF leak. SBF incidence was positively correlated with year of clinical presentation (r -squared 0.78, p  < 0.001). Among CSF leaks, 42% were conservatively managed, 52% were treated with lumbar drain, and 7% required surgical repair. Meningitis developed in 28% CSF leak patients. The 1-year mortality for all SBF patients was 11%, for patients with CSF leaks was 12%, and for patients with meningitis was 16%. Conclusion  In the largest institutional review of SBF patients in the 21st century, we found CSF leak incidence to be 4%. This is lower than the widely cited range of 10 to 30%. Nevertheless, morbidity and mortality associated with this complication remains clinically significant, and SBF patients should continue to be monitored for CSF leaks. We provide here our institutional treatment algorithm for these patients that may help to inform the treatment strategy at other institutions. [ABSTRACT FROM AUTHOR]

Objectives  Cerebrospinal fluid (CSF) leaks are a possible complication in patients with skull base fractures (SBFs). The widely cited incidence of CSF leaks is 10 to 30% in SBF patients; however, this estimate is based only on a few outdated studies. A recent report found CSF leaks in <2% SBF patients, suggesting the incidence may be lower now. To investigate this, we report here our institutional series. Design  This study is a retrospective chart review. Setting  The study was conducted at two major academic medical centers (2000–2018). Participants  Adult patients with SBF were included in this study. Main Outcome Measures  Variables included age, gender, CSF leak within 90 days, management regimen, meningitis within 90 days, and 1-year mortality. Results  Among 4,944 patients with SBF, 199 (4%) developed a CSF leak. SBF incidence was positively correlated with year of clinical presentation (r -squared 0.78, p  < 0.001). Among CSF leaks, 42% were conservatively managed, 52% were treated with lumbar drain, and 7% required surgical repair. Meningitis developed in 28% CSF leak patients. The 1-year mortality for all SBF patients was 11%, for patients with CSF leaks was 12%, and for patients with meningitis was 16%. Conclusion  In the largest institutional review of SBF patients in the 21st century, we found CSF leak incidence to be 4%. This is lower than the widely cited range of 10 to 30%. Nevertheless, morbidity and mortality associated with this complication remains clinically significant, and SBF patients should continue to be monitored for CSF leaks. We provide here our institutional treatment algorithm for these patients that may help to inform the treatment strategy at other institutions. [ABSTRACT FROM AUTHOR]