Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

PURPOSE: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established (CDKN2A/B and TERT), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference P = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

A Mobile Health Approach for Improving Outcomes in Suicide Prevention (SafePlan).

BACKGROUND: Suicide is a prominent cause of death worldwide, particularly among young people. It was the second leading cause of death among those aged 15-29 years globally in 2016. Treatment for patients with suicidal thoughts or behaviors often includes face-to-face psychological therapy with a mental health professional. These forms of interventions may involve maintaining and updating paper-based reports or worksheets in between sessions. Mobile technology can offer a way to support the implementation of evidence-based psychological techniques and the acquisition of protective coping skills. OBJECTIVE: This study aims to develop a mobile app to facilitate service users' access to mental health support and safety planning. This process involved eliciting expert input from clinicians who are actively engaged in the provision of mental health care. METHODS: A survey was distributed to targeted health care professionals to determine what features should be prioritized in a new mobile app relating to suicide prevention. On the basis of the survey results, a clinical design group, comprising 6 members with experience in fields such as mobile health (mHealth), clinical psychology, and suicide prevention, was established. This group was supplemented with further input from additional clinicians who provided feedback over three focus group sessions. The sessions were centered on refining existing app components and evaluating new feature requests. This process was iterated through regular feedback until agreement was reached on the overall app design and functionality. RESULTS: A fully functional mobile app, known as the SafePlan app, was developed and tested with the input of clinicians through an iterative design process. The app's core function is to provide an interactive safety plan to support users with suicidal thoughts or behaviors as an adjunct to face-to-face therapy. A diary component that facilitates the generalization of skills learned through dialectical behavior therapy was also implemented. Usability testing was carried out on the final prototype by students from a local secondary school, who are representative of the target user population in both age and technology experience. The students were asked to complete a system usability survey (SUS) at the end of this session. The mean overall SUS rating was 71.85 (SD 1.38). CONCLUSIONS: The participatory process involving key stakeholders (clinicians, psychologists, and information technology specialists) has resulted in the creation of an mHealth intervention technology that has the potential to increase accessibility to this type of mental health service for the target population. The app has gone through the initial testing phase, and the relevant recommendations have been implemented, and it is now ready for trialing with both clinicians and their patients.

Radiosurgery for dural arteriovenous malformations.

Intracranial dural arteriovenous malformations (DAVFs) are relatively uncommon vascular lesions characterized by the direct connection of dural arteries into dural venous sinuses or leptomeningeal veins. Strategies for the treatment of these complex lesions have evolved significantly over the past three decades, and include open surgical disconnection, endovascular embolization, stereotactic radiosurgery (SRS), or a combination of these approaches. Radiosurgical intervention is unique in offering significant benefits to patients while exposing them to few of the risks associated with more invasive interventions. In this chapter we provide an overview of DAVFs and discuss the features of these lesions that affect management. We focus, in particular, on radiosurgical management of these lesions, describing present treatment paradigms, the procedure for the treatment of DAVFs with SRS, and expected clinical outcomes using SRS.

Delayed hemorrhage from the tissue of an occluded arteriovenous malformation after stereotactic radiosurgery: report of 3 cases.

Stereotactic radiosurgery is widely used to treat cerebral arteriovenous malformations (AVMs), with the goal of complete angiographic obliteration. A number of case series have challenged the assumption that absence of residual AVM on follow-up angiograms is consistent with elimination of the risk of hemorrhage. The authors describe 3 cases in which patients who had angiographic evidence of AVM occlusion presented with late hemorrhage in the area of their prior lesions. They compare the radiographic, angiographic, and histological features of these patients with those previously described in the literature. Delayed hemorrhage from the tissue of occluded AVMs has been reported as early as 4 and as late as 11 years after initial stereotactic radiosurgery. In all cases for which data are available, hemorrhage occurred in the area of persistent imaging findings despite negative findings on conventional angiography. The hemorrhagic lesions that were resected demonstrated a number of distinct histological findings. While rare, delayed hemorrhage from the tissue of occluded AVMs may occur from a number of distinct, angiographically occult postirradiation changes. The hemorrhages in the authors' 3 cases were symptomatic and localized. The correlation of histological and imaging findings in delayed hemorrhage from occluded AVMs is an area requiring further investigation.

Air travel with known pneumocephalus following outpatient sinus surgery.

BACKGROUND: Intracranial air is a common finding after many neurosurgical procedures and trauma to the head. In patients requiring transport via air to reach a destination there is risk of expansion of the intracranial air and development of neurological complications. Though relatively uncommon after functional endoscopic sinus surgery (FESS), pneumocephalus may be encountered. CASE REPORT: We describe one of our patients in whom intracranial air was introduced during FESS. Following the procedure she required commercial air transportation from our center to her home. A 45-min commercial flight to the destination was safely completed without the patient experiencing any neurological sequellae. DISCUSSION: This case highlights the controversy surrounding air travel with pneumocephalus and provides an example of safe commercial air travel after diagnosis of post-FESS pneumocephalus.

Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.

Vascular tissue engineering: the next generation.

It is the ultimate goal of tissue engineering: an autologous tissue engineered vascular graft (TEVG) that is immunologically compatible, nonthrombogenic, and can grow and remodel. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. However, in many cases these are damaged, have already been harvested, or are simply unusable. The use of synthetic conduits is severely limited in smaller diameter vessels due to increased incidence of thrombosis, infection, and graft failure. Current research has therefore energetically pursued the development of a TEVG that can incorporate into a patient's circulatory system, mimic the vasoreactivity and biomechanics of the native vasculature, and maintain long-term patency.