Gene expression analysis during progression of malignant meningioma compared to benign meningioma.

OBJECTIVE: Meningioma is the most common primary intracranial neoplasm. Only 1%-3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. METHODS: The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients' earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas. RESULTS: The authors' data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation. CONCLUSIONS: The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

Ultrasound-assisted thrombolysis for acute intermediate-high-risk pulmonary embolism.

INTRODUCTION: Eustachian tube dysfunction (ETD) may result in hearing loss, chronic otitis and cholesteatoma. With advances in treatment options, the identification of patients with obstructive ETD is becoming increasingly important. The objective of this study was to validate a Danish translation of the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). METHODS: All participants underwent tympanometry, otomicroscopy and completed the ETDQ-7. We included 34 ears from patients with obstructive ETD who had abnormal tympanometry curves but no history of cholesteatoma or adhesive otitis. As a control group, 48 otherwise healthy ears with a normal tympanometry curve were included from patients with known sensorineural hearing loss or normal hearing. RESULTS: A Cronbach's alpha of 0.77 indicated a good internal consistency reliability of the questionnaire. The mean ETDQ-7 score in the obstructive ETD group was 31 versus 13.5 in the control group (p = 0.00). A receiver operating characteristics analysis produced an area under the curve of 94%, showing excellent discriminatory abilities between the groups. CONCLUSIONS: The ETDQ-7 has previously been validated in English, German, Dutch and Portuguese, demonstrating good clinical relevance. The Danish translation of the ETDQ-7 has produced similar results and may be valuable in diagnosing obstructive ETD and in monitoring the effect of balloon dilation of the Eustachian tube. FUNDING: none. The study was approved by the Danish Data Protection Agency (VD-2018-33, I-Suite 6229).