Background Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a three-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management. Methods We evaluated whether chromosomal copy-number data improved prediction of time to recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in two independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms. Results We developed a three-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent AUC, average precision, and the Brier score. Conclusion We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.

Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive life threatening infection that is seen most commonly among immunocompromised patients. We present a case series of 18 patients clinically and histopathologically diagnosed with AIFRS with a mean follow-up of 9.11 ± 2.51 months (range 6-17). Demographic data, apparent symptoms and signs, underlying disorders, and outcomes are discussed. The mean age was 39.56 ± 20.66 years (range 2-75). The most common underlying diseases were diabetes mellitus (50 %) and leukemia (44.44 %). Mucosal biopsy confirmed fungal invasion of the nasal mucosa in all cases. The main fungi were Rhizopus oryzae (55.56 %), Absidia mucor (16.67 %), and Aspergillus fumigatus (27.78 %). Headache and facial pain (77.8 %), facial paresthesia (55.6 %), and ophthalmoplegia (33.3 %) were the most common symptoms and signs. Computed tomography and endoscopic findings showed various stages of sinonasal (100 %), pterygopalatine fossa (55.56 %), orbital (44.45 %), and cerebral (5.56 %) involvement. All patients underwent serial surgical debridement (3.78 ± 1.80 times; range 2-8) simultaneously with systemic antifungal therapy and proper management of the underlying disease. The most extreme case with brain involvement survived and recovered with no evidence of recurrent disease following treatment. All patients were considered cured after two endoscopic negative histopathologic evaluations. Three patients (16.67 %) died, one from uncontrolled leukemia and two due to renal failure. AIFRS is a potentially fatal condition, however, early diagnosis and management of the underlying disease accompanied with systemic antifungal and aggressive serial surgical intervention appears to be effective in reducing mortality in most patients.

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.