Development and Validation of a Multivariable Model to Predict Surgical Outcome in Patients with Chiari malformations.

Background: Surgical outcome predictive models for Chiari malformations (CM) which are applicable to all age groups and simple enough to use on outpatient basis are lacking. Objective: The aim of this study was to develop and validate a preoperative index for predicting long-term outcomes in Chiari 1 (CM1) and Chiari 0 (CM0) malformations. Materials and Methods: It was a single-institution, ambidirectional, cohort study from 2014 to 2019, having patients between 5 to 70 years. Outcome was assessed using Chicago Chiari outcome score (CCOS) over 2 years follow-up. Preoperative clinical and radiological factors were analyzed using Chi-square test and Mann Whitney U test, in relation to CCOS and those attaining P value ≤0.05, were used to develop model - Chiari Outcome Predictive Index (COPI). COPI was internally validated using 10-fold cross-validation and c-statistic for discrimination. Results: A total of 88 patients (66 in development and 22 in validation cohort) were included in the study. Outcome was negatively associated with presence of motor, sensory or cranial nerve symptoms, poor functional status, basilar invagination, and tonsillar descent. It was positively associated with shorter duration of presenting symptom (<9 months) and syrinx diameter <6 mm. COPI predicted CCOS with 91.1% accuracy (10-fold cross-validation). It had excellent discrimination for improved outcome (c = 0.968 in development and 0.976 in validation cohort), at threshold index of -1. Conclusions: COPI is simple tool that can be administered in outpatient setting. It can facilitate evidence-based preoperative counseling of patients, to help them develop reasonable expectations regarding surgical outcomes.

Immuno-phenotyping of IDH-mutant grade 3 astrocytoma and IDH-wildtype glioblastoma reveals specific differences in cells of myeloid origin.

Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade 3 and grade 4 or GBM) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high-grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, IDH-wild type) or grade 3 IDH-mutant gliomas. We observe that neutrophils are highly heterogeneous among individuals with glioma, and are different from healthy controls. We also show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade 3 IDH-mutant glioma tissue, and a larger proportion of granulocytic myeloid-derived suppressor cells are present in grade 3 IDH-mutant gliomas when compared to GBM. Finally, we demonstrate that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor and suggest that these may be used as possible markers for prognosis.