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Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

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Luca Massimi, Giuseppe Maria Della Pepa, Gianpiero Tamburrini, and Concezio Di Rocco

Chiari malformation Type I (CM-I) is usually suspected in patients with slowly progressing neurological symptoms. However, in some instances, especially if syringomyelia is associated, an abrupt clinical onset is reported and is accompanied by an acknowledged risk of potentially severe clinical signs or even sudden death. Little is known about such a critical course in CM-I/syringomyelia complex.

The authors describe 3 challenging cases of the abrupt onset of CM-I/syringomyelia to reveal more information on the clinical presentation and pathogenetic mechanisms of this sudden and potentially severe clinical phenomenon: a 38-year-old man experienced acute respiratory failure requiring intubation following acute decompensation of hydrocephalus associated with Noonan syndrome, a 1-year-old boy had sudden hemiparesis and Horner syndrome after a minor head/neck injury, and a 2.5-year-old boy presented with quickly progressing tetraplegia and dyspnea after a mild flexion and extension neck injury a few hours before. All 3 patients showed a CM-I/syringomyelia complex at diagnosis, and all of them had a good neurological outcome after surgery despite the ominous clinical presentation.

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Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

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Ismail Zaed, Daniele Bongetta, Giuseppe Maria Della Pepa, Cesare Zoia, Teresa Somma, Matteo Zoli, Giovanni Raffa, and Grazia Menna

OBJECTIVE

Imposter syndrome (IS) occurs when high-achieving individuals have a pervasive sense of self-doubt combined with fear of being exposed as a fraud, despite objective measures of success. This is one of the main causes of burnout among professionals, threatening their mental health and general well-being. The prevalence and severity of IS among neurosurgery residents and young neurosurgeons has not been yet studied. The primary outcomes of this study were the prevalence and severity of IS.

METHODS

An anonymous cross-sectional survey including both a demographic questionnaire (Clance Imposter Phenomenon Survey) and compensatory mechanisms was distributed to young neurosurgeons and residents in neurosurgery in Italy.

RESULTS

A total of 103 responses were collected. The prevalence rate was 81.6%. Among the respondents with IS, 42.7% showed moderate signs, 27.2% frequent, and only 11.7% had an intense symptomatology. Level of education, female sex, and academic achievements were all identified as predictive factors of IS.

CONCLUSIONS

A total of 81.6% of respondents reported potentially significant levels. The implications of IS on both the outcomes in patients and the well-being of neurosurgeons should be evaluated in future studies.

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Grazia Menna, Ivana Manini, Daniela Cesselli, Miran Skrap, Alessandro Olivi, Tamara Ius, and Giuseppe Maria Della Pepa

OBJECTIVE

Glioma-associated stem cells (GASCs) have been indicated as possible players in supporting growth and recurrence in glioblastoma. However, their role in modulating immune response in the peritumoral area has not yet been described. In this study, the authors aimed to investigate programmed death-ligand 1 (PD-L1) differential expression at the protein level in GASCs derived from different tumor areas (core, periphery, and surrounding healthy brain).

METHODS

Tumor tissue samples were collected from patients who underwent surgery for a histopathologically confirmed diagnosis of glioblastoma. Sampling sites were confirmed via neuronavigation and categorized on 5-aminolevulinic acid (5-ALA) fluorescence as bright (ALA+), pale (ALA PALE), or negative (ALA−), which corresponds to the tumor mass, infiltrated peritumoral area, and healthy brain, respectively, during surgery. GASCs were first isolated from the 3 regions and analyzed; then Western blot analysis was used to evaluate the level of PD-L1 expression in the GASCs.

RESULTS

Overall, 7 patients were included in the study. For all patients, the mean values ± SD of PD-L1 expression in GASCs for ALA+, ALA PALE, and ALA− were 1.12 ± 1.14, 0.89 ± 0.63, and 0.57 ± 0.18, respectively. The differentially expressed values of PD-L1 in GASCs sampled from the 3 areas were found to be significant (p < 0.05) for 3 of the 7 patients: patient S470 (ALA+ vs ALA− and ALA PALE vs ALA−), patient S473 (ALA+ vs ALA PALE and ALA PALE vs ALA−), and patient S509 (ALA+ vs ALA−).

CONCLUSIONS

This analysis showed, for the first time, that GASCs expressed a constitutive level of PD-L1 and that PD-L1 expression in GASCs was not uniform among patients or within the same patient. GASC analysis combined with 5-ALA–guided sampling (from core to periphery) made it possible to highlight the role of the tumor microenvironment at the infiltrating margin, which might cause clinical resistance, opening interesting perspectives for the future.

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Giuseppe Maria Della Pepa, Quintino Giorgio D’Alessandris, Benedetta Burattini, Davide Quaranta, Carmelo Lucio Sturiale, Pier Paolo Mattogno, Roberto Pallini, and Alessandro Olivi

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Giuseppe Maria Della Pepa, Grazia Menna, Vito Stifano, Angelo Maria Pezzullo, Anna Maria Auricchio, Alessandro Rapisarda, Valerio Maria Caccavella, Giuseppe La Rocca, Giovanni Sabatino, Enrico Marchese, and Alessandro Olivi

OBJECTIVE

Providing new tools to improve surgical planning is considered a main goal in meningioma treatment. In this context, two factors are crucial in determining operating strategy: meningioma-brain interface and meningioma consistency. The use of intraoperative ultrasound (ioUS) elastosonography, a real-time imaging technique, has been introduced in general surgery to evaluate similar features in other pathological settings such as thyroid and prostate cancer. The aim of the present study was to evaluate ioUS elastosonography in the intraoperative prediction of key intracranial meningioma features and to evaluate its application in guiding surgical strategy.

METHODS

An institutional series of 36 meningiomas studied with ioUS elastosonography is reported. Elastographic data, intraoperative surgical findings, and corresponding preoperative MRI features were classified, applying a score from 0 to 2 to both meningioma consistency and meningioma-brain interface. Statistical analysis was performed to determine the degree of agreement between meningioma elastosonographic features and surgical findings, and whether intraoperative elastosonography was a better predictor than preoperative MRI in assessing meningioma consistency and slip-brain interface, using intraoperative findings as the gold standard.

RESULTS

A significantly high degree of reliability and agreement between ioUS elastographic scores and surgical finding scores was reported (intraclass correlation coefficient = 0.848, F = 12.147, p < 0.001). When analyzing both consistency and brain-tumor interface, ioUS elastography proved to have a rather elevated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive (LR+) and negative likelihood ratio (LR−). This consideration was true especially for meningiomas with a hard consistency (sensitivity = 0.92, specificity = 0.96, PPV = 0.92, NPV = 0.96, LR+ = 22.00, LR− = 0.09) and for those presenting with an adherent slip-brain interface (sensitivity = 0.76, specificity = 0.95, PPV = 0.93, NPV = 0.82, LR+ = 14.3, LR− = 0.25). Furthermore, predictions derived from ioUS elastography were found to be more accurate than MRI-derived predictions, as demonstrated by McNemar’s test results in both consistency (p < 0.001) and interface (p < 0.001).

CONCLUSIONS

While external validation of the data is needed to transform ioUS elastography into a fully deployable clinical tool, this experience confirmed that it may be integrated into meningioma surgical planning, especially because of its rapidity and cost-effectiveness.

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Tamara Ius, Teresa Somma, Roberto Altieri, Filippo Flavio Angileri, Giuseppe Maria Barbagallo, Paolo Cappabianca, Francesco Certo, Fabio Cofano, Alessandro D’Elia, Giuseppe Maria Della Pepa, Vincenzo Esposito, Marco Maria Fontanella, Antonino Germanò, Diego Garbossa, Miriam Isola, Giuseppe La Rocca, Francesco Maiuri, Alessandro Olivi, Pier Paolo Panciani, Fabrizio Pignotti, Miran Skrap, Giannantonio Spena, and Giovanni Sabatino

OBJECTIVE

Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients.

METHODS

Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score.

RESULTS

Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell’s c-index of 0.75 (95% CI 0.76–0.81).

CONCLUSIONS

The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.