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Background: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. Methods: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. Results: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. Conclusions: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success. [ABSTRACT FROM AUTHOR]

Simple Summary: In a case study, real-time neuropsychological testing (RTNT) and music listening were applied for resections in the left temporal–parietal lobe during awake surgery (AS). The preoperative, intraoperative, and postoperative neuropsychological evaluation of patients with brain tumors and those treated neurosurgically has become part of clinical protocols. It allows for the evaluation of the presence of any neuropsychological deficits and their severity, provides reliable indications regarding the patients' tolerability of an intervention in AS, and examines the cognitive and emotional motivational status of patients in the postoperative phase, thereby providing indications of the rehabilitation treatment and quality-of-life level. Moreover, we demonstrated that before/during AS and after music listening, the patient reported a decrease in depression and anxiety, in addition to an improvement in all the collected cognitive parameters. In conclusion, RTNT (also integrated with music listening) maximizes the surgical resection of lesions and minimizes the risks of post-operative neuropsychological and neurological sequelae through improving the quality of life of patients. In this case report, real-time neuropsychological testing (RTNT) and music listening were applied for resections in the left temporal–parietal lobe during awake surgery (AS). The case is based on a 66-year-old with glioblastoma and alterations in expressive language and memory deficit. Neuropsychological assessment was run at baseline (2–3 days before surgery), discharge from hospital (2–3 days after surgery), and follow-up (1 month and 3 months). RTNT was started before beginning the anesthetic approach (T0) and during tumor excision (T1 and T2). At T0, T1, and T2 (before performing neuropsychological tests), music listening was applied. Before AS and after music listening, the patient reported a decrease in depression and anxiety. During AS, an improvement was shown in all cognitive parameters collected at T0, T1, and T2. After the excision and music listening, the patient reported a further decrease in depression and anxiety. Three days post surgery, and at follow-ups of one month and three months, the patient reported a further improvement in cognitive aspects, the absence of depression, and a reduction in anxiety symptoms. In conclusion, RTNT has been useful in detecting cognitive function levels during tumor excision. Music listening during AS decreased the patient's anxiety and depression symptoms. [ABSTRACT FROM AUTHOR]

Our anesthetic technique proposed for awake craniotomy is the monitored anesthesia care (MAC) technique, with the patient in sedation throughout the intervention. Our protocol involves analgo-sedation through the administration of dexmedetomidine and remifentanil in a continuous intravenous infusion, allowing the patient to be sedated and in comfort, but contactable and spontaneously breathing. Pre-surgery, the patient is pre-medicated with intramuscular clonidine (2 µg/kg); it acts both as an anxiolytic and as an adjuvant in pain management and improves hemodynamic stability. In the operating setting, dexmedetomidine in infusion and remifentanil in target controlled infusion (TCI) for effect are started. The purpose of the association is to exploit the pharmacodynamics of dexmedetomidine which guarantees the control of respiratory drive, and the pharmacokinetics of remifentanil characterized by insensitivity to the drug. Post-operative management: at the end of the surgical procedure, the infusion of drugs was suspended. Wake-up craniotomy is associated with reduced hospital costs compared to craniotomy performed in general anesthesia, mainly due to reduced costs in the operating room and shorter hospital stays. Greater patient satisfaction and the benefits of avoiding hospital stay have led to the evolution of outpatient intracranial neurosurgery. [ABSTRACT FROM AUTHOR]

Skull primary intraosseous cavernous hemangiomas (PICHs) are uncommon, benign, and slowgrowing tumors. These lesions are not widely known, specifically as regards the pathogenesis. The researchers wanted to describe the clinical presentations and radiological characteristics through a literature review of 140 cranial patients who received surgical treatment and histological diagnosis. Although PICH is uncommon, it should always be considered when a hard, steadily expanding skull lesion is seen. Surgical resection should be the first line of therapy for symptomatic individuals and aesthetic motivation, and their long-term results following complete removal are excellent. Moreover, we describe four patients with PICH to enrich the literature. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is an incurable tumor, with a median survival rate of only 14–15 months. Along with heterogeneity and unregulated growth, a central matter in dealing with GBMs is cell invasiveness. Thus, improving prognosis requires finding new agents to inhibit key multiple pathways, even simultaneously. A subset of GBM stem-like cells (GSCs) may account for tumorigenicity, representing, through their pathways, the proper cellular target in the therapeutics of glioblastomas. GSCs cells are routinely enriched and expanded due to continuous exposure to specific growth factors, which might alter some of their intrinsic characteristic and hide therapeutically relevant traits. Methods: By removing exogenous growth factors stimulation, here we isolated and characterized a subset of GSCs with a "mitogen-independent" phenotype (I-GSCs) from patient's tumor specimens. Differential side-by-side comparative functional and molecular analyses were performed either in vitro or in vivo on these cells versus their classical growth factor (GF)-dependent counterpart (D-GSCs) as well as their tissue of origin. This was performed to pinpoint the inherent GSCs' critical regulators, with particular emphasis on those involved in spreading and tumorigenic potential. Transcriptomic fingerprints were pointed out by ANOVA with Benjamini-Hochberg False Discovery Rate (FDR) and association of copy number alterations or somatic mutations was determined by comparing each subgroup with a two-tailed Fisher's exact test. The combined effects of interacting in vitro and in vivo with two emerging GSCs' key regulators, such as Wnt5a and EphA2, were then predicted under in vivo experimental settings that are conducive to clinical applications. In vivo comparisons were carried out in mouse-human xenografts GBM model by a hierarchical linear model for repeated measurements and Dunnett's multiple comparison test with the distribution of survival compared by Kaplan–Meier method. Results: Here, we assessed that a subset of GSCs from high-grade gliomas is self-sufficient in the activation of regulatory growth signaling. Furthermore, while constitutively present within the same GBM tissue, these GF-independent GSCs cells were endowed with a distinctive functional and molecular repertoire, defined by highly aggressive Wnt5aHigh/EphA2Low profile, as opposed to Wnt5aLow/EphA2High expression in sibling D-GSCs. Regardless of their GBM subtype of origin, I-GSCs, are endowed with a raised in vivo tumorigenic potential than matched D-GSCs, which were fast-growing ex-vivo but less lethal and invasive in vivo. Also, the malignant I-GSCs' transcriptomic fingerprint faithfully mirrored the original tumor, bringing into evidence key regulators of invasiveness, angiogenesis and immuno-modulators, which became candidates for glioma diagnostic/prognostic markers and therapeutic targets. Particularly, simultaneously counteracting the activity of the tissue invasive mediator Wnt5a and EphA2 tyrosine kinase receptor addictively hindered GSCs' tumorigenic and invasive ability, thus increasing survival. Conclusion: We show how the preservation of a mitogen-independent phenotype in GSCs plays a central role in determining the exacerbated tumorigenic and high mobility features distinctive of GBM. The exploitation of the I-GSCs' peculiar features shown here offers new ways to identify novel, GSCs-specific effectors, whose modulation can be used in order to identify novel, potential molecular therapeutic targets. Furthermore, we show how the combined use of PepA, the anti-Wnt5a drug, and of ephrinA1-Fc to can hinder GSCs' lethality in a clinically relevant xenogeneic in vivo model thus being conducive to perspective, novel combinatorial clinical application. [ABSTRACT FROM AUTHOR]

The association of a meningioma and intratumoral aneurysm is extremely rare. The coexistence of both lesions may cause difficulties in diagnosis and treatment. We present the case of a 65 y.o. woman with a left temporal meningioma and an intralesional ruptured aneurysm of a terminal branch of the middle cerebral artery whose parental vessel fed the tumor. The tumor and the embedded aneurysm were removed safely with improvement of her symptoms. [ABSTRACT FROM AUTHOR]

Background and Aims: The WHO has solicited all countries to eliminate HCV by 2030. The Italian government started routine screening for HCV infection in January 2021, initially targeting subjects born between 1969 and 1989. With the aim of achieving micro-elimination, we designed a hospital-wide project focusing on inpatients born from 1935 to 1985 and conducted it in our institution. Method: All inpatients aged 35 to 85, admitted from 10 February 2020 to 9 February 2021 for many different diseases and conditions underwent HCV antibody (HCVAb) testing by third-generation ELISA. When positive, reflex HCV RNA testing and genotyping were performed. Clinical history, fibrosis diagnosis, laboratory data and concomitant medications were available for all. Results: The HCV screening rate of inpatients was 100%. In total, 11,748 participants were enrolled, of whom 53.50% were male. The HCVAb positivity rate was 3.03%. The HCVAb rate increased with age and was higher for patients born between 1935 and 1944 (4.81%). The rate of HCV RNA positivity was 0.97%. The vast majority (80.70%) of HCV RNA-positive participants were 55 or older; in about 40% of cases, HCV RNA-positive patients were unaware of their infection. Although 16 patients died after HCV chronic infection diagnosis (two due COVID-19) or HCV treatment prescription (one due to COVID-19), 74.56% of patient HCV diagnoses were linked to HCV treatment, despite their co-morbidities. All patients older than 65 who died had an active HCV infection. Conclusion: The present study revealed a rate of active HCV infections among inpatients lower than what has been reported in the past in the general population; this appears to be a result of the widespread use of pangenotypic direct-acting antiviral agents (DAAs). The overall rate of active infection was lower than the rate observed in the 1935–1954 cohort. The high rate of inpatients unaware of HCV infections and the high number of deaths among subjects with an active HCV infection born from 1935 to 1954, suggest that, at least in southern Italy, targeted screening of this birth cohort may be required to reduce the number of undiagnosed cases and hidden infections. [ABSTRACT FROM AUTHOR]

Simple Summary: The most frequent intracranial neoplasm is meningioma. About 30% of these are represented by skull base meningiomas (SBMs). Patients with SBMs can be treated with a multimodal approach based on surgery, medical treatment and radiation-based therapy; however, the gold standard treatment for the majority of symptomatic meningiomas is still surgery. Surgical intervention is performed with the goal of maximum safe resection. This, however, poses technical challenges because of the proximity of these tumors with deep critical neurovascular structures, tumoral texture and consistency. A multimodal treatment, in combination with stereotactic radiosurgery and radiation therapy, is thus of utmost importance to achieve a satisfactory functional outcome and tumor control. The aim of this review was based on the identification of optimal multidisciplinary management of patients with SBMs. The investigation includes the relevant biological and clinical characteristics, the novel therapeutic approaches, highlighting the importance of a specialized multidisciplinary team, which is mandatory for SBM management. The surgical management of Skull Base Meningiomas (SBMs) has radically changed over the last two decades. Extensive surgery for patients with SBMs represents the mainstream treatment; however, it is often challenging due to narrow surgical corridors and proximity to critical neurovascular structures. Novel surgical technologies, including three-dimensional (3D) preoperative imaging, neuromonitoring, and surgical instruments, have gradually facilitated the surgical resectability of SBMs, reducing postoperative morbidity. Total removal is not always feasible considering a risky tumor location and invasion of surrounding structures and brain parenchyma. In recent years, the use of primary or adjuvant stereotactic radiosurgery (SRS) has progressively increased due to its safety and efficacy in the control of grade I and II meningiomas, especially for small to moderate size lesions. Patients with WHO grade SBMs receiving subtotal surgery can be monitored over time with surveillance imaging. Postoperative management remains highly controversial for grade II meningiomas, and depends on the presence of residual disease, with optional upfront adjuvant radiation therapy or close surveillance imaging in cases with total resection. Adjuvant radiation is strongly recommended in patients with grade III tumors. Although the currently available chemotherapy or targeted therapies available have a low efficacy, the molecular profiling of SBMs has shown genetic alterations that could be potentially targeted with novel tailored treatments. This multidisciplinary review provides an update on the advances in surgical technology, postoperative management and molecular profile of SBMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Subtyping for meningioma is urgently required to stratify the patients with high risks of recurrence and progression due to the intertumoral heterogeneity in meningioma. Here, we performed a consensus clustering of 179 meningiomas and identified progressive subtype (subtype 3) based the transcriptome profiles. Loss of chromosome 1q along with Neurofibromin 2 (NF2) mutation or loss of chromosome 22p is exclusively presented in subtype 3 meningioma. DNA methylation analyses of meningioma subtypes also suggested hypermethylation was observed in subtype 3 meningioma. Our findings identified low expression of Alkaline Phosphatase (ALPL) is the most significant feature in progressive subtype of meningioma. We constructed and validated a meningioma progression score (MPscore) to characterize the progressive phenotype in meningioma. The predictive accuracy has also been validated in three independent cohorts. Therefore, MPscore can be potentially useful for meningioma recurrence prediction and stratification. Meningioma is the most common tumor in central nervous system (CNS). Although most cases of meningioma are benign (WHO grade I) and curable by surgical resection, a few tumors remain diagnostically and therapeutically challenging due to the frequent recurrence and progression. The heterogeneity of meningioma revealed by DNA methylation profiling suggests the demand of subtyping for meningioma. Therefore, we performed a clustering analyses to characterize the progressive features of meningioma and constructed a meningioma progression score to predict the risk of the recurrence. A total of 179 meningioma transcriptome from RNA sequencing was included for progression subtype clustering. Four biologically distinct subtypes (subtype 1, subtype 2, subtype 3 and subtype 4) were identified. Copy number alternation and genomewide DNA methylation of each subtype was also characterized. Immune cell infiltration was examined by the microenvironment cell populations counter. All anaplastic meningiomas (7/7) and most atypical meningiomas (24/32) are enriched in subtype 3 while no WHO II or III meningioma presents in subtype 1, suggesting subtype 3 meningioma is a progressive subtype. Stemness index and immune response are also heterogeneous across four subtypes. Monocytic lineage is the most immune cell type in all meningiomas, except for subtype 1. CD8 positive T cells are predominantly observed in subtype 3. To extend the clinical utility of progressive meningioma subtyping, we constructed the meningioma progression score (MPscore) by the signature genes in subtype 3. The predictive accuracy and prognostic capacity of MPscore has also been validated in three independent cohort. Our study uncovers four biologically distinct subtypes in meningioma and the MPscore is potentially helpful in the recurrence risk prediction and response to treatments stratification in meningioma. [ABSTRACT FROM AUTHOR]