Topographic Patterns of Intracranial Meningioma Recurrences-Systematic Review with Clinical Implication.

BACKGROUND: While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence. METHODS: The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed. RESULTS: Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it. CONCLUSIONS: Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information.

Process and quality evaluation of different improved composts made with a smart laboratory pilot plant.

This study monitored the process and investigated the quality of compost obtained from different biomasses. Five blends of agri-food waste were composted by a laboratory pilot plant named COMPOSTER, that is designed to optimize biodegradation, and produce compost efficiently. The COMPOSTER consists of two 35-liter nearly adiabatic, aerated bioreactors that simulate an industrial process involving the typical sequence of mesophilic-thermophilic-mesophilic phases. It continuously monitors and records temperature, internal pressure, and biomass weight, while controlling and quantifying oxygen consumption and carbon dioxide emissions resulting from aerobic biodegradation. All composts were characterized for their main chemical, physical, and molecular features, as well as their suppressiveness against Fusarium oxysporum f.sp. lycopersici (FOL), tested on tomato seedlings. Optimized biodegradation yielded 50-60 % mature compost with a cumulative oxygen consumption ranging from 282 to 456 gO2 per kg of dry matter, with peaks of 2.55 gO2 per kg of volatile solids per hour, and carbon dioxide emissions of 22-36 % of the initial carbon content, with peaks of 5.89 g CO2 per kg of volatile solids per hour. Blends containing more ligno-cellulosic ingredients showed higher yields and lower CO2 emissions. Most of the nitrogen present initially was retained in the final compost; indeed, all mixtures exhibited an apparent nitrogen concentration increase due to carbon loss. Composting determined deep modifications in the molecular structure of the organic matter. 13C CPMAS-NMR and off-line thermochemolysis GC-MS analyses highlighted decomposition degree of polysaccharides and peptidic moieties, selective preservation of aliphatic and aromatic recalcitrant compounds, and optimal ongoing humification. All composts were non-phytotoxic, except for that including pepper crop residues, and all resulted rich in macro- and micro-elements for plant nutrition and proved to be active in controlling FOL disease. Compost comprising 81.2 % tomato crop waste exhibited the best growth performance and pathogen control on tomato. Mature, non-phytotoxic, nutrient-rich, and suppressive composts represent promising by-products that can be successfully recycled in agriculture, including high-value applications, leading to lower use of fertilizers and pesticides.

Application of the NSE score (Neurology-Stability-Epidural compression assessment) to establish the need for surgery in spinal metastases of elderly patients: a multicenter investigation.

PURPOSE: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. METHODS: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. RESULTS: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. CONCLUSION: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients.

Two-Dimensional Layered Heterojunctions for Photoelectrocatalysis.

Two-dimensional (2D) layered nanomaterial heterostructures, arising from the combination of 2D materials with other low-dimensional species, feature a large surface area to volume ratio, which provides a high density of active sites for catalytic applications and for (photo)electrocatalysis (PEC). Meanwhile, their electronic band structure and high electrical conductivity enable efficient charge transfer (CT) between the active material and the substrate, which is essential for catalytic activity. In recent years, researchers have demonstrated the potential of a range of 2D material interfaces, such as graphene, graphitic carbon nitride (g-C3N4), metal chalcogenides (MCs), and MXenes, for (photo)electrocatalytic applications. For instance, MCs such as MoS2 and WS2 have shown excellent catalytic activity for hydrogen evolution, while graphene and MXenes have been used for the reduction of carbon dioxide to higher value chemicals. However, despite their great potential, there are still major challenges that need to be addressed to fully realize the potential of 2D materials for PEC. For example, their stability under harsh reaction conditions, as well as their scalability for large-scale production are important factors to be considered. Generating heterojunctions (HJs) by combining 2D layered structures with other nanomaterials is a promising method to improve the photoelectrocatalytic properties of the former. In this review, we inspect thoroughly the recent literature, to demonstrate the significant potential that arises from utilizing 2D layered heterostructures in PEC processes across a broad spectrum of applications, from energy conversion and storage to environmental remediation. With the ongoing research and development, it is likely that the potential of these materials will be fully expressed in the near future.

Image-Guided Surgery in Complex Skull Base and Facial Fractures: Initial Experience on the Role of Intra-Operative Computer Tomography.

Surgery of fractures involving the skull base and the facial skeleton often presents challenges that should be addressed to prevent secondary brain injuries (i.e., cerebro-spinal fluid leak), preserve visual functioning, and guarantee a good esthetic result. Complex craniofacial reconstruction can be aided by navigation and pre-operative planning. In recent years, computerized planning of surgical reconstruction drastically increased the safety and efficacy of surgery, but the impact of intraoperative high quality image devices such as an intraoperative computed tomography (CT) scan has not been investigated yet. This case-control study reports the institutional preliminary experience of using intraoperative CT scans in the surgical management of complex cranio-facial fractures. The results in terms of accuracy of bony reconstruction and neurological or surgical complications have been analyzed in 12 consecutive patients treated with (6 cases) or without (6 cases) i-CT. Comparative analysis demonstrated a greater accuracy of reconstruction in patients treated with the assistance of i-CT. Intraoperative CT is a useful tool with a promising role in a multidisciplinary surgical approach to complex cranio-facial surgery.

Direct Transpedicular C2 Fixation for the Surgical Management of Hangman's Fractures: A "Second Youth" for the Judet Approach.

PURPOSE: The optimal management of hangman's fractures is controversial and the standard of care has been neither established nor supported by strong evidence. The Judet approach has been introduced in 1970 as surgical option to treat selected cases of hangman's fractures, harboring the advantage to preserve motion of the craniovertebral junction and to restore the C2 vertebra anatomy by insertion of transpedicular screws through the fracture line. This paper reviews the literature on hangman's fractures surgically managed by Judet approach, and reports two new illustrative cases. METHODS: The PubMed database was searched for the review process. After initial screening of abstracts and papers, 13 manuscripts were included in the present review.Two cases of hangman's fractures, a Levine-Edwards type I and a type IIA, respectively, treated with direct transpedicular C2 screw fixation are reported. Surgical steps of the Judet approach are also described. RESULTS: Our literature review revealed that the technique described by Judet is gaining appeal only in recent years and there is no consensus on surgical indications.No surgery-related complications were observed in the two reported cases. Patients experienced a significant reduction of neck pain postoperatively. Motion of craniovertebral junction was preserved in both patients at 3-, 6-, and 12-month follow-ups. CONCLUSIONS: Direct transpedicular osteosynthesis of C2-pars interarticularis fracture has been already demonstrated as effective in type II and IIA hangman's fractures. The application of such technique in selected patients with atypical type I fractures should also be considered in order to achieve early mobilization and avoid external fixation.

Brain Metastases from Breast Cancer Histologically Exhibit Solid Growth Pattern with at Least Focal Comedonecrosis: A Histopathologic Study on a Monocentric Series of 30 Cases.

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable of suggesting the mammary origin of a metastatic carcinoma in the brain. The following histological features were collected from a series of 30 cases of brain metastases from breast cancer: (i) a solid growth pattern; (ii) the presence of comedonecrosis; and (iii) glandular differentiation. Our results showed that most cases histologically exhibited a solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility for leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 in the immunohistochemical panel.

Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.

Editorial: Frontiers in Neuro Oncology and Neurosurgery.

Despite advances in our knowledge and treatments, Central Nervous System (CNS) Tumors remain the most difficult clinical challenge for the worldwide medical community [...].

Metabolic delineation of IDH1 wild-type glioblastoma surgical anatomy: how to plan the tumor extent of resection.

PURPOSE: Magnetic resonance imaging (MRI) is the current standard for preoperative planning of glioblastoma (GBM) surgery. However, recent data on the use of 11 C-methionine positron emission tomography (11[C]-MET PET) suggest its role in providing additional information beyond MRI. The purpose of this study is to establish if there is a correlation between anatomical and metabolic data. METHODS: We retrieved all GBM cases treated from 2014 to January 2021. Preoperative MRI (Enhancing Nodule -EN-, FLAIR and Total Tumor Volume -TTV-), PET volumes and histological samples obtained from the different tumor regions were evaluated to analyze potential correlations between anatomical, metabolic and pathological data. RESULTS: 150 patients underwent surgery for GBM and 49 of these were also studied preoperatively with 11[C]-MET PET; PET volume was evaluated in 47 patients. In 33 patients (70.21%) preoperative 11[C]-MET PET volume > preoperative EN volume and in 11 (23.4%) preoperative 11[C]-MET PET volume > preoperative TTV. We found a significant correlation between preoperative TTVs and PET volumes (p = 0.016) as well as between preoperative EN volumes and PET volumes (p = < 0.001). Histologically, 109 samples were evaluated. ENs samples exhibited the conventional GBM morphology while samples from the FLAIR regions showed white matter tissue, with focal to diffuse tumor cells infiltration and areas of reactive astrogliosis. CONCLUSION: We submit that 11[C]-MET PET volume generally overcome EN. The presence of neoplastic cells confirm these metabolic data. It should be considered in the surgical planning to achieve a Supra Total Resection (SupTR).

Short Efficacy Evaluation of External Ventricular Drains Versus Ventriculosubgaleal Shunt in the Management of Neonatal Posthemorrhagic Hydrocephalus: A Retrospective Single-Center Cohort Study.

BACKGROUND: Different temporizing neurosurgical procedures are available for the management of posthemorrhagic hydrocephalus in preterm newborns. OBJECTIVE: To evaluate the short efficacy of the external ventricular drains (EVDs) and the ventriculosubgaleal (VSG) shunt. METHODS: This is a Strengthening the Reporting of Observational Studies in Epidemiology-conformed retrospective cohort study. The inclusion criteria were (1) gestational age <37 weeks, (2) birth weight <1500 g, (3) posthemorrhagic hydrocephalus because of intraventricular hemorrhage grade II/III, and (4) EVD or VSG shunt procedure before ventriculoperitoneal (VP)-definite shunt. Twenty-four newborns were collected from 2006 to 2022. The end points considered were infectious events, proteinorrachia, reintervention rate, and time to conversion to definite VP shunt. RESULTS: Overall, 12/24 newborns underwent EVD, and the remnant had a VSG shunt. The results showed a statistically significant difference ( P = .02) concerning cerebrospinal fluid infections between the EVD group (50%) and VSG shunt 1 (8.33%). The reintervention rate of EVD was significantly higher (66.67%) compared with that of the VSG shunt group (8.33%). A statistically significant difference was stated between the 2 groups (t[13] = -8.250; P < .001) (mean difference ± standard error; 10.5 ± 1.273) in the mean number of days elapsed from the achievement of the ideal weight (2000 g) to the definitive VP drainage. CONCLUSION: The increased infectious risk and the higher reintervention rate in EVD were confirmed in this study. In addition, a significant delay in the time to -conversion from EVD to VP shunt was demonstrated. Despite these optimal results, the VSG shunt remains a low practiced intervention, probably because of the limited operator experience.

Histologic Definition of Enhancing Core and FLAIR Hyperintensity Region of Glioblastoma, IDH-Wild Type: A Clinico-Pathologic Study on a Single-Institution Series.

The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity areas of GBM IDHwt are often visible beyond the conventional EC. Therefore, the need to extend the surgical resection also to the FLAIR hyperintensity areas is a matter of debate. Since little is known about the histological composition of FLAIR hyperintensity regions, in this study we aimed to provide a comprehensive description of the histological features of EC and FLAIR hyperintensity regions sampled intraoperatively using neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence, in 33 patients with GBM, IDHwt. Assessing a total 109 histological samples, we found that FLAIR areas consisted in: (i) fragments of white matter focally to diffusely infiltrated by tumor cells in 76% of cases; (ii) a mixture of white matter with reactive astrogliosis and grey matter with perineuronal satellitosis in 15% and (iii) tumor tissue in 9%. A deeper knowledge of the histology of FLAIR hyperintensity areas in GBM, IDH-wt may serve to better guide neurosurgeons on the choice of the most appropriate surgical approach in patients with this neoplasm.

Lactate modulates microglia polarization via IGFBP6 expression and remodels tumor microenvironment in glioblastoma.

Lactic acidosis has been reported in solid tumor microenvironment (TME) including glioblastoma (GBM). In TME, several signaling molecules, growth factors and metabolites have been identified to induce resistance to chemotherapy and to sustain immune escape. In the early phases of the disease, microglia infiltrates TME, contributing to tumorigenesis rather than counteracting its growth. Insulin-like Growth Factor Binding Protein 6 (IGFBP6) is expressed during tumor development, and it is involved in migration, immune-escape and inflammation, thus providing an attractive target for GBM therapy. Here, we aimed at investigating the crosstalk between lactate metabolism and IGFBP6 in TME and GBM progression. Our results show that microglia exposed to lactate or IGFBP6 significantly increased the Monocarboxylate transporter 1 (MCT1) expression together with genes involved in mitochondrial metabolism. We, also, observed an increase in the M2 markers and a reduction of inducible nitric oxide synthase (iNOS) levels, suggesting a role of lactate/IGFBP6 metabolism in immune-escape activation. GBM cells exposed to lactate also showed increased levels of IGFBP6 and vice-versa. Such a phenomenon was coupled with a IGFBP6-mediated sonic hedgehog (SHH) ignaling increase. We, finally, tested our hypothesis in a GBM zebrafish animal model, where we observed an increase in microglia cells and igfbp6 gene expression after lactate exposure. Our results were confirmed by the analysis of human transcriptomes datasets and immunohistochemical assay from human GBM biopsies, suggesting the existence of a lactate/IGFBP6 crosstalk in microglial cells, so that IGFBP6 expression is regulated by lactate production in GBM cells and in turn modulates microglia polarization.

Post-traumatic intra-orbital meningoencephalocele in adults: technical note on a rare entity and review of the literature.

Post-traumatic orbital meningoencephaloceles related to orbital roof fractures are a challenging clinical entity because of their rarity and difficult differential diagnosis. We report a case of post-traumatic intra-orbital meningoencephalocele in a 69-year-old man, secondary to a likely trapdoor mechanism, treated with a modified one-piece orbitozygomatic craniotomy. We also performed an extensive literature review of traumatic Intra-Orbital Encephalocele related to Orbital Roof Fracture focused on adult patients on electronic databases including Scopus, MEDLINE/PubMed, and Google Scholar. Patient well recovered after surgery with immediate exophthalmos resolution and discharged without visual or neurological deficits. The literature review included 22 papers with a total of 28 patients: 22 males (78.6%) and 6 females (21.4%), with a median age of 34.7 years. Twenty-six patients (92.9%) reported ocular injuries, with associated intracranial complications in 16 cases (61.5%). Twenty-seven patients (96.4%) were surgically treated, 18 of those underwent unilateral or bilateral frontal approach. Most orbital roof fractures can be managed nanoperatively if asymptomatic. Indeed, when the intra-orbital volume decreases, for example due to an encephalocele, the intra-orbital pressure could increase and determine an orbital compartment syndrome. In our case, we performed a one-piece modified orbitozygomatic approach, which has several advantages in comparison to the frequent unilateral or bilateral frontal craniotomy like the better exposure of the brain and orbit and a minimum brain retraction.

circSMARCA5 Is an Upstream Regulator of the Expression of miR-126-3p, miR-515-5p, and Their mRNA Targets, Insulin-like Growth Factor Binding Protein 2 (IGFBP2) and NRAS Proto-Oncogene, GTPase (NRAS) in Glioblastoma.

The involvement of non-coding RNAs (ncRNAs) in glioblastoma multiforme (GBM) pathogenesis and progression has been ascertained but their cross-talk within GBM cells remains elusive. We previously demonstrated the role of circSMARCA5 as a tumor suppressor (TS) in GBM. In this paper, we explore the involvement of circSMARCA5 in the control of microRNA (miRNA) expression in GBM. By using TaqMan® low-density arrays, the expression of 748 miRNAs was assayed in U87MG overexpressing circSMARCA5. Differentially expressed (DE) miRNAs were validated through single TaqMan® assays in: (i) U87MG overexpressing circSMARCA5; (ii) four additional GBM cell lines (A172; CAS-1; SNB-19; U251MG); (iii) thirty-eight GBM biopsies; (iv) twenty biopsies of unaffected brain parenchyma (UC). Validated targets of DE miRNAs were selected from the databases TarBase and miRTarbase, and the literature; their expression was inferred from the GBM TCGA dataset. Expression was assayed in U87MG overexpressing circSMARCA5, GBM cell lines, and biopsies through real-time PCR. TS miRNAs 126-3p and 515-5p were upregulated following circSMARCA5 overexpression in U87MG and their expression was positively correlated with that of circSMARCA5 (r-values = 0.49 and 0.50, p-values = 9 × 10-5 and 7 × 10-5, respectively) in GBM biopsies. Among targets, IGFBP2 (target of miR-126-3p) and NRAS (target of miR-515-5p) mRNAs were positively correlated (r-value = 0.46, p-value = 0.00027), while their expression was negatively correlated with that of circSMARCA5 (r-values = -0.58 and -0.30, p-values = 0 and 0.019, respectively), miR-126-3p (r-value = -0.36, p-value = 0.0066), and miR-515-5p (r-value = -0.34, p-value = 0.010), respectively. Our data identified a new GBM subnetwork controlled by circSMARCA5, which regulates downstream miRNAs 126-3p and 515-5p, and their mRNA targets IGFBP2 and NRAS.

Anatomical distribution of cancer stem cells between enhancing nodule and FLAIR hyperintensity in supratentorial glioblastoma: time to recalibrate the surgical target?

It is ge nerally accepted that glioblastoma (GBM) arise from cancer stem cells (CSC); however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs. The inclusion criterion was the intraoperative sampling of different tumor regions individualized, thanks to neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). Thirty-three patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score), and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p = 0.851, ES p = 0.561, IRS p = 1.000) and the CD133 biomarker (IS p = 0.653, ES p = 0.409, IRS p = 0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Decision-Making Challenge of Ping-Pong Fractures in Children: Case Exemplification and Systematic Review of Literature.

Ping-pong fractures have become less frequent, and no definite predictors to determine which fractures will elevate spontaneously and which should undergo surgical treatment have been clearly defined. Herein, the authors present a revision of the literature, in which 54 papers were included, with a total of 228 children studied. Patients who underwent surgery accounted for 30%; elevation through obstetrical vacuum or other aspiration systems was applied in 30%; and spontaneous resolution occurred in 40%; in 4 patients, percutaneous microscrew elevation was applied. Overall, in 96.4% of patients, the outcome was favorable because we found no significant increase in the incidence of post-traumatic seizures or neurologic sequelae with no significant differences between treated patients and spontaneous elevation. Statistical analysis showed no significant differences among the different treatment methods (P = 0.53). Our results suggest that simple compound ping-pong fractures without brain compression, hematomas, or dural tears could benefit from conservative management. In cases of nonspontaneous resolution after 6 months, operative strategies should be performed, considering that there is no evidence of differences between vacuum elevation and surgical elevation.