82 results on '"Agosti E"'
Search Results
2. Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study
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Agresta, G., primary, Campione, A., additional, Veiceschi, P., additional, Gallo, D., additional, Agosti, E., additional, Massimi, L., additional, Piatelli, G., additional, Consales, A., additional, Linsler, S., additional, Oertel, J., additional, Pozzi, F., additional, Tanda, M. L., additional, Castelnuovo, P., additional, and Locatelli, D., additional
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- 2022
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3. Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy
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Bongetta, D., Zoia, C., Agosti, E., Doglietto, F., Fiorindi, A., Spena, G., Fontanella, M.M., and Giussani, C.G.
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- 2022
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4. Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy
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Daniele, Bongetta, Cesare, Zoia, Edoardo, Agosti, Francesco, Doglietto, Alessandro, Fiorindi, Giannantonio, Spena, Marco M, Fontanella, Carlo G, Giussani, Bongetta, D, Zoia, C, Agosti, E, Doglietto, F, Fiorindi, A, Spena, G, Fontanella, M, and Giussani, C
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Aneurysm, SAH, Epidemiology, risk factor ,Surgery ,Neurology (clinical) - Abstract
Background: In recent years there have been significant advances in the diagnosis, management and treatment of intracranial aneurysms (IAs) in Italy. Changes in prevalence of several epigenetic risk factors in the population as well as in environmental factors may have influenced the epidemiological burden of this disease. No long-term, population-based study about the incidence of treated ruptured IAs (rIAs) in Italy has yet been reported in literature. Methods: A long-term (January 2015 - December 2020), nationwide epidemiology study was performed by using discharge data collected by the Italian National Agency for Regional Healthcare Services with a particular focus on the treatment incidence of rIAs. A sub-analysis per macro-areas (north, center, and south and islands) was also performed, including the data about regional healthcare systems organization. The prevalence of common epigenetic and environmental risk factors has been also assessed. Results: Over 6 years, the mean incidence of rIAs treatment was 2.7 x 100.000 per year (ds ± 0.1; range: 2.6-2.9). In 2020, there was a significant north-south decreasing gradient in incidence (north vs center vs south and islands: 3.4 vs 2.4 vs 1.8 x 100.000/year; all p
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- 2022
5. Endoscopic-assisted transorbital extended orbital exenteration: A multi-institutional preclinical study.
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Roccuzzo G, Vyskocil E, Hirtler L, Kandathil SA, Peris-Celda M, Agosti E, Kuan EC, Wang EW, Leong S, Sharma R, Borsetto D, Herman P, Vinciguerra A, Verillaud B, Bresson D, Taboni S, Erovic BM, Vural A, Dallan I, Doglietto F, Schreiber A, Mattavelli D, Rampinelli V, Arosio AD, Battaglia P, Valentini M, Turri-Zanoni M, Pozzi F, Volpi L, Bignami M, Castelnuovo P, Nicolai P, and Ferrari M
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- Humans, Surveys and Questionnaires, Paranasal Sinus Neoplasms surgery, Paranasal Sinus Neoplasms pathology, Orbital Neoplasms surgery, Female, Male, Neoplasm Invasiveness pathology, Endoscopy methods, Orbit Evisceration, Feasibility Studies
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Background: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE)., Methods: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized., Results: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported., Conclusions: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes., (© 2024 Wiley Periodicals LLC.)
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- 2024
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6. Lessons learned during COVID-19 pandemic, a worldwide survey: evolution of global neurosurgical practice.
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Deora H, Raheja A, Mishra S, Tandon V, Agosti E, Veiceschi P, Garg K, Naik V, Kedia S, Meena R, Munjal SS, Chaurasia B, Wellington J, Locatelli D, Fontanella MM, Singh M, Chandra PS, Kale SS, and Arnautovic K
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- Humans, Surveys and Questionnaires, Neurosurgery, SARS-CoV-2, Pandemics, Adult, Telemedicine, Male, COVID-19 epidemiology, Neurosurgeons, Neurosurgical Procedures trends
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Background: During the COVID-19 pandemic, a multitude of surveys have analyzed the impact virus spreading on the everyday medical practice, including neurosurgery. However, none have examined the perceptions of neurosurgeons towards the pandemic, their life changes, and the strategies they implemented to be able to deal with their patients in such a difficult time., Methods: From April 2021 to May 2021 a modified Delphi method was used to construct, pilot, and refine the questionnaire focused on the evolution of global neurosurgical practice during the pandemic. This survey was distributed among 1000 neurosurgeons; the responses were then collected and critically analyzed., Results: Outpatient department practices changed with a rapid rise in teleservices. 63.9% of respondents reported that they have changed their OT practices to emergency cases with occasional elective cases. 40.0% of respondents and 47.9% of their family members reported to have suffered from COVID-19. 56.2% of the respondents reported having felt depressed in the last 1 year. 40.9% of respondents reported having faced financial difficulties. 80.6% of the respondents found online webinars to be a good source of learning. 47.8% of respondents tried to improve their neurosurgical knowledge while 31.6% spent the extra time in research activities., Conclusions: Progressive increase in operative waiting lists, preferential use of telemedicine, reduction in tendency to complete stoppage of physical clinic services and drop in the use of PPE kits were evident. Respondents' age had an impact on how the clinical services and operative practices have evolved. Financial concerns overshadow mental health.
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- 2024
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7. Thyroid Eye Disease: Advancements in Orbital and Ocular Pathology Management.
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Scarabosio A, Surico PL, Singh RB, Tereshenko V, Musa M, D'Esposito F, Russo A, Longo A, Gagliano C, Agosti E, Jhanji E, and Zeppieri M
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Thyroid Eye Disease (TED) is a debilitating autoimmune condition often associated with thyroid dysfunction, leading to significant ocular and orbital morbidity. This review explores recent advancements in the management of TED, focusing on both medical and surgical innovations. The introduction of Teprotumumab, the first FDA-approved drug specifically for TED, marks a pivotal development in medical therapy. Teprotumumab targets the insulin-like growth factor-1 receptor (IGF-1R), effectively reducing inflammation and tissue remodeling. Clinical trials demonstrate its efficacy in reducing proptosis and improving quality of life, making it a cornerstone in the treatment of active, moderate-to-severe TED. Surgical management remains critical for patients with chronic TED or those unresponsive to medical therapy. Advancements in orbital decompression surgery, including image-guided and minimally invasive techniques, offer improved outcomes and reduced complications. Innovations in eyelid and strabismus surgery enhance functional and cosmetic results, further improving patient satisfaction. The management of TED necessitates a multidisciplinary approach involving endocrinologists, ophthalmologists, oculoplastic surgeons, radiologists, and other specialists. This collaborative strategy ensures comprehensive care, addressing the diverse aspects of TED from thyroid dysfunction to ocular health and psychological well-being. Future directions in TED treatment include emerging pharmacological therapies targeting different aspects of the disease's pathophysiology and advanced surgical techniques aimed at enhancing precision and safety. This review underscores the importance of a personalized, multidisciplinary approach in managing TED, highlighting current advancements, and exploring potential future innovations to improve patient outcomes and quality of life.
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- 2024
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8. Glioma Stem Cells as Promoter of Glioma Progression: A Systematic Review of Molecular Pathways and Targeted Therapies.
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Agosti E, Antonietti S, Ius T, Fontanella MM, Zeppieri M, and Panciani PP
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- Humans, Molecular Targeted Therapy, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms therapy, Brain Neoplasms metabolism, Animals, Signal Transduction, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Glioma genetics, Glioma pathology, Glioma therapy, Glioma metabolism, Disease Progression
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Gliomas' aggressive nature and resistance to therapy make them a major problem in oncology. Gliomas continue to have dismal prognoses despite significant advancements in medical science, and traditional treatments like surgery, radiation (RT), and chemotherapy (CT) frequently prove to be ineffective. After glioma stem cells (GSCs) were discovered, the traditional view of gliomas as homogeneous masses changed. GSCs are essential for tumor growth, treatment resistance, and recurrence. These cells' distinct capacities for differentiation and self-renewal are changing our knowledge of the biology of gliomas. This systematic literature review aims to uncover the molecular mechanisms driving glioma progression associated with GSCs. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. The first literature search was performed on 1 March 2024, and the search was updated on 15 May 2024. Employing MeSH terms and Boolean operators, the search focused on molecular mechanisms associated with GCSs-mediated glioma progression. Inclusion criteria encompassed English language studies, preclinical studies, and clinical trials. A number of 957 papers were initially identified, of which 65 studies spanning from 2005 to 2024 were finally included in the review. The main GSC model distribution is arranged in decreasing order of frequency: U87: 20 studies (32.0%); U251: 13 studies (20.0%); A172: 4 studies (6.2%); and T98G: 2 studies (3.17%). From most to least frequent, the distribution of the primary GSC pathway is as follows: Notch: 8 studies (12.3%); STAT3: 6 studies (9.2%); Wnt/β-catenin: 6 studies (9.2%); HIF: 5 studies (7.7%); and PI3K/AKT: 4 studies (6.2%). The distribution of molecular effects, from most to least common, is as follows: inhibition of differentiation: 22 studies (33.8%); increased proliferation: 18 studies (27.7%); enhanced invasive ability: 15 studies (23.1%); increased self-renewal: 5 studies (7.7%); and inhibition of apoptosis: 3 studies (4.6%). This work highlights GSC heterogeneity and the dynamic interplay within the glioblastoma microenvironment, underscoring the need for a tailored approach. A few key pathways influencing GSC behavior are JAK/STAT3, PI3K/AKT, Wnt/β-catenin, and Notch. Therapy may target these pathways. This research urges more study to fill in knowledge gaps in the biology of GSCs and translate findings into useful treatment approaches that could improve GBM patient outcomes.
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- 2024
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9. Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study.
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Rampinelli V, Paderno A, Conti C, Testa G, Modesti CL, Agosti E, Dohin I, Saccardo T, Vinciguerra A, Ferrari M, Schreiber A, Mattavelli D, Nicolai P, Holsinger C, and Piazza C
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Purpose: Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos., Methods: Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation., Results: The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%., Conclusions: The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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10. 3-Dimensional Printed Model of the Temporal Bone for Neurosurgical Training.
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Piazza A, Corvino S, Colosso GQ, Campeggi A, Agosti E, Serioli S, Frati A, and Santoro A
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Background and Objectives: The development of neurosurgical skills stands out as a paramount objective for neurosurgery residents during their formative years. Mastery of intricate and complex procedures is a time-intensive process marked by a gradually ascending learning curve. Consequently, the study and simulation on surgical models assume significant importance. One of the most intricate neuroanatomical regions includes the petrous and mastoid portions of the temporal bone. These regions host critical, highly functional, and vital neurovascular structures, including the facial nerve, cochlea, semicircular canals, internal carotid artery, and middle ear. This fully open-source 3-dimensional (3D) model of the temporal bone, created for educational purposes, should be easily and economically reproducible using a 3D printer, offering all residents the opportunity to understand the spatial location, three-dimensional anatomical structures, and fundamental intricacies of mastoidectomy., Methods: A 3D model of the temporal bone was fabricated using a computed tomography (CT) scan derived from an actual human body. The CT scan of the model was meticulously juxtaposed with the reference sample CT scan. Neurosurgical residents were recruited as participants for this study. Each participant was tasked with executing a mastoidectomy on 2 separate occasions, with a 2-week interval between attempts. Throughout these sessions, various parameters, including the time taken for task completion, the volume of bone removal, and any potential complications, were systematically registered., Results: The mean volume of bone removed increased by 34.5%, and the mean task time and the mean number of complications decreased by 10.3% and 25%, respectively, during the training., Conclusion: Engaging in training with cost-effective anatomical models constitutes a valuable tool for refining technical skills during residency. We posit that this type of model training should be incorporated as part of the trainee's curriculum during the residency program because of the myriad advantages evidenced by the findings of this study., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
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- 2024
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11. CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies.
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Agosti E, Garaba A, Antonietti S, Ius T, Fontanella MM, Zeppieri M, and Panciani PP
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- Humans, T-Lymphocytes immunology, T-Lymphocytes metabolism, Animals, Glioblastoma therapy, Glioblastoma immunology, Immunotherapy, Adoptive methods, Brain Neoplasms therapy, Brain Neoplasms immunology, Receptors, Chimeric Antigen immunology, Receptors, Chimeric Antigen genetics, Receptors, Chimeric Antigen metabolism
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The most common primary brain tumor is glioblastoma (GBM), yet the current therapeutic options for this disease are not promising. Although immunotherapeutic techniques have shown poor success in GBM thus far despite efforts, new developments provide optimism. One of these developments is chimeric antigen receptor (CAR)-T cell treatment, which includes removing and genetically modifying autologous T cells to produce a receptor that targets a GBM antigen before reintroducing the cells into the patient's body. A number of preclinical studies have produced encouraging results, which have led to the start of clinical trials assessing these CAR-T cell treatments for GBM and other brain tumors. Although results in tumors such as diffuse intrinsic pontine gliomas and lymphomas have been promising, preliminary findings in GBM have not produced any clinical benefits. The paucity of particular antigens in GBM, their inconsistent expression patterns, and the possible immunoediting-induced loss of these antigens after antigen-targeted therapy are some possible causes for this discrepancy. The goal of this systematic literature review is to assess potential approaches for creating CAR-T cells that are more effective for this indication, as well as the clinical experiences that are already being had with CAR-T cell therapy in GBM. Up until 9 May 2024, a thorough search was carried out across the three main medical databases: PubMed, Web of Science, and Scopus. Relevant Medical Subject Heading (MeSH) terms and keywords associated with "glioblastoma", "CAR-T", "T cell therapy", "overall survival", and "progression free survival" were employed in the search approach. Preclinical and clinical research on the application of CAR-T cells as a therapeutic approach for GBM are included in the review. A total of 838 papers were identified. Of these, 379 articles were assessed for eligibility, resulting in 8 articles meeting the inclusion criteria. The included studies were conducted between 2015 and 2023, with a total of 151 patients enrolled. The studies varied in CAR-T cell types. EGFRvIII CAR-T cells were the most frequently investigated, used in three studies (37.5%). Intravenous delivery was the most common method of delivery (62.5%). Median OS ranged from 5.5 to 11.1 months across the studies. PFS was reported in only two studies, with values of 7.5 months and 1.3 months. This systematic review highlights the evolving research on CAR-T cell therapy for GBM, emphasizing its potential despite challenges. Targeting antigens like EGFRvIII and IL13Rα2 shows promise in treating recurrent GBM. However, issues such as antigen escape, tumor heterogeneity, and immunosuppression require further optimization. Innovative delivery methods, combination therapies, and personalized approaches are crucial for enhancing CAR-T cell efficacy. Ongoing research is essential to refine these therapies and improve outcomes for GBM patients.
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- 2024
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12. Generative Adversarial Networks (GANs) in the Field of Head and Neck Surgery: Current Evidence and Prospects for the Future-A Systematic Review.
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Michelutti L, Tel A, Zeppieri M, Ius T, Agosti E, Sembronio S, and Robiony M
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Background: Generative Adversarial Networks (GANs) are a class of artificial neural networks capable of generating content such as images, text, and sound. For several years already, artificial intelligence algorithms have shown promise as tools in the medical field, particularly in oncology. Generative Adversarial Networks (GANs) represent a new frontier of innovation, as they are revolutionizing artificial content generation, opening opportunities in artificial intelligence and deep learning. Purpose: This systematic review aims to investigate what the stage of development of such technology is in the field of head and neck surgery, offering a general overview of the applications of such algorithms, how they work, and the potential limitations to be overcome in the future. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in conducting this study, and the PICOS framework was used to formulate the research question. The following databases were evaluated: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, ClinicalTrials.gov, ScienceDirect, and CINAHL. Results: Out of 700 studies, only 9 were included. Eight applications of GANs in the head and neck region were summarized, including the classification of craniosynostosis, recognition of the presence of chronic sinusitis, diagnosis of radicular cysts in panoramic X-rays, segmentation of craniomaxillofacial bones, reconstruction of bone defects, removal of metal artifacts from CT scans, prediction of the postoperative face, and improvement of the resolution of panoramic X-rays. Conclusions: Generative Adversarial Networks may represent a new evolutionary step in the study of pathology, oncological and otherwise, making the approach to the disease much more precise and personalized.
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- 2024
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13. Endoscopic-Assisted Anterior Petrosectomy for a Recurrent Petrous Chondrosarcoma in Ollier Disease: 2-Dimensional Operative Video.
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Agosti E, Grouls M, Jiang T, Charitos D, Justo J, Passeri T, Mandonnet E, and Froelich S
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Ollier disease (OD) is characterized by the formation of multiple enchondromas. Patients with OD can develop malignant tumors, most often chondrosarcomas. When chondrosarcomas occur at the skull base in OD, cure is often difficult to obtain by surgery being lesion limits poorly distinguishable within the extensive pathological bone. Owing to the possible multiplicity of lesions over time, radiotherapy, in particular proton therapy, should be used with caution. The goal of surgery is therefore maximal resection with functional preservation followed with a careful follow-up. In this video, the case of a 13-year-old girl with an OD and an incidentally found petrous apex chondrosarcoma is presented. An endoscopic endonasal biopsy was performed confirming the diagnosis of chondrosarcoma. Conservative management was chosen initially. Because of symptoms progression and significant tumor growth, surgical removal was proposed. Considering the limited pneumatization of the sphenoid sinus and the lateral location of the lesion, an endoscopic-assisted anterior petrosal approach was chosen. A small remnant of tumor was left below the internal auditory canal. Because of its progressive growth, an additional resection using the same surgical approach was performed, with additional anterior petrosal drilling along and below the cochlea under endoscopic guidance to remove the part of the lesion located under the internal auditory canal. Ultimately, gross total resection of the lesion was achieved. All human studies have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The patient's relatives provided informed consent to the surgical treatment, video recording, and publication of the data. The patient's relatives provided consent to the procedures. This work was performed according to the ethical standards of our Institutional Review Board, without the need for dedicated IRB approval., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
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- 2024
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14. Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.
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Agosti E, Zeppieri M, Ghidoni M, Ius T, Tel A, Fontanella MM, and Panciani PP
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Background: Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity., Aim: To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms., Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR)., Results: In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( e.g., LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( e.g., cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies., Conclusion: GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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15. The Current Diagnostic Performance of MRI-Based Radiomics for Glioma Grading: A Meta-Analysis.
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De Maria L, Ponzio F, Cho HH, Skogen K, Tsougos I, Gasparini M, Zeppieri M, Ius T, Ugga L, Panciani PP, Fontanella MM, Brinjikji W, and Agosti E
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- Humans, Neuroimaging standards, Neuroimaging methods, Radiomics, Glioma diagnostic imaging, Glioma pathology, Magnetic Resonance Imaging standards, Magnetic Resonance Imaging methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Neoplasm Grading
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Background: Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma., Methods: A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis., Results: In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used., Conclusions: Our findings confirm that present radiomics' diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)
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- 2024
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16. Surgery versus endovascular treatment for spinal dural arteriovenous fistulas: a multicenter experience and systematic literature review.
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Zanin L, Di Bonaventura R, Agosti E, di Bergamo LT, Daniele D, Saraceno G, Auricchio AM, Sturiale CL, Bergui M, Mardighian D, Stura G, Pedicelli A, Bresciani E, Migliorati K, Yohan A, Marchese E, Albanese A, Gasparotti R, Bernat AL, Houdart E, Olivi A, Froelich S, Bresson D, Fontanella MM, and Doglietto F
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- Humans, Neurosurgical Procedures methods, Male, Female, Middle Aged, Treatment Outcome, Aged, Postoperative Complications epidemiology, Embolization, Therapeutic methods, Central Nervous System Vascular Malformations surgery, Endovascular Procedures methods
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Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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17. Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review.
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Agosti E, Antonietti S, Zeppieri M, Ius T, Fiorindi A, Tel A, Robiony M, Panciani PP, and Fontanella MM
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Background : Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods : A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results : Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral ( n = 8, 44.4%), followed by clivus ( n = 7, 38.9%) and lumbar spine ( n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery ( n = 10, 55.6%), RT ( n = 9, 50.0%), and systemic treatments ( n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions : This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.
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- 2024
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18. In Reply: Commentary: Letter: Visual Field Defects in the Setting of Suprasellar Lesions: Could Vascularization Patterns of the Optic Chiasm Play a Role?
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Agosti E, Alexander AY, Pinheiro-Neto CD, Link MJ, Meyer FB, and Peris-Celda M
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- Humans, Vision Disorders, Skull, Optic Chiasm, Visual Fields
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- 2024
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19. Comparative Efficacy of Transsphenoidal and Transcranial Approaches for Treating Tuberculum Sellae Meningiomas: A Systematic Review and Meta-Analysis.
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Agosti E, Alexander AY, Antonietti S, Zeppieri M, Piazza A, Panciani PP, Fontanella MM, Pinheiro-Neto C, Ius T, and Peris-Celda M
- Abstract
Background/Objectives : Tuberculum sellae meningiomas (TSMs) constitute 5-10% of intracranial meningiomas, often causing visual impairment. Traditional microsurgical transcranial approaches (MTAs) have been effective, but the emergence of innovative surgical trajectories, such as endoscopic endonasal approaches (EEAs), has sparked debate. While EEAs offer advantages like reduced brain retraction, they are linked to higher cerebrospinal fluid leak (CSF leak) risk. This meta-analysis aims to comprehensively compare the efficacy and safety of EEAs and MTAs for the resection of TSMs, offering insights into their respective outcomes and complications. Methods : A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on TSMs treated with either EEA or MTA until 2024. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. Results : A total of 291 papers were initially identified, of which 18 studies spanning from 2000 to 2024 met the inclusion criteria. The exclusion of 180 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and a lack of details on method/results. The 18 studies comprised a total sample of 1093 patients: 444 patients who underwent EEAs and 649 patients who underwent MTAs for TSMs. Gross total resection (GTR) rates ranged from 80.9% for EEAs to 79.8% for MTAs. The rate of visual improvement was 86.6% in the EEA group and 65.4% in the MTA group. The recurrence rate in the EEA group was 6.9%, while it was 5.1% in MTA group. The postoperative complications analyzed were CSF leak, infections, dysosmia, intracranial hemorrhage (ICH), and endocrine disorders. The rate of CSF leak was 9.8% in the EEA group and 2.1% in MTA group. The rate of infections in the EEA group was 5.7%, while it was 3.7% in the MTA group. The rate of dysosmia ranged from 10.3% for MTAs to 12.9% for EEAs. The rate of ICH in the EEA group was 0.9%, while that in the MTA group was 3.8%. The rate of endocrine disorders in the EEA group was 10.8%, while that in the MTA group was 10.2%. No significant difference was detected in the rate of GTR between the EEA and MTA groups (OR 1.15, 95% CI 0.7-0.95; p = 0.53), while a significant benefit in visual outcomes was shown in EEAs (OR 3.54, 95% CI 2.2-5.72; p < 0.01). There was no significant variation in the recurrence rate between EEA and MTA groups (OR 0.92, 95% CI 0.19-4.46; p = 0.89). While a considerably increased chance of CSF leak from EEAs was shown (OR 4.47, 95% CI 2.52-7.92; p < 0.01), no significant difference between EEA and MTA groups was detected in the rate of infections (OR 1.92, 95% CI 0.73-5.06; p = 0.15), the rate of dysosmia (OR 1.25, 95% CI 0.31-4.99; p = 0.71), the rate of ICH (OR 0.61, 95% CI 0.20-1.87; p = 0.33), and the rate of endocrine disorders (OR 1.16, 95% CI 0.69-1.95; p = 0.53). Conclusions : This meta-analysis suggests that both EEAs and MTAs are viable options for TSM resection, with distinct advantages and drawbacks. The EEAs demonstrate superior visual outcomes in selected cases while GTR and recurrence rates support the overall effectiveness of MTAs and EEAs. Endoscopic endonasal approaches had a higher chance of CSF leaks, but there are no appreciable variations in other complications. These results provide additional insights regarding patient outcomes in the intricate clinical setting of TSMs.
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- 2024
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20. 360° around the orbit: key surgical anatomy of the microsurgical and endoscopic cranio-orbital and orbitocranial approaches.
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Agosti E, Alexander AY, Plou P, Leonel LCPC, De Bonis A, Bauman MMJ, García-Lliberós A, Piazza A, Torregrossa F, Pinheiro Neto CD, and Peris Celda M
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- Humans, Endoscopy methods, Cranial Fossa, Middle surgery, Craniotomy methods, Cadaver, Neurosurgical Procedures methods, Orbit surgery
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Objective: Several pathologies either invade or arise within the orbit. These include meningiomas, schwannomas, and cavernous hemangiomas among others. Although several studies describing various approaches to the orbit are available, no study describes all cranio-orbital and orbitocranial approaches with clear, surgically oriented anatomical descriptions. As such, this study aimed to provide a comprehensive guide to the microsurgical and endoscopic approaches to and through the orbit., Methods: Six formalin-fixed, latex-injected cadaveric head specimens were dissected in the surgical anatomy laboratory at the authors' institution. In each specimen, the following approaches were modularly performed: endoscopic transorbital approaches (ETOAs), including a lateral transorbital approach and a superior eyelid crease approach; endoscopic endonasal approaches (EEAs), including those to the medial orbit and optic canal; and transcranial approaches, including a supraorbital approach, a fronto-orbital approach, and a 3-piece orbito-zygomatic approach. Each pertinent step was 3D photograph-documented with macroscopic and endoscopic techniques as previously described., Results: Endoscopic endonasal approaches to the orbit afforded excellent access to the medial orbit and medial optic canal. Regarding ETOAs, the lateral transorbital approach afforded excellent access to the floor of the middle fossa and, once the lateral orbital rim was removed, the cavernous sinus could be dissected and the petrous apex drilled. The superior eyelid approach provides excellent access to the anterior cranial fossa just superior to the orbit, as well as the dura of the lesser wing of the sphenoid. Craniotomy-based approaches provided excellent access to the anterior and middle cranial fossa and the cavernous sinus, except the supraorbital approach had limited access to the middle fossa., Conclusions: This study outlines the essential surgical steps for major cranio-orbital and orbitocranial approaches. Endoscopic endonasal approaches offer direct medial access, potentially providing bilateral exposure to optic canals. ETOAs serve as both orbital access and as a corridor to surrounding regions. Cranio-orbital approaches follow a lateral-to-medial, superior-to-inferior trajectory, progressively allowing removal of protective bony structures for proportional orbit access.
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- 2024
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21. Current status and future perspectives on stem cell transplantation for spinal cord injury.
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Agosti E, Zeppieri M, Pagnoni A, Fontanella MM, Fiorindi A, Ius T, and Panciani PP
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Background: Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption., Aim: To offer an up-to-date systematic literature review of clinical trial results con cerning stem cell therapy for SCI., Methods: A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI., Results: In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional impro vement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy., Conclusion: In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice., Competing Interests: Conflict-of-interest statement: All the author declare no conflict of interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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22. Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies.
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Agosti E, Zeppieri M, Antonietti S, Ius T, Fontanella MM, and Panciani PP
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Background: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance., Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects., Results: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%)., Conclusions: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.
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- 2024
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23. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.
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Agosti E, Zeppieri M, Antonietti S, Battaglia L, Ius T, Gagliano C, Fontanella MM, and Panciani PP
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Background: The blood-brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery., Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases., Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications., Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial.
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- 2024
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24. Superior Ethmoidal Approach to an Olfactory Groove Meningioma: Maximizing Preservation of Nasal Anatomy: 2-Dimensional Operative Video.
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Alexander AY, Agosti E, Pinheiro-Neto CD, and Peris-Celda M
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- 2024
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25. A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.
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De Maria L, Panciani PP, Zeppieri M, Ius T, Serioli S, Piazza A, Di Giovanni E, Fontanella MM, and Agosti E
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- Humans, Neuroglia, Aggression, Antibodies, Monoclonal, ErbB Receptors, Platelet-Derived Growth Factor, Glioma drug therapy
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High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to "high-grade gliomas", "metabolism", "target therapies", "monoclonal antibodies", "overall survival", and "progression-free survival". The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.
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- 2024
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26. Advancing Craniopharyngioma Management: A Systematic Review of Current Targeted Therapies and Future Perspectives.
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Agosti E, Zeppieri M, Antonietti S, Piazza A, Ius T, Fontanella MM, Fiorindi A, and Panciani PP
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- Humans, Imidazoles, Oximes, Ameloblastoma, Craniopharyngioma drug therapy, Craniopharyngioma genetics, Pituitary Neoplasms drug therapy, Pituitary Neoplasms genetics
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Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
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- 2024
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27. 360 Degrees Endoscopic Access to and Through the Orbit.
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Locatelli D, Veiceschi P, Arosio AD, Agosti E, Peris-Celda M, and Castelnuovo P
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- Humans, Cranial Fossa, Posterior, Confined Spaces, Sitting Position, Orbit surgery, Endoscopy
- Abstract
The treatment of pathologies located within and surrounding the orbit poses considerable surgical challenges, due to the intricate presence of critical neurovascular structures in such deep, confined spaces. Historically, transcranial and craniofacial approaches have been widely employed to deal with orbital pathologies. However, recent decades have witnessed the emergence of minimally invasive techniques aimed at reducing morbidity. Among these techniques are the endoscopic endonasal approach and the subsequently developed endoscopic transorbital approach (ETOA), encompassing both endonasal and transpalpebral approaches. These innovative methods not only facilitate the management of intraorbital lesions but also offer access to deep-seated lesions within the anterior, middle, and posterior cranial fossa via specific transorbital and endonasal corridors. Contemporary research indicates that ETOAs have demonstrated exceptional outcomes in terms of morbidity rates, cosmetic results, and complication rates. This study aims to provide a comprehensive description of endoscopic-assisted techniques that enable a 360° access to the orbit and its surrounding regions. The investigation will delve into indications, advantages, and limitations associated with different approaches, while also drawing comparisons between endoscopic approaches and traditional microsurgical transcranial approaches., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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28. Treatment strategy for vertebral metastases from anal squamous cell carcinoma: a comprehensive literature review and case report.
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Agosti E, Serioli S, Garg K, Pietrantoni A, Poliani PL, and Fontanella MM
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- Male, Humans, Aged, Spine, Combined Modality Therapy, Radiography, Magnetic Resonance Imaging, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell pathology
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Purpose/aim of the study: Purpose/aim of the study:Central nervous system (CNS), skull, and vertebral metastases from anal squamous cell carcinoma (SCC) are an exceedingly rare entity. We report the first case of multiple vertebral metastases from a primary anal SCC with the aim of define a target therapeutic strategy. Case presentation: We present the case of a 68-year-old male admitted to our hospital for acute exacerbation chronic low back pain and left L2 radiculopathy. His medical history included the diagnosis of a human papilloma virus related, moderately differentiated anal SCC (cT3N0M0-stage IIB), treated with standard chemoradiotherapy regimen two years earlier. Spinal magnetic resonance imaging revealed an isolated solid lesion of the L2 vertebral body. After the surgical removal, histopathological examination confirmed the diagnosis of moderately differentiated SCC. At 1-month radiological follow-up, two new lesions at the level of T7 to T11 were identified. Additional chemotherapy and radiotherapy for metastatic localization of L2, T7, and T11 were administered. Two-year follow-up demonstrated a radiologically and clinically well-controlled disease. To supplement our case, a systematic literature review on the CNS, skull, and vertebral metastases and their treatments has been performed. Conclusion: Despite several proposed guidelines for the management of vertebral metastases, at present, a universally accepted treatment strategy for vertebral metastases from anal SCC has not been defined. Based on our clinical experience and literature review, in case of vertebral metastases from anal SCC, a prompt and aggressive, local and systemic, and multimodal treatment of the vertebral lesions may be paramount to improve the patient outcomes.
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- 2023
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29. Non-surgical management of chronic subdural hematoma: insights and future perspectives from an international survey including neurosurgeons from 90 countries worldwide.
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De Maria L, Chaurasia B, Agosti E, Garg K, Burkhardt JK, Goehre F, Borghei-Razavi H, Servadei F, and Fontanella MM
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Background: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical conditions. Although surgical evacuation is still the gold standard for treatment, recent advances have led to the development of other management strategies, such as medical therapies and endovascular middle meningeal artery (MMA) embolization. Through this international survey, we investigated the global trends in cSDH management, focusing on medical and endovascular treatments., Design and Participants: A 14-question, web-based, anonymous survey was distributed to neurosurgeons worldwide., Results: Most responders do not perform MMA embolization (69.5%) unless for specific indications (29.6%). These indications include residual cSDH after surgical evacuation (58.9%) or cSDH in patients on antiplatelet medications to avoid surgical evacuation (44.8%). Survey participants from teaching versus non-teaching hospitals ( p = 0.002), public versus private hospitals ( p = 0.022), and Europe versus other continents ( p < 0.001) are the most users of MMA embolization. A large number of participants (51%) declare they use a conservative/medical approach, mainly to avoid surgery in patients with small cSDH (74.8%)., Conclusions: This survey highlights the current trends of cSDH management, focusing on conservative and MMA embolization treatment strategies. Most responders prefer a conservative approach for patients with small cSDHs not requiring surgical evacuation. However, in higher-risk scenarios such as residual hematomas after surgery or patients on antiplatelet medications, MMA embolization is regarded as a reasonable option by participants. Future studies should clarify the indications of MMA embolization, including appropriate patient selection and efficacy as a stand-alone procedure.
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- 2023
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30. Targeting microbiota in dietary obesity management: a systematic review on randomized control trials in adults.
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Caputo M, Pigni S, Antoniotti V, Agosti E, Caramaschi A, Antonioli A, Aimaretti G, Manfredi M, Bona E, and Prodam F
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- Adult, Humans, Phylogeny, Obesity, Diet, Gastrointestinal Microbiome, Metabolic Diseases
- Abstract
Obesity is an alarming public health problem. Tailored nutritional therapy is advisable since emerging evidence on complex cross-talks among multifactorial agents. In this picture, the gut microbiota is highly individualized and intricately dependent on dietary patterns, with implications for obesity management. Most of the papers on the topic are observational and often conflicting. This review aimed to systematically organize the body of evidence on microbiota deriving from dietary trials in adult obesity giving the most certain phylogenetic, and metabolomic signatures in relation to both the host metabolism and phenotype changes published until now. We retrieved 18 randomized control trials on 1385 subjects with obesity who underwent several dietary interventions, including standard diet and healthy dietary regimens. Some phyla and species were more related to diets rich in fibers and others to healthy diets. Weight loss, metabolism improvements, inflammatory markers decrease were specifically related to different microorganisms or functions. The Prevotella/Bacteroides ratio was one of the most reported predictors. People with the burden of obesity comorbidities had the most significant taxonomic changes in parallel with a general improvement. These data emphasize the possibility of using symbiotic approaches involving tailored diets, microbiota characteristics, and maybe drugs to treat obesity and metabolic disorders. We encourage Authors to search for specific phylogenetic associations beyond a too generally reported Firmicutes/Bacteroides ratio.
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- 2023
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31. Cigarette Smoking and Intracranial Aneurysms: A Pilot Analysis of SNPs in the CYP2A6 Gene in the Italian Population.
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Ferrari E, Cornali C, Fiorindi A, Agosti E, Gallone S, Rubino E, Ponzio F, Fontanella MM, and De Maria L
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- Humans, Polymorphism, Single Nucleotide genetics, Risk Factors, Italy epidemiology, Cytochrome P-450 CYP2A6 genetics, Cigarette Smoking adverse effects, Cigarette Smoking epidemiology, Cigarette Smoking genetics, Intracranial Aneurysm epidemiology, Intracranial Aneurysm genetics
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Background: Cigarette smoking is a modifiable risk factor associated with formation and rupture of intracranial aneurysms (IAs). Cytochrome P450 2A6 (CYP2A6) is the main enzyme implied in catabolism of nicotine and xenobiotics, giving rise to oxidative stress products. Our study investigated the associations between specific single-nucleotide polymorphisms (SNPs) in the CYP2A6 gene and the presence of sporadic IAs in a cluster of Italian patients, as well as their rupture regarding cigarette smoking habit., Methods: Three hundred and thirty-one Italian patients with sporadic IAs were recruited in a single institution. We recorded data on clinical onset with subarachnoid hemorrhage (SAH) and smoking habit. Genetic analysis was performed with a standard procedure on peripheral blood samples: CYP2A6 ∗1B2, CYP2A6 ∗2, and CYP2A6 ∗14 SNPs were analyzed in the study group along with 150 healthy control subjects. Statistical analysis was conducted according to genetic association study guidelines., Results: In the patient cohort, the frequency of aSAH was significantly higher in current smokers (P < 0.001; OR=17.45), regardless of the pattern of CYP2A6 SNPs. There was a correlation between IA rupture and cigarette smoking in patients with the heterozygous CYP2A6 ∗1B2 allele (P < 0.001; OR=15.47). All patients carrying the heterozygous CYP2A6 ∗14 allele had an aSAH event (100%), regardless of smoking habit, although this correlation was not statistically significant (P = 1)., Conclusions: According to our findings, a cigarette smoker carrying a fully active CYP2A6 enzyme (heterozygous ∗1B2 allele) may have an increased risk of IA rupture compared to those with functionally less active variants: further investigation on a larger sample is needed to verify this result. The role of the heterozygous CYP2A6 ∗14 allele in aSAH is yet to be clarified., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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32. Quantitative Anatomical Comparison of Surgical Approaches to Meckel's Cave.
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Zanin L, Agosti E, Ebner F, de Maria L, Belotti F, Buffoli B, Rezzani R, Hirt B, Ravanelli M, Ius T, Zeppieri M, Tatagiba MS, Fontanella MM, and Doglietto F
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Background: Meckel's cave is a challenging surgical target due to its deep location and proximity to vital neurovascular structures. Surgeons have developed various microsurgical transcranial approaches (MTAs) to access it, but there is no consensus on the best method. Newer endoscopic approaches have also emerged. This study seeks to quantitatively compare these surgical approaches to Meckel's cave, offering insights into surgical volumes and exposure areas., Methods: Fifteen surgical approaches were performed bilaterally in six specimens, including the pterional approach (PTA), fronto-temporal-orbito-zygomatic approach (FTOZA), subtemporal approach (STA), Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), endoscopic endonasal transpterygoid approach (EETPA), inferolateral transorbital approach (ILTEA) and superior eyelid approach (SEYA). All the MTAs were performed both with 10 mm and 15 mm of brain retraction, to consider different percentages of surface exposure. A dedicated navigation system was used to quantify the surgical working volumes and exposure of different areas of Meckel's cave (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Microsurgical transcranial approaches were quantified with two different degrees of brain retraction (10 mm and 15 mm). Statistical analysis was performed using a mixed linear model with bootstrap resampling., Results: The RSAS with 15 mm of retraction offered the maximum exposure of the trigeminal stem (TS). If compared to the KWA, the RSA exposed more of the TS (69% vs. 46%; p = 0.01). The EETPA and ILTEA exposed the Gasserian ganglion (GG) mainly in the anteromedial portion, but with a significant 20% gain in exposure provided by the EETPA compared to ILTEA (42% vs. 22%; p = 0.06). The STA with 15 mm of retraction offered the maximum exposure of the GG, with a significant gain in exposure compared to the STA with 10 mm of retraction (50% vs. 35%; p = 0.03). The medial part of the three trigeminal branches was mainly exposed by the EETPA, particularly for the ophthalmic (66%) and maxillary (83%) nerves. The EETPA offered the maximum exposure of the medial part of the mandibular nerve, with a significant gain in exposure compared to the ILTEA (42% vs. 11%; p = 0.01) and the SEY (42% vs. 2%; p = 0.01). The FTOZA offered the maximum exposure of the lateral part of the ophthalmic nerve, with a significant gain of 67% ( p = 0.03) and 48% ( p = 0.04) in exposure compared to the PTA and STA, respectively. The STA with 15 mm of retraction offered the maximum exposure of the lateral part of the maxillary nerve, with a significant gain in exposure compared to the STA with 10 mm of retraction (58% vs. 45%; p = 0.04). The STA with 15 mm of retraction provided a significant exposure gain of 23% for the lateral part of the mandibular nerve compared to FTOZA with 15 mm of retraction ( p = 0.03)., Conclusions: The endoscopic approaches, through the endonasal and transorbital routes, can provide adequate exposure of Meckel's cave, especially for its more medial portions, bypassing the impediment of major neurovascular structures and significant brain retraction. As far as the most lateral portion of Meckel's cave, MTA approaches still seem to be the gold standard in obtaining optimal exposure and adequate surgical volumes.
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- 2023
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33. Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.
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Agosti E, Zeppieri M, De Maria L, Tedeschi C, Fontanella MM, Panciani PP, and Ius T
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- Humans, Immune Checkpoint Inhibitors pharmacology, Neoplasm Recurrence, Local drug therapy, Immunotherapy methods, Immunotherapy, Adoptive, Tumor Microenvironment, Glioblastoma drug therapy, Cancer Vaccines therapeutic use, Cancer Vaccines pharmacology, Glioma drug therapy, Brain Neoplasms drug therapy
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Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
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- 2023
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34. Endoscopic-assisted en-bloc pterygomaxillectomy: Identifying an efficient and safe location for the pterygoid osteotomy.
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García-Lliberós A, Martin-Jimenez DI, Mondesir RJ, Agosti E, Alexander AY, Leonel LCPC, Choby G, Peris-Celda M, and Pinheiro-Neto CD
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- Humans, Maxillary Sinus, Osteotomy, Pterygopalatine Fossa diagnostic imaging, Pterygopalatine Fossa surgery, Endoscopy, Sphenoid Bone surgery
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Background: For aggressive maxillary sinus and pterygopalatine fossa (PPF) tumors, an en-bloc pterygomaxillectomy may be indicated., Methods: Five head specimens were used to study the feasibility of an en-bloc pterygomaxillectomy. Eighty-five non-pathological CT scans were used to compare the superior edge of the inferior turbinate (IT) and the middle turbinate tail (MT) as landmarks for the pterygoid osteotomy., Results: Through a combined sublabial-subperiosteal incision and transoral route, a mid-sagittal osteotomy through the hard palate and an axial osteotomy below the infraorbital foramen were performed. For the endoscopic pterygoid osteotomy, an infra-vidian transpterygoid approach was performed, subsequently removing the pterygomaxillectomy en-bloc. As landmarks, the osteotomies at the level of the MT tail and IT resected the pterygoid plates completely, but the IT osteotomy was further away from the vidian canal (7.5 vs. 6 mm)., Conclusions: The endoscopic-assisted en-bloc pterygomaxillectomy is feasible. The IT landmark is safe and ensures complete resection of the pterygoid plates., (© 2023 Wiley Periodicals LLC.)
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- 2023
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35. Surgical Treatment of Spheno-Orbital Meningiomas: A Systematic Review and Meta-Analysis of Surgical Techniques and Outcomes.
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Agosti E, Zeppieri M, De Maria L, Mangili M, Rapisarda A, Ius T, Spadea L, Salati C, Tel A, Pontoriero A, Pergolizzi S, Angileri FF, Fontanella MM, and Panciani PP
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Background: Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary treatment approach for SOMs. Several surgical approaches have been described during the decades, including microsurgical transcranial (MTAs), endoscopic endonasal (EEAs), endoscopic transorbital (ETOAs), and combined approaches, and the choice of surgical approach remains a topic of debate., Purpose: This systematic review and meta-analysis aim to compare the clinical and surgical outcomes of different surgical approaches used for the treatment of SOMs, discussing surgical techniques, outcomes, and factors influencing surgical decision making., Methods: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on the role of surgery for the treatment of SOMs until 2023. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications., Results: A total of 59 studies comprising 1903 patients were included in the systematic review and meta-analysis. Gross total resection (GTR) rates ranged from 23.5% for ETOAs to 59.8% for MTAs. Overall recurrence rate after surgery was 20.7%. Progression-free survival (PFS) rates at 5 and 10 years were 75.5% and 49.1%, respectively. Visual acuity and proptosis improvement rates were 57.5% and 79.3%, respectively. Postoperative cranial nerve (CN) focal deficits were observed in 20.6% of cases. The overall cerebro-spinal fluid (CSF) leak rate was 3.9%, and other complications occurred in 13.9% of cases. MTAs showed the highest GTR rates (59.8%, 95%CI = 49.5-70.2%; p = 0.001) but were associated with increased CN deficits (21.0%, 95%CI = 14.5-27.6%). ETOAs had the lowest GTR rates (23.5%, 95%CI = 0.0-52.5%; p = 0.001), while combined ETOA and EEA had the highest CSF leak rates (20.3%, 95%CI = 0.0-46.7%; p = 0.551). ETOAs were associated with better proptosis improvement (79.4%, 95%CI = 57.3-100%; p = 0.002), while anatomical class I lesions were associated with better visual acuity (71.5%, 95%CI = 63.7-79.4; p = 0.003) and proptosis (60.1%, 95%CI = 38.0-82.2; p = 0.001) recovery. No significant differences were found in PFS rates between surgical approaches., Conclusion: Surgical treatment of SOMs aims to preserve visual function and improve proptosis. Different surgical approaches offer varying rates of GTR, complications, and functional outcomes. A multidisciplinary approach involving a skull base team is crucial for optimizing patient outcomes.
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- 2023
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36. Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods.
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Agosti E, De Maria L, Mattogno PP, Della Pepa GM, D'Onofrio GF, Fiorindi A, Lauretti L, Olivi A, Fontanella MM, and Doglietto F
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Background: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery., Methods: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R., Results: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data., Conclusion: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.
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- 2023
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37. Editorial: Veins in the brain.
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Crobeddu E, Agosti E, Cossandi C, Tardivo V, De Maria L, Serioli S, Fontanella MM, and Valvassori L
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2023
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38. Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Endoscopic Endonasal Middle-Inferior Clivectomy, Odontoidectomy, and Far-Medial Approach.
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Agosti E, Alexander AY, Leonel LCPC, Gompel JJV, Link MJ, Choby G, Pinheiro-Neto CD, and Peris-Celda M
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Introduction The clival, paraclival, and craniocervical junction regions are challenging surgical targets. To approach these areas, endoscopic endonasal transclival approaches (EETCAs) and their extensions (far-medial approach and odontoidectomy) have gained popularity as they obviate manipulating and working between neurovascular structures. Although several cadaveric studies have further refined these contemporary approaches, few provide a detailed step-by-step description. Thus, we aim to didactically describe the steps of the EETCAs and their extensions for trainees. Methods Six formalin-fixed cadaveric head specimens were dissected. All specimens were latex-injected using a six-vessel technique. Endoscopic endonasal middle and inferior clivectomies, far-medial approaches, and odontoidectomy were performed. Results Using angled endoscopes and surgical instruments, an endoscopic endonasal midclivectomy and partial inferior clivectomy were performed without nasopharyngeal tissue disruption. To complete the inferior clivectomy, far-medial approach, and partially remove the anterior arch of C1 and odontoid process, anteroinferior transposition of the Eustachian-nasopharynx complex was required by transecting pterygosphenoidal fissure tissue, but incision in the nasopharynx was not necessary. Full exposure of the craniocervical junction necessitated bilateral sharp incision and additional inferior mobilization of the posterior nasopharynx. Unobstructed access to neurovascular anatomy of the ventral posterior fossa and craniocervical junction was provided. Conclusion EETCAs are a powerful tool for the skull-base surgeon as they offer a direct corridor to the ventral posterior fossa and craniocervical junction unobstructed by eloquent neurovasculature. To facilitate easier understanding of the EETCAs and their extensions for trainees, we described the anatomy and surgical nuances in a didactic and step-by-step fashion., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)
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- 2023
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39. Combined endoscopic endonasal and sublabial transmaxillary approaches for resection of intracranially extended juvenile nasopharyngeal angiofibroma.
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Marshall C, Agosti E, Peris-Celda M, and Pinheiro-Neto CD
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- Humans, Endoscopy, Treatment Outcome, Angiofibroma diagnostic imaging, Angiofibroma surgery, Angiofibroma pathology, Nasopharyngeal Neoplasms diagnostic imaging, Nasopharyngeal Neoplasms surgery, Nasopharyngeal Neoplasms pathology
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Background: Juvenile nasopharyngeal angiofibromas (JNAs) are rare, benign, and locally invasive nasopharyngeal tumors. Endoscopic endonasal resection is effective, non-invasive, with low complication rates. Until recently, endoscopic resection was not suitable for intracranially invasive tumors., Purpose/method: We describe resection steps of an intracranially extending JNA with a combined endoscopic endonasal and endoscopic-assisted sublabial transmaxillary approaches. Indications, advantages, and approach-specific complications are also discussed. The main surgical steps are shown in an operative video., Conclusion: Surgical excision of JNAs by a combined endoscopic endonasal and sublabial transmaxillary approaches represents a safe and effective treatment for selected intracranially invasive JNA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2023
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40. Comparison Between the Supracerebellar Infratentorial and Precuneal Interhemispheric, Transtentorial Approaches to the Cerebellomesencephalic Fissure: An Anatomoradiological Study and Illustrative Cases.
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Alexander AY, Agosti E, Leonel LCPC, Lanzino G, and Peris-Celda M
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- Humans, Brain Stem diagnostic imaging, Brain Stem surgery, Brain Stem pathology, Neurosurgical Procedures methods, Craniotomy methods, Cerebellum diagnostic imaging, Cerebellum surgery, Cerebellum blood supply, Brain surgery
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Background: The dorsal brainstem and cerebellomesencephalic fissure are challenging surgical targets. To afford a preferentially craniocaudal trajectory to this region, the precuneal interhemispheric transtentorial approach (PCIT) has been proposed., Objective: To didactically describe and compare exposures and anatomic indications of the supracerebellar infratentorial approach (SCIT) and PCIT to the cerebellomesencephalic fissure., Methods: Nine formalin-fixed, latex-injected cadaveric head specimens were used to perform a midline SCIT and bilateral PCITs and measure the distance of each approach. Twenty-four formalin-fixed specimens were used to measure the distance from the most posterior cortical bridging vein entering the superior sagittal sinus to the calcarine sulcus and the torcula. Fifty-one magnetic resonance images were reviewed to calculate the angle of each approach. Three illustrative surgical cases were described., Results: Mean distances from the brain or cerebellar surface to the operative target of the PCIT and SCIT were 7.1 cm (range: 5-7.7 cm) and 5.5 cm (range: 3.8-6.2 cm), respectively. The SCIT provided direct access to structures of the quadrigeminal cistern bilaterally. The PCIT provided access from the ipsilateral inferior colliculus to the ipsilateral infratrochlear zone. The PCIT's benefit was the direct access it provided to the cerebellomesencephalic fissure because of its superior to inferior trajectory., Conclusion: The PCIT is indicated for unilateral lesions of the cerebellomesencephalic fissure and dorsal brainstem that harbor a craniocaudal long axis and do not have a superior extension beyond the superior colliculi. The SCIT is beneficial for lesions that extend bilaterally, have an anteroposterior long axis, or involve the Galenic complex., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)
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- 2023
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41. Tumor Microenvironment and Glioblastoma Cell Interplay as Promoters of Therapeutic Resistance.
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Agosti E, Panciani PP, Zeppieri M, De Maria L, Pasqualetti F, Tel A, Zanin L, Fontanella MM, and Ius T
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The invasive nature of glioblastoma is problematic in a radical surgery approach and can be responsible for tumor recurrence. In order to create new therapeutic strategies, it is imperative to have a better understanding of the mechanisms behind tumor growth and invasion. The continuous cross-talk between glioma stem cells (GSCs) and the tumor microenvironment (TME) contributes to disease progression, which renders research in this field difficult and challenging. The main aim of the review was to assess the different possible mechanisms that could explain resistance to treatment promoted by TME and GSCs in glioblastoma, including the role of M2 macrophages, micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) from exosomes from the TME. A systematic review of the literature on the role of the TME in developing and promoting radioresistance and chemoresistance of GBM was performed according to PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. A dedicated literature review search was also performed on the immunotherapeutic agents against the immune TME. We identified 367 papers using the reported keywords. The final qualitative analysis was conducted on 25 studies. A growing amount of evidence in the current literature supports the role of M2 macrophages and non-coding RNAs in promoting the mechanisms of chemo and radioresistance. A better insight into how GBM cells interact with TME is an essential step towards comprehending the mechanisms that give rise to resistance to standard treatment, which can help to pave the way for the development of novel therapeutic strategies for GBM patients., Competing Interests: The authors have no conflict of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report.
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- 2023
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42. Surgical Anatomy and Approaches of the Anterior Cranial Fossa from a Transcranial and Endonasal Perspective.
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Plou P, Serioli S, Leonel LCPC, Alexander AY, Agosti E, Vilany L, Graepel S, Choby G, Pinheiro-Neto CD, and Peris-Celda M
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The anterior cranial fossa (ACF) is a complex anatomical region that can be affected by a broad spectrum of pathology. For the surgical treatment of these lesions, many approaches have been described, each of them with different scope and potential surgical complications, often associated with significant morbidity. Traditionally, tumors involving the ACF have been operated by transcranial approaches; however, in the last two decades, endoscopic endonasal approaches (EEAs) have been gaining popularity. In this work, the authors review and describe the anatomical aspects of the ACF and the technical nuances of transcranial and endoscopic approaches for tumors located in this region. Four approaches were performed in embalmed cadaveric specimens and the key steps were documented. Four illustrative cases of ACF tumors were selected to demonstrate the clinical application of anatomical and technical knowledge, which are essential in the preoperative decision-making process.
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- 2023
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43. Lessons learned during COVID-19 pandemic, a worldwide survey: impact of SARS-CoV-2 vaccination on neurosurgeons and neurosurgical practice.
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Agosti E, Garg K, Tandon V, Deora H, Veiceschi P, Naik V, Mishra S, Kedia S, Raheja A, Meena R, Shiva Munjal S, Chaurasia B, Phalak M, Locatelli D, Fontanella MM, Arnautovic K, Singh M, Chandra PS, and Kale SS
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- Humans, Neurosurgeons, SARS-CoV-2, COVID-19 Vaccines, Pandemics prevention & control, Neurosurgical Procedures, Vaccination, COVID-19 prevention & control, COVID-19 epidemiology
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- 2023
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44. Correction to: COVID‑19‑associated Guillain‑Barré syndrome in the early pandemic experience in Lombardia (Italy).
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Martinelli-Boneschi F, Colombo A, Bresolin N, Sessa M, Bassi P, Grampa G, Magni E, Versino M, Ferrarese C, Zarcone D, Albanese A, Micieli G, Zanferrari C, Cagnana A, Ferrante C, Zilioli A, Locatelli D, Calloni MV, Delodovici ML, Pozzato M, Patisso V, Bortolan F, Foresti C, Frigeni B, Canella S, Xhani R, Crabbio M, Clemenzi A, Mauri M, Beretta S, La Spina I, Bernasconi S, De Santis T, Cavallini A, Ranieri M, D'Adda E, Fruguglietti ME, Peverelli L, Agosti E, Leoni O, Rigamonti A, and Salmaggi A
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- 2023
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45. Developmental venous anomaly associated with dural arteriovenous fistula: Etiopathogenesis and hemorrhagic risk.
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Agosti E, De Maria L, Panciani PP, Serioli S, Mardighian D, Fontanella MM, and Lanzino G
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Introduction: Developmental venous anomalies (DVAs) have traditionally been defined as non-pathological congenital lesions. Compared to isolated DVAs, the association of DVAs with arteriovenous shunts seems to have a more adverse clinical connotation. In this review, we describe the association between DVA and dAVF and discuss the hemorrhagic risk. We also advance a hypothesis about the potential de novo formation of a DVA and challenge the dogma about their "developmental" or "congenital" nature., Methods: A systematic review of the literature on the association of DVA and dAVF was performed in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines., Results: A number of 678 papers was initially identified, but only 9 studies were included in the final qualitative analysis. Most of the patients presented with bleeding (56%), with a median GCS of 14 (range 10-15). In 56% of the cases the DVA had a supratentorial location. Supratentorial DVAs mostly drained in the superior sagittal sinus (80%), while all of infratentorial/combined DVAs drained in deep ependymal veins of the 4th ventricle. All the supratentorial dAVFs drained into the superior sagittal sinus, while the infratentorial/combined dAVFs mostly drained in the jugular bulb, Vein of Rosenthal, or transverse-sigmoid sinuses (75%). Most of the dAVFs were classified as Cognard type IIa + b (67%), while in a smaller number of cases type I (22%) and type V (11%). The dAVF was the target of treatment in each case and most patients underwent endovascular treatment (78%). The dAVF was completely occluded in 78% of cases and no periprocedural complications were reported., Conclusion: The clinical presentation, radiological findings, and treatment outcomes of DVAs and associated dAVFs have been discussed. Despite the general opinion that DVAs are benign congenital lesions, increasing epidemiological and radiological evidence supports a potential acquired origin, and the venous system seem to play a pivotal role in their post-natal genesis and development., Competing Interests: GL is a Consultant for Superior Medical Editors and Nested Knowledge. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Agosti, De Maria, Panciani, Serioli, Mardighian, Fontanella and Lanzino.)
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- 2023
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46. Microsurgical transcranial approaches to the posterior surface of petrosal portion of the temporal bone: quantitative analysis of surgical volumes and exposed areas.
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Serioli S, Agosti E, Buffoli B, Raffetti E, Alexander AY, Salgado-López L, Hirtler L, Rezzani R, Maroldi R, Draghi R, Borghesi I, Calbucci F, Peris-Celda M, Fontanella MM, and Doglietto F
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- Humans, Neurosurgical Procedures, Microsurgery, Cerebellopontine Angle surgery, Cadaver, Temporal Bone surgery, Petrous Bone surgery, Petrous Bone anatomy & histology
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Different microsurgical transcranial approaches (MTAs) have been described to expose the posterior surface of the petrous bone (PPB). A quantitative, anatomical comparison of the most used MTAs, for specific areas of the PPB, is not available. Anatomical dissections were performed on five formalin-fixed, latex-injected cadaver heads (10 sides). Six MTAs were analyzed: Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), retrolabyrinthine approach (RLA), translabyrinthine approach (TLA), and transcochlear approach (TCA). Surgical volumes and exposed areas of each approach were quantified with a dedicated neuronavigation system (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada) and adjuvant software (ITK-SNAP and Autodesk Meshmixer 3.5). Areas and volumes were compared using linear mixed models. TCA provided the best exposure of Trautmann's triangle and the retromeatal, suprameatal, meatal, and premeatal regions. RSAs provided the best exposure of the inframeatal region, with RSAS gaining significant exposure of the suprameatal region. KWA had the highest surgical volume, and RLA the lowest. Transpetrosal approaches offer the widest exposure of PPB proportionally to their invasiveness. Retrosigmoid approaches, which get to the studied region through a postero-lateral path, are paramount for the exposure of the inframeatal and suprameatal region and, given the adequate exposure of the remaining PPB, represent an effective approach for the cerebellopontine angle (CPA). These anatomical findings must be considered with approach-related morbidity and the pathological features in order to choose the most appropriate approach in clinical practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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47. COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).
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Martinelli-Boneschi F, Colombo A, Bresolin N, Sessa M, Bassi P, Grampa G, Magni E, Versino M, Ferrarese C, Zarcone D, Albanese A, Micieli G, Zanferrari C, Cagnana A, Ferrante C, Zilioli A, Locatelli D, Calloni MV, Delodovici ML, Pozzato M, Patisso V, Bortolan F, Foresti C, Frigeni B, Canella S, Xhani R, Crabbio M, Clemenzi A, Mauri M, Beretta S, La Spina I, Bernasconi S, De Santis T, Cavallini A, Ranieri M, D'Adda E, Fruguglietti ME, Peverelli L, Agosti E, Leoni O, Rigamonti A, and Salmaggi A
- Subjects
- Adult, Humans, Male, Middle Aged, SARS-CoV-2, Pandemics, Italy epidemiology, COVID-19 complications, COVID-19 epidemiology, Guillain-Barre Syndrome diagnosis
- Abstract
Objective: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia., Methods: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO)., Results: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia., Conclusions: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures., (© 2022. The Author(s).)
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- 2023
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48. Endoscopic endonasal surgical anatomy of the optic canal: key anatomical relationships between the optic nerve and ophthalmic artery.
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Agosti E, Leonel LCPC, Alexander AY, Graepel S, Pinheiro-Neto CD, and Peris-Celda M
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- Humans, Cadaver, Nose, Optic Nerve surgery, Optic Nerve anatomy & histology, Ophthalmic Artery surgery, Ophthalmic Artery anatomy & histology, Endoscopy methods
- Abstract
Purpose: A detailed understanding of the neurovascular relationships between the optic nerve (ON) and the ophthalmic artery (OA) in the optic canal (OC) is paramount for safe surgery. We focused on the neurovascular anatomy of this area from both an endoscopic endonasal and transcranial trajectories to compare the surgical exposures and perspectives offered by these different views and provide recommendations to increase the intraoperative safety., Methods: Twenty sides of ten formalin-fixed, latex-injected head specimens were utilized. The surgical anatomy and anatomical relationships of the OA in relationship to the ON along their intracranial and intracanalicular segments was studied from endoscopic endonasal and transcranial perspectives., Results: Three types of OA-ON relationships at the origin of the OA were identified: inferomedial (type 1, 35%), inferior (type 2, 55%), and inferolateral (type 3, 10%). The endoscopic endonasal trajectory offers an inferomedial perspective of the ON-OA neurovascular complex, in which the OA, especially when located inferomedially, is first encountered. When comparing with the transcranial view, all OA were covered by the nerve, type 1 was located below the medial third, type 2 below the middle third, and type 3 below the lateral third of the OC. The mean extension of the intracanalicular portion of both OA and ON was 8.9 mm, while the intracranial portion of the OA and ON were 9.3 mm and 12.4 mm, respectively. The OA, endoscopically, is located within the inferior half of the OC, and occupies 39%, 43%, and 42% of the OC height at its origin, mid, and end points, respectively. The mean distance between the superior margin of the OC at its origin and superior margin of the OA is 1.4 mm., Conclusions: Detailed anatomical understanding of the OC, and the ON and OA at their intracranial and intracanalicular segments is paramount to safe surgery. When opening the OC dura endoscopically, our results suggest that a medial incision along the superior third of the OC with a proximal to distal direction is recommended to avoid injury of the OA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2023
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49. Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Endoscopic Endonasal and Endoscopic-Assisted Transmaxillary Transpterygoid Approaches.
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Agosti E, Rezende NC, Leonel LCPC, Alexander AY, Pinheiro-Neto CD, and Peris-Celda M
- Abstract
Introduction The endoscopic endonasal transpterygoid approach (EETPA) with or without the addition of the endoscopic-assisted sublabial anterior transmaxillary approach (ESTA) has become increasingly utilized for lesions posterior to the pterygopalatine fossa (PPF), including infratemporal fossa (ITF), lateral recess of the sphenoid sinus, Meckel's cave, petrous apex, and parapharyngeal space. The main goal of this study is to develop an educational resource to learn the steps of the EETPA for trainees. Methods EETPA and ESTA were performed in 12 specimens by neurosurgery trainees, under supervision from the senior authors. One EETPA and one ESTA were performed on each specimen on opposite sides. Dissections were supplemented with representative cases. Results After a wide unilateral sphenoidotomy, ethmoidectomy, and partial medial maxillectomy, the anteromedial bone limits of the PPF were identified and drilled out. The pterygoid progress was modularly removed. By enlarging the opening of the posterior and lateral walls of the maxillary sinus through EETPA and ESTA, respectively, the neurovascular and muscular compartments of the PPF and ITF were better identified. The EETPA opens direct corridors to the PPF, medial ITF, middle cranial fossa, cavernous sinus, Meckel's cave, petrous apex, and internal carotid artery. If a more lateral exposure of the ITF is needed, the ESTA is an appropriate addition. Conclusion Despite the steep learning curve of the EETPA, granular knowledge of its surgical anatomy and basic surgical steps are vital for those advancing their learning in complex endoscopic approaches to the ventral skull base when expanding the approach laterally in the coronal plane., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)
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- 2022
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50. The Lingual Process of the Sphenoid Bone and the Petrolingual Ligament: Surgical Anatomy, Landmarks, and Clinical Relevance.
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Leonel LCPC, Rezende NC, Alexander AY, Agosti E, Rush D, Kenning TJ, Link MJ, Pinheiro-Neto CD, and Peris-Celda M
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- Humans, Cadaver, Cranial Fossa, Middle surgery, Ligaments surgery, Sphenoid Bone surgery, Sphenoid Bone anatomy & histology, Petrous Bone surgery
- Abstract
Background: The lingual process of the sphenoid bone (LP) and the petrolingual ligament (PLL) surround laterally the internal carotid artery within the middle cranial fossa (MCF)., Objective: To study the LP and the PLL and anatomical variations considering their relationships with different structures and landmarks within the MCF, especially oriented toward the endoscopic endonasal approaches., Methods: Seventy-two sides of dry skulls and 20 sides of embalmed specimens were studied. The measurements of the LP and the PLL were obtained, considering important landmarks in the MCF., Results: The LP had a mean length and height of 5 mm and 3 mm, respectively. Its distance from the foramen lacerum was 6 mm, from the foramen ovale 10 mm, foramen rotundum 15 mm, and petrous apex 9 mm. In 44 sides (61.11%), the LP partially closed the lateral aspect of the carotid sulcus; in 17 sides (23.61%), it was found as a near-ring; and in 11 sides (15.2%), it was considered rudimentary. Considering the PLL, its length and height were, respectively, 9 mm, and 4 mm., Conclusion: The LP and PLL separate the carotid artery at the inferior aspect of Meckel's cave and constitute important landmarks for endoscopic endonasal approaches to Meckel's cave and MCF, and their identification and removal is essential for internal carotid artery mobilization in this area., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
- Published
- 2022
- Full Text
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