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1. COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Author: 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, M, Delodovici, M, 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, M, Peverelli, L, Agosti, E, Leoni, O, Rigamonti, A, Salmaggi, A, 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 M. V., Delodovici M. L., 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 M. E., Peverelli L., Agosti E., Leoni O., Rigamonti A., Salmaggi A., 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, M, Delodovici, M, 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, M, Peverelli, L, Agosti, E, Leoni, O, Rigamonti, A, Salmaggi, A, 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 M. V., Delodovici M. L., 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 M. E., Peverelli L., Agosti E., Leoni O., Rigamonti A., and Salmaggi A.
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.
Published: 2023

2. Correction to: COVID‐19‐associated Guillain‐Barré syndrome in the early pandemic experience in Lombardia (Italy) (Neurological Sciences, (2023), 44, 2, (437-446), 10.1007/s10072-022-06429-6)

Author: Martinelli-Boneschi F., 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, M, Delodovici, M, 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, M, Peverelli, L, Agosti, E, Leoni, O, Rigamonti, A, Salmaggi, A, 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 M. V., Delodovici M. L., 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 M. E., Peverelli L., Agosti E., Leoni O., Rigamonti A., Salmaggi A., Martinelli-Boneschi F., 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, M, Delodovici, M, 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, M, Peverelli, L, Agosti, E, Leoni, O, Rigamonti, A, Salmaggi, A, 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 M. V., Delodovici M. L., 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 M. E., Peverelli L., Agosti E., Leoni O., Rigamonti A., and Salmaggi A.
Abstract: The above article was published with error. The affiliation address of the authors Alberto Albanese and Tiziana De Santis has been modified to: “U.O. Neurologia, IRCCS Istituto Clinico Humanitas, Milan, Italy”.The Original article has been corrected.
Published: 2023

3. Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy

Author: Fiorindi, A, Vezzoli, M, Doglietto, F, Zanin, L, Saraceno, G, Agosti, E, Barbieri, A, Bellocchi, S, Bernucci, C, Bongetta, D, Cardia, A, Costi, E, Egidi, M, Fioravanti, A, Gasparotti, R, Giussani, C, Grimod, G, Latronico, N, Locatelli, D, Mardighian, D, Nodari, G, Poli, J, Rasulo, F, Roca, E, Sicuri, G, Spena, G, Stefini, R, Vivaldi, O, Zoia, C, Calza, S, Fontanella, M, Cenzato, M, Fiorindi A., Vezzoli M., Doglietto F., Zanin L., Saraceno G., Agosti E., Barbieri A., Bellocchi S., Bernucci C., Bongetta D., Cardia A., Costi E., Egidi M., Fioravanti A., Gasparotti R., Giussani C., Grimod G., Latronico N., Locatelli D., Mardighian D., Nodari G., Poli J. C., Rasulo F., Roca E., Sicuri G. M., Spena G., Stefini R., Vivaldi O., Zoia C., Calza S., Fontanella M. M., Cenzato M., Fiorindi, A, Vezzoli, M, Doglietto, F, Zanin, L, Saraceno, G, Agosti, E, Barbieri, A, Bellocchi, S, Bernucci, C, Bongetta, D, Cardia, A, Costi, E, Egidi, M, Fioravanti, A, Gasparotti, R, Giussani, C, Grimod, G, Latronico, N, Locatelli, D, Mardighian, D, Nodari, G, Poli, J, Rasulo, F, Roca, E, Sicuri, G, Spena, G, Stefini, R, Vivaldi, O, Zoia, C, Calza, S, Fontanella, M, Cenzato, M, Fiorindi A., Vezzoli M., Doglietto F., Zanin L., Saraceno G., Agosti E., Barbieri A., Bellocchi S., Bernucci C., Bongetta D., Cardia A., Costi E., Egidi M., Fioravanti A., Gasparotti R., Giussani C., Grimod G., Latronico N., Locatelli D., Mardighian D., Nodari G., Poli J. C., Rasulo F., Roca E., Sicuri G. M., Spena G., Stefini R., Vivaldi O., Zoia C., Calza S., Fontanella M. M., and Cenzato M.
Abstract: Background: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. Methods: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017–2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. Results: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The “diagnostic delay” was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while “therapeutic delay” did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. Conclusions: We documented a significantly increased “diagnostic delay” for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was expe
Published: 2022

4. Microsurgical transcranial approaches to the posterior surface of petrosal portion of the temporal bone: quantitative analysis of surgical volumes and exposed areas

Author: Serioli, S., Agosti, E., Buffoli, B., Raffetti, E., Alexander, A. Y., Salgado-Lopez, L., Hirtler, L., Rezzani, R., Maroldi, R., Draghi, R., Borghesi, I., Calbucci, F., Peris-Celda, M., Fontanella, M. M., Doglietto, Francesco, Doglietto F. (ORCID:0000-0002-7438-0734), Serioli, S., Agosti, E., Buffoli, B., Raffetti, E., Alexander, A. Y., Salgado-Lopez, L., Hirtler, L., Rezzani, R., Maroldi, R., Draghi, R., Borghesi, I., Calbucci, F., Peris-Celda, M., Fontanella, M. M., Doglietto, Francesco, and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: 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.
Published: 2023

5. The impact of COVID-19 pandemic on surgical neuro-oncology: A survey from the Italian society of neurosurgery (SINch)

Author: Zanin, L., Ius, T., Panciani, P. P., Esposito, F., Gori, A., Fontanella, M. M., Tropeano, M. P., Raco, A., Angileri, F. F., Sabatino, Giovanni, Olivi, Alessandro, Esposito, V., Pessina, F., Agosti, E., Aiello, S., Aiudi, D., Aleo, D., Altieri, R., Amoroso, R., Auricchio, A. M., Barbagallo, G., Barbanera, A., Beggio, G., Bianco, A., Boccaletti, R., Borsa, S., Canova, G., Cappabianca, P., Caroli, M., Cavallo, M. A., Certo, F., Chimenti, M., Chioffi, F., Cioffi, V., Cofano, F., Cossandi, C., D'Andrea, G., De Falco, R., D'Elia, A., Della Pepa, G. M., Della Puppa, A., Della Torre, A., Ferroli, P., Garbossa, D., Germano, A., Giaquinta, A., Guida, F., Iacoangeli, M., Iacopino, D. G., Lavano, A., Maimone, G., Maiola, V., Mauferi, R., Melatini, A., Moro, M., Murrone, D., Muscas, G., Oppido, P. A., Pignotti, F., Policicchio, D., Proto, P., Quaglietta, P., Renisi, G., Ricciardi, L., Romeo, F., Rossetto, M., Scerrati, A., Schwarz, A., Skrap, M., Somma, C., Somma, T., Spena, G., Telera, S., Tosatto, L., Volpin, F., Volpin, L., Zoia, C., Sabatino G. (ORCID:0000-0002-4227-0434), Olivi A. (ORCID:0000-0002-4489-7564), Zanin, L., Ius, T., Panciani, P. P., Esposito, F., Gori, A., Fontanella, M. M., Tropeano, M. P., Raco, A., Angileri, F. F., Sabatino, Giovanni, Olivi, Alessandro, Esposito, V., Pessina, F., Agosti, E., Aiello, S., Aiudi, D., Aleo, D., Altieri, R., Amoroso, R., Auricchio, A. M., Barbagallo, G., Barbanera, A., Beggio, G., Bianco, A., Boccaletti, R., Borsa, S., Canova, G., Cappabianca, P., Caroli, M., Cavallo, M. A., Certo, F., Chimenti, M., Chioffi, F., Cioffi, V., Cofano, F., Cossandi, C., D'Andrea, G., De Falco, R., D'Elia, A., Della Pepa, G. M., Della Puppa, A., Della Torre, A., Ferroli, P., Garbossa, D., Germano, A., Giaquinta, A., Guida, F., Iacoangeli, M., Iacopino, D. G., Lavano, A., Maimone, G., Maiola, V., Mauferi, R., Melatini, A., Moro, M., Murrone, D., Muscas, G., Oppido, P. A., Pignotti, F., Policicchio, D., Proto, P., Quaglietta, P., Renisi, G., Ricciardi, L., Romeo, F., Rossetto, M., Scerrati, A., Schwarz, A., Skrap, M., Somma, C., Somma, T., Spena, G., Telera, S., Tosatto, L., Volpin, F., Volpin, L., Zoia, C., Sabatino G. (ORCID:0000-0002-4227-0434), and Olivi A. (ORCID:0000-0002-4489-7564)
Abstract: Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.
Published: 2023

6. Quantitative Anatomical Comparison of Surgical Approaches to Meckel’s Cave

Author: Zanin, L., Agosti, E., Ebner, F., de Maria, L., Belotti, F., Buffoli, B., Rezzani, R., Hirt, B., Ravanelli, M., Ius, T., Zeppieri, M., Tatagiba, M. S., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Zanin, L., Agosti, E., Ebner, F., de Maria, L., Belotti, F., Buffoli, B., Rezzani, R., Hirt, B., Ravanelli, M., Ius, T., Zeppieri, M., Tatagiba, M. S., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: 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%
Published: 2023

7. Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods

Author: Agosti, E., De Maria, L., Mattogno, Pier Paolo, Della Pepa, Giuseppe Maria, D'Onofrio, Ginevra Federica, Fiorindi, A., Lauretti, Liverana, Olivi, Alessandro, Fontanella, Marco Maria, Doglietto, Francesco, Mattogno P. P., Della Pepa G. M. (ORCID:0000-0001-8698-3359), D'Onofrio G. F., Lauretti L. (ORCID:0000-0002-6463-055X), Olivi A. (ORCID:0000-0002-4489-7564), Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Agosti, E., De Maria, L., Mattogno, Pier Paolo, Della Pepa, Giuseppe Maria, D'Onofrio, Ginevra Federica, Fiorindi, A., Lauretti, Liverana, Olivi, Alessandro, Fontanella, Marco Maria, Doglietto, Francesco, Mattogno P. P., Della Pepa G. M. (ORCID:0000-0001-8698-3359), D'Onofrio G. F., Lauretti L. (ORCID:0000-0002-6463-055X), Olivi A. (ORCID:0000-0002-4489-7564), Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: 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.
Published: 2023

8. Quantitative Anatomic Comparison of Endoscopic Transnasal and Microsurgical Transcranial Approaches to the Anterior Cranial Fossa

Author: Agosti, E., Saraceno, G., Rampinelli, V., Raffetti, E., Veiceschi, P., Buffoli, B., Rezzani, R., Giorgianni, A., Hirtler, L., Alexander, A. Y., Deganello, A., Piazza, C., Nicolai, P., Castelnuovo, P., Locatelli, D., Peris-Celda, M., Fontanella, M. M., Doglietto, Francesco, Doglietto F. (ORCID:0000-0002-7438-0734), Agosti, E., Saraceno, G., Rampinelli, V., Raffetti, E., Veiceschi, P., Buffoli, B., Rezzani, R., Giorgianni, A., Hirtler, L., Alexander, A. Y., Deganello, A., Piazza, C., Nicolai, P., Castelnuovo, P., Locatelli, D., Peris-Celda, M., Fontanella, M. M., Doglietto, Francesco, and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: BACKGROUND: Several microsurgical transcranial approaches (MTAs) and endoscopic transnasal approaches (EEAs) to the anterior cranial fossa (ACF) have been described. OBJECTIVE: To provide a preclinical, quantitative, anatomic, comparative analysis of surgical approaches to the ACF. METHODS: Five alcohol-fixed specimens underwent high-resolution computed tomography. The following approaches were performed on each specimen: EEAs (transcribriform, transtuberculum, and transplanum), anterior MTAs (transfrontal sinus interhemispheric, frontobasal interhemispheric, and subfrontal with unilateral and bilateral frontal craniotomy), and anterolateral MTAs (supraorbital, minipterional, pterional, and frontotemporal orbitozygomatic approach). An optic neuronavigation system and dedicated software (ApproachViewer, part of GTx-Eyes II-UHN) were used to quantify the working volume of each approach and extrapolate the exposure of different ACF regions. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: EEAs offer a large and direct route to the midline region of ACF, whose most anterior structures (ie, crista galli, cribriform plate, and ethmoidal roof) are also well exposed by anterior MTAs, whereas deeper ones (ie, planum sphenoidale and tuberculum sellae) are also well exposed by anterolateral MTAs. The orbital roof region is exposed by both anterolateral and lateral MTAs. The posterolateral region (ie, sphenoid wing and optic canal) is well exposed by anterolateral MTAs. CONCLUSION: Anterior and anterolateral MTAs play a pivotal role in the exposure of most anterior and posterolateral ACF regions, respectively, whereas midline regions are well exposed by EEAs. Furthermore, certain anterolateral approaches may be most useful when involvement of the optic canal and nerves involvement are suspected.
Published: 2022

9. Letter to the Editor: “Olfactory nerve sparing technique for anterior skull base meningiomas: How I do it”

Author: Agosti, E., Alexander, A. Y., Doglietto, Francesco, Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella M. M., Agosti, E., Alexander, A. Y., Doglietto, Francesco, Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), and Fontanella M. M.
Abstract: Not available
Published: 2022

10. Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas

Author: Fontanella, Marco Maria, Zanin, L., Panciani, P., Belotti, F., Doglietto, Francesco, Cremonesi, A., Migliorati, K., Roca, E., De Maria, L., Franzin, A., Vivaldi, O., Griva, F., Narducci, A., Draghi, R., Calbucci, F., Borghesi, I., Crobeddu, E., Cossandi, C., Fioravanti, A., Arias, J. A., Scerrati, A., De Bonis, P., Locatelli, D., Agosti, E., Veiceschi, P., Ceraudo, M., Zona, G., Gasparotti, R., Terzi di Bergamo, L., Rigamonti, D., Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella, Marco Maria, Zanin, L., Panciani, P., Belotti, F., Doglietto, Francesco, Cremonesi, A., Migliorati, K., Roca, E., De Maria, L., Franzin, A., Vivaldi, O., Griva, F., Narducci, A., Draghi, R., Calbucci, F., Borghesi, I., Crobeddu, E., Cossandi, C., Fioravanti, A., Arias, J. A., Scerrati, A., De Bonis, P., Locatelli, D., Agosti, E., Veiceschi, P., Ceraudo, M., Zona, G., Gasparotti, R., Terzi di Bergamo, L., Rigamonti, D., Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Objective: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. Methods: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from –1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. Results: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). Conclusions: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.
Published: 2022

11. Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Author: Bongetta, D, Zoia, C, Agosti, E, Doglietto, F, Fiorindi, A, Spena, G, Fontanella, M, Giussani, C, Bongetta, Daniele, Zoia, Cesare, Agosti, Edoardo, Doglietto, Francesco, Fiorindi, Alessandro, Spena, Giannantonio, Fontanella, Marco M, Giussani, Carlo G, Bongetta, D, Zoia, C, Agosti, E, Doglietto, F, Fiorindi, A, Spena, G, Fontanella, M, Giussani, C, Bongetta, Daniele, Zoia, Cesare, Agosti, Edoardo, Doglietto, Francesco, Fiorindi, Alessandro, Spena, Giannantonio, Fontanella, Marco M, and Giussani, Carlo G
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<0.001). There were no meaningful differences between macro-areas in terms of access to emergency care and number of neurosurgical wards per population. The rate of unruptured IAs (uIAs) treatment did not show a correlation to that of ruptured ones. Minor regional differences were retrieved for high-risk hypertension as well as for alcohol abuse prevalence. Air pollutants and temperature charts showed a north-south gradient similar to that of the incidence in the treated rIAs. Conclusions: The mean incidence of treated rIAs was stable over the 2015-2020 period in Italy. A north-south decreasing gradient in rIAs treatment incidence was reported. Neither the Regional healthcare organizations nor the rate of uIAs treatment were significant factors explainin
Published: 2022

12. Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy

Author: Fiorindi, A., Vezzoli, M., Doglietto, Francesco, Zanin, L., Saraceno, G., Agosti, E., Barbieri, A., Bellocchi, S., Bernucci, C., Bongetta, D., Cardia, A., Costi, E., Egidi, M., Fioravanti, A., Gasparotti, R., Giussani, C., Grimod, G., Latronico, N., Locatelli, D., Mardighian, D., Nodari, G., Poli, J. C., Rasulo, F., Roca, E., Sicuri, G. M., Spena, G., Stefini, R., Vivaldi, O., Zoia, C., Calza, S., Fontanella, Marco Maria, Cenzato, M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella M. M., Fiorindi, A., Vezzoli, M., Doglietto, Francesco, Zanin, L., Saraceno, G., Agosti, E., Barbieri, A., Bellocchi, S., Bernucci, C., Bongetta, D., Cardia, A., Costi, E., Egidi, M., Fioravanti, A., Gasparotti, R., Giussani, C., Grimod, G., Latronico, N., Locatelli, D., Mardighian, D., Nodari, G., Poli, J. C., Rasulo, F., Roca, E., Sicuri, G. M., Spena, G., Stefini, R., Vivaldi, O., Zoia, C., Calza, S., Fontanella, Marco Maria, Cenzato, M., Doglietto F. (ORCID:0000-0002-7438-0734), and Fontanella M. M.
Abstract: Background: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. Methods: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017–2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. Results: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The “diagnostic delay” was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while “therapeutic delay” did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. Conclusions: We documented a significantly increased “diagnostic delay” for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was expe
Published: 2022

13. Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Author: Bongetta, D., Zoia, C., Agosti, E., Doglietto, F., Fiorindi, A., Spena, G., Fontanella, M.M., and Giussani, C.G.
Published: 2022
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14. Do neurosurgeons follow the guidelines? A world-based survey on severe traumatic brain injury

Author: Saraceno, G., Servadei, F., Di Bergamo, L. T., Iaccarino, C., Rubiano, A. M., Zoia, C., de Bonis, P., Raffa, G., Hawryluk, G., Grotenhuis, A., Demetriades, A. K., Sala, F., Belotti, F., Zanin, L., Doglietto, F., Panciani, P. P., Biroli, A., Agosti, E., Serioli, S., Rasulic, L., Bruneau, M., Germano, I. M., Bosnjak, R., Thome, C., Regli, L., Vukic, M., Tessitore, E., Schaller, K., Chaurasia, B., El-Ghandour, N. M. F., Di Ieva, A., Bongetta, D., Borghesi, I., Fazio, M., Esene, I. N., Rosseau, G., El Abbadi, N., Baccanelli, M., Vajkoczy, P., Fontanella, M. M., Saraceno, Giorgio [0000-0002-6711-0824], Servadei, Franco [0000-0002-3595-3464], Iaccarino, Corrado [0000-0002-5133-6327], Rubiano, Andrés Mariano [0000-0001-8931-3254], Zoia, Cesare [0000-0001-7304-6120], De Bonis, Pasquale [0000-0002-9879-8940], Raffa, Giovanni [0000-0001-8623-4964], Sala, Francesco [0000-0003-1263-9859], Surgical clinical sciences, Neuroprotection & Neuromodulation, and Neurosurgery
Subjects: Traumatic, medicine.medical_specialty, Traumatic brain injury, Low resource, Neuroscience(all), medicine.medical_treatment, Temporal bone, Brain injuries, traumatic, Intracranial hypertension, Humans, Surveys and Questionnaires, Brain Injuries, Traumatic, Neurosurgeons, MEDLINE, Brain injuries, Brain Injuries, Traumatic/surgery, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Brain trauma, Hueso temporal, Cause of death, business.industry, Hipertensión intracraneal, medicine.disease, 3. Good health, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Clinical Practice, Lesiones Cerebrales, Brain Injuries, Emergency medicine, Intracranial pressure monitoring, Traumatismos, Surgery, Decompressive craniectomy, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: ANTECEDENTES: La lesión cerebral traumática (LCT) será la tercera causa de muerte en todo el mundo, según la OMS. Dos encuestas europeas sugirieron que el cumplimiento de las directrices sobre traumatismos craneoencefálicos es deficiente. Ningún estudio ha comparado el cumplimiento entre países de ingresos bajos (LMIC) y países de ingresos altos (UHIC). Por lo tanto, este estudio tuvo como objetivo investigar las diferencias en el manejo de pacientes con TBI grave, comparando ingresos bajos y altos, y la adherencia a las pautas de BTF. MÉTODOS: se difundió una encuesta basada en la web a través de la fundación global Neuro, diferentes sociedades neuroquirúrgicas y las redes sociales. RESULTADOS: participaron un total de 803 neurocirujanos: 70,4 de UHIC y 29,6% de LMIC. El 73 % y el 65 % de los que respondieron en LMIC y UHIC, respectivamente (P = 0,016), administraron hipertónico como medida temprana. El 66 % y el 58 % de los neurocirujanos de los LMIC y los UHIC recomendaron una monitorización invasiva de la presión intracraneal, respectivamente (p
Published: 2021

15. Quantitative Anatomic Comparison of Microsurgical Transcranial, Endoscopic Endonasal, and Transorbital Approaches to the Spheno-Orbital Region

Author: Agosti, E., Turri-Zanoni, M., Saraceno, G., Belotti, F., Karligkiotis, A., Rocca, G., Buffoli, B., Raffetti, E., Hirtler, L., Rezzani, R., Rodella, L. F., Ferrari, M., Nicolai, P., Bresson, D., Herman, P., Dallan, I., Castelnuovo, P., Locatelli, D., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Agosti, E., Turri-Zanoni, M., Saraceno, G., Belotti, F., Karligkiotis, A., Rocca, G., Buffoli, B., Raffetti, E., Hirtler, L., Rezzani, R., Rodella, L. F., Ferrari, M., Nicolai, P., Bresson, D., Herman, P., Dallan, I., Castelnuovo, P., Locatelli, D., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: BACKGROUND: The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches. OBJECTIVE: To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR. METHODS: These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent. CONCLUSION: This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.
Published: 2021

16. Cerebral cavernous malformation remnants after surgery: a single-center series with long-term bleeding risk analysis

Author: Fontanella, Marco Maria, Agosti, E., Zanin, L., di Bergamo, L. T., Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella, Marco Maria, Agosti, E., Zanin, L., di Bergamo, L. T., Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: The aim of this work is to investigate the long-term bleeding risk of cerebral cavernous malformation (CCM) remnants. A review of clinical, radiological, operative, and post-operative data of a cerebral cavernous malformation (CCMs) prospective database was performed. Fisher’s exact test and Mann-Whitney U-test were used to assess differences between non-hemorrhagic and hemorrhagic CCM remnants for 14 variables. Recursive partitioning analysis was performed to assess the order of variables most associated with CCM remnant bleeding. Twenty-four patients out of 126 had a CCM post-surgical remnant. Of these, 7 had at least one post-operative hemorrhagic event. The mean follow-up was 80.7 months (range 12–144). CCM post-surgical remnant bleeding presented mostly with acute headache (50%) and focal neurological deficit (25%); in the remaining cases, the hemorrhage was asymptomatic. Retreatment was performed in two patients, with surgery and radiosurgery, respectively; no treatment was performed in the majority of cases. All patients ranked as non-II, according to Zabramski classification, did not show any post-surgical bleeding. The presence of a pre-operative perilesional hemosiderin ring was highly significant in predicting post-surgical bleeding (sensitivity = 0.94, specificity = 0.88) and incorrectly predicted bleeding in only two of the 24 patients. This study provides an evaluation of clinical and radiological factors influencing the bleeding risk of a CCM post-surgical remnant in a homogeneous population. Perilesional hemosiderin ring and Zabramski Type II appear to strongly condition the bleeding risk of a CCM post-surgical remnant.
Published: 2021

17. Bleeding risk after cavernous malformation surgery: Remnant or recurrence?

Author: Agosti, E., Doglietto, Francesco, Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella M. M., Agosti, E., Doglietto, Francesco, Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), and Fontanella M. M.
Abstract: Letter to the Editor
Published: 2021

18. Endoscopic Subtemporal Epidural Key-Hole Approach: Quantitative Anatomic Analysis of Three Surgical Corridors

Author: Rampinelli, V., Agosti, E., Saraceno, G., Ferrari, M., Taboni, S., Mattavelli, D., Schreiber, A., Tomasoni, M., Gualtieri, T., Ravanelli, M., Buffoli, B., Rezzani, R., Fontanella, Marco Maria, Nicolai, P., Piazza, C., Deganello, A., Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Rampinelli, V., Agosti, E., Saraceno, G., Ferrari, M., Taboni, S., Mattavelli, D., Schreiber, A., Tomasoni, M., Gualtieri, T., Ravanelli, M., Buffoli, B., Rezzani, R., Fontanella, Marco Maria, Nicolai, P., Piazza, C., Deganello, A., Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Background: The endoscope-assisted subtemporal key-hole epidural approach (ESKEA) has been recently described. The aim of this study was to measure working volumes and exposure of key areas of the middle cranial fossa provided by this approach. Methods: Four fresh frozen cadaver heads were dissected to analyze 3 modular corridors (1A, 1B, and 2) harvested through ESKEA. A step-by-step dissection was performed, and key anatomic landmarks were recorded. A GTxEyesII-ApproachViewer was used to quantify the working volume and exposure of 4 different regions (sphenoorbital, parasellar, superior petrous apex, and squamopetrous). For each corridor, 3 incremental degrees of temporal dural retraction (5, 10, and 15 mm) were tested. Results: The working volume of all corridors progressively increased with degree of retraction: Corridors 1A, 1B, and 2 showed a gain in working volume of 21%, 27%, and 19% from 5 mm to 10 mm retraction, respectively, and a gain of 40%, 45%, and 44% from 5 mm to 15 mm retraction, respectively. The sphenoorbital area was exposed (27%−45%) through corridor 1A, and exposure significantly increased with the degree of retraction. Corridor 1B provided optimal exposure of parasellar areas (86%−100%) and superior petrous apex (70%−87%) regardless of the degree of retraction. The squamopetrous area was satisfactorily addressed through corridor 2 (88%) only with the highest degree of retraction. Conclusions: ESKEA can be conceived as a modular approach: the 3 surgical corridors have specific working volumes, which are clearly influenced by the degree of temporal lobe retraction, and provide exposure of different middle cranial fossa areas.
Published: 2021

19. An international call for a new grading system for cerebral and cerebellar cavernomas

Author: Fontanella, Marco Maria, Bacigaluppi, S., Doglietto, Francesco, Zanin, L., Agosti, E., Panciani, P., Belotti, F., Saraceno, G., Spena, G., Draghi, R., Fiorindi, A., Cornali, C., Biroli, A., Kivelev, J., Chiesa, M., Retta, S. F., Gasparotti, R., Kato, Y., Hernesniemi, J., Rigamonti, D., Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella, Marco Maria, Bacigaluppi, S., Doglietto, Francesco, Zanin, L., Agosti, E., Panciani, P., Belotti, F., Saraceno, G., Spena, G., Draghi, R., Fiorindi, A., Cornali, C., Biroli, A., Kivelev, J., Chiesa, M., Retta, S. F., Gasparotti, R., Kato, Y., Hernesniemi, J., Rigamonti, D., Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Surgical indications for cerebral cavernous malformations remain significantly center- and surgeon-dependent. Available grading systems are potentially limited, as they do not include epileptological and radiological data. A novel grading system is proposed for supratentorial and cerebellar cavernomas: it considers neuroradiological features (bleeding, increase in size), neurological status (focal deficits and seizures), location of the lesion and age of the patient. The score ranges from -1 to 10; furthermore, surgery should be considered when a score of 4 or higher is present. Based on neuroradiological characteristics, 0 points are assigned if the CCM is stable in size at different neuroradiological controls, 1 point if there is an increase in volume during follow-up, 2 points if intra- or extra-lesional bleeding <1 cm is present and 3 points if the CCM produced a hematoma >1 cm. Regarding focal neurological deficits, 0 points are assigned if absent and 2 points if present. For seizures, 0 points are assigned if absent, 1 point if present, but controlled by medications, and 2 points if drug resistant. We considered the site of the CCM, and in case of deep-seated lesions in a critical area (basal ganglia, thalamus) 1 point (-1) is subtracted, while for subcortical or deep cerebellar lesions 0 points are assigned, for CCMs in a cortical critical area 1 point is assigned and in case of lesions in cortical not in critical area or superficial cerebellar area, 2 points are assigned. As far as age is concerned, 0 points are assigned for patients older than 50 years and 1 point for patients younger than 50. In conclusion, a novel grading for surgical decision making in cerebral cavernomas, based on the experience of selected neurosurgeons, basic scientists, and patients, is suggested with the aim of further improving and standardizing the treatment of CCMs. The aim of this paper was also to call for both retrospective and prospective multicenter studies with the ai
Published: 2021

20. Anxiety in neurosurgical patients undergoing nonurgent surgery during the COVID-19 pandemic

Author: Doglietto, Francesco, Vezzoli, Marika, Biroli, A., Saraceno, G., Zanin, L., Pertichetti, M., Calza, S., Agosti, E., Arias, J. M. A., Assietti, R., Bellocchi, S., Bernucci, C., Bistazzoni, S., Bongetta, D., Fanti, A., Fioravanti, A., Fiorindi, A., Franzin, A., Locatelli, D., Pugliese, R., Roca, E., Sicuri, G. M., Stefini, R., Venturini, M., Vivaldi, O., Zattra, C., Zoia, C., Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), Vezzoli M., Fontanella M. M., Doglietto, Francesco, Vezzoli, Marika, Biroli, A., Saraceno, G., Zanin, L., Pertichetti, M., Calza, S., Agosti, E., Arias, J. M. A., Assietti, R., Bellocchi, S., Bernucci, C., Bistazzoni, S., Bongetta, D., Fanti, A., Fioravanti, A., Fiorindi, A., Franzin, A., Locatelli, D., Pugliese, R., Roca, E., Sicuri, G. M., Stefini, R., Venturini, M., Vivaldi, O., Zattra, C., Zoia, C., Fontanella, Marco Maria, Doglietto F. (ORCID:0000-0002-7438-0734), Vezzoli M., and Fontanella M. M.
Abstract: OBJECTIVE The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor asso
Published: 2020

21. Hybrid Robotics for Endoscopic Skull Base Surgery: Preclinical Evaluation and Surgeon First Impression

Author: Zappa, F., Mattavelli, D., Madoglio, A., Rampinelli, V., Ferrari, M., Tampalini, F., Fontanella, Marco Maria, Nicolai, P., Doglietto, Francesco, Agosti, E., Battaglia, P., Biroli, A., Bresson, D., Castelnuovo, P., Fiorindi, A., Herman, P., Karligkiotis, A., Locatelli, D., Pozzi, F., Saraceno, G., Schreiber, A., Verillaud, B., Turri Zanoni, M., Fontanella M., Doglietto F. (ORCID:0000-0002-7438-0734), Zappa, F., Mattavelli, D., Madoglio, A., Rampinelli, V., Ferrari, M., Tampalini, F., Fontanella, Marco Maria, Nicolai, P., Doglietto, Francesco, Agosti, E., Battaglia, P., Biroli, A., Bresson, D., Castelnuovo, P., Fiorindi, A., Herman, P., Karligkiotis, A., Locatelli, D., Pozzi, F., Saraceno, G., Schreiber, A., Verillaud, B., Turri Zanoni, M., Fontanella M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Background: A robotic endoscope holder should theoretically provide various advantages in transnasal endoscopic skull base surgery, but only recently has a robotic system become commercially available. The objective of this study was to provide a preclinical evaluation of potential advantages and surgeon first impression of this robotic hybrid solution. Methods: Thirty skull base surgeons, attending the Joint European Diploma of Endoscopic Skull Base Surgery 2018–2019 in Paris, France, were enrolled. A questionnaire, mainly concerning personal surgical experience and habits, was administered. The test phase consisted of 2 different dry-lab tasks, performed with and without EndoscopeRobot, according to randomization and on 2 different days. A modified NASA Task Load Index test was subsequently administered via e-mail to all participants. Completion times and modified Global Evaluative Assessment of Robotic Skills in Endoscopy scores of the videotaped tasks were recorded. Results: Nineteen otorhinolaryngologic surgeons and 11 neurosurgeons, with different surgical habits and endoscopic experience, were enrolled. No one appeared unfavorable a priori to robotic endoscopic surgery. Although the robot did not provide an advantage in the simple grasping task 1, a trend toward better completion times and efficacy was evident in the bimanual task 2, when performed with the robot and bimanually. According to the modified NASA Task Load Index test, surgeons felt more successful with the robot in task 2, finding it less stressful and mentally demanding. Conclusions: Endoscopic skull base surgeons seem to view a hybrid robotic solution positively. EndoscopeRobot seems to provide a benefit to the single surgeon with experience in bimanual endoscopic surgery. Further preclinical and clinical evaluation of this technology is necessary.
Published: 2020

22. Quantitative anatomical comparison of transnasal and transcranial approaches to the clivus

Author: Agosti, E., Saraceno, G., Qiu, J., Buffoli, B., Ferrari, M., Raffetti, E., Belotti, F., Ravanelli, M., Mattavelli, D., Schreiber, A., Hirtler, L., Rodella, L. F., Maroldi, R., Nicolai, P., Gentili, F., Kucharczyk, W., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Agosti, E., Saraceno, G., Qiu, J., Buffoli, B., Ferrari, M., Raffetti, E., Belotti, F., Ravanelli, M., Mattavelli, D., Schreiber, A., Hirtler, L., Rodella, L. F., Maroldi, R., Nicolai, P., Gentili, F., Kucharczyk, W., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Background and objective: The clivus was defined as “no man’s land” in the early 1990s, but since then, multiple approaches have been described to access it. This study is aimed at quantitatively comparing endoscopic transnasal and microsurgical transcranial approaches to the clivus in a preclinical setting, using a recently developed research method. Methods: Multiple approaches were performed in 5 head and neck specimens that underwent high-resolution computed tomography (CT): endoscopic transnasal (transclival, with hypophysiopexy and with far-medial extension), microsurgical anterolateral (supraorbital, mini-pterional, pterional, pterional transzygomatic, fronto-temporal-orbito-zygomatic), lateral (subtemporal and subtemporal transzygomatic), and posterolateral (retrosigmoid, far-lateral, retrolabyrinthine, translabyrinthine, and transcochlear). An optic neuronavigation system and dedicated software were used to quantify the working volume of each approach and calculate the exposure of different clival regions. Mixed linear models with random intersections were used for statistical analyses. Results: Endoscopic transnasal approaches showed higher working volume and larger exposure compared with microsurgical transcranial approaches. Increased exposure of the upper clivus was achieved by the transnasal endoscopic transclival approach with intradural hypophysiopexy. Anterolateral microsurgical transcranial approaches provided a direct route to the anterior surface of the posterior clinoid process. The transnasal endoscopic approach with far-medial extension ensured a statistically larger exposure of jugular tubercles as compared with other approaches. Presigmoid approaches provided a relatively limited exposure of the ipsilateral clivus, which increased in proportion to their invasiveness. Conclusions: This is the first anatomical study that quantitatively compares in a holistic way exposure and working volumes offered by the most used modern approaches to the cli
Published: 2020

23. Quantitative Anatomical Comparison of Anterior, Anterolateral and Lateral, Microsurgical and Endoscopic Approaches to the Middle Cranial Fossa

Author: Saraceno, G., Agosti, E., Qiu, J., Buffoli, B., Ferrari, M., Raffetti, E., Belotti, F., Ravanelli, M., Mattavelli, D., Schreiber, A., Hirtler, L., Rodella, L. F., Maroldi, R., Nicolai, P., Gentili, F., Kucharczyk, W., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Saraceno, G., Agosti, E., Qiu, J., Buffoli, B., Ferrari, M., Raffetti, E., Belotti, F., Ravanelli, M., Mattavelli, D., Schreiber, A., Hirtler, L., Rodella, L. F., Maroldi, R., Nicolai, P., Gentili, F., Kucharczyk, W., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)
Abstract: Objective: To quantitatively compare different microsurgical and endoscopic approaches to the middle cranial fossa in a preclinical setting with a novel, computer-based research method. Methods: Different approaches were performed bilaterally in 5 head and neck specimens that underwent high-resolution computed tomography scans: 5 transcranial anterolateral (supraorbital, mini-pterional, pterional, pterional-transzygomatic, fronto-temporal-orbito-zygomatic) without and with anterior clinoidectomy; 2 transcranial lateral (subtemporal and subtemporal-transzygomatic); 2 endoscopic transnasal (transpterygoid, transpterygoid to infratemporal fossa); 2 endoscopic transorbital (superior eyelid and inferolateral), and endoscopic transmaxillary. A dedicated navigation system was used to quantify surgical working volumes and exposure of different areas of the middle cranial fossa (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Statistical analysis was performed using a mixed linear model with bootstrap resampling. Results: Endoscopic transnasal and fronto-temporal-orbito-zygomatic approaches with anterior clinoidectomy showed the largest surgical volumes. Endoscopic approaches allowed a wider exposure of medial anatomical surfaces (e.g., the petrous apex) compared with transcranial ones. Transcranial approaches with larger craniotomies allowed the widest exposure of superomedial anatomical structures (e.g., roof of cavernous sinus). The resection of the zygomatic arch allowed exposure of more medial surfaces with an inferior to superior trajectory. Conclusions: This study implemented a novel neuronavigation-based research method to quantitatively compare different approaches to the middle cranial fossa; its results might guide, after consideration of clinical implications, the choice of the neurosurgical approach to different areas of this complex skull base region.
Published: 2020

24. Pressing Issues in COVID-19: Probable Cause to Seize SARS-CoV-2 for Its Preferential Involvement of Posterior Circulation Manifesting as Severe Posterior Reversible Encephalopathy Syndrome and Posterior Strokes

Author: D’Amore, F., primary, Vinacci, G., additional, Agosti, E., additional, Cariddi, L.P., additional, Terrana, A.V., additional, Vizzari, F.A., additional, Mauri, M., additional, and Giorgianni, A., additional
Published: 2020
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25. Intestinal permeability, atopic eczema and oral disodium cromoglycate

Author: VENTURA, ALESSANDRO, RINALDI S, FLOREAN P, AGOSTI E., Ventura, Alessandro, Rinaldi, S, Florean, P, and Agosti, E.
Published: 1991

26. Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT

Author: De Manzini, A., Andolina, M., Agosti, E., Giorgi, R., Locatelli, F., Bonetti, L., Miniero, R., Busca, A., Porta, F., Lanfranchi, A., Rossetti, F., and Colleselli, P.
Published: 1993

27. THERAPY WITH AMINOHYDROXYPROPYLIDENE BISPHOSPHONATE IN YOUNG PATIENTS WITH SEVERE OSTEOPOROSIS

Author: Marinoni, S, primary, Bembi, B, additional, Tonini, G, additional, Nassimbeni, G, additional, and Agosti, E, additional
Published: 1993
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28. 'Impianto di cellule epiteliali amniotiche umane crioconservate in un soggetto affetto da malattia di Niemann-Pick tipo B.'

Author: SCAGGIANTE, BRUNA, MARZARI, ROBERTO, PINESCHI A., SUSTERSICH M., ANDOLINA M., AGOSTI E., Scaggiante, Bruna, Pineschi, A., Sustersich, M., Andolina, M., Agosti, E., and Marzari, Roberto
Published: 1987

29. IL LABORATORIO NEL TRAPIANTO DI MIDOLLO

Author: Agosti, E., Andolina, M., Belvedere, M. C., Consolini, R., Destro, R., Drobniz, M. G., Fornasari, P., Gazzola, M. V., Paolucci, Paolo, Granchi, D., Martinelli, M., Meraviglia, L., Millar, J. L., Perticari, S., Porta, F. A., and Preti, P.
Subjects: TRAPIANTO DI MIDOLLO OSSEO IN PEDIATRIA, TECNICHE E ORGANIZZAZIONE DEL LABORATORIO
Published: 1985

30. Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Author: 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
Subjects: 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
Published: 2022

31. Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial

Author: Roberta Ricotti, Giorgio Bellomo, Nicole Bozzi Cionci, Arianna Solito, Antonella Petri, Gianni Bona, Enza Giglione, Marina Caputo, Francesca Archero, Emanuela Agosti, Marco Pane, Diana Di Gioia, Nicola Vitulo, Gillian E. Walker, Simonetta Bellone, Flavia Prodam, Lucia Vannini, Matteo Calgaro, Iderina Hasballa, Gianluca Aimaretti, Angela Amoruso, Solito A., Bozzi Cionci N., Calgaro M., Caputo M., Vannini L., Hasballa I., Archero F., Giglione E., Ricotti R., Walker G.E., Petri A., Agosti E., Bellomo G., Aimaretti G., Bona G., Bellone S., Amoruso A., Pane M., Di Gioia D., Vitulo N., and Prodam F.
Subjects: Male, medicine.medical_specialty, Pediatric Obesity, Adolescent, ved/biology.organism_classification_rank.species, Placebo-controlled study, Gut flora, Bifidobacterium breve, Critical Care and Intensive Care Medicine, Placebo, Probiotic, Gastroenterology, law.invention, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Insulin, Adverse effect, Child, Nutrition and Dietetics, Cross-Over Studies, biology, business.industry, ved/biology, Probiotics, Microbiota, Cross-Over Studie, medicine.disease, biology.organism_classification, Insulin sensitivity, Obesity, Gastrointestinal Microbiome, Treatment Outcome, Female, Insulin Resistance, business, Human
Abstract: Background & aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6–18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. Results: All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0–0.03) and during OGTT (ISI, 0.654 CI95%-0.11–1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. Conclusion: An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. Trial registration: NCT03261466.
Published: 2021

32. Antifibrotic activity of acylated and unacylated ghrelin

Author: Nicoletta Filigheddu, Andrea Graziani, Michele Ferrara, Emanuela Agosti, Elia Angelino, Simone Reano, Angelino, E, Reano, S, Ferrara, M, Agosti, E, Graziani, Andrea, and Filigheddu, N.
Subjects: medicine.medical_specialty, Necrosis, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Review Article, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Extracellular matrix, Endocrinology, Fibrosis, Internal medicine, medicine, Receptor, Fibroblast, media_common, lcsh:RC648-665, Endocrine and Autonomic Systems, business.industry, digestive, oral, and skin physiology, Appetite, medicine.disease, medicine.anatomical_structure, Apoptosis, Ghrelin, medicine.symptom, business
Abstract: Fibrosis can affect almost all tissues and organs, it often represents the terminal stage of chronic diseases, and it is regarded as a major health issue for which efficient therapies are needed. Tissue injury, by inducing necrosis/apoptosis, triggers inflammatory response that, in turn, promotes fibroblast activation and pathological deposition of extracellular matrix. Acylated and unacylated ghrelin are the main products of the ghrelin gene. The acylated form, through its receptor GHSR-1a, stimulates appetite and growth hormone (GH) release. Although unacylated ghrelin does not bind or activate GHSR-1a, it shares with the acylated form several biological activities. Ghrelin peptides exhibit anti-inflammatory, antioxidative, and antiapoptotic activities, suggesting that they might represent an efficient approach to prevent or reduce fibrosis. The aim of this review is to summarize the available evidence regarding the effects of acylated and unacylated ghrelin on different pathologies and experimental models in which fibrosis is a predominant characteristic.
Published: 2015

33. La Resistenza nella rappresentazione delle istituzioni: celebrazioni, calendari civili

Author: RIDOLFI M, a cura di Aldo Agosti e Chiara Colombini, and Ridolfi, M
Published: 2012

34. Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells

Author: Silvana Rapelli, Gigliola Montorfano, Bruno Berra, Alberto Pineschi, Bruno Bembi, Eriberto Agosti, Rosalba Gornati, Domenico Romeo, Bruna Scaggiante, Marina Comelli, Bembi, B, Comelli, M, Scaggiante, Bruna, Pineschi, A, Rapelli, S, Gornati, R, Montorfano, G, Berra, B, Agosti, E, and Romeo, D.
Subjects: Male, medicine.medical_specialty, Adolescent, Urinary system, Epithelium, Fetal membrane, Internal medicine, Leukocytes, medicine, Humans, Amnion, Child, Cells, Cultured, Phospholipids, Genetics (clinical), Niemann-Pick Diseases, business.industry, medicine.disease, Sphingomyelin Phosphodiesterase, Endocrinology, medicine.anatomical_structure, Amniotic epithelial cells, Vomiting, Female, medicine.symptom, Sphingomyelin, business, Niemann–Pick disease, Respiratory tract
Abstract: Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays.
Published: 1992

35. 'Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane'

Author: Bruna Scaggiante, Alberto Pineschi, Massimo Sustersich, Domenico Romeo, Marino Andolina, Eriberto Agosti, Scaggiante, Bruna, Pineschi, A., Sustersich, M, Andolina, M., Agosti, E., and AND ROMEO, D.
Subjects: Male, Cell type, medicine.medical_specialty, Pathology, Adolescent, Epithelium, Pregnancy, Internal medicine, Medicine, Humans, Amnion, Niemann-Pick Diseases, Transplantation, business.industry, Phosphoric Diester Hydrolases, Graft Survival, Enzyme replacement therapy, medicine.disease, Endocrinology, medicine.anatomical_structure, Sphingomyelin Phosphodiesterase, Host vs Graft Reaction, Female, business, Niemann–Pick disease
Abstract: In a patient with a lysosomal storage disorder, not involving the CNS, repeated implantations of human amniotic sheets have proved to provide a successful approach to enzyme replacement therapy. Implantation of pure epithelial cells, separated from the other cell types of the amnion, might markedly improve the procedure, avoiding some risks of host-versus-graft rejection.
Published: 1987

36. Repeated Implantations of Human Amniotic Epithelial Cells as a Curative Therapy of Niemann-Pick Disease

Author: Alberto Pineschi, Eriberto Agosti, Domenico Romeo, Bruna Scaggiante, Bruno Bembi, Salvayre R., Douste-Blazy L., Gatt S., Scaggiante, Bruna, Pineschi, A., Bembi, B., Agosti, E., and Romeo, D.
Subjects: Gangrene, medicine.medical_specialty, Amnion, business.industry, Niemann-Pick, Amniotic sac, medicine.disease, Surgery, Biological dressing, medicine.anatomical_structure, Amniotic epithelial cells, Medicine, Definite Improvement, business, Wound healing, Niemann–Pick disease
Abstract: By a popular tradition, a baby delivered when still wrapped in the amniotic sac is destined for great luck throughout his or her life: people say that he or she was born with a caul. Besides its putative magic properties, a true scientific interest in the “protective” activity of the amniotic membrane dates back to the first half of the Century, when a certain number of experiments were carried out, in Germany and Eastern Europe, to investigate its possible clinical applications. Satisfactory results were achieved by using sheets of sterile, dried human amnion as a peritoneal graft in gangrene or as a biological dressing for the treatment of extensive wounds and burns, always recording a definite improvement of wound healing and decrease of pain1.
Published: 1988

37. Thyroid Eye Disease: Advancements in Orbital and Ocular Pathology Management.

Author: 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
Abstract: 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.
Published: 2024
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38. Glioma Stem Cells as Promoter of Glioma Progression: A Systematic Review of Molecular Pathways and Targeted Therapies.

Author: Agosti E, Antonietti S, Ius T, Fontanella MM, Zeppieri M, and Panciani PP
Subjects: 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
Abstract: 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.
Published: 2024
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39. CAR-T Cells Therapy in Glioblastoma: A Systematic Review on Molecular Targets and Treatment Strategies.

Author: Agosti E, Garaba A, Antonietti S, Ius T, Fontanella MM, Zeppieri M, and Panciani PP
Subjects: 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
Abstract: 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.
Published: 2024
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40. Generative Adversarial Networks (GANs) in the Field of Head and Neck Surgery: Current Evidence and Prospects for the Future-A Systematic Review.

Author: Michelutti L, Tel A, Zeppieri M, Ius T, Agosti E, Sembronio S, and Robiony M
Abstract: 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.
Published: 2024
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41. Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.

Author: Agosti E, Zeppieri M, Ghidoni M, Ius T, Tel A, Fontanella MM, and Panciani PP
Abstract: 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.)
Published: 2024
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42. The Current Diagnostic Performance of MRI-Based Radiomics for Glioma Grading: A Meta-Analysis.

Author: 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
Subjects: 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
Abstract: 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.)
Published: 2024
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43. Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review.

Author: Agosti E, Antonietti S, Zeppieri M, Ius T, Fiorindi A, Tel A, Robiony M, Panciani PP, and Fontanella MM
Abstract: 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.
Published: 2024
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44. Comparative Efficacy of Transsphenoidal and Transcranial Approaches for Treating Tuberculum Sellae Meningiomas: A Systematic Review and Meta-Analysis.

Author: 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.
Published: 2024
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45. 360° around the orbit: key surgical anatomy of the microsurgical and endoscopic cranio-orbital and orbitocranial approaches.

Author: 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
Subjects: Humans, Endoscopy methods, Cranial Fossa, Middle surgery, Craniotomy methods, Cadaver, Neurosurgical Procedures methods, Orbit surgery
Abstract: 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.
Published: 2024
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46. Current status and future perspectives on stem cell transplantation for spinal cord injury.

Author: Agosti E, Zeppieri M, Pagnoni A, Fontanella MM, Fiorindi A, Ius T, and Panciani PP
Abstract: 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.)
Published: 2024
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47. Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies.

Author: Agosti E, Zeppieri M, Antonietti S, Ius T, Fontanella MM, and Panciani PP
Abstract: 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.
Published: 2024
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48. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.

Author: Agosti E, Zeppieri M, Antonietti S, Battaglia L, Ius T, Gagliano C, Fontanella MM, and Panciani PP
Abstract: 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.
Published: 2024
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49. A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.

Author: De Maria L, Panciani PP, Zeppieri M, Ius T, Serioli S, Piazza A, Di Giovanni E, Fontanella MM, and Agosti E
Subjects: Humans, Neuroglia, Antibodies, Monoclonal, ErbB Receptors, Platelet-Derived Growth Factor, Glioma drug therapy
Abstract: 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.
Published: 2024
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50. Advancing Craniopharyngioma Management: A Systematic Review of Current Targeted Therapies and Future Perspectives.

Author: Agosti E, Zeppieri M, Antonietti S, Piazza A, Ius T, Fontanella MM, Fiorindi A, and Panciani PP
Subjects: Humans, Imidazoles, Oximes, Ameloblastoma, Craniopharyngioma drug therapy, Craniopharyngioma genetics, Pituitary Neoplasms drug therapy, Pituitary Neoplasms genetics
Abstract: 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.
Published: 2024
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