Combined Endoscopic Endonasal Transclival and Contralateral Transmaxillary Approach to the Petrous Apex and the Petroclival Synchondrosis: Working "Around the Corner" of the Internal Carotid Artery-Quantitative Anatomical Study and Clinical Applications.

The endoscopic contralateral transmaxillary (CTM) approach has been proposed as a potential route to widen the corridor posterolateral to the internal carotid artery (ICA). In this study, we first refined the surgical technique of a combined multiportal endoscopic endonasal transclival (EETC) and CTM approach to the petrous apex (PA) and petroclival synchondrosis (PCS) in the dissection laboratory, and then validated its applications in a preliminary surgical series. The combined EETC and CTM approach was performed on three cadaver specimens based on four surgical steps: (1) the nasal, (2) the clival, (3) the maxillary and (4) the petrosal phases. The CTM provided a "head-on trajectory" to the PA and PCS and a short distance to the surgical field considerably furthering surgical maneuverability. The best operative set-up was achieved by introducing angled optics via the endonasal route and operative instruments via the transmaxillary corridor exploiting the advantages of a non-coaxial multiportal surgery. Clinical applications of the combined EETC and CTM approach were reported in three cases, a clival chordoma and two giant pituitary adenomas. The present translational study explores the safety and feasibility of a combined multiportal EETC and CTM approach to access the petroclival region though different corridors.

CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study.

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma.

The Posterior Auricularis Muscle as Superficial Landmark for the Sigmoid Sinus and Transverse-Sigmoid Sinus Junction: An Anatomical Study.

OBJECTIVE: Neuronavigation systems coupled with previously reported external anatomical landmarks assist neurosurgeons during intracranial procedures. We aimed to verify whether the posterior auricularis muscle (PAM) could be used as an external landmark for identifying the sigmoid sinus (SS) and the transverse-sigmoid sinus junction (TSSJ) during posterior cranial fossa surgery. METHODS: The PAM was dissected in 10 adult cadaveric heads and after drilling the underlying bone, the relationships with the underlying SS and TSSJ were noted. The width and length of the PAM, and the distance between the muscle and reference points (asterion, mastoid tip, and midline), were measured. RESULTS: The PAM was identified in 18 sides (9 left, 9 right). The first 20 mm of the muscle length (mean 28.28 mm) consistently overlay the mastoid process anteriorly and the proximal half of the SS slightly posteriorly on all sides. The superior border was a mean of 2.22 mm inferior to the TSSJ and, especially when the muscle length exceeded 20 mm, this border extended closer to the transverse sinus; it was usually found at a mean of 3.11 mm (range 0.0-13.80 mm) inferior to the distal third of the transverse sinus. CONCLUSIONS: Superficial landmarks give surgeons improved surgical access, avoiding overexposure of deep neurovascular structures and reducing brain retraction. On the basis of our cadaveric study, the PAM is a reliable and accurate direct landmark for identifying the SS and TSSJ. The PAM could potentially be used for guiding the retrosigmoid approach.

Intrasellar Dermoid Cyst: Case Report of a Rare Lesion and Systematic Literature Review Comparing Intrasellar, Suprasellar, and Parasellar Locations.

OBJECTIVE: Intracranial dermoid cyst (DC) is a rare benign, slow-growing lesion, most commonly arising along the midline. They can occur in the supratentorial compartment, very rarely involve the sellar region and only exceptionally are intrasellar. The aim of our study is to address the challenges in the diagnosis and management of sellar DCs. METHODS: We performed a systematic review of sellar DCs, in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and described an intrasellar DC in a 32-year-old female who presented with bilateral blurring vision. RESULTS: The review identified 4 intrasellar, 29 suprasellar, and 28 parasellar cases. Intrasellar DCs more likely present with progressive visual impairment and pituitary hormone dysfunctions during the fifth decade of life. Suprasellar and parasellar DCs are typically diagnosed during the third decade of life because of diplopia, ptosis, trigeminal hypoaesthesia/para-esthesia or cyst's rupture. Sellar DCs are typically hypodense on computed tomography scans and contain calcifications. Magnetic resonance imaging features include T1 hyperintensity, T2 heterogeneous intensity, no restriction on diffusion-weighted images, and no contrast enhancement. Surgery is the treatment of choice. Gross total resection is achieved in 60% of intrasellar and 61.9% of suprasellar and parasellar DCs. Early postoperative complications are reported in 40.0%, 16.7%, and 23.8% of intrasellar, suprasellar, and parasellar DCs, respectively. CONCLUSIONS: Intrasellar DCs are rare lesions typically diagnosed later than suprasellar and parasellar DCs due to their different clinical presentations. However, they should be considered in the differential diagnosis of cystic lesions of the sella, including epidermoid cysts, craniopharyngiomas, Rathke's cleft cysts, and teratomas.

An anatomical study of the sigmoid sinus artery: Application to the transmastoid approach.

INTRODUCTION: We aimed to investigate the morphological features of the artery that traverse the sigmoid sinus's lateral surface and to discuss this structure's clinical relevance. METHODS: Ten sides from five cadaveric Caucasian heads were used for gross anatomical dissection to investigate the morphological features of the sigmoid sinus artery (SSA), and additional five sides were used for histological observation. RESULTS: The SSA was found on eight out of ten sides (80%). The mean diameter of the SSA was 0.3 mm. The mean distance from the tip of the mastoid process to the artery was 20.3 mm. Histological observation identified extradural and intradural courses of SSA. The intradural course was further categorized into protruding and non-protruding types. In the protruding type, the SSA traveled within the dura but indented into the bone, making it more or less an intraosseous artery. In the non-protruding type, the SSA traveled within the dura but did not protrude into the bone but rather indented into the lumen of the SS. In all sections, both intradural and extradural courses were identified simultaneously. CONCLUSIONS: When the mastoid foramen is observed, it does not always only carry an emissary vein but also an artery. The SSA could be considered a "warning landmark" during bone drilling for the transmastoid approach.

Anatomical study of the mastoid foramina and mastoid emissary veins: classification and application to localizing the sigmoid sinus.

The mastoid foramen (MF) is located on the mastoid process of the temporal bone, adjacent to the occipitomastoid suture or the parietomastoid suture, and contains the mastoid emissary vein (MEV). In retrosigmoid craniotomy, the MEV has been used to localize the position of the sigmoid sinus and, thus, the placement of the initial burr hole. Therefore, this study aimed to examine the exact location and variants of the MF and MEV to determine if their use in localizing the sigmoid sinus is reasonable. The sample in this study comprised 22 adult dried skulls (44 sides). MF were identified and classified into five types based on location, prevalence, whether they communicated with the sigmoid sinus and exact entrance into the groove of the sigmoid sinus. The diameters and relative locations of the MF in the skull were measured and recorded. Finally, the skulls were drilled to investigate the course of the MEV. Additionally, ten latex-injected sides from human cadavers were also dissected to follow the MEV, especially in cases with more than one vein. We found that type I MFs (single foramen) were the most prevalent (50%). These MFs were mainly located on the occipitomastoid suture; only one case on the right side was adjacent to the parietomastoid suture. Type II (paired foramina) was the second most prevalent (22.73%), followed by type III (13.64%), type 0 (9.09%), and type IV (4.55%). The diameter of the external opening in a connecting MF (2.43 ± 0.79) was twice that of a non-connecting MF (1.14 ± 0.56). Interestingly, on one side, two MFs on the external surface shared a single internal opening; the MEV bifurcated. MFs followed three different courses: ascending, almost horizontal, and descending. Regardless of how many external openings there were for the MF, these all ended at a single opening in the groove for the sigmoid sinus. For cadaveric specimens with multiple MEVs, all terminated in the sigmoid sinus as a single vein, with the more medial veins terminating more medially into the sinus. Based on our study, the MF/MEV can guide the surgeon and help localize the deeper-lying sigmoid sinus. Knowledge of this anatomical relationship could be an adjunct to neuronavigational technologies.

The Occipitalis Muscle as an Adjunct Superficial Landmark for the Transverse Sinus and Transverse-Sigmoid Junction: An Anatomical Study With Application to Posterior Cranial Fossa Surgery.

INTRODUCTION: Although neuronavigation systems are widely used for identifying deep intracranial structures, additional superficial anatomical landmarks can be useful when this technology is not available or is not working properly. Herein, we investigate the potential of the occipitalis muscle (OM), rarely mentioned in neurosurgical literature, as a superficial landmark for the transverse sinus (TS) and transverse-sigmoid sinus junction (TSJ). METHODS: Eighteen adult cadaveric heads underwent dissection. The borders of the OM were identified and measured. The muscle was then removed and the bone underlying the muscle was drilled. The relationships between the OM and the underlying dural venous sinuses were then investigated by using a surgical microscope. RESULTS: The OM is a quadrangular-shaped muscle, that invariably crosses the lambdoid suture, showing relationships with the TS inferiorly and the TSJ laterally. The medial border was located a mean of 2.7 cm from the midline and its lower edge was a mean of 1.6 cm above the TS. The inferior border was found between the lambdoid suture and the superior nuchal line in all the specimens. The medial half of the inferior margin was placed on average 1.1 cm superiorly to the TS while the lateral margin ran just above or over the TS. The lateral border was located a mean of 1.1 cm medially to the asterion and approximated the mastoid notch, being within 1-2 cm from it. The TSJ was between 2.1 and 3.4 cm lateral to OM lateral border. CONCLUSION: A combination of superficial anatomical landmarks can be useful for surgical planning. We found that the OM represents a valuable aide for neurosurgeons and is a reliable landmark for the deeper-lying TS and TSJ.

How I do it - The "drum skin" duraplasty technique after foramen magnum decompression for Chiari malformations.

BACKGROUND: Chiari malformations are a spectrum of posterior cranial fossa anomalies characterized by herniation of the cerebellar tonsils through the foramen magnum. Surgery is the treatment of choice for selected patients with good postoperative outcomes. METHODS: We describe foramen magnum decompression (FMD) with dural opening and a "drum skin" duraplasty technique. CONCLUSIONS: In our experience, FMD with "drum skin" duraplasty is a safe and effective procedure, reducing the risk of CSF leakage and arachnoidal adhesions and yielding better long-term clinical and radiological outcomes than other traditional techniques.

Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal.

BACKGROUND: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. METHODS: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. RESULTS: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. CONCLUSIONS: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models.

Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood-brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-ß-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THG@SiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.

Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report.

With the advent of immunotherapies, the field of cancer therapy has been revived with new hope, especially for cancers with dismal prognoses, such as the glioblastoma multiforme (GBM). Currently, immunotherapies should potentiate the host's own antitumor immune response against cancer cells, but it has been documented that they are effective only in small subsets of patients. Therefore, accurate predictors of response are urgently needed to identify who will benefit from immune-modulatory therapies. Brain tumors are challenging in terms of treatments. The immune response in the brain is highly regulated, and the immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes (TILs, CD3+ T cells) in certain patients and, therefore, may serve as a potential treatment target. In our study, we performed immunohistochemistry for CD3 and PD-L1 along the routine assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status and the IDH1 and 2 status in a single center cohort of 69 patients with GBM (58 primary tumors and 11 recurrences) who underwent standard multimodal therapies (surgery/radiotherapy/adjuvant temozolamide). We analyzed the association of PD-L1 tumor expression and TILs with overall survival (OS). The PD-L1 expression was observed in 25 of 58 (43%) newly diagnosed primary glioblastoma specimens. The sparse-to-moderate density of TILs, identified with CD3+ expression, was found in 48 of 58 (83%) specimens. Neither PD-L1 expression nor TILs were associated with overall survival. In conclusion, TILs and/or PD-L1 expression are detectable in the majority of glioblastoma samples, and even if they slightly relate to the outcome, they do not show a statistically significant correlation.

A Newly Discovered Dural Venous Sinus of the Skull Base: The Anterior Petroclinoid Sinus.

INTRODUCTION: Neurosurgeons must master microanatomy and its variants that occur at the skull base. To the best of our knowledge, we describe a previously unreported dural venous sinus (DVS) within the anterior petroclinoid fold and discuss its potential surgical relevance. METHODS: Fifteen latex-injected human cadaveric heads (30 sides) underwent skull base dissection using a surgical microscope. The anterior petroclinoid fold was opened in search of evidence of an embedded DVS. When identified, this sinus was documented, photographed, and measured with microcalipers. RESULTS: An anterior petroclinoid sinus (APCS) was identified in 67% of sides. These DVSs had a mean diameter of 0.65 mm and a length ranging from 8 to 15 mm (mean: 12.5 mm). The APCS ran from the anterior aspect of the cavernous sinus, arising just lateral (60%), posterior (20%), or medial (20%) to the anterior clinoid process, to the superior petrosal sinus (65%) or the posterior aspect of the cavernous sinus (35%), at the level of the posterior clinoid process. Along the course of the APCS, the oculomotor nerve was located medially at the oculomotor porus. Although slightly more common and larger on the right side, there was no statistically significant side difference. CONCLUSIONS: An improved knowledge of variant DVSs can lower the risk of intraoperative complications and increase our understanding of the venous outflow from the cavernous sinus. Future neuroimaging techniques might also seek to identify the APCS. This is the first description of a DVS contained within the anterior petroclinoid fold.

Posterior Petrous Meningiomas: Surgical Classification and Postoperative Outcomes in a Case Series of 130 Patients Operated via the Retrosigmoid Approach.

OBJECTIVE: A standardized definition and classification of primary posterior petrous meningiomas (PPMs) is lacking, with consequent challenges in comparing different case series. This study aimed to provide an anatomical description and classification of PPMs analyzing a homogeneous series of patients operated via the retrosigmoid approach. METHODS: PPMs originate laterally to the petro-occipital fissure within the venous ring composed of the superior petrosal, sigmoid, inferior petrosal, and cavernous sinuses. We proposed a classification based on tumor site of origin, direction of growth relative to the internal acoustic meatus, and cranial nerves' displacement. Four types of PPMs were defined: retromeatal (type A), meatal (type B), premeatal (type C), and broad-based (type D). We performed a retrospective analysis of 130 consecutive patients with PPMs who underwent surgery as first-line treatment. RESULTS: The PPM classification predicted clinical presentation, postoperative morbidity, and resection rates. Headache, hydrocephalus, and cerebellar deficits were more common in type A (59.0%, 37.7%, 49.2%) and type D (66.7%, 66.7%, 33.3%). Hypoacusia/anacusia was more common in type B (87.5%), while trigeminal hypoesthesia/anesthesia was more common in type C (85.0%). After surgery, patients with type A and D PPMs were at higher risk to develop cerebellar deficits (11.5%-22.2%), whereas patients with type B and C PPMs presented with hypoacusia/anacusia (12.5%) and trigeminal deficits (10.0%), respectively. The near-total resection rate was higher in type A (91.8%), followed by types B (82.5%), C (80.0%), and D (77.8%) PPMs. CONCLUSIONS: The PPM surgical classification has an operative and prognostic relevance. In expert hands, the retrosigmoid approach represents a safe and effective approach to remove PPMs.

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

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.

Anatomo-functional evaluation for management and surgical treatment of insular cavernous malformation: a case series.

BACKGROUND: Insular cavernous malformations (iCMs) are very rare vascular lesions. Their surgical management is challenging, due to their complex functional and vascular relationship. The continuous improvement of intra-operative tools and neuroimaging techniques has progressively enhanced the safety of iCM surgery. Nevertheless, the best surgical approach remains controversial. OBJECTIVE: To analyze the potential role of an anatomo-functional classification to guide the iCMs' management. METHODS: The study included patients affected by iCMs and referred to the Senior Author (FA). All cases were divided in 2 groups, according to a mainly pial growth pattern (exophytic group) or a subcortical one (endophytic group). Endophytic iCM was further subdivided in 3 subgroups, based on the insular gyri involved. According to this classification, each patient underwent a specific additional neuroimaging investigation and surgical evaluation. RESULTS: A total of 24 patients were included. In the surgical group, trans-sylvian (TS) approach was used in 6 patients with exophytic or Zone I endophytic iCMs. The transcortical (TC) approach with awake monitoring was used in 6 cases of Zone II endophytic vascular lesions. Both TS and trans-intraparietal sulcal (TIS) approach were used for 3 cases of Zone III endophytic iCM. At follow-up, 3 patients were fully recovered from a transient speech impairment while a permanent morbidity was observed in one case. CONCLUSIONS: ICMs represent a single entity with peculiar clinical and surgical aspects. The proposed iCM classification focuses on anatomical and functional concerns, aiming to suggest the best pre-operative work-up and the surgical evaluation.

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

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 experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

BRAF Signaling Inhibition in Glioblastoma: Which Clinical Perspectives?

IDH-wild type (wt) glioblastoma (GB) accounts for approximately 90% of all GB and has a poor outcome. Surgery and adjuvant therapy with temozolomide and radiotherapy is the main therapeutic approach. Unfortunately, after relapse and progression, which occurs in most cases, there are very limited therapeutic options available. BRAF which plays a role in the oncogenesis of several malignant tumors, is also involved in a small proportion of IDH-wt GB. Previous successes with anti-B-Raf targeted therapy in tumors with V600E BRAF mutation like melanoma, combined with the poor prognosis and paucity of therapeutic options for GB patients is leading to a growing interest in the potential efficacy of this approach. This review is thus focused on dissecting the state of the art and future perspectives on BRAF pathway inhibition in IDH-wt GB. Overall, clinical efficacy is mostly described within case reports and umbrella trials, with promising but still insufficient results to draw more definitive conclusions. Further studies are needed to better define the molecular and phenotypic features that predict for a favorable response to treatment. In addition, limitations of B-Raf-inhibitors, in monotherapy or in combination with other therapeutic partners, to penetrate the blood-brain barrier and the development of acquired resistance mechanisms responsible for tumor progression need to be addressed.

Endoscopic sublabial transmaxillary approach to the inferior orbit: pearls and pitfalls-A comparative anatomical study.

OBJECTIVE: Although orbital surgery has always represented a challenge for neurosurgeons, keyhole and endoscopic techniques are gradually surging in popularity maximizing functional and esthetic outcomes. This quantitative anatomical study first compared the surgical operability achieved through three endoscopic approaches within the inferior orbit: the endoscopic sublabial transmaxillary (ESTMax), the endoscopic endonasal transethmoidal (EETEth), and the endoscope-assisted lateral orbitotomy (ELO). METHODS: Each of these approaches was performed bilaterally on five specimens. We described the ESTMax step-by-step, underlining its advantages and pitfalls in comparison with EETEth and ELO. Then, we assessed surgical measurements and operability in ESTMax, EETEth, and ELO. RESULTS: The ESTMax provided the most favorable operative window (278.9 ± 43.8 mm2; EETEth: 240.8 ± 21.5 mm2, p < 0.001; ELO: 263.1 ± 19.8 mm2, p = 0.006), the broadest surgical field area (415.9 ± 26.4 mm2; EETEth: 386.7 ± 30.1 mm2, p = 0.041; ELO: 305.2 ± 26.3 mm2, p < 0.001), surgical field depths significantly shorter than EETEth (p < 0.001) but similar to ELO, the widest surgical angles of attack (45°-65°; EETEth: 20°-30°, p < 0.001; ELO: 25°-50°, p < 0.001), and the greatest surgical mobility areas (EETEth: p < 0.001; ELO: p < 0.001). Furthermore, the ESTMax allowed multi-angled exposure and handy maneuverability around all the inferior intraorbital targets. Small anterior antrostomy, blunt intraorbital dissections, direct targets' approach, orbital floor reconstruction, and maxillary bone flap replacement may limit the ESTMax morbidity rates. CONCLUSIONS: The ESTMax is a minimally invasive "head-on" orbital approach that exploits endoscopic surgery advantages avoiding the cranio-orbital and trans-nasal approach limitations and possible complications. It represents a promising alternative to EETEth and ELO because of its optimal operability for resecting lesions extending into the entire inferior orbit.

Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study.

OBJECTIVES: Canakinumab is an IL-1ß antibody that neutralises the activity of IL-1ß. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. DESIGN: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2). RESULTS: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2:FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9-96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6-89.1) for Cohort 2. CONCLUSIONS: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care.