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Susanna Bacigaluppi,1– 3 Nicola L Bragazzi,4 Federico Ivaldi,1 Federica Benvenuto,1 Antonio Uccelli,1,5,* Gianluigi Zona1,2,* 1DINOGMI, University of Genoa, Genoa, Italy; 2Department of Neurosurgery and Neurotraumatology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 3Department of Neurosurgery, E.O. Ospedali Galliera, Genoa, Italy; 4DISSAL-University of Genoa, Genoa, Italy; 5Department of Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy*These authors contributed equally to this workCorrespondence: Susanna Bacigaluppi, Department of Neurosurgery and Neurotraumatology, DINOGMI, University of Genoa, IRCCS Policlinico San Martino, Largo Rosanna Benzi 10, Genoa, 16132, Italy, Email susanna.bacigaluppi@unige.itObjective: It is well known that spontaneous non-aneurysmal subarachnoid hemorrhage (SAH), also known as sine materia SAH (smSAH), has usually a better course and prognosis than its aneurysmal counterpart (aSAH). This might depend on different inflammatory mechanisms initiated by bleeding events of different origins. The aim of the present study was to explore the systemic inflammatory response in spontaneous SAH, comparing aSAH and smSAH.Methods: We performed a prospective observational study over a consecutive series of patients with SAH. For these patients, we collected all clinical data and, furthermore, performed venous blood sampling over six time points to analyze blood cells. We further performed the analysis of lymphocytes and monocytes by means of flow cytometry to quantify common subtypes. Statistical analysis included a t-student test, Chi-square test, multivariate logistic regression, and ROC analysis.Results: 48 patients were included: six (12.5%) with a diagnosis of spontaneous smSAH, and forty-two patients (87.5%) with aSAH. Significant differences on Day 0 were found for neutrophils and a systemic neuro-inflammatory index, namely, systemic inflammatory response index (SIRI). At the ROC analysis, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and SIRI exhibited satisfactory predictive power on day 0. At the multivariable logistic regression analysis, the combined index (NLR, LMR, SIRI at day 0) yielded an OR of 0.59 (95% CI 0.29– 1.21]). LMR at day 0 yielded an OR of 1.25 ([95% CI 0.94– 1.68]), NLR at day 0 exhibited an OR of 0.68 ([95% CI 0.42– 1.09]), and SIRI at day 0 displayed an OR of 0.31 ([95% CI 0.06– 1.49]).Conclusion: This preliminary study indicated a possible role of some inflammatory indices that point out the importance of innate and adaptive immunity in the etiopathogenetic mechanisms. Drugs modulating these responses could eventually counteract or, at least, reduce secondary damage associated with SAH.Keywords: SAH, aneurysmal SAH, sine materia SAH, SAH of unknown origin, systemic inflammation, neutrophils, inflammatory indices

Giuliana Corica,1,2 Marco Ceraudo,3 Claudia Campana,1,2 Federica Nista,1,2 Francesco Cocchiara,2 Mara Boschetti,1,2 Gianluigi Zona,3 Diego Criminelli,3 Diego Ferone,1,2 Federico Gatto1 1Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 2Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI) and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy; 3Neurosurgery Unit, Department of Neurosciences (DINOGMI), IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, ItalyCorrespondence: Diego FeroneEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa 16132, ItalyTel +39 010 3537946Fax +39 010 3537060Email ferone@unige.itAbstract: Acromegaly is a rare and severe disease caused by an increased and autonomous secretion of growth hormone (GH), thus resulting in high circulating levels of insulin-like growth factor 1 (IGF-1). Comorbidities and mortality rate are closely related to the disease duration. However, in most cases achieving biochemical control means reducing or even normalizing mortality and restoring normal life expectancy. Current treatment for acromegaly includes neurosurgery, radiotherapy and medical therapy. Transsphenoidal surgery often represents the recommended first-line treatment. First-generation somatostatin receptor ligands (SRLs) are the drug of choice in patients with persistent disease after surgery and are suggested as first-line treatment for those ineligible for surgery. However, only about half of patients treated with octreotide (or lanreotide) achieve biochemical control. Other available drugs approved for clinical use are the second-generation SRL pasireotide, the dopamine agonist cabergoline, and the GH-receptor antagonist pegvisomant. In the present paper, we revised the current literature about the management of acromegaly, aiming to highlight the most relevant and recent therapeutic strategies proposed for patients resistant to first-line medical therapy. Furthermore, we discussed the potential molecular mechanisms involved in the variable response to first-generation SRLs. Due to the availability of different medical therapies, the choice for the most appropriate drug can be currently based also on the peculiar clinical characteristics of each patient.Keywords: acromegaly, biochemical control, medical therapy, resistance, somatostatin receptor ligands

Progressive dysphagia and dyspnoea presenting after major neck trauma can occasionally be secondary to post-traumatic inflammation and mass effect associated with a calcified osteophytic anterior longitudinal ligament, a frequent finding in diffuse idiopathic skeletal hyperostosis, though rarely enough to cause such symptoms. In these circumstances, surgical decompression may prove effective. [ABSTRACT FROM AUTHOR]

Background: Trauma, including traumatic brain injury (TBI), is the leading cause of nonobstetric maternal mortality during pregnancy. Few data are available regarding the optimal management of pregnant patients with TBI, leading to a lack of dedicated guidelines. We performed an international survey to examine the management of severe TBI in pregnant patients, focusing on monitoring, therapy, and intensive care practices., Methods: This survey, endorsed by the World Society of Emergency Surgery, was composed of a questionnaire with 79 items divided into four sections: (1) general information (items 1-7), (2) management of the maternal-fetal unit (items 8-43), (3) management of intracranial hypertension (items 44-76), and (4) specific considerations (items 77-79)., Results: One hundred and twenty-two physicians from 110 centers in 35 countries responded. The main findings related to TBI care in pregnant patients included the following: (1) a lack of availability of a specific TBI protocol in pregnancy; (2) an increase in the utilization of magnetic resonance imaging as the primary neuroimaging tool; (3) higher hemoglobin thresholds for transfusion; and (4) a lower utilization of therapeutic hypothermia, neuromuscular blocking agents, and barbiturate coma. We also report large variability in the timing of cesarean section in pregnant patients with TBI (≥ 23 weeks of gestation) needing an emergency craniotomy (simultaneously 23% vs. later cesarean section 50.8%)., Conclusions: Great variability in the management of pregnant patients with severe TBI was identified worldwide from the results of our survey. These findings, highlighting the lack of robust evidence on this topic, will be helpful to stimulate future investigations and to promote educational efforts on this difficult scenario., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: High-grade glioma (HGG) patients post-radiotherapy often face challenges distinguishing true tumor progression (TTP) from pseudoprogression (PsP). This study evaluates the effectiveness of systemic inflammatory markers and volume of enhancing tissue on post-contrast T1 weighted (T1WCE) MRI images for this differentiation within the first six months after treatment., Material and Methods: We conducted a retrospective analysis on a cohort of HGG patients from 2015 to 2021, categorized per WHO 2016 and 2021 criteria. We analyzed treatment responses using modified RANO criteria and conducted volumetry on T1WCE and T2W/FLAIR images.Blood parameters assessed included neutrophil/lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). We employed Chi-square, Fisher's exact test, and Mann-Whitney U test for statistical analyses, using log-transformed predictors due to multicollinearity. A Cox regression analysis assessed the impact of PsP- and TTP-related factors on overall survival (OS)., Results: The cohort consisted of 39 patients, where 16 exhibited PsP and 23 showed TTP. Univariate analysis revealed significantly higher NLR and SII in the TTP group [NLR: 4.1 vs 7.3, p = 0.002; SII 546.5 vs 890.5p = 0.009]. T1WCE volume distinctly differentiated PsP from TTP [2.2 vs 11.7, p < 0.001]. In multivariate regression, significant predictors included NLR and T1WCE volume in the "NLR Model," and T1WCE volume and SII in the "SII Model." The study also found a significantly lower OS rate in TTP patients compared to those with PsP [HR 3.97, CI 1.59 to 9.93, p = 0.003]., Conclusion: Elevated both, SII and NLR, and increased T1WCE volume were effective in differentiating TTP from PsP in HGG patients post-radiotherapy. These results suggest the potential utility of incorporating these markers into clinical practice, though further research is necessary to confirm these findings in larger patient cohorts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers., Research Question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy., Materials and Methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers., Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request., Discussion and Conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: All available recommendations about the management of antithrombotic therapies (ATs) in patients who experienced traumatic brain injury (TBI) are mainly based on expert opinion because of the lack of strength in the available evidence-based medicine. Currently, the withdrawal and the resumption of AT in these patients is empirical, widely variable, and based on the individual assessment of the attending physician. The main difficulty is to balance the thrombotic and hemorrhagic risks to improve patient outcome., Methods: Under the endorsement of the Neurotraumatology Section of Italian Society of Neurosurgery, the Italian Society for the Study about Haemostasis and Thrombosis, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care, and the European Association of Neurosurgical Societies, a working group (WG) of clinicians completed two rounds of questionnaires, using the Delphi method, in a multidisciplinary setting. A table for thrombotic and bleeding risk, with a dichotomization in high risk and low risk, was established before questionnaire administration. In this table, the risk is calculated by matching different isolated TBI (iTBI) scenarios such as acute and chronic subdural hematomas, extradural hematoma, brain contusion (intracerebral hemorrhage), and traumatic subarachnoid hemorrhage with patients under active AT treatment. The registered indication could include AT primary prevention, cardiac valve prosthesis, vascular stents, venous thromboembolism, and atrial fibrillation., Results: The WG proposed a total of 28 statements encompassing the most common clinical scenarios about the withdrawal of antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients who experienced blunt iTBI. The WG voted on the grade of appropriateness of seven recommended interventions. Overall, the panel reached an agreement for 20 of 28 (71%) questions, deeming 11 of 28 (39%) as appropriate and 9 of 28 (32%) as inappropriate interventions. The appropriateness of intervention was rated as uncertain for 8 of 28 (28%) questions., Conclusions: The initial establishment of a thrombotic and/or bleeding risk scoring system can provide a vital theoretical basis for the evaluation of effective management in individuals under AT who sustained an iTBI. The listed recommendations can be implemented into local protocols for a more homogeneous strategy. Validation using large cohorts of patients needs to be developed. This is the first part of a project to update the management of AT in patients with iTBI., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance., Research Question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems., Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction.", Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain.", Discussion and Conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care., Competing Interests: No conflict of interest is to be disclosed by Salvatore Chibbaro, Thomas Sauvigny, Ivan Timofeev, Harry Mee, and Ismail Zaed. Corrado Iaccarino received educational grants from 10.13039/100009006Integra Lifescience. Franco Servadei received consultancy and speaker fees from Finceramica, Integra Life Sciences, and Upsurgeon. Silvio Franchetti received education grants producing HA., (© 2024 The Authors.)

Background and Importance: COVID-19 is a viral infection that mainly affects the respiratory tract, but can also cause multiple inflammatory reactions, including neurological and cerebrovascular manifestations. We report the case of a COVID-19 patient who developed 'de novo' multiple cerebral aneurysms with no risk factors for aneurysm formation., Clinical Presentation: A 55-year-old man with SARS-CoV-2 infection came to our attention for left eye blindness accompanied by ptosis, palpebral chemosis and retro-orbital pain. Brain CT and CT-angiography were negative for hemorrhages and for vascular malformations. Repeated intracerebral hemorrhages and neurological deterioration then occurred, and a new CT-angiography showed multiple intracranial aneurysms that were not present before., Conclusion: Intracranial aneurysm formation as a complication of COVID-19 has not been previously reported. As other viral infections do, COVID-19 may be able to determine a vascular damage that can ultimately lead to development of an aneurysm. It is reasonable to hypothesize an involvement of the renin-angiotensin system as a pathogenic mechanism. A conservative therapy aiming at inflammatory modulation and vascular damage prevention may be warranted in these patients.

Background: Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes., Methods: Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions., Results: Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis., Conclusions: We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease., Methods: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool., Results: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear., Conclusions: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

Introduction: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients. The second aim is to verify the most important spatio-temporal parameters in INPH assessment and their possible correlations with clinical outcome measures., Methods: Between January 2019 and June 2022, we evaluated 70 INPH subjects. We assessed balance performances with the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), and TUG, both single (ST) and dual task (DT). We also performed an instrumental gait assessment with the GAITRite electronic walkway system, asking the patients to walk on the carpet for one minute at normal speed, fast speed, and while performing a dual task. We compared the results with those of 20 age-matched healthy subjects (HS)., Results: INPH patients obtained statistically significant lower scores at the BBS, SPPB, and TUG DT but not at the TUG ST, likely because the DT involves cognitive factors altered in these subjects. Concerning instrumental gait evaluation, we found significant differences between HS and INPH patients in almost all spatio-temporal parameters except cadence, which is considered a relevant factor in INPH guidelines. We also found significant correlations between balance outcome measures and gait parameters., Discussion: Our results confirm the usefulness of BBS and suggest improving the assessment with SPPB. Although the TUG ST is the most commonly used test in the literature to evaluate INPH performances, it does not identify INPH; the TUG DT, instead, might be more useful. The GAITRite system is recognized as a quick and reliable tool to assess walking abilities and spatio-temporal parameters in INPH patients, and the most useful parameters are stride length, stride width, speed, and the percentage of double support. Both clinical and instrumental evaluation may be useful in recognizing subjects at risk for falls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mori, Collino, Marzi, Pellegrino, Ponzano, Chiaro, Maestrini, Caneva, Pardini, Fiaschi, Zona, Trompetto and Ligurian INPH Study.)

During the Coronavirus-disease-2019 (COVID-19) pandemic emergency, neurosurgeons may have to decide to prioritize treatments to patients with the best chance of survival, as in a war setting triage. In this paper, we discussed factors that should be considered in the perioperative period and neurocritical care management of neurosurgical patients during a pandemic emergency; in particular, we focused on the decision on whether to operate or not a patient during the COVID-19 pandemic. A multidisciplinary expert panel composed by specialists with direct experience in COVID-19 management discussed and reviewed the criteria that should be taken into account in the decision to operate or not a patient during the COVID-19 pandemic. Disease-related factors should be first considered in order to precisely know the enemy we are facing. Patient-related factors should be then evaluated to understand the battleground on which we are facing the enemy. After these considerations, we must ascertain costs and expected outcomes of our surgical intervention by evaluation of surgery-related factors. Finally, the last factor that need to be evaluated before surgery is the availability of resources, staff, and ward availability for perioperative care. All these considerations will lead to the optimal organization and management of neurosurgical emergencies during pandemic times, considering the community and not only the single patient. We provided schematic preoperative considerations that we hope will help neurosurgeons to guide their decisions in these challenging times.

Background: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality., Methods: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included., Results: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001)., Conclusions: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS., (© 2023. The Author(s).)

Introduction: Anticoagulation management in high-grade gliomas is a widely studied but still debated topic, since the increased thrombotic risk is accompanied by the high background rate of intralesional bleeding. Currently, the main challenge when prescribing anticoagulants to HGG patients is to balance the risk between ICH and VTE both in the perioperative period and in the postoperative follow-up during adjuvant chemo- and radiotherapic treatment., Evidence Acquisition: A systematic review according to PRISMA-P Guidelines was performed: 12 observational studies were selected, eight retrospective and four prospective. Regarding the reviews 3 were selected, two of which analyzed bleeding complications of anticoagulation therapy and one on thrombotic events., Evidence Synthesis: In the selected studies, the risk of VTEs was between 4 and 33%, while in patients with VTEs subsequently subjected to anticoagulant therapy the cases of ICH ranged from 0% to 15.4%. Regarding the reviews, two meta-analyses have evaluated the incidence of ICH in patients undergoing anticoagulation therapy following thromboembolic events, they agree in quantifying the increased risk of bleeding., Conclusions: The results of our review are generally consistent in stating that the thrombotic risk is increased in patients with HGG, suggesting that more extensive antithrombotic prophylaxis could positively impact the outcome of these patients, even if currently there are no conclusive elements in indicating or contraindicating prolonged antithrombotic prophylaxis - considering that anticoagulant administration in these patients involves an increased risk of ICH. All the studies examined have considered a prolonged heparin treatment without considering the new oral anticoagulants, so further studies about this topic are needed.

Vertebral body metastases (VBM) are one of the most frequent sites of bone metastasis, and their adequate therapeutic management still represents an insidious challenge for both oncologists and surgeons. A possible alternative treatment for VBM is radiofrequency ablation (RFA), a percutaneous technique in which an alternating current is delivered to the tumor lesion producing local heating and consequent necrosis. However, RFA alone could alter the biomechanics and microanatomy of the vertebral body, thus increasing the risk of post-procedure vertebral fractures and spine instability, and indeed the aim of the present study is to investigate the effects of RFA on spine stability. A systematic review according to PRISMA-P guidelines was performed, and 17 papers were selected for the systematic review. The results show how RFA is an effective, safe, and feasible alternative to conventional radiotherapy for the treatment of VBM without indication for surgery, but spine stability is a major issue in this context. Although exerting undeniable benefits on pain control and local tumor recurrence, RFA alone increases the risk of spine instability and consequent vertebral body fractures and collapses. Concomitant safe and feasible therapeutic strategies such as percutaneous vertebroplasty and kyphoplasty have shown synergic positive effects on back pain and improvement in spine stability.

Study Design: Retrospective multicenter., Objectives: diffuse idiopathic skeletal hyperostosis (DISH) involving the cervical spine is a rare condition determining disabling aero-digestive symptoms. We analyzed impact of preoperative settings and intraoperative techniques on outcome of patients undergoing surgery for DISH., Methods: Patients with DISH needing for anterior cervical osteophytectomy were collected. Swallow studies and endoscopy supported imaging in targeting bone decompression. Patients characteristics, clinico-radiological presentation, outcome and surgical strategies were recorded. Impact on clinical outcome of duration and time to surgery and different surgical techniques was evaluated through ANOVA., Results: 24 patients underwent surgery. No correlation was noted between specific spinal levels affected by DISH and severity of pre-operative dysphagia. A trend toward a full clinical improvement was noted preferring the chisel ( P = 0.12) to the burr ( P = 0.65), and whenever C2-C3 was decompressed, whether hyperostosis included that level ( P = 0.15). Use of curved chisel reduced the surgical times ( P = 0.02) and, together with the nasogastric tube, the risk of complications, while bone removal involving 3 levels or more ( P = 0.04) and shorter waiting times for surgery ( P < 0.001) positively influenced a complete swallowing recovery. Early decompressions were preferred, resulting in 66.6% of patients reporting disappearance of symptoms within 7 days. One and two recurrences respectively at clinical and radiological follow-up were registered 18-30 months after surgery., Conclusion: The "age of DISH" counts more than patients' age with timeliness of decompression being crucial in determining clinical outcome even with a preoperative mild dysphagia. Targeted bone resections could be reasonable in elderly patients, while in younger ones more extended decompressions should be preferred.

Background: The meningo-orbital band (MOB) is a dural structure which runs around the superior orbital fissure (SOF) tethering the frontotemporal basal dura to the periorbita, through the SOF. MOB division is important to expose and remove the anterior clinoid process, to access to proximal carotid artery and cavernous sinus area. The aim of this study was to measure how the MOB could be safely incised without cranial nerves and cavernous sinus injuries., Methods: Anatomical dissections and extradural exposure of the anterior clinoid process was performed on 20 cadavers (40 sides). Measurement of the MOB thickness was performed before its incision, after dura propria dissection, and retraction off the inner cavernous membrane, to expose the cranial nerves., Results: We analyzed 20 cadaveric formalin-fixed heads injected with colored silicone, 11 man and 9 women of Caucasian race. The average length of a safe incision of the MOB was 10.6±1.1 mm on the right side, and 10.65±1.09 mm on the left side., Conclusions: In our study the average length of a safe incision of the MOB was 10.6±1.1 mm. Thus, the incision length of the MOB should not exceed 9 mm; the peeling of the anterior cavernous sinus and of the SOF, dissecting the two layers of the dura throughout the incision of the MOB, is a useful technique to avoid cranial nerves and cavernous sinus lesions.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Questions remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance regarding this topic. Specifically, in this manuscript (part 2), we aim to provide a list of experts' recommendations regarding the management of SAH patients in a center with neurosurgical/neuroendovascular facilities after aneurysm treatment., Methods: A multidisciplinary consensus panel composed by 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted., Results: A total of 33 statements were discussed, voted, and approved. Consensus was reached on 30 recommendations (28 strong and 2 weak). In 3 cases, where consensus could not be agreed upon, no recommendation was provided., Conclusions: This consensus provides practical recommendations (and not mandatory standard of practice) to support clinician's decision-making in the management of SAH patients in centers with neurosurgical/neuroendovascular facilities after aneurysm securing., (© 2022. The Author(s).)

Purpose: Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length., Methods: Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts., Results: Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p < 0.001), and yearly cost/patient (€4927 vs €9161; p < 0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1 ≤ 1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p = 1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p = 0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p = 0.019)., Conclusions: Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units., Case Presentation: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient., Conclusion: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology., (© 2022. The Author(s).)