BACKGROUND:Posterior fossa approaches are commonly used during routine neurosurgery. Cerebrospinal fluid (CSF) leakage is one of the most important posterior fossa surgery-related complications. CSF leakage can manifest as both pseudomeningocele and external leakage. If craniotomy or craniectomy is performed, the skull defect can be repaired using heterologous polymethylmethacrylate (PMMA) cranioplasty. The aim of this study was to evaluate the clinical results of the O-ring technique in terms of postoperative complications. METHODS:Patients treated using the retrosigmoid (RS), key-hole RS, or cerebellar hemispheric approach with O-ring PMMA cranioplasty were selected. Data analysis considered age, sex, pathology, surgical approach, presence of preoperative hydrocephalus, wound closure problems, and CSF-related complications postoperatively and at one- and three-month follow-ups. RESULTS:Thirty-three patients were selected, and meningioma was the most common disease. The majority of patients (60.6%) were treated with the standard RS approach. No patient presented with surgical complications in terms of pseudomeningocele or external CSF leakage, neither postoperatively nor at the one-month follow-up. On three-month follow-up MRI, subcutaneous fluid collection was observed in two patients (6.1%). CONCLUSIONS:Our study shows promising results that the O-ring technique could represent a valid option to reduce postoperative CSF leakage in posterior fossa surgery.

BackgroundSevere asthma limits exercise to avoid respiratory symptoms. The objective of the present study was to investigate the role of the 6-min walk test (6MWT) in severe asthma.MethodsConsecutive patients with severe eosinophilic asthma were enrolled. A 6MWT was performed before and after 12 months. Inhaled therapy dose, oral corticosteroids dose, pulmonary function tests, eosinophil blood count, fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) score and responses to the Asthma Quality of Life Questionnaire (AQLQ) were also recorded.ResultsOf the 22 patients enrolled, 13 were treated with mepolizumab 100 mg every 4 weeks in addition to conventional therapy and nine with conventional therapy only. The majority of the patients were treated with high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists, while approximately half were on continuous oral corticosteroids. After 12 months, the mepolizumab group only showed a significant improvement in pulmonary function tests (percentage forced expiratory volume in 1 s and percentage forced expiratory flow at 25–75% forced vital capacity (FEF25–75%), both p<0.001; percentage forced vital capacity, p<0.01) and clinical laboratory parameters (eosinophil count,FeNOmeasured at a flow rate of 50 mL·s−1, ACT and AQLQ, p<0.001). No significant changes in the proportion of patients using continuous oral corticosteroids and high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists were observed in either group (p>0.05). By paired comparisons, statistically significant improvements of the mean 6-min walk distance (6MWD) were observed in the mepolizumab (p<0.001) and conventional therapy (p<0.01) groups, while no improvement was seen in dyspnoea Borg scale, heart rate, percentage oxygen saturation or systolic and diastolic blood pressure. 6MWD showed significant direct correlations with ACT (r=0.5998, p<0.001), AQLQ (r=0.3978, p=0.009) and FEF25–75%(r=0.3589, p=0.017).ConclusionsThe 6MWT could complement severe asthma assessment and be relevant in evaluating the objective response to treatment, including biological therapies like mepolizumab.

Cerebral retraction is frequently required in cranial surgery to access deep areas. Brain retractors have been systematically used in the past, but they have been associated with brain injury. Nonetheless, they are still used and, even recently, new systems have been advocated. The aim of this study is to provide a systematic and critical review of brain retraction injury. A systematic literature review was performed in February 2023 according to PRISMA statement. Search terms included brain retraction and injury, with their variations and pertinent associations. Studies reporting qualitative and quantitative data on brain retraction injury were included. Out of 1689 initially retrieved articles, 90 and 26 were included in the systematic review for qualitative and quantitative data, respectively. The definition of brain retraction injury varies and its reported incidence in clinical studies is 5-10%, up to 47% if cerebral edema is considered. Some studies have hypothesized threshold values of pressures to be respected in order to prevent complications, with most data deriving from animal studies. At present, there are no instruments for brain retraction that can guarantee full safety. Some form of cerebral retraction might always be necessary for specific scenarios. Further studies are needed to collect quantitative and, ideally, clinical and comparative data on pressure thresholds to develop retraction systems that can reduce injury to a minimum.

Background: The increasing complexity of transnasal endoscopic skull base surgery has led to a significant increase in operating times and, therefore, to the demand for an endoscope holder. A robotic endoscope holder might provide various advantages in transnasal endoscopic skull base surgery, but only recently the first clinical evaluations of robotic systems have been published. Objective: A systematic review of the literature was performed to provide a comprehensive critical overview of robotic systems developed for transnasal endoscopic skull base surgery and evaluated in a clinical setting. Methods: A systematic review was performed on PubMed and Scopus databases, using different keywords. The retrieved papers were analyzed, recording the following features: name of the robotic system, function of the robotic system, number of treated patients, and key findings. Results: Clinical studies included in the review were divided into the following categories: transoral robotic skull base surgery with free-hand endoscopic transnasal approach; robotic armrest (iArms); robotic endoscope holders (ENDOFIXexo; Endoscope Robot®). Each category has specific advantages and limitations. Clinical experiences are increasingly reported but they still remain limited. Conclusions: A few clinical applications of robotic endoscopic skull base surgery have been described. To improve the present results, the need for close collaboration with the industry and engineering research centers is evident and of paramount importance for future developments.

Neurosurgery is a highly specialized field: it often involves surgical manipulation of noble structures and cerebral retraction is frequently necessary to reach deep-seated brain lesions. There are still no reliable methods preventing possible retraction complications. The objective of this study was to design work chambers well suited for transcranial endoscopic surgery while providing safe retraction of the surrounding brain tissue. The chamber is designed to be inserted close to the intracranial point of interest; once it is best placed it can be opened. This should guarantee an appreciable workspace similar to that of current neurosurgical procedures. The experimental aspect of this study involved the use of a force sensor to evaluate the pressures exerted on the brain tissue during the retraction phase. Following pterional craniotomy, pressure measurements were made during retraction with the use of a conventional metal spatula with different inclinations. Note that, although the force values necessary for retraction and exerted on the spatula by the neurosurgeon are the same, the local pressure exerted on the parenchyma at the edge of the spatula at different inclinations varied greatly. A new method of cerebral retraction using a chamber retractor (CR) has been designed to avoid any type of complication due to spatula edge overpressures and to maintain acceptable pressure values exerted on the parenchyma.

Background Spinal angiolipomas (SAs) are rare, benign tumors, representing 0.0004 to 1.2% of angiolipomas, usually located at the extradural and posterior thoracic level, with multimetameric extension. Methods A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The authors searched on PubMed and Scopus databases for published articles with the Mesh term "spinal angiolipoma" and pertinent associations. Language restriction to English papers was applied. The authors also reported three emblematic cases of patients who underwent surgical resection of spindle-shaped (type IA) and dumbbell-shaped (type II) SAs between 2014 and 2020. Results Of the 256 retrieved articles, 33 were included in the meta-analysis. These 33 studies, together with our 3 reported cases, included a total of 60 patients, 36 females (60%) and 24 males (40%), with a mean age of 53.12 +/- 12.82 years (range: 12-77 years). T5 was the most represented level (22 patients). Usually, the localization of SA was extradural, with 53 patients suffering from spindle-shaped type IA SA (88.3%) and 7 patients from dumbbell-shaped type II SA (11.6%). Almost all patients underwent laminectomy (78.3%) and presented a full recovery of motor deficits (85%). Gross total removal (GTR) was performed in 93.3% of patients. The mean follow-up was of 22.71 +/- 21.45 months (range: 2-80 months). There was no documented recurrence at follow-up magnetic resonance imaging in any of the patients. Conclusions SAs are rare, benign tumors with a great vascular component that presents a favorable outcome. GTR is the gold standard treatment and usually an adjuvant therapy is not required. Even infiltrative lesions, which are more complex, can be treated successfully with a good prognosis. Dumbbell-shaped SAs must be differentiated from schwannomas and meningiomas, and require different surgical techniques, given the profuse bleeding associated with the attempt of debulking. En block resection is the key to treat these common benign tumors with acceptable blood loss.

BACKGROUND: Convexity meningiomas are considered low-risk tumors, with high possibility of cure and low risk of relapse after resection. Very few studies have investigated meningiomas located in or around highly eloquent regions (namely perirolandic and perisylvian fissures). This study aimed to determine the differences in preoperative characteristics and postoperative outcomes between convexity meningiomas at eloquent area and non-eloquent areas.METHODS: Retrospective study on patients who underwent surgical resection for convexity meningioma. Patients were divided into eloquent and non-eloquent area. Statistical analysis was made comparing preoperative and postoperative data of both groups.RESULTS: The study included a total of 117 patients: 80 with eloquent area tumor and 37 with non-eloquent area tumor. Statistically significant differences were detected between the groups in preoperative KPS (93±10 in eloquent vs. 97±6 in non-eloquent; P=0.008) and in large-caliber vein involvement (76.3% in cases vs. 16.2% in controls; P<0.001). Postoperatively, patients with eloquent area tumors showed initial deterioration in neurological status followed by recovery; final outcomes were comparable to that of patients with non-eloquent area tumors. However, patients with eloquent area meningiomas had higher propensity to suffer from seizures postoperatively. Postoperative complications and long-term outcomes were not significantly different between the two groups.CONCLUSIONS: Patients with eloquent areas convexity meningiomas do not appear to have higher surgical risk. Neurological status is more likely to worsen immediately after surgery, but long-term recovery is satisfactory. Seizure control after surgery appears to be poorer in patients with perirolandic meningioma.

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 he 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.

Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion into the MR hyper intense tissue which typically surrounds the tumor, the so-called supra marginal resection (SMR). Though it should be associated with better overall survival (OS), a potential harmful resection must be avoided in order not to create new neurological deficits. Through this work, we aimed to perform a critical review of SMR in patients with Glioblastoma. A Medline database search and a pooled meta-analysis of HRs were conducted; 19 articles were included. Meta-analysis revealed a pooled OS HR of 0.64 (p = 0.052). SMR is generally considered as the resection of any T1w gadolinium-enhanced tumor exceeding FLAIR volume, but no consensus exists about the amount of volume that must be resected to have an OS gain. Equally, the role and the weight of several pre-operative features (tumor volume, location, eloquence, etc.), the intraoperative methods to extend resection, and the post-operative deficits, need to be considered more deeply in future studies.

This study focuses on the variations in the brain tissue dynamic behaviour pointing out new insight into the material nonlinear viscoelasticity. Shear dynamic response curves are obtained in different working conditions in terms of strain sweep and superimposed static compression offsets (SCO) applied in orthogonal direction to the shear. The strain sweep mode is used to study the storage and loss moduli dependence on the amplitude of the applied strain. It is found that the material exhibits linear viscoelastic behaviour up to about 0.1% strain amplitude. Above this critical threshold, the storage modulus G' decreases rapidly with increasing dynamic strain amplitude and this effect is gradually intensified as the SCO are increased. In addition, it is observed that the loss factor (G''/G') increases by increasing the SCO applied to the specimens. The dynamic strain amplitude results of the storage modulus reveal that the elastic component of the brain tissue's stiffness (G') evaluated at low strain strongly increases with increasing static superimposed compression strain while the loss factor in the same strain range appears to be SCO independent. Finally, dynamic stiffness recovery after a large strain deformation is considered. The reduction in low amplitude dynamic modulus and subsequent recovery kinetics due to a perturbation is found to be independent of the level of the SCO. The same assessments were carried out on 5 consecutive strain sweep cycle loading. It has been noticed that at the last cycle, the dissipation peak is reduced, and the non-linearity of the curve begins earlier. This could be explained by the effects of cerebral edema on cells and their surrounding environment.

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. 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. 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. 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.

Early prediction of COVID-19 in-hospital mortality relies usually on patients’ preexisting comorbidities and is rarely reproducible in independent cohorts. We wanted to compare the role of routinely measured biomarkers of immunity, inflammation, and cellular damage with preexisting comorbidities in eight different machine-learning models to predict mortality, and evaluate their performance in an independent population. We recruited and followed-up consecutive adult patients with SARS-Cov-2 infection in two different Italian hospitals. We predicted 60-day mortality in one cohort (development dataset, n = 299 patients, of which 80% was allocated to the development dataset and 20% to the training set) and retested the models in the second cohort (external validation dataset, n = 402).Demographic, clinical, and laboratory features at admission, treatments and disease outcomes were significantly different between the two cohorts. Notably, significant differences were observed for %lymphocytes (p < 0.05), international-normalized-ratio (p < 0.01), platelets, alanine-aminotransferase, creatinine (all p < 0.001). The primary outcome (60-day mortality) was 29.10% (n = 87) in the development dataset, and 39.55% (n = 159) in the external validation dataset. The performance of the 8 tested models on the external validation dataset were similar to that of the holdout test dataset, indicating that the models capture the key predictors of mortality. The shap analysis in both datasets showed that age, immune features (%lymphocytes, platelets) and LDH substantially impacted on all models' predictions, while creatinine and CRP varied among the different models. The model with the better performance was model 8 (60-day mortality AUROC 0.83 ± 0.06 in holdout test set, 0.79 ± 0.02 in external validation dataset). The features that had the greatest impact on this model's prediction were age, LDH, platelets, and %lymphocytes, more than comorbidities or inflammation markers, and these findings were highly consistent in both datasets, likely reflecting the virus effect at the very beginning of the disease.

Abstract BACKGROUND The behavior of meningiomas under influence of progestin therapy remains unclear. OBJECTIVE To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA). METHODS This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment. RESULTS Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of −0.54 mm3/day) after discontinuation of PCA. CONCLUSION Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal. Graphical Abstract Graphical Abstract

From the Summary: "Since 31 December 2019 and as of 2 August 2020, 17 841 669 cases of COVID-19 [coronavirus disease 2019] have been reported worldwide, including 685 281 deaths European Union/European Economic Area (EU/EEA) countries and the United Kingdom (UK) have reported 1 733 550 cases (10% of all cases), including 182 639 deaths (27% of all deaths) The COVID-19 pandemic continues to pose a major public health threat to EU/EEA countries and the UK and to countries worldwide As cases increased, peaking in early April 2020 in the EU/EEA, many countries implemented a range of response measures which led to a reduction in incidence As countries regained control of transmission and alleviated the burden on healthcare, many measures were relaxed or removed to allow for a more viable way of life with the virus in circulation Subsequently, a recent increase in COVID-19 cases has been reported in many EU/EEA countries While many countries are now testing mild and asymptomatic cases, which has resulted in increased case reports, there is a true resurgence in cases in several countries as a result of physical distancing measures being relaxed "

Background: Incidence of chronic subdural hematomas (cSDH) is expected to progressive rise in the next decades. There is no univocal indication of the approach to be used. Furthermore, there is no data about the efficacy of twist drill craniostomy (TDC) in hematomas with membranes. Objective: To describe our modified technique for TDC in patients affected by cSDH with membranes and in treatment with antiplatelets. Methods: We analyzed a group of 37 patients, affected by cSDH with membrane (type D laminar membrane and type G trabecular membrane according to Nakaguchi classification), treated with mushroom TDC using a modified technique. Results: After surgery the average maximum thickness of the common postoperative liquoral subdural collection decreased from 18.8 to 6.21 mm. We documented one acute subdural hematoma (2.7%), asymptomatic and not treated, and one recurrence of cSDH (2.7%) after 2 months that needed re-intervention with single burr hole. Conclusions: We presented a modified twist drill technique, characterized by the introduction of an application of a new device that optimizes both surgical results, clinical outcome and surgical procedure time. The presence of membrane type D and G does not affect the efficacy of drainage, that is negatively related to the presence of clots or acute hematoma. This modified technique is safe, fast, effective and represents a valid first line treatment of an unstable and unpredictable pathology such as cSDH. We suggest performing such technique on a larger patients' cohort to further validate its effectiveness.

In mammals, mechanics at multiple stages-nucleus to cell to ECM-underlie multiple physiological and pathological functions from its development to reproduction to death. Under this inspiration, substantial research has established the role of multiple aspects of mechanics in regulating fundamental cellular processes, including spreading, migration, growth, proliferation, and differentiation. However, our understanding of how these mechanical mechanisms are orchestrated or tuned at different stages to maintain or restore the healthy environment at the tissue or organ level remains largely a mystery. Over the past few decades, research in the mechanical manipulation of the surrounding environment-known as substrate or matrix or scaffold on which, or within which, cells are seeded-has been exceptionally enriched in the field of tissue engineering and regenerative medicine. To do so, traditional tissue engineering aims at recapitulating key mechanical milestones of native ECM into a substrate for guiding the cell fate and functions towards specific tissue regeneration. Despite tremendous progress, a big puzzle that remains is how the cells compute a host of mechanical cues, such as stiffness (elasticity), viscoelasticity, plasticity, non-linear elasticity, anisotropy, mechanical forces, and mechanical memory, into many biological functions in a cooperative, controlled, and safe manner. High throughput understanding of key cellular decisions as well as associated mechanosensitive downstream signaling pathway(s) for executing these decisions in response to mechanical cues, solo or combined, is essential to address this issue. While many reports have been made towards the progress and understanding of mechanical cues-particularly, substrate bulk stiffness and viscoelasticity-in regulating the cellular responses, a complete picture of mechanical cues is lacking. This review highlights a comprehensive view on the mechanical cues that are linked to modulate many cellular functions and consequent tissue functionality. For a very basic understanding, a brief discussion of the key mechanical players of ECM and the principle of mechanotransduction process is outlined. In addition, this review gathers together the most important data on the stiffness of various cells and ECM components as well as various tissues/organs and proposes an associated link from the mechanical perspective that is not yet reported. Finally, beyond addressing the challenges involved in tuning the interplaying mechanical cues in an independent manner, emerging advances in designing biomaterials for tissue engineering are also explored.