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Purpose To assess the rate, timing of diagnosis, and repairing strategies of vascular injuries in thoracic and lumbar spine surgery as their relationship to the approach. Methods PubMed, Medline, and Embase databases were utilized for a comprehensive literature search based on keywords and mesh terms to find articles reporting iatrogenic vascular injury during thoracic and lumbar spine surgery. English articles published in the last ten years were selected. The search was refined based on best match and relevance. Results Fifty-six articles were eligible, for a cumulative volume of 261 lesions. Vascular injuries occurred in 82% of instrumented procedures and in 59% during anterior approaches. The common iliac vein (CIV) was the most involved vessel, injured in 49% of anterior lumbar approaches. Common iliac artery, CIV, and aorta were affected in 40%, 28%, and 28% of posterior approaches, respectively. Segmental arteries were injured in 68% of lateral approaches. Direct vessel laceration occurred in 81% of cases and recognized intraoperatively in 39% of cases. Conclusions Incidence of iatrogenic vascular injuries during thoracic and lumbar spine surgery is low but associated with an overall mortality rate up to 65%, of which less than 1% for anterior approaches and more than 50% for posterior ones. Anterior approaches for instrumented procedures are at risk of direct avulsion of CIV. Posterior instrumented fusions are at risk for injuries of iliac vessels and aorta. Lateral routes are frequently associated with lesions of segmental vessels. Suture repair and endovascular techniques are useful in the management of these severe complications.

Nearly 250 years ago, Antonio Scarpa became a professor of anatomy and surgery only 2 years after he graduated from the University of Padua. The young lecturer soon became one of the most renowned anatomists in Italy and a director of the Faculty of Medicine at the University of Pavia. He worked in the fields of general surgery and ophthalmology. Several anatomic structures have been named after him, mainly Scarpa fascia and Scarpa triangle. His interest in neuroanatomy was ardent, despite being occasionally neglected. Scarpa's contributions to the fields of neurosciences have been significant. He was the first to describe the round window and the secondary tympanic membrane, and he eventually focused on the auditory and olfactory organs. Notably, the vestibular ganglion is now known as Scarpa ganglion. Scarpa's magnum opus was the book Tabulae Neurologicae, in which he described the path of several cranial nerves including the vagus nerve and innervation of the heart. Since his death in 1832, Scarpa's head has been preserved at the University History Museum of the University of Pavia. In this historical vignette, we aim to describe Antonio Scarpa's troubled life and brilliant career, focusing on his core contributions to neuroanatomy, neurosurgery, and otoneurosurgery.

Extrinsic compression of the subaxial vertebral artery (VA) may cause rotational occlusion syndrome (ROS) and contribute to vertebrobasilar insufficiency potentially leading to symptoms and in severe cases, to posterior circulation strokes. The present literature review aimed to report the main clinical findings, diagnostic work-up, and surgical management of the subaxial VA-ROS, the diagnosis of which can be difficult and is often underestimated. An illustrative case is also presented. A thorough literature search was conducted to retrieve manuscripts that have discussed the etiology, diagnosis, and treatment of ROS. Total 41 articles were selected based on the best match and relevance and mainly involved case reports and small cases series. The male/female ratio and average age were 2.6 and 55.6±11 years, respectively. Dizziness, visual disturbances, and syncope were the most frequent symptoms in order of frequency, while C5 and C6 were the most affected levels. Osteophytes were the cause in >46.2% of cases. Dynamic VA catheter-based angiography was the gold standard for diagnosis along with computed tomography angiography. Except in older patients and those with prohibitive comorbidities, anterior decompressive surgery was always performed, mostly with complete recovery, and zero morbidity and mortality. A careful neurological evaluation and dynamic angiographic studies are crucial for the diagnosis of subaxial VA-ROS. Anterior decompression of the VA is the cure of this syndrome in almost all cases.

Background Human placenta is recognized as a valuable vascular microneurosurgery training model because of its abundant availability, ethical acceptance, and analogous vasculature with other vessels of the human body; however, human placenta laboratory preparation techniques are not well described in the literature. This study outlines a detailed and standardized laboratory protocol for preparation of a color-perfused human placenta model. Survey-based validation of the model is also reported herein. Methods The protocol involved cleaning and cannulation of the umbilical vein and arteries, irrigation with heparin, and storage at 3°C or freezing at −18°C. Before use, arteries were perfused with carmine/cochineal, and veins were perfused with methylthioninium chloride. A questionnaire with five questions was administered to 40 participants among attending or resident neurosurgeons, otolaryngologists, and maxillo-facial surgeons on four consecutive microsurgical courses to assess the reliability of the placenta model. Trainees were divided into three groups based on their experience. A Chi-squared test was used to identify differences between groups. Results Forty-two placentas were considered appropriate for training and were successfully perfused with dyes. Thirty-three participants completed the questionnaire, of which most, especially advanced and intermediate participants, indicated the placenta as a valuable, accurate, and reproducible model. No differences were observed among the groups. Conclusions The human placenta is an excellent tool for vascular microneurosurgery laboratory training. Color perfusion enhances the reliability of this model, which was validated by most surgeons, regardless of their experience.

Objective To review and discuss surgical treatment options for giant intracranial aneurysms (GIAs), focusing on indications, technical aspects, and results, along with some illustrative cases. Methods We reviewed the data of 82 consecutive patients surgically managed between January 2000 and December 2019 for treatment of a GIA. Results Male sex and hemorrhage at presentation were prevalent. The average follow-up was 81.2 ± 45 months. The anterior circulation was involved in 76.8% of GIAs. If the GIA showed a clear neck, minimal atherosclerosis, or intrasaccular thrombosis, and ≤2 branches arising from the neck, it was reconstructed. This procedure was possible in 78% of cases. The technique also involved temporary clipping, remodeling, and thrombectomy, as well as fragmentation techniques. Angioarchitectural features other than these techniques underwent bypass and aneurysm trapping. Most bypasses were extracranial to intracranial and high flow. Flow capacity, collateral circulation, and availability of the donor vessel mainly affected the choice of the type of bypass. Overall, successful exclusion of the GIA was 91.4%. The need for retreatment and complication rate were 3.6% and 19.5%, respectively. A good overall outcome (modified Rankin Scale score 0–3) was achieved in 84.2% of patients, and mortality was 10%. Conclusions Microneurosurgical techniques still maintain a significant role for most GIAs, with a high durability and acceptable rate of morbidity and mortality. Clip reconstruction is the first-line surgical treatment option, whereas bypass is indicated in cases of planned or unplanned sacrifice of the parent artery to prevent long-term ischemic complications.

Introduction A critical appraisal of the surgical results of paraclinoid aneurysms is essential in the flow diverters era. This study overviews the data of a three-decade surgical series of paraclinoid aneurysms while focusing on their technical remarks. Methods Overall data of a surgical consecutive series of paraclinoid aneurysms treated between 1993 and 2021 were retrospectively reviewed. Aneurysms were classified according to size and projection. Indications for surgery were different based on the availability of endovascular techniques, especially flow diverter, at the time of treatment. A statistical comparison between ruptured and unruptured aneurysms was accomplished. Results 58 patients were operated upon. Ophthalmic aneurysms were 68%, giant aneurysms 20%, and ruptured aneurysms 45%. Clipping and bypass were executed in 91% and 9% of cases, respectively. An mRS of 0–2 was achieved in 77% of patients, independently by the clinical onset. The mortality rate was 5%. Visual field was improved or unchanged in 71% of elective patients, whereas the incidence of de novo third and sixth cranial nerves deficit was 8% and 5%, respectively. On an average follow-up of 53.3 ± 38 months, a complete and durable aneurysm exclusion was achieved in 91.3% of patients with a single surgery. Conclusions Microneurosurgery is still a valuable treatment option for selected ruptured and unruptured paraclinoid aneurysms. In our experience, it has proven to be definitive and durable, with acceptable morbidity and mortality. Clipping is the treatment of choice in most surgical cases, achieving a good visual outcome in symptomatic patients.

Background Schwannomas encompassing the superior parapharyngeal space are challenging lesions because of the anatomical complexity of this region and the frequent involvement of the neurovascular structures of the jugular foramen. The purpose of this study is to report the technical aspects and the advantages of the anterolateral approach, here proposed for schwannomas of this complex area. Methods The main steps of the anterolateral approach are described in detail, along with the results of a consecutive series of 38 patients with a retrostyloid superior parapharyngeal schwannoma involving the jugular foramen operated on by means of this route between 1999 and 2019. Results The supine position is generally preferred. The medial border of the sternocleidomastoid muscle, mastoid tip, and superior nuchal line are the landmarks for the hockey-stick skin incision. The accessory nerve is retrieved and mobilized cranially. Detachment of the sternocleidomastoid, digastric, and nuchal muscles allows for a 180° exposure of the extracranial side of the jugular foramen. Three working corridors, namely the pre-carotid, pre-jugular, and retro-jugular, allow access to the deeper part of the jugular foramen area and the superior parapharyngeal space. In the present series, a gross total resection was achieved in 89.4% of the patients. Three recurrences occurred after an average follow-up of 80.5 ± 51 months. Conclusions The anterolateral approach is highly effective in the treatment of retrostyloid superior parapharyngeal space schwannomas involving the jugular foramen. Its simplicity of execution, versatility, and very low morbidity are among its main strengths.

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Tandem intracranial aneurysms (TandIAs) are rare but inherently complex, and special technical considerations are required for their surgical management. The present case highlights the key surgical aspects of two carotid-ophthalmic TandIAs incidentally found in a 60-year-old female. Both the aneurysms were superiorly projecting, regular in size, and involved the left ophthalmic segment of the internal carotid artery (ICA). The minimum distance between the necks was 3 mm. The patient underwent microsurgery because of the reported major complications rate of the endovascular treatment in the case of a very short minimum distance between the TandIAs. After cervical ICA exposure, both the aneurysms were excluded through a pterional approach. Intradural anterior clinoidectomy and unroofing of the optic canal allowed the mobilization of the left optic nerve. The more distal aneurysm was clipped before the opening of the distal dural ring of the ICA. The proximal aneurysm was clipped with two straight clips stacked perpendicular to the ICA. A small remnant was intentionally left to avoid the stenosis of the ophthalmic artery. Postoperative angiography showed the exclusion of both the aneurysms with a small dog-ear of the more proximal one. The patient was discharged neurologically intact and, after one year, the remnant remained stable. Microsurgical clipping is a definitive and durable treatment for carotid-ophthalmic TandIAs. In the case of a very short minimum distance between the aneurysms, the distal one should be clipped first to make the anterior clinoidectomy, opening of the distal dural ring of the ICA, and clipping of the more proximal aneurysm easier.

Introduction: The petroclival region is among the most challenging anatomical areas to deal with in skull base surgery. Drilling of the anterior part of the petrous bone during the anterior transpetrosal approach involves the risk of injury of the cochlea, superior semicircular canal, internal carotid artery, and internal auditory canal. A thorough understanding of the microneurosurgical anatomy of this region is mandatory to execute the transpetrosal approaches, decreasing the risk of complications. The aim of this study is to describe the anatomical structures of the petroclival region, highlighting the importance of neuronavigation for safe performance of the anterior transpetrosal approach. Methods: Three adult cadaveric human heads were formalin-fixed and injected with colored silicone. They underwent an axial 1 mm slab CT scan, which was used for neuronavigation during the surgical approaches. The anterior petrosectomy was performed with the aid of neuronavigation during the drilling of the petrous bone. The surgical management of a patient harboring a petroclival meningioma, operated on using an anterior transpetrosal approach, was reported as an illustrative case. Results: The anterior petrosectomy was completed accurately with wide exposure of the surgical target without injuring the cochlea and other structures in all three cadaveric specimens. In the surgical case, no approach-related complications occurred, and a gross total resection of the tumor was achieved. Conclusions: Deep knowledge of the location and relationships of the vital elements located within the temporal bone, along with the use of neuronavigation, are the key aspects to perform the anterior transpetrosal approach safely, reducing the risk of complications.

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p &gt, 0.05), as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%, p &lt, 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%, 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

Among the posterolateral corridors to the ventral foramen magnum (FM), the transcondylar fossa (supracondylar transjugular tubercle) approach (TCFA) is indicated for lesions lying anteriorly to the dentate ligament and above the jugular foramen and hypoglossal canal.1-13 It involves the drilling of the condylar fossa, namely the exocranial surface of the jugular tubercle. Despite the anatomic variability of the condyle and posterior condylar emissary vein,14,15 they are important landmarks for the TCFA. The extradural jugular tuberculectomy has no risk of iatrogenic mechanical instability compared with the transcondylar approach. This 2-dimensional operative video (Video 1) aims to show the key technical aspects of the TCFA through the case description of an anterolateral FM meningioma. A 35-year-old male patient with a left anterolateral FM meningioma underwent TCFA in a semisitting position. Drilling of the condylar fossa led to an extradural resection of the jugular tubercle. Posterior condylar emissary veins connecting the sigmoid sinus/jugular bulb with the vertebral venous plexus marked the lateral limit of the approach. Through a suprahypoglossal working corridor, the meningioma was debulked and dissected. Postoperative magnetic resonance imaging confirmed complete resection of the tumor, and the patient was discharged neurologically intact on the third postoperative day. TCFA is a valuable technical option for selected anterolateral FM meningiomas. The perfect knowledge and intraoperative use of specific anatomic landmarks are critical to safely perform the TCFA while maximizing the exposure of the surgical target and decreasing the risk of postoperative mechanical instability of the craniovertebral junction.

OBJECTIVE The theoretical advantages of augmented reality (AR) with diffusion tensor imaging (DTI)–based high-definition fiber tractography (HDFT) and sodium fluorescein (F) in high-grade glioma (HGG) surgery have not been investigated in detail. In this study, the authors aimed to evaluate the safety and efficacy profiles of HDFT-F microscope-based AR cytoreductive surgery for newly diagnosed supratentorial HGGs. METHODS Data of patients with newly diagnosed supratentorial HGGs who underwent surgery using the AR HDFT-F technique were reviewed and compared with those of a cohort of patients who underwent conventional white-light surgery assisted by infrared neuronavigation. The safety and efficacy of the techniques were reported based on the postoperative Neurological Assessment in Neuro-Oncology (NANO) scores, extent of resection (EOR), and Kaplan-Meier curves, respectively. The chi-square test was conducted for categorical variables. A p value < 0.05 was considered statistically significant. RESULTS A total of 54 patients underwent surgery using the AR HDFT-F technique, and 63 underwent conventional white-light surgery assisted by infrared neuronavigation. The mean postoperative NANO scores were 3.8 ± 2 and 5.2 ± 4 in the AR HDFT-F group and control group, respectively (p < 0.05). The EOR was higher in the AR HDFT-F group (p < 0.05) than in the control group. With a mean follow-up of 12.2 months, the rate of progression-free survival (PFS) was longer in the study group (log-rank test, p = 0.006) than in the control group. Moreover, the complication rates were 9.2% and 9.5% in the study and control groups, respectively. CONCLUSIONS Overall, AR HDFT-F–assisted surgery is safe and effective in maximizing the EOR and PFS rate for patients with newly diagnosed supratentorial HGGs, and in optimizing patient functional outcomes.

The data presented in this brief paper aims to summarize the overall results of 82 consecutive patients surgically treated over 20 years for a giant intracranial aneurysm (GIA) in the context of the endovascular era. Data were retrospectively collected from the database of two different tertiary referral Italian hospitals. A retrospective analysis of the patients' cohort was performed. Data are presented as they relate to the demographic and clinical aspects, the prevalence of GIAs according to anterior and posterior circulation, aneurysm angioarchitectural features, surgical treatment options, complications, outcome, and main microneurosurgical techniques required explicitly for GIAs, namely temporary clipping, aneurysm remodeling, thrombectomy, fragmentation, and bypass. Furthermore, data about the effects of implementing the flow-diverter/flow-disruptor on the surgical case volume over the years are also reported. The data presented herein are related to our previously published research article titled "Surgical Management of Giant Intracranial Aneurysms: Overall Results of a Large Series" (2020) [1].

To report the results of a retrospective series and a technical note about the anterolateral approach for the treatment of the rotational occlusion syndrome (ROS) involving the subaxial V2 segment of the vertebral artery (VA).We retrospectively reviewed the data of a cohort of patients that underwent an anterolateral approach to decompress the VA as they suffered from ROS secondary to a subaxial compression. A dynamic study with ultrasonography, CT, MRI, and catheter-based angiography were obtained in all cases. Severe symptomatology and cerebellar-brainstem strokes were indications for surgery. The anterolateral approach involved a pre-sternocleidomastoid precarotid exposure. The retro-longus colli and pre-scalenic corridors were used to access the C5-C6 and C3-C4 segment, respectively, and to perform the decompression.Twelve patients were treated. Recurrent drop attacks were present in all cases. Osteophytes at C5 and C6 were the most common causes of subaxial VA compression. Anterior decompression stand-alone was performed in all but 1 patient. A recurrent laryngeal nerve palsy and a numbness of the C5 nerve root were the only complications observed, both transient. A satisfactory untethering of the VA with a complete recovery was achieved in all patients, apart from those with severe infratentorial strokes.Anterolateral approach allows for an effective and safe treatment of the ROS involving the subaxial portion of the VA. Retro-longus colli and pre-scalenic corridors, developed through a precarotid exposure, have an anatomical rationale in decreasing the risks of complications. Decompression stand-alone is adequate in almost the totality of cases.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined, however, this result must take into account the very small number of patients needing surgery.

Objective: To report the physical and technical principles, clinical applications, and outcomes of the minimal invasive piezoelectric osteotomy in a consecutive veterinary neurosurgical series. Methods: A series of 292 dogs and 32 cats underwent an osteotomy because a neurosurgical pathology performed with a Mectron Piezosurgery® bone scalpel (Mectron Medical Technology, Genoa, Italy) was retrospectively reviewed. Efficacy, precision, safety, and blood loss were evaluated intraoperatively by two different surgeons, on a case-by-case basis. Postoperative Rx and CT scans were used to assess the selectivity and precision of the osteotomy. A histological study on bony specimens at the osteotomized surface was carried out to evaluate the effects of piezoelectric cutting on the osteocytes and osteoblasts. All the patients underwent a six-months follow-up. A series of illustrative cases was reported. Results: All the osteotomies were clear-cut and precise. A complete sparing of soft and nervous tissues and vasculature was observed. The operative field was blood- and heat-free in all cases. A range of inserts, largely different in shape and length, were allowed to treat deep and difficult-to-reach sites. Two mechanical complications occurred. Average blood loss in dogs’ group was 52, 47, and 56 mL for traumatic, degenerative, and neoplastic lesions, respectively, whereas it was 25 mL for traumatized cats. A fast recovery of functions was observed in most of the treated cases, early on, at the first sixth-month evaluation. Histology on bone flaps showed the presence of live osteocytes and osteoblasts at the osteotomized surface in 92% of cases. Conclusions: Piezosurgery is based on the physical principle of the indirect piezo effect. Piezoelectric osteotomy is selective, effective, and safe in bone cutting during neurosurgical veterinary procedures. It can be considered a minimal invasive technique, as it is able to spare the neighboring soft tissues and neurovascular structures.

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was &gt, 10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE &lt, &minus, 6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy.

The region of Lombardy was the epicenter of the COVID-19 outbreak in Italy. Emergency Hospital 19 (EH19) was built in the Milan metropolitan area during the pandemic’s second wave as a facility of Humanitas Clinical and Research Center (HCRC). The present study aimed to assess whether the implementation of EH19 was effective in improving the quality of care of COVID-19 patients during the second wave compared with the first one. The demographics, mortality rate, and in-hospital length of stay (LOS) of two groups of patients were compared: the study group involved patients admitted at HCRC and managed in EH19 during the second pandemic wave, while the control group included patients managed exclusively at HCRC throughout the first wave. The study and control group included 903 (56.7%) and 690 (43.3%) patients, respectively. The study group was six years older on average and had more pre-existing comorbidities. EH19 was associated with a decrease in the intensive care unit admission rate (16.9% vs. 8.75%, p &lt, 0.001), and an equal decrease in invasive oxygen therapy (3.8% vs. 0.23%, p &lt, 0.001). Crude mortality was similar but overlap propensity score weighting revealed a trend toward a potential small decrease. The adjusted difference in LOS was not significant. The implementation of an additional COVID-19 hospital facility was effective in improving the overall quality of care of COVID-19 patients during the first wave of the pandemic when compared with the second. Further studies are necessary to validate the suggested approach.

Objective Examination of the current trends and future perspectives of the cell-based therapies in neurosurgery. Methods A PubMed/MEDLINE-based systematic review has been performed combining the main Medical Subject Headings (MeSH) regarding the cell- and tissue-based therapies with the “Brain”, “Spinal Cord”, “Spine” and “Skull” MeSH terms. Only articles in English published in the last 10 years and pertinent to neurosurgery have been selected. Results A total of 1,173 relevant articles have been chosen. Somatic cells and gene-modification technologies have undergone the greatest development. Immunotherapies and gene therapies have been tested for the cure of glioblastoma, stem cells mainly for brain and spinal cord traumatic injuries. Stem cells have also found a rationale in the treatment of the cranial and spinal bony defects, and of the intervertebral disc degeneration, as well. Most of the completed or ongoing trials concerning the cell-based therapies in neurosurgery are on phase 2. Future perspectives involve the need to overcome issues related to immunogenicity, oncogenicity and routes for administration. Refinement and improvement of vector design and delivery are required within the gene therapies. Conclusion The last decade has been characterised by a progressive evolution of neurosurgery from a purely mechanical phase to a new biological one. This trend has followed the rapid and parallel development of translational medicine and nanotechnologies. The introduction of new technologies, the optimisation of the already existing ones, and the reduction of costs are among the main challenges of the foreseeable future., Neuroscience; Immunology; Biotechnology; Molecular biology; Cancer research; Regenerative medicine; Oncology; Evidence-based medicine; Clinical research; CAR T-Cell therapy; Cell- and tissue-based therapy; Genetic therapy; Glioblastoma; Immunotherapy; Neurosurgery; Stem cells

Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies.

The exact molecular pathways underlying the multifactorial natural history of intracranial aneurysms (IAs) are still largely unknown, to the point that their understanding represents an imperative challenge in neurovascular research. Wall shear stress (WSS) promotes the genesis of IAs through an endothelial dysfunction causing an inflammatory cascade, vessel remodeling, phenotypic switching of the smooth muscle cells, and myointimal hyperplasia. Aneurysm growth is supported by endothelial oxidative stress and inflammatory mediators, whereas low and high WSS determine the rupture in sidewall and endwall IAs, respectively. Angioarchitecture, age older than 60 years, female gender, hypertension, cigarette smoking, alcohol abuse, and hypercholesterolemia also contribute to growth and rupture. The improvements of aneurysm wall imaging techniques and the implementation of target therapies targeted against inflammatory cascade may contribute to significantly modify the natural history of IAs. This narrative review strives to summarize the recent advances in the comprehension of the mechanisms underlying the genesis, growth, and rupture of IAs.

Introduction: Major trauma is the leading cause of mortality in the world in patients younger than 40 years. However, the proportion of elderly people who suffer trauma has increased significantly. The purpose of this study is to assess the correlation of old age with mortality and other unfavorable outcomes. Methods: We assessed on one hand, anatomical criteria such as ISS values and the number of body regions affected, on the other hand, hemodynamic instability criteria, various shock indices, and Glasgow Coma Scale. Finally, we also evaluated biochemical parameters, such as lactate, BE, and pH values. We conducted a prospective and monocentric observational study of all the patients referred to the Emergency Department of the IRCCS Fondazione Policlinico S. Matteo in Pavia for major trauma in 13 consecutive months: January 1, 2018–January 30, 2019. We compared the elderly population (>75 years) and the younger population (≤75). Results: We included 501 patients, among which 10% were over the age of 75 years. The mortality rate was higher among the older patients than among the younger (4% vs. 1.33%; P = 0.050). Hemodynamic instability was more common in the older patients than in the younger (26% vs. 9%; P < 0.001). More older patients (44%) had an ISS >16, in comparison with 32% of younger patients (P = 0.01). Conclusions: The elderly showed worse outcomes in terms of mortality, hospitalization rate, hemodynamic instability criteria, and anatomical and biochemical parameters.

Background: Pathophysiological mechanisms underlying the syringomyelia associated with Chiari I malformation (CM-1) are still not completely understood, and reliable predictors of the outcome of posterior fossa decompression (PFD) are lacking accordingly. The reported prospective case-series study aimed to prove the existence of a pulsatile, biphasic systolic–diastolic cerebrospinal fluid (CSF) dynamics inside the syrinx associated with CM-1 and to assess its predictive value of patients' outcome after PFD. Insights into the syringogenesis are also reported. Methods: Fourteen patients with symptomatic CM-1 syringomyelia underwent to a preoperative neuroimaging study protocol involving conventional T1/T2 and cardiac-gated cine phase-contrast magnetic resonance imaging sequences. Peak systolic and diastolic velocities were acquired at four regions of interest (ROIs): syrinx, ventral, and dorsal cervical subarachnoid space and foramen magnum region. Data were reported as mean ± standard deviation. After PFD, the patients underwent a scheduled follow-up lasting 3 years. One-way analysis of variance with Bonferroni Post hoc test of multiple comparisons was performed P was

Objective The present short report summarizes some clinical characteristics of six patients affected by stroke while being on angiotensin-converting enzyme (ACE)2 inhibitors and angiotensin II receptor blockers (ARBs) before and during COVID-19. Methods Medical charts and images of six patients affected by stroke while being on ACE-Is and ARBs therapy before and during COVID-19 outbreak in Lombardy region, Italy, were reviewed. Results Three patients had a dural sinus thrombosis, whereas the remaining suffered by an arterial ischemia, which was a middle cerebral artery occlusion in one case, and a posterior-inferior cerebellar artery occlusion in the remaining two. All patients showed clinical features typical of SARS-CoV-2 infection and positive chest CT scan, and were treated with ACE-Is as needed. Hypercoagulability panel was negative in any case. A recovery was achieved in all cases, although in a variable manner. Conclusions Whether or not and in which manner the pharmacomodulation of the renin-angiotensin system may had affect the clinical course of the reported six COVID-19 patients affected by stroke has to be still clarified. An urgent need of randomized clinical trials aimed to assess the safety profile and neuroprotective properties of ACE-Is and ARBs in COVID-19 patients diagnosed with stroke does exists.