Preoperative elastoplasty of aggressive vertebral hemangiomas in elderly patients: a new strategy for reducing intraoperative bleeding and complications.

PURPOSE: Preoperative elastoplasty could be an alternative strategy for treating aggressive vertebral hemangiomas (VHs) in frail patients needing for spinal cord decompression, combining the advantages of embolization and vertebroplasty. METHODS: Three elderly patients with spinal cord compression from thoracic aggressive VHs underwent XperCT-guided percutaneous injection of silicone (VK100), filling the whole affected vertebra, followed by a decompressive laminectomy. At 12-months follow-up no recurrences, vertebral collapse or segmental kyphosis were noted at the CT scans, with patients reporting an improvement of preoperative neurological deficits, VAS and Smiley-Webster pain scale (SWPS) parameters. RESULTS: With its elastic modulus, non-exothermic hardening, and lower viscosity than PMMA, VK100 allowed a preoperative augmentation of the affected vertebral body, pedicles, and laminae without complications, with a controlled silicone delivery even in part of VH's epidural components thanks to XperCT-guidance. CONCLUSION: When facing highly bony erosive VH encroaching the spinal canal, VK100 combines the advantages of embolization and vertebroplasty especially in elderly patients, permeating the whole VH's angioarchitecture, significantly reducing tumor.

Gait analysis, trunk movements, and electromyographic patterns after minimally invasive spine surgery for lumbar instability: An observational prospective study.

Objective: The aim of the present study was to investigate trunk kinematics and spine muscle activation during walking after minimally invasive surgery in patients with L4-L5 degenerative spondylolisthesis suffering from lumbar instability (LI). Methods: Eleven patients suffering from LI and 13 healthy controls (HC) were enrolled. Trunk kinematics and spine muscle activation patterns during walking were collected. Maximal trunk ranges of motion were also recorded from standing position. Assessments were performed pre-operatively (T0), 1 month (T1) and 3 months (T2) after MIS. Results: We found significant improvement in spine muscle activation during walking at T2 compared to T0, mainly involving right/left symmetry at the operated level (L4-L5) and up-down synchronization from L3 to S1. Significant improvements in trunk rotation nearing to the HC group during walking were also found at T2 after surgery, though no changes were observed in the maximal range of motion of the trunk during standing. Furthermore, trunk rotation improvement correlated with a lower grade of residual disability. Conclusions: Our findings indicate that trunk rotation improves after surgery, and impaired aspects of spine muscle activation can be improved with surgery. These biomechanical parameters could represent novel tools for monitoring the effect of surgery in LI and preventing impaired spine mobility and muscle activation.

The neurosurgical outpatient clinic: comparison between accesses in public and private activities.

BACKGROUND: Neurosurgical clinic assesses presence and extent of pathologies of central and peripheral nervous system or disorders affecting the spine, to identify most effective treatment and possible recourse to surgery. The aim of the study is to evaluate the appropriateness of request for a neurosurgical consult both in private and in public outpatient clinics. MATERIALS AND METHODS: We collected and analyzed all the reports of outpatient visits of public and private clinic over a period between January and December 2018. RESULTS: There were 0.62% real urgent visits in the public sector and 1.19% in the private sector (p = 0.05). Peripheral pathologies represented 12.53% and 6.21% of pathologies evaluated in public and private sector respectively (p < 0.00001). In addition, 15.76% of visits in public lead to surgery, while they represented 11.45% in private (p = 0.0003). CONCLUSIONS: No study is available comparing accesses of patients in neurosurgical outpatient clinics. In public clinic, visits are booked as urgent on the prescription of the general practitioner: in reality, only 5% of these visits were really confirmed as urgent by the specialist. Peripheral pathologies are more frequent in public clinic, while cranial pathologies are more frequent in private one. Patients with cranial pathologies prefer to choose their surgeon by accessing private clinic.

Defining the Learning Curve of the Exoscope in Spine Surgery.

INTRODUCTION: In recent years, introduction of the exoscope system has been responsible for a new era of optics in surgery. Such a system has started to be widely used in neurosurgery. More recently, the exoscope has also been increasingly used for spinal procedures. Thus, we aimed to explore the potential for exoscope-assisted spinal procedures and define the advantages and drawbacks of implementing the system into our daily routine. METHODS: To achieve the aim of the study, we retrospectively reviewed the case series of patients treated by a senior surgeon and analyzed the results, complications, and operative time. The operating times were compared between the exoscope-assisted procedures and microscope-assisted procedures. RESULTS: A total of 24 spinal procedure were performed with the exoscope in a 2-month period. In this first patient series performed by a single surgeon without experience with the exoscope, the learning curve seemed to be relatively low, with mastery of the instrument achieved after the performance of only a few cases. Comparing the cases after the plateau of the learning curve had been reached with those performed during the still active phase of the learning curve, a significant difference was found in the operative times. No statistically significant difference was detected in terms of blood loss or intraoperative complications. CONCLUSIONS: Based on our first experience, use of the exoscope shows promising potential for opening up new frontiers in spinal microsurgery. In addition, it has a low learning curve for experienced surgeons.

Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet.

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation.

Introduction: The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, two pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described in bronchiolar epithelium of COPD patients versus controls and in vitro cytokine- and cigarette smoke-challenged human airway epithelial cells, prompting the identification of epithelial AUF-1-targeted transcripts and function, and investigation on the mechanism of its loss. Results: RNA immunoprecipitation-sequencing (RIP-Seq) identified, in the human airway epithelial cell line BEAS-2B, 494 AUF-1-bound mRNAs enriched in their 3'-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif. AUF-1 association with selected transcripts and with a synthetic GC-rich motif were validated by biotin pulldown. AUF-1-targets' steady-state levels were equally affected by partial or near-total AUF-1 loss induced by cytomix (TNFα/IL1ß/IFNγ/10 nM each) and siRNA, respectively, with differential transcript decay rates. Cytomix-mediated decrease in AUF-1 levels in BEAS-2B and primary human small-airways epithelium (HSAEC) was replicated by treatment with the senescence- inducer compound etoposide and associated with readouts of cell-cycle arrest, increase in lysosomal damage and senescence-associated secretory phenotype (SASP) factors, and with AUF-1 transfer in extracellular vesicles, detected by transmission electron microscopy and immunoblotting. Extensive in-silico and genome ontology analysis found, consistent with AUF-1 functions, enriched RIP-Seq-derived AUF-1-targets in COPD-related pathways involved in inflammation, senescence, gene regulation and also in the public SASP proteome atlas; AUF-1 target signature was also significantly represented in multiple transcriptomic COPD databases generated from primary HSAEC, from lung tissue and from single-cell RNA-sequencing, displaying a predominant downregulation of expression. Discussion: Loss of intracellular AUF-1 may alter posttranscriptional regulation of targets particularly relevant for protection of genomic integrity and gene regulation, thus concurring to airway epithelial inflammatory responses related to oxidative stress and accelerated aging. Exosomal-associated AUF-1 may in turn preserve bound RNA targets and sustain their function, participating to spreading of inflammation and senescence to neighbouring cells.

Two-Level Corpectomy and Fusion vs. Three-Level Anterior Cervical Discectomy and Fusion without Plating: Long-Term Clinical and Radiological Outcomes in a Multicentric Retrospective Analysis.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) represent effective alternatives in the management of multilevel cervical spondylotic myelopathy (CSM). A consensus on which of these techniques should be used is still missing. METHODS: The databases of three centers were reviewed (January 2011-December 2018) for patients with three-level CSM, who underwent three-level ACDF without plating or two-level ACCF with expandable cage (VBRC) or mesh (VBRM). Demographic data, surgical strategy, complications, and implant failure were analyzed. The Neck Disability Index (NDI), the Visual Analog Scale (VAS), and the cervical lordosis were compared between the two techniques at 3 and 12 months. Logistic regression analyses investigated independent factors influencing clinical and radiological outcomes. RESULTS: Twenty-one and twenty-two patients were included in the ACDF and ACCF groups, respectively. The median follow-up was 18 months. ACDFs were associated with better clinical outcomes at 12 months (NDI: 8.3% vs. 19.3%, p < 0.001; VAS: 1.3 vs. 2.6, p = 0.004), but with an increased risk of loss of lordosis correction ≥ 1° (OR = 4.5; p = 0.05). A higher complication rate in the ACDF group (33.3% vs. 9.1%; p = 0.05) was recorded, but it negatively influenced only short-term clinical outcomes. ACCFs with VBRC were associated with a higher risk of major complications but ensured better 12-month lordosis correction (p = 0.002). No significant differences in intraoperative blood loss were noted. CONCLUSIONS: Three-level ACDF without plating was associated with better clinical outcomes than two-level ACCF despite worse losses in lordosis correction, which is ideal for fragile patients without retrovertebral compressions. In multilevel CSM, the relationship between the degree of lordosis correction and clinical outcome advantages still needs to be investigated.

Stand-Alone Oblique Lumbar Interbody Fusion (OLIF) for the Treatment of Adjacent Segment Disease (ASD) after Previous Posterior Lumbar Fusion: Clinical and Radiological Outcomes and Comparison with Posterior Revision Surgery.

Background: Radiological evidence of adjacent segment disease (ASD) has been reported to have a prevalence of more than 30% and several risk factors have been reported. The aim of this study is to evaluate the clinical and radiological outcomes of patients with symptomatic ASD treated with stand-alone OLIF and compare results with a posterior revision surgery cohort. Methods: This is a retrospective case-control study. Clinical-patient-reported outcomes were obtained at preoperative, postoperative and final follow-up visits using the Short Form (SF-36) scale, the Oswestry Disability Index (ODI) and the visual analog scale (VAS). Radiological measures include lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence-lumbar lordosis (PI-LL) mismatch, segmental coronal Cobb angle and intervertebral disc height (DH). The data are compared with a retrospective series of patients that underwent a posterior revision surgery for ASD. Results: Twenty-eight patients in the OLIF group and 25 patients in the posterior group meet inclusion criteria. The mean ages at the time of the surgery are 65.1 years and 67.5, respectively. The mean follow-up time is 36.1 months (range of 14-56). The clinical outcomes significantly improve from preoperative values from the surgery in both groups. The radiological parameters are significantly improved postoperatively and were maintained at the last follow-up in both groups. A statistically significant difference is observed between the two groups for minor complication rate, length of surgery, blood loss and DH restoration. Conclusions: Stand-alone OLIF is an effective and safe technique with low morbidity and complication rates for the treatment of selected patients with symptomatic ASD following a previous lumbar fusion.

Comparison Between Intrasylvian and Intracerebral Hematoma Associated with Ruptured Middle Cerebral Artery Aneurysms: Clinical Implications, Technical Considerations, and Outcome Evaluation.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to a middle cerebral artery (MCA) aneurysm rupture is often associated with an intracerebral hematoma (ICH) or intrasylvian hematoma (ISH). METHODS: We reviewed 163 patients with ruptured MCA aneurysms associated with pure SAH or SAH plus ICH or ISH. The patients were first dichotomized according to the presence of a hematoma (ICH or ISH). Next, we performed a subgroup analysis comparing ICH versus ISH to explore their relationship with the most relevant demographic, clinical, and angioarchitectural features. RESULTS: Overall, 85 patients (52%) had a pure SAH, and 78 (48%) had presented with an associated ICH or ISH. No significant differences were observed in the demographics or angioarchitectural features between the 2 groups. However, the Fisher grade and Hunt-Hess score were higher for the patients with hematomas. A good outcome was observed in a higher percentage of patients with pure SAH compared with those with an associated hematoma (76% vs. 44%), although the mortality rates were comparable. Age, Hunt-Hess score, and treatment-related complications were the main outcome predictors on multivariate analysis. Patients with ICH appeared worse clinically compared with those with ISH. We also found that older age, a higher Hunt-Hess score, larger aneurysms, decompressive craniectomy, and treatment-related complications were associated with poor outcomes among the patients with an ISH, but not an ICH, which appeared, per se, as a more severe clinical condition. CONCLUSIONS: Our study has confirmed that age, Hunt-Hess score, and treatment-related complications influence the outcome of patients with ruptured MCA aneurysms. However, in the subgroup analysis of patients with SAH associated with an ICH or ISH, only the Hunt-Hess score at onset appeared as an independent predictor of the outcome.

RNA-Binding Proteins as a Molecular Link between COPD and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) represents an independent risk factor for lung cancer development. Accelerated cell senescence, induced by oxidative stress and inflammation, is a common pathogenic determinant of both COPD and lung cancer. The post transcriptional regulation of genes involved in these processes is finely regulated by RNA-binding proteins (RBPs), which regulate mRNA turnover, subcellular localization, splicing and translation. Multiple pro-inflammatory mediators (including cytokines, chemokines, proteins, growth factors and others), responsible of lung microenvironment alteration, are regulated by RBPs. Several mouse models have shown the implication of RBPs in multiple mechanisms that sustain chronic inflammation and neoplastic transformation. However, further studies are required to clarify the role of RBPs in the pathogenic mechanisms shared by lung cancer and COPD, in order to identify novel biomarkers and therapeutic targets. This review will therefore focus on the studies collectively indicating the role of RBPs in oxidative stress and chronic inflammation as common pathogenic mechanisms shared by lung cancer and COPD.

Lumbar interbody fusion using oblique (OLIF) and lateral (LLIF) approaches for degenerative spine disorders: a meta-analysis of the comparative studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Historically, posterior approaches to the lumbar spine have allowed surgeons to manage degenerative conditions affecting the lumbar spine. However, spinal muscles injury, post-surgical vertebral instability, cerebrospinal fluid (CSF) leakage, and failed back surgery syndrome (FBSS) represent severe complications that may occur after these surgeries. Lumbar interbody fusion using anterior (ALIF), oblique (OLIF), or lateral (LLIF) approaches may represent valuable surgical alternatives, in case fusion is indicated on single or multiple levels. METHODS: The present study is a systematic review, conducted according to the PRISMA statement, of comparative studies on OLIF, and LLIF for degenerative spine disorders, and a meta-analysis of their clinical-radiological outcomes and complications. RESULTS: After screening 1472 papers on PubMed, Scopus, and Cochrane Library, only 3 papers were included in the present study. 318 patients were included for data meta-analysis, 128 in OLIF group, and 190 in LLIF group. There were no significative differences in terms of surgical (intraoperative blood loss and surgical duration) and clinical (VAS-back, VAS-leg, and ODI scores) outcomes, or fusion rates at last follow-up (> 2 years). Significantly higher rates of abdominal complications, system failure, and vascular injuries were recorded in the OLIF group. Conversely, postoperative neurological symptoms and psoas weakness were significatively more common in LLIF group. CONCLUSIONS: The meta-analysis suggests that OLIF and LLIF are both effective for lumbar degenerative disorders, although each of them presents specific complications and this should represent a relevant element in the surgical planning.

Percutaneous carbon-PEEK instrumentation for spine tumors: a prospective observational study.

BACKGROUND: Minimally invasive spine surgery (MISS) has been progressively accepted as a useful approach for spine tumors. Recently released carbon-PEEK implants have been already reported as effective in open surgeries for spine tumors. This study aimed to evaluate the feasibility, surgical, clinical and radiological outcomes of a new percutaneous carbon-PEEK instrumentations for spine tumors. METHODS: This is a prospective case-control observational study. Demographical, clinical, surgical, and radiological data were collected from May 2018 to August 2019. Visual Analogue Scale for back pain (VAS), the Oswestry Disability Index (ODI) Questionnaire, EORTC QLQ-C30 questionnaire for quality of life, and ASIA Impairment Scale (AIS) were collected before surgery and at 6 weeks and follow-up (FU) visits. Data were compared with the control group, a retrospective series of 23 metastatic patients that underwent titanium pedicle screw fixation. RESULTS: Twenty-one patients met inclusion criteria. Mean age was 59.2 years (range, 35-78) and mean FU was 14.2 months (7-22). Thoracic spine was involved in 14 (66.7%) cases, lumbar spine in 7 (33.3%). The mean length of surgery was 75 (42-185) minutes, mean blood loss was 90ml (50-215) and every patient was mobilized within 24 hours after surgery. The VAS (8.3±1.1 to 2.9±1.0, P<0.05) and ODI (54.6±11.7 to 25.1±5.4, P<0.05) scores significantly improved over follow-up. AIS improved in 7 (33.3%) patients and remained unchanged in 14 (66.7%). The EORTC QLQ-C30 global health/QoL, functional and symptomatic scales significantly improved postoperatively and at the last follow-up. Only two minor complications (9.5%) were recorded. No statistically significant difference was observed between the two groups related to clinical, radiological outcomes, complications rate and implant failure. CONCLUSIONS: Percutaneous Carbon/PEEK implants could be considered as alternative to standard titanium implants in oncological patients, according to their lower rate of MRI artifacts, facilitating radiological FU and adjuvant radiotherapy. Further clinical trials and biomechanical evaluations are needed to confirm our preliminary results.

Facing the pandemic with a smile: the case of Memedical and its impact on cardiovascular professionals.

Since its outbreak, the Coronavirus disease 2019 (COVID-19) has profoundly changed the world we were acquainted with. After the first known contact with humankind in Wuhan, China, in December 2019, the reckless spread of such pathogen put the healthcare system to the test, leading to harmful consequences affecting human lives in every aspect. As of February 2022, the death toll amounts to almost 6 million deaths, but the pathogenic profile of SARS-CoV-2 goes way beyond the mere biological interaction between the viral particle and our organism. People had to deal with the severe psychological impact caused by the only available weapon to fight this infection, i.e., social distancing. The human psychological profile has been strained with repercussions we still are unaware of nowadays. Healthcare professionals were among the most hit categories, not only because of the quarantine but above all for the situations they had to bear every day, constantly facing desperation, death, isolation, and rage. In such circumstances, social media represented a powerful shelter, giving people the ability to keep in contact and to feel connected even if miles apart. In our country, the power of communication was strongly emphasized by launching an Italian Facebook group called "Memedical," where members can share ironic memes to feel closer and give a glimmer of happiness in such a challenging moment. Our review highlights the severity of this pandemic's impact, deteriorating the global population's physical and mental health, and shows how wise use of social media can benefit the quality of life.

Percutaneous pedicle screw fixation without arthrodesis of 368 thoracolumbar fractures: long-term clinical and radiological outcomes in a single institution.

PURPOSE: Traumatic thoracolumbar (TL) fractures are the most common vertebral fractures. Although a consensus on the preferred treatment is missing, percutaneous pedicle screw fixation (PPSF) has been progressively accepted as treatment option, since it is related to lower soft tissues surgical-injury and perioperative complications rate. This study aims to evaluate the long-term clinical-radiological outcomes after PPSF for TL fractures at a single tertiary academic hospital. METHODS: This is a retrospective cohort study. Back pain was obtained at preoperative, postoperative and final follow-up using Visual Analog Scale. Patient-reported outcomes, the Oswestry Disability Index and the 36-Item Short Form, were obtained to asses disability during follow-up. Radiological measures included Cobb angle, mid-sagittal index, sagittal index (SI) and vertebral body height loss. A multivariate regression analysis on preoperative radiological features was performed to investigate independent risk factors for implant failure. RESULTS: A total of 296 patients with 368 TL fractures met inclusion criteria. Mean follow-up was 124.3 months. The clinical and radiological parameters significantly improved from preoperative to last follow-up measurements. The multivariate analysis showed that Cobb angle (OR = 1.3, p < 0.001), SI (OR = 1.5, p < 0.001) and number of fractures (OR = 1.1, p = 0.05), were independent risk factors for implant failure. The overall complication rate was 5.1%, while the reoperation rate for implant failure was 3.4%. CONCLUSIONS: In our case series, PPSF for TL injuries demonstrated good long-term clinical-radiological outcomes, along with low complication and reoperation rates. Accordingly, PPSF could be considered as a valuable treatment option for neurologically intact patients with TL fractures. Additionally, in this cohort, number of fractures ≥ 2, Cobb angle ≥ 15° and sagittal index ≥ 21° were independent risk factors for implant failure.

The Potential Role of Dysregulated miRNAs in Adolescent Idiopathic Scoliosis and 22q11.2 Deletion Syndrome.

Background: Adolescent idiopathic scoliosis (AIS), affecting 2-4% of adolescents, is a multifactorial spinal disease. Interactions between genetic and environmental factors can influence disease onset through epigenetic mechanisms, including DNA methylation, histone modifications and miRNA expression. Recent evidence reported that, among all clinical features in individuals with 22q11.2 deletion syndrome (DS), scoliosis can occur with a higher incidence than in the general population. Methods: A PubMed and Ovid Medline search was performed for idiopathic scoliosis in the setting of 22q11.2DS and miRNA according to PRISMA guidelines. Results: Four papers, accounting for 2841 individuals, reported clinical data about scoliosis in individuals with 22q11.2DS, showing that approximately 35.1% of the individuals with 22q11.2DS developed scoliosis. Conclusions: 22q11.2DS could be used as a model for the study of AIS. The DGCR8 gene seems to be essential for microRNA biogenesis, which is why we propose that a possible common pathological mechanism between scoliosis and 22q11.2DS could be the dysregulation of microRNA expression. In the current study, we identified two miRNAs that were altered in both 22q11.2DS and AIS, miR-93 and miR-1306, thus, corroborating the hypothesis that the two diseases share common molecular alterations.

Kinetic model for the dehydration of xylose to furfural from a boronate diester precursor.

A comprehensive kinetic model describes the dehydration of xylose starting from the boronate diester-protected xylose (PBA2X). The model incorporates (de)esterification of PBA2X, partitioning, and xylose dehydration, and aims to evaluate the effects of the solvent system on these steps. The model explores the effect of the water contents in monophasic solvent systems, and that of ionic strength and mixing in biphasic aqueous-organic systems. At low water content, hydrolysis of PBA2X is the rate-limiting step, while xylose dehydration is fast. Conversely, in a monophasic three-solvent system, where the water content is higher, complete hydrolysis of the diester is achieved quickly. Under biphasic conditions, xylose dehydration is fast at high ionic strengths, but the slower partitioning/hydrolysis of PBA2X results in an overall slower furfural production. Furthermore, the observed different but high, constant xylose-to-furfural selectivities observed experimentally are tentatively ascribed to a higher order of parallel side-product formation.

Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma.

The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine.

Does the Timing of the Surgery Have a Major Role in Influencing the Outcome in Elders with Acute Subdural Hematomas?

BACKGROUND: The incidence of traumatic acute subdural hematomas (ASDH) in the elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays no clear role as a predictor. We investigated whether the timing of surgery had a major role in influencing the outcome in these patients. METHODS: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 year period in five Italian hospitals. Patients were divided into three surgical timing groups from hospital arrival: ultra-early (within 6 h); early (6-24 h); and delayed (after 24 h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at the Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed. RESULTS: We included 136 patients. About 33% died as a result of the consequences of ASDH and among the survivors, only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting the Glasgow Outcome Scale (GCS), which was on average lower in the ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared to be neither associated with survival nor with functional outcome, also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. CONCLUSIONS: An earlier surgery was offered to patients with worse clinical-radiological findings. Additionally, after stratification for GCS, it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.