Spliced FKBP51s predicts unfavorable prognosis of glioblastoma patients.

The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by magnetic resonance imaging (MRI). However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAMs) are abundant in GBM microenvironment (TME) and are found in peripheral blood (PB). FKBP51 expression, with its canonical and spliced isoforms, is constitutive in immune cells and aberrant in GBM. Spliced FKBP51s supports M2-polarization. To find an immunological signature that combined with MRI could advance in diagnosis, we immunophenotyped the macrophages of TME and PB from 37 GBM patients using FKBP51s and classical M1-M2 markers. We also determined the tumor levels of FKBP51s, PD-L1, and HLA-DR. Tumors expressing FKBP51s showed an increase in various M2 phenotypes and Tregs in PB, indicating immunosuppression. Tumors expressing FKBP51s also activated STAT3 and were associated with reduced survival. Correlative studies with MRI and tumor/macrophages co-cultures allowed to interpret TAMs. Tumor volume correlated with M1 infiltration of TME. Co-cultures with spheroids produced M1 polarization, suggesting that M1 macrophages may infiltrate alongside cancer stem-cells. Co-cultures of adherent cells developed the M2 phenotype CD163/FKBP51s expressing pSTAT6, a transcription factor enabling migration and invasion. In patients with recurrences, increased counts of CD163/FKBP51s monocyte/macrophages in PB correlated with callosal infiltration and was accompanied by a concomitant decrease in TME-infiltrating M1 macrophages. PB PD-L1/FKBP51s connoted necrotic tumors. In conclusion, FKBP51s identifies a GBM subtype that significantly impairs the immune system. Moreover, FKBP51s marks PB macrophages associated with MRI features of glioma malignancy that can aid in patient monitoring.

Safety and Efficacy of Zero-Profile Polyetheretherketone (PEEK) Cages Filled with Biphasic Calcium Phosphate (BCP) in Anterior Cervical Discectomy and Fusion (ACDF): A Case Series.

Background: In the evolving landscape of anterior cervical discectomy and fusion (ACDF), the integration of biomechanical advancements and proper fusion-enhancing materials is crucial for optimizing patient outcomes. This case series evaluates the efficacy and clinical implications of employing zero-profile polyetheretherketone (PEEK) cages filled with biphasic calcium phosphate (BCP) in ACDF procedures, focusing on fusion and subsidence rates alongside patient disability, residual pain, and quality of life. Methods: This case series comprises 76 consecutive patients, with a median follow-up of 581 days. The Bridwell classification system was used for assessing fusion rates while subsidence occurrence was recorded, correlating these radiographic outcomes with clinical implications. Results: The results demonstrated a satisfactory fusion rate (76.4% for grades I and II). The subsidence rate was low (6.74% of segments). Significant clinical improvements were observed in pain, disability, and quality-of-life metrics, aligning with the minimum clinically important difference thresholds; however, subgroup analyses demonstrated that subsidence or pseudoarthrosis group improvement of PROMs was not statistically significant with respect to baseline. ANOVA analyses documented that subsidence has a significant weight over final follow-up pain and disability outcomes. No dysphagia cases were reported. Conclusions: These findings underscore the efficacy of zero-profile PEEK cages filled with BCP in ACDF, highlighting their potential to improve patient outcomes while minimizing complications. Pseudoarthrosis and subsidence have major implications over long-term PROMs. The study reinforces the importance of selecting appropriate surgical materials to enhance the success of ACDF procedures.

Navigating Complexity: A Comprehensive Approach to Middle Cerebral Artery Aneurysms.

Background: The concept of aneurysm "complexity" has undergone significant changes in recent years, with advancements in endovascular treatments. However, surgical clipping remains a relevant option for middle cerebral artery (MCA) aneurysms. Hence, the classical criteria used to define surgically complex MCA aneurysms require updating. Our objective is to review our institutional series, considering the impacts of various complexity features, and provide a treatment strategy algorithm. Methods: We conducted a retrospective review of our institutional experience with "complex MCA" aneurysms and analyzed single aneurysmal-related factors influencing treatment decisions. Results: We identified 14 complex cases, each exhibiting at least two complexity criteria, including fusiform shape (57%), large size (35%), giant size (21%), vessel branching from the sac (50%), intrasaccular thrombi (35%), and previous clipping/coiling (14%). In 92% of cases, the aneurysm had a wide neck, and 28% exhibited tortuosity or stenosis of proximal vessels. Conclusions: The optimal management of complex MCA aneurysms depends on a decision-making algorithm that considers various complexity criteria. In a modern medical setting, this process helps clarify the choice of treatment strategy, which should be tailored to factors such as aneurysm morphology and patient characteristics, including a combination of endovascular and surgical techniques.

The Pathogenic RET Val804Met Variant in Acromegaly: A New Clinical Phenotype?

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a RET pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the RET mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the RET pathogenic variant, represented by aggressive acromegaly, and suggests consideration for RET mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.

A novel risk score predicting 30-day hospital re-admission of patients with acute stroke by machine learning model.

BACKGROUND: The 30-day hospital re-admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re-admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30-day hospital re-admissions after discharge of AS patients and define an early re-admission risk score (RRS). METHODS: This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re-admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. RESULTS: Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re-admitted within 30 days from discharge. After identifying the predictors of early re-admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0-1), medium (RRS = 2-3) and high (RRS >3) with re-admission rates of 5%, 8% and 14%, respectively. CONCLUSIONS: The identification of risk factors for early re-admission after AS and the elaboration of a score to stratify at discharge time the risk of re-admission can provide a tool for clinicians to plan a personalized follow-up and contain healthcare costs.

Predictive value of intraoperative vagus nerve corticobulbar motor evoked potentials to assess the risk of dysphagia in fourth ventricle surgery.

OBJECTIVE: Dysphagia is a significant complication in fourth ventricle surgery. Corticobulbar motor evoked potentials (CB-MEPs) of the lower cranial nerves may provide real-time information possibly correlating with postoperative swallowing dysfunction, and the vagus nerves may prove ideal for this purpose. However, the literature is heterogeneous, non-systematic, and inconclusive on this topic. The object of this retrospective study was to evaluate the correlation between CB-MEPs of the vagus nerve and postoperative worsening or new-onset swallowing deficits in intraaxial fourth ventricle surgery. METHODS: In 21 consecutive patients undergoing surgery for fourth ventricle intraaxial tumors between February 2018 and October 2022, endotracheal tubes with two applied electrodes contacting the vocal cords were used to record vagus nerve MEPs including values at baseline, the end of surgery, and the minimum value during the operation. From the mean value of right and left vagus nerve MEP amplitudes, the minimum-to-baseline amplitude ratio (MBR) and final-to-baseline amplitude ratio (FBR) were calculated. These indexes were correlated with postoperative swallowing function. RESULTS: Given their clinical significance, receiver operating characteristic curves were obtained to evaluate the performance of these indexes in predicting postoperative swallowing function. The area under the curve (AUC) was 0.850 (p < 0.001) and the best cutoff for FBR was 67.55% for the worsening of swallowing in the postoperative period. The AUC was 0.750 (p = 0.026) and the best cutoff was 46.37% in MBR for the absence of a swallowing disorder at the late follow-up. CONCLUSIONS: This study confirmed that vagus nerve MEPs are reliable predictors of postoperative swallowing function in fourth ventricle surgery and can be feasibly used as an intraoperative monitoring technique.

Post-mortem Imaging of Brain/Spine Injuries: The Importance of a Comprehensive Forensic Approach.

In forensic investigations, the limitations of the traditional purely autoptic approach can be overcome through post-mortem imaging (virtopsy). Virtospy has several applications to the investigation of brain and spinal injuries, whose analysis can be of forensic interest, especially in cases of suspected malpractice. In this scoping review, we briefly describe the main applications of the two most common post-mortem radiological techniques (computed tomography (CT) and magnetic resonance imaging (MRI)) to the forensic investigation of brain and spinal injuries in cases of medical malpractice or traumatic (accidental/homicidal/suicidal) deaths. Although CT represents the traditional approach to post-mortem imaging, MRI is proving to be a valuable tool to investigate brain and spinal injuries and lesions. These post-mortem radiological techniques can also be used to guide the surgeons in simulated surgical procedures on corpses in the context of training programs, thus helping operators to improve technical and non-technical skills and to reduce the risk of avoidable errors.

Percutaneous Balloon Compression for Trigeminal Neuralgia. A Comparative Study Between the Fluoroscope Guided and Neuronavigated Technique.

Percutaneous balloon compression (PBC) is a safe and effective procedure in the treatment of trigeminal neuralgia (TN) due to its simplicity, low cost and the possibility of being repeated in case of pain recurrence. Foramen ovale (FO) cannulation is accomplished with the assistance of intraoperative C-arm fluoroscopy. Recently, several authors have reported successful application of intraoperative CT navigation as well. The reported advantages of CT navigation are linked to better spatial orientation and the low rate of attempts for FO cannulation. However, these advantages should be considered in the face of concerns regarding increased radiation dose to the patient and its possible adverse effects. Here we compared the fluoroscopic guided and neuronavigated PBC techniques in terms of efficacy and radiological exposure. We retrospectively analyzed 37 patients suffering for TN and submitted to PBC. We observed a significant improvement of pain at 1 month FU compared with the pre-operative in both groups (p < 0.0001 and p < 0.0001, respectively). A significant increase in radiation exposure was found in the neuronavigated group compared with the fluoroscopy group (p < 0.0001). We suggest the use of neuronavigated PBC only in selected cases, such as patients with multiple previous operations, in whom a difficult access can be pre-operatively hypothesized.

Spinal Cord High-Frequency Stimulation. The Current Experience and Future Directions.

Spinal cord stimulation (SCS) is a neuromodulation technology that has emerged as a valid treatment for chronic intractable neuropathic pain. After conventional tonic SCS, new waveforms of stimulation, like high frequency (HF), have proved that they can provide safe and effective pain relief. In addition, SCS is now being utilized more broadly as a potential treatment for a range of indications, including motor disorders and spasticity. Our study presents a retrospective analysis of 20 patients with heterogenous aetiologies of neuropathic pain treated with HF stimulation, after a standardized protocol in a temporary trial. We observed a significant improvement in pain relief according to comparisons of numerical rating scale (NRS) scores before the procedure, after the clinical trial and at latest follow-up. Two unusual clinical cases were also reported, and the pertinent literature was discussed.

Atlantoaxial Anterior Transarticular Screw Fixation: Indications and Surgical Technique.

Posterior atlantoaxial screw fixation is a widely adopted therapeutic option for C1-C2 instability secondary to fractures or dislocation, degenerative diseases, or tumors at this level. Anterior transarticular screw fixation (ATSF) is an effective alternative to the posterior approaches, presenting several advantages despite being scarcely known and rarely chosen.In this chapter, we describe the ATSF step by step, illustrating its variations reported in literature, and we critically analyze the several advantages and contraindications of this technique. Moreover, we provide a list of tips and tricks on the surgical procedure, including critical operating room settings-the result of more than 10 years of experience in the field by a senior author.ATSF is a valid strategy for the treatment of different diseases occurring at the level of the atlantoaxial complex that needs consideration. Given the significant learning curve of this strategy, some hints may be essential to begin introducing this technique in the personal armamentarium of a spine surgeon so that they can perform ATSF safely and effectively.

Spinal Epidural Atypical Meningioma: Case Report and Review of the Literature.

Spinal atypical meningiomas are rare, and those whose main extension is in the epidural space are anecdotal. Here, we report a case of a young woman presenting with sensory disturbances and a radiological diagnosis of a dorsal epidural sleeve-like mass. The surgical resection of the lesion allowed the decompression of the spinal cord and led to the histopathological diagnosis of atypical meningioma. At the 3-month follow-up, her neurological recovery was complete. Because of the gross total removal of the lesion, adjuvant radiotherapy was not performed: At the 2-year follow-up, no recurrence of disease was detected. A comprehensive literature review was performed, and just two more case reports on epidural atypical meningiomas were found in the English literature. Through this case report and literature review, we described a rare manifestation of spinal meningioma that entered into a differential diagnosis for extradural spinal lesions, such as secondary malignancies.

Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways.

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.

The multi-biomarker acro-TIME score predicts fg-SRLs response: preliminary results of a retrospective acromegaly cohort.

BACKGROUND: The prompt control of acromegaly is a primary treatment aim, for reducing related disease morbidity and mortality. First-generation somatostatin receptor ligands (fg-SRL) are the cornerstone of medical therapies. A non-negligible number of patients do not respond to this treatment. Several predictors of fg-SRL response were identified, but a -comprehensive prognostic model is lacking. We aimed at designing a prognostic model based on clinical, biochemical parameters, pathological features, including data on immune tumor microenvironment.Patients and methods: A retrospective, monocenter cohort study was performed on 67 medical naïve acromegaly patients. Fifteen clinical, pathological, and radiological features were collected and analyzed as independent risk factors of fg-SRLs response, though an univariable and multivariable logistic regression analyses. A stepwise selection method was applied to identify the final regression model. A nomogram was then obtained. RESULTS: Thirty-seven patients were fg-SRLs responders. An increased risk to poor response to fg-SRLs were observed in somatotropinomas with absent/cytoplasmatic SSTR2 expression (OR: 5.493 95%IC: 1.19-25.16, p=0.028), with low CD68+/CD8+ ratio (OR: 1.162, 95%IC: 1.01-1.33, p=0.032). Radical surgical resection was associated to a low risk of poor fg-SRLs response (OR: 0.106, 95%IC:0.025-0.447 p=0.002). The nomogram obtained from the stepwise regression model was based on CD68+/CD8+ ratio, SSTR2 score and the persistence of post-surgery residual tumor and was able to predict the response to fg-SRLs with good accuracy (AUC:0.85). CONCLUSION: Although our predictive model should be validated in prospective studies, our data suggest that this nomogram may represent an easy-to-use tool, for early predicting the fg-SRLs outcome.

Ultra-Early Treatment of Neurosurgical Emergencies with Endoscopic Endonasal Approach: Experience from Three Italian Referral Centers.

PURPOSE: the aim of this multicenter study is to preliminarily assess the role of the Endoscopic Endonasal Approach (EEA) in ultra-early (i.e., within 12 h) management of selected neurosurgical emergencies in terms of clinical and radiological outcomes. METHODS: 26 patients affected by sellar/parasellar pathologies with rapid progression of symptoms were managed with EEA within 12 h from diagnosis in three Italian tertiary referral Centers from January 2016 to December 2019. Both clinical and radiological data have been collected preoperatively as well as post-operatively in order to perform retrospective analysis. RESULTS: The average time from admission to the operating room was 5.5 h (±2.3). The extent of resection was gross-total in 20 (76.9%), subtotal in 6 (23.1%) patients. One patient experienced re-bleeding after a subtotal removal of a hemorrhagic lesion. Patients with a longer time from admission (>4 h) to the operatory room (OR) experienced stable impairment of the visual acuity (p = 0.033) and visual field (p = 0.029) in the post-operative setting. CONCLUSIONS: The Endoscopic Endonasal Approach represents a safe, effective technique that can be efficiently used with good results in the management of selected neurosurgical emergencies in centers with adequate experience.

Reliability of intraoperative visual evoked potentials (iVEPs) in monitoring visual function during endoscopic transsphenoidal surgery.

OBJECTIVE: To refine a reliable and reproducible intraoperative visual evoked potentials (iVEPs) monitoring protocol during endoscopic transsphenoidal surgery. To assess the reliability of baseline iVEPs in predicting preoperative visual status and perioperative iVEP variation in predicting postoperative visual outcome. METHODS: Sixty-four patients harboring tumors of the pituitary region were included. All patients underwent endoscopic endonasal approach (EEA) with iVEPs monitoring, using a totally intravenous anesthetic protocol. Ophthalmological evaluation included visual acuity and visual field studies. RESULTS: Preoperatively, visual acuity was reduced in 86% and visual field in 76.5% of cases. Baseline iVEPs amplitude was significantly correlated with preoperative visual acuity and visual field (p = 0.001 and p = 0.0004, respectively), confirming the reliability of the neurophysiological/anesthetic protocol implemented. Importantly, perioperatively the variation in iVEPs amplitude was significantly correlated with the changes in visual acuity (p < 0.0001) and visual field (p = 0.0013). ROC analysis confirmed that iVEPs are an accurate predictor of perioperiative visual acuity improvement, with a 100% positive predictive value in patients with preoperative vision loss. CONCLUSIONS: iVEPs during EEA is highly reliable in describing preoperative visual function and can accurately predict postoperative vision improvement. SIGNIFICANCE: iVEPs represent a promising resource for carrying out a more effective and safe endoscopic transsphenoidal surgery.

Training models and simulators for endoscopic transsphenoidal surgery: a systematic review.

Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no systematic review is available. To provide a systematic and critical literature review and up-to-date description of the training models or simulators dedicated to endoscopic transsphenoidal surgery. A search was performed on PubMed and Scopus databases for articles published until February 2023; Google was also searched to document commercially available. For each model, the following features were recorded: training performed, tumor/arachnoid reproduction, assessment and validation, and cost. Of the 1199 retrieved articles, 101 were included in the final analysis. The described models can be subdivided into 5 major categories: (1) enhanced cadaveric heads; (2) animal models; (3) training artificial solutions, with increasing complexity (from "box-trainers" to multi-material, ct-based models); (4) training simulators, based on virtual or augmented reality; (5) Pre-operative planning models and simulators. Each available training model has specific advantages and limitations. Costs are high for cadaver-based solutions and vary significantly for the other solutions. Cheaper solutions seem useful only for the first stages of training. Most models do not provide a simulation of the sellar tumor, and a realistic simulation of the suprasellar arachnoid. Most artificial models do not provide a realistic and cost-efficient simulation of the most delicate and relatively common phase of surgery, i.e., tumor removal with arachnoid preservation; current research should optimize this to train future neurosurgical generations efficiently and safely.

Treatment of Clival Chordomas: A 20-Year Experience and Systematic Literature Review.

Clival chordomas are rare but aggressive skull base tumors that pose significant treatment challenges and portend dismal prognosis. The aim of this study was to highlight the advantages and limitations of available treatments, to furnish prognostic indicators, and to shed light on novel therapeutic strategies. We conducted a retrospective study of clival chordomas that were surgically treated at our institution from 2003 to 2022; for comparison purposes, we provided a systematic review of published surgical series and, finally, we reviewed the most recent advancements in molecular research. A total of 42 patients underwent 85 surgeries; median follow-up was 15.8 years, overall survival rate was 49.9% at 10 years; meanwhile, progression-free survival was 26.6% at 10 years. A significantly improved survival was observed in younger patients (<50 years), in tumors with Ki67 ≤ 5% and when adjuvant radiotherapy was performed. To conclude, clival chordomas are aggressive tumors in which surgery and radiotherapy play a fundamental role while molecular targeted drugs still have an ancillary position. Recognizing risk factors for recurrence and performing a molecular characterization of more aggressive lesions may be the key to future effective treatment.

Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods.

BACKGROUND: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery. METHODS: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R. RESULTS: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data. CONCLUSION: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.