Cultivating Ex Vivo Patient-Derived Glioma Organoids Using a Tissue Chopper.

Glioblastoma, IDH-wild type, CNS WHO grade 4 (GBM) is a primary brain tumor associated with poor patient survival despite aggressive treatment. Developing realistic ex vivo models remain challenging. Patient-derived 3-dimensional organoid (PDO) models offer innovative platforms that capture the phenotypic and molecular heterogeneity of GBM, while preserving key characteristics of the original tumors. However, manual dissection for PDO generation is time-consuming, expensive and can result in a number of irregular and unevenly sized PDOs. This study presents an innovative method for PDO production using an automated tissue chopper. Tumor samples from four GBM and one astrocytoma, IDH-mutant, CNS WHO grade 2 patients were processed manually as well as using the tissue chopper. In the manual approach, the tumor material was dissected using scalpels under microscopic control, while the tissue chopper was employed at three different angles. Following culture on an orbital shaker at 37 °C, morphological changes were evaluated using bright field microscopy, while proliferation (Ki67) and apoptosis (CC3) were assessed by immunofluorescence after 6 weeks. The tissue chopper method reduced almost 70% of the manufacturing time and resulted in a significantly higher PDOs mean count compared to the manually processed tissue from the second week onwards (week 2: 801 vs. 601, P = 0.018; week 3: 1105 vs. 771, P = 0.032; and week 4:1195 vs. 784, P < 0.01). Quality assessment revealed similar rates of tumor-cell apoptosis and proliferation for both manufacturing methods. Therefore, the automated tissue chopper method offers a more efficient approach in terms of time and PDO yield. This method holds promise for drug- or immunotherapy-screening of GBM patients.

Investigating the relationship between high-dose norepinephrine administration and the incidence of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage: A single-center retrospective evaluation.

BACKGROUND: One of the longest-standing treatments to prevent delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains raising the blood pressure to a certain level of mean arterial pressure. This may require high doses of norepinephrine, which has been associated with severe end organ damage. With this study, we aimed to investigate the effects of norepinephrine on the incidence of DCI in a clinical setting. METHODS: We conducted a retrospective evaluation of patients with aSAH admitted to our institution between November 2018 and March 2021. Potential risk factors for DCI were analyzed and significant predictors were assessed by means of a logistic regression analysis to account for potential confounders. RESULTS: In this study, 104 patients were included. Hereof, 39 (38%) showed radiologic signs of DCI between day three and 14 post-intervention. These patients had more frequent vasospasms (n = 37 vs. 30, p = 0.022), a higher Hunt & Hess score (3 ± 2 vs. 2 ± 1, p = 0.004), a lower initial Glasgow Coma Scale score (9 ± 5 vs. 12 ± 4, p = 0.003) and received a higher median norepinephrine dose (20,356µg vs. 6,508µg, p < 0.001). A logistic regression analysis revealed that only high-dose norepinephrine administration (OR 2.84, CI 1.56-7.8) and vasospasm (OR 3.07, CI 1.2-7.84) appeared to be significant independent risk factors for DCI. CONCLUSION: Our results indicate a significant association between higher dose norepinephrine administration and the occurrence of DCI. Future research including greater sample sizes and a prospective setting will be necessary to further investigate the relationship.

War-related traumatic brain injuries during the Syrian armed conflict in Damascus 2014-2017: a cohort study and a literature review.

BACKGROUND: The decade-long Syrian armed conflict killed or injured more than 11% of the Syrian population. Head and neck injuries are the most frequent cause of war-related trauma, about half of which are brain injuries. Reports about Syrian brain trauma victims were published from neighboring countries; However, none are available from Syrian hospitals. This study aims to report war-related traumatic brain injuries from the Syrian capital. METHODS: We conducted a retrospective cohort study between 2014 and 2017 at Damascus Hospital, the largest public hospital in Damascus, Syria. Target patients were the victims of combat-related traumatic brain injuries who arrived alive and were admitted to the neurosurgery department or to another department but followed by the neurosurgery team. The collected data included the mechanism, type, and site of injury based on imaging findings; types of invasive interventions; intensive-care unit (ICU) admissions; as well as neurological status at admission and discharge including several severity scales. RESULTS: Our sample consisted of 195 patients; Ninety-six of them were male young adults, in addition to 40 females and 61 children. Injuries were caused by shrapnel in 127 (65%) cases, and by gunshots in the rest, and most of them (91%) were penetrating. Sixty-eight patients (35%) were admitted to the ICU, and 56 (29%) underwent surgery. Neurological impairment was reported in 49 patients (25%) at discharge, and the mortality rate during hospitalization was 33%. Mortality and neurological impairment associated significantly with higher values on clinical and imaging severity scores. CONCLUSIONS: This study captured the full spectrum of war-related brain injuries of civilians and armed personnel in Syria without the delay required to transport patients to neighboring countries. Although the clinical presentation of injuries at admission was not as severe as that in previous reports, the inadequate resources (i.e., ventilators and operation rooms) and the lack of previous experience with similar injuries might have resulted in the higher mortality rate. Clinical and imaging severity scales can provide a handy tool in identifying cases with low probability of survival especially with the shortage of personal and physical resources.

Technical nuances and approach-related morbidity of anterolateral and posterolateral lumbar corpectomy approaches-a systematic review of the literature.

PURPOSE: Approaches for lumbar corpectomies can be roughly categorized into anterolateral (AL) and posterolateral (PL) approaches. It remains controversial to date whether one approach is superior to the other, and no comparative studies exist for the two approaches for lumbar corpectomies. METHODS: A systematic review of the literature was performed through a MEDLINE/PubMed search. Studies and case reports describing technique plus outcomes and possible complications were included. Thereafter, estimated blood loss (EBL), length of operation (LOO), utilized implants, neurological outcomes, complication rates, and reoperation rates were analyzed. RESULTS: A total of 64 articles reporting on 702 patients including 513 AL and 189 PL corpectomies were included in this paper. All patients in the PL group were instrumented via the same approach used for corpectomy, while in the AL group the majority (68.3%) of authors described the use of an additional approach for instrumentation. The EBL was higher in the AL group (1393 ± 1341 ml vs. 982 ± 567 ml). The LOO also was higher in the AL group (317 ± 178 min vs. 258 ± 93 min). The complication rate (20.5% vs. 29.1%, p = 0.048) and the revision rate (3.1% vs. 9.5%, p = 0.004) were higher in the PL group. Neurological improvement rates were 43.8% (AL) vs. 39.2% (PL), and deterioration was only noted in the AL group (6.0%), while 50.2% (AL) and 60.8% (PL) showed no change from initial presentation to the last follow-up. CONCLUSION: While neurological outcomes of both approaches are comparable, the results of the present review demonstrated lower complication and revision rates in anterolateral corpectomies. Nevertheless, individual patient characteristics must be considered in decision-making.

Clinical Significance of Redundant Nerve Roots in Patients with Lumbar Stenosis Undergoing Minimally Invasive Tubular Decompression.

OBJECTIVE: Symptomatic lumbar spinal stenosis (LSS) is a common indication for surgery in the elderly. Preoperative radiographic evaluation of patients with LSS often reveals redundant nerve roots (RNRs). The clinical significance of RNRs is uncertain. RNRs have not been studied in the setting of minimally invasive surgery. This study investigates the relationship between RNRs and clinical outcomes after minimally invasive tubular decompression. METHODS: Chart review was performed for patients with degenerative LSS who underwent minimally invasive decompression. Preoperative magnetic resonance imaging parameters were assessed, and patient-reported outcomes were analyzed. RESULTS: Fifty-four patients underwent surgery performed at an average of 1.8 ± 0.8 spinal levels. Thirty-one patients (57%) had RNRs. Patients with RNRs were older (median = 72 years vs. 66 years, P = 0.050), had longer median symptom duration (32 months vs. 15 months, P < 0.01), and had more levels operated on (2.1 vs. 1.4; P < 0.01). The median follow-up after surgery was 2 months (range = 1.3-12 months). Preoperative and postoperative patient-reported outcomes were similar based on RNR presence. Patients without RNRs had larger lumbar cross-sectional areas (CSAs) (median = 121 mm2 vs. 95 mm2, P = 0.014) and the index-level CSA (52 mm2 vs. 34 mm2, P = 0.007). The CSA was not correlated with RNR morphology or location. CONCLUSIONS: Preoperative RNRs are associated with increased age, symptom duration, and lumbar stenosis severity. Patients improved after minimally invasive decompression regardless of RNR presence. RNR presence had no effect on short-term clinical outcomes. Further study is required to assess their long-term significance.

A scoring system for the preoperative evaluation of prognosis in spinal infection: the MSI-20 score.

BACKGROUND CONTEXT: Spinal infection (SI) is a life-threatening condition and its treatment remains challenging. Recent studies have supported early and aggressive surgery, but mortality still reaches 5% to 10% and it remains unclear, if an aggressive surgical strategy also applies for severely sick patients. PURPOSE: The aim of this analysis was to generate an assessment score to predict mortality of SI in order to facilitate decision-making. STUDY DESIGN: Retrospective risk factor analysis. PATIENT SAMPLE: Two hundred fifty-two patients were retrospectively analyzed. OUTCOME MEASURES: Physiologic measures, functional measures. METHODS: Diagnosis was based on clinical presentation, imaging findings and inflammatory markers. Factors associated with mortality were identified by multivariate analysis, weighted according to their relative risk ratio (RR) and included in the novel assessment score. RESULTS: Eight parameters were included: (1) BMI, (2) ASA score, (3) presence of sepsis, (4) age-adjusted Charlson Comorbidity Index, (5) presence and degree of renal failure, (6) presence of hepatopathy, (7) neurological deficits and (8) CRP levels at diagnosis. Each parameter was assigned a certain range of points, resulting in a maximum total score of 20. The mortality in spinal infection (MSI-20) score - indicating poorer status with higher values - was obtained for each patient and correlated with mortality. CONCLUSION: An MSI-20 score of 11 or more points seems to identify the small group of patients being "too sick to undergo surgery," while early surgery can be recommended in the remainder (MSI-20 ≤10). Our results need to be confirmed in prospective studies, but may give guidance for indicating surgery even in rather sick and comorbid patients.

Novel MIS 3D NAV Single Step Pedicle Screw System (SSPSS): Workflow, Accuracy and Initial Clinical Experience.

STUDY DESIGN: Prospective case series. OBJECTIVE: SSPSS (single step pedicle screw system) was developed for minimally invasive spine surgery. We performed this study to report on safety, workflow, and our initial clinical experience with this novel technique. METHODS: The prospective study was conducted on patients who underwent pedicle screw fixation between October 2017 and April 2018 using a novel single step 3D navigated pedicle screw system for MIS. Outcome measurements were obtained from intraoperative computerized tomography. The images were evaluated to determine pedicle wall penetration. We used a grading system to assess the severity of the pedicle wall penetration. Breaches were classified as grade 1 (<2 mm), grade 2 (2-4 mm), or grade 3 (<4 mm),1 and as cranial, caudal, medial, and lateral. RESULTS: Our study includes 135 screws in 24 patients. SSPSS eliminated K-wires and multiple steps traditionally necessary for MIS pedicle screw insertion. The median time per screw was 2.45 minutes. 3 screws were corrected intraoperatively. Pedicle wall penetration occurred in 14 screws (10%). Grade 1 breaches occurred in 4 screws (3%) and grade 2 breaches occurred in 10 screws (7%). Lateral breaches were observed more often than medial breaches. The accuracy rate in our study was 90% (Grade 0 breach). No revision surgeries were needed and no complications occurred. CONCLUSIONS: Our study suggests that SSPSS could be a safe, accurate, and efficient tool. Our accuracy rate is comparable to that found in the literature.

Surgical management of spinal metastases involving the cervicothoracic junction: results of a multicenter, European observational study.

OBJECTIVE: Surgical management of spinal metastases at the cervicothoracic junction (CTJ) is highly complex and relies on case-based decision-making. The aim of this multicentric study was to describe surgical procedures for metastases at the CTJ and provide guidance for clinical and surgical management. METHODS: Patients eligible for this study were those with metastases at the CTJ (C7-T2) who had been consecutively treated in 2005-2019 at 7 academic institutions across Europe. The Spine Instability Neoplastic Score, neurological function, clinical status, medical history, and surgical data for each patient were retrospectively assessed. Patients were divided into four surgical groups: 1) posterior decompression only, 2) posterior decompression and fusion, 3) anterior corpectomy and fusion, and 4) anterior corpectomy and 360° fusion. Endpoints were complications, surgical revision rate, and survival. RESULTS: Among the 238 patients eligible for inclusion this study, 37 were included in group 1 (15%), 127 in group 2 (53%), 18 in group 3 (8%), and 56 in group 4 (24%). Mechanical pain was the predominant symptom (79%, 189 patients). Surgical complications occurred in 16% (group 1), 20% (group 2), 11% (group 3), and 18% (group 4). Of these, hardware failure (HwF) occurred in 18% and led to surgical revision in 7 of 8 cases. The overall complication rate was 34%. In-hospital mortality was 5%. CONCLUSIONS: Posterior fusion and decompression was the most frequently used technique. Care should be taken to choose instrumentation techniques that offer the highest possible biomechanical load-bearing capacity to avoid HwF. Since the overall complication rate is high, the prevention of in-hospital complications seems crucial to reduce in-hospital mortality.

Elastic Image Fusion Software to Coregister Preoperatively Planned Pedicle Screws With Intraoperative Computed Tomography Data for Image-Guided Spinal Surgery.

BACKGROUND: For complex spinal cases, especially when robotic guidance is used, preoperative planning of pedicle screws can be helpful. Transfer of these preoperatively planned pedicle screws to intraoperative 3-dimensional imaging is challenging because of changes in anatomic alignment between preoperative supine and intraoperative prone imaging, especially when multiple levels are involved. In the spine, where each individual vertebra is subject to independent movement from adjacent level, rigid image fusion is confined to a single vertebra and can display fusion inaccuracies on adjacent levels. A novel elastic fusion algorithm is introduced to overcome these disadvantages. This study aimed to investigate image registration accuracy of preoperatively planned pedicle screws with an elastic fusion algorithm vs. rigid fusion for intraoperative placement with image-guided surgery. METHODS: A total of 12 patients, were selected depending on the availability of a preoperative spinal computed tomography (CT) and an intraoperative AIRO CT scan (BrainLAB AG, Munich, Germany) of the same spinal region. To verify accuracy differences between rigid fusion and elastic fusion 76 bilateral screw trajectories were virtually defined in the preoperative CT image, and they were transferred via either rigid fusion or elastic fusion to the intraoperative CT scan. Accuracy of the transferred screws in the rigid and elastic fusion group was determined by measuring pedicle breaches on the intraoperative CT. RESULTS: In the rigid fusion group 1.3% of screws showed a breach of less than 2 mm, 9.2% showed breaches between 2 and 4 mm, and 18.4% of the screws showed an error above 4 mm. The elastic fusion group showed no breaches and provided high accuracy between preoperative and intraoperative screw placement. CONCLUSION: Elastic fusion provides high registration accuracy and represents a considerable step towards efficiency and safety in CT-based image-guided surgery. LEVEL OF EVIDENCE: 3.

Adenosine-induced transient circulatory arrest in transvenous embolization of cerebral arteriovenous malformations.

Due to advances in interventional techniques, the transvenous approach may present an effective treatment option for embolization of brain arteriovenous malformations (AVMs). Contrary to the transarterial method, the transvenous approach can only be utilized in a specific subset of patients and is not suitable as a standard procedure for all AVM lesions. While this technique can be helpful in certain patients, careful patient selection to ensure patient safety and favorable clinical outcomes is important. However, especially in high-flow AVMs, targeted deposition of embolic materials through a transvenous access can be challenging. Therefore, a temporary flow arrest may prove helpful. Transient cardiac arrest by use of adenosine has been applied in cerebrovascular surgery but is not common for endovascular embolization. Adenosine-induced arrest and systemic hypotension may be a feasible, safe method to reduce flow and help endovascular transvenous embolization of certain AVMs. Our study evaluated the efficiency and safety of adenosine-induced circulatory arrest for transvenous embolization of cerebral AVMs.

Gender-Specific Differences in Presentation and Management of Spinal Infection: A Single-Center Retrospective Study of 159 Cases.

STUDY DESIGN: A retrospective single-center analysis of 159 cases. OBJECTIVE: To investigate differences between male and female patients, as spinal infection (SI) represents a life-threatening condition and numerous factors may facilitate the course and outcome of SI, including patients' age and comorbidities, as well as gender. To date, no comparative data investigating sex differences in SI is available. Thus, the purpose of the present retrospective trial was to investigate differences between male and female patients. METHODS: A total of 159 patients who were treated for a spinal infection between 2010 and 2016 at our department were included in the analysis. The patients were categorized into 2 groups based on gender. Evaluation included magnetic resonance imaging, laboratory values, clinical outcome, and conservative/operative management. RESULTS: Male patients suffered from SI significantly more often than female patients (n = 101, 63.5% vs n = 58, 36.5%, P = .001). However, female patients were initially affected more severely, as infection parameters were significantly higher (P = .032) and vertebral destruction was more serious (P = .018). Furthermore, women suffered from intraoperative complications more often (P = .024) and received erythrocyte concentrates more frequently (P = .01). Nevertheless, mortality rates and outcome were comparable. Pain scales were significantly higher in female patients at 12-month follow-up (P = .042). CONCLUSION: Although male patients show a higher incidence for SI, the course of disease and the management is more challenging in female patients. Nevertheless, outcome after 12 months is comparably good. Underlying mechanisms may include a better immune response and dissimilar effects of antibiotic treatment in women. Pain management in female patients is still unsatisfactory after 12 months.

Endovascular reconstruction of iatrogenic internal carotid artery injury following endonasal surgery: a systematic review.

The objective of this study is to provide an update on endovascular treatments for iatrogenic internal carotid artery (ICA) injuries following endonasal surgery. A systematic review of the literature was performed by using Medline, Cochrane library, and Scopus from 1999 to 2019. We used a combination of the MeSH terms "internal carotid artery," "iatrogenic disease," and "endovascular procedure." Twenty-six articles including 46 patients were identified for in this systematic review. The mean age of the patients was 49 years (CI: ± 4.2). The most common site of ICA injury was in cavernous segment (18 patients; 39%). The most common type of iatrogenic ICA injury was a traumatic pseudoaneurysm documented in 28 patients (60%). Endoluminal reconstruction was performed using covered stents in 28 patients, the Pipeline embolization device (PED) in 13 patients, the Surpass flow diverter device in three, the SILK flow diverter in one, and one case was treated using a combined approach of a covered stent and a PED. Flow diversion and covered stents resulted in a good clinical outcome in 94% and 89% of patients, respectively. This difference did not reach statistical significance (p = 1.0). Even though this systematic review was limited due to articles of small sample sizes and considerable heterogeneity, the results indicate that flow diverting devices and covered stents are good therapeutic options for endoluminal reconstruction of iatrogenic ICA injuries following endonasal surgery.

Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II-IV: a multicenter retrospective case series.

INTRODUCTION: Primary malignant spinal astrocytomas present rare oncological entities with limited median survival and rapid neurological deterioration. Evidence on surgical therapy, adjuvant treatment, and neurological outcome is sparse. We aim to describe the treatment algorithm and clinical features on patients with infiltrating intramedullary astrocytomas graded WHO II-IV. METHODS: The following is a multicentered retrospective study of patients treated for spinal malignant glioma WHO II-IV in five high-volume neurosurgical departments from 2008 to 2019. Pilocytic astrocytomas were excluded. We assessed data on surgical technique, perioperative neurological status, adjuvant oncological therapy, and clinical outcome. RESULTS: 40 patients were included (diffuse astrocytoma WHO II n = 11, anaplastic astrocytoma WHO III n = 12, WHO IV n = 17). Only 40% were functionally independent before surgery, most patients presented with moderate disability (47.5%). Most patients underwent a biopsy (n = 18, 45%) or subtotal tumor resection (n = 15, 37.5%), and 49% of the patients deteriorated after surgery. Patients with WHO III and IV tumors were treated with combined radiochemotherapy. Median overall survival (OS) was 46.5 months in WHO II, 25.7 months in WHO III, and 7.4 months in WHO IV astrocytomas. Preoperative clinical status and WHO significantly influenced the OS, and the extent of resection did not. CONCLUSION: Infiltrating intramedullary astrocytomas WHO II-IV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.

Lateralization of inferior petrosal sinus sampling in Cushing's disease correlates with cavernous sinus venous drainage patterns, but not tumor lateralization.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is known as the gold standard to distinguish whether excessive adrenocorticotropin hormone (ACTH) production origins from the pituitary gland or an ectopic source. However, due to a number of factors, the value of IPSS for adenoma lateralization may be limited. Aim of this study was to evaluate the influence of parasellar venous drainage (VD) patterns on IPSS findings in predicting lateralization of pituitary microadenomas. METHODS: We retrospectively reviewed records of confirmed cases of Cushing's disease which were evaluated by IPSS prior to endoscopic tansnasal trans-sphenoidal surgery (ETSS) to assess the ability of IPSS to predict adenoma laterality. RESULTS: Seventeen patients with pathologically confirmed Cushing's disease were retrospectively reviewed. The median age of the included patients was 37 years. Laterality of parasellar VD perfectly associated with lateralization as measured by IPSS. Symmetrical VD was associated with symmetrical ACTH gradient on IPSS. However, lateralization measured by IPSS did not show any significant correlation with lateralization detected during ETSS. CONCLUSION: Our study suggests that IPSS lateralization results strongly depend on parasellar VD pattern but show no significant correlation with the adenoma lateralization found during ETSS. Thus, IPSS does not appear to be an appropriate modality to predict adenoma lateralization.

Early surgery may lower mortality in patients suffering from severe spinal infection.

PURPOSE: Spinal infection (SI) is a life-threatening condition and treatment remains challenging. Numerous factors influence the outcome of SI and both conservative and operative care can be applied. As SI is associated with mortality rates between 2 and 20% even in developed countries, the purpose of the present study was to investigate the occurrence and causes of death in patients suffering from SI. METHODS: A retrospective analysis was performed on 197 patients, categorized into two groups according to their outcome: D (death) and S (survival). The diagnosis was based on clinical and imaging (MRI) findings. Data collected included demographics, clinical characteristics, comorbidities, infection parameters, treatment details, outcomes, and causes of death. RESULTS: The number of deaths was significantly higher in the conservative group (n = 9/51, 18%) compared with the operative counterpart (n = 8/146, 6%; p = 0.017). Death caused by septic multiorgan failure was the major cause of fatalities (n = 10/17, 59%) followed by death due to cardiopulmonary reasons (n = 4/17, 24%). The most frequent indication for conservative treatment in patients of group D included "highest perioperative risk" (n = 5/17, 29%). CONCLUSION: We could demonstrate a significantly higher mortality rate in patients solely receiving conservative treatment. Mortality is associated with number and type of comorbidities, but also tends to be correlated with primarily acquired infection. As causes of death are predominantly associated with a septic patient state or progression of disease, our data may call for an earlier and more aggressive treatment. Nevertheless, prospective clinical trials will be mandatory to better understand the pathogenesis and course of spinal infection, and to develop high quality, evidence-based treatment recommendations.