Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours.

BACKGROUND: PTEN is a tumour suppressor gene and well-known for being frequently mutated in several cancer types. Loss of immunogenicity can also be attributed to PTEN loss, because of its role in establishing the tumour microenvironment. Therefore, this study aimed to represent the link between PTEN and cGAS-STING activity, a key mediator of inflammation, in tumour samples of glioblastoma patients. METHODS: Tumour samples of 36 glioblastoma patients were collected. After DNA isolation, all coding regions of PTEN were sequenced and analysed. PTEN expression status was also evaluated by qRT-PCR, western blot, and immunohistochemical methods. Interferon-stimulated gene expressions, cGAMP activity, CD8 infiltration, and Granzyme B expression levels were determined especially for the evaluation of cGAS-STING activity and immunogenicity. RESULTS: Mutant PTEN patients had significantly lower PTEN expression, both at mRNA and protein levels. Decreased STING, IRF3, NF-KB1, and RELA mRNA expressions were also found in patients with mutant PTEN. Immunohistochemistry staining of PTEN displayed expressional loss in 38.1% of the patients. Besides, patients with PTEN loss had considerably lower amounts of IFNB and IFIT2 mRNA expressions. Furthermore, CD8 infiltration, cGAMP, and Granzyme B levels were reduced in the PTEN loss group. CONCLUSION: This study reveals the immunosuppressive effects of PTEN loss in glioblastoma tumours via the cGAS-STING pathway. Therefore, determining the PTEN status in tumours is of great importance, like in situations when considering the treatment of glioblastoma patients with immunotherapeutic agents.

Intraoperative mixed-reality spinal neuronavigation system: a novel navigation technique for spinal intradural pathologies.

OBJECTIVE: The objective of this study was to assess the intraoperative accuracy and feasibility of 3D-printed marker-based mixed-reality neurosurgical navigation for spinal intradural pathologies. METHODS: The authors produced 3D segmentations of spinal intradural tumors with neighboring structures by using combined CT and MRI, and preoperative registration of pathology and markers was successfully performed. A patient-specific, surgeon-facilitated application for mobile devices was built, and a mixed-reality light detection and ranging (LIDAR) camera on a mobile device was employed for cost-effective, high-accuracy spinal neuronavigation. RESULTS: Mobile device LIDAR cameras can successfully overlay images of virtual tumor segmentations according to the position of a 3D-printed marker. The surgeon can visualize and manipulate 3D segmentations of the pathology intraoperatively in 3D. CONCLUSIONS: A 3D-printed marker-based mixed-reality spinal neuronavigation technique was performed in spinal intradural pathology procedures and has potential to be clinically feasible and easy to use for surgeons, as well as being time saving, cost-effective, and highly precise for spinal surgical procedures.

Three-dimensional-printed marker-based augmented reality neuronavigation: a new neuronavigation technique.

OBJECTIVE: The aim of this study was to assess the precision and feasibility of 3D-printed marker-based augmented reality (AR) neurosurgical navigation and its use intraoperatively compared with optical tracking neuronavigation systems (OTNSs). METHODS: Three-dimensional-printed markers for CT and MRI and intraoperative use were applied with mobile devices using an AR light detection and ranging (LIDAR) camera. The 3D segmentations of intracranial tumors were created with CT and MR images, and preoperative registration of the marker and pathology was performed. A patient-specific, surgeon-facilitated mobile application was developed, and a mobile device camera was used for neuronavigation with high accuracy, ease, and cost-effectiveness. After accuracy values were preliminarily assessed, this technique was used intraoperatively in 8 patients. RESULTS: The mobile device LIDAR camera was found to successfully overlay images of virtual tumor segmentations according to the position of a 3D-printed marker. The targeting error that was measured ranged from 0.5 to 3.5 mm (mean 1.70 ± 1.02 mm, median 1.58 mm). The mean preoperative preparation time was 35.7 ± 5.56 minutes, which is longer than that for routine OTNSs, but the amount of time required for preoperative registration and the placement of the intraoperative marker was very brief compared with other neurosurgical navigation systems (mean 1.02 ± 0.3 minutes). CONCLUSIONS: The 3D-printed marker-based AR neuronavigation system was a clinically feasible, highly precise, low-cost, and easy-to-use navigation technique. Three-dimensional segmentation of intracranial tumors was targeted on the brain and was clearly visualized from the skin incision to the end of surgery.

An Overview of Spinal Injuries due to Dive or Fall into Shallow Water: Our Long-Term, Double-Center Experience from the Aegean Coast.

PURPOSE: We aimed to evaluate the demographic and clinical features of patients with cervical spinal injuries secondary to shallow-water diving and share our therapeutic outcomes. METHODS: A retrospective study was carried out using data extracted from the medical files of 39 patients (3 females and 36 males) who were treated surgically (n = 29) or conservatively (n = 10). Demographics, clinical features, operative data, American Spine Injury Association (ASIA) impairment scales, and Karnofsky Performance Status (KPS) results were noted. RESULTS: The average age of our series (n = 39) was 31.59 ± 14.80 (range, 14 to 92) years. The vast majority of patients (n = 34, 87.2%) presented with isolated cervical trauma. At initial admission, neurological deficits were diagnosed in 22 (56.4%) patients. A single-level cervical involvement was noted in 18 (46.2%) patients, while 21 cases (53.8%) displayed injury involving multiple levels. The levels of cervical injury were C5 (n = 16, 41%), C6 (n = 11, 28.2%), C7 (n = 6, 15.4%), C1 (n = 5, 12.8%), and C4 (n = 1, 2.6%). A total of 22 patients had neurological deficits at admission. Surgery was performed using anterior (n = 21, 72.4%), posterior (n = 7, 24.1%), and combined anterior and posterior (n = 1, 3.4%) routes. Nine patients (23.1%) exhibited improvement in their neurological deficits. There were significant improvements in both the ASIA impairment scale and KPS results after treatment. CONCLUSION: Our data indicated that dive- or fall-related cervical spinal injuries are associated with profound morbidity. Reinforcement of primary prevention, identification of target population, and increased awareness on this topic are the key steps to minimize the frequency and severity of complications and to optimize therapeutic outcomes.