MedNexus
Volume 41 · Issue 03 · 2025
MedNexus
Low-grade glioma (LGG), although less malignant, has a risk of evolving into high-grade glioma, and therapeutic strategies are controversial. It was found that isocitrate dehydrogenase (IDH) mutation is closely related to the occurrence, development and prognosis of LGG. IDH inhibitors block tumor growth by specifically inhibiting the activity of mutated IDH enzymes, correcting epigenetic changes and cellular metabolic disorders, etc. IDH inhibitors have shown certain application potential in the treatment of LGG, but they also face some controversies and challenges. Objectively looking at the application prospects of IDH inhibitors in the treatment of LGG and the changes they may bring will help to promote the further development of clinical decision-making and treatment models.
To explore the prognostic factors of recurrent adult-type diffuse brain gliomas.
Based on the Chinese Glioma Genome Atlas (CGGA) Database, a total of 468 patients with recurrent adult-type diffuse brain gliomas were retrospectively enrolled into this study. All patients underwent surgery from January 2006 to June 2021 and received regular follow-up after surgery. All patients were diagnosed according to the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system(CNS), including 217 patients with recurrent astrocytoma, isocitrate dehydrogenase (IDH)-mutant; 64 patients with recurrent oligodendroglioma, IDH-mutant with 1p/19q codeleted; and 187 patients with recurrent glioblastoma, IDH wild-type. Univariate and multivariate Cox proportional hazards regression models were applied for survival analysis, and factors with P<0.05 in the univariate analysis were included in the multivariate Cox proportional hazards regression model.
For patients with recurrent astrocytoma, IDH-mutant, the median overall survival (OS) of WHO CNS grades 2, 3, and 4 were 118.4, 18.8 and 11.5 months, respectively, and the median progression-free survival (PFS) were 42.8, 17.2 and 8.5 months, respectively. For patients with recurrent oligodendroglioma, IDH-mutant with 1p/19q codeleted, WHO CNS grades 2 and 3, the median OS were 70.6 and 61.7 months, respectively, and the median PFS were 54.3 and 42.8 months, respectively. For patients with recurrent glioblastoma, IDH wild-type, the median OS and median PFS were 9.0 and 6.9 months, respectively. The results of univariate and multivariate Cox proportional hazards regression model analysis showed that gender, age, O6-methylguanine-DNA methyltransferase promoter methylation, or preoperative epileptic seizure was not prognostic factor for OS and PFS in the three types of patients with brain gliomas (all P>0.05), while gross total tumor resection was a protective factor for OS (univariate analysis HR: 0.300-0.385, multivariate analysis HR: 0.360-0.388) and PFS (univariate analysis HR: 0.395-0.469, multivariate analysis HR: 0.393-0.436) in the three types of patients with brain gliomas (all P<0.05); higher WHO CNS grade was a risk factor for OS (multivariate analysis HR=2.170, 95%CI: 1.710-2.753) and PFS (multivariate analysis HR=2.131, 95%CI: 1.695-2.679) in patients with recurrent astrocytoma, IDH-mutant (both P<0.001); postoperative epileptic seizure was a protective factor for OS (multivariate analysis HR=0.505, 95%CI: 0.321-0.794) and PFS (multivariate analysis HR=0.542, 95%CI: 0.348-0.845) in patients with recurrent glioblastoma, IDH wild-type (both P<0.05).
The survival prognosis in the three types of patients with recurrent adult-type diffuse brain gliomas can benefit from gross total tumor resection. Higher WHO CNS grade in patients with recurrent astrocytoma, IDH-mutant, is associated with poorer survival prognosis. Patients with recurrent glioblastoma, IDH wild-type, who have postoperative epileptic seizures show a relatively better survival prognosis.
To explore the relationship between the expression of annexin A2 (ANXA2) in peritumoral brain edema (PTBE) region and prognosis of glioblastoma.
A retrospective cohort study was conducted on 94 patients with primary supratentorial GBM who underwent tumor resection in the Department of Neurosurgery, Peking University Third Hospital from June 2018 to October 2022. After the brain tissue of PTBE region was retained, the expression of ANXA2 gene was detected by quantitative real-time PCR (qRT-PCR) and the expression of ANXA2 protein was detected by Western Blot (WB). According to the median of gene or protein expression, the patients were divided into high expression group and low expression group, with 47 cases in each group. Kaplan-Meier method was used to analyze the difference in survival time between patients with high and low expression of ANXA2 in PTBE region. Multivariate Cox regression analysis was used to evaluate the correlation between the expression level of ANXA2 in PTBE and the overall survival of patients.
The results of qRT-PCR showed that the median expression of ANXA2 gene in PTBE region was 13.48 (0.36-121.37). The median expression of ANXA2 protein detected by WB was 0.68 (0.07-8.53). The median follow-up time of 94 patients was 21 (1-49) months, and 32 patients died. Kaplan-Meier survival analysis showed that the median overall survival of patients with low expression of ANXA2 gene and protein in the PTBE region was 20 (3-46) months, while the high expression group had a median survival of 10 (1-29) months.Log-rank test showed that there were significant differences in survival time between ANXA2 gene or protein high expression group and low expression group (all P<0.01). Multivariate Cox regression analysis showed that the high expression of ANXA2 gene (HR=1.833, 95%CI: 1.040-3.231) and that of protein (HR=2.043, 95%CI: 1.158-3.604) in PTBE region, rather than 1p/19q non-codeletion type, O6-methylguanine-DNA methyltransferase promoter non-methylation type and increasing age, were independent risk factors affecting the survival of GBM patients (all P<0.05).
The high expression of ANXA2 in PTBE is related to the poor prognosis of GBM patients.
To explore the clinical efficacy of neuroendoscopy in the treatment of gliomas.
A retrospective analysis was conducted on the clinical data of 46 patients with gliomas who underwent neuroendoscopic surgery at the Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University from June 2023 to August 2024. The length of the surgical incision was 7 cm, and the size of the bone flap was 3.5 cm×4.0 cm or 4.0 cm×4.5 cm. The extent of tumor resection was evaluated based on the criteria for tumor resection. The postoperative neurological deficits, incidence of complications, and mortality rate were documented. The Karnofsky Performance Status (KPS) score was used to assess the life quality of patients at discharge and at 1 to 3 months post operation.
All 46 patients successfully completed the surgery, and no postoperative intracranial hematoma occurred. The intraoperative bleeding volume was 100-300 ml, with an average of 168.7±60.2 ml. The operation time was 3.0-9.5 h, with an average of 4.5±1.4 h. Total resection was achieved in 34 patients (73.9%), near-total resection in 9 patients (19.6%), and subtotal resection in 3 patients (6.5%). There were 6 patients with neurological dysfunction after surgery, including 5 cases of limb movement disorders (including 3 cases with speech impairment) and 1 case of consciousness disorder. At discharge, the KPS score ranged from 30 to 90 points, with an average of 80.1±15.0 points. None of the patients experienced new complications or death. During the 1-3 month follow-up after surgery, the KPS score ranged from 50 to 100 points, with an average of 88.9±8.7 points. Five patients who experienced limb dysfunction after surgery had varying degrees of functional recovery.
The use of neuroendoscopy to treat brain gliomas has shown good safety and effectiveness. It can ensure a high tumor resection rate and good control of complications with minimal trauma.
To explore the surgical techniques and preliminary efficacy of transcortical resection of insular low-grade gliomas.
The clinical data of 37 patients with insular low-grade gliomas who underwent resection via the transcortical approach and were treated at the Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University from October 2019 to June 2024 were retrospectively analyzed. Among them, 16 patients presented with new-onset seizures. During the operation, different cortical approaches were selected according to the Berger-Sanai classification or the location and size of the tumor to expose the tumor, and the tumor was resected according to the anatomical boundaries. Clinical and imaging assessment was carried out at 1 week and 3 months post operation to evaluate the degree of tumor resection and postoperative complications. The Chinese version of the Western Aphasia Battery, Mini-Mental State Examination (MMSE), standard motor function grading, and Karnofsky Performance Status (KPS) score were used to evaluate the neurological functions of patients including language, cognition, movement and quality of life.
The operations of all 37 patients were successfully completed. Under general anesthesia, 34 patients underwent the operation via the frontal cortex approach, 1 patient via the temporal operculum approach; 1 patient via the frontal operculum approach and 1 patient via the parietal operculum approach under awake anesthesia. Total resection was achieved in 30 patients (81.1%), and near total resection in 7 patients (18.9%). Post-operative pathological examination confirmed that all 37 gliomas were World Health Organization (WHO) grade 2. Among them, there were 28 cases of diffuse astrocytoma [75.7%, isocitrate dehydrogenase (IDH) mutant type], 1 case of pleomorphic xanthoastrocytoma (2.7%, IDH wild-type), and 8 cases of oligodendroglioma (21.6%, IDH mutant and 1p/19q co-deletion type). Post-operative cranial CT or MRI showed no obvious edema or hematoma. Cranial MRI diffusion-weighted imaging of 1 patient showed cerebral infarction. Four patients developed neurological deficits after the operation, including 3 cases of language dysfunction and 1 case of motor dysfunction. The 3-month follow-up post operation showed that the functions of all 4 patients with neurological deficits recovered. The MMSE score was 27.0±1.6 points, and the KPS score was 94.1± 6.0 points. Among the 16 patients with seizure onset before the operation, 14 patients had no seizures after the operation, and 2 patients had occasional minor seizures, which were well controlled with antiseizure medicine.
Transcortical resection of insular low-grade gliomas is safe and effective with mild postoperative complications. Identification of important anatomical boundary markers during operation helps to achieve the maximum safe resection of insular gliomas.
To investigate the clinical efficacy and safety of tumor treating fields (TTFields) combined with immune checkpoint inhibitor pembrolizumab in the treatment of glioblastoma (GBM) patients.
A retrospective analysis was conducted on the clinical data of 5 GBM patients who were treated with TTFields combined with pembrolizumab at the Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences between August 2022 and September 2024. Three of the newly diagnosed GBM patients received adjuvant chemotherapy with temozolomide (TMZ) and TTFields combined with pembrolizumab at 4 weeks after concurrent chemoradiotherapy. TTFields therapy was initiated simultaneously with TMZ therapy in 2 to 6 weeks after diagnosis of relapsed GBM patients and further combined with pembrolizumab after disease progression. All patients were followed up every 2 to 4 months to assess survival and treatment-related adverse events, which were assessed using the Common Terminology Standard for Adverse Events.
The median duration of treatment with the combination of TTFields and pabolizumab was 9.3 months (3.1 to 21.8 months), and the median duration of daily wear of TTFields was 19.9 hours (13.4 to 22.6 hours). One patient had a grade 1 adverse event, and none of the other 4 patients had combination-related adverse events. The median follow-up time of the five patients was 9.2 months (4.9 to 14.3 months). Up to the last follow-up, 2 patients with relapse had disease progression, and their progression-free survival (PFS) were 6.3 months and 6.5 months respectively. One newly diagnosed patient died, and the PFS and overall survival (OS) were 14.6 and 25.7 months respectively. The remaining 2 newly diagnosed GBM patients were in a stable state of disease.
TTFields combined with immune checkpoint inhibitors in the treatment of GBM is well-tolerated and demonstrted certain efficacy, and has the potential to improve the prognosis of GBM patients.
To evaluate the hand-held effectiveness of the miniaturized epi-fluorescent widefield microscope (MEW-M) system in intra-operative differentiation of lesions from normal brain tissues in the central nervous system (CNS).
Sixteen patients who underwent craniotomy and spinal surgery at the Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from September 2022 to April 2023 were prospectively enrolled. All patients underwent tissue biopsy at the lesion boundary under neuronavigation guidance, and MEW-M and frozen tissue pathology (referred to as frozen section pathology) diagnosis were performed during the operation. The diagnosis based on HE staining pathology of postoperative paraffin-embedded tissue sections (referred to as paraffin histopathology) was used as the standard. The accuracy of diagnosis and procedure duration were compared between MEW-M and frozen section pathology.
A total of 52 tissues were examined, including 42 abnormal tissues and 10 tissues as diagnoses by HE staining of paraffin sections. The morphology of vessels, cells, nuclei and other subcellular structures were clearly identified using MEW-M. Among 52 tissues, 8 abnormal samples were incorrectly interpreted as normal tissue through MEW-M, including 3 tumor samples of primary central nervous system lymphoma (PCNSL) and 5 samples of ganglioglioma. Three tumor samples of PCNSL were incorrectly interpreted through the frozen section examination. Setting paraffin-embedded section with HE staining examination as standard, the MEW-M had a sensitivity of 0.81 (34/42), specificity of 1.00 (10/10), accuracy of 0.85 (44/52) and an area under the curve (AUC) value of 0.90. The frozen section pathology had a sensitivity of 0.93 (39/42), specificity of 1.00 (10/10), accuracy of 0.94 (49/52) and AUC value of 0.96. The MEW-M exhibited a sensitivity of 0.87 (34/39), specificity of 1.00 (13/13) and accuracy of 0.90 (47/52) when compared with the frozen section pathology. Among malignant tumors, MEW-M exhibited a sensitivity of 0.91 (29/32), specificity of 1.00 (9/9), accuracy of 0.94 (38/42) and AUC value of 0.95 when compared to paraffin-embedded section with HE staining examination. MEW-M showed completely consistent results as the frozen section pathology for samples from malignant tumors. For non-malignant lesions, MEW-M exhibited a sensitivity of 0.50 (5/10) and accuracy of 0.55 (6/11), and the frozen section pathology showed completely consistent results with HE staining examination. The median time required for MEW-M to diagnose each sample was 5 min (range: 3-7 min), the median time required for frozen pathology diagnosis was 27 min (range: 22-34 min), and the difference was statistically significant (P<0.001).
Preliminary research shows that the ability of MEW-M to distinguish CNS malignant tumor tissue from normal tissue has the potential to be non-inferior to frozen section pathology. However, further experience is needed in the interpretation of benign lesions. The time required for identification using MEW-M is much shorter than that of frozen section pathology diagnosis.
To preliminarily investigate the effect of free muscle combined with biological protein glue on prevention of cerebrospinal fluid (CSF) leak after acoustic neuroma surgery via the retrosigmoid approach.
This study was conducted on patients with vestibular schwannomas treated at the Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2021 to October 2023. All patients underwent surgery via the suboccipital retrosigmoid approach, with the posterior wall of the internal auditory canal removed and the open posterior wall sealed with free muscle combined with biological protein glue. Follow-up was conducted via telephone and outpatient visits. Surgical outcomes were evaluated using the House-Brackmann (H-B) facial nerve function grading system. The occurrence of CSF leak and other related complications was documented.
A total of 184 patients with acoustic neuroma were included, among whom 175 (95.11%) achieved gross total or near-total tumor resection, and 9 (4.89%) underwent subtotal resection. The facial nerve function preservation rate was 97.28% (179/184). Nine patients (4.89%) developed postoperative CSF rhinorrhea and underwent continuous lumbar cistern drainage, among whom 3 (1.63%) had central nervous system infection. All patients were followed up, with a median follow-up time period of 28.3 months (range: 12.3 to 45.7 months). At the last follow-up, 179 patients (97.28%) had H-B grade Ⅰ-Ⅱ, and 5 patients (2.72%) had H-B grade Ⅲ. No recurrence of CSF leak was documented during the follow-up period.
This preliminary study suggests that free muscle combined with biological protein glue is an effective method for sealing the open mastoid air cells during surgery, which helps prevent postoperative CSF leak with minimal complications.
To explore the safety and efficacy of the Pipeline embolization device (PED) in the treatment of small and medium-sized intracranial aneurysms (with the maximum diameter of the aneurysm ≤ 10 mm).
The clinical and imaging data of 90 patients with small and medium-sized intracranial aneurysms treated with PED at the Department of Neurosurgery, Nanfang Hospital, Southern Medical University from January 2018 to December 2021 were retrospectively collected. Clinical and digital subtraction angiography(DSA)follow-up was carried out on the patients at 6, 12, and 24 months post operation. The O′Kelly-Marotta (OKM) grading system was used to evaluate the degree of aneurysm occlusion, and the modified Rankin Scale (mRS) score was used to evaluate the outcomes of the patients. The mRS score of 0-2 was considered a good outcome.
All 90 patients (108 aneurysms) successfully completed the PED treatment and a total of 90 PEDs were implanted. Peri-operative complications occurred in 5 patients (5.6%), including 4 cases of postoperative cerebral infarction, 1 case of delayed intracerebral hemorrhage, and 1 case of in-stent thrombosis. The lumen became unobstructed after thrombolytic treatment. No intraoperative, postoperative delayed aneurysm rupture or patient death occurred. All 90 patients were followed up clinically, with a follow-up time period of 11.0(5.0, 13.0) [M(Q1, Q3)]months. The last follow-up showed that the rate of good outcome was 92.2% (83/90). A total of 79 patients (94 aneurysms) were followed up by DSA, with a follow-up time period of 14.9 (12.0, 16.0)[M(Q1, Q3)] months. The last follow-up showed that according to the OKM grading system of arterial aneurysm, there was 1 case (1.1%) of grade A, 5 cases (5.3%) of grade B, 10 cases (10.6%) of grade C, and 78 cases (83.0%) of grade D. In-stent stenosis occurred in 1 patient (1.3%), stenosis or occlusion of the ophthalmic artery branches occurred in 5 patients (6.3%), and proximal stenosis of the parent artery outside the stent occurred in 2 patients (2.5%), while no obvious clinical symptoms appeared.
PED seems safe and effective in the treatment of small and medium-sized intracranial aneurysms, with a relatively low incidence of complications.
To compare and analyze the safety and efficacy of Fastunnel balloon versus Gateway balloon dilatation combined with intracranial stent implantation in the treatment of atherosclerotic stenosis (AS) in the M1 segment of the middle cerebral artery.
This retrospective study analyzed clinical and imaging data from 75 patients who underwent treatment for AS in the M1 segment of the middle cerebral artery using either Fastunnel or Gateway balloons combined with intracranial stent implantation at the Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University from June 2023 to February 2024. Patients were divided into two groups based on the balloon brand used: the Fastunnel balloon group (34 patients) and the Gateway balloon group (41 patients). Balloon dilation pressures and number of balloon inflations were compared between the two groups. Preoperative stenosis rates, post-balloon dilation stenosis rates, and post-stent implantation residual stenosis rates were analyzed using by digital subtraction angiography (DSA). The operative complications were observed and recorded. The modified Rankin scale (mRS) was used to evaluate the neurological function of the patients after operation, and DSA and CT angiography (CTA) were used to evaluate the patency of blood flow in the stent follow-up at 3–6 months post surgery.
Regarding technical success, the Gateway balloon group had a 100%(41/41) one-time success rate for balloon dilation and subsequent intracranial stent implantation, while the Fastunnel group had a success rate of 94.1% (32/34), and there was no statistically significant difference between the two groups (P=0.202). However, in the Fastunnel group, there were 2 cases of stent delivery failure. In one case, the stent was successfully deployed after catheter deflation and adjustment, but showed a distortion at the proximal marker. In another case, multiple stent delivery attempts failed, and stent release was successful only after switching to a compatible microcatheter. Regarding vessel stenosis, preoperative stenosis rate was (78.32±10.15)% in the Gateway group and (79.87±10.55)% in the Fastunnel group. After balloon dilation, the stenosis rate was reduced to (17.40±6.92)% in the Gateway group and (17.24±6.48)% in the Fastunnel group. After stent placement, the stenosis rate was (14.20±5.71)% in the Gateway group and (13.54±5.12%) in the Fastunnel group. There were no statistically significant differences in stenosis rates at any stage (all P>0.05). In terms of complications, 17 cases (7 in the Gateway group and 10 in the Fastunnel group) developed mild local arterial dissection during the procedure. However, dissections resolved after stent placement, and there were no instances of vessel rupture, bleeding, or distal embolism in either group. And there was no significant difference in minor complications between the two groups (P=0.204). The follow-up time of 75 patients was (6.49±1.99) months (3-10 months). Until the last follow-up, there was no significant difference in mRS scores between the two groups (P=1.000). Seventy-one patients (39 in the Gateway group and 32 in the Fastunnel group) completed imaging follow-up at 3-6 months after surgery (56 DSA cases and 15 CTA cases). Four patients (3 in the Gateway group and 1 in the Fastunnel group) developed mild to moderate in-stent stenosis, while the remaining 67 patients had patent stents. There was no statistically significant difference between the two groups in short-term stent patency (P=0.622).
Compared with the Gateway balloon, Fastunnel balloon dilation combined with stent implantation for treating AS in the M1 segment of the middle cerebral artery shows similar safety and efficacy. However, attention should be paid to the possible failure of intraductal stent delivery.
To investigate the surgical approach and clinical efficacy in patients with atlantoaxial dislocation(AAD) accompanied by retro-odontoid pseudotumor(ROP).
A retrospective analysis was conducted on the clinical data of 11 patients with AAD accompanied by ROP who underwent surgical treatment in the Department of Neurosurgery at the First Affiliated Hospital of Zhengzhou University between August 2019 and July 2024. Among them, 4 mixed-type and 2 cystic patients underwent posterior fusion + pseudotumor resection (intradural approach) + spinal canal decompression; 3 solid-type and 1 mixed-type patients received posterior fusion + spinal canal decompression; and 1 solid-type patient underwent posterior fusion only. Postoperative imaging and clinical follow-ups were conducted, with surgical outcomes evaluated using the Japanese Orthopaedic Association (JOA) score.
Among the 11 patients, 2 with cystic ROP had successful resection and decompression. In 4 cases of mixed-type ROP, resection was difficult and ineffective for decompression. The 4 patients who received posterior fusion plus laminectomy and those who had posterior fusion only completed surgery smoothly. All patients underwent both imaging and clinical follow-up. The postoperative follow-up period ranged from 3 to 24 months, with an average of 8.6±6.0 months. The maximum diameter [M(Q1, Q3)] of the pseudotumor reduced from 10.1(6.8, 13.3) mm preoperatively to 2.3(1.8, 5.4)mm postoperatively (Z=-2.94, P=0.003), while the JOA score improved from 12 (8, 14) points preoperatively to 15(13, 16) points postoperatively (Z=-2.84, P=0.005). One patient experienced postoperative dysphagia, which resolved after rehabilitation. No postoperative complications occurred in the remaining 10 patients.
For patients with AAD accompanied by ROP, posterior fusion combined with pseudotumor resection and spinal canal decompression can lead to satisfactory imaging and clinical outcomes.
To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) in peripheral blood for assessing mortality in patients with traumatic brain injury (TBI) and to analyze the clinical factors influencing in-hospital mortality in TBI patients.
Data from 1 602 TBI patients who were first admitted to the intensive care unit (ICU) between 2008 and 2019 were extracted from the MIMIC-Ⅳ (2.0) database. Clinical characteristics of patients in the in-hospital survival group (1 425 patients) and the in-hospital mortality group (177 patients) were collected and analyzed. Univariate and multivariate logistic regression analyses were conducted to screen for independent factors influencing in-hospital mortality of TBI patients. The predictive performance of NLR was assessed using the receiver operating characteristic (ROC) curve and area under the curve (AUC) for in-hospital mortality and compared with the sequential organ failure assessment (SOFA) score.
Compared with those in the in-hospital survival group, patients in the in-hospital mortality group were older, had a higher proportion of female, a higher incidence of congestive heart failure and renal disease complications, lower mean arterial pressure, and higher heart rates (all P<0.05). Laboratory indicators showed that patients in the in-hospital mortality group had increased NLR and white blood cell count, decreased hemoglobin and platelet counts, increased anion gap, elevated urea nitrogen levels, increased sodium and potassium levels, prolonged international normalized ratio related to coagulation function, and prolonged prothrombin time (PT) and activated partial thromboplastin time (all P<0.05). Compared with those in the in-hospital survival group, patients in the in-hospital mortality group had higher SOFA scores and a higher proportion of patients with a Glasgow Coma Scale (GCS) score ≤ 12 (both P<0.05). Additionally, a higher proportion of patients in the in-hospital mortality group received antibiotics compared with those in the in-hospital survival group (P<0.05). Multivariate logistic regression analysis revealed that age, heart rate, NLR, sodium, potassium, PT, SOFA score and GCS score were independent risk factors in-hospital mortality (all P<0.05). ROC curve analysis showed that the AUC values for NLR and SOFA score were 0.78 and 0.76 respectively, with no statistically significant difference (P>0.05). Further analysis indicated that the cutoff value for NLR to predict in-hospital mortality of TBI patients was 12.14.
Similar to the SOFA score, NLR can be used to evaluate the in-hospital mortality of TBI patients, and it can provide a more comprehensive assessment of in-hospital mortality in TBI patients in combination with other clinical factors.
To investigate the expression pattern of membrane spanning 4-domains A6A(MS4A6A) gene in different types of gliomas and its clinical significance.
The mRNA sequencing data sets and matched clinical data in the Chinese Glioma Genome Atlas (CGGA) database were retrospectively analyzed, including 325 samples in dataset 1 and 693 samples in dataset 2. The differences in MS4A6A gene expression in patients with different clinical and pathological features were evaluated. Twelve cases of primary glioma were collected and diagnosed at the Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University. Immunohistochemical (IHC) staining was used to verify the expression of MS4A6A protein in different tissue types of gliomas. The whole exome sequencing data of 286 gliomas in CGGA database (dataset 3) were included. According to the median expression of MS4A6A, the gliomas were divided into low expression group (116 cases) and high expression group (115 cases), and the copy number variation of the two groups was detected, and the gene mutation spectrum was analyzed. Kaplan-Meier method was used to analyze the difference in overall survival (OS) of patients with different expression levels of MS4A6A. Univariate and multivariate Cox regression analyses were used to analyze the effect of MS4A6A expression level on OS of patients. For dataset 1, functional enrichment analysis was used to analyze the biological functions of genes related to MS4A6A expression. The relative abundance of 22 infiltrating immune cells was estimated by the CIBERSORT software to verify the correlation between different immune cell subsets and MS4A6A expression level.
The analysis results of dataset 1 and 2 showed that the expression of MS4A6A gene was up-regulated with the increase of World Health Organization tumor grade; the expression of isocitrate dehydrogenase (IDH) wild type was higher than that of mutant type; in IDH mutant type, the expression of MS4A6A gene in 1p/19q non-codeletion type was higher than that in 1p/19q codeletion type (all P<0.001). The expression of MS4A6A gene in glioblastoma (GBM) was higher than that in oligodendroglioma and astrocytoma (both P<0.001). IHC results showed that MS4A6A protein expression was up-regulated with the increase of malignant degree of tumor tissue (P<0.05). Clinical data analysis showed that MS4A6A gene expression was lower in young patients, primary, low-grade, IDH mutation with 1p/19q co-deletion tumors (all P<0.001). In the analysis of gene mutation and copy number change in dataset 1, the chi-square test showed that the mutation rates of IDH1, CIC and ARID1A in the MS4A6A low expression group were higher than those in the MS4A6A high expression group (all P<0.05), and the copy number amplification frequency of APOBEC3 and other genes was higher in the low expression group. The high expression group had a higher frequency of copy number amplification of genes such as TTN and copy number loss of genes such as SHOX (all P<0.01). In datasets 1 and 2, the MS4A6A high expression group had shorter OS than the MS4A6A low expression group (both P<0.05). Multivariate Cox regression analysis showed that old paitents, recurrent glioma, GBM, 1p/19q non co-deletion and MS4A6A high expression were risk factors affecting the prognosis of glioma patients (all P<0.01). Biological function analysis suggested that MS4A6A might be related to synaptic organization, positive regulation of leukocyte mediated immunity and cytokine production in gliomas. The analysis of immune cell infiltration showed that MS4A6A gene was closely related to the immune response and played a key role in M2 macrophages.
MS4A6A gene shows different expression levels in different types of gliomas and is closely related to the OS and immune microenvironment of patients.
To preliminarily investigate the impact of glycogen metabolism in brain gliomas on their malignant biological behaviors.
Glioma samples from two patients (one with high-grade and one with low-grade glioma) who underwent surgical treatment at the Department of Neurosurgery, West China Hospital, Sichuan University were subjected to periodic acid-Schiff (PAS) staining to identify glycogen distribution in glioma tissues of different grades. Data extraction and analysis were performed on brain glioma patients from West China Hospital (West cohort, 83 cases), the Cancer Genome Atlas (TCGA) dataset including glioblastoma and low-grade gliomas (TCGA cohort, 624 cases), and the Chinese Glioma Genome Atlas (CGGA) mRNAseq_325 dataset (CGGA cohort, 221 cases). The TCGA cohort was divided into a training set (375 cases) and an internal validation set (249 cases) in a 6 ∶4 ratio, while the CGGA and West cohorts served as external validation sets. In the TCGA training set, key genes related to glycogen metabolism were identified using the Least Absolute Shrinkage and Selection Operator-Cox regression model. Glycogen metabolism related genes risk score (GMRS) was the sum of the products of the expression levels of key genes and their corresponding regression coefficients. In both internal and external validation sets, patients were categorized into high-risk and low-risk groups based on the optimal cutoff value of the GMRS model using the "survminer" package in the R software, and survival outcomes between these two groups were compared. Univariate and multivariate Cox regression models were used to assess whether the high-risk GMRS model group was an independent risk factor for survival prognosis in glioma patients. The predictive performance of the GMRS model for 6-, 12-, and 18-month survival prognosis was evaluated using receiver operating characteristic (ROC) curves, with an area under the curve (AUC)>0.5 indicating predictive validity. In vitro experiments were performed using the human glioblastoma cell line U87, with the experimental group treated with a glycogen phosphorylase inhibitor (10 μmol/L) and the control group untreated (n=3 for each group). Cell proliferation was assessed by CCK-8 assay, and cell migration was evaluated using Transwell assays.
PAS staining revealed significant glycogen accumulation in the cell bodies of both high-grade and low-grade glioma tissues. In the TCGA training set, the key glycogen metabolism-related genes identified for the GMRS model were HK3, AKT2, PGM1, UBB, PPP2R5D, HKDC1, EPM2A, and PHKG2. Multivariate Cox regression analysis showed that PHKG2, EPM2A, HKDC1, and PPP2R5D were protective genes, while PGM1, UBB, HK3, and AKT2 were risk genes (all P<0.05). In the internal validation set of TCGA, and in the CGGA and West cohorts, the optimal cutoff values for GMRS model were 0.043, 0.219, and 0.001, respectively. Patients in the low-risk GMRS model group had significantly higher survival rates compared with those in the high-risk group in each cohort (all P<0.05). In the TCGA full dataset, multivariate Cox regression analyses confirmed that the high-risk GMRS model group was an independent risk factor for poor survival prognosis in glioma patients (HR=1.734, 95%CI: 1.040-2.888, P=0.035). In the internal validation set of TCGA, the AUCs for the GMRS model to predict 6-, 12-, and 18-month survival were 0.831, 0.664, and 0.682 respectively; in the CGGA cohort, the AUCs were 0.497, 0.528, and 0.591 respectively; and in the West cohort, the AUCs were 0.692, 0.630, and 0.655 respectively. CCK-8 proliferation assays showed that both the experimental and control groups exhibited increasing absorbance over time (all P<0.001), but the experimental group had significantly lower absorbance at 24, 48, and 72 hours compared with the control group (all P<0.001). This indicated that inhibiting glycogen breakdown reduced the proliferation of glioma cells. Transwell migration assays revealed that the number of migration cells in the experimental group (137±6) was significantly lower than that in the control group (361±20) (t=18.520, P<0.001).
The GMRS model can be used to effectively predict the survival prognosis of brain glioma patients. The malignant progression of glioma may be closely related to the glycogen metabolism in tumor cells. Intervention in the glycogen metabolism of glioma cells may play an important role in inhibiting the malignant progression of gliomas.
Brain glioma is the most common intracranial malignant tumor in adults, with high mortality and disability rates. In recent years, the rapid development of biological detection technology has provided support for the accurate identification of glioma and the formulation of personalized treatment plans. The progress of technology and the improvement of database have jointly promoted brand-new cancer research. The two complement each other and jointly promote the precision of glioma diagnosis and treatment. Taking the cancer genome map and the Chinese glioma genome map as the starting point, this paper summarizes the current research status of glioma-related databases, and provides the basis for further exploration of glioma.
Intracranial mesenchymal tumors in children with FET-CREB fusion are rare in clinical practice. In June 2023, the Department of Neurosurgery of Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine admitted a child with intracranial mesenchymal tumors with FET-CREB fusion. The onset of the disease was fever, and the preoperative MRI of the skull showed a solid occupation of the right anterior pontic cistern slope. After total surgical resection, the tissue and molecular pathology confirmed the mesenchymal tumors with FET-CREB fusion, and adjuvant radiotherapy and chemotherapy were performed after surgery. The prognosis of the children followed up 14 months after surgery was good, and no tumor recurrence was seen.
Gliosarcoma (GS) is a high-grade malignant tumor with rapid progression and poor prognosis. Because of its rare incidence, it is easy to be misdiagnosed, and there are few literature reports on the characteristics of GS gene and targeted therapy. A patient with intracranial primary right temporal lobe GS was admitted to the Department of Neurosurgery, Huaihe Hospital, Henan University in October 2024. The patient was diagnosed with right temporal lobe space-occupying lesion before operation, and underwent right temporal lobe space-occupying resection under neuroendoscopy; Postoperative pathology confirmed GS. Genetic testing showed tumor tissue BRAF gene mutation and unmethylated MGMT promoter. Therefore, radiotherapy + targeted drug anlotinib was used for postoperative treatment. However, 5 months after operation, MRI showed that the edema around the lesion was aggravated and there were space-occupying lesions, so tumor recurrence was considered. The patient died 6 months after surgery.
Mitochondria are important organelles that maintain cell physiological activities. The active energy metabolism and rapid growth and division of glioma cells depend on the regulation of mitochondria. Therefore, the behavior patterns of mitochondria in glioma cells are increasingly concerned by researchers. This paper focuses on the mechanism of mitochondrial metastasis in glioma, which depends on intercellular communication network, and the metabolic reprogramming and intracellular signaling network regulation mediated by this phenomenon. This phenomenon of mitochondrial metastasis in glioma cells and the concept of bidirectional crosstalk between "tumor and microenvironment" provide a pioneering idea for exploring new targets for glioma treatment in the future.
Neuroinflammation is an important contributor to many central nervous system (CNS) diseases. Recent studies have shown that the bone marrow of the skull is very important for forming the immune response between the meninges and the brain, and there is a channel between the three that transports immune cells and antigen molecules, namely the skull-meninges-brain axis. During the occurrence and development of CNS diseases, immune cells can penetrate into the brain parenchyma through this axis to cause inflammatory response, thus affecting the long-term neurological prognosis of the body. Therefore, a deep study of the specific mechanism of action of this axis can help to further understand the interaction between CNS diseases and neuroimmunity. In view of the latest research progress of skull-meninge-brain axis, the role of skull-meninge-brain axis in neuroimmunity is described in detail, so as to provide new ideas for clinical treatment of CNS diseases.
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